SCMR Edition – Issue 56

Issue Number 1/2014 | SCMR Edition

56

Editorial Comment Orlando Simonetti Page 2

The Clinical Role of T1 and T2 Mapping Page 6

Myocardial T1 Mapping Techniques and Clinical Application Page 10

Compressed Sensing for the Assessment of Left Ventricular Function Page 18

Accelerated Segmented Cine TrueFISP Using k-t-sparse SENSE Page 27

mMR in Hypertrophic Cardiomyopathy Page 32

mMR for Myocardial Tissue Imaging Page 36

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MAGNETOM FlashThe Magazine of MRI

One could easily argue that cardio-vascular magnetic resonance (CMR) is in the midst of another technical revolution. Those of us who have worked in the field for the last two decades have seen similar periods in the past, when major advances in hardware technology like array coils and fast gradients, in software technology like parallel acquisition techniques, and pulse sequences like balanced steady-state free precession have spawned dramatic improvements in the efficiency and effectiveness of CMR. Three of the most exciting recent advances: myocardial parameter mapping, MR-PET, and compressed sensing are highlighted in the six articles of this issue of MAGNETOM Flash. Relaxation parameter mapping has initiated an exciting new direc-tion of research into the clinical implications of diffuse changes in myocardial tissue (e.g., fibrosis or edema) that can accompany a variety of diseases. The novel combination of CMR and PET is enabling the power-ful diagnostic combination of the exquisite assessment of myocardial tissue structure and function pro-vided by CMR, together with the eval-uation of metabolism by PET. New approaches to sampling and recon-

struction using compressed sensing are dramatically reducing the data acquisition requirements, and thereby significantly enhancing the efficiency of CMR. Together, these advances are indicative of the ever-changing nature of CMR; a technology that continues to improve thanks to the passion, creativity, and tireless effort of the researchers around the world who have made this their life’s work.

The article by Moon et al., from University College London Hospitals, London, UK, discusses recent trends in the development and investigation of techniques for quantitative mapping of myocardial T1 and T2 relaxation parameters. Quantitative mapping addresses many of the technical limi-tations of conventional T1-weighted and T2-weighted sequences, most importantly offering the capability to assess diffuse changes in myocardial tissue that can accompany many dis-ease states. The article by Fernandes et al., from University of Campinas, Brazil, nicely summarizes the tech-niques that are employed for myocar-dial T1 mapping, and reviews recent investigations of this technology in patients with a variety of diseases including amyloid, aortic stenosis, and various cardiomyopathies. As noted

in both articles, the early evidence suggests that myocardial relaxation parameter mapping has fantastic poten-tial as a diagnostic tool that may be sensitive to early pathological changes in myocardial tissue potentially missed by other imaging methods. Challenges remain in standardization of these methods to ensure consistent quantitative results across patients and imaging platforms.

The article by Schwitter et al., from the Cardiac Magnetic Resonance Center of the University Hospital of Lausanne in Switzerland nicely demonstrates an important advantage of highly acceler-ated cine imaging using compressed sensing data acquisition and recon-struction strategies. The ability to acquire sufficient cine slices to cover the entire heart in multiple orienta-tions in a single breath-hold (2 beats per slice) not only reduces exam times, but also facilitates more accurate LV volume calculations using a three dimensional modeling approach rather than the traditional Simpson’s Method. Reducing the potential for mis-regis-tration of slices avoids one of the pri-mary limitations of the 3D approach to LV volume calculations. Thus, the effi-ciency gains achieved via compressed sensing data acquisition and recon-

Dear MAGNETOM Flash reader,

Editorial

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Editorial

struction strategies can positively impact the clinical value of CMR from several different perspectives.

The article by Carr et al., from the group at Northwestern University in Chicago highlights the tremendous potential of iterative reconstruction techniques to dramatically accelerate cardiac cine imaging. The results shown indicate that efficiency gains of at least a factor of two are possible over con-ventional parallel acquisition tech-niques. The time-consuming nature of most CMR techniques, and the require-ments of repeated patient breath-holds and regular cardiac rhythm are factors that have constrained the widespread acceptance of CMR into the clinical routine. While there is still work remaining to optimize data sampling and reduce image reconstruction times, the gains in scanning efficiency demonstrated in this study could have far-reaching implications in moving CMR further into the mainstream as a cost-effective diagnostic imaging modality.

The potential advantages of simulta-neous CMR and PET acquisitions are explored in two articles of this issue of MAGNETOM Flash. Drs. Cho and Kong from Yeungnam University Hospital, Daegu, South Korea, demonstrate in a patient with hypertrophic cardiomyo-pathy the ability to characterize myo-cardial fibrosis using both Late Gado-linium Enhancement and 18F-FDG PET.

The article by Dr. James A. White from The Lawson Health Research Institute, London, Ontario, Canada, nicely describes the potential for advanced myocardial tissue charac-terization using the synergistic capa-bilities of CMR and PET. Dr. White points out how the complementary and unique information provided by CMR and PET may better characterize pathological changes in myocardial tissue in diseases such as sarcoidosis. The evaluation of cellular metabolic activity using PET may fill the role that MR spectroscopy has promised but as yet been unable to deliver in the clinical setting. The field of meta-bolic imaging is rapidly evolving,

Orlando P. Simonetti, Ph.D., is a Professor of Internal Medicine and Radiology at The Ohio State University in Columbus, Ohio. He joined the OSU faculty in 2005 as the Research Director of Cardiovascular MR and CT.

His current research interests include fast imaging, flow quantification, parameter mapping, and exercise stress CMR.

Dr. Simonetti has dedicated his entire career to the advance-ment of cardiovascular magnetic resonance technology, and is widely recognized for his contributions to the field.

“The 3 new technologies of myocardial parameter mapping, CMR-PET, and compressed sensing offer the potential to significantly improve the efficiency and effectiveness of CMR, and to expand the information CMR can provide to physicians to better diagnose and treat cardiovascular disease.”

Review BoardLars Drüppel, Ph.D. Global Segment Manager Cardiovascular MR

Sunil Kumar S.L., Ph.D. Senior Manager Applications

Reto Merges Head of Outbound Marketing MR Applications

Edgar Müller Head of Cardiovascular Applications

Heike Weh Clinical Data Manager

Michael Zenge, Ph.D. Cardiovascular Applications

Orlando P. Simonetti, Ph.D.

Editorial BoardAntje Hellwich Associate Editor

Wellesley Were MR Business Development Manager

Ralph Strecker MR Collaborations Manager

Sven Zühlsdorff, Ph.D. Clinical Collaboration Manager

Gary R. McNeal, MS (BME) Adv. Application Specialist

Peter Kreisler, Ph.D. Collaborations & Applications

however, and the continued develop-ment of hyperpolarized 13C offers exciting possibilities as well.

In summary, the three new technolo-gies of myocardial parameter mapping, CMR-PET, and compressed sensing discussed in this issue represent some of the most exciting recent advances in CMR. They offer the potential to significantly improve the efficiency and effectiveness of CMR, and to expand the information CMR can pro-vide to physicians to better diagnose and treat cardiovascular disease.

We appreciate your comments. Please contact us at [email protected]

Content 6 New generation cardiac

parametric mapping: The clinical role of T1 and T2 mapping James C. Moon, et al.

10 Myocardial T1 mapping: Techniques and clinical applications Juliano Lara Fernandes, et al.

18 Preliminary experiences with compressed sensing1 multi-slice cine acquisitions for the assessment of left ventricular function

J. Schwitter, et al.

27 Accelerated segmented cine TrueFISP of the heart on a 1.5T MAGNETOM Aera using k-t-sparse SENSE1

Maria Carr, et al.

32 Combined 18F-FDG PET and MRI evaluation of a case of hypertrophic cardiomyopathy using Biograph mMR

Ihn-ho Cho, et al.

36 Myocardial tissue imaging using simultaneous cardiac molecular MRI James A. White

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Add a new layer of pixel-based diagnostic information to cardiac diagnoses. Based on HeartFreeze Inline Motion Correction, MyoMaps1 provides pixel-based myocardial quantification, on the fly. Now address diffuse, myocardial pathologies (T1 Map), cardiac edema (T2 Map) and improve early detection of iron overload (T2* Map) to guide cardiovascular therapy, starting earlier and more efficiently.

The information presented in MAGNETOM Flash is for illustration only and is not intended to be relied upon by the reader for instruction as to the practice of medicine. Any health care practitioner reading this information is reminded that they must use their own learning, training and expertise in dealing with their individual patients. This material does not substitute for that duty and is not intended by Siemens Medical Solutions to be used for any purpose in that regard. The treating physician bears the sole responsibility for the diagnosis and treatment of patients, including drugs and doses prescribed in connection with such use. The Operating Instructions must always be strictly followed when operating the MR System. The source for the technical data is the corresponding data sheets. The statements by Siemens’ customers described herein are based on results that were achieved in the customer’s unique setting. Since there is no “typical” setting and many variables exist there can be no guarantee that other customers will achieve the same results.

1 WIP, the product is currently under development and is not for sale in the US and other countries. Its future availability cannot be ensured.

T1 Map courtesy of Peter Kellman, National Institutes of Health, Bethesda, USA.

Content

The entire editorial staff at The Ohio State University and at Siemens Healthcare extends their appreciation to all the radiologists, technologists, physicists, experts and scholars who donate their time and energy – without payment – in order to share their expertise with the readers of MAGNETOM Flash.

MAGNETOM Flash – Imprint

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Guest Editor: Orlando P. Simonetti, Ph.D. Professor of Internal Medicine and Radiology The Ohio State University, Columbus, Ohio, USA

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Editorial Board: Wellesley Were; Ralph Strecker; Sven Zühlsdorff, Ph.D.; Gary R. McNeal, MS (BME); Peter Kreisler, Ph.D.

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The information presented in these articles and case reports is for illustration only and is not intended to be relied upon by the reader for instruction as to the practice of medicine. Any health care practitioner reading this information is reminded that they must use their own learning, training and expertise in dealing with their individual patients. This material does not substitute for that duty and is not intended by Siemens Medical Solutions to be used for any purpose in that regard. The drugs and doses mentioned herein are consistent with the approval labeling for uses and/or indications of the drug. The treating

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T1 mapping

Initial T1 measurement methods were multi-breath-hold. These were time consuming and clunky, but were able to measure well diffuse myocardial fibrosis, a fundamental myocardial property with high potential clinical significance [1]. Healthy volunteers and those with disease had different extents of diffuse fibrosis [2], and these were shown to be clinically significant in a number of diseases. T1 mapping methods based on the MOLLI* approach with modifications for shorter breath-holds, better heart rate independence and better image registration for cleaner maps, however, transformed the field – albeit still with a variety of potential sequences in use [3-5]. There are two key ways of using T1 mapping: Without (or

designed to optimize contrast between ‘normal’ and abnormal – a dichotomy of health and disease. As a result, global myocardial patholo-gies such as diffuse infiltration (fibro-sis, amyloid, iron, fat, pan-inflamma-tion) are missed.

Recently, rapid technical innovations have generated new ‘mapping’ tech-niques. Rather than being ‘weighted’, these create a pixel map where each pixel value is the T1 or T2 (or T2*), displayed in color. These new sequences are single breath-hold, increasingly robust and now widely available. With T1 mapping, clever contrast agent use also permits the measurement of the extracellular volume (ECV), quantifying the inter-stitium (odema, fibrosis or amyloid), also as a map. Early results with these methodologies are exciting – poten-tially representing a new era of CMR.

Introduction

Cardiovascular magnetic resonance (CMR) is an essential tool in cardiol-ogy and excellent for cardiac function and perfusion. However, a key, unique advantage is its ability to directly scrutinize the fundamental material properties of myocardium – ‘myocar-dial tissue characterization’.

Between 2001 and 2011, the key methods for tissue characterization have been sequences ‘weighted’ to a magnetic property – T1-weighted imaging for scar (LGE) and T2-weighted for edema (area at risk, myocarditis). These, particularly LGE imaging, have changed our understanding and clini-cal practice in cardiology.

However, there are limitations to these approaches: Both are difficult to quantify – the LGE technique in particular is very robust in infarction, but harder to quantify in non-ischemic cardiomyopathy. A more fundamental difference is that sequences are

New Generation Cardiac Parametric Mapping: the Clinical Role of T1 and T2 MappingViviana Maestrini; Amna Abdel-Gadir; Anna S. Herrey; James C. Moon

The Heart Hospital Imaging Centre, University College London Hospitals, London, UK

before) contrast – Native T1 mapping; and with contrast, typically by sub-tracting the pre and post maps with hematocrit correction to generate the ECV [6].

Native T1

Native T1 mapping (pre-contrast T1) can demonstrate intrinsic myocardial contrast (Fig. 1). T1, measured in mil-liseconds, is higher where the extra-cellular compartment is increased. Fibrosis (focal, as in infarction, or dif-fuse) [7-8], odema [9-10] and amy-loid [11], are examples. T1 is lower in lipid (Anderson Fabry disease, AFD) [12], and iron [13] accumulation.

These changes are large in some rare disease. Global myocardial changes are robustly detectable without con-trast, even in early disease. In iron, AFD and amyloid, changes appear before any other abnormality – there may be no left ventricular hypertrophy, a nor-mal electrocardiogram, and normal conventional CMR, for example – gen-uinely new information. In established disease, low T1 values in AFD appear to absolutely distinguish it from other causes of left ventricular hypertrophy [12] whilst in established amyloid T1 elevation tracks known markers of cardiac severity [11].

A note of caution, however. Native T1, although stable between healthy volunteers to 1 part in 30, is depen-dent on platform (magnet manufac-turer, sequence and sequence variant, field strength) [14]. Normal reference ranges for your setup are needed.

The signal acquired is also a compos-ite signal – generated by both inter-stitium and myocytes. The use of an extracellular contrast agent adds another dimension to T1 mapping and the ability to characterize the extracellular compartment specifically.

Extracellular volume (ECV)

Initially, post-contrast T1 was mea-sured, but this is confounded by renal clearance, gadolinium dose, body composition, acquisition time post bolus, and hematocrit. Better is mea-suring the ECV. The ratio of change of T1 between blood and myocardium after contrast, at sufficient equilibrium (e.g. after 15 minutes post-bolus – no infusion generally needed) [15, 16], represents the contrast agent parti-tion coefficient [17], and if corrected for the hematocrit, the myocardial extracellular space – ECV [1]. The ECV

is specific for extracellular expansion, and well validated. Clinically this occurs in fibrosis, amyloid and odema. To distinguish, the degree of ECV change and the clinical context is important. A multiparametric approach (e. g. T2 mapping or T2-weighted imaging in addition) may therefore be useful. Amyloid can have far higher ECVs than any other disease [18] whereas ageing has small changes – near the detection limits, but of high potential clinical impor-tance [19, 20]. For low ECV expan-sion diseases, biases from blood pool partial volume errors need to be metic-ulously addressed. Nevertheless, even modest ECV changes appear prognos-tic. In 793 consecutive patients (all-comers but excluding amyloid and HCM, measuring outside LGE areas) followed over 1 year, global ECV pre-dicted short term-mortality (Fig. 2)

ECV in non scar areas (LGE excluded) is associated with all-cause mortality [21].2

2

A patient with myocarditis. On the left side a native T1 map showing the higher T1 value in the inferolateral wall (1115 ms); in the centre, a post-contrast T1 map showing the shortened T1 value after contrast administration (594 ms); on the right side the derived ECV map showing higher value of ECV (58%) compared to remote myocardium.

3

3A 3B 3C 100%

0%

Pro

po

rtio

n S

urv

ivin

g

Years of Follow-up

1.0

0.9

0.8

0.7

0.6

0.50 0.5 1.0 1.5 2.0

Lowest ECV Tertile Middle ECV Tertile Highest ECV Tertile

p < 0.001 fortrend p < 0.015 for Middle Tertile compared to others

MAGNETOM Flash | 1/2014 | www.siemens.com/magnetom-world 76 MAGNETOM Flash | 1/2014 | www.siemens.com/magnetom-world Reprinted from MAGNETOM Flash 5/2013 Reprinted from MAGNETOM Flash 5/2013

Clinical Cardiology Cardiology Clinical

* The product is currently under develop-ment; is not for sale in the U.S. and other countries, and its future availability cannot be ensured.

Native T1 maps of (1A) healthy volunteer (author VM): the myocardium appears homogenously green and the blood is red; (1B) cardiac amyloid: the myocardium has a higher T1 (red); (1C) Anderson Fabry disease: the myocardium has a lower T1 (blue) from lipid – except the inferolateral wall where there is red from fibrosis; (1D) myocarditis, the myocardium has a higher T1 (red) from edema, which is regional; (1E) iron overload: the myocardium has a lower T1 (blue) from iron.

1

1A 1B 1C

1D 1E

Progress is rapid; challenges remain. Delivery across sites and standard-ization is now beginning with new draft guidelines for T1 mapping in preparation. Watch this space. References

1 Flett AS, Hayward MP, Ashworth MT, Hansen MS, Taylor AM, Elliott PM, McGregor C, Moon JC. Equilibrium Contrast Cardiovascular Magnetic Resonance for the measurement of diffuse myocardial fibrosis: preliminary validation in humans. Circulation 2010;122:138-144.

2 Sado DM, Flett AS, Banypersad SM, White SK, Maestrini V, Quarta G, Lachmann RH, Murphy E, Mehta A, Hughes DA, McKenna WJ, Taylor AM, Hausenloy DJ, Hawkins PN, Elliott PM, Moon JC. Cardiovascular magnetic resonance measurement of myocardial extracellular volume in health and disease. Heart 2012;98:1436-1441.

3 Piechnik SK, Ferreira VM, Dall’Armellina E, Cochlin LE, Greiser A, Neubauer S, Robson MD. Shortened Modified Look-Locker Inversion recovery (ShMOLLI) for clinical myocardial T1 mapping at 1.5 and 3 T within a 9 heartbeat breathhold. J Cardiovasc Magn Reson 2010;12:69.

4 Messroghli DR, Greiser A, Fröhlich M, Dietz R, Schulz-Menger J. Optimization and validation of a fully-integrated pulse sequence for modified look-locker inversion-recovery (MOLLI) T1 mapping of the heart. J Magn Reson Imaging 2007;26:1081–1086.

5 Fontana M, White SK, Banypersad SM, Sado DM, Maestrini V, Flett AS, Piechnik SK, Neubauer S, Roberts N, Moon JC. Comparison of T1 mapping techniques for ECV quantification. Histological validation and reproducibility of ShMOLLI versus multibreath-hold T1 quantification equilibrium contrast CMR. J Cardiovasc Magn Reson 201;14:88.

6 Kellman P, Wilson JR, Xue H, Ugander M, Arai AE. Extracellular volume fraction mapping in the myocardium, part 1: evaluation of an automated method. J Cardiovasc Magn Reson 2012;14:63.

7 Dass S, Suttie JJ, Piechnik SK, Ferreira VM, Holloway CJ, Banerjee R, Mahmod M, Cochlin L, Karamitsos TD, Robson MD, Watkins H, Neubauer S. Myocardial tissue characterization using magnetic resonance non contrast T1 mapping in hypertrophic and dilated cardiomyopathy. Circ Cardiovasc Imaging. 2012; 6:726-33.

8 Puntmann VO, Voigt T, Chen Z, Mayr M, Karim R, Rhode K, Pastor A, Carr-White G, Razavi R, Schaeffter T, Nagel E. Native T1 mapping in differentiation of normal myocardium from diffuse disease in hypertrophic and dilated cardiomy-opathy. J Am Coll Cardiovasc Imgaging 2013;6:475–84.

Contact

Dr. James C. MoonThe Heart Hospital Imaging CentreUniversity College London Hospitals 16–18 Westmoreland StreetLondon W1G 8PHUKPhone: +44 (20) 34563081 Fax: +44 (20) [email protected]

[21]. The same group also found (n ~1000) higher ECVs in diabetics. Those on renin-angiotensin-aldoste-rone system blockade had lower ECVs. ECV also predicted mortality and/or incident hospitalization for heart failure in diabetics [22].

The use and capability of ECV quanti-fication is growing. T1 mapping is getting better and inline ECV maps are now possible where each pixel carries directly the ECV value (Fig. 3) – a more biologically relevant figure than T1 [6].

T2 mapping

T2-weighted CMR identifies myocar-dial odema both in inflammatory pathologies and acute ischemia, delin-eating the area at risk. However, these imaging techniques (e. g. STIR) are fragile in the heart and can be chal-lenging, both to acquire and to inter-pret. Preliminary advances were made with T2-weighted SSFP sequences,

(4A) T2 mapping in a normal volunteer (author VM). (4B) High T2 value in patient with myocarditis – here epicardial edema. (4C) Edema in acute myocardial infarction – here patchy due to microvascular obstruction – see LGE, (4D).

4

4A 4B

4D4C

which reduce false negatives and positives [23, 24]. T2 mapping seems a further increment [25] (Fig. 4). As with T1 mapping, global diseases such as pan-myocarditis may now be iden-tified by T2 mapping, and preliminary results are showing this in several rheumatologic diseases (lupus, sys-temic capillary leak syndrome) and transplant rejection, detecting early rejection missed by other modalities [26, 27].

Conclusion

Mapping – T1, T2, ECV mapping of myocardium is an emerging topic with the potential to be a powerful tool in the identification and quantification of diffuse myocardial processes with-out biopsy. Early evidence suggests that this technique detects early stage disease missed by other imaging methods and has potential as a prog-nosticator, as a surrogate endpoint in trials, and to monitor therapy.

9 Ferreira VM, Piechnik SK, Dall’Armellina E, Karamitsos TD, Francis JM, Choudhury RP, Friedrich MG, Robson MD, Neubauer S. Non-contrast T1 mapping detects acute myocardial edema with high diagnostic accuracy: a comparison to T2-weighted cardiovascular magnetic resonance. J Cardiovasc Magn Reson 2012; 14:42.

10 Dall’Armellina E, Piechnik SK, Ferreira VM, Si Ql, Robson MD, Francis JM, Cuculi F, Kharbanda RK, Banning AP, Choudhury RP, Karamitsos TD, Neubauer S. Cardio-vascular magnetic resonance by non contrast T1 mapping allows assessment of severity of injury in acute myocardial infarction. J Cardiovasc Magn Reson 2012;14:15.

11 Karamitsos TD, Piechnik SK, Banypersad SM, Fontana M, MD, Ntusi NB, Ferreira VM, Whelan CJ, Myerson SG, Robson MD, Hawkins PN, Neubauer S, Moon JC. Non-contrast T1 Mapping for the Diagnosis of Cardiac Amyloidosis. J Am Coll Cardiol Img 2013;6:488–97.

12 Sado DM, White SK, Piechnik SK, Banypersad SM, Treibel T, Captur G, Fontana M, Maestrini V, Flett AS, Robson MD, Lachmann RH, Murphy E, Mehta A, Hughes D, Neubauer S, Elliott PM, Moon JC. Identification and assessment of Anderson-Fabry Disease by Cardiovas-cular Magnetic Resonance Non-contrast myocardial T1 Mapping clinical perspective. Circ Cardiovasc Imaging 2013;6:392-398.

13 Pedersen SF, Thrys SA, Robich MP, Paaske WP, Ringgaard S, Bøtker HE, Hansen ESS, Kim WY. Assessment of intramyocardial hemorrhage by T1-weighted cardiovas-cular magnetic resonance in reperfused acute myocardial infarction. J Cardiovasc Magn Reson 2012; 14:59.

14 Raman FS, Kawel-Boehm N, Gai N, Freed M, Han J, Liu CY, Lima JAC, Bluemke DA, Liu S. Modified look-locker inversion recovery T1 mapping indices: assessment of accuracy and reproducibility between magnetic resonance scanners. J Cardiovasc Magn Reson 2013; 15:64.

15 White SK, Sado DM, Fontana M, Banypersad SM, Maestrini V, Flett AS, Piechnik SK, Robson MD, Hausenloy DJ, Sheikh AM, Hawkins PN, Moon JC. T1 Mapping for Myocardial Extracellular Volume measurement by CMR: Bolus Only Versus Primed Infusion Technique, 2013 Apr 5 [Epub ahead of print].

16 Schelbert EB, Testa SM, Meier CG, Ceyrolles WJ, Levenson JE, Blair AJ, Kellman P, Jones BL, Ludwig DR, Schwartzman D, Shroff SG, Wong TC. Myocardial extravascular extracellular volume fraction measurement by gadolinium cardiovascular magnetic resonance in humans: slow infusion versus bolus. J Cardiovasc Magn Reson 2011, Mar 4;13-16.

17 Flacke SJ, Fischer SE, Lorenz CH. Measurement of the gadopentetate dimeglumine partition coefficient in human myocardium in vivo: normal distribution and elevation in acute and chronic infarction. Radiology 2001;218:703-10.

18 Banypersad SM, Sado DM, Flett AS, Gibbs SDG, Pinney JH, Maestrini V, Cox AT, Fontana M, Whelan CJ, Wechalekar AD, Hawkins PN, Moon JC. Quantification of myocardial extracellular volume fraction in systemic AL amyloi-dosis: An Equilibrium Contrast Cardio-vascular Magnetic Resonance Study. Circ Cardiovasc Imaging 2013;6:34-39.

19 Ugander M, Oki AJ, Hsu LY, Kellman P, Greiser A, Aletras AH, Sibley CT, Chen MY, Bandettini WP, Arai AE. Extracellular volume imaging by magnetic resonance imaging provides insights into overt and sub-clinical myocardial pathology. Eur Heart J 2012; 33: 1268–1278.

20 Liu CY, Chang Liu Y, Wu C, Armstrong A, Volpe GJ, van der Geest RJ, Liu Y, Hundley WG, Gomes AS, Liu S, Nacif M, Bluemke DA, Lima JAC. Evaluation of age related interstitial myocardial fibrosis with Cardiac Magnetic Resonance Contrast-Enhanced T1 Mapping in the Multi-ethnic Study of Atherosclerosis (MESA). J Am Coll Cardiol 2013 Jul 3 [Epub ahead of print].

21 Wong TC, Piehler K, Meier CG, Testa SM, Klock AM, Aneizi AA, Shakesprere J, Kellman P, Shroff SG, Schwartzman DS, Mulukutla SR, Simon MA, Schelbert EB. Association between extracellular matrix expansion quantified by cardiovascular magnetic resonance and short-term mortality. Circulation 2012 Sep 4;126(10):1206-16.

22 Wong TC, Piehler KM, Kang IA, Kadakkal A, Kellman P, Schwartzman DS, Mulukutla SR, Simon MA, Shroff SG, Kuller LH, Schelbert EB. Myocardial extracellular volume fraction quantified by cardiovas-cular magnetic resonance is increased in diabetes and associated with mortality and incident heart failure admission. Eur Heart J 2013 Jun 11 [Epub ahead of print].

23 Giri S, Chung YC, Merchant A, Mihai G, Rajagopalan S, Raman SV, Simonetti OP. T2 quantification for improved detection of myocardial edema. J Cardiovasc Magn Reson 2009; 11:56.

24 Verhaert D, Thavendiranathan P, Giri S, Mihai G, Rajagopalan S, Simonetti OP, Raman SV. Direct T2 Quantification of Myocardial Edema in Acute Ischemic Injury. J Am Coll Cardiol Img 2011;4: 269-78.

25 Ugander M, Bagi PS, Oki AB, Chen B, Hsu LY, Aletras AH, Shah S, Greiser A, Kellman P, Arai AE. Myocardial oedema as detected by Pre-contrast T1 and T2 CMR delineates area at risk associated with acute myocardial infarction. J Am Coll Cardiol Img 2012;5:596–603.

26 ThavendiranathanP, Walls M, Giri S, Verhaert D, Rajagopalan S, Moore S, Simonetti OP, Raman SV. Improved detection of myocardial involvement in acute inflammatory cardiomyopathies using T2 Mapping. Circ Cardiovasc Imaging 2012;5:102-110.

27 Usman AA, Taimen K, Wasielewski M, McDonald J, Shah S, Shivraman G, Cotts W, McGee E, Gordon R, Collins JD, Markl M, Carr JC. Cardiac Magnetic Resonance T2 Mapping in the monitoring and follow-up of acute cardiac transplant rejection: A Pilot Study. Circ Cardiovasc Imaging. 2012; 6:782-90.

120ms

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Clinical Cardiology Cardiology Clinical


Introduction

Cardiovascular magnetic resonance (CMR) has been an increasingly used imaging modality which has experi-enced significant advancements in the last years [1]. One of the most used techniques that have made CMR so important is late gadolinium

Myocardial T1 Mapping: Techniques and Clinical ApplicationsJuliano Lara Fernandes1; Ralph Strecker2; Andreas Greiser3; Jose Michel Kalaf1

1 Radiologia Clinica de Campinas; University of Campinas, Brazil 2 Healthcare MR, Siemens Ltda, Sao Paulo, Brazil 3 MR Cardiology, Siemens Healthcare, Erlangen, Germany

enhancement (LGE) and the demon-stration of localized areas of infarct and scar tissue [2–4]. However, despite being very sensitive to small areas of regional fibrosis, LGE tech-niques are mostly dependent on the comparison to supposedly normal

reference areas of myocardium, thus not being able to depict more diffuse disease.

Myocardial interstitial fibrosis, with a diffuse increase in collagen content in myocardial volume, develops as a result of many different stimuli includ-

1A 1B

1C

MOLLI images (1A) with respective signal-time curves (1B) and reconstructed T1 map (1C) at 3T. The mean T1 time for this patient was 1152 ms (pre-contrast).

1

Table 1: Comparison of the MOLLI sequences available for T1 mapping

SequenceOriginal MOLLI T1

sequence [15]Optimized MOLLI

sequence [17]Shortened MOLLI

sequence [18]

PreparationNon-selective inversion

recoveryNon-selective inversion

recoveryNon-selective inversion

recovery

Bandwidth 1090 Hz/px 1090 Hz/px 1090 Hz/px

Flip angle 50° 35° 35°

Base matrix 240 192 192

Phase resolution 151 128 144

FOV × % phase 380 × 342 256 × 100 340 × 75

TI 100 ms 100 ms 100 ms

Slice thickness 8 mm 8 mm 8 mm

Acquisition window 191.1 ms 202 ms 206 ms

Trigger delay 300 ms 300 ms 500 ms

Inversions 3 3 3

Acquisition heartbeats 3,3,5 3,3,5 5,5,1

Recovery heartbeats 3,3,1 3,3,1 1,1,1

TI increment 100 –150 ms 80 ms 80 ms

Scan time 17 heartbeats 17 heartbeats 9 heartbeats

Spatial resolution 2.26 × 1.58 × 8 mm 2.1 × 1.8 × 8 mm 1.8 × 1.8 × 8 mm

Cardiology Clinical

MAGNETOM Flash | 1/2014 | www.siemens.com/magnetom-world 11

Clinical Cardiology

10 MAGNETOM Flash | 1/2014 | www.siemens.com/magnetom-world Reprinted from MAGNETOM Flash 1/2012 Reprinted from MAGNETOM Flash 1/2012

curves and map are shown in Figure 1. One disadvantage of this implementa-tion of MOLLI is its dependence on heart rate, mostly true for T1 values less than 200 msec or greater than 750 msec. However, because the devi-ation is systematic, raw values can be corrected using the formula T1corrected = T1raw – (2.7 × [heart rate -70]), bring-ing the coefficient of variation down to 4.6% after applying the correction. An optimized MOLLI sequence was subsequently described where heart rate correction might not be even nec-essary [17]. In the optimized sequence, the authors tested variations in readout flip angle, minimum inversion time, inversion time increments and number of pauses between each readout sequence. The conclusion from these experiments showed that a flip angle of 35°, a minimum inversion time of 100 msec, increments of 80 msec and three heart cycle pauses allowed for the most accurate measurement of myocardial T1 (Table 1). Because T1 assessment may be sensitive to motion

artifacts and not all patients might be able to hold their breaths through-out all the necessary cardiac cycles used in MOLLI’s sequence implemen-tation, more recently a shortened version sequence (ShMOLLI) using only 9 heart beats was presented to account for those limitations [18]. Using incomplete recovery of the lon-gitudinal magnetization that is cor-rected directly in the scanner by conditional interpretation, ShMOLLI was directly compared to MOLLI in patients over a wide range of T1 times and heart rates both at 1.5 and 3T. The results showed that despite an increase in noise and slight increase in the coefficient of variation (espe-cially at 1.5T), T1 times were not sig-nificantly different using ShMOLLI with the advantage of much shorter acquisition times (9.0 ± 1.1 sec versus 17.6 ± 2.9 sec). An example of MOLLI and ShMOLLI images from the same patient is presented in Figure 2.

Up to now, after acquiring images for T1 mapping, one had to analyze

them using in-house developed soft-ware, dedicated commercial pro-grams or open-source solutions [19], not always a simple and routine task, leading to difficulty in post-process-ing the data and generating T1 values. Recent advances have provided new inline processing techniques that will generate the T1 maps automatically after image acquisition with MOLLI, without the need for further post-pro-cessing, accelerating the whole pro-cess. An example of such automated T1 map is presented in Figure 3. At the same time, inline application of motion correction permits more accu-rate pixel-wise maps, avoiding errors due to respiratory deviations. An example of an image with and with-out motion correction is presented in Figure 4.

Clinical applications

Potentially, T1 mapping can be used to assess any disease that affects the myocardium promoting diffuse fibro-sis. However, because of its recent

ing pressure overload, volume overload, aging, oxidative stress and activation of the sympathetic and renin-angiotensin-aldosterone sys-tem [5]. Different from replacement fibrosis, where regional collagen deposits appear in areas of myocyte injury, LGE has a limited sensitivity for interstitial diffuse fibrosis [6]. Therefore, if one wants to image dif-fuse interstitial fibrosis within the myocardium other techniques might be more suitable.

While echocardiogram backscatter and nuclear imaging techniques may be applied for that purpose [7, 8], myocardial tissue characterization is definitely an area where CMR plays a large role. While equilibrium contrast CMR and myocardial tagging have been shown to reflect diffuse myocardial fibrosis, T1 mapping techniques have been most widely used. In the follow-ing, we describe the developments in T1 mapping as well as their possible current and future uses.

T1 mapping

By directly quantifying T1 values for each voxel in the myocardium, a parametric map can be generated representing the T1 relaxation times of any region of the heart without the need to compare it to a normal reference standard before or after the use of a contrast agent. The first attempts to measure T1 times in the myocardium used the original Look-Locker sequence and were done using free breathing with acquisition times of over 1 minute per image [9, 10], not allowing for pixel-based-mapping but only for regions-of-interest analy-sis. Another implementation of T1 mapping used variable sampling of the k-space in time (VAST), acquir-ing images in three to four breath-holds and correlating that data to invasive biopsy [11]. Other sequences have been used for quantification of T1 as well using inversion recovery TrueFISP [12, 13] or multishot satura-tion recovery images [14] but their

reproducibility and accuracy have not been extensively validated.

The most widely used T1 mapping sequence is based on the Modified Look-Locker Inversion-recovery (MOLLI) technique. Described originally by Messroghli et al. [15] it consists of a single shot TrueFISP image with acqui-sitions over different inversion time readouts allowing for magnetization recovery of a few seconds after 3 to 5 readouts. The parameters for the original MOLLI sequence are described in Table 1. The advantages of this sequence over previous methods are its acquisition in only one relatively short breath-hold, the higher spatial resolution (1.6 × 2.3 × 8 mm) and increased dynamic signal. Reproduc-ibility studies using this sequence have shown that the method is very accu-rate with a coefficient of variation of 5.4% [16] although an underestima-tion of 8% should be expected based on phantom data. An example of MOLLI images and its respective signal-time

MOLLI (2A) versus ShMOLLI (2B) in a single patient at 3T post-contrast. The calculated values for the 11 MOLLI images were 551 ms versus 544 ms for the 8 images of the shMOLLI set. The time to acquire the MOLLI images were 21 seconds versus 14 seconds for the shMOLLI sequence (with a patient heart rate of 61 bpm).

2

2B2A 3A 3B

An example of an automated T1 map generated on the fly with inline processing after acquisition of a MOLLI sequence at 3T. In (3A) the original images acquired and in (3B) the inline map. The T1 for this patient was calculated at 525 ms post-contrast.

3


Cardiology ClinicalClinical Cardiology

Reprinted from MAGNETOM Flash 1/2012 Reprinted from MAGNETOM Flash 1/2012

development, the technique has only been evaluated on a small number of patients although the clinical scenar-ios are varied.

The first clinical description of direct T1 mapping in pathological situa-tions was done in patients with acute myocardial infarction [20]. While the authors did not use the described MOLLI sequence, they did note that pre-contrast infarct areas had an 18 ± 7% increase in T1 times com-pared to normal myocardium and that after contrast the same areas showed a 27 ± 4% reduction compared to non-infarcted areas (P < 0.05 for both). In chronic myocardial infarction, where LGE has proven so useful, these changes were also observed although differences were not as pronounced as in the acute setting [21].

In amyloidosis, post-contrast T1 times were also detected to be shorter in the subendocardial regions compared to other myocardium areas [22]. The combination of both LGE identifica-tion and T1 times < 191 msec in the subendocardium at 4 minutes pro-vided a 97% concordance in diagnosis of cardiac amyloidosis and T1 values significantly correlated to markers of amyloid load such as left ventricular mass, wall thickness, interatrial thick-ness and diastolic function.

In valve disease, an attempt to show differences in T1 values in patients with chronic aortic regurgitation using MOLLI sequence did not find any changes in the overall group before

or after contrast [23]. However, the authors did notice that differences were observed regionally in segments that demonstrated impaired wall motion in cine images. The small num-ber of patients (n = 8) in the study might have affected the conclusions and further evaluation of similar data might yield other conclusions. A more recent study showed that, using equi-librium contrast CMR, diffuse fibrosis measured in aortic stenosis patients provided significant correlations to quantification on histology [24].

In heart failure, the use of T1 map-ping has been more widely studied and directly correlated to histology evaluation [11]. In this paper, the authors evaluated patients with isch-emic, idiopathic and restrictive car-diomyopathies showing that post-contrast T1 times at 1.5T were significantly shorter than controls even after exclusion of areas of LGE (429 ± 22 versus 564 ± 23 msec, P < 0.0001). We have investigated a similar group of patients on a 3T MAGNETOM Verio scanner and have found that both dilated and hypertro-phic cardiomyopathy patients have lower post-contrast T1 times com-pared to controls, but non-infarcted areas from ischemic cardiomyopathy patients do not show significant differences (unpublished data). Examples of a myocardial T1 map at 3T from a patient with dilated cardio-myopathy and suspected hypertro-phic cardiomyopathy are seen in Fig-ure 5 and 6 respectively.

Finally, in patients with both type 1 and 2 diabetes melitus, T1 mapping using CMR was able to show that these patients may have increased interstitial fibrosis compared to controls as T1 times were significantly shorter (425 ± 72 msec versus 504 ± 34 msec, P < 0.001) and correlated to global longitudinal strain by echocardiography, demonstrating impaired myocardial systolic function.

Future directions

Certainly with the research of T1 mapping in different clinical scenarios the applicability of the method will increase substantially. In the mean-time, more effort has been made to further standardize values across dif-ferent patients and time points. As T1 time, especially after injection of con-trast, depends on both physiologic and scan acquisitions, methods have been described to account for these factors, with normalization of T1 values [25]. More than that, standardization of normal values across a larger number of normal individuals is also necessary since most papers provide data on much reduced cohorts, mostly limited to single center data. In that regard, a large multicenter registry is already collecting data at 3T in patients from 20 to 80 years of age in Latin America [Fernandes JL et al. – www.clinicaltri-als.gov – NCT01030549]. Besides that, other techniques are under develop-ment that might allow T1 measurement with larger coverage of the heart using 3D methods [26].

Nevertheless, with the current tech-niques available there are already much more clinical applications to explore and certainly quantitative T1 mapping will become one of the key applica-tions in CMR in the near future.

4A

4B

Example of a MOLLI sequence obtained without (4A) and with (4B) motion correction. Notice the deviation from baseline of the left ventricle during the image acqui-sition cycle, fully corrected in (4B).

4

References 1 Fernandes JL, Pohost GM. Recent advances

in cardiovascular magnetic resonance. Rev Cardiovasc Med 2011;12:e107-12.

2 Kim RJ, Wu E, Rafael A, et al. The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction. N Engl J Med 2000;343: 1445-53.

3 Assomull RG, Prasad SK, Lyne J, et al. Cardiovascular magnetic resonance, fibrosis, and prognosis in dilated cardiomy-opathy. J Am Coll Cardiol 2006;48: 1977-85.

4 Ordovas KG, Higgins CB. Delayed contrast enhancement on MR images of myocardium: past, present, future. Radiology 2011;261:358-74.

5 Jellis C, Martin J, Narula J, Marwick TH. Assessment of nonischemic myocardial fibrosis. J Am Coll Cardiol 2010;56:89-97.

6 Mewton N, Liu CY, Croisille P, Bluemke D, Lima JA. Assessment of myocardial fibrosis with cardiovascular magnetic resonance. J Am Coll Cardiol 2011;57:891-903.

7 Picano E, Pelosi G, Marzilli M, et al. In vivo quantitative ultrasonic evaluation of myocardial fibrosis in humans. Circulation 1990;81:58-64.

17 Messroghli DR, Greiser A, Frohlich M, Dietz R, Schulz-Menger J. Optimization and validation of a fully-integrated pulse sequence for modified look-locker inversion-recovery (MOLLI) T1 mapping of the heart. J Magn Reson Imaging 2007;26:1081-6.

18 Piechnik SK, Ferreira VM, Dall’Armellina E, et al. Shortened Modified Look-Locker Inversion recovery (ShMOLLI) for clinical myocardial T1 mapping at 1.5 and 3 T within a 9 heartbeat breathhold. J Cardiovasc Magn Reson 2010;12:69.

19 Messroghli DR, Rudolph A, Abdel- Aty H, et al. An open-source software tool for the generation of relaxation time maps in magnetic resonance imaging. BMC Med Imaging 2010; 10:16.

20 Messroghli DR, Niendorf T, Schulz-Menger J, Dietz R, Friedrich MG. T1 mapping in patients with acute myocardial infarction. J Cardiovasc Magn Reson 2003;5:353-9.

21 Messroghli DR, Walters K, Plein S, et al. Myocardial T1 mapping: appli-cation to patients with acute and chronic myocardial infarction. Magn Reson Med 2007;58:34-40.

22 Maceira AM, Joshi J, Prasad SK, et al. Cardiovascular magnetic resonance in cardiac amyloidosis. Circulation 2005;111:186-93.

23 Sparrow P, Messroghli DR, Reid S, Ridgway JP, Bainbridge G, Sivana-nthan MU. Myocardial T1 mapping for detection of left ventricular myocardial fibrosis in chronic aortic regurgitation: pilot study. AJR Am J Roentgenol 2006;187:W630-5.

24 Flett AS, Hayward MP, Ashworth MT, et al. Equilibrium contrast cardiovas-cular magnetic resonance for the measurement of diffuse myocardial fibrosis: preliminary validation in humans. Circulation 2010; 122:138-44.

8 van den Borne SW, Isobe S, Verjans JW, et al. Molecular imaging of interstitial alterations in remodeling myocardium after myocardial infarction. J Am Coll Cardiol 2008;52:2017-28.

9 Flacke SJ, Fischer SE, Lorenz CH. Measurement of the gadopentetate dimeglumine partition coefficient in human myocardium in vivo: normal distribution and elevation in acute and chronic infarction. Radiology 2001;218:703-10.

10 Brix G, Schad LR, Deimling M, Lorenz WJ. Fast and precise T1 imaging using a TOMROP sequence. Magn Reson Imaging 1990;8:351-6.

11 Iles L, Pfluger H, Phrommintikul A, et al. Evaluation of diffuse myocardial fibrosis in heart failure with cardiac magnetic resonance contrast-enhanced T1 mapping. J Am Coll Cardiol 2008;52: 1574-80.

12 Schmitt P, Griswold MA, Jakob PM, et al. Inversion recovery TrueFISP: quantifi-cation of T(1), T(2), and spin density. Magn Reson Med 2004;51:661-7.

13 Bokacheva L, Huang AJ, Chen Q, et al. Single breath-hold T1 measurement using low flip angle TrueFISP. Magn Reson Med 2006;55:1186-90.

14 Wacker CM, Bock M, Hartlep AW, et al. Changes in myocardial oxygenation and perfusion under pharmacological stress with dipyridamole: assessment using T*2 and T1 measurements. Magn Reson Med 1999;41:686-95.

15 Messroghli DR, Radjenovic A, Kozerke S, Higgins DM, Sivananthan MU, Ridgway JP. Modified Look-Locker inversion recovery (MOLLI) for high-resolution T1 mapping of the heart. Magn Reson Med 2004;52: 141-6.

16 Messroghli DR, Plein S, Higgins DM, et al. Human myocardium: single-breath-hold MR T1 mapping with high spatial resolution--reproducibility study. Radiology 2006;238:1004-12.




Contact

Juliano L FernandesR. Antonio Lapa 1032Campinas-SP – 13025-292BrazilPhone: +55-19-3579-2903 Fax: [email protected]

25 Gai N, Turkbey EB, Nazarian S, et al. T1 mapping of the gadolinium-enhanced myocardium: adjustment for factors affecting interpatient comparison. Magn Reson Med 2011;65:1407-15.

26 Coolen BF, Geelen T, Paulis LE, Nauerth A, Nicolay K, Strijkers GJ. Three-dimensional T1 mapping of the mouse heart using variable flip angle steady-state MR imaging. NMR Biomed 2011;24:154-62.

5A 5B

T1 mapping at 3T after contrast of a patient with (5A) dilated cardiomyopathy (T1 of 507 ms) in comparison to (5B) a control patient (T1 of 615 ms).

5

T1 mapping of a patient with (6A) suspected hypertrophic cardiomyopathy (T1 of 466 ms) in comparison to (6B) a control patient (with a T1 of 615 ms).

6

6A 6B


Clinical Cardiology

Reprinted from MAGNETOM Flash 1/2012

Your benefits

1. Complements the MR Cardiac Reading workflow

2. Enables you to specifically synchronize rest- and stress-perfusion series

3. Simplifies visual assessment of perfusion defects due to Siemens unique “HeartFreeze” Motion Correction

This feature is currently under development; it is not for sale in the U.S. and all other countries. Its future availability cannot be guaranteed.

*

Answers for life.

www.siemens.com/cmr

syngo.MR Cardiac Perfusion* provides interactivecolored pixel maps for real-time dynamic analysis

1846_Ad_Cardiac_Perfusion_K5.indd 1 16.12.13 10:12

ize pathological myocardial tissue was the basis to assign a class 1 indication for patients with known or suspected heart failure to undergo CMR in the new Heart Failure Guidelines of the European Society of Cardiology [3].

decision making [3] e.g. to start [4] or stop [5] specific drug treatments or to implant devices [6]. CMR is generally accepted as the gold stan-dard method to yield most accurate measures of LV ejection fraction and LV volumes. This capability and the additional value of CMR to character-

Introduction

Left ventricular (LV) ejection fraction is one of the most important measures in cardiology and part of every car-diac imaging evaluation as it is recog-nized as one of the strongest predic-tors of outcome [1]. It allows to assess the effect of established or novel treatments [2], and it is crucial for

Preliminary Experiences with Compressed Sensing Multi-Slice Cine Acquisitions for the Assessment of Left Ventricular Function: CV_sparse WIPG. Vincenti, M.D.1; D. Piccini2,4; P. Monney, M.D.1; J. Chaptinel3; T. Rutz, M.D.1; S. Coppo3; M. O. Zenge, Ph.D.4; M. Schmidt4; M. S. Nadar5; Q. Wang5; P. Chevre1, 6; M.; Stuber, Ph.D.3; J. Schwitter, M.D.1

1 Division of Cardiology and Cardiac MR Center, University Hospital of Lausanne (CHUV), Lausanne, Switzerland 2 Advanced Clinical Imaging Technology, Siemens Healthcare IM BM PI, Lausanne, Switzerland 3 Department of Radiology, University Hospital (CHUV) and University of Lausanne (UNIL) / Center for Biomedical Imaging (CIBM), Lausanne, Switzerland 4 MR Applications and Workflow Development, Healthcare Sector, Siemens AG, Erlangen, Germany 5 Siemens Corportate Technology, Princeton, USA

6 Department of Radiology, University Hospital Lausanne, Switzerland

The evaluation of LV volumes and LV ejection fraction are based on well-defined protocols [7] and it involves the acquisition of a stack of LV short axis cine images from which volumes are calculated by applying Simpson’s rule. These stacks are typically acquired in multiple breath-holds. Quality crite-ria [8] for these functional images are available and are implemented e.g. for the quality assessment within the European CMR registry which currently holds approximately 33,000 patients and connects 59 centers [9].

Recently, compressed sensing (CS) techniques emerged as a means to considerably accelerate data acquisi-tion without compromising signifi-cantly image quality. CS has three requirements:

1) transform sparsity, 2) incoherence of undersampling artifacts, and 3) nonlinear reconstruction (for details, see below).

Based on these prerequisites, a CS approach for the acquisition of cardiac cine images was developed and tested*. In particular, the potential to acquire several slices covering the heart in different orientations within

a single breath-hold would allow to apply model-based analysis tools which theoretically could improve the motion assessment at the base of the heart, where considerable through-plane motion on short-axis slices can introduce substantial errors in LV volume and LV ejection fraction cal-culations. Conversely, with a multi-breath-hold approach, there are typi-cally small differences in breath-hold positions which can introduce errors in volume and function calculations. The pulse sequence tested here allows for the acquisition of 7 cine slices within 14 heartbeats with an excellent temporal and spatial resolution.

Such a pulse sequence would also offer the advantage to obtain func-tional information in at least a single plane in patients unable to hold their breath for several heartbeats or in patients with frequent extrasystoles or atrial fibrillation. However, it should be mentioned that accurate quantita-tive measures of LV volumes and function cannot be obtained in highly arrhythmic hearts or in atrial fibrilla-tion, as under such conditions vol-umes and ejection fraction change from beat to beat due to variable fill-ing conditions. Nevertheless, rough estimates of LV volumes and function would still be desirable in arrhythmic patients.

In a group of healthy volunteers and patients with different LV patholo-gies, the novel single-breath-hold CS cine approach was compared with the standard multi-breath-hold cine technique with respect to measure LV volumes and LV ejection fraction.

The CV_sparse work-in- progress (WIP)

The CV_sparse WIP package imple-ments sparse, incoherent sampling and iterative reconstruction for car-diac applications. This method in principle allows for high acceleration factors which enable triggered 2D real-time cine CMR while preserving high spatial and/or temporal resolu-tion of conventional cine acquisi-tions. Compressed sensing methods exploit the potential of image com-pression during the acquisition of raw input data. Three components [10] are crucial for the concept of compressed sensing to work

I. Sparsity: In order to guarantee compressibility of the input data, sparsity must be present in a specific transform domain. Sparsity can be computed e.g. by calculating differ-ences between neighboring pixels or by calculating finite differences in angiograms which then detect pri-marily vessel contours which typically represent a few percent of the 1 Display of the

planning of the 7 slices (4 short axis and 3 long axis slices) acquired within a single breath-hold with the three localizers.

1

1

2A 2B

Displays of the data analysis tools for the conventional short axis stack of cine images covering the entire LV (2A) and the 4D analysis tool (2B), which is model-based and takes long axis shortening of the LV, i.e. mitral annulus motion into account. Note that with both analysis tools, LV trabeculations are included into the LV volume, particularly in the end-diastolic images (corresponding images on the left of top row in 2A and 2B).

2

* Work in progress: The product is still under development and not commercially available yet. Its future availability cannot be ensured.


Clinical Cardiovascular Imaging Cardiovascular Imaging Clinical


entire image data only. Furthermore, sparsity is not limited to the spatial domain: the acquisition of cine images of the heart can be highly sparsified in the temporal dimension.

II. Incoherent sampling: The alias-ing artifacts due to k-space unders-ampling must be incoherent, i.e. noise-like, in that transform domain. Here, it is to mention that fully ran-dom k-space sampling is suboptimal as k-space trajectories should be smooth for hardware and physiologi-cal considerations. Therefore, inco-herent sampling schemes must be designed to avoid these concerns while fulfilling the condition of ran-dom, i.e. incoherent sampling.

III. Reconstruction: A non-linear iter-ative optimization corrects for sub-sampling artifacts during the process of image reconstruction yielding to a best solution with a sparse representation in a specific transform domain and which is consistent with the input data. Such compressed sensing techniques can also be com-bined with parallel imaging tech-niques [11].

WIP CV_sparse Sequence

The current CV_sparse sequence [12] realizes incoherent sampling by initially distributing the readouts pseudo-randomly on the Cartesian grid in k-space. In addition, for cine-CMR imaging, a pseudo-random offset is applied from frame-to-frame which results in an incoherent tem-poral jitter. Finally, a variable sam-pling density in k-space stabilizes the iterative reconstruction. To avoid eddy current effects for balanced steady-state free precession (bSSFP) acquisitions, pairing [13] can also be applied. Thus, the tested CV_sparse sequence is characterized by sparse, incoherent sampling in space and time, non-linear iterative reconstruc-tion integrating SENSE, and L1 wave-let regularization in the phase encod-ing direction and/or the temporal dimension. With regard to reconstruc-tion, the ICE program runs a non- linear iterative reconstruction with k-t regularization in space and time specifically modified for compressed sensing. The algorithm derives from a parallel imaging type reconstruc-tion which takes coil sensitivity maps into account, thus supporting pre-dominantly high acceleration factors. For cine CMR, no additional reference scans are needed because – similar to TPAT – the coil sensitivity maps are calculated from the temporal average of the input data in a central region of k-space consisting of not more

than 48 reference lines. The exten-sive calculations for image recon-struction typically running 80 itera-tions are performed online on all CPUs on the MARS computer in paral-lel, in order to reduce reconstruction times.

Volunteer and Patient studies

In order to obtain insight into the image quality of single-breath-hold multi-slice cine CMR images acquired with the compressed sensing (CS) approach, we studied a group of healthy volunteers and a patient group with different pathologies of the left ventricle. In addition to the evaluation of image quality, the robustness and the precision of the CS approach for LV volumes and LV ejection fraction was also assessed in comparison with a standard high- resolution cine CMR approach. All CMR examinations were performed on a 1.5T MAGNETOM Aera (Siemens Healthcare, Erlangen, Germany). The imaging protocol consisted of a set of cardiac localizers followed by the acquisition of a stack of conventional short-axis SSFP cine images covering the entire LV with a spatial and tem-

poral resolution of 1.2 x 1.6 mm2, and approximately 40 ms, respectively (slice thickness: 8 mm; gap between slices: 2 mm). LV 2-chamber, 3-cham-ber, and 4-chamber long-axis acquisi-tions were obtained for image quality assessment but were not used for LV volume quantifications. As a next step, to test the new CS-based technique, slice orientations were planned to cover the LV with 4 short-axis slices distrib-uted evenly over the LV long axis com-plemented by 3 long-axis slices (i.e. a 2-chamber, 3-chamber, and 4-chamber slice) (Fig. 1). These 7 slices were then acquired in a single breath-hold maneuver lasting 14 heart beats (i.e. 2 heart beats per slice) resulting in an acceleration factor of 11.0 with a tem-poral and spatial resolution of 30 ms and 1.5 x 1.5 mm2, respectively (slice thickness: 6 mm). As the reconstruc-tion algorithm is susceptible to aliasing in the phase-encoding direction, the 7 slices were first acquired with a non-cine acquisition to check for correct phase-encoding directions and, if needed, to adjust the field-of-view

to avoid fold-over artifacts. After confirmation of correct imaging parameters, the 7-slice single- breath-hold cine CS-acquisition was performed. In order to obtain a refer-ence for the LV volume measurement, a phase-contrast flow measurement in the ascending aorta was per-formed to be compared with the LV stroke volumes calculated from the standard and CS cine data.

The conventional stack of cine SSFP images was analyzed by the Argus software (Siemens Argus 4D Ventric-ular Function, Fig. 2A). The CS cine data were analyzed by the 4D-Argus software (Siemens Argus, Fig. 2B). Such software is based on an LV model and, with relatively few opera-tor interactions, the contours for the LV endocardium and epicardium are generated by the analysis tool. Of note, this 4D analysis tool automati-cally tracks the 3-dimensional motion of the mitral annulus throughout the cardiac cycle which allows for an accurate volume calculation particu-larly at the base of the heart.

Results and discussion Image quality – robustness of the technique

Overall, a very good image quality of the single-breath-hold multi-slice CS acquisitions was obtained in the 12 volunteers and 14 patient studies. All CS data sets were of adequate quality to undergo 4D analysis. Small structures such as trabeculations were visualized in the CS data sets as shown in Figures 3 and 4. However, very small structures, detectable by the conventional cine acquisitions, were less well discernible by the CS images. Therefore, it should be men-tioned here, that this accelerated single-breath-hold CS approach would be adequate for functional measure-ments, i.e. LV ejection fraction assessment (see also results below), whereas assessment of small struc-tures as present in many cardiomyop-athies is more reliable when per-formed on conventional cine images. Temporal resolution of the new tech-nique appears adequate to even detect visually the dyssynchroneous contraction pattern in left bundle branch block. Also, the image con-trast between the LV myocardium and the blood pool was high on the CS images allowing for an easy assessment of the LV motion pattern. As a result, the single-breath-hold cine approach permits to reconstruct the LV in 3D space with high tempo-ral resolution as illustrated in Figure 5. Since these data allow to correctly include the 3D motion of the base of the heart during the cardiac cycle, the LV stroke volume appears to be measurable by the CS approach with higher accuracy than with the con-ventional multi-breath-hold approach (see results below). With an accurate measurement of the LV stroke vol-ume, the quantification of a mitral insufficiency should theoretically ben-efit (when calculating mitral regurgi-tant volume as ‘LV stroke volume minus aortic forward-flow volume’).

As a current limitation of the CS approach, its susceptibility for fold-over artifacts should be mentioned (Figs. 6A). Therefore, the field-of-view must cover the entire anatomy and thus, some penalty in spatial res-

Standard cine 9 heartbeats

CV_SPARSE 3 heartbeats

CV_SPARSE 2 heartbeats

CV_SPARSE 1 heartbeat

Examples of visualization of small trabecular structures in the LV (in the rectangle) with the standard cine SSFP sequence (image on the left) and the accelerated compressed sensing sequences (images on the right). Despite increasing acceleration most infor-mation on small intraluminal structures remains visible.

3

Example demonstrating the performance of the compressed sensing technique visualizing small structures such as the right coronary artery (RCA) with high temporal and spatial resolution acquired within 2 heart-beats. Short-axis view of the base of the heart (1 out of 17 frames).

4

RCA

3

4



olution may occur in relation to the patient’s anatomy. In addition, the sparsity in the temporal domain may be limited in anatomical regions of very high flow, and therefore, in some acquisitions, flow-related arti-facts occurred in the phase-encoding direction during systole (Figs. 6B, C). Also, in its current version, the sequence is prospective, thus it does not cover the very last phases of the cardiac cycle and the reconstruction times for the CS images lasted sev-eral minutes precluding an immediate assessment of the image data quality or using this image information to plan next steps of a CMR examination.

Performance of the single-breath-hold CS approach in comparison with the stan-dard multi-breath-hold cine approach

From a quantitative point-of-view, the accurate and reliable measure-ment of LV volumes and function is crucial as many therapeutic decisions directly depend on these measures [3–6]. In this current relatively small study group, LV end-diastolic and end-systolic volumes measured by the single-breath-hold CS approach were comparable with those calcu-lated from the standard multi-breath-

hold cine SSFP approach. LVEDV and LVESV differed by 10 ml ± 17 ml and 2 ml ± 12 ml, respectively. Most impor-tantly, LV ejection fraction differed by only 1.3 ± 4.7% (50.6% vs 49.3% for multi-breath-hold and single-breath-hold, respectively, p = 0.17; regres-sion: r = 0.96, p < 0.0001; y = 0.96x + 0.8 ml). Thus, it can be concluded that the single-breath-hold CS approach could potentially replace the multi-breath-hold standard technique for the assessment of LV volumes and systolic function.

What about the accuracy of the novel single-breath-hold CS technique?

To assess the accuracy of the LV vol-ume measurements, LV stroke volume was compared with the LV output measured in the ascending aorta with phase-contrast MR. As the flow mea-surements were performed distally to the coronary arteries, flow in the coro-naries was estimated as the LV mass multiplied by 0.8 ml/min/g. An excel-lent agreement was found with a mean of 86.8 ml/beat for the aortic flow measurement and 91.9 ml/beat for the LV measurements derived from the single-breath-hold CS data (r = 0.93, p < 0.0001). By Bland-Altman analysis, the stroke volume approach overestimated by 5.2 ml/beat versus the reference flow measurement. For the conventional stroke volume mea-surements, this difference was 15.6 ml/beat (linear regression analysis vs aortic flow: r = 0.69, p < 0.01). More importantly, the CS LV stroke data were not only more precise with a smaller mean difference, the variability of the CS data vs the reference flow data was less with a standard deviation as low as 6.8 ml/beat vs 12.9 ml/beat for the standard multi-breath-hold approach (Fig. 7). Several explanations may apply for the higher accuracy of the single-breath-hold multi-slice CS approach in comparison to the conventional multi-breath-hold approach:

1) With the single-breath-hold approach, all acquired slices are cor-rectly co-registered, i.e. they are cor-rectly aligned in space, a prerequisite for the 4D-analysis tool to work properly.

2) This 4D-analysis tool allows for an accurate tracking of the mitral valve plane motion during the cardiac cycle as shown in Figure 5, which is impor-tant as the cross-sectional area of the heart at its base is large and thus, inac-curate slice positioning at the base of

Display of the 3D reconstruction derived from the 7 slices acquired within a single breath-hold. Note the long-axis shortening of the LV during systole allowing for accurate LV volume measurements (5A, 5B, yellow plane). Any orientation of the 3D is available for inspection of function (5A–D).

5

A typical fold-over artifact along the phase-encoding direction in a short axis slice, oriented superior-inferior for demonstrative purpose.

6A

No flow-related artifacts are visible on the end-diastolic phases, while small artifacts in phase-encoding direction (Artif, arrows) occur in mid-systole projecting over the mitral valve (6C).

6B

5A 5B

5C 5D

6A

6B

6C

Artif

Artif



the heart with conventional short-axis slices typically translate in relatively large errors. Nevertheless, we observed a systematic overesti-mation of the stroke volume by the CS approach of 5.2 ml/beat in com-parison to the flow measurements. In normal hearts with tricuspid aortic valves, an underestimation of aortic flow by the phase-contrast technique is very unlikely [14]. Thus, overesti-mation of stroke volume by the volume approach is to consider. In the vol-ume contours, the papillary muscles are excluded as illustrated in Figure 8. As these papillary muscles are excluded in both the diastolic and systolic con-tours, this aspect should not affect net LV stroke volume. However, as shown in Figure 8, smaller trabecula-tions of the LV wall are included into the LV blood pool contour in the diastolic phase, while these trabecu-

lations, when compacted in the end-systolic phase, are excluded from the blood pool resulting in a small overestimation of the end-diastolic volume, and thus, LV stroke volume. This explanation is likely as Van Rossum et al. demonstrated a slight underestimation of the LV mass when calculated on end-diastolic phases versus end-systolic phases, as trabec-ulations in end-diastole are typically excluded from the LV walls [15].

In summary, this novel very fast acquisition strategy based on a CS technique allows to cover the entire LV with high temporal and spatial resolution within a single breath-hold. The image quality based on these preliminary results appears adequate to yield highly accurate measures of LV volumes, LV stroke volume, LV mass, and LV ejection fraction.

Testing of this very fast multi-slice cine approach for the atria and the right ventricle is currently ongoing. Finally, these preliminary data show that com-pressed sensing MR acquisitions in the heart are feasible in humans and compressed sensing might be imple-mented for other important cardiac sequences such as fibrosis/viability imaging, i.e. late gadolinium enhance-ment, coronary MR angiography, or MR first-pass perfusion.

The Cardiac MR Center of the University Hospital Lausanne

The Cardiac Magnetic Resonance Center (CRMC) of the University Hospital of Lausanne (Centre Hospitalier Universi-taire Vaudois; CHUV) was established in 2009. The CMR center is dedicated to high-quality clinical work-up of car-diac patients, to deliver state-of-the-art

training in CMR to cardiologists and radiologists, and to pursue research. In the CMR center education is pro-vided for two specialties while focus-ing on one organ system. Traditionally, radiologists have focussed on using one technique for different organs, while cardiologists have concentrated on one organ and perhaps one tech-nique. Now in the CMR center the focus is put on a combination of spe-cialists with different background on one organ. Research at the CMR center is devoted to four major areas: the study of

1.) cardiac function and tissue charac-terization, specifically to better under-stand diastolic dysfunction, 2.) the development of MR-compatible cardiac devices such as pacemakers and ICDs; 3.) the utilization of hyperpolarized 13C-carbon contrast media to investi-gate metabolism in the heart, and

An excellent corre-lation is obtained for the LV stroke volume calculated from the compressed sensing data with the flow volume in the aorta measured by phase-contast technique. Variability of the conventional LV stroke volume data appears higher than for the compressed sensing data.

7

LV stroke volume: comparison vs aortic forward flow

LV short-axis slice: CV_SPARSE

4.) the development of 19F-fluorine-based CMR techniques to detect inflammation and to label and track cells non-invasively.

For the latter two topics, the CMR center established tight collabora-tions with the Center for Biomedical Imaging (CIBM), a network around Lake Geneva that includes the Ecole Polytechnique Fédérale de Lausanne (EPFL), and the universities and uni-versity hospitals of Lausanne and Geneva. In particular, strong collab-orative links are in place with the CVMR team of Prof. Matthias Stuber, a part of the CIBM and located at the University Hospital Lausanne and with Prof. A. Comment, with whom we perform the studies on real-time metabolism based on the 13C-carbon hyperpolarization (DNP) technique. In addition, collaborative studies are ongoing with the Heart Failure and Cardiac Transplantation Unit led by Prof. R. Hullin (detection of graft rejection by tissue characterization)

and the Oncology Department led by Prof. Coukos (T cell tracking by 19F-MRI in collaboration with Prof. Stuber, R. van Heeswijk, CIBM, and Prof. O. Michielin, Oncology). This structure allows for a direct interdis-ciplinary interaction between physi-cians, engineers, and basic scientists on a daily basis with the aim to enable innovative research and fast translation of these techniques from bench to bedside.

The CMRC is also the center of com-petence for the quality assessment of the European CMR registry which holds currently approximately 33,000 patient studies acquired in 59 centers across Europe.

The members of the CRMC team are: Prof. J. Schwitter (director of the center), PD Dr. X. Jeanrenaud, Dr. D. Locca, MER, Dr. P. Monney, Dr. T. Rutz, Dr. C. Sierro, and Dr. S. Koest-ner (cardiologists, staff members),

Overestimation of end-diastolic LV volumes by volumetric measurements. In comparison to ejected blood from the LV as measured with phase-contrast techniques, the volumetric measurements of LV stroke volume overestimated by approximately 5 ml, most likely by overestimation of LV end-diastolic volume. Small trabculations (yellow contours in 8A) are included into the LV blood volume (red contour in 8A) in diastole, while these trabeculations (yellow contours in 8B) are typically included in the end-systolic phase (red contours in 8B). For the same reasons, LV mass (= green contour minus red contour) is often slightly underestimated in diastole vs systole.

8

7

8A 8B

End-diastolic frame End-systolic frame

ml/beat (aortic forward flow by PC)

60 70

ml/b

eat

(LV

str

oke

vo

lum

e)

80 90 100 110

CS technique

Standard technique

120 13050

60

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130



References 1 Curtis JP, Sokol SI, Wang Y, Rathore SS,

Ko DT, Jadbabaie F, Portnay EL, Marshalko SJ, Radford MJ, Krumholz HM. The associ-ation of left ventricular ejection fraction, mortality, and cause of death in stable outpatients with heart failure. Journal of the American College of Cardiology. 2003;42(4):736-42.

2 Sürder D, Manka R, Lo Cicero V, Moccetti T, Rufibach K, Soncin S, Turchetto L, Radrizzani M, Astori G, Schwitter J, Erne P, Jamshidi P, Auf Der Maur C, Zuber M, Windecker S, Moschovitis A, Wahl A, Bühler I, Wyss C, Landmesser U, Lüscher T, Corti R. Intracoronary injection of bone marrow derived mononuclear cells, early or late after acute myocardial infarction: Effects on global LV-function: 4 months results of the SWISS-AMI trial. Circulation. 2013;127:1968-79.

Contact

Professor Juerg SchwitterMédecin Chef CardiologieDirecteur du Centre de la RM Cardiaque du CHUVCentre Hospitalier Universitaire Vaudois – CHUVRue du Bugnon 461011 LausanneSuissePhone: +41 21 314 [email protected]

11 Liang D, Liu B, Wang J, Ying L. Accelerating SENSE using compressed sensing. Magnetic Resonance in Medicine. 2009;62(6): 1574-84.

12 Liu J. Dynamic cardiac MRI reconstruction with weighted redundant Haar wavelets. Magn Reson Med. 2012;Proc. ISMRM 2012,abstract.

13 Bieri O, Markl M, Scheffler K. Analysis and compensation of eddy currents in balanced SSFP. Magn Reson Med. 2005;54:129-37.

14 Muzzarelli S, Monney P, O’Brien K, Faletra F, Moccetti T, Vogt P, Schwitter J. Quantifi-cation of aortic valve regurgitation by phase-contrast magnetic resonance in patients with bicuspid aortic valve: where to measure the flow? . Eur Heart J - CV Imaging. 2013:in press.

15 Papavassiliu T, Kühl HP, Schröder M, Süselbeck T, Bondarenko O, Böhm CK, Beek A, Hofman MMB, van Rossum AC. Effect of Endocardial Trabeculae on Left Ventricular Measurements and Measurement Reproducibility at Cardio-vascular MR Imaging1. Radiology. 2005 July 1, 2005;236(1):57-64.

Dr. G. Vincenti (cardiologist) and Dr. N. Barras (cardiologist in training, rotation), PD. Dr. S. Muzzarellli (affili-ated cardiologist), Prof. C. Beigelman and Dr. X. Boulanger (radiologists, staff members), Dr. G.L. Fetz (radiol-ogist in training, rotation), C. Gonza-les, PhD (19F-fluorine project leader), H. Yoshihara, PhD (13C-carbon project leader), V. Klinke (medical student, doctoral thesis), C. Bongard (medical student, master thesis), P. Chevre (chief CMR technician), and F. Recor-don and N. Lauriers (research nurses).

Acknowledgements

The authors would like to thank all the members of the team of MR tech-nologists at the CHUV for their highly valuable participation, helpfulness and support during the daily clinical CMR examinations and with the research protocols. Finally, a very important acknowledgment goes to Dr. Michael Zenge, Ms. Michaela Schmidt, and the whole Siemens MR Cardio team of Edgar Müller in Erlangen.

3 McMurray JJV, Adamopoulos S, Anker SD, Auricchio A, Böhm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Sanchez MAG, Jaarsma T, Køber L, Lip GYH, Maggioni AP, Parkhomenko A, Pieske BM, Popescu BA, Rønnevik PK, Rutten FH, Schwitter J, Seferovic P, Stepinska J, Trindade PT, Voors AA, Zannad F, Zeiher A. ESC Guide-lines for the diagnosis and treatment of acute and chronic heart failure 2012. European Heart Journal. 2012 May 19, 2012(33):1787–847.

4 Zannad F, McMurray JJV, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, Vincent J, Pocock SJ, Pitt B. Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms. New England Journal of Medicine. 2011;364(1):11-21.

5 Gharib MI, Burnett AK. Chemotherapy-induced cardiotoxicity: current practice and prospects of prophylaxis. European Journal of Heart Failure. 2002 June 1, 2002;4(3):235-42.

6 Bardy GH, Lee KL, Mark DB, Poole JE, Packer DL, Boineau R, Domanski M, Troutman C, Anderson J, Johnson G, McNulty SE, Clapp-Channing N, Davidson-Ray LD, Fraulo ES, Fishbein DP, Luceri RM, Ip JH. Amiodarone or an Implantable Cardioverter–Defibrillator for Congestive Heart Failure. New England Journal of Medicine. 2005;352(3):225-37.

7 Schwitter J. CMR-Update. 2. Edition ed. Lausanne, Switzerland. www.herz-mri.ch.

8 Klinke V, Muzzarelli S, Lauriers N, Locca D, Vincenti G, Monney P, Lu C, Nothnagel D, Pilz G, Lombardi M, van Rossum A, Wagner A, Bruder O, Mahrholdt H, Schwitter J. Quality assessment of cardiovascular magnetic resonance in the setting of the European CMR registry: description and validation of standardized criteria. Journal of Cardiovascular Magnetic Resonance. 2013;15(1):55.

9 Bruder O, Wagner A, Lombardi M, Schwitter J, van Rossum A, Pilz G, Nothnagel D, Steen H, Petersen S, Nagel E, Prasad S, Schumm J, Greulich S, Cagnolo A, Monney P, Deluigi C, Dill T, Frank H, Sabin G, Schneider S, Mahrholdt H. European Cardiovascular Magnetic Resonance (EuroCMR) registry-multi national results from 57 centers in 15 countries. J Cardiovasc Magn Reson. 2013;15:1-9.

10 Lustig M, Donoho D, Pauly JM. Sparse MRI: The application of compressed sensing for rapid MR imaging. Magnetic Resonance in Medicine. 2007;58(6):1182-95.

Introduction

Cine MRI of the heart is widely regarded as the gold standard for assessment of left ventricular volume and myocardial mass and is increas-ingly utilized for assessment of car-diac anatomy and pathology as part of clinical routine. Conventional cine imaging approaches typically require 1 slice per breath-hold, resulting in lengthy protocols for complete cardiac coverage. Parallel imaging allows some shortening of the acquisition time, such that 2–3 slices can be acquired in a single breath-hold. In cardiac cine imaging artifacts become more prevalent with increasing accel-eration factor. This will negatively impact the diagnostic utility of the images and may reduce accuracy of quantitative measurements. However, regularized iterative reconstruction

Accelerated Segmented Cine TrueFISP of the Heart on a 1.5T MAGNETOM Aera Using k-t-sparse SENSE Maria Carr1; Bruce Spottiswoode2; Bradley Allen1; Michaela Schmidt2; Mariappan Nadar4; Qiu Wang4; Jeremy Collins1; James Carr1; Michael Zenge2

1 Northwestern University, Feinberg School of Medicine, Chicago, IL, USA 2 Siemens Healthcare 3 Siemens Corporate Technology, Princeton, United States

techniques can be used to consider-ably improve the images obtained from highly undersampled data. In this work, L1-regularized iterative SENSE as proposed in [1] was applied to reconstruct under-sampled k-space data. This technique* takes advan-tage of the de-noising characteristics of Wavelet regularization and prom-ises to very effectively suppress sub-sampling artifacts. This may allow for high acceleration factors to be used, while diagnostic image quality is preserved.

The purpose of this study was to compare segmented cine TrueFISP images from a group of volunteers and patients using three acceleration and reconstruction approaches: iPAT factor 2 with conventional recon-struction; T-PAT factor 4 with conven-

Table 1: MRI conventional and iterative imaging parameters

Parameters Conventional iPAT 2 Conventional T-PAT 4 Iterative T-PAT 4

Iterative recon No No Yes

Parallel imaging iPAT2 (GRAPPA) TPAT4 TPAT4

TR/TE (ms) 3.2 / 1.6 3.2 / 1.6 3.2 / 1.6

Flip angle (degrees) 70 70 70

Pixel size (mm2) 1.9 × 1.9 1.9 × 1.9 1.9 × 1.9

Slice thickness (mm) 8 8 8

Temp. res. (msec) 38 38 38

Acq. time (sec) 7 3.2 3.2

tional reconstruction; and T-PAT factor 4 with iterative k-t-sparse SENSE reconstruction.

Technique

Cardiac MRI seems to be particularly well suited to benefit from a group of novel image reconstruction methods known as compressed sensing [2] which promise to significantly speed up data acquisition. Compressed sensing methods were introduced to MR imaging [3, 4] just a few years ago and have since been successfully combined with parallel imaging [5, 6]. Such methods try to utilize the

* Work in progress: The product is still under development and not commercially available yet. Its future availability cannot be ensured.

Clinical Cardiovascular Imaging


Cardiovascular Imaging Technology

MAGNETOM Flash | 1/2014 | www.siemens.com/magnetom-world 27Reprinted from MAGNETOM Flash 5/2013 Reprinted from MAGNETOM Flash 5/2013

As outlined by Liu et al. in [1], the image reconstruction can be formu-lated as an unconstrained optimization problem. In the current implementa-tion, this optimization is solved using a Nesterov-type algorithm [7]. The L1-regularization with a redundant Haar transform is efficiently solved using a Dykstra-type algorithm [8]. This allowed a smooth integration into the current MAGNETOM platform and, therefore, facilitates a broad clinical evaluation.

Materials and methods

Nine healthy human volunteers (57.4 male/56.7 female) and 20 patients (54.4 male/40.0 female) with suspected cardiac disease were scanned on a 1.5T MAGNETOM Aera system under an approved institutional review board protocol. All nine volun-teers and 16 patients were imaged using segmented cine TrueFISP sequences with conventional GRAPPA factor 2 acceleration (conventional iPAT 2) T-PAT factor 4 acceleration (conventional T-PAT 4), and T-PAT factor 4 acceleration with iterative k-t-sparse SENSE reconstruction (iterative T-PAT 4). The remaining 4 patients were scanned using only conventional iPAT 2 and iterative T-PAT 4 techniques. Note that the iterative technique is fully integrated into the standard reconstruction environment.

The imaging parameters for each imaging sequence are provided in Table 1. All three sequences were run in 3 chamber and 4 chamber views, as well as a stack of short axis slices.

Quantitative analysis was performed on all volunteer data sets at a syngo MultiModality Workplace (Leonardo) using Argus post-processing software (Siemens Healthcare, Erlangen, Germany) by an experienced cardio-vascular MRI technician. Ejection frac-tion, end-diastolic volume, end-systolic volume, stroke volume, cardiac out-put, and myocardial mass were calcu-lated. In all volunteers and patients,

blinded qualitative scoring was per-formed by a radiologist using a 5 point Likert scale to assess overall image quality (1 – non diagnostic; 2 – poor; 3 – fair; 4 – good; 5 – excellent). Images were also scored for artifact and noise (1 – severe; 2 – moderate; 3 – mild; 4 – trace; 5 – none).

All continuous variables were com-pared between groups using an unpaired t-test, while ordinal qualita-tive variables were compared using a Wilcoxon signed-rank test.

Results

All images were acquired successfully and image quality was of diagnostic quality in all cases. The average scan time per slice for conventional iPAT 2, conventional T-PAT 4 and iterative T-PAT 4 were for patients 7.7 ± 1.5 sec, 5.6 ± 1.5 sec and 2.9 ± 1.5 sec and for the volunteers 9.8 ± 1.5 sec, 3.2 ± 1.5 sec and 3.0 ± 1.5 sec, respectively. The results in scan time are illustrated in Figure 1. In both patients and volun-teers, conventional iPAT 2 were signifi-cantly longer than both conventional T-PAT 4 and iterative T-PAT 4 techniques (p < 0.001 for each group).

The results for ejection fraction (EF) for all three imaging techniques are provided in Figure 2. The average EF for conventional T-PAT 4 was slightly lower than that measured for con-ventional iPAT 2 and iterative T-PAT, but the group size is relatively small (9 subjects) and this difference was not significant (p = 0.34 and p = 0.22 respectively).There was no statisti-cally significant difference in ejection fraction between the conventional iPAT 2 and the iterative T-PAT 4 sequences (p = 0.48).

The results for image quality, noise and artifact are provided in Figure 3. The iterative T-PAT 4 images had com-parable image quality, noise and arti-fact scores compared to the conven-tional iPAT 2 images. The conventional T-PAT 4 images had lower image qual-ity, more artifacts and higher noise compared to the other techniques.

Figures 4 and 5 show an example of 4-chamber and mid-short axis images from all three techniques in a patient with basal septal hypertrophy. In both series’, the conventional iPAT 2 and iterative T-PAT 4 images are compara-ble in quality, while the conventional T-PAT 4 image is visibly noisier.

Discussion

This study compares a novel acceler-ated segmented cine TrueFISP tech-nique to conventional iPAT 2 cine TrueFISP and T-PAT 4 cine TrueFISP in a cohort of normal subjects and patients. The iterative reconstruction technique provided comparable mea-surements of ejection fraction to the clinical gold standard (conventional iPAT 2). The accelerated segmented cine TrueFISP with T-PAT 4, which was used as comparison technique, produced slightly lower EF values compared to the other techniques, although this was not found to be statistically significant. The iterative reconstruction produced comparable image quality, noise and artifact scores to the conventional reconstruc-tion using iPAT 2. The conventional T-PAT 4 technique had lower image quality and higher noise scores com-pared to the other two techniques.

The iterative T-PAT 4 segmented cine technique allows for greater than 50% reduction in acquisition time for comparable image quality and spatial resolution as the clinically used iPAT 2 cine TrueFISP technique. This itera-tive technique could be extended to permit complete heart coverage in a single breath-hold thus greatly sim-plifying and shortening routine clini-cal cardiac MRI protocols, which has been one of the biggest obstacles to wide acceptance of cardiac MRI. With a shorter cine acquisition, additional advanced imaging techniques, such as perfusion and flow, can be more readily added to patient scans within a reasonable protocol length.

Single slice scan time in patients and volunteers. There was a statistically significant reduction in scan time compared to the standard iPAT2 for both TPAT4 acceleration and iterative reconstruction TPAT4 acceleration.

1Qualitative scores in patients and volunteers. Image quality was highest and noise and artifact were lowest with iterative T-PAT 4 and conventional iPAT 2 compared to conventional T-PAT 4.

3

full potential of image compression during the acquisition of raw input data. In the case of highly subsam-pled input data, a non-linear iterative optimization avoids sub-sampling artifacts during the process of image reconstruction. The resulting images represent the best solution consis-tent with the input data, which have a sparse representation in a specific transform domain. In the most favor-able case, residual artifacts are not visibly perceptible or are diagnosti-cally irrelevant.

0Conventional iPAT 2

Scan

Tim

e (s

ec)

Conventional T-PAT 4 Iterative T-PAT 4

2

4

6

8

10

12

Standard iPAT 2 T-PAT 4 Acceleration Iterative Reconstruction T-PAT 4 Accel.

0

1

2

3

4

5

Quality Noise Artifact

1 3

Ejection fraction in volunteers. Quantitatively measured ejection fractions were comparable across all three techniques.

2

40,00

45,00

50,00

55,00

60,00

65,00

Conventional iPAT 2

Ejec

tio

n F

ract

ion

(%

)

Conventional T-PAT 4 Iterative T-PAT 4

2

Technology Cardiovascular Imaging


Cardiovascular Imaging Technology


There are currently some limitations to the technique. Firstly, the use of SENSE implies that aliasing artifacts can occur if the field-of-view is smaller than the subject, which is sometimes difficult to avoid in the short axis orientation. But a solution to this is promised to be part of a future release of the current proto-type. Secondly, the image reconstruc-tion times of the current implemen-tation seems to be prohibitive for routine clinical use. However, we anticipate future algorithmic

Contact

Maria Carr, RT (CT)(MR)CV Research TechnologistDepartment of RadiologyNorthwestern UniversityFeinberg School of Medicine737 N. Michigan Ave. Suite 1600Chicago, IL 60611USAPhone: +1 [email protected]

References 1 Liu J, Rapin J, Chang TC, Lefebvre A,

Zenge M, Mueller E, Nadar MS. Dynamic cardiac MRI reconstruction with weighted redundant Haar wavelets. In Proceedings of the 20th Annual Meeting of ISMRM, Melbourne, Australia, 2002. p 4249.

2 Candes EJ, Wakin MB. An Introduction to compressive sampling. IEEE Signal Processing Magazine 2008. 25(2):21-30. doi: 10.1109/MSP.2007.914731.

improvements with increased compu-tational power to reduce the recon-struction time to clinically acceptable values.

Of course, iterative reconstruction techniques are not just limited to cine imaging of the heart. Future work may see this technique applied to time intense techniques such as 4D flow phase contrast MRI and 3D coronary MR angiography, making them more clinically applicable. Furthermore, higher acceleration rates might be achieved by using an incoherent sampling pattern [9].

With sufficiently high acceleration, the technique can also be used effectively for real time cine cardiac imaging in patients with breath-holding difficul-ties or arrhythmia. Figure 6 shows that real-time acquisition with T-PAT 6 and k-t iterative reconstruction still results in excellent image quality.

In conclusion, cine TrueFISP of the heart with inline k-t-sparse iterative reconstruction is a promising tech-nique for obtaining high quality cine images at a fraction of the scan time compared to conventional techniques.

Acknowledgement

The authors would like to thank Judy Wood, Manger of the MRI Department at Northwestern Memorial Hospital, for her continued support and collabo-ration with our ongoing research through the years. Secondly, we would like to thank the magnificent Cardio-vascular Technologist’s Cheryl Jarvis, Tinu John, Paul Magarity, Scott Luster for their patience and dedication to research. Finally, the Resource Coordi-nators that help us make this possible Irene Lekkas, Melissa Niemczura and Paulino San Pedro.

3 Block KT, Uecker M, Frahm J. Unders-ampled Radial MRI with Multiple Coils. Iterative Image Reconstruction Using a Total Variation Constraint. Magn Reson Med 2007. 57(6):1086-98.

4 Lustig M, Donoho D, Pauly JM. Sparse MRI: The application of compressed sensing for rapid MR imaging. Magn Reson Med 2007. 58(6):1182-95.

5 Liang D, Liu B, Wang J, Ying L. Acceler-ating SENSE using compressed sensing. Magn Reson Med 2009. 62(6):154-84. doi: 10.1002/mrm.22161.

6 Lustig M, Pauly, JM. SPIRiT: Iterative self-consistent parallel imaging reconstruction from arbitrary k-space. Magn Reson Med 2010. 64(2):457-71. doi: 10.1002/mrm.22428.

7 Beck A, Teboulle M. A fast iterative shrinkage-thresholding algorithm for linear inverse problems. SIAM J Imaging Sciences 2009. 2(1): 183-202.

8 Dykstra RL. An algorithm for restricted least squares regression. J Amer Stat Assoc 1983 78(384):837-842.

9 Schmidt M, Ekinci O, Liu J, Lefebvre A, Nadar MS, Mueller E, Zenge MO. Novel highly accelerated real-time CINE-MRI featuring compressed sensing with k-t regularization in comparison to TSENSE segmented and real-time Cine imaging. J Cardiovasc Magn Reson 2013. 15(Suppl 1):P36.


Technology Cardiovascular Imaging Cardiovascular Imaging Technology

Four chamber cine TrueFISP from a normal volunteer. (4A) Conventional iPAT 2, acquisition time 8 s. (4B) Conventional T-PAT 4, acquisition time 3 seconds. (4C) Iterative T-PAT 4, acquisition time 3 seconds.

4

End-systolic short axis cine TrueFISP images from a patient with a history of myocardial infarction. A metal artifact from a previous sternotomy is noted in the sternum. There is wall thinning in the inferolateral wall with akinesia on cine views, consistent with an old infarct in the circumflex territory. (5A) Conventional iPAT 2, (5B) conventional T-PAT 4, (5C) iterative T-PAT 4.

5

4A 4B 4C

5A 5B 5C

Real-time cine TrueFISP T-PAT 6 images reconstructed using (6A) conventional, and (6B) iterative techniques.6

6A 6B


Introduction

Hypertrophic cardiomyopathy (HCM) is a common condition causing left ventricular outflow obstruction, as well as cardiac arrhythmias. Cardiac MRI is a key modality for evaluation of HCM. Apart from estimating left ventricular (LV) wall thickness, LV function and aortic flow, MRI is capa-ble of estimating the late gadolinium enhancement in affected myocardium, which has been shown to have a direct correlation with incidence and

Combined 18F-FDG PET and MRI Evaluation of a case of Hypertrophic Cardiomyopathy Using Simultaneous MR-PETIhn-ho Cho, M.D.; Eun-jung Kong, M.D.

Department of Nuclear Medicine, Yeungnam University Hospital, Daegu, South Korea

Patient history

A 25-year-old man presented to the cardiology department with inciden-tal ECG abnormality after fractures to his left 2nd and 4th fingers. Although he had not consulted a doctor, he had been suffering from mild dyspnea with chest discomfort at rest and exacerbation at exercise since May 2012. Echocardiography revealed non-obstructive hypertrophic cardio-myopathy (Maron III) with trivial MR. The patient was referred for a simul-taneous MR-PET study for 18F-FDG PET and cardiac MRI with Gadolinium (Gd) contrast for evaluation of the morphological and metabolic status of the hypertrophic myocardium.

The patient was injected with 10 mCi 18F- FDG following glucose loading. Simultaneous MR-PET study per-formed on a Biograph mMR was started one hour following tracer injection. Following standard Dixon sequence acquisition for attenuation correction, the comprehensive car-diac MRI sequences were acquired including MR perfusion after Gd con-trast infusion, as well as post contrast late Gd enhancement studies. Static 18F-FDG PET was acquired simultane-ously during the MRI acquisition.

Discussion

The late Gd enhancement within the hypertrophic septum along with the non-uniform glucose metabolism demonstrated by the patchy 18F-FDG uptake within the hypertrophic septum exactly corresponding to the area of Gd enhancement reflect myocardial fibrosis within the asymmetric septal hypertrophy. Myocardial fibrosis and the presence of late Gd enhancement on MRI has been shown to be associ-ated with increased risk of cardiac arrhythmia [1] as evident from the symptoms of this patient.

severity of arrhythmias in HCM [1]. In patients with HCM, late gadolinium enhancement (LGE) on CE-MRI is pre-sumed to represent intramyocardial fibrosis. PET myocardial per fusion studies have shown slight impairment of myocardial blood flow with phar-macological stress in hypertrophic myocardium in HCM, presumably related to microvascular disease [2]. 18F-FDG PET has been sporadically studied in HCM, mostly for evalua-

tion of the metabolic status of the hypertrophic myocardial segment, espe-cially after interventions such as trans-coronary ablation of septal hypertro-phy (TASH) [3] or to demonstrate partial myocardial fibrosis [4]. This clinical example illustrates the value of integrated simultaneous 18F-FDG PET and MRI acquisition performed on the Biograph mMR system.

Short-axis views of end diastole and end systole at 3 different sections in the left ventricle obtained from gated TrueFISP cine MRI acquisitions performed on Biograph mMR. Note the thick hypertrophic septum (white arrow), which demonstrates the degree of asymmetric septal hypertrophy.

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Simultaneous MR-PET acquisition provides combined acquisition of both modalities, thereby ensuring accurate fusion between morphologi-cal and functional images due to simultaneous PET acquisition for every MR sequence. The exact coregistra-tion of the patchy 18F-FDG uptake in the area of Gd enhancement within the hypertrophic upper septum reflects the advantage of simultane-ous acquisition.

End diastolic and end systolic views of 2-chamber and 4-chamber views obtained from gated cine TrueFISP acqui-sitions showing thickness of the asymmetric septal hyper-trophy (white arrow).

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Static 18F-FDG PET images in short-axis, horizontal long-axis and vertical long- axis views demonstrating normal uptake in the LV myocardium except the non-uniform uptake pattern in the hypertro-phied septum (white arrows). LV cavity size appears normal.

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Cardiovascular Imaging Clinical


Clinical Cardiovascular Imaging

32 MAGNETOM Flash | 1/2014 | www.siemens.com/magnetom-world Reprinted from MAGNETOM Flash 5/2013 Reprinted from MAGNETOM Flash 5/2013

Contact

Ihn-ho Cho, M.D.Department of Nuclear MedicineYeungnam UniversityCollege of MedicineDaegu Hyunchungro 170South [email protected]

References 1 Rubinstein et al. Characteristics and

Clinical Significance of Late Gadolinium Enhancement by Contrast-Enhanced Magnetic Resonance Imaging in Patients With Hypertrophic Cardiomyopathy. Circ Heart Fail. 2010;3:51-58.

2 Bravo et al. PET/CT Assessment of Symptomatic Individuals with Obstructive and Nonobstructive Hypertrophic Cardio-myopathy. J Nucl Med 2012; 53:407–414.

Transverse, short-axis and vertical long-axis MR and fused MR-PET images show hypertrophied septum (white arrows) and normal thickness of rest of left ventricular myocardium with corresponding normal 18F-FDG uptake. The T2-weighted STIR (fat suppression) image shows slight hyperintensity in the middle of the hyper-trophied septum which shows corresponding non-uniformity in 18F-FDG uptake.

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Post-contrast MR short-axis images demonstrate late Gd enhancement within the hypertrophied septum (white arrow), which shows corresponding non-uniform patchy uptake of 18F-FDG.

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T2 HASTE T2 STIR T1 FAT SAT

4 Funabashi N et al. Partial myocardial fibrosis in hypertrophic cardiomyopathy demonstrated by 18F-fluoro-deoxy-glucose positron emission tomography and multislice computed tomography. Int J Cardiol. 2006 Feb 15;107(2):284-6.

3 Kuhn et al. Changes in the left ventricular outflow tract after transcoronary ablation of septal hypertrophy (TASH) for hypertrophic obstructive cardiomy-opathy as assessed by transoesophageal echocardiography and by measuring myocardial glucose utilization and.perfusion. European Heart Journal (1999) 20, 1808–1817.


Clinical Cardiovascular Imaging Further Reading


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Cardiac MRI is the main investigation modality for a wide range of clinical applications and has emerged as a virtual ‘one-stop-shop’ for imaging conditions such as Cardiomyopathies.

CMR has added uniquely to the methods for non-invasive assessment of myocardial viability by a combina-tion of cine imaging and delayed hyper-enhancement. CMR provides excellent depiction of pericardium in conditions such as pericarditis,

pericardial effusions, and masses. It provides optimal assessment of the location, functional characteristics, and soft tissue features of cardiac tumors, allowing accurate differen-tiation of benign and malignant lesions.

MRI is ideally suited to serve as the primary imaging modality in patients with congenital heart disease due its non-invasive and biologically harm-less nature, and its ability to provide

accurate anatomical and functional information. Several investigators have confirmed the SNR advantages of CMR at 3T. These indicate an overall quan-titative improvement in SNR and CNR, thus improving imaging capabilities.

Dr. Bidarkar and colleagues (Depart-ments of Radiology and Cardiology, Jupiter Hospital, Thane, Maharashtra, India) illustrate 80 cases of cardiac MRI imaged between January 2012 and August 2013 on a 3T MAGNETOM Verio.

Cardiac MRI at 3T: An Indian Experience of 80 Cases

Contrast-enhanced study of the LV myxoma.(18E, F) PSIR images acquired 5 minutes and 15 minutes post Gd adminis-tration reveal minimal to no enhancement in the 5 min scan and intense homog-enous enhancement in the delayed scan (solid white arrows).

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Congenital heart diseases

Congenital heart disease is a com-mon clinical entity and occurs in 0.8% of newborns [23]. Major advances in hardware design, new pulse sequences, and faster image reconstruction techniques allow rapid high resolution imaging of complex cardiovascular anatomy and physiology [24].

In our study, we imaged one 9-year-old male patient with complaints of progressive dyspnoea. Since contact of patients with CHDs referred for cardiac MRI exam is limited, we frag-mented a single case of complicated CHD to demonstrate various cardiac anomalies.

The CMR study demonstrated the following cardiac anomalies:

• Ventricular septal defect: A com-mon congenital heart disease clas-sified into membranous, muscular,

endocardial cushion defects, and conal [23] (Fig. 21A).

• Atroial septal defect: The main types of ASD are secundum (middle of atrial septum) as seen in figure 21B, sinus venosus (at junction of SVC and right atrium superiorly), and primum (near the AV valves) [23].

• Patent ductus arteriosus: PDA is the persistence of the 6th aortic arch and accounts for 10% of congenital heart disease. MRI demonstrates a persistent connection between the origin of left pulmonary artery to the descending aorta just beyond origin of the left subclavian artery [23] as seen in figure 22.

• Transposition of great arteries: The most common congenital heart lesion found in neonates, found in 5–7% of congenital cardiac malfor-mations. Congenitally-corrected

transposition refers atrioventricular discordance, ventricular inversion transposition, and inversion of great arteries [25] (Fig. 19).

Also observed in the same patient was situs inversus as shown in figure 20.

Limitations

A few technical limitations we encoun-tered during our study on a 3T MRI were:

• Inability to achieve optimal myocar-dial nulling: Optimal TI scout was not obtained in three of our patients despite repeated attempts

• Exaggerated flow artifacts: Flow arti-facts seemed to be more pronounced in areas of turbulent blood flow.

These technical issues have been for-warded to the Siemens application team and are currently under review. The team has in the past overcome many technical challenges of cardiac

Coronal T2-weighted image shows liver situated on left side of the abdomen – situs inversus.

20 Figure 21A: Shows ventricular septal defect (arrow).(21B) Shows atrial septal defect, secundum type (arrow).

21

(22A, B) Demonstrate persistent ductus arteriosus (PDA) connecting aorta to pulmonary artery.

22

MRI on 3T due to high gradient factors in comparison with 1.5T, and opti-mized the protocol of cardiac MRI on 3T. With this experience, the team appears confident of being able to pro-vide a solution to these limitations in the near future.

Conclusion

Cardiac MRI forms a mainstay investi-gation modality for a wide range of clinical applications and has emerged as a virtual ‘one-stop’ for imaging conditions like Cardiomyopathies [11].

CMR has added uniquely to the meth-ods for non-invasive assessment of myocardial viability by a combination of cine imaging and delayed hyper-enhancement (LGE).

18E 18F

Figure 19A: Shows right sided aortic arch (asterisk). (19B) Shows that the aorta arises from the morpho-logical right ventricle (curved arrow).

19

19A 19B

(22C) Demonstrates multiple aortopulmonary collaterals (MAPCAs) (red arrows).(22D) Shows the atretic pulmonary trunks and main branch pulmonary arteries measuring 4 mm in diameter (yellow asterisk).

20 21A 21B

22A 22B

22C 22D



46-year-old asymptomatic male patient with a family history of sudden cardiac deaths came to our institution for CMR evaluation.(15A, B) SSFP short axis images reveal severe non-compaction of the apex, mid lateral and mid anterior walls with a ratio of NC/C being 2.7 suggestive of non-compaction CMP. Left atrial dilatation was also observed.

15

Another case of non-compaction CMP in a 28-year-old post-partum female with mild dyspnoea on exertion.(16A, B) SSFP 4-chamber view and short axis images reveal moderate cardio-megaly with non-compaction seen along the lateral, inferior and posterior walls and the apex (white solid arrows).

16

Figures 15, 16 demonstrate the imag-ing characteristics in non-compaction CMP.

Cardiac masses

CMR is widely recognised as the imag-ing modality of choice in evaluation of cardiac masses. Invasion in to adjacent structures, precise compartmental localisation can be easily accomplished narrowing the differential diagnosis [9].

1) Thrombus: a common differential diagnosis for cardiac tumors is intracardiac thrombus.

Thrombi may appear isointense or slightly hyperintense relative to the myocardium on black blood pre-pared HASTE images [21] .Contrast-

enhanced MRI enables differentia-tion between thrombus and surrounding myocardium as throm-bus being avascular is character-ized by lack of contrast uptake. Rarely, large chronic thrombi may show peripheral enhancement and be diagnostically challenging [17].

Figure 17 shows a case of a patient suspected to have a LV clot (on echocardiography), confirmed on CMR.

2) Cardiac myxomas: These account for 20–25% of cardiac tumors. The most common locations are in the left atrium (60–75%), right atrium (20–28%), but rarely in both the atria and ventricles [17].

Their contours are round or oval, sometimes lobulated with a smooth surface and a narrow pedicle. They have a gelatinous structure and may be relatively high in signal on SSFP and static images. They typi-cally demonstrate heterogeneous enhancement on delayed-enhance-ment images [9] (Fig. 18).

We encountered one patient referred for a CMR for assessment of a mass attached to the inter-ventricular septum (as seen on echocardiography). Although the location was uncommon, the mass showed morphologic and enhance-ment characteristics of a myxoma and was diagnosed as such.

LV clots in a 65-year-old male patient with dyspnoea.(17A, B) PSIR images acquired 15 minutes post Gd administration reveal transmural LGE in the apex and the anteroseptal wall suggestive of non-viable myocardium in the LAD. A layered non-enhancing clot is seen at the apex adjacent to the akinetic apical myocardium (thin yellow arrows).

17

55-year-old male patient with a history of recurrent TIAs for CMR evaluation. (18A, B) SSFP 4-chamber and short axis views reveal a nodular soft tissue mass adherent to the IV septum (solid white arrows).

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(15C, D) PSIR images acquired 15 minutes after Gd administration showed moderate patchy LGE involving the anterior wall and interventricular septum, predominantly at the RV insertion sites (asterisk in C).



15A 15B

15C 15D

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16C 16D (16C, D) PSIR images acquired 15 minutes post Gd administration reveal mild subendocardial LGE in the septal region, anterior and posterior walls, not conforming to any vascular territory (thin yellow arrows).

17A 17B

18A 18B

18C 18D (18C, D) T1-weighted short axis and STIR 4-chamber views respectively demonstrate the mass which appears isointense to the myocardium on T1w and hyperintense on STIR images (myxoid content) suggestive of LV myxoma (solid red arrows).

NC/C ratio = 2.7

21-year-old male patient with complaints of progressive dyspnoea since childhood was referred for CMR.(12A, B) SSFP 4- and 2-chamber views reveal moderate cardiomegaly.

12

Example of an advanced case of idiopathic dilated cardiomyopathy in a 34-year-old female patient with dyspnoea and intermittent chest pain.(13A, B) SSFP 4- and 2-chamber views respectively, show dilatation of all the cardiac chambers.

13

myocytes. The abnormalities seen in primary dilated cardiomyopathies are fairly similar to those seen as an end result of CAD (ischemic cardiomyopa-thy) [7]. LGE can be seen in both entities. However, ischemic injury pro-gresses as a wavefront from the subendocardium to epicardium and shows a territorial distribution (Fig. 11). Hyper-enhancement patterns that spare the subendocardium and are limited to middle or epicardial portions of the LV, are clearly in a non-CAD dis-tribution [9] (Fig. 12).

Restrictive cardiomyopathy

Restrictive CMP is characterised by reduced ventricular filling and diastolic volume, leading to atrial dilatation and venous stasis, with preserved systolic function. Restrictive CMP may be idio-pathic, secondary to infiltrative and storage disorders (such as amyloidosis and sarcoidosis) or associated with myocardial disorders such as hypereo-sinophilic syndrome.

Cardiac MRI is a fundamental diagnos-tic tool because it helps in differentiat-ing between restrictive CMP and con-strictive pericarditis which have

different therapeutic approaches. Although reduced ventricular filling and diastolic volumes may be a fea-ture of both, pericardial thickening > 4 mm is typical of pericarditis [12] (Fig. 5).

Cardiac MRI also helps in the differ-entiation between the above entities in cases with minimally thickened pericardium. Morphologic images in restrictive CMP may show atrial enlargement. Cine images allow assessment of altered diastolic ven-tricular filling. Cine MRI assessment of diastolic ventricular septal move-ments and real time MRI imaging of septal movements during respiration show that in restrictive CMP, septal convexity is maintained in all respira-tory phases, whereas in constrictive pericarditis, septal flattening can be seen in early inspiration [12] (Fig. 6). The issue of LGE in idiopathic restric-tive CMP has not been specifically addressed in the literature, although late enhancement patterns in specific causes of restrictive CMP have been described [12].

Figure 14 illustrates a case of Restric-tive CMP.

Non-compaction cardiomyopathy

Left ventricular myocardial non com-paction (LVNC) is a recently recog-nised form of primary and genetic cardiomyopathy. Also known as spongy myocardium, LVNC is charac-terised by prominent ventricular myocardial trabeculations and deep intertrabecular recesses communicat-ing with the ventricular cavity. LVNC is secondary to arrest in the normal process of myocardial compaction during fetal life.

CMR can clearly display the com-pacted and non-compacted myocar-dium layers better than echocardiog-raphy [13].

In a normal ventricle, the proportion of ventricular wall formed by trabec-ulations never exceeds thickness of the compacted layer. In LVNC, the thickness of non-compact myocardium is greater than that of compacted layer which is thinned. It is suggested that a NC/C ratio > 2.3 in diastole dis-tinguishes pathological non compac-tion from pronounced trabeculae seen in other CMPs [13].

(12C, D) PSIR images acquired 15 minutes post Gd administration reveal no LGE in the myocardium to suggest fibrosis. The patient was diagnosed as idiopathic/non ischaemic dilated cardiomyopathy.

(13C, D) PSIR images acquired 15 minutes post Gd administration reveal diffuse subendocardial LGE in the septal, anterior and posterior walls (thin yellow arrows). Mild pericardial effusion can be appre-ciated on the short axis view (white solid arrow).

12A 12B

12C 12D

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13C 13D

13-year-old female patient with a history of progressive dyspnoea.(14A) SSFP images in the horizontal long axis view reveals significant bi-atrial dilatation (thin yellow arrows) with normal sized ventricular cavities.(14B, C) PSIR images acquired 15 minutes post Gd administration demonstrate no enhancement in the myocardium.Findings were suggestive of restrictive cardiomyopathy.

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14A 14B 14C



32-year-old male patient with a history of sudden atrial fibrillation was evaluated by CMR.(9A, B) SSFP sequential 3-chamber SSFP cine MR images in the diastolic and mid-systolic phases respectively reveal LV hyper-trophy (double headed arrow in 9B) and LA dilatation (thin yellow arrow). (9C) Systolic phase demonstrates anterior motion of the mitral leaflet causing obstruction at the LVOT (solid yellow arrow) with resultant turbulent jets in the LA and at the LVOT – systolic anterior motion (SAM).

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Preclinical HCM. Shown are images of a 35-year-old asymptomatic male patient with a family history of HCM. (10A, B) SSFP sequential 4-chamber and short axis SSFP cine MR images reveal mid biatrial dilatation (thin yellow arrows) with no significant myocardial hypertrophy (double headed blue arrows).

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entities. Mass-like HCM more pre-cisely parallels the homogenous signal intensity characteristics and perfusion of adjacent normal myo-cardium, while tumors show hetero-geneous signal intensity, enhance-ment, and perfusion characteristics that differ from those of remainder of the left ventricle [20].

6) Pre-clinical HCM Screening of family members of patients with HCM is important

because first-degree relatives of such patients have a 50% chance of being a gene carrier.

Cardiac MRI is a useful screening tool in patients with a normal LV thickness who have symptoms of HCM or in asymptomatic HCM mutation carriers. However, dis-ease expression can be heteroge-nous and varied, even with the same mutation; hence follow-up screening needs to be considered

every 2 to 5 years, particularly in young patients [20].

Figure 10 illustrates CMR finding s in a 36-year-old asymptomatic male patient with a family history of HCM.

Dilated cardiomyopathy (DCM)

These are a common cause of con-gestive heart failure characterized by fibrosis and decreased number of

CMR of a 65-year-old male patient with a history of anterior wall MI. (11A, B) SSFP 4- and 2-chamber chamber views reveal moderately dilated left ventricle.(11B, C) PSIR images acquired 15 minutes post Gd administration reveals transmural LGE in the antero-septal wall, suggestive of non-viable myocardium in the LAD and RCA territories (thin yellow arrows).The patient was diagnosed as ischaemic dilated cardiomyopathy.

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9A 9B 9C

(10C, D) PSIR images acquired 15 minutes post Gd administration reveal LGE along the inferior and posterior walls suggestive of early fibrosis.

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10C 10D

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11C 11D



C) Cardiomyopathies (CMPs) Cardiomyopathies are chronic progressive diseases of the myo-cardium with often genetic / inflammation / injury as factors contributing to their development [7]. Cardiac MRI has become an important tool for the diagno-sis and follow-up of patients with cardiomyopathies. It has a unique ability to differentiate between different enhancement patterns in diseased myocardium on inversion recovery delayed Gadolinium-enhanced images, making it suit-able for evaluation of cardiomyop-athies [18].

Hypertrophic cardiomyopathy (HCM): A genetically-acquired condition resulting from abnormal-ity in the sarcomere, it results in hypertrophy of the myocardium.

MRI has proven to be an important tool in the evaluation of patients with suspected HCM since it helps readily diagnose those with phe-notypic expression of the disorder and potentially identify the subset of patients at risk of sudden car-diac deaths. MRI is also capable of detecting regions of localised hypertrophy that are missed by echocardiography.

A significant percentage of patients with HCM demonstrate LGE char-acteristically involving regions of hypertrophy, junctions of interven-tricular septum and RV free wall [9]. LGE is usually patchy and mid-wall in location. LGE in HCM also has a predilection for the anterior and posterior insertion points. An exception to this is in areas of burnt-out myocardium where the left ventricular wall is thinned and enhancement is full thickness [18].

The presence of LGE denotes scar tissue, a potential nidus for fatal arrhythmias. CMR can be used to follow the patients following ventricular septal resection / percu-taneous ablation [7].

Phenotypes of HCM1) Asymmetric HCM

This is the most common morpho-logic presentation of HCM, the anteroseptal being the commonly

hypertrophied segment. Asymmet-ric septal wall hypertrophy causes LVOT obstruction in 20–30% of cases.

Asymmetric / septal HCM may be diagnosed when septal thickness is greater than or equal to 15 mm or when the ratio of septal thick-ness to the thickness of inferior wall of the left ventricle is greater than 1.5 at the midventricular level [20].

Abnormalities of the mitral valve may occur due to primary abnor-mality of the valve itself or due to LVOT obstruction. Systolic anterior motion of the mitral valve (SAM) is a phenomenon in which a por-tion of the anterior leaflet of the mitral valve distal to the coaptation gets displaced / pulled in to the LVOT by venture or drag forces, leading to transient LVOT obstruc-tion [7] (Fig. 9). Over time, the systolic anterior motion of the mitral valve leads to sub-aortic mitral impact lesion on the sep-tum which undergoes fibrosis; thickening of mitral leaflet and chordae from the resultant trauma; a posteriorly directed mitral regur-gitant jet in to the left atrium and a systolic gradient along the LVOT [18].

Patients with LVOT obstruction unresponsive to medical therapy (5%) are candidates for surgical myectomy or septal alcohol abla-tion [20]. Our patient, however, was put on medical therapy.

2) Apical HCM The apical variant of HCM shows an absolute apical thickness of > 15 mm or a ratio 1.3 to 1.5. More subjective criteria are the oblitera-tion of LV apical cavity in systole and failure to identify a normal pro-gressive reduction in LV wall thick-ness towards the apex.

The left ventricle shows a charac-teristic ‘spade-like’ configuration on vertical long axis views.

An apical aneurysm formation with delayed enhancement is sometimes seen referred to as the ‘burnt-out apex’ resulting from ischemia due to reduced capillary

density resulting in ischemic fibro-sis. Similar appearance of ‘burnt-out apex’ is also seen in HCM causing mid- ventricular obstruction with apical aneurysm formation, as described in figure 8.

The LV apex may not be assessed well with echocardiography leading to false negative interpretations. Hence cardiac MRI is strongly rec-ommended as optimal imaging modality for evaluation of apical HCM [20].

3) HCM with mid-ventricular obstruction A variant of asymmetric HCM pre-dominantly involving the middle third of the left ventricle may result in severe mid-ventricular narrowing and obstruction. This condition may be associated with formation of an apical aneurysm which is thought to result from increased generation of systolic pressures within the apex from the mid-ventricular obstruction [18] (Fig. 8).

4) Symmetric HCM This variant is encountered in about 42% of HCM cases and is character-ized by a concentric LV hypertrophy with a small cavity dimension and no evidence of a secondary cause. This entity has to be differentiated from other causes of diffuse LV wall thickening including athlete’s heart, amyloidosis, sarcoidosis, Fabry’s dis-ease, and secondary adaptive pat-tern of LV hypertrophy due to hyper-tension or aortic stenosis, since the treatment strategies differ. Cardiac MRI is known to play an important role in differentiating other causes of myocardial hypertrophy from HCM because of the unique ability of DE MRI imaging to characterize differ-ent enhancement patterns in dis-eased myocardium [20]. Figure 7 illustrates a case of concentric HCM in a symptomatic patient.

5) Mass-like HCM Mass-like HCM manifests as a mass-like hypertrophy because of focal segmental location of myocardial disarray and fibrosis which may be differentiated from neoplastic masses. MR imaging with first pass perfusion and DE technique helps to differentiate between the two

Concentric HCM in a symptomatic 35-year-old male patient.(7A, B) Short axis and vertical long axis SSFP images show symmetrically thickened LV walls (arrows) with atrial dilatation.

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HCM with mid-ventricular obstruction. CMR evaluation of a 55-year-old male patient with a family history of sudden cardiac deaths.(8A, B) Horizontal long axis SSFP cine MR images reveal significant hypertrophy of the LV myocardium (16–17 mm width). The thickened myocardium (asterisk in 8A) causes mid-cavity obstruction with apical thinning and outpouching resulting in a ‘dumbbell shaped LV’.(8C, D) PSIR images acquired 15 minutes post Gd administration show subendocardial LGE (solid white arrows), around 50% in the proximal areas and transmural in the apex (burnt out apex) suggestive of ischaemic fibrosis.

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(7C, D) PSIR images acquired 15 minutes post Gd administration reveal patchy transmural LGE in the thickened IV septum and RV insertion sites, suggestive of scarred tissue (solid white arrows).

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7C 7D

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3A, B, 4C, 2C views reveal moderate dilated LA and LV with thinning of LV anterior wall, interventricular regions and the apex. Aneurysmal dilatation of the thinned apex is seen (thin yellow arrows).

3

(3B, C) PSIR images taken 15 minutes post Gd administration reveal transmural LGE in these (solid white arrows) areas suggestive of non-viable myocardium in the LAD territory.

Figure 4 demonstrates CMR findings in acute myocardial infarction, seen as edema on T2-weighted images and perfusion defect (microvascular obstruction) on the post-contrast PSIR images.

B) Pericardium MRI is particularly suitable for eval-uation of pericardial inflammation,evaluation of small or loculatedpericardial effusions, functionalabnormalities caused by pericardialconstriction, and for characteriza-tion of pericardial masses [19].

The diagnosis of constrictive peri-carditis is greatly aided by excellentdepiction of pericardium at MRimaging. Normal pericardium is lessthan 3 mm thick. Pericardial thick-ness of 4 mm or more indicatesabnormal thickening, and whenaccompanied by clinical signs ofheart failure is highly suggestive ofconstrictive pericarditis [10]. Peri-cardial thickening may be limited tothe right side of the heart or evena smaller area such as the rightatrio-ventricular groove.

In chronic constrictive pericarditisthere is typically bi-atrial enlarge-ment. Also, the central cardiovascu-lar structures show a characteristicmorphology with the right ventricleshowing a narrow tubular configu-ration [10].

Cine images are useful to judgethe pathophysiologic consequenceof pericardial thickening and the‘Diastolic Septal bounce’ [7].

Diastolic septal bounce is a hemo-dynamic hallmark of ventricularconstriction seen due to increasedinterventricular dependence anddemonstrated as abnormal ventric-ular septal

motion towards the left ventriclein early diastole during onset ofinspiration [9]. This finding is help-ful in distinguishing between con-strictive pericarditis and restrictivecardiomyopathy [9] (Fig. 6).

Figure 5 illustrates the characteristicfindings of thickened pericardiumand diffuse pericardial enhancementin a case of constrictive pericarditis.

42-year-old male patient with symptoms of acute myocardial infarction.(4A, B) SSFP 4-chamber and short axis images reveal mildly thickened interventricular septum with subtle hyperintense areas suggestive of post-MI edema (solid red arrows).

4

35-year-old male patient on treatment for pulmonary Koch’s disease, presented with dyspnoea. (5A, B) Horizontal long axis black and white blood images reveal thickened pericardium (6 mm).(5C, D) Post-contrast images acquired 15 minutes post Gd administration reveal diffuse pericardial enhancement consistent with the diagnosis of constrictive pericarditis.

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(4C, D) PSIR images acquired immediately post Gd administration demonstrate perfusion defect in the LAD territory corresponding to microvascular obstruction (solid white arrows).

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An example of Diastolic septal bounce. Septal flattening / inversion seen in constrictive pericarditis, since outward expansion of the right ventricle is limited by a non-compliant pericardium.(6A) Shows IV septum in mid systolic phase.(6B) Diastolic phase reveals mild leftward bowing of the septum.

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6A 6B



the LAD, 10 in the RCA and 4 in the LCX territories, corresponding to non-viable myocardium (Table 3).

11 patients demonstrated < 50% of myocardial LGE. Of these, 5 belonged to LAD territory and 2 and 4 to the LCX and RCA territories, respectively (Table 3).

On follow up, 7 patients underwent revascularisation procedures. All of these reported to experience symp-tomatic relief.

15 patients were evaluated for cardio-myopathy. All patients with CMP are managed by medical therapy and are doing well.

We evaluated 2 patients for constric-tive pericarditis. Both were started on anti-Koch’s therapy and are symp-tomatically better.

5 patients were referred for evalua-tion of cardiac masses after an echo-cardiographic study. 3 of these

had revealed a LV clot and 1 patient had demonstrated a nodular mass attached to the LV wall. One patient suspected to have a mass posterior to left atrium on echocardiography was diagnosed with straight back syndrome with the thoracic vertebral body indenting the left atrium. LV clots were confirmed on CMR and the patients were put on anticoagulation therapy.

One patient diagnosed as LV myxoma being managed on medical therapy, is doing well.

Discussion

A) Myocardial viabilityIschemic heart disease (IHD) istoday one of the leading causes ofdeath all over the world. CardiacMRI plays an important role com-plementary to other imagingmodalities in evaluation of patientswith IHD. Myocardial infarctionresults from rupture of an athero-sclerotic plaque in a coronary arteryleading to thrombus formation.The subendocardium is most vul-nerable to ischemia and an infarctexpands form subendocardiumto subepicardium [7].

Myocardial infarction, scarring and viability are simultaneously exam-ined using technique of delayed enhancement MRI.

Delayed / late gadolinium hyper-enhancement is caused by delayed washout of contrast agent from the myocardium. Delayed enhancement is performed 10–15 minutes after i.v. administration of 0.15 to 0.2 mmol/kg of gadolinium. An inversion recovery sequence is used in which normal myocardium is nulled to accentuate the delayed enhancement [7].

Both acute and chronic infarctions enhance. In acute infarctions, con-trast enters the damaged myocar-dial cells due to membrane disrup-tion (microvascular obstruction / no reflow zones). These regions are recognised as dark central areas surrounded by hyperenhanced necrotic myocardium. This finding indicates the presence of damaged microvasculature in the core of an area of infarction. The presence of

a ‘no-reflow’ zone appears to be associated with worse LV remodel-ling and outcome [7, 9]. CMR can be safely carried out in patients with acute MI and primary angio-plasty and aids in risk stratification. T2-weighted imaging allows the detection of myocardial edema, allowing for early diagnosis of myo-cardial ischemia, area at risk, and salvage [22] (Fig. 4).

In chronic infarctions, the LGE is a result of retention of contrast medium in large interstitial space between collagen fibres in the fibrotic tissue.

Stunning and hibernating myocardium

Cine imaging in combination with delayed enhancement MRI allows identification of:

1) Myocardial stunning: Stunning isdefined as post-ischemic myocardialdysfunction (seen in the setting ofacute myocardial ischemia) whichpersists despite restoration of normalblood flow. Over time there can bea gradual return of contractile func-tion depending on transmurality ofthe ischemia. If the degree of trans-murality as seen on delayedenhancement images is < 50%, themyocardial function is likely torecover.

2) Hibernating myocardium: A statein which some segments of themyocardium exhibit abnormalitiesof contractile function at rest. Thisphenomenon is clinically significantsince it manifests in the setting ofchronic ischemia that is potentiallyreversible by revascularisation. Thereduced coronary perfusion causesthe myocytes to enter into a lowenergy ‘sleep mode’ to conserveenergy. There is an inverse relation-ship between transmural extent ofhyperenhancement, and likelihoodof wall motion recovery followingrevascularisation [5].

Multiple experimental studies have demonstrated excellent spatial correla-tion between the extent of hyper-enhancement and areas of myocardial necrosis (acute MI) or scarring (chronic MI) at histopathology.

Specifically, there is an inverse rela-tionship between transmural extent of hyperenhancement and likelihood of wall motion recovery following revas-cularisation. Hence it follows that myocardial regions which show little or no evidence of hyper-enhancement (i.e. infarction) have a high likelihood of recovery, whereas regions with transmural hyperenhancement have virtually no chance of recovery [9].

Moving from a 1.5T to a 3T system involves doubling of SNR which can be used to increase either spatial or tem-poral resolution. This translates into potentially increased contrast between perfused and non-perfused images leading to increased contrast-to-noise ratio (CNR) with better LGE in setting of chronic ischemia [1].

Figures 1–3 demonstrate LGE in the RCA & LCX, LCX and LAD territories, respectively, significant other non-via-ble myocardium in these regions.

Table 3

Transmural extent

LAD LCX RCA

> 50% 30 4 10

< 50% 5 2 4

Table 4

IndicationsNumber of

patients

1) Myocardial viability 55

2) Recent MI 2

3) Cardiomyopathies 15

a) Hypertrophiccardiomyopathy

8

b) Dilatedcardiomyopathy

5

c) Non compactioncardiomyopathy

2

d) Restrictivecardiomyopathy

1

4) Cardiac masses 5

5) Congenitalheart disease

1

6) Pericardium (constrictive pericarditis)

2

Table 5 [9]: Differentiation between acute and chronic MI.

Acute MI Chronic MI

Bright on pre-contrast STIR (or T2w) imaging Not bright on pre-contrast STIR(or T2w) imaging

Walls may be thicker than usual Walls may be thinned

May have a ‘no-reflow zone’ Does not have a ‘no-reflow zone’

Diagram 1 [7]: A schematic representation of three zones of affection in case of an MI:

Myocardium protected by collateralisation

Myocardium capable of reperfusion

No reflow territory / microvascular obstruction

PSIR short axis image acquired immediately post Gd administration in a 60-year-old female patient reveals suben-docardial 1st pass defect in the lateral wall (solid white arrow).

2A

PSIR images taken 15 minutes after Gd admin-istration reveal subendo-cardial LGE with trans-mural extent suggestive of non-viable myocardium in the LCX territory (solid white arrow).

2B

2A 2B

Cardiology Clinical


Clinical Cardiology


AbstractDiagnostic clinical cardiac magnetic resonance imaging (MRI) requires an appropriate combination of temporal and spatial resolution. Cardiovascular imaging is making considerable advances toward the fulfillment of these requirements, largely because of continued improvements in MRI hardware and software. Optimal diag-nostic-quality MRI implies a balance among signal-to-noise ratio (SNR), tissue contrast, acquisition time, and spatial and temporal resolution. Mag-netic field strength is one of the major factors affecting image SNR [3]. The transition from 1.5T to 3T has resulted in faster imaging and better SNR. However, cardiac MRI protocols on 3T have not yet been optimized in the way that they have been optimized for 1.5T over the last decade.

This article illustrates 80 cases of car-diac MRI imaged on a 3T MRI system

Cardiac MRI at 3T: An Indian Experience of 80 Cases of Cardiac MRI with Review of LiteratureKalashree A. Bidarkar DNB; Nikhil Kamat, M.D., DMRD, DNB; M. L. Rokade, M.D., DNB; Nitin Burkule, M.D., DM; Shubra Gupta

Departments of Radiology and Cardiology, Jupiter Hospital, Thane, Maharashtra, India

(MAGNETOM Verio, 32-channel sys-tem) at our institution done between January 2012 and August 2013. This is probably the largest study of car-diac MRI done on a 3T in India.

Introduction

The role of magnetic resonance imaging (MRI) has significantly evolved over the last decade. MRI is now considered useful in the evalua-tion of pericardium, complex congen-ital heart disease, cardiac masses, and ischemic heart disease for myo-cardial viability, hibernating and stunned myocardium and the right ventricle.

In 2002, the US Food and Drug Administration’s (FDA) approval of 3 Tesla opened the way for multiple clinical applications. Compared to 1.5T, the higher field strength results in doubling of SNR due to increased

spin polarisation. Furthermore, imag-ing at higher field strengths with gad-olinium-based agents can produce fur-ther improvements in image contrast. Cardiac imaging at 3T is, however, noticeably different from imaging at 1.5T because of a variety of artifacts that result from susceptibility effects and augmentation of radiofrequency (RF) inhomogeneity [3].

The adoption of 3T for body applica-tions, especially cardiac applications, has been somewhat slower. The slower acceptance of 3T for cardiac applications is due to the unique chal-lenges posed by cardiac imaging: Requirement of a large field-of-view, the motion of the heart, position of the heart within the body, proximity of heart to the lungs, and high RF power deposition required in many fast car-diac imaging sequences [1]. Cardiac MRI has largely been done on a 1.5T in

India. Due to optimization done on 1.5T and apprehension of challenges on a 3T system, no significant work was done on 3T in India. We present probably the largest number of cardiac MRI cases performed till date on a 3T in India.

There are several advantages which motivate users to perform cardiovascu-lar magnetic resonance (CMR) at higher filed strengths. First, the bulk magnetisation increases as the mag-netic field strength is increased result-ing in higher SNR. Second, the increas-ing field strength increases the frequency separation of off-resonance spins. The enhanced frequency differ-ences may be exploited for improve-ment in spectroscopic imaging and potentially in fat suppression. A third advantage is increased T1 signal of many tissues, resulting in beneficial effects in some applications, such as myocardial tagging and myocardial perfusion sequences [1].

Methods and Materials

A) Patient populationEighty patients with an age rangeof 5 to 70 years with a suspectedcardiac pathology were evaluatedby cardiac MRI (CMR) at our institutefrom January 2012 to August 2013.All patients had undergone a priorechocardiography.

B) Patient preparationA detailed history was elicited fromeach patient including principalsymptoms and signs, echocardio-graphic and cardiac catheterisationdata. For all patients in this study,MR compatible electrocardiographicleads were placed in the anteriorchest wall before imaging andattached to the MR imaging unitfor electrocardiographic gating. Formost sequences, electrocardio-graphic triggering was used to syn-chronise imaging with the onsetof systole and offset cardiac motionand match each image to thedesired cardiac phase.

C) Cardiac MRI protocolCardiac MRI was performedusing a whole-body 3T scanner (MAGNETOM Verio, Siemens Healthcare, Erlangen, Germany).MR imaging protocol commenced

with a localiser using TrueFISP (steady-state free precision) sequence. A list of protocols is given in table 2. Axial and coronal scans of 5 mm slice thickness were obtained from the aortic arch to diaphragm. All diagnostic sequences were acquired in stan-dard angulations (4-, 2-chamber view and short axis) using a matrix of at least 256 × 256. Myocardial function was evaluated by cine TrueFISP sequences; T2-weighted dark blood turbo spin echo sequences were acquired 5 and 15 minutes after injection of 0.15 mmol gadolinium diethylene triamine penta-acetic acid (DTPA) (Magnevist, Schering, Berlin, Germany) per kilogram of body weight.

Inversion recovery prepared turbo sequences (FLASH and TrueFISP) were performed to visualise the myocardial and blood pool gadolinium kinetics, and to adjust inversion time. An inversion time (TI) scout was acquired and the optimal TI value was found. Endocardial counters of the left ven-tricle were manually drawn using dedicated software (Argus, Siemens Healthcare, Erlangen, Germany) to calculate end-diastolic volume, end- systolic volume, stroke volume and ejection fraction of the left ventricle [8]. In the case of evaluation of con-genital heart diseases, scans were obtained till below the diaphragm including IVC and the hepatic veins [23].

A summary of the basic cardiac protocols is presented in table 1.

Modified sequences were acquired for specific indications which have been summarised in table 2.

D) ResultsThe study comprised 80 patients.The age range was 5 to 70 years.There were 57 male and 23 femalepatients. The commonest indica-tion for a CMR study was evalua-tion of myocardial viability.

The variety of indications for which cardiac MRI was performed is summarised in table 4.

Images were analysed by one radi-ologist and one cardiologist. The

morphological information com-prised of chamber anatomy, thick-ness of the ventricular walls and assessment of presence and extent of late gadolinium hyper-enhance-ment on delayed post contrast PSIR images.

Functional information comprised of assessment of wall motion abnormalities, calculation of ejec-tion fraction and evaluation of the outflow tracts.

In cases of congenital heart dis-ease, cine imaging in horizontal long axis provided dynamic infor-mation of the cardiac size, valve morphology, wall thickness cham-ber size, and septum morphology and aortopulmonary connections [23].

55 patients were referred for eval-uation of myocardial viability. Of these, 30 showed transmural late gadolinium enhancement (LGE) in

Table 1: MR sequencing

Anatomy HASTE 2D

FunctionCine SSFP

(2CV,4CV,SA)

Morphology

T1-weighted (2CV,4CV,SA)

STIR dark blood (2CV,4CV,SA)

Fluid contentT2-weighted (2CV,4CV,SA)

Gadolinium kinetics

TI scout baseline

Delayed enhancement

IR turbo TrueFISP 2D

Abbreviations: 2D, 2 dimensional ; CV, chamber view; IR, inversion recovery; SA, short axis; TI, inversion time; STIR, Short TI Inversion Recovery; TSE, turbo spin echo

Table 2: Special considerations

Acute MIT2-weighted or STIR dark blood

Cardiac mass or thrombus

TSE dark blood T1, TSE dark

blood T2 fat sat

68-year-old male patient imaged for evaluation of myocardial viability. PSIR sequence taken 15 minutes post Gd administration reveals transmural LGE in the inferior wall conforming to RCA and the LCX territory (solid white arrows) suggestive of non-viable myocardium.

1A

Horizontal long axis view of the same patient showing the extent of transmural LGE.

1B

1A 1B

Cardiology Clinical


Clinical Cardiology


Reprinted from MAGNETOM Flash 5/2013

Molecular MRI in London Ontario

The Lawson Health Research Institute (the “Lawson”) is located within St. Joseph’s Healthcare in London Ontario, and is affiliated with West-ern University. This group received the first Biograph mMR in Canada in March 2012. With strong existing research groups in MRI and nuclear medicine this group is ideally posi-tioned to drive research and innova-tion using this platform. In advance of the installation of the hybrid molecular MR, researchers at the Lawson had been developing novel MR-based attenuation correction methods, and novel tracer develop-ments. In addition to the molecular MR this site has a PET-CT, a SPECT-CT, and an Inveon small animal PET as well as two 1.5T MAGNETOM Aera

Myocardial Tissue Imaging Using Simultaneous Cardiac Molecular MRI James A. White, M.D., FRCPC

The Lawson Health Research Institute, London, Ontario, Canada

systems, a 16.5MeV medical cyclo-tron and radiochemistry facilities.

Myocardial tissue imaging

Hybrid imaging platforms incorporat-ing PET have become available for cardiovascular imaging applications over the past decade. These platforms have been primarily aimed at provid-ing superior tissue attenuation correc-tion of the emitted photon signal and to provide spatial anatomic registra-tion for the localization of abnormal tracer signal. While this has resulted in substantial improvements in the clini-cal performance of cardiac PET, the exploitation of complementary imag-ing data has yet to be fully realized.

The recent availability of hybrid plat-forms allows for an expansive range of PET applications to be explored.

For example the capacity of cardiovas-cular MRI to provide complementary 2D and 3D morphological data with excellent soft tissue contrast and high temporal resolution is of benefit for anatomic registration and novel motion correction algorithms. However, its incremental capacity to provide exqui-site tissue characterization through intrinsic tissue contrast and altered kinetics of exogenous paramagnetic contrast is of particular interest in the context of the PET imaging environment.

Clinical adoption of myocardial tissue imaging is expanding in response to mounting evidence that the ‘health’ of myocardium strongly modulates bene-fit from heart failure therapies (phar-macologic, surgical and device-based) and is predictive of future arrhythmic events among patients with ischemic and non-ischemic cardiomyopathy [1-5]. To date, this literature has focused on isolated and disparate markers of tissue health using both PET and MRI. However, within this brief report we discuss several synergies of these platforms that hold promise towards a new era of hybrid imaging for the optimal performance of myocardial tissue imaging.

Molecular MRI in the setting of acute ischemic injury

Among those surviving acute myocar-dial infarction (AMI), appropriate myo-cardial healing is believed to be reliant upon a highly choreographed process of early inflammatory cell invasion, collagen degredation, debris removal by activated macrophages, and myo-fibroblast proliferation with reconstitu-tion of a new collagen matrix. While

The Lawson Health Research Institute.1

such findings can be characterized histologically, our capacity to quantify markers of the inflammatory process in vivo, and evaluate influences of its modulation on the remodeling process has been limited.

We have started examining this pro-cess in a canine infarct model using the Biograph mMR 3T-PET platform using simultaneous 3D LGE / 18F-FDG imaging, the latter imaged following normal myocardial glucose metabolism using intravenous heparin and lipid infusion. In these experiments we have focused on evaluating the influence of microvascular obstruction (MO) on mitigating appropriate inflammatory cell recruitment to the infarct core – a postulated mechanism of how MO may adversely impact on left ventricu-lar remodeling post infarct. Figure 2 illustrates how the region of MO can

be elegantly visualized using both LGE imaging and T1 mapping CMR techniques. 18F-FDG imaging shows intense inflammatory activity within the perfused infarct rim, however a marked reduction in activity is seen in regions of MO. This imaging may therefore provide novel insights towards mechanisms by which MO contributes to adverse outcomes fol-lowing AMI, and offers a new tool to evaluate therapies aimed at modu-lation of this pathway.

Molecular MRI in the setting of acute non-ischemic (inflammatory) injury

Both PET and CMR have been investi-gated for their diagnostic accuracy in the setting of suspected inflamma-tory cardiomyopathy – particularly among patients with known pulmo-

nary Sarcoid. While their respective diagnostic performance has been compared in the past, this remains inappropriate, as the information gathered and interpreted from each technique could not be more unique. PET imaging (typically performed using 18F-FDG following prolonged fasting, fatty meal consumption and intravenous heparin to suppress nor-mal myocardial glucose utilization) exploits the hypermetabolic signal of activated inflammatory cells (i.e. macrophages) and therefore indi-cates disease ‘activity’ among patients with active cardiac Sarcoid. In con-trast, LGE imaging indicates regions of mature granulomatous fibrosis among patients with prior or current cardiac Sarcoid. Therefore, these two commonly employed diagnostic tech-niques provide complementary but unique information.

Example of a non-reperfused myocardial infarction from LAD ligation in a canine model, imaged one week post ligation. A large area of microvascular obstruction (MO) is seen by LGE imaging with a corresponding marked prolongation of T1 shown using MOLLI-based T1 mapping. Simultaneously acquired FDG imaging (binned to cardiac phase) has been fused to both LGE imaging and raw T1 map and illustrates a marked reduction in inflammation within the region of MO. There is intense inflammatory activity evident within the perfused infarct rim.

2

LGE T1-map (raw) T1-map (color)

LGE / FDG FDG (raw) T1-map/FDG

2A 2B 2C

2D 2E 2F

Cardiology Clinical


Clinical Cardiology


1

Figure 3 illustrates the capacity of hybrid MR and PET to spatially register these techniques using simultane-ously acquired data, and potentially improve diagnostic accuracy while expanding our understanding of dis-ease pathophysiology. In this case of a 72-year-old female presenting with heart failure and non-sustained ventricular tachycardia we can iden-tify a leading edge of inflammation (intense FDG uptake) with a trailing edge of irreversible injury or ‘scar’ (indicated by hyperenhancement on LGE imaging) at the sub-epicardial zone. This approach ushers in a new era of imaging for inflammatory-mediated disease where a more com-plete spectrum of disease activity can be visualized in a single, spatially registered examination.

Molecular MRI in the setting of non-acute myocardial disease

Another clinical setting where MR and PET have established their respec-tive roles for therapeutic decision-

making is for the assessment of tissue viability in chronic ischemic cardiomyopathy. Evidence supports that both the regional reduction of FDG signal [6, 7] and regional scar transmurality by LGE are strongly predictive of absence of functional recovery following coronary revas-cularization. The performance of these studies are therefore commonly considered to be mutually exclusive, with absence of FDG signal being the sine qua non of myocardial scar, and the lack of scar by LGE imaging being equivalent to tissue health. However, it is recognized that the spatial resolution and signal-to-noise of LGE imaging is superior to FDG for the detection of subendocar-dial scar, and also for the character-ization of tissue viability among those with marked thinning of the ventricular wall [8]. Conversely, FDG-PET based metabolic abnormalities can be documented within tissue that fails to demonstrate myocardial scar on LGE MRI, lack of FDG uptake being predictive of absence of func-

tional recovery. Accordingly, the marriage of PET-based metabolic imag-ing and LGE-based scar imaging may provide a more robust platform for the prediction of improved outcomes following coronary revascularization.

In figure 4 we see a 42-year-old male referred for viability imaging prior to coronary artery bypass surgery late following myocardial infarction. Cine imaging shows a large region of thinned and akinetic myocardium in the distribution of the left anterior descending artery, this territory dem-onstrating varying degrees of trans-mural scar following gadolinium administration. Simultaneous MR and PET with 18F FDG imaging shows meta-bolic activity within non-scarred regions surrounding the infarct zone and normal metabolic tracer activity within remote myocardium.

42-year-old male with large anterior wall myocardial infarction being considered for surgical revascular-ization in the setting of triple vessel disease. Cine MRI shows akinesia of the septum and apex with a reduced ejection fraction of 32%. Late gadolinium enhancement (LGE) imaging shows a large infarct of the LAD territory with variable scar trans-murality ranging from 25% to 100% throughout the infarct region. FDG-PET imaging, shown fused with LGE imaging, shows matched reductions in metabolic tracer uptake.

4

72-year-old female with suspected new-onset heart failure and non-sustained ventricular tachycardia and prior history of biopsy-proven systemic Sarcoid. Top rows show late gadolinium enhancement (LGE) imaging with characteristic sub-epicaridal based scar (arrows), consistent with prior inflammatory injury. Lower row shows fused FDG-PET images with evidence of focal signal enhancement, consistent with active inflammation surrounding regions of established scar.

3

References 1 Gulati A, Jabbour A, Ismail TF, Guha K,

Khwaja J, Raza S, Morarji K, Brown TD, Ismail NA, Dweck MR, Di Pietro E, Roughton M, Wage R, Daryani Y, O’Hanlon R, Sheppard MN, Alpendurada F, Lyon AR, Cook SA, Cowie MR, Assomull RG, Pennell DJ, Prasad SK. Association of fibrosis with mortality and sudden cardiac death in patients with nonischemic dilated cardiomyopathy. JAMA. 2013;309:896-908.

2 Gao P, Yee R, Gula L, Krahn AD, Skanes A, Leong-Sit P, Klein GJ, Stirrat J, Fine N, Pallaveshi L, Wisenberg G, Thompson TR, Prato F, Drangova M, White JA. Prediction of arrhythmic events in ischemic and dilated cardiomyopathy patients referred for implantable cardiac defibrillator: Evaluation of multiple scar quantification measures for late gadolinium enhancement magnetic resonance imaging. Circ Cardiovasc Imaging. 2012;5:448-456.

3 Kwon DH, Halley CM, Carrigan TP, Zysek V, Popovic ZB, Setser R, Schoenhagen P, Starling RC, Flamm SD, Desai MY. Extent of left ventricular scar predicts outcomes in ischemic cardiomyopathy patients with significantly reduced systolic function: A delayed hyperenhancement cardiac magnetic resonance study. JACC Cardiovasc Imaging. 2009;2:34-44.

Contact

James A. White, M.D., FRCPCRobarts Research Institute P.O. Box 5015, 100 Perth Drive London ON, CanadaN5K 5K8 Phone: +1 [email protected]

4 Klem I, Shah DJ, White RD, Pennell DJ, van Rossum AC, Regenfus M, Sechtem U, Schvartzman PR, Hunold P, Croisille P, Parker M, Judd RM, Kim RJ. Prognostic value of routine cardiac magnetic resonance assessment of left ventricular ejection fraction and myocardial damage: An inter-national, multicenter study. Circ Cardiovasc Imaging. 2011;4:610-619.

5 Neilan TG, Coelho-Filho OR, Danik SB, Shah RV, Dodson JA, Verdini DJ, Tokuda M, Daly CA, Tedrow UB, Stevenson WG, Jerosch-Herold M, Ghoshhajra BB, Kwong RY. CMR quantification of myocardial scar provides additive prognostic information in nonischemic cardiomyopathy. JACC Cardiovasc Imaging. 2013;6:944-954.

6 Romero, J, Xue X, Gonzalez W, Garcia MJ. CMR Imaging Assessing Viability in Patients

3A 3B 3C

3D 3E 3F

4A 4B

4C 4D



With Chronic Ventricular Dysfunction Due to Coronary Artery Disease: A Meta-Analysis of Prospective Trials. J. Amer. Coll Cardiol Img 2012;5:494 -508.

7 Lee Fong Ling, Thomas H. Marwick, Demetrio Roland Flores, Wael A. Jaber, Richard C. Brunken, Manuel D. Cerqueira and Rory Hachamovitch. Identification of Therapeutic Benefit from Revascularization in Patients With Left Ventricular Systolic Dysfunction : Inducible Ischemia Versus Hibernating Myocardium. Circ Cardiovasc Imaging 2013;6;363-372.

8 Klein C, Nekolla SG, Bengel FM, Momose M, Sammer A, Haas F, et al. Assessment of myocardial viability with contrast-enhanced magnetic resonance imaging: Comparison with positron emission tomography. Circulation 2002;105:162-7.

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