Attenuation Correction Single-Photon Emission Computed …medlib.yu.ac.kr/eur_j_oph/se_n_u/s_n_u/35_1_37.pdf · 2008-11-21 · Attenuation Correction Single-Photon Emission Computed

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ttenuation Correctioningle-Photon Emission Computedomography Myocardial Perfusion Imaging

imothy M. Bateman, MD,*,† and S. James Cullom, PhD†

Clinicians now rely heavily on the results of single-photon emission computed tomography(SPECT) myocardial perfusion imaging for diagnosing coronary disease and for planningtherapy. However, the technique is imperfect for these purposes, mainly because oftechnical limitations, the most prominent of which is the effect of soft-tissue attenuation onapparent tracer distribution. Providers have attempted to compensate for this by a numberof indirect approaches. Recently, validated hardware and software solutions for directlycorrecting image data for soft-tissue attenuation have become widely available commer-cially. Optimal application requires an understanding of the technical details that differsomewhat from system to system, the quality control prerequisites, knowledge of theimportance of the transmission map quality, and how dedicated SPECT and SPECT–computed tomography systems present different challenges. In addition, the clinical liter-ature is expanding rapidly, including studies on diagnostic accuracy, image appearances,quantitative analysis, appropriate patients for attenuation correction, clinical utility, incre-mental value in relation to ECG-gating, and risk stratification.Semin Nucl Med 35:37-51 © 2005 Elsevier Inc. All rights reserved.

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ingle-photon emission computed tomography (SPECT)myocardial perfusion imaging is now relied on daily

round the world for diagnosing coronary artery diseaseCAD), risk-stratifying patients for likelihood of myocardialnfarction or cardiac death, and guiding management deci-ions for people with known or suspected CAD. By manytandards, it has become a “mature” technique, with onlyimited new developmental research. Specifically, the lack ofew radionuclides and minimal changes in acquisitionquipment have relegated much of the current research to itslinical applications. A notable exception is attenuation cor-ection. Through equipment modifications and new soft-are, these methods address the major shortcomings ofPECT imaging: inaccuracies in diagnoses and inefficienciesn patient management resulting from mistaking soft-tissuettenuation artifacts for true perfusion defects.

This subject has been of intense interest to practitioners, in-ustrial competitors and has involved professional societies, aseta-analyses have demonstrated that attenuation artifacts limit

Mid America Heart Institute, Kansas City, MO.Cardiovascular Imaging Technologies, LLC, Kansas City, MO.ddress reprint requests to Timothy M. Bateman, MD, Cardiovascular Con-

sultants, PC, 4330 Wornall Road, Suite 2000, Kansas City, MO 64111.
sE-mail: [email protected]
001-2998/05/$-see front matter © 2005 Elsevier Inc. All rights reserved.oi:10.1053/j.semnuclmed.2004.09.003

PECT’s diagnostic accuracy and impact cost-effectiveness.1,2

he necessity of a solution has led to new FDA-approved hard-are and software products from all major vendors, statements

rom professional societies,3,4 attempts to realize new Currentrocedural Terminology codes to recognize the additional costsssociated with attenuation correction, and a plethora of scien-ific and clinical research concerning methods of acquiring at-enuation corrected studies and its impact on accuracy.

ndirect Approacheso Addressingoft-Tissue Attenuation

olutions to the impact of attenuation fall largely into theategories of historically indirect approaches and direct ap-roaches involving measurement of patient-specific attenua-ion. Four indirect approaches are commonly used in dailyuclear cardiology practice to address the frequent problemf soft-tissue attenuation: adjunctive planar acquisitions,rone imaging, ECG-gating, and image quantitation.

lanar Imagingnspection of a steep lateral planar image can be helpful in
eparating the inferior wall of the heart from the effects of an
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38 T.M. Bateman and S.J. Cullom

verlapping hemidiaphragm.5 Additionally, in women, theeft breast can be lifted up and out of the field of view, taped,nd the lower border can be delineated with a lead marker. Ift proves impossible to remove the breast from the field ofiew, at a minimum the marker serves as a quality controlool to ensure that the breast is positioned identically at stressnd at rest imaging. With thallium-201 (201Tl) imaging, thearly poststress images can also be useful for visualizing anduantifying lung-uptake of 201Tl. Limitations of this ap-roach to recognizing and overcoming the problems of soft-issue attenuation are several: it requires additional imagecquisitions; a declining number of technologists and physi-ians are comfortable with planar images; the technique isot helpful unless done with careful attention to patient andreast positioning; and there is no published data on its effectn SPECT’s diagnostic accuracy or patient outcomes.

upine Plus Prone Imagingcquisition of an additional SPECT image with the patient lyingrone, performed after supine imaging, has been shown in someatients to overcome inferior wall attenuation artifacts. Thisechnique rarely will be helpful with attenuation from breastissue or underarm fat-pads. Its impact on diagnostic accuracyas only limited validation,6 but a recent publication has shownhat the event rate after supine only, or supine plus prone imag-ng if the supine image shows an inferior wall abnormality wasimilar.7 The limitations are the negative effects on laboratoryhrough-put and efficiency, scant supportive literature, uncer-ainty about the limits of normality for inferior wall appearanceshen images are acquired prone, and frequent creation of an

nterior wall defect.8

CG Gatingnspection of functional images from ECG-gated SPECT cane useful in distinguishing attenuation artifact from coronaryisease: if there is a corresponding regional perfusion andall motion abnormality, the diagnosis of CAD can be madeith certainty.9 However, normal wall motion in the pres-

nce of a reversible or partially reversible perfusion defecteither confirms nor refutes an attenuating source. Further-ore, some patients with normal wall motion and fixed per-

usion defects at stress and rest may have CAD with nontrans-ural injury and, therefore, this pattern cannot be ascribed

o artifact with any degree of certainty.

uantitationuantitative analysis of myocardial perfusion compares a pa-

ient’s relative distribution of tracer against a database of pa-ients with known coronary anatomy. It was not designed tovercome attenuation, and in fact these programs all incor-orate significant compromises in recognition of the frequentccurrence of attenuation artifacts: different criteria for ab-ormality in women versus men, and wider limits of accep-ance of normality for the anterior wall in women and thenferior wall in men.10 Quantitation has been shown to notmprove declining interpretive accuracy by visual assessment
n obese patients.11 a
irect Approaches tottenuation Correction

he lack of widespread adaptation and standardization of all ofhe aforementioned “indirect” approaches to overcoming atten-ation artifacts has led to a multifaceted effort to devise algo-ithms that directly address the problem. After “first-generation”ttenuation correction solutions failed to achieve desired results,he Society of Nuclear Medicine and the American Society ofuclear Cardiology published a blueprint for providers and in-ustry describing what was perceived as the ideal: methods thatid not interfere with workflow efficiencies, that did not createew interpretive artifacts, that would result in gender indepen-ent distributions of tracer, and that optimally would provideuality assurance tools.3 The importance of the transmissionap used for attenuation correction was emphasized, alongith the need to ensure adequate count density. As of this writ-

ng, most single-photon camera vendors have commerciallyvailable hardware and software attenuation correction capa-ility.

echnical Issueshysics of Attenuationttenuation of photons within the patient is generally ac-epted as the physical factor most affecting quantitative ac-uracy and interpretation of myocardial perfusion SPECTmages.9,12,13 Physical models of attenuation describe a com-lex set of energy and tissue-dependent interactions as pho-ons traverse the body.14 The energies of single photon-emit-ing radioisotopes (70-360 keV) and physical properties ofissues show the predominant effects are photoelectric ab-orption and Compton scattering interactions.14,15

Attenuation is an exponential process described by theinear attenuation coefficient (�), commonly expressed innits of cm�1, and represents the probability per unit path

ength that interactions will occur.14 When � is measured,he value obtained depends on the proportion of scatter in-luded in the measurement.14 In computed tomographyCT), � is expressed in Hounsfield units relating all � valueso the value for water.15 Attenuation interactions also can beharacterized by the half-value layer, which represents theath length required to reduce the beam intensity by0%.14,15 For the relevant energy range, these values are ap-roximately 4 to 6 cm in soft tissue and illustrate the dramatic

mpact of attenuation. For SPECT, the spatial distribution ofand its impact on the projection images is unknown and

herefore additional information is needed to correct forhese effects. As will be described, independent measurementf the attenuation distribution is utilized with new recon-truction algorithms to perform attenuation correction.

Figure 1 illustrates the impact of photoelectric and Comptoncattering and the widely variable values of � in the thorax. Inontrast to PET imaging where the integral attenuation is alwaysalculated along the total path through the body along a line ofesponse,16 SPECT attenuation correction requires the integral
ttenuation from the point of emission in the direction of the

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Attenuation correction SPECT myocardial perfusion imaging 39

etector along the line of response only. Therefore, reconstruc-ion of the attenuation distribution is required.17,18 Early studieshowed that attenuation correction methods applied to homo-eneous distributions of � such as with abdominal SPECT werensufficient.19-21 It also was recognized that precise emission andransmission alignment was required to account for such factorss patient movement or changes in anatomical position betweencans in response to stress. The trend was therefore toward pa-ient-specific rest and stress measurements acquired simulta-eously with the emission data when possible. These key re-uirements largely shaped the current approach to SPECTttenuation correction systems.

quipment for SPECTttenuation Correctionommercialized SPECT attenuation correction systems mea-

ure the nonhomogeneous attenuation distribution utilizingxternal collimated radionuclide sources17,18 or x-ray CTith hybrid systems.22,23 The latter use conventional diag-ostic x-ray sources and detector arrays in serial alignmentith the SPECT scanner. Both approaches have unique tech-ical requirements and implications for laboratory efficiency.

xternal Radionuclide Source Systemsigure 2 illustrates the basic configurations currently used foryocardial perfusion SPECT attenuation correction. Figure 2A

hows the most widely implemented approach on dual 90° de-ector systems in which 2 collimated line sources scan uniformlycross the field of view of the opposing detector. Gadolinium-53 (153Gd; t1/2 � 242 days, 97 keV and 103 keV) is most widely

mplemented as the source on these systems.20 A collimatedlanar beam of photons traverses the patient forming a completerojection profile as the source moves across the full field ofiew parallel to the system axis. Within the detector, an elec-ronic mask defines a narrow spatial “window” opposite theource and moving in unison. Photons detected in this spatial

igure 1 Attenuation of photons and impact on measured projec-ions. (A) photoelectric absorption. (B) Compton scattering illus-rating multiple possible paths. Attenuation causes quantitative er-ors as well as distortions in the projection profiles that areropagated into the reconstructed images. Knowledge of the atten-ating distribution is required for attenuation correction. Solid linesepict true profile; dotted lines depict attenuated profile.

indow are subject to the energy window settings for the trans- s

ission source. This approach allows maximal separation of theransmission and emission images. Transmission sensitivity isimited by the restricted field of view, limited source strength,nd effect of source and detector collimation. In practice, cross-ver of photons between the emission and transmission sourcesequires compensation and may result in technical artifacts24

ith diagnostic implications if improperly implemented.25 Thisffect may restrict the imaging protocol sequence or utilize hard-are and software techniques for compensation.26

Figure 2B illustrates an external radionuclide source ap-roach whereby a series of 14 collimated and shuttered lineources are positioned in an “array” opposite each detectoruch that the full detector field of view is irradiated simulta-eously.27 The sources are also 153Gd and are designed with

ncreasing activity toward the central field of view to maxi-ize counts through the more attenuating regions of theatient. This approach provides significantly greater trans-ission sensitivity compared with a scanning line source

pproach as the full field of view is irradiated. A limitation ishat crossover of photons is increased proportionally to theransmission field of view and limits acquisition to sequentialrotocols for 201Tl studies.Figure 2C illustrates a third approach to transmission im-

ging that uses 2 scanning point sources collimated to bencident at oblique angles on the opposing detectors.28 133Baoint sources (t1/2 � 10.5 years, 356 keV gamma emissions)ranslate along the system axis simultaneously or sequentiallyith the emission acquisition. The transmission source isositioned such that the beam is incident on the detectors atn angle to the hole axes. Transmission photons penetrate theollimator septa for detection. 133Ba has significantly highermission energy and places it well above the emissions of9mTc and 201Tl but may have significantly increased down-catter into the emission window. For all radionuclide sourceonfigurations, the result is a set of transmission projectionsor reconstruction of attenuation coefficient distributions onransverse planes and subsequent reconstruction of attenua-ion corrected images.

omputed Tomography-Based Systemsecently, hybrid SPECT/CT systems consisting of multidetectorPECT coupled with conventional CT systems have been intro-uced.22,23 Developed primarily for anatomical and metabolic

mage fusion in the oncology community, these systems use theT image for attenuation correction of myocardial perfusionPECT images. Early systems included low-energy CT capabil-ties but have recently been expanded to include high-quality

ultislice imaging systems. Figure 3A illustrates the basic con-guration for a hybrid SPECT/CT system and representative CT

mages (Fig. 3B). All studies are acquired sequentially on theseystems as a result of positioning of the SPECT and CT compo-ents. Because of the very high photon flux from the x-rayource, the attenuation map may be acquired using fast (feweconds) or slow (few minutes) protocols with spiral and in-exed modes. The very high degree of resolution allows visual-

zation of artifacts not seen in lower resolution radionuclide
ource images. However, CT systems may have unique artifacts

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esulting from the impact of oral and intravenous contrast andeam-hardening artifacts from metallic objects such as with cor-nary stenting29,30 that are not readily observable with the scin-illation-based images. The impact and management of theseffects is still under study.

uality Control forPECT Attenuation Correction

t is well accepted that a high quality attenuation map appliedppropriately is essential for accurate attenuation correc-
ion.4,31,32 Early publications of clinical attenuation correc- n
ion studies commented little or not at all on quality controlethods or criteria for acceptance of quality.33 High-quality

ttenuation maps provide a valuable indicator of the overalluality of the transmission study. Attenuation maps of highuality are characterized by high count density, minimal oro truncation of the transmission projections, high qualityeference scans, precise alignment of emission and transmis-ion data and minimal noise.31

ransmission Count Density Requirementseveral factors within the radionuclide source system can

igure 2 Common radionuclide-based hardware configurations forttenuated correction SPECT.

Fa

egatively impact count density. These include mechanical

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isalignment or malfunction of the source housing, decay ofransmission sources, or insufficient imaging acquisitionime; the latter becoming more significant in patients witharge body habitus or excessive attenuation. Some systemsrovide software to estimate optimal acquisition time re-uirements directed at assuring sufficient counts using ahort prescan with the transmission sources.34 With x-ray CTransmission, the abundant photon flux from these systemsrovides adequate counts, provided proper calibration isaintained.23

mage Truncation andruncation Compensationruncation of the transmission scan occurs when a portion of

he patient’s body moves outside of the field of view for aumber of angles and must be minimized or prevented.35-37

igure 4 illustrates a truncation artifact in an attenuation mapbtained on a radionuclide based system. The measured at-enuation distribution is incorrect, as indicated by the veryright regions and may produce attenuation correction arti-acts as the errors are propagated into the corrected emissionmages.38 The location of the artifact is critical and has differ-nt implications depending on the orbital range affected.39,40

regoriou and coworkers36 have shown that the detection oferfusion defects can be significantly decreased in the pres-nce of severe truncation. This has led to the development of

igure 3 Representative attenuation maps from x-ray SPECT/CT (lefto right, inferior to superior).

obust reconstruction algorithms that are less sensitive to the p

issing information26,37,41-44 and special consideration to therbital set up of the study. Interestingly, in early studies usingivergent beam geometry for transmission imaging on a tri-le detector system, essentially all patients were truncated toome degree41,42 This was accomplished by use of reconstruc-ion algorithms that compensated intrinsically for truncationut these systems were not commercialized.41,42

The likelihood of truncation increases with increasingody size and decreasing detector field of view. A currentrend in gamma camera design is toward dedicated cardiacystems with small field of view detectors. These systems willave increased truncation based their dimensions. Attenua-ion correction methods currently being implemented onhese systems use new algorithms for compensation and willequire new criteria for artifact recognition. Chen and co-orkers recently demonstrated the impact of truncation ar-

ifacts on attenuation corrected images for small field of viewtudies based on simulated truncation from nontruncatedarge field of view patient studies.40 Additionally, Case andoworkers have performed preliminary validation of a con-ugate symmetry reconstruction method to compensate forransmission truncation on small field of view systems.45 Fig-re 5 illustrates patient attenuation maps reconstructed with-ut truncation and with significant truncation simulated on amall field of view system. X-ray SPECT/CT systems gener-lly have a large field of view and truncation is less likely, butan occur, particularly with subjects who have a large bodyass index (BMI). The system field of view may be smaller

han the gantry opening and therefore large patients mayxperience truncation.

eference (“Blank”) Scansransmission reconstruction requires independent measuref the response of the detector to the incident flux in thebsence of attenuating media (table, gantry componentstc.). “Reference scans” for radionuclide and x-ray CT sys-ems measure this quantity along each line of response. Theyre required to remain stable over time as a single referencecan is typically applied to all projections in a patient study.he profile of the reference scan is determined by the geom-try of the source-detector combination and the shape of thencident photon beam. Evans and coworkers recently de-cribed artifacts in the reference scan and the impact on at-enuation corrected images for a scanning line source geom-try using 153Gd.46 Some systems require multiple measures

igure 4 Illustration of severe truncation artifacts in a very large
atient on the left and right sides.

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f the reference scans at various angles to compute an averageesponse to minimize any potential variation with angle.PECT/CT systems use a similar approach to reference scaneasurement or they may use an indirect approach whereby

he attenuation coefficients are calibrated against a phan-om.22,23

ownscatter Artifactsttenuation correction studies are inherently multi-energytudies and require separation of photopeaks. Figure 6 illus-rates the impact of 99mTc tracer photons detected in the53Gd transmission energy window and the characteristic un-erestimation of attenuation coefficients in the attenuationap. This artifact may be avoided by timing of acquisitions

ased on the emission and transmission photopeak energiesnd software or hardware methods. The appearance of thesertifacts in the attenuation map indicates a compromisedttenuation correction study and should be carefully re-iewed before clinical interpretation. 201Tl SPECT studies re-

Figure 5 (Top row) Attenuation maps reconstructed withrow) Illustration of truncation artifact when imaged on a“arc” on right side of patient.

Figure 6 Illustration of errors in the attenuation map on100-keV photopeak of the 153Gd transmission source. Timage and the bottom row the corresponding transvers
caused by the “spine,” which has greater attenuating density a
uire special consideration for downscatter because of theelatively low energy of the major photopeaks relative to mostransmission source energies. With 133Ba transmissionources, there is considerable downscatter to the commonmission energies and the preferred approach would be se-uential (separate) acquisition of the emission and transmis-ion scans. However, with this scheme, movement betweencans becomes a source of error. CT-based studies are per-ormed sequentially and the very high flux dominates theount rates from 99mTc and 201Tl in the x-ray window and,herefore, crossover is negligible.

isregistration ofmission and Transmission Scanss a result of the exponential nature of the attenuation pro-ess and the large differences in attenuation coefficients ofdjacent soft and lung tissues in the thorax, alignment of theransmission and emission data is critical for all methods of

ncation on a large field of view SPECT system. (Bottomfield of view SPECT system. Artifact is shown as bright

sive transverse planes from 99mTc downscatter into therepresents the effect of downscatter into transmission

es after correction. Note image scaling differences are

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ttenuation correction. Stone and coworkers47 showed that,or transverse and axial shifts of 2.9 cm, the normalized myo-ardial SPECT activity was decreased in certain regions of theeart by 20% to 35%. For a 12-degree rotational shift, therror was on the order of 10% to 20%, compared with aormalized variation of 20% to 25% in the image with nottenuation correction. The results indicate that registrationrrors of 2 to 3 cm can seriously affect image quality in bothhantom and human images. McCord and coworkers48

ound regional count losses of 30% from a 2-cm shift with8F-2-deoxyglucose (FDG)-PET studies, a similar result usingxternal 68Ge road sources for transmission imaging. Loghinnd coworkers recently reported that of 1177 rest-dipyri-amole PET perfusion studies, 252 (21.4%) had artifactualefects due to attenuation-emission misregistration,49 high-

ighting the significant frequency of occurrence and the im-ortance of correction methods.A more subtle source of misregistration is the mismatch

etween the very high spatial resolution of CT images and theower spatial resolution of SPECT images. Nanette and co-orkers showed with FDG-PET that mismatches as a resultf smoothing the transmission images to minimize noise ar-ifacts, can result in errors in absolute and relative quantita-ion of regional perfusion.49 Misregistration at tissue bound-ries, such as the lateral wall and lung interface can result inrtifacts and interpretive errors. Although this work investi-ated these effects for PET, the principle applies to SPECT/T.The relative merits of using a “fast” or “slow” CT image

cquisition protocol is under debate for myocardial perfusionPECT/CT applications.51 Acquisitions times ranging from aew seconds to one minute for a total volume CT are possiblen modern systems.52 Fast acquisitions minimize blurringrom cardiac and respiratory motion but sample the heart andnatomy at a specific instance in the cardiac cycle, therebyotentially leading to mismatch artifacts and attenuation cor-ection weighted toward a single point in the cycle. Slowerrotocols integrate the information, sampling over multipleardiac cycles, but provided lower resolution images fromardiac and respiratory motion. Breatholding techniques arelso under investigation to minimize the impact of blurringnd mismatch as a result of respiratory motion.52,53 Becausef the very rapid (�1 s/slice) capabilities of current x-rayystems, respiratory motion becomes significant during theime of acquisition. In contrast, radionuclide-based systemsave a slower acquisition rate and the data are integrated overultiple respiratory cycles resulting in a “blurring” of the

ransmission images. In effect, AC is performed with an av-raged attenuation map. The current trend is toward theevelopment of faster methods to maximize laboratory effi-iency and the development of methods to recognize andorrect misregistration when it occurs.

mpact of Attenuation Correction inhe Presence of Extracardiac Activityn the conventional (nonattenuation corrected) SPECT scan,
ttenuation by subdiaphragmatic structures greatly sup- 1
resses the detection of activity from this region.54 Whenttenuation correction is applied in the presence of excessiveubdiaphragmatic activity, the relative magnitude of this ac-ivity is enhanced and may be superimposed on the myocar-ium, particularly toward the inferior region of the heart.54

isualization and quantitation of cardiac perfusion may beompromised and ‘hot-spots’ may result that can lead to im-roper image scaling of other regions of the myocardium.his effect has been proposed as a source of artifact with theppearance of decreased perfusion in the critical anterior re-ion of the heart and can occur with both radionuclide- and-ray CT-based systems.

catter Compensationn Attenuation Correctionhe detection of scattered photons in the emission photo-eak causes loss of contrast resolution and quantitative accu-acy in the measurement of attenuation coefficient values.cattered photons are detected in both radionuclide-basednd CT transmission images. Scatter content is significantly aess in CT because of the detection process. Optimal attenu-tion correction requires a quantitative matching betweenhe energy content of the emission images and the attenua-ion coefficient values. Ideally, there is complete scatter re-ection in both and only photopeak photons at a single energyre represented. In this case, simple scaling procedures cane used to relate the energy differences between tissues. Cur-ent scintillation detector systems do not permit scatter-freeeasurements and, therefore, attenuation correction meth-

ds use approximate methods for scatter compensation.55

nsufficient accommodation of scatter has been shown toffect the accuracy of attenuation corrected images.13,44 Basedn physical principles and comparison with PET studies,here contrast resolution is significantly greater than SPECT,

he sensitivity of attenuation correction for the detection andocalization of perfusion defects is expected to improve as

ore accurate scatter correction evolves. The trend is towardhe use of broader regions of the spectrum permitted by moreeneralized energy window capabilities56-58 and list modepplication to improve scatter estimation. Scatter corrections more complicated for 201Tl SPECT than for 99mTc agentsecause of the greater complexity of the emission spectrum.owever, recent advances suggest that emerging methods of

ttenuation correction will include scatter correction and wille applied to 99Tc and 201Tl images, allowing application toingle and dual isotope protocols.

osimetry of Transmissioncans for Attenuation Correction

everal published reports have examined the radiation doseo the patient as a result of performing external radionuclide-ased transmission scanning for attenuation correction.lmeida and coworkers used anthropomorphic phantomtudies and thermoluminescent dosimeters to demonstratehat for myocardial perfusion SPECT studies with acquisitionime of 15 to 30 min, and 2 153Gd scanning line sources of
08.1 mCi each, the effective dose was approximately 1.1

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rem.59 Bellemann and coworkers60 recently confirmedhese results in an independent study calculating an effectiveose of 0.73 mrem for a 20-min san also using 153Gd scan-ing line sources. Although effective dose will increase with

ncreased imaging time or higher transmission sensitivity sys-ems, these studies suggest that effective dose from radionu-lide source transmission scans is very low compared withhe dose from the imaging tracer.

Estimates of effective dose from x-ray SPECT/CT systemsre determined largely by the same factors determining dosen conventional radiological chest CT. SPECT/CT provides aignificantly higher quality of attenuation measurement as aesult of the greater photon flux and corresponding higherpatial resolution. Chenen and coworkers, using Li-F basedhermoluminescent dosimetry and the Alderson phantom as-essed the radiation exposure of patients in several standardrotocols in multislice CT They found for different chestrotocols, an effective dose of 750 to 1290 mrem,61 consid-rably higher than for radionuclide based protocols. How-ver, use of lower resolution CT scanners and advanced puls-ng methods for attenuation correction application mayeduce the effective dose considerably from these values.23

terative Reconstructionttenuation correction advanced to clinical implementations a result of new reconstruction algorithms referred to col-ectively as iterative algorithms.19,62-64 Iterative algorithmsrovide a broad mathematical framework that permits theodeling of physical processes and noise characteristics from

he emission and detection processes.19 These algorithms arepplied to reconstruct attenuation maps and for reconstruc-ion of the attenuation corrected images. Algorithms closelyelated to the maximum-likelihood expectation-maximiza-ion (MLEM) algorithm,19 or the ordered subset expectationaximization,65 are most commonly used in commercial sys-

ems. The ordered subset expectation maximization (OSEM)lgorithm accelerates reconstruction speed by utilizing sub-ets of the projection data in a specified order. All iterativelgorithms use a model of the image acquisition process (for-ard projection) and are derived to converge to an optimally

ccurate image. Starting with an estimate of the image onach transverse plane, projection is calculated based on theorward projection of the estimate through the attenuation

ap. Differences between these calculated projections andhe measured data are used to “update” the transverse planestimate to a more accurate image. Successive application ofhis process increases the likelihood that the estimated trans-erse image is the source of the measured projection dataiven the model of the imaging process. Although theoreticalriteria are well described for stopping the reconstructionrocess,66 most practical applications are based largely onmpirical study of the various implementations. The modelf the imaging process also may include scatter processes andffects of distance-dependent spatial resolution of the colli-ated detector.67 The distance-dependent change in spatial

esolution contributes to the inconsistency between mea-
ured projections and has been approximated through filter- u
ng techniques68,69 and through incorporating the spatial res-lution information in the reconstruction model.70 Figure 6llustrates the iterative reconstruction process using a Bayes-an approach applied to the transmission projection data ac-uired from 153Gd scanning line sources (Fig. 6A) generatinghe attenuation map, and the reconstruction of the transversemission images corrected using the previously calculatedttenuation map (Fig. 6B). SPECT/CT systems also may in-orporate iterative methods for attenuation map reconstruc-ion. However, given the abundant x-ray flux from theseystems, conventional reconstruction methods such as fil-ered backprojection are quantitative and accurate for esti-ating the attenuation map and therefore are most fre-

uently used. Iteratively reconstructed images appearifferent than filtered backprojection images, as illustrated inlater section, as some contrast may be lost because of the

bsence of a ramp filter with filtered back projection recon-truction. Hutton and coworkers and Miller and cowork-rs71,72 have discussed some of the differences relevant tolinical interpretation.

linical Issueshe literature contains considerable documentation of theole of attenuation correction in daily nuclear medicine prac-ice. Its impact on diagnostic accuracy, performance in thebese, and incremental value to ECG-gating have been dem-nstrated. Gender-independent quantitation programs arencreasingly available commercially, and patient outcometudies are beginning to appear in the literature.

he Attenuation-Corrected Scanhen implemented optimally, the distribution of radionu-

lide to all myocardial regions should be nearly uniform inhe absence of significant coronary artery disease. Male andemale distributions should be similar. The right ventriclehould be more visible. The basal septum and lateral wallsften appear longer in the long-axis images.Links and coworkers73 have reported that with one of the

ardware/software approaches there may be fewer counts athe apex even in the absence of significant CAD. Their datandicate that apical thinning is seen as frequently with asithout attenuation correction and that coronary disease is

nferred only when it is severe. Because others have not re-orted this, this may not be common to all attenuation cor-ection methods. In fact, although gradually becoming moreimilar in their technical approach, attenuation correctionethods remain largely nonstandardized compared with

onventional imaging.For the most part, it is best to interpret attenuation cor-

ected studies in conventional fashion—inspecting first theotating projection images for quality control, appearance ofhe left and right heart, potential sources of artifact, and forossible regions of abnormal uptake or absence of uptake ofracer; then the static images; and finally the ECG-gated im-ges. Only then would the interpreter also inspect the atten-
ation corrected images, to assist in resolution of whether

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ndings on the nonattenuation corrected images may be ar-ifactual. Most often, the attenuation corrected images willppear more uniform in tracer distribution, and there will betendency to read fewer studies as probably normal or prob-bly abnormal or equivocal.74 When a new perfusion defectecomes apparent, it is indicative of hypoperfusion thatould have been missed on nonattenuation-corrected im-

ges. The usual etiology of this is “matched” attenuation ar-ifacts so that a truly hypoperfused region appears to haveimilar counts to an opposing region that in fact is attenuated.

As indicated previously, the attenuation corrected imagesill be affected by liver and loops of bowel if these contain a

ignificant amount of radionuclide. The inferior wall may note interpretable in some cases, and the anterior wall mayppear relatively photopenic. Especially with 99mTc sestamibind pharmacologic stress, there needs to be fastidious atten-ion to detail to avoid this as much as possible. Patientshould present after 4 to 8 h of fasting, and imaging needs toe delayed up to 45 minutes after resting or posthyperemicharmacologic stress.If attenuation correction is performed with dual-isotope

rotocols, in which the technetium but not the 201Tl imagesre attenuation corrected, it can be helpful to inspect the 2mage sets separately and then with the 2 stress image setsogether, one attenuation corrected and one not.

Because the individual frames of the gated images are notttenuation-corrected, attenuation correction will have noffect on either visual or quantitative functional assessments.owever, if quantitative programs that were developed foronattenuation corrected studies are employed for objectivevaluation of perfusion, they will often spuriously identifybnormalities at the base of the heart. This is because with

Figure 7 Large male patient with an apparent perfusionimages (A) and uniform count distribution after attentreadmill with no chest pain and no ST segment change

ttenuation correction, basal portions of the heart and sur- i

ounding structures such as the atria tend to be more prom-nent and get incorporated into the search parameters of theoftware. Software developed specifically for attenuation-orrected images should be employed; in this case, the mapsill be independent of gender.

ffects on Diagnostic Accuracypecificityne of the major goals of attenuation correction is improved

pecificity through a homogeneous distribution of tracer inormal patients. Several investigators have studied low-like-

ihood patients and demonstrated significant advantages tottenuation correction. Ficaro and coworkers41 showed lat-ral-to-posterior and basal-to apical wall ratios of near unityn 10 healthy volunteers studied with 201Tl. In later studies,icaro and coworkers42 and then Prvulovich and coworkers75

emonstrated not only improved normalcy in patients with5% likelihood of CAD but also a gender-independent

uantitative distribution of tracer. Other investigators75-77

ave reported improvements in specificity in patients withollow-up angiography, in comparison with nonattenuation-orrected images. Figure 7A shows an example of a maleatient with what appears to be a partially reversible perfu-ion defect inferiorly on the nonattenuation-corrected im-ges, whereas Figure 7B shows after attenuation correctionormal inferior wall uptake. Figure 8A shows an anterior wallartially reversible defect in a female patient, that normalizesfter attenuation correction.

ensitivityhe impact of attenuation correction on sensitivity has beenore difficult to determine, partly because in many of the

t of the inferior wall in the nonattenuation-correctedcorrection (B). He exercised for 7 min on the Bruce

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mages were or were not attenuation corrected. This has theffect of forcing the readers to assume that abnormalitiesight be artifactual, with resulting sensitivities of corrected

nd uncorrected images being similar. However, a numberf studies have shown a consistent small increase inensitivity, 58,75-78 and there are numerous anecdotes to sug-est that in some circumstances attenuation correction canoth detect CAD that would otherwise be missed and betterharacterize the full extent and severity of disease. There areeveral potential explanations for this. One is that with un-orrected data, the reader may recognize the presence of anttenuation artifact, and mistakenly attribute the entire ab-ormality to artifact when in fact there is a combination ofypoperfusion and artifact. Second is that by making theistribution of tracer more uniform, milder degrees of hypo-erfusion may become evident. Consider a male patient withignificant inferior wall attenuation; if the anterior wall isypoperfused, this may be overlooked because it appearsore normal than the inferior wall. A third cause was referred

o earlier, and might best be appreciated by considering aale with both a protuberant abdomen and a thick upper

orso. Because the anterior and inferior walls will have re-uced “apparent” counts, it will be easy to miss lateral wallypoperfusion because the image may now seem close toomogeneous. The technical incorporation of accurate scat-er correction methods that provide spatially dependentompensation, may potentially provide improved defect con-rast without the introduction of additional artifact, espe-ially for mild and moderate disease not adequately detectedith current methods. Figure 9 is an example of a patient inhom attenuation correction has resulted in recognition of

n ischemic region missed by nonattenuation-correctedPECT.

Duvernoy and coworkers79 hypothesized that because at-

Figure 8 Female patient with a reversible apical perfusiorected images in A), that is normal after attenuation cor

enuation correction eliminates regional perfusion biases, it a

ould increase sensitivity for recognizing left main CAD.hey studied 28 patients with left main disease and 34 “con-

rols” with 2-vessel CAD. A left main defect pattern wasresent on 64% of attenuation corrected versus only 7% ofncorrected images. Specificity was equal. More disease wasecognized in a greater number of territories with correctedersus uncorrected SPECT: 2.14 versus 1.43.

CG Gating,ttenuation Correction, or Both?ecause ECG-gating is performed routinely today withPECT perfusion imaging and because it can be helpful inifferentiating artifact from coronary disease, it is importanto know whether attenuation correction adds accuracy notust to static SPECT perfusion images, but after the informa-ion provided by gating also has been factored in. Links andoworkers80 recently examined this matter in a study thatncluded 66 subjects; 32 had coronary angiography (27 withignificant CAD) and 34 had a statistical low-likelihood forAD. Studies were read by consensus of 2 readers who werelinded to all clinical information, for presence of CAD andor coronary territory of abnormality. The readers interpretedtatic images and then added the information from gating.oth sensitivity and normalcy improved progressivelyhrough static (85%/54%), gated but noncorrected (78%/2%), static attenuation corrected (93%/77%), to gated at-enuation-corrected (96%/85%) image sets. Sensitivity washe highest for all 3 coronary territories for the combinationf gating and attenuation correction, while normalcy wasighest with gating and attenuation correction for the rightnd left anterior descending coronary arteries.

A larger study has more recently been completed and re-orted in abstract form. Bateman and coworkers81 performed

ct suggesting left anterior descending ischemia (uncor-(B).

n defe

consensus blinded read of images from 247 patients, of

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hom 118 had angiography within 90 days (90 of whom hadignificant CAD and 28 did not) and 129 had a low-likeli-ood of disease. The interpreters scored gated attenuationorrected and gated nonattenuation-corrected images inde-endently and without knowledge of whether the imagesere or were not attenuation-corrected. The results showed

hat the attenuation-corrected studies were associated with aignificant improvement in both specificity (64% to 86%)nd normalcy (93% to 98%), with no change in sensitivity.aken together, these 2 studies confirm that gating and at-

enuation correction provide synergistic and complementarynformation and should be used together for optimal diag-ostic accuracy.

erformance in the Obeselthough it can be difficult to predict who will have imagesompromised by attenuation artifacts, obese men andomen present 2 important issues for attenuation correc-

ion: will the current algorithms work as well in the obeses in the nonobese and will the value of attenuation cor-ection be greater in this patient population? Previousork by Hansen11 has shown that diagnostic accuracy ofonattenuation corrected SPECT is lower in the obese, anduantitative analysis does not improve this.Three studies have addressed the performance of atten-

ation correction in the obese. Heller and coworkers74

ompared interpretive certainty, diagnostic accuracy, anderceived need for a rest study in 90 patients studied withtress-only imaging, with the patients subdivided intohose who were or were not obese (BMI �30 kg/m2). Theercent of studies that could be interpreted as definitelyormal or abnormal was similar for obese (79%) andonobese (87%) people, with the corresponding percent-

Figure 9 Obese male patient (BMI � 35) with a large pinfarction (uncorrected images; A). After attenuation cothere is now evident a reversible perfusion defect of thcoronary artery was occluded and the left anterior desce

ges for nonattenuation corrected images being 28% and *

3%. The perceived need for a rest image after a stress-nly attenuation-corrected image was also the same forbese (45%) as for nonobese (42%) people. Diagnosticccuracy was unaffected by BMI.

Bateman and coworkers82 also examined this through alinded consensus read of 116 patients. Body mass index wasormal (�30) in 60 patients and 30 or greater in 56. Allatients underwent coronary angiography within 60 days.ated noncorrected and corrected images were presented

andomly and independent of one another. For the obese andonobese population, sensitivity was the same for attenua-ion corrected and noncorrected images (Table 1). Specificityas higher overall for attenuation-corrected images. In addi-

ion, specificity fell dramatically as BMI increased withoutttenuation correction, but remained high with attenuationorrection.

Finally, Grossman and coworkers83 recently applied quan-itative analysis to compare the performance of attenuation-orrected and uncorrected SPECT in 95 overweight persons,aving mean BMI of 32 kg/m2. Normalcy improved from2% to 90%, and specificity improved from 29% to 57% withttenuation correction.

n defect inferiorly in a region of previous myocardialn (B), the inferior wall fixed defect is unchanged, butior wall and apex. At coronary angiography, the righthad an 80% stenosis.

able 1 Sensitivity and Specificity of Corrected and Noncor-ected 99mTc Sestamibi SPECT in Nonobese (BMI <30) andbese (BMI >30) Patients (Adapted from Bateman et al82)

Sensitivity (%) Specificity (%)

Non-AC AC Non-AC AC

ll patients 88 86 50* 79MI <30 90 90 64 82MI >30 87 82 41* 76

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These 3 studies suggest that attenuation correction per-orms well in the obese, and unlike nonattenuation-cor-ected studies, does not appear to have accuracy erodeith increasing body habitus. They do not imply that at-

enuation correction should only be used in the obese, ashere is a large accumulated data to indicate that attenua-ion correction also enhances specificity and normalcy inhe nonobese. Perhaps an appropriate conclusion is thatttenuation correction is preferred if available, and is es-ecially useful in the obese.

ender-Independent Quantitative Programshe commercially available software programs for quantita-

ively assessing SPECT myocardial perfusion assume regionalariations in the perceived distribution of tracer to accountor anticipated attenuation differences between individuals.bviously all variations in body habitus cannot be accounted

or, but data indicate that at least using gender-specific anal-ses has helped to enhance diagnostic specificity. Becausettenuation correction eliminates these apparent differencesn tracer distribution, a single quantitative database can besed independent of gender. As discussed above, Ficaro andoworkers41 first showed this in a series of patients in whomuantitative specificity improved from 46% to 82%, and nor-alcy improved from 76% to 95%, comparing noncorrectedith attenuation corrected data. The same study also dem-nstrated a statistical improvement in detection of individualoronary stenoses.

Grossman and coworkers83 recently reported the deriva-ion and then the clinical validation of a new gender-ndependent quantitative program for normal distributionf tracer and criteria for abnormality. The control data-ase, developed by evaluation of 112 patients, showed noignificant segmental differences in mean and standardeviation of counts for male and female populations forttenuation corrected data, with 7 of 20 segments showingignificant differences between the same men and womensing nonattenuation corrected data. In the validationroup, the single database for men and women improvedpecificity and normalcy, with no loss in sensitivity, com-ared with noncorrected quantitative analyses.

tress-Only Imagingt is recognized that a normal stress image connotes a low-isk for subsequent events, just as has been demonstrated fortress/rest image sets. However, stress-only imaging has noteen commonly performed, largely because there is enoughonhomogeneity of tracer in the stress images for most read-rs to require the rest study for comparison to arrive at a moreonfident interpretation. As a result, the technique is lessfficient and more costly than it might be if a significantroportion of studies could be completed with one image set.ith attenuation correction, it is presumed that more “equiv-

cal” images would appear definitely normal; in addition, ifhere is a perfusion defect that can be confidently ascribed tooronary disease and associated wall motion and thickening
s normal, then ischemia can be diagnosed without the ne- t
essity for a rest image. Only in the presence of both a per-usion defect and regional contraction abnormality would aest image be needed, to differentiate scar from hibernating ortunned myocardium.

A recently published study by Heller and coworkers74

ddresses the potential of stress-only imaging when com-ined with attenuation correction. Ten experienced nu-lear cardiologists independently interpreted 90 stress-nly gated 99mTc sestamibi SPECT images; among 41atients with follow-up angiography, 30 had significantAD. Another 49 patients had less than 5% likelihood ofAD. Images were interpreted for diagnostic certainty

definitely normal, probably normal, equivocal, probablybnormal, definitely abnormal) and perceived need for aest image. After “averaging” the readers’ scores, only 37%f nonattenuation corrected studies could be interpreteds definitely normal or abnormal, and the readers per-eived the need for a rest image in 77% of studies. Inter-stingly, gating did not impact on either diagnostic cer-ainty, as has been shown with combined stress and restmaging, or on the perceived need for a rest study. How-ver, attenuation-corrected data increased significantlyhe number of studies that could be interpreted as defi-itely normal or abnormal to 84% and decreased the needor a rest image to 43%. The diagnostic accuracy for atten-ation-corrected stress-only imaging was 84%, with sen-itivity 97% and specificity 84%.

Gal and Ahmad84 were the first to examine the prognosticeaning of a normal stress-only image. More recently, Gib-

on and coworkers85 investigated the safety of stress-onlymaging in 729 patients with chest pain and with an interme-iate (37%) likelihood for CAD but with a normal attenua-ion-corrected scan. After a mean follow-up of 22 months,he overall cardiac event rate was only 0.6% (one myocardialnfarction and 3 patients with progressive angina who wereubsequently referred to angiography). Without attenuationorrection, 37% of the images were not normal and wereormalized after attenuation correction. This affirms both thelinical usefulness and the safety of patient reclassificationased on image appearance changes after attenuation correc-ion.

atient-Outcomes Studieshere currently is a dearth of outcomes studies based onttenuation-corrected data. The single investigation haseen discussed previously in relation to stress-only imag-

ng. It might be hypothesized that attenuation correctedata could lead to substantively different patient classifi-ations and thus different management decisions. For ex-mple, a good percent of current images interpreted asildly or moderately abnormal, or probably abnormal or

quivocal, might be reflective of attenuation artifacts, andith attenuation correction be interpreted as definitelyormal studies. Furthermore, current beliefs that mild

schemia is “benign” may be derived from pooled data thatncludes a significant percent of true control patients such
hat when the population only includes those with isch-

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mia, event rates may be higher. These realities underscorehe importance of outcomes studies based on either com-ined data or attenuation-corrected data alone.It would appear that several conclusions could be

eached concerning contemporary SPECT attenuation cor-ection. There are clearly a number of technical issues thateed to be well understood by both technologist and phy-ician. Equipment needs to be appropriately quality-con-rolled and patients need optimal preparation. Both tech-ologist and physician need to be particularly attentive tohe quality of the transmission map. There will be moreechnical and professional work, but the result should beuperior quality images, less over-diagnosis as a result ofistaking artifact for CAD, less unnecessary referral to

oronary angiography, and in some cases better delinea-ion of the full extent of CAD.

One remaining issue is the need for more investigationf the various approaches to attenuation correction be-ause validation of one hardware/software solution doesot ensure that others will perform the same. Even more

mportant is re-examination of the prognostic meaning ofcan results in the era of attenuation correction. Currentecisions are driven by population-based studies derivedrom nonattenuation corrected data that may or may note extrapolatable from attenuation-corrected images.

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Attenuation Correction Single-Photon Emission Computed …medlib.yu.ac.kr/eur_j_oph/se_n_u/s_n_u/35_1_37.pdf · 2008-11-21 · Attenuation Correction Single-Photon Emission Computed