12/5/13 Most Cited Academic Radiology Articles
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The most cited articles published since 2008, extracted from Scopus.
Lung Perfusion with Dual-energy Multidetector-row CT (MDCT). Feasibility for the Evaluation
of Acute Pulmonary Embolism in 117 Consecutive Patients
Volume 15, Issue 12, December 2008, Pages 1494-1504
Pontana, F. | Faivre, J.-B. | Remy-Jardin, M. | Flohr, T. | Schmidt, B. | Tacelli, N. | Pansini, V. | Remy, J.
Rationale and Objectives: To investigate the accuracy of dual-energy computed tomography in the depiction
of perfusion defects in patients with acute pulmonary embolism (PE). Materials and Methods: One hundred
seventeen consecutive patients with clinical suspicion of acute PE underwent dual-energy multidetector
computed tomographic (CT) angiography of the chest with a standard injection protocol. Two radiologists
evaluated, by consensus, the presence of endoluminal clots on (1) transverse "diagnostic" scans
(contiguous 1-mm-thick averaged images from tubes A and B) and (2) lung perfusion scans. Results:
Seventeen patients showed CT features of acute PE, with the depiction of 75 clots within the lobar (n = 15),
segmental (n = 43) and subsegmental (n = 17) pulmonary arteries. A total of 17 clots were identified as
complete filling defects (ie, obstructive clots), located within segmental (12 of 17) and subsegmental (5 of
17) arteries. Fourteen of the 17 obstructive clots were seen with the concurrent presence of corresponding
perfusion defects, whereas cardiac motion and/or contrast-induced artifacts precluded the confident
recognition of perfusion abnormalities in the remaining two segments and one subsegment. Four
subsegmental perfusion defects were depicted without the visualization of endoluminal thrombi within the
corresponding arteries. Perfusion defects were identified beyond five nonobstructive clots. Conclusion:
Simultaneous information on the presence of endoluminal thrombus and lung perfusion impairment can
be obtained with dual-energy computed tomography. © 2006.
Recent Developments in the Dorfman-Berbaum-Metz Procedure for Multireader ROC Study
Analysis
Volume 15, Issue 5, May 2008, Pages 647-661
Hillis, S.L. | Berbaum, K.S. | Metz, C.E.
Rationale and objectives: The Dorfman-Berbaum-Metz (DBM) method has been one of the most popular
methods for analyzing multireader receiver-operating characteristic (ROC) studies since it was proposed in
1992. Despite its popularity, the original procedure has several drawbacks: it is limited to jackknife accuracy
estimates, it is substantially conservative, and it is not based on a satisfactory conceptual or theoretical
model. Recently, solutions to these problems have been presented in three papers. Our purpose is to
summarize and provide an overview of these recent developments. Materials and Methods: We present and
discuss the recently proposed solutions for the various drawbacks of the original DBM method. Results: We
compare the solutions in a simulation study and find that they result in improved performance for the DBM
procedure. We also compare the solutions using two real data studies and find that the modified DBM
procedure that incorporates these solutions yields more significant results and clearer interpretations of the
variance component parameters than the original DBM procedure. Conclusions: We recommend using the
modified DBM procedure that incorporates the recent developments. © 2008 AUR.
Evaluation of Diffusion-weighted MR Imaging for Detection of Bowel Inflammation in Patients
with Crohn's Disease
Volume 16, Issue 5, May 2009, Pages 597-603
Oto, A. | Zhu, F. | Kulkarni, K. | Karczmar, G.S. | Turner, J.R. | Rubin, D.
Rationale and Objectives: The aims of this study were to determine the feasibility of diffusion-weighted
magnetic resonance imaging (DWI) in the detection of bowel inflammation and to investigate the changes
in apparent diffusion coefficient (ADC) values in the inflamed bowel in patients with Crohn's disease.
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Materials and Methods: Eleven patients who underwent magnetic resonance enterography (including DWI)
for Crohn's disease and colonoscopy or surgery within 4 weeks of examination were recruited. Two
radiologists reviewed diffusion-weighted images and ADC maps to evaluate for inflammation in each bowel
segment (terminal ileum, cecum, ascending colon, transverse colon, descending colon, and rectosigmoid
colon) and measured the ADC values of each bowel segment. Endoscopic and pathologic results were
correlated with DWI findings. Results: Fifty-three segments (19 with inflammation, 34 normal) were
included. DWI detected inflammation in 18 of 19 segments (94.7%) and showed normal results in 28 of 34
segments (82.4%). On diffusion-weighted images, bowel segments with inflammation revealed higher
signal compared to normal segments. Artifact levels were none or minimal in 10 of 11 patients (90.9%) and
moderate in one patient. On quantitative analysis, ADC values of inflamed and normal bowel were
measured as 0.47 - 2.60 × 10 -3 and 1.39 - 4.03 × 10 -3 mm 2/s, respectively (P < .05). Conclusion: DWI
with parallel imaging is a feasible technique for the detection of inflammation in patients with Crohn's
disease. ADC values are decreased in inflamed bowel segments, indicating restricted diffusion. © 2009
AUR.
Human Pulmonary Imaging and Spectroscopy with Hyperpolarized 129Xe at 0.2T
Volume 15, Issue 6, June 2008, Pages 713-727
Patz, S. | Muradian, I. | Hrovat, M.I. | Ruset, I.C. | Topulos, G. | Covrig, S.D. | Frederick, E. | Hatabu, H. |
Hersman, F.W. | Butler, J.P.
Rationale and Objectives: Using a novel 129Xe polarizer with high throughput (1-2 L/hour) and high
polarization (∼55%), our objective was to demonstrate and characterize human pulmonary applications at
0.2T. Specifically, we investigated the ability of 129Xe to measure the alveolar surface area per unit volume
of gas, SA/Vgas. Materials and Methods: Variable spin echo time (TE) gradient and radiofrequency (RF)
echoes were used to obtain estimates of the lung's contribution to both T2* and T2. Standard multislice
ventilation images were obtained and signal-to-noise ratio (SNR) determined. Whole-lung, time-dependent
measurements of 129Xe diffusion from gas to septal tissue were obtained with a chemical shift saturation
recovery (CSSR) method. Four healthy subjects were studied, and the Butler et al CSSR formalism (J Phys
Condensed Matter 2002; 14:L297-L304) was used to calculate SA/Vgas. A single-breath version of the
xenon transfer contrast (SB-XTC) method was implemented and used to image 129Xe diffusion between
alveolar gas and septal tissue. A direct comparison of CSSR and SB-XTC was performed. Results: T2* =
135 ± 29 ms amd T2 = 326.2 ± 9.5 ms. Maximum SNR = 36 for ventilation images from inhalation of 1L
86% 129Xe and voxel volume = 0.225 mL. CSSR analysis showed SA/Vgas decreased with increasing lung
volume in a manner very similar to that observed from histology measurements; however, the absolute
value of SA/Vgas was ∼40% smaller than histology values. SB-XTC images in different postures
demonstrate gravitationally dependent values. Initial comparison of CSSR with XTC showed fairly good
agreement with expected ratios. Conclusions: Hyperpolarized 129Xe human imaging and spectroscopy are
very promising methods to provide functional information about the lung. © 2008 AUR.
Validation and Statistical Power Comparison of Methods for Analyzing Free-response
Observer Performance Studies
Volume 15, Issue 12, December 2008, Pages 1554-1566
Chakraborty, D.P.
Rationale and Objectives: The aim of this work was to validate and compare the statistical powers of
proposed methods for analyzing free-response data using a search-model-based simulator. Materials and
Methods: A free-response data simulator is described that can model a single reader interpreting the same
cases in two modalities, or two computer-aided detection (CAD) algorithms, or two human observers,
interpreting the same cases in one modality. A variance components model, analogous to the Roe and
Metz receiver-operating characteristic (ROC) data simulator, is described; it models intracase and
intermodality correlations in free-response studies. Two generic observers were simulated: a quasi-human
observer and a quasi-CAD algorithm. Null hypothesis (NH) validity and statistical powers of ROC, jackknife
alternative free-response operating characteristic (JAFROC), a variant of JAFROC termed JAFROC-1, initial
detection and candidate analysis (IDCA), and a nonparametric (NP) approach were investigated. Results:
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All methods had valid NH behavior over a wide range of simulator parameters. For equal numbers of
normal and abnormal cases, for the human observer, the statistical power ranking of the methods was
JAFROC-1 > JAFROC > (IDCA ∼ NP) > ROC. For the CAD algorithm, the ranking was (NP ∼ IDCA) >
(JAFROC-1 ∼ JAFROC) > ROC. In either case, the statistical power of the highest ranked method exceeded
that of the lowest ranked method by about a factor of two. Dependence of statistical power on simulator
parameters followed expected trends. For data sets with more abnormal cases than normal cases,
JAFROC-1 power significantly exceeded JAFROC power. Conclusion: Based on this work, the
recommendation is to use JAFROC-1 for human observers (including human observers with CAD assist)
and the NP method for evaluating CAD algorithms. © 2008 AUR.
Computer-Assisted Segmentation of White Matter Lesions in 3D MR Images Using Support
Vector Machine
Volume 15, Issue 3, March 2008, Pages 300-313
Lao, Z. | Shen, D. | Liu, D. | Jawad, A.F. | Melhem, E.R. | Launer, L.J. | Bryan, R.N. | Davatzikos, C.
Rationale and Objectives: Brain lesions, especially white matter lesions (WMLs), are associated with
cardiac and vascular disease, but also with normal aging. Quantitative analysis of WML in large clinical
trials is becoming more and more important. Materials and Methods: In this article, we present a computer-
assisted WML segmentation method, based on local features extracted from multiparametric magnetic
resonance imaging (MRI) sequences (ie, T1-weighted, T2-weighted, proton density-weighted, and fluid
attenuation inversion recovery MRI scans). A support vector machine classifier is first trained on expert-
defined WMLs, and is then used to classify new scans. Results: Postprocessing analysis further reduces
false positives by using anatomic knowledge and measures of distance from the training set. Conclusions:
Cross-validation on a population of 35 patients from three different imaging sites with WMLs of varying
sizes, shapes, and locations tests the robustness and accuracy of the proposed segmentation method,
compared with the manual segmentation results from two experienced neuroradiologists. © 2008 AUR.
Diagnostic Performance of Positron Emission Tomography in the Detection of Coronary
Artery Disease. A Meta-analysis
Volume 15, Issue 4, April 2008, Pages 444-451
Nandalur, K.R. | Dwamena, B.A. | Choudhri, A.F. | Nandalur, S.R. | Reddy, P. | Carlos, R.C.
Rationale and Objectives: Although myocardial perfusion positron emission tomography (PET), using either
cyclotron-produced ammonia or generator-produced rubidium 82, has reported excellent diagnostic
capabilities in the detection of coronary artery disease (CAD) in individual studies, the technique is not
widely used in practice. This may be driven by cost and availability or by unawareness of performance. The
purpose of our study was to conduct an evidence-based evaluation of PET in the diagnosis of CAD.
Materials and Methods: We examined studies from January 1977 to July 2007 using MEDLINE and
EMBASE. A study was included if it (1) used PET as a diagnostic test for CAD and (2) used catheter x-ray
angiography as the reference standard (≥50% diameter stenosis). Analysis was performed on a subject
and coronary territory level. Results: Nineteen studies (1442 patients) met the inclusion criteria. On a patient
level, PET demonstrated a sensitivity of 0.92 (95% confidence interval [CI]: 0.90-0.94) and specificity of 0.85
(CI: 0.79-0.90), with a positive likelihood ratio (LR+) of 6.2 (CI: 3.3-11.8) and negative likelihood ratio (LR-) of
0.11 (CI: 0.08-0.14). On a coronary territory level (n = 1130), PET showed a sensitivity of 0.81 (CI: 0.77-0.84)
and specificity of 0.87 (CI: 0.84-0.90), with an LR+ of 5.9 (CI: 4.5-7.9) and an LR- of 0.19 (CI: 0.09-0.38).
Conclusion: PET demonstrates excellent diagnostic properties in the diagnosis of CAD, especially at the
patient level. The capabilities appear superior to those reported in meta-analyses for perfusion imaging
with Tl-201 and sestamibi, or anatomical imaging with coronary MDCT angiography or MRA. Given that
previous studies have found PET to be cost-effective and the current findings of excellent sensitivity and
specificity, the modality should be more widely considered as an initial test in the diagnosis of CAD. © 2008
AUR.
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Computerized Detection of Lung Nodules in Thin-Section CT Images by Use of Selective
Enhancement Filters and an Automated Rule-Based Classifier
Volume 15, Issue 2, February 2008, Pages 165-175
Li, Q. | Li, F. | Doi, K.
Rationale and Objectives: We have been developing a computer-aided diagnostic (CAD) scheme for lung
nodule detection in order to assist radiologists in the detection of lung cancer in thin-section computed
tomography (CT) images. Materials and Methods: Our database consisted of 117 thin-section CT scans
with 153 nodules, obtained from a lung cancer screening program at a Japanese university (85 scans, 91
nodules) and from clinical work at an American university (32 scans, 62 nodules). The database included
nodules of different sizes (4-28 mm, mean 10.2 mm), shapes, and patterns (solid and ground-glass
opacity (GGO)). Our CAD scheme consisted of modules for lung segmentation, selective nodule
enhancement, initial nodule detection, feature extraction, and classification. The selective nodule
enhancement filter was a key technique for significant enhancement of nodules and suppression of normal
anatomic structures such as blood vessels, which are the main sources of false positives. Use of an
automated rule-based classifier for reduction of false positives was another key technique; it resulted in a
minimized overtraining effect and an improved classification performance. We used a case-based four-fold
cross-validation testing method for evaluation of the performance levels of our computerized detection
scheme. Results: Our CAD scheme achieved an overall sensitivity of 86% (small: 76%, medium-sized:
94%, large: 95%; solid: 86%, mixed GGO: 89%, pure GGO: 81%) with 6.6 false positives per scan; an
overall sensitivity of 81% (small: 69%, medium-sized: 91%, large: 91%; solid: 79%, mixed GGO: 88%, pure
GGO: 81%) with 3.3 false positives per scan; and an overall sensitivity of 75% (small: 60%, medium-sized:
88%, large: 87%; solid: 70%, mixed GGO: 87%, pure GGO: 81%) with 1.6 false positives per scan.
Conclusion: The experimental results indicate that our CAD scheme with its two key techniques can
achieve a relatively high performance for nodules presenting large variations in size, shape, and pattern. ©
2008 AUR.
Quantitative Analysis of Lesion Morphology and Texture Features for Diagnostic Prediction in
Breast MRI
Volume 15, Issue 12, December 2008, Pages 1513-1525
Nie, K. | Chen, J.-H. | Yu, H.J. | Chu, Y. | Nalcioglu, O. | Su, M.-Y.
Rationale and Objectives: To investigate the feasibility using quantitative morphology/texture features of
breast lesions for diagnostic prediction, and to explore the association of computerized features with lesion
phenotype appearance on magnetic resonance imaging. Materials and Methods: Forty-three malignant/28
benign lesions were used in this study. A systematic approach from automated lesion segmentation,
quantitative feature extraction, diagnostic feature selection using an artificial neural network (ANN), and
lesion classification was carried out. Eight morphologic parameters and 10 gray level co-occurrence matrix
texture features were obtained from each lesion. The diagnostic performance of selected features to
differentiate between malignant and benign lesions was analyzed using receiver-operating characteristic
analysis. Results: Six features were selected by an ANN using leave-one-out cross validation, including
compactness, normalized radial length entropy, volume, gray level entropy, gray level sum average, and
homogeneity. The area under the receiver-operating characteristic curve was 0.86. When dividing the
database into half training and half validation set, a classifier of five features selected in the half training set
achieved an area under the curve of 0.82 in the other half validation set. The selected morphology feature
"compactness" was associated with shape and margin in the Breast Imaging Reporting and Data System
lexicon, round shape and smooth margin for the benign lesions, and more irregular shape for the
malignant lesions. The selected texture features were associated with homogeneous/heterogeneous
patterns and the enhancement intensity. The malignant lesions had higher intensity and broader
distribution on the enhancement histogram (more heterogeneous) compared to the benign lesions.
Conclusion: Quantitative analysis of morphology/texture features of breast lesions was feasible, and these
features could be selected by an ANN to form a classifier for differential diagnosis. Establishing the link
between computer-based features and visual descriptors defined in the BI-RADS lexicon will provide the
foundation for the acceptance of quantitative diagnostic features in the development of computer-aided
diagnosis. © 2008 AUR.
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4-D Imaging in Cerebrovascular Disorders by Using 320-Slice CT. Feasibility and Preliminary
Clinical Experience
Volume 16, Issue 2, February 2009, Pages 123-129
Klingebiel, R. | Siebert, E. | Diekmann, S. | Wiener, E. | Masuhr, F. | Wagner, M. | Bauknecht, H.-C. | Dewey,
M. | Bohner, G.
Rationale and Objectives: The authors report study protocols and initial clinical experience in assessing
patients with acute and chronic cerebrovascular disorders using the recently introduced technique of
volume computed tomography (VCT). Materials and Methods: Thirteen patients with presumptive
cerebrovascular insufficiency underwent VCT using a 320-slice scanner (detector width, 160 mm), including
time-resolved whole-brain perfusion and cerebral angiography (four-dimensional computed tomographic
angiography [CTA] and computed tomographic perfusion [CTP]). Unenhanced cranial CT (cCT) and helical
cervicocranial CT (three-dimensional CTA) were added according to clinical requirements. Study protocols
are presented, and image quality, data management, and radiation exposure issues are discussed.
Results: In 12 of 13 patients, the procedure was performed successfully on admission; in the other patient,
the study was aborted for clinical reasons and repeated. Total scan time amounted to about 5 minutes, and
data reconstruction times were up to 10 minutes. About 9000 primary images were generated, partially in
the enhanced Digital Imaging and Communications in Medicine format, thus requiring new data
postprocessing and management strategies. Image artifacts restricted the use of single-rotation cCT and
incremental VCT (three-dimensional CTA). Overall exposure figures (computed tomographic dose index
and dose-length product) were increased by 65% on average when three-dimensional CTA was added to
volume cCT and four-dimensional CTA and CTP (5.0 mSv and 2178 mGy · cm, respectively). Conclusion:
Preliminary clinical experience indicates that whole-brain four-dimensional CTA and CTP is a robust
technique that provides relevant clinical information with respect to whole-brain perfusion as well as
cerebral hemodynamics. The exposure benefit of deriving time-resolved perfusion and vessel images from
one source data set is compromised when adding three-dimensional CTA to the protocol. Other acquisition
techniques specific to VCT, such as single-rotation cCT and incremental three-dimensional CTA, suffer
from restrictions in terms of image quality at present. © 2009 AUR.
Large Production System for Hyperpolarized 129Xe for Human Lung Imaging Studies
Volume 15, Issue 6, June 2008, Pages 683-692
Hersman, F.W. | Ruset, I.C. | Ketel, S. | Muradian, I. | Covrig, S.D. | Distelbrink, J. | Porter, W. | Watt, D. | Ketel,
J. | Brackett, J. | Hope, A. | Patz, S.
Rationale and Objectives: Hyperpolarized gases such as 129Xe and 3He have high potential as imaging
agents for functional lung magnetic resonance imaging (MRI). We present new technology offering 129Xe
production rates with order-of-magnitude improvement over existing systems, to liter per hour at 50%
polarization. Human lung imaging studies with xenon, initially limited by the modest quantity and quality of
hyperpolarized gas available, can now be performed with multiliter quantities several times daily. Materials
and Methods: The polarizer is a continuous-flow system capable of producing large quantities of highly-
polarized 129Xe through rubidium spin-exchange optical pumping. The low-pressure, high-velocity
operating regime takes advantage of the enhancement in the spin exchange rate provided by van der Waals
molecules dominating the atomic interactions. The long polarizing column moves the flow of the gas
opposite to the laser direction, allowing efficient extraction of the laser light. Separate sections of the system
assure full rubidium vapor saturation and removal. Results: The system is capable of producing 64%
polarization at 0.3 L/hour Xe production rate. Increasing xenon flow reduces output polarization. Xenon
polarization was studied as a function of different system operating parameters. A novel xenon trapping
design was demonstrated to allow full recovery of the xenon polarization after the freeze-thaw cycle. Delivery
methods of the gas to an offsite MRI facility were demonstrated in both frozen and gas states. Conclusions:
We demonstrated a new concept for producing large quantities of highly polarized xenon. The system is
operating in an MRI facility producing liters of hyperpolarized gas for human lung imaging studies. © 2007
AUR.
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Automated Segmentation of the Liver from 3D CT Images Using Probabilistic Atlas and
Multilevel Statistical Shape Model
Volume 15, Issue 11, November 2008, Pages 1390-1403
Okada, T. | Shimada, R. | Hori, M. | Nakamoto, M. | Chen, Y.-W. | Nakamura, H. | Sato, Y.
Rationale and Objectives: An atlas-based automated liver segmentation method from three-dimensional
computed tomographic (3D CT) images has been developed. The method uses two types of atlases, a
probabilistic atlas (PA) and a statistical shape model (SSM). Materials and Methods: Voxel-based
segmentation with a PA is first performed to obtain a liver region, then the obtained region is used as the
initial region for subsequent SSM fitting to 3D CT images. To improve reconstruction accuracy, particularly
for highly deformed livers, we use a multilevel SSM (ML-SSM). In ML-SSM, the entire shape is divided into
patches, with principal component analysis applied to each patch. To avoid inconsistency among patches,
we introduce a new constraint called the "adhesiveness constraint" for overlapping regions among patches.
Results: The PA and ML-SSM were constructed from 20 training datasets. We applied the proposed method
to eight evaluation datasets. On average, volumetric overlap of 89.2 ± 1.4% and average distance of 1.36 ±
0.19 mm were obtained. Conclusions: The proposed method was shown to improve segmentation
accuracy for datasets including highly deformed livers. We demonstrated that segmentation accuracy is
improved using the initial region obtained with PA and the introduced constraint for ML-SSM. © 2008 AUR.
Molecular PET/CT Imaging-Guided Radiation Therapy Treatment Planning
Volume 16, Issue 9, September 2009, Pages 1108-1133
Zaidi, H. | Vees, H. | Wissmeyer, M.
The role of positron emission tomography (PET) during the past decade has evolved rapidly from that of a
pure research tool to a methodology of enormous clinical potential. 18F-fluorodeoxyglucose (FDG)-PET is
currently the most widely used probe in the diagnosis, staging, assessment of tumor response to
treatment, and radiation therapy planning because metabolic changes generally precede the more
conventionally measured parameter of change in tumor size. Data accumulated rapidly during the last
decade, thus validating the efficacy of FDG imaging and many other tracers in a wide variety of malignant
tumors with sensitivities and specificities often in the high 90 percentile range. As a result, PET/computed
tomography (CT) had a significant impact on the management of patients because it obviated the need for
further evaluation, guided further diagnostic procedures, and assisted in planning therapy for a
considerable number of patients. On the other hand, the progress in radiation therapy technology has been
enormous during the last two decades, now offering the possibility to plan highly conformal radiation dose
distributions through the use of sophisticated beam targeting techniques such as intensity-modulated
radiation therapy (IMRT) using tomotherapy, volumetric modulated arc therapy, and many other promising
technologies for sculpted three-dimensional (3D) dose distribution. The foundation of molecular imaging-
guided radiation therapy lies in the use of advanced imaging technology for improved definition of tumor
target volumes, thus relating the absorbed dose information to image-based patient representations. This
review documents technological advancements in the field concentrating on the conceptual role of
molecular PET/CT imaging in radiation therapy treatment planning and related image processing issues
with special emphasis on segmentation of medical images for the purpose of defining target volumes.
There is still much more work to be done and many of the techniques reviewed are themselves not yet
widely implemented in clinical settings. © 2009 AUR.
Significant Differentiation of Focal Breast Lesions. Calculation of Strain Ratio in Breast
Sonoelastography
Volume 17, Issue 5, May 2010, Pages 558-563
Thomas, A. | Degenhardt, F. | Farrokh, A. | Wojcinski, S. | Slowinski, T. | Fischer, T.
Rationale and Objectives: Initial data suggest that elastography can improve the specificity of ultrasound in
differentiating benign and malignant breast lesions. The aim of this study was to compare elastography
and B-mode ultrasound to determine whether the calculation of strain ratios (SRs) can further improve the
differentiation of focal breast lesions. Materials and Methods: A total of 227 women with histologically
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proven focal breast lesions (113 benign, 114 malignant) were included at two German breast centers. The
women underwent a standardized ultrasound procedure using a high-end ultrasound system with a 9-MHz
broadband linear transducer. B-mode scans and sonoelastograms were analyzed by two experienced
readers using the Breast Imaging Reporting and Data System criteria. SRs were calculated from a tumor-
adjusted region of interest (mean color pixel density) and a comparable region of interest placed in the
lateral fatty tissue. Sensitivity, specificity, and cutoff values were calculated for SRs (receiver-operating
characteristic analysis). Results: The women had a mean age of 54 years (range, 19-87 years). The mean
lesion diameter was 1.6 ± 0.9 cm. Sensitivity and specificity were 96% and 56% for B-mode scanning, 81%
and 89% for elastography, and 90% and 89% for SRs. An SR cutoff value of 2.45 (area under the curve,
0.949) allowed significant differentiation (P < .001) of malignant (mean, 5.1 ± 4.2) and benign (mean, 1.6 ±
1.0) lesions. The quantitative method of SR calculation was superior to subjective interpretation of
sonoelastograms and B-mode scans, with a positive predictive value of 89% compared to 68% and 84% for
the other two methods. Conclusions: Calculation of SRs contributes to the standardization of
sonoelastography with high sensitivity and allows significant differentiation of benign and malignant breast
lesions with higher specificity compared to B-mode ultrasound but not elastography. © 2010 AUR.
Multiparametric Tissue Characterization of Brain Neoplasms and Their Recurrence Using
Pattern Classification of MR Images
Volume 15, Issue 8, August 2008, Pages 966-977
Verma, R. | Zacharaki, E.I. | Ou, Y. | Cai, H. | Chawla, S. | Lee, S.-K. | Melhem, E.R. | Wolf, R. | Davatzikos, C.
Rationale and Objectives: Treatment of brain neoplasms can greatly benefit from better delineation of bulk
neoplasm boundary and the extent and degree of more subtle neoplastic infiltration. Magnetic resonance
imaging (MRI) is the primary imaging modality for evaluation before and after therapy, typically combining
conventional sequences with more advanced techniques such as perfusion-weighted imaging and
diffusion tensor imaging (DTI). The purpose of this study is to quantify the multiparametric imaging profile of
neoplasms by integrating structural MRI and DTI via statistical image analysis methods to potentially
capture complex and subtle tissue characteristics that are not obvious from any individual image or
parameter. Materials and Methods: Five structural MRI sequences, namely, B0, diffusion-weighted images,
fluid-attenuated inversion recovery, T1-weighted, and gadolinium-enhanced T1-weighted, and two scalar
maps computed from DTI (ie, fractional anisotropy and apparent diffusion coefficient) are used to create an
intensity-based tissue profile. This is incorporated into a nonlinear pattern classification technique to create
a multiparametric probabilistic tissue characterization, which is applied to data from 14 patients with newly
diagnosed primary high-grade neoplasms who have not received any therapy before imaging. Results:
Preliminary results demonstrate that this multiparametric tissue characterization helps to better differentiate
among neoplasm, edema, and healthy tissue, and to identify tissue that is likely to progress to neoplasm in
the future. This has been validated on expert assessed tissue. Conclusion: This approach has potential
applications in treatment, aiding computer-assisted surgery by determining the spatial distributions of
healthy and neoplastic tissue, as well as in identifying tissue that is relatively more prone to tumor
recurrence. © 2008 AUR.
Breast MRI for Cancer Detection and Characterization. A Review of Evidence-Based Clinical
Applications
Volume 15, Issue 4, April 2008, Pages 408-416
DeMartini, W. | Lehman, C. | Partridge, S.
Rationale and Objectives: Breast MRI is an important new tool in the imaging armamentarium for the
detection and characterization of breast carcinoma. Understanding the evidence-supported benefits and
potential harms of breast MRI is important to ensure the appropriate utilization of this medical resource.
Materials and Methods: This article reviews the clinical settings in which MRI for breast cancer assessment
has been shown to be advantageous. The evidence regarding the diagnostic accuracy of MRI and the
impact of this imaging tool on clinical outcomes are described. Novel breast MRI techniques which may
lead to future improvements in performance are discussed. Results: Breast MRI has been shown in
multiple studies to be advantageous for screening patients at high risk, evaluating patients with a new
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breast cancer diagnosis, monitoring treatment response in patients undergoing neoadjuvant chemotherapy
and evaluating patients with metastatic axillary adenocarcinoma and unknown primary site. Among the
limitations of MRI are its high cost and modest specificity resulting in false positive examinations.
Conclusions: When used in evidence-supported clinical settings, the high sensitivity of MRI results in
earlier cancer detection or greater accuracy of detection compared to existing tests for breast carcinoma.
Further scientific endeavors are crucial to optimize the future performance and application of breast MRI. ©
2008 AUR.
Breast Cancer. Sentinel Node Identification and Classification after Neoadjuvant
Chemotherapy-Systematic Review and Meta Analysis
Volume 16, Issue 5, May 2009, Pages 551-563
Kelly, A.M. | Dwamena, B. | Cronin, P. | Carlos, R.C.
Rationale and Objectives: Breast cancer is the leading cause of mortality in women worldwide. Lymphatic
mapping with sentinel node biopsy has the potential to reduce the morbidity associated with breast cancer
staging in women after neoadjuvant therapy. Materials and Methods: A systematic search of world literature
between 1996 and 2007 of sentinel node mapping in patients with early-stage breast carcinoma after
chemotherapy was undertaken. Potentially eligible studies were identified using database-specific search
strategies incorporating appropriate Boolean combinations of the keywords sentinel node biopsy or
sentinel node localization or lymphatic mapping; breast cancer or malignancy or neoplasm; and
preoperative or neoadjuvant chemotherapy. The electronic searches were augmented with a manual
search of reference lists from identified articles. Successful lymph node mapping, defined as successful
identification rate (SIR), and false-negative rate (FNR) was summarized using a bivariate random effects
mixed model. The extent of heterogeneity was assessed using the inconsistency statistic. The effect of
study level covariates, such as use of immunohistochemistry or dual mapping technique, and individual
quality criteria, such as study design or multi-institution participation, on SIR and FNR were analyzed using
metaregression. Results: A total of 24 trials of 1799 subjects were reported that met eligibility criteria. All
studies identified were published between 2000 and 2007. Lymph node involvement was found in 758
patients (37%) and ranged from 25% to 96% across studies. The proportion of patients who had
successful lymph node mapping ranged from 63% to 100%, with 79% of studies reporting a rate of less
than 95%. The summary successful identification rate was 0.896 (95% confidence interval [CI] 0.860-0.923)
with moderate heterogeneity. The summary FNR was 0.084 (95% CI 0.064-0.109) with no significant
heterogeneity. Increasing prevalence of lymph node involvement and same-day mapping and lymph node
dissection both significantly reduced the FNR. Conclusions: The present systematic review demonstrates
robust estimates of successful identification rate and false-negative rates of sentinel lymph node mapping
and biopsy after neoadjuvant therapy for early-stage breast cancer patients. With a 90% SIR and 8% FNR,
this technique is a reliable tool for planning treatment in this population as an alternative to completion
axillary lymph node dissection. © 2009 AUR.
Registration Methodology for Histological Sections and In Vivo Imaging of Human Prostate
Volume 15, Issue 8, August 2008, Pages 1027-1039
Park, H. | Piert, M.R. | Khan, A. | Shah, R. | Hussain, H. | Siddiqui, J. | Chenevert, T.L. | Meyer, C.R.
Rationale and Objectives: Registration enables quantitative spatial correlation of features from different
imaging modalities. Our objective is to register in vivo imaging with histologic sections of the human
prostate so that histologic truth can be correlated with in vivo imaging features. Materials and Methods: In
vivo imaging of the prostate included T2-weighted anatomic and diffusion weighted 3-T magnetic
resonance imaging (MRI) as well as 11C-choline positron emission tomography (PET). In addition, ex vivo
3-T MRI of the prostate specimen, histology, and associated block face photos of the prostate specimen
were obtained. A standard registration method based on mutual information (MI) and thin-plate spline (TPS)
was applied. Registration among in vivo imaging modalities is well established; however, accurate
registration involving histology is difficult. Our approach breaks up the difficult direct registration of histology
and in vivo imaging into achievable subregistration tasks involving intermediate ex vivo modalities like block
face photography and specimen MRI. Results of subregistration tasks are combined to compute the
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intended, final registration between in vivo imaging and histology. Results: The methodology was applied to
two patients and found to be clinically feasible. Overall registered anatomic MRI, diffusion MRI, and 11C-
choline PET aligned well with histology qualitatively for both patients. There is no ground truth of registration
accuracy as the scans are real patient scans. An indirect validation of the registration accuracy has been
proposed comparing tumor boundary markings found in diffusion MRI and histologic sections. Registration
errors for two patients between diffusion MRI and histology were 3.74 and 2.26 mm. Conclusion: This proof
of concept paper demonstrates a method based on intrinsic image information content for successfully
registering in vivo imaging of the human prostate with its post-resection histology, which does not require
the use of extrinsic fiducial markers. The methodology successfully mapped histology onto the in vivo
imaging space, allowing the observation of how well different in vivo imaging features correspond to
histologic truth. The methodology is therefore the basis for a systematic comparison of in vivo imaging for
staging of human prostate cancer. © 2008 AUR.
Evaluation of Structure-Function Relationships in Asthma using Multidetector CT and
Hyperpolarized He-3 MRI
Volume 15, Issue 6, June 2008, Pages 753-762
Fain, S.B. | Gonzalez-Fernandez, G. | Peterson, E.T. | Evans, M.D. | Sorkness, R.L. | Jarjour, N.N. | Busse,
W.W. | Kuhlman, J.E.
Rationale and Objectives: Although multiple detector computed tomography (MDCT) and hyperpolarized
gas magnetic resonance imaging (HP MRI) have demonstrated ability to detect structural and ventilation
abnormalities in asthma, few studies have sought to exploit or cross-validate the regional information
provided by these techniques. The purpose of this work is to assess regional disease in asthma by
evaluating the association of sites of ventilation defect on HP MRI with other regional markers of airway
disease, including air trapping on MDCT and inflammatory markers on bronchoscopy. Materials and
Methods: Both HP MRI using helium-3 and MDCT were acquired in the same patients. Supervised
segmentation of the lung lobes on MRI and MDCT facilitated regional comparisons of ventilation
abnormalities in the lung parenchyma. The percentage of spatial overlap was evaluated between regions of
ventilation defect on HP MRI and hyperlucency on MDCT to determine associations between obstruction
and likely regions of gas trapping. Similarly, lung lobes with high defect volume were compared to lobes
with low defect volume for differences in inflammatory cell number and percentage using bronchoscopic
assessment. Results: There was significant overlap between sites of ventilation defect on HP MRI and
hyperlucency on MDCT suggesting that sites of airway obstruction and air trapping are associated in
asthma. The percent (r = 0.68; P = .0039) and absolute (r = 0.61; P = .0125) number of neutrophils on
bronchoalveolar lavage for the sampled lung lobe also directly correlated with increased defect volume.
Conclusions: These results show promise for using image guidance to assess specific regions of
ventilation defect or air trapping in heterogeneous obstructive lung diseases such as asthma. © 2008 AUR.
The Value of Diffusion-Weighted Imaging in Characterizing Focal Liver Masses
Volume 16, Issue 10, October 2009, Pages 1208-1214
Sandrasegaran, K. | Akisik, F.M. | Lin, C. | Tahir, B. | Rajan, J. | Aisen, A.M.
Rationale and Objectives: To determine if focal liver masses could be differentiated as benign or malignant
on the basis of diffusion-weighted imaging (DWI). Methods and Materials: A total of 104 patients with focal
liver masses were scanned using 1.5 T magnetic resonance imaging (MRI). DWI was performed with b
values of 0, 50, and 400 s/mm2. Of these, 76 patients had lesions larger than 2 cm diameter, radiologic or
pathologic characterization of the lesion, and diagnostic quality DWI. The apparent diffusion coefficient
(ADC) of the largest liver lesion was measured. The liver masses were diagnosed on histology or had
characteristic computed tomography/MRI findings and follow up of more than 6 months. The analyzed
lesions were hemangioma (n = 17), cysts (n = 5), hepatocellular cancer (HCC) (n = 41), adenoma (n = 3),
focal nodular hyperplasia (FNH) (n = 6), and metastases (n = 4). Results: The mean (standard deviation)
ADC values (10-5 mm2/second) of hemangiomas, cysts, FNH, and HCC were 156.8 (54.1), 190.2 (43.0),
130.1 (81.9), and 107.6 (32.7). The ADC of cysts and hemangiomas were significantly higher than that of
other lesions (P = .0003, t-test). There was no significant difference between ADC values of solid, benign
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liver lesions (FNH, adenoma) and malignant lesions (HCC, metastases) (P = .62). Conclusion: Solid liver
lesions have a lower ADC than cysts and hemangiomas. However, there is no significant difference in ADC
between solid benign and malignant lesions. DWI appears to have only minimal additional value over
currently used MRI sequences in characterizing liver masses. © 2009 AUR.
Ultrasonic Viscoelasticity Imaging of Nonpalpable Breast Tumors. Preliminary Results
Volume 15, Issue 12, December 2008, Pages 1526-1533
Qiu, Y. | Sridhar, M. | Tsou, J.K. | Lindfors, K.K. | Insana, M.F.
Rationale and Objectives: Improvements in the diagnosis of early breast cancers depend on a physician's
ability to obtain the information necessary to distinguish nonpalpable malignant and benign
tumors.Viscoelastic features that describe mechanical properties of tissues may help to distinguish these
types of lesions. Materials and Methods: Twenty-one patients with nonpalpable, pathology-confirmed Breast
Imaging Reporting and Data System (BIRADS) 4 or 5 breast lesions (10 benign, 11 malignant) detected by
mammography were studied. Viscoelastic parameters were extracted from a time sequence of ultrasonic
strain images, and differences in the parameters between malignant and benign tumors were compared.
Parametric data were color coded and superimposed on sonograms. Results: The strain retardance time
parameter, T1, provided the best discrimination between malignant and benign tumors (P < .01). T1
measures the time required for tissues to fully deform (strain) once compressed; therefore, it describes the
time-varying viscous response of tissue to a small deforming force. Compared to the surrounding
background tissues, malignant lesions have smaller average T1 values, whereas benign lesions have
higher T1 values. This tissue-specific contrast correlates with known changes in the extracellular matrix of
breast stroma. Conclusion: Characterization of nonpalpable breast lesions is improved by the addition of
viscoelastic strain imaging parameters. The differentiation of malignant and benign BI-RADS 4 or 5 tumors
is especially evident with the use of the retardation time estimates, T1. © 2008 AUR.
Hyperpolarized 3He Magnetic Resonance Imaging of Chronic Obstructive Pulmonary
Disease. Reproducibility at 3.0 Tesla
Volume 15, Issue 10, October 2008, Pages 1298-1311
Mathew, L. | Evans, A. | Ouriadov, A. | Etemad-Rezai, R. | Fogel, R. | Santyr, G. | McCormack, D.G. | Parraga,
G.
Rationale and Objectives: We assessed subjects with stage II and stage III chronic obstructive pulmonary
disease (COPD) and age-matched healthy volunteers at a single center using 3He magnetic resonance
imaging (MRI) at 3.0 T. Measurements of the 3He apparent diffusion coefficient (ADC) and center coronal
slice 3He ventilation defect volume (VDV) were examined for same-day and 7-day reproducibility as well as
subgroup comparisons. Materials and Methods: Twenty-four subjects who provided written informed
consent (15 males; mean age 67 ±7 years) with stage II (n = 9), stage III COPD (n = 7), and age-matched
healthy volunteers (n = 8) were enrolled based on their age and pulmonary function test results. All subjects
underwent plethysmography, spirometry, and MRI at 3.0 T. The time frame between scans was 7 ± 2
minutes (same-day rescan) and again 7 ± 2 days later (7-day rescan). 3He ADC and VDV reproducibility
was evaluated using linear regression, intraclass correlation coefficients (ICC) and Lin's concordance
correlation coefficients (CCC). Results: ADC reproducibility was high for same-day rescan (r2 = 0.934) and
7-day rescan (r2 = 0.960, ICC and CCC of 0.96 and 0.98, respectively). Same-day rescan VDV
reproducibility evaluated using the ICC and CCC (0.97 and 0.98, respectively) as well as linear regression
(r2 = 0.941) was also high, but VDV 7-day rescan reproducibility was lower and significantly different (r2 =
0.576, P < .001, ICC 0.74, CCC 0.75, P < .01). Conclusions: Hyperpolarized 3He MRI was well-tolerated in
subjects with stage II and stage III COPD. Seven-day repeated scanning was highly reproducible for ADC
and moderately reproducible for VDV. © 2008 AUR.
Semi-quantitating Stiffness of Breast Solid Lesions in Ultrasonic Elastography
Volume 15, Issue 11, November 2008, Pages 1347-1353
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Zhi, H. | Xiao, X.-Y. | Yang, H.-Y. | Wen, Y.-L. | Ou, B. | Luo, B.-M. | Liang, B.-l.
Rationale and Objectives: To explore whether strain ratio measurement could semi-quantitatively evaluate
the stiffness of breast lesions. Materials and Methods: From January 2008 to May 2008, 148 patients with
254 solid lesions (183 benign, 71 malignant) in the breast were included in the study. Ultrasound
sonography found the lesions and ultrasonic elastography obtained the strain images. By using the strain
ratio measurement method together with the ultrasound machine, the strain index of the lesion was
calculated. Different depths of breast tissue were selected as the reference. The strain indexes of
malignant and benign solid lesions were calculated with the same level of breast tissue as the reference.
Results: The strain indexes of breast lesions were different compared to the same depth of breast tissue
and the superior level of fat tissue (P = 0.000). The strain indexes of breast lesions were different compared
to different depths of breast glandular tissues (P = 0.003). At the same level of the breast lesions, 212
lesions were glandular tissue, 11 were fat tissue, and 40 were both. In the lesion plane, six lesions had
almost no glandular tissue and 20 had almost no superior fat tissue. Compared to the same depth of
breast tissue, the strain indexes of benign lesions (range, 0.62-11.07) and malignant lesions (range, 3.12-
39.28) were different (P = 0.000). Conclusion: Using the strain ratio measurement, stiffness of breast
lesions could be semi-quantitated with the same depth of breast tissue as the reference. This method may
provide another diagnostic method in addition to the 5-point scoring system used with ultrasonic
elastography in the future. © 2008 AUR.
Design and Implementation of a Compact Low-Dose Diffraction Enhanced Medical Imaging
System
Volume 16, Issue 8, August 2009, Pages 911-917
Parham, C. | Zhong, Z. | Connor, D.M. | Chapman, L.D. | Pisano, E.D.
Rationale and Objectives: Diffraction-enhanced imaging (DEI) is a new x-ray imaging modality that differs
from conventional radiography in its use of three physical mechanisms to generate contrast. DEI is able to
generate contrast from x-ray absorption, refraction, and ultra-small-angle scatter rejection (extinction) to
produce high-contrast images with a much lower radiation dose compared to conventional radiography.
Materials and Methods: A prototype DEI system was constructed using a 1-kW tungsten x-ray tube and a
single silicon monochromator and analyzer crystal. The monochromator crystal was aligned to reflect the
combined Kα1 (59.32 keV) and Kα2 (57.98 keV) characteristic emission lines of tungsten using a tube
voltage of 160 kV. System performance and demonstration of contrast were evaluated using a nylon
monofilament refraction phantom, full-thickness breast specimens, a human thumb, and a live mouse.
Results: Images acquired using this system successfully demonstrated all three DEI contrast
mechanisms. Flux measurements acquired using this 1-kW prototype system demonstrated that this
design can be scaled to use a more powerful 60-kW x-ray tube to generate similar images with an image
time of approximately 30 seconds. This single-crystal pair design can be further modified to allow for an
array of crystals to reduce clinical image times to <3 seconds. Conclusions: This paper describes the
design, construction, and performance of a new DEI system using a commercially available tungsten
anode x-ray tube and includes the first high-quality low-dose diffraction-enhanced images of full-thickness
human tissue specimens. © 2009 AUR.
Normal Thoracic Aorta Diameter on Cardiac Computed Tomography in Healthy Asymptomatic
Adults. Impact of Age and Gender
Volume 15, Issue 7, July 2008, Pages 827-834
Mao, S.S. | Ahmadi, N. | Shah, B. | Beckmann, D. | Chen, A. | Ngo, L. | Flores, F.R. | Gao, Y.l. | Budoff, M.J.
Rationale and Objectives: To establish the normal criterion of ascending aortic diameter (AAOD) measured
by 64 multidetector computed tomography (MDCT) and electron beam computed tomography (EBT) based
on gender and age. Materials and Methods: A total of 1442 consecutive subjects who were referred for
evaluation of possible coronary artery disease underwent coronary computed tomographic (CT)
angiography (CTA) and coronary artery calcium scanning (CACS) (55 + 11 years, 65% male) without known
coronary heart disease, hypertension, chronic pulmonary and renal disease, diabetes, and severe aortic
calcification. The AAOD aortic diameter, descending aortic diameter (DAOD), pulmonary artery (PAD), and
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chest anteroposterior diameter (CAPD), posterior border of the sternal bone to the anterior border of the
spine, were measured at the slice level of mid-right pulmonary artery using end systolic trigger imaging.
The volume of four chambers, ejection fraction of left ventricle, and cardiac output were measured in 56% of
the patients. Patients' demographic information, age, gender, weight, height, and body surface area were
recorded. The mean value and age-specific and gender-adjusted upper normal limits (mean ± 2 standard
deviation) were calculated. The linear correlation analysis was done between AAOD and all parameters.
The reproducibility, wall thickness, and difference between end-systole and end-diastole were calculated.
Results: AAOD has significant linear association with age, gender, DAOD, and pulmonary artery diameter
(P < .05). There is no significant correlation between AAOD and body surface area, four-chamber volume,
left ventricular ejection fraction, cardiac output, and CAPD. The mean intraluminal AAOD was 31.1 ± 3.9 and
33.6 ± 4.1 mm in females and males, respectively. The upper normal limits (mean ± 2 standard deviations)
of intraluminal AAOD, were 35.6, 38.3, and 40 mm for females and 37.8, 40.5, and 42.6 mm for males in
age groups 20-40, 41-60, and older than 60 years, respectively. Intraluminal aortic diameters should
parallel echocardiography and invasive angiography. Traditional cross-sectional imaging (with CT and
magnetic resonance imaging) includes the vessel wall. The mean total AAOD was 33.5 and 36.0 mm in
females and males, respectively. The upper normal limits (mean ± 2 standard deviations) of intraluminal
AAOD were 38.0, 40.7 and 42.4 mm for females and 40.2, 42.9, and 45.0 mm for males in age group 20 to
40, 41 to 60, and older than 60 years, respectively. The inter- and intraobserver, scanner, and repeated
measurement variabilities were low (r value >0.91, P < .001, coefficient variation <3.2%). AAOD was 1.7 mm
smaller in end-diastole than end-systole (P < .001). Conclusions: The AAOD increases with age and male
gender. Gender-specific and age-adjusted normal values for aortic diameters are necessary to differentiate
pathologic atherosclerotic changes in the ascending aorta. Use of intraluminal or total aortic diameter
values depends on the comparison study employed. © 2008 AUR.
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