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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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