Michael L. Lieber

Morphology, Attenuation, Size, and Structure (MASS) Criteria: Assessing Response and Predicting Clinical Outcome in Metastatic Renal Cell Carcinoma on Antiangiogenic Targeted Therapy

OBJECTIVE The objective of our study was to evaluate response assessment and predict clinical outcome in patients with metastatic renal cell carcinoma (RCC) receiving antiangiogenic targeted therapy. Target lesions were assessed on routine contrast-enhanced CT (CECT) images obtained during the portal venous phase using new response criteria. MATERIALS AND METHODS Standard CECT examinations of patients with metastatic clear cell RCC on first-line sunitinib or sorafenib therapy (n = 84) were retrospectively evaluated using Mass, Attenuation, Size, and Structure (MASS) Criteria; Response Evaluation Criteria in Solid Tumors (RECIST); Size and Attenuation CT (SACT) Criteria; and modified Choi Criteria. The objective response to therapy was compared with clinical outcomes including time to progression (TTP) and disease-specific survival. The Kaplan-Meier method was used to estimate survival functions. RESULTS A favorable response according to MASS Criteria had a sensitivity of 86% and specificity of 100% in identifying patients with a good clinical outcome (i.e., progression-free survival of > 250 days) versus 17% and 100%, respectively, for RECIST partial response. The objective categories of response used by MASS Criteria-favorable response, indeterminate response, and unfavorable response-differed significantly from one another with respect to TTP (p < 0.0001, log-rank test) and disease-specific survival (p < 0.0001, log-rank test). CONCLUSION Assessment of metastatic RCC target lesions on CECT for changes in morphology, attenuation, size, and structure by MASS Criteria is more accurate than response assessment by SACT Criteria, RECIST, or modified Choi Criteria. Furthermore, the use of MASS Criteria for imaging response assessment showed high interobserver agreement and may predict disease outcome in patients with metastatic RCC on targeted therapy.

Non-invasive assessment of plaque morphology and remodeling in mildly stenotic coronary segments: comparison of 16-slice computed tomography and intravascular ultrasound

BackgroundNon-invasive identification and characterization of mildly stenotic atherosclerotic lesions is an increasingly important focus of coronary imaging. DesignWe examined the accuracy of multi (16)-slice computed tomography (MSCT) for imaging of these lesions in comparison with intravascular ultrasound (IVUS). MaterialsMildly stenotic segments of the left coronary artery were identified by coronary angiography and analyzed using IVUS and contrast-enhanced MSCT. Independent reviewers evaluated the accuracy of MSCT for presence, composition and distribution of atherosclerotic plaque and remodeling response in comparison to IVUS using receiver operating characteristic (ROC) data analysis. ResultsOf 46 segments in 14 patients, diagnostic characterization by MSCT was possible in 37 (80.4%) segments. In these segments the accuracy of MSCT for identifying plaque presence, calcification, distribution and positive remodeling was consistently greater than 0.90 (reader 1) and 0.87 (reader 2). ConclusionState-of-the-art MSCT can accurately identify mildly stenotic coronary atherosclerosis and provide an assessment of morphology and remodeling response.

Assessing Tumor Response and Detecting Recurrence in Metastatic Renal Cell Carcinoma on Targeted Therapy: Importance of Size and Attenuation on Contrast-Enhanced CT

OBJECTIVE The aim of this study was to improve response assessment in patients with metastatic renal cell carcinoma (RCC) on antiangiogenic targeted therapy by evaluating changes in both tumor size and attenuation and by detecting unique patterns of contrast enhancement on contrast-enhanced CT (CECT). MATERIALS AND METHODS Tumor long-axis measurements and volumetric mean tumor attenuation of target lesions on CECT images were correlated with time to progression in 53 patients with metastatic clear cell RCC treated with first-line sorafenib or sunitinib. The frequencies of specific patterns of tumor progression were assessed. The data were used to develop new imaging criteria, the size and attenuation CT (SACT) criteria. CECT findings were evaluated using the SACT criteria, Response Evaluation Criteria in Solid Tumors (RECIST), and modified Choi criteria, and the Kaplan-Meier method was used to estimate survival functions. RESULTS One or more target metastatic lesions had decreased attenuation of >or=40 HU in 59% of patients with progression-free survival of >250 days (n=44) after initiating targeted therapy; 0% of patients with earlier disease progression (n=9) had this finding. A favorable response based on SACT criteria had a sensitivity of 75% and specificity of 100% for identifying patients with progression-free survival of >250 days, versus 16% and 100%, respectively, for RECIST and 93% and 44% for the modified Choi criteria. CONCLUSION Objectively measuring changes in both tumor size and attenuation on the first CECT study after initiating targeted therapy for metastatic RCC markedly improves response assessment. Distinct patterns of disease recurrence are seen in patients with metastatic RCC on targeted therapy.

Confidence intervals for the receiver operating characteristic area in studies with small samples

RATIONALE AND OBJECTIVES The authors performed this study to address two practical questions. First, how large does the sample size need to be for confidence intervals (CIs) based on the usual asymptotic methods to be appropriate? Second, when the sample size is smaller than this threshold, what alternative method of CI construction should be used? MATERIALS AND METHODS The authors performed a Monte Carlo simulation study where 95% CIs were constructed for the receiver operating characteristic (ROC) area and for the difference between two ROC areas for rating and continuous test results--for ROC areas of moderate and high accuracy--by using both parametric and nonparametric estimation methods. Alternative methods evaluated included several bootstrap CIs and CIs with the Student t distribution. RESULTS For the difference between two ROC areas, CIs based on the asymptotic theory provided adequate coverage even when the sample size was very small (20 patients). In contrast, for a single ROC area, the asymptotic methods do not provide adequate CI coverage for small samples; for ROC areas of high accuracy, the sample size must be large (more than 200 patients) for the asymptotic methods to be applicable. The recommended alternative (bootstrap percentile, bootstrap t, or bootstrap bias-corrected accelerated method) depends on the estimation approach, format of the test results, and ROC area. CONCLUSION Currently, there is not a single best alternative for constructing CIs for a single ROC area for small samples.

Do segmented reconstruction algorithms for cardiac multi-slice computed tomography improve image quality?

Purpose: To evaluate segmented reconstruction algorithms for spiral multi-slice computed tomography (MSCT) that use data from two cardiac cycles to improve temporal resolution (τ) for imaging of the heart. Materials and Methods: An initial group of 78 cardiac patients (heart rates [HR] = 63–167 beats per minute [bpm]) were imaged on a 4-slice, 500 ms gantry rotation time scanner (scanner 1). Images were reconstructed with a single-segment algorithm using data from one cardiac cycle with a reconstruction window of fixed length (τ = 250 ms). Images were also reconstructed with two variants of a multi-segment algorithm using data from two cardiac cycles where only one end of the reconstruction window was fixed and the other end was freely moveable to allow adjustment of τ according to HR: (1) “2-segment fixed start” with fixed start of reconstruction, (2) “2-segment fixed end” with fixed end of reconstruction (for both, τ = 125–250 ms). The resulting image sets were ranked from best to worst (1–3, respectively) in a side-by-side, blinded comparison by two independent readers. A second group of 26 patients (HR = 74–90 bpm) were imaged on a 12-slice, 420 ms gantry rotation time scanner (scanner 2). Data were reconstructed with a single-segment algorithm (τ = 210 ms) and a “2-segment fixed start” algorithm (τ = 105–210 ms) and image sets were ranked from best to worst (1–2, respectively). Results: There was no clear evidence that any one technique is superior for imaging on scanner 1. Reader 1 ranked single-segment images the highest for all HRs, but statistically significant differences among the three algorithms were only found for the lowest HRs (< 80 bpm), where reader 1 preferred singlesegment over “2-segment fixed end” techniques (p = 0.048). The highest rankings given by reader 2 varied according to HR: single-segment images were superior for lowest HRs, while “2-segment fixed start” images were superior for HRs > 80 bpm; none of these comparisons reached statistical significance. Improved performance of 2-segment reconstruction was found with scanner 2. Both readers ranked “2-segment fixed start” images the highest (p < 0.01). Conclusions: The added value of 2-segment cardiac reconstruction algorithms for spiral MSCT was not demonstrated for a 4-slice, 500 ms gantry rotation time scanner but shown to be beneficial for a 12-slice, 420 ms gantry rotation time scanner in the crucial HR range of 74–90 bpm.Hintergrund und Ziel: Die im Vergleich zu Elektronenstrahl-Computertomographie, Magnetresonanztomographie, Fluoroskopie und Ultraschall relativ geringe zeitliche Auflösung (τ) und entsprechend längere Bildakquisitionszeit gegenwärtiger Mehrschicht-Computertomographie-(MSCT-)Systeme sind ein wichtiger limitierender Faktor für kardiovaskuläre Untersuchungen. Mehrere spezielle Rekonstruktionsalgorithmen wurden mit dem Ziel entwickelt, die zeitliche Auflösung (τ) für kardiovaskuläre MSCT-Untersuchungen zu verbessern. Bei Einzelsegment-Rekonstruktionsalgorithmen stammt die gesamte Bildinformation jedes Schnittbildes aus einem einzelnen Herzzyklus, und die zeitliche Auflösung (τ) entspricht der Gantry-Rotationszeit (trot)/2. Mehrsegment-Rekonstruktionsalgorithmen werden für Patienten mit hoher Herzfrequenz (HR) empfohlen (HR > 65–70 Schläge/min, abhängig vom benutzten System und Algorithmus), um die effektive zeitliche Auflösung im Vergleich zu Einzelsegmentalgorithmen zu erhöhen. Mehrsegmentalgorithmen reduzieren das Aufnahmezeitintervall, das durch Nutzung der Bildinformation aus derselben Phase von n aufeinander folgenden Herzzyklen zu jedem Schnittbild beiträgt. Mehrsegmentrekonstruktion erreicht eine zeitliche Auflösung zwischen trot/2n und trot/2, abhängig von der Herzfrequenz (Abbildungen 1 und 2). Das Ziel dieser Studie war zu untersuchen, ob Mehrsegment Rekonstruktionsalgorithmen die Bildqualität tatsächlich verbessern. Die Bildqualität von 4- und 12-Schicht-Systemen wurde in Einzel- und Mehrsegmentrekonstruktionen mit n = 2 Herzzyklen verglichen. Material und Methodik: Eine Gruppe von 78 Patienten (HR = 63–167 Schläge/min) wurde mit einem 4-Schicht-System mit 500 ms Gantry-Rotationszeit (SOMATOM Sensation 4, Siemens Medical Solutions, Erlangen; Scanner 1) untersucht. Die Untersuchungen wurden nach Kontrastmittelgabe in retrospektiv EKG-getriggerter Spiraltechnik durchgeführt. Die Bildrekonstruktion erfolgte mit einem Einzelsegmentalgorithmus der Bildinformation aus einem einzelnen Herzzyklus mit einem Rekonstruktionsfenster konstanter Länge (τ = 250 ms; Abbildung 3a). Darüber hinaus wurde die Bildrekonstruktion mit zwei verschiedenen Mehrsegmentalgorithmen durchgeführt. Diese Mehrsegmentalgorithmen nutzten die Bildinformation aus zwei Herzzyklen, wobei ein Ende des Rekonstruktionsfenster fixiert war und das andere Ende verschoben werden konnte mit dem Ziel, die zeitliche Auflösung (τ) der jeweiligen Herzfrequenz anzupassen. Die beiden Varianten wurden beschrieben als 1. “2-segment fixed start” mit festgelegtem Ausgangspunkt der Rekonstruktion (Abbildung 3b) und 2. “2-segment fixed end” mit festgelegtem Endpunkt der Rekonstruktion (für beide Varianten: τ = 125–250 ms; Abbildung 3c). Die Bildqualität der entsprechenden Bildsätze wurde auf einer Skala von 1 (höchste Qualität) bis 3 (niedrigste Qualität) mit einem “side-by-side” verblindeten Vergleich von zwei Untersuchern bewertet. Eine zweite Gruppe von Patienten mit Herzfrequenzen zwischen 74 und 90 Schlägen/min wurde mit einen 12-Schicht-System mit 420 ms Gantry-Rotationszeit (SOMATOM Sensation 16, Siemens Medical Solutions, Erlangen; Scanner 2) untersucht. Die Untersuchungen wurden nach Kontrastmittelgabe in retrospektiv EKG-getriggerter Spiraltechnik durchgeführt. Die Bildrekonstruktion erfolgte mit einem Einzelsegmentalgorithmus (τ = 210 ms) und einem “2-segment fixed start”-Algorithmus (τ = 105–210 ms). Die Bildqualität der entsprechenden Bildsätze wurde auf einer Skala von 1 (höchste Qualität) bis 2 (niedrigste Qualität) von zwei Untersuchern gewertet. Ergebnisse: Die Mittelwerte (“mean rank”) der Bildqualität für die drei Bildsätze der mit Scanner 1 untersuchten Patienten sind in Tabelle 1 für zwei Untersucher zusammengefasst. Die Mittelwerte (“mean rank”) der Bildqualität für die drei Bildsätze in Abhängigkeit von der Herzfrequenz zeigt Tabelle 2. Die Bewertung der verschiedenen Rekonstruktionstechniken mit Scanner 1 war untersucherabhängig (Abbildung 4). Untersucher 1 bewertete die Bildqualität der Einzelsegmentrekonstruktion für alle Herzfrequenzen höher, signifikante Unterschiede zwischen den drei Rekonstruktionsalgorithmen wurden jedoch nur für niedrige Herzfrequenzen (HR < 80 Schläge/min) gefunden. Für diese Herzfrequenzen bewertete Untersucher 1 Einzelsegment- höher als “2-segment fixed end”-Techniken (p = 0,048). Die Bewertung der Bildqualität durch Untersucher 2 hing von der Herzfrequenz ab: Die Bildqualität von Einzelsegmentrekonstruktionen war für niedrigere Herzfrequenzen höher, während die Bildqualität von “2-segment fixed start”-Rekonstruktionen für Herzfrequenzen > 80 Schläge/min höher bewertet wurde. Allerdings erreichten diese Unterschiede für Untersucher 2 in keinem der Vergleiche statistische Signifikanz. Insgesamt zeigten die Ergebnisse der mit dem 4-Schicht-System untersuchten Patienten, dass Einzelsegmentalgorithmen für Herzfrequenzen zwischen 63 and 80 Schlägen/min bevorzugt wurden und dass die “2-segment fixed end”-Algorithmen für alle Herzfrequenzen keinen Vorteil aufwiesen. Allerdings erreichten die Unterschiede zwischen den verschiedenen Rekonstruktionstechniken mit Scanner 1 keine statistische Signifikanz. Die Mittelwerte (“mean rank”) der Bildqualität für die Bildsätze der mit Scanner 2 untersuchten Patienten sind in Tabelle 3 für zwei Untersucher zusammengefasst. 2-Segment-Rekonstruktionen hatten bei Untersuchungen mit dem 12-Schicht-System einen größeren Einfluss (Abbildung 5). Beide Untersucher bewerteten die Bildqualität mit “2-segment fixed start”-Rekonstruktionen höher (p < 0,01). Schlussfolgerung: Beim Einsatz von 4-Schicht-MSCT-Systemen mit 500 ms Gantry-Rotationszeit führte die höhere effektive zeitliche Auflösung (τ) mit 2-Segment-Rekonstruktion kardiovaskulärer Untersuchungen nicht zu einer verbesserten Bildqualität (Abbildung 6). Im Gegensatz dazu konnten bei Verwendung von “state-of-the-art” 12-Schicht-Systemen mit 420 ms Gantry-Rotationszeit Verbesserungen der Bildqualität mit 2-Segment-Rekonstruktion im Vergleich zu Einzelsegmentrekonstruktion für Herzfrequenzen zwischen 74 und 90 Schlägen/min erreicht werden.

Quantitative assessment of myocardial scar in delayed enhancement magnetic resonance imaging.

To characterize the extent and distribution of left ventricular myocardial scar in delayed enhancement magnetic resonance imaging (MRI).

Bosniak Category IIF and III Cystic Renal Lesions: Outcomes and Associations

PURPOSE To evaluate clinical outcomes, pathologic subtypes, metastatic disease rate, and clinical features associated with malignancy in Bosniak category IIF and III cystic renal lesions. MATERIALS AND METHODS This retrospective study was institutional review board approved and HIPAA compliant. Informed consent was waived. Radiology and hospital information systems were searched for Bosniak IIF and Bosniak III lesions in computed tomographic (CT) reports from January 1, 1994 to August 31, 2009. Patients 18 years and older with unenhanced and contrast material-enhanced CT results and with lesions either surgically resected or with 1 year or more of surveillance were included. Data recorded were history of renal cell carcinoma, number of renal lesions, presence of a coexistent solid renal mass, surgical pathologic findings, and presence of metastatic disease from a renal malignancy. Sixty-two patients with 69 Bosniak IIF lesions and 131 patients with 144 Bosniak III lesions were identified. Proportions from independent groups were compared by using the Fisher exact test; continuous variables were compared by using a two-tailed two-sample t test or a Wilcoxon two-sample test. RESULTS The malignancy rate of resected Bosniak IIF lesions was 25% (four of 16) and that for Bosniak III lesions was 54% (58 of 107) (P = .03). Thirteen percent (nine of 69) of Bosniak IIF lesions progressed at follow-up, and 50% (four of eight) of these resected cysts were malignant. History of primary renal malignancy, coexisting Bosniak category IV lesion and/or solid renal mass, and multiplicity of Bosniak III lesions were each associated with an increased malignancy rate in Bosniak III lesions. No patients developed locally advanced or metastatic disease from a Bosniak IIF or III lesion. CONCLUSION Although the malignancy rate in surgically excised Bosniak IIF and Bosniak III cystic renal lesions was 25% and 54%, respectively, in our study, the malignancy rate was higher in patients with a history of primary renal malignancy or coexisting Bosniak IV lesion and/or solid renal neoplasm.

Data analysis for detection and localization of multiple abnormalities with application to mammography

RATIONALE AND OBJECTIVES In assessing diagnostic accuracy it is often essential to determine the readers ability both to detect and to correctly locate multiple abnormalities per patient. The authors developed a new approach for the detection and localization of multiple abnormalities and compared it with other approaches. MATERIALS AND METHODS The new approach involves partitioning the image into multiple regions of interest (ROIs). The reader assigns a confidence score to each ROI. Statistical methods for clustered data are used to assess and compare reader accuracy. The authors applied this new method to a reader-performance study of conventional film images and digitized images used to detect and locate malignant breast cancer lesions. RESULTS The ROI-based approach, the free-response receiver operating characteristic (FROC) curve, and the patient-based approach handle the estimation of the false-positive rate (FPR) quite differently. These differences affect the measures of the respective areas under the curves. In the ROI-based approach the denominator is the number of ROIs without a malignant lesion. In the FROC approach the average number of false-positive findings per patient is plotted on the x axis of the curve. In contrast, the patient-based approach mishandles the FPR by ignoring multiple detection and/or localization errors in the same patient. The FROC approach does not lend itself easily to statistical evaluations. CONCLUSION The ROI-based approach appropriately captures both the detection and localization tasks. The interpretation of the ROI-based accuracy measures is simple and clinically relevant. There are statistical methods for estimating and comparing ROI-based estimates of accuracy.

Correlation Between Loss of Renal Function and Loss of Renal Volume After Partial Nephrectomy for Tumor in a Solitary Kidney

PURPOSE We assessed the correlation between reduced renal function and parenchymal volume following partial nephrectomy. MATERIALS AND METHODS In 21 of 42 patients with tumors in a solitary kidney who were enrolled in a study measuring function before and after surgery underwent computerized tomography, and measurement of the glomerular filtration rate and estimated glomerular filtration rate (the latter at baseline and 2 to 6 months) before and after surgery. A segmentation algorithm was used to measure renal parenchymal volume. The percent of renal parenchymal volume loss was correlated with the percent loss in glomerular filtration rate using the Pearson correlation coefficient. RESULTS Mean +/- SD net preoperative volume was 284 +/- 67 cc (range 179 to 413) and mean net postoperative volume was 240 +/- 61 cc (range 119 to 346) with an absolute functional volume loss of between 5 and 160 cc. The average percent of parenchymal volume loss was 15% (range -2% to 47%). The mean loss of the measured glomerular filtration rate 3 days postoperatively was 33.9% (range -70.7% to 74.4%) and the estimated glomerular filtration rate 2 to 6 months postoperatively was 19.7 % (-6.0% to 45.5%). There was a low degree of correlation between the percent volume loss and the percent measured glomerular filtration rate loss at 3 days (r = 0.28, p = 0.22). However, there was a moderate degree of correlation between the percent volume loss and the percent estimated glomerular filtration rate loss at 2 to 6 months (r = 0.48, p = 0.03). CONCLUSIONS In patients with partial nephrectomy the renal parenchymal volume loss correlates best with the renal function loss several months after surgery. Estimates of volume loss may be useful for predicting postoperative renal function when planning partial nephrectomy in patients with a solitary kidney.

Potential of dual-energy computed tomography to characterize atherosclerotic plaque: ex vivo assessment of human coronary arteries in comparison to histology

BACKGROUND Noninvasive characterization of coronary atherosclerotic plaque is limited with current computed tomography (CT) techniques. Dual-energy CT (DECT) has the potential to provide additional attenuation data for better differentiation of plaque components. OBJECTIVE We attempted to characterize coronary atherosclerotic plaque with DECT. METHODS Seven human coronary arteries acquired at autopsy were scanned consecutively at 80 and 140 kVp with CT. Vessels were perfused with saline, and data were acquired before and after contrast agent injection. Lesions were identified, and attenuation measurements were made from CT image quadrants. CT quadrants were classified as densely calcified, fibrocalcific, fibrous, lipid-rich, or normal vessel wall, corresponding to matched histology images. Attenuation values at each peak tube voltage were compared within plaque types for both noncontrast and contrast scans. Further, dual-energy index (DEI) values computed from attenuation were analyzed for classification of plaque. RESULTS In 14 lesions, a total of 56 quadrants were identified. Histology results classified 8 (14%) as densely calcified, 8 (14%) as fibrocalcific, 9 (16%) as fibrous, 5 (9%) as lipid-rich, and 25 (45%) as normal vessel wall. Calcified lesions attenuated significantly more at 80 kVp in both contrast and noncontrast scans, whereas fibrous plaque attenuated more at 80 kVp only for contrast-enhanced scans. No differences were found for lipid-rich plaques. Using DEI values, only densely calcified plaques could be distinguished from other plaque types except fibrocalcific plaques in contrast images. CONCLUSIONS Only densely calcified and fibrocalcific plaques showed a true change in attenuation at 80 versus 140 kVp. Therefore, calcified plaques could be distinguished from noncalcified plaques with DECT, but further classification of plaque types was not possible.