Chaya S. Moskowitz

Diffusion-weighted Endorectal MR Imaging at 3 T for Prostate Cancer: Tumor Detection and Assessment of Aggressiveness

PURPOSE To assess the incremental value of diffusion-weighted (DW) magnetic resonance (MR) imaging over T2-weighted MR imaging at 3 T for prostate cancer detection and to investigate the use of the apparent diffusion coefficient (ADC) to characterize tumor aggressiveness, with whole-mount step-section pathologic analysis as the reference standard. MATERIALS AND METHODS The Internal Review Board approved this HIPAA-compliant retrospective study and waived informed consent. Fifty-one patients with prostate cancer (median age, 58 years; range, 46-74 years) underwent T2-weighted MR imaging and DW MR imaging (b values: 0 and 700 sec/mm(2) [n = 20] or 0 and 1000 sec/mm(2) [n = 31]) followed by prostatectomy. The prostate was divided into 12 regions; two readers provided a score for each region according to their level of suspicion for the presence of cancer on a five-point scale, first using T2-weighted MR imaging alone and then using T2-weighted MR imaging and the ADC map in conjunction. Areas under the receiver operating characteristic curve (AUCs) were estimated to evaluate performance. Generalized estimating equations were used to test the ADC difference between benign and malignant prostate regions and the association between ADCs and tumor Gleason scores. RESULTS For tumor detection, the AUCs for readers 1 and 2 were 0.79 and 0.76, respectively, for T2-weighted MR imaging and 0.79 and 0.78, respectively, for T2-weighted MR imaging plus the ADC map. Mean ADCs for both cancerous and healthy prostatic regions were lower when DW MR imaging was performed with a b value of 1000 sec/mm(2) rather than 700 sec/mm(2). Regardless of the b value used, there was a significant difference in the mean ADC between malignant and benign prostate regions. A lower mean ADC was significantly associated with a higher tumor Gleason score (mean ADCs of [1.21, 1.10, 0.87, and 0.69] × 10(-3) mm(2)/sec were associated with Gleason score of 3 + 3, 3 + 4, 4 + 3, and 8 or higher, respectively; P = .017). CONCLUSION Combined DW and T2-weighted MR imaging had similar performance to T2-weighted MR imaging alone for tumor detection; however, DW MR imaging provided additional quantitative information that significantly correlated with prostate cancer aggressiveness.

Prostate Cancer: Identification with Combined Diffusion-weighted MR Imaging and 3D 1H MR Spectroscopic Imaging—Correlation with Pathologic Findings1

PURPOSE To retrospectively measure the mean apparent diffusion coefficient (ADC) with diffusion-weighted magnetic resonance (MR) imaging and the mean metabolic ratio (MET) with three-dimensional (3D) hydrogen 1 ((1)H) MR spectroscopic imaging in regions of interest (ROIs) drawn over benign and malignant peripheral zone (PZ) prostatic tissue and to assess ADC, MET, and combined ADC and MET for identifying malignant ROIs, with whole-mount histopathologic examination as the reference standard. MATERIALS AND METHODS The institutional review board approved this HIPAA-compliant retrospective study and issued a waiver of informed consent. From among 61 consecutive patients with prostate cancer, 38 men (median age, 61 years; range, 42-72 years) who underwent 1.5-T endorectal MR imaging before radical prostatectomy and who fulfilled all inclusion criteria of no prior hormonal or radiation treatment and at least one PZ lesion (volume, >0.1 cm(3)) at whole-mount pathologic examination were included. ADC maps were generated from diffusion-weighted MR imaging data, and MET maps of (choline plus polyamine plus creatine)/citrate were calculated from 3D (1)H MR spectroscopic imaging data. ROIs in the PZ identified by matching pathologic slides with T2-weighted images were overlaid on MET and ADC maps. Areas under the receiver operating characteristic curves (AUCs) were used to evaluate accuracy. RESULTS The mean ADC +/- standard deviation, (1.39 +/- 0.23) x 10(-3) mm(2)/sec, and mean MET (0.92 +/- 0.32) for malignant ROIs differed significantly from the mean ADC, (1.69 +/- 0.24) x 10(-3) mm(2)/sec, and mean MET (0.73 +/- 0.18) for benign ROIs (P < .001 for both). In distinguishing malignant ROIs, combined ADC and MET (AUC = 0.85) performed significantly better than MET alone (AUC = 0.74; P = .005) and was also better than ADC alone (AUC = 0.81), although the difference was not statistically significant (P = .09). CONCLUSION The combination of ADC and MET performs significantly better than MET for differentiating between benign and malignant ROIs in the PZ.

Magnetic Resonance Imaging for Predicting Prostate Biopsy Findings in Patients Considered for Active Surveillance of Clinically Low Risk Prostate Cancer

PURPOSE A barrier to the acceptance of active surveillance for men with prostate cancer is the risk of underestimating the cancer burden on initial biopsy. We assessed the value of endorectal magnetic resonance imaging in predicting upgrading on confirmatory biopsy in men with low risk prostate cancer. MATERIALS AND METHODS A total of 388 consecutive men (mean age 60.6 years, range 33 to 89) with clinically low risk prostate cancer (initial biopsy Gleason score 6 or less, prostate specific antigen less than 10 ng/ml, clinical stage T2a or less) underwent endorectal magnetic resonance imaging before confirmatory biopsy. Three radiologists independently and retrospectively scored tumor visibility on endorectal magnetic resonance imaging using a 5-point scale (1-definitely no tumor to 5-definitely tumor). Inter-reader agreement was assessed with weighted kappa statistics. Associations between magnetic resonance imaging scores and confirmatory biopsy findings were evaluated using measures of diagnostic performance and multivariate logistic regression. RESULTS On confirmatory biopsy, Gleason score was upgraded in 79 of 388 (20%) patients. Magnetic resonance imaging scores of 2 or less had a high negative predictive value (0.96-1.0) and specificity (0.95-1.0) for upgrading on confirmatory biopsy. A magnetic resonance imaging score of 5 was highly sensitive for upgrading on confirmatory biopsy (0.87-0.98). At multivariate analysis patients with higher magnetic resonance imaging scores were more likely to have disease upgraded on confirmatory biopsy (odds ratio 2.16-3.97). Inter-reader agreement and diagnostic performance were higher for the more experienced readers (kappa 0.41-0.61, AUC 0.76-0.79) than for the least experienced reader (kappa 0.15-0.39, AUC 0.61-0.69). Magnetic resonance imaging performed similarly in predicting low risk and very low risk (Gleason score 6, less than 3 positive cores, less than 50% involvement in all cores) prostate cancer. CONCLUSIONS Adding endorectal magnetic resonance imaging to the initial clinical evaluation of men with clinically low risk prostate cancer helps predict findings on confirmatory biopsy and assess eligibility for active surveillance.

Prostate Tumor Volume Measurement with Combined T2-weighted Imaging and Diffusion-weighted MR: Correlation with Pathologic Tumor Volume

PURPOSE To retrospectively determine the accuracy of diffusion-weighted (DW) magnetic resonance (MR) imaging for identifying cancer in the prostate peripheral zone (PZ) and to assess the accuracy of tumor volume measurements made with T2-weighted imaging and combined T2-weighted and DW MR imaging by using surgical pathologic examination as the reference standard. MATERIALS AND METHODS The institutional review board issued a waiver of informed consent for this HIPAA-compliant study. Forty-two patients underwent endorectal MR at 1.5 T before undergoing radical prostatectomy for prostate cancer and had at least one PZ tumor larger than 0.1 cm(3) at surgical pathologic examination. On T2-weighted images, an experienced radiologist outlined suspected PZ tumors. Two apparent diffusion coefficient (ADC) cutoff values were identified by using the Youden index and published literature. Image cluster analysis was performed on voxels within the suspected tumor regions. Associations between volume measurements from imaging and from pathologic examination were assessed by using concordance correlation coefficients (CCCs). The sensitivity and specificity of ADCs for identifying malignant PZ voxels were calculated. RESULTS In identifying malignant voxels, respective ADC cutoff values of 0.0014 and 0.0016 mm(2)/sec yielded sensitivity of 82% and 95% and specificity of 85% and 65%, respectively. Sixty PZ cancer lesions larger than 0.1 cm(3) were found at pathologic examination; 43 were detected by the radiologist. CCCs between imaging and pathologic tumor volume measurements were 0.36 for T2-weighted imaging, and 0.46 and 0.60 for combined T2-weighted and DW MR imaging with ADC cutoffs of 0.0014 and 0.0016 mm(2)/sec, respectively; the CCC of combined T2-weighted and DW MR imaging (ADC cutoff, 0.0016 mm(2)/sec) was significantly higher (P = .006) than that of T2-weighted imaging alone. CONCLUSION Adding DW MR to T2-weighted imaging can significantly improve the accuracy of prostate PZ tumor volume measurement. SUPPLEMENTAL MATERIAL http://radiology.rsnajnls.org/cgi/content/full/252/2/449/DC1.

Prostate Cancer Aggressiveness: Assessment with Whole-Lesion Histogram Analysis of the Apparent Diffusion Coefficient

PURPOSE To evaluate the relationship between prostate cancer aggressiveness and histogram-derived apparent diffusion coefficient (ADC) parameters obtained from whole-lesion assessment of diffusion-weighted magnetic resonance (MR) imaging of the prostate and to determine which ADC metric may help best differentiate low-grade from intermediate- or high-grade prostate cancer lesions. MATERIALS AND METHODS The institutional review board approved this retrospective HIPAA-compliant study of 131 men (median age, 60 years) who underwent diffusion-weighted MR imaging before prostatectomy for prostate cancer. Clinically significant tumors (tumor volume > 0.5 mL) were identified at whole-mount step-section histopathologic examination, and Gleason scores of the tumors were recorded. A volume of interest was drawn around each significant tumor on ADC maps. The mean, median, and 10th and 25th percentile ADCs were determined from the whole-lesion histogram and correlated with the Gleason score by using the Spearman correlation coefficient (ρ). The ability of each parameter to help differentiate tumors with a Gleason score of 6 from those with a Gleason score of at least 7 was assessed by using the area under the receiver operating characteristic curve (Az). RESULTS In total, 116 clinically significant lesions (89 in the peripheral zone, 27 in the transition zone) were identified in 85 of the 131 patients (65%). Forty-six patients did not have a clinically significant lesion. For mean ADC, median ADC, 10th percentile ADC, and 25th percentile ADC, the Spearman ρ values for correlation with Gleason score were -0.31, -0.30, -0.36, and -0.35, respectively, whereas the Az values for differentiating lesions with a Gleason score of 6 from those with a Gleason score of at least 7 were 0.704, 0.692, 0.758, and 0.723, respectively. The Az of 10th percentile ADC was significantly higher than that of the mean ADC for all lesions and peripheral zone lesions (P = .0001). CONCLUSION When whole-lesion histograms were used to derive ADC parameters, 10th percentile ADC correlated with Gleason score better than did other ADC parameters, suggesting that 10th percentile ADC may prove to be optimal for differentiating low-grade from intermediate- or high-grade prostate cancer with diffusion-weighted MR imaging.

Bilateral Contrast-enhanced Dual-Energy Digital Mammography: Feasibility and Comparison with Conventional Digital Mammography and MR Imaging in Women with Known Breast Carcinoma

PURPOSE To determine feasibility of performing bilateral dual-energy (DE) contrast agent-enhanced (CE) digital mammography and to evaluate its performance compared with conventional digital mammography and breast magnetic resonance (MR) imaging in women with known breast cancer. MATERIALS AND METHODS This study was approved by the institutional review board and was HIPAA compliant. Written informed consent was obtained. Patient accrual began in March 2010 and ended in August 2011. Mean patient age was 49.6 years (range, 25-74 years). Feasibility was evaluated in 10 women with newly diagnosed breast cancer who were injected with 1.5 mL per kilogram of body weight of iohexol and imaged between 2.5 and 10 minutes after injection. Once feasibility was confirmed, 52 women with newly diagnosed cancer who had undergone breast MR imaging gave consent to undergo DE CE digital mammography. Positive findings were confirmed with pathologic findings. RESULTS Feasibility was confirmed with no adverse events. Visualization of tumor enhancement was independent of timing after contrast agent injection for up to 10 minutes. MR imaging and DE CE digital mammography both depicted 50 (96%) of 52 index tumors; conventional mammography depicted 42 (81%). Lesions depicted by using DE CE digital mammography ranged from 4 to 67 mm in size (median, 17 mm). DE CE digital mammography depicted 14 (56%) of 25 additional ipsilateral cancers compared with 22 (88%) of 25 for MR imaging. There were two false-positive findings with DE CE digital mammography and 13 false-positive findings with MR imaging. There was one contralateral cancer, which was not evident with either modality. CONCLUSION Bilateral DE CE digital mammography was feasible and easily accomplished. It was used to detect known primary tumors at a rate comparable to that of MR imaging and higher than that of conventional digital mammography. DE CE digital mammography had a lower sensitivity for detecting additional ipsilateral cancers than did MR imaging, but the specificity was higher.

Breast Cancer After Chest Radiation Therapy for Childhood Cancer

PURPOSE The risk of breast cancer is high in women treated for a childhood cancer with chest irradiation. We sought to examine variations in risk resulting from irradiation field and radiation dose. PATIENTS AND METHODS We evaluated cumulative breast cancer risk in 1,230 female childhood cancer survivors treated with chest irradiation who were participants in the CCSS (Childhood Cancer Survivor Study). RESULTS Childhood cancer survivors treated with lower delivered doses of radiation (median, 14 Gy; range, 2 to 20 Gy) to a large volume (whole-lung field) had a high risk of breast cancer (standardized incidence ratio [SIR], 43.6; 95% CI, 27.2 to 70.3), as did survivors treated with high doses of delivered radiation (median, 40 Gy) to the mantle field (SIR, 24.2; 95% CI, 20.7 to 28.3). The cumulative incidence of breast cancer by age 50 years was 30% (95% CI, 25 to 34), with a 35% incidence among Hodgkin lymphoma survivors (95% CI, 29 to 40). Breast cancer-specific mortality at 5 and 10 years was 12% (95% CI, 8 to 18) and 19% (95% CI, 13 to 25), respectively. CONCLUSION Among women treated for childhood cancer with chest radiation therapy, those treated with whole-lung irradiation have a greater risk of breast cancer than previously recognized, demonstrating the importance of radiation volume. Importantly, mortality associated with breast cancer after childhood cancer is substantial.

A Pilot Study of Volume Measurement as a Method of Tumor Response Evaluation to Aid Biomarker Development

Purpose: Tissue biomarker discovery is potentially limited by conventional tumor measurement techniques, which have an uncertain ability to accurately distinguish sensitive and resistant tumors. Semiautomated volumetric measurement of computed tomography imaging has the potential to more accurately capture tumor growth dynamics, allowing for more exact separation of sensitive and resistant tumors and a more accurate comparison of tissue characteristics. Experimental Design: Forty-eight patients with early stage non–small cell lung cancer and clinical characteristics of sensitivity to gefitinib were studied. High-resolution computed tomography was done at baseline and after 3 weeks of gefitinib. Tumors were then resected and molecularly profiled. Unidimensional and volumetric measurements were done using a semiautomated algorithm. Measurement changes were evaluated for their ability to differentiate tumors with and without sensitizing mutations. Results: Forty-four percent of tumors had epidermal growth factor receptor–sensitizing mutations. Receiver operating characteristic curve analysis showed that volumetric measurement had a higher area under the curve than unidimensional measurement for identifying tumors harboring sensitizing mutations (P = 0.009). Tumor volume decrease of >24.9% was the imaging criteria best able to classify tumors with and without sensitizing mutations (sensitivity, 90%; specificity, 89%). Conclusions: Volumetric tumor measurement was better than unidimensional tumor measurement at distinguishing tumors based on presence or absence of a sensitizing mutation. Use of volume-based response assessment for the development of tissue biomarkers could reduce contamination between sensitive and resistant tumor populations, improving our ability to identify meaningful predictors of sensitivity. Clin Cancer Res; 16(18); 4647–53. ©2010 AACR.

Performance Characteristics of MR Imaging in the Evaluation of Clinically Low-Risk Prostate Cancer: A Prospective Study

PURPOSE To prospectively evaluate diagnostic performance of T2-weighted magnetic resonance (MR) imaging and MR spectroscopic imaging in detecting lesions stratified by pathologic volume and Gleason score in men with clinically determined low-risk prostate cancer. MATERIALS AND METHODS The institutional review board approved this prospective, HIPAA-compliant study. Written informed consent was obtained from 183 men with clinically low-risk prostate cancer (cT1-cT2a, Gleason score≤6 at biopsy, prostate-specific antigen [PSA] level<10 ng/mL [10 μg/L]) undergoing MR imaging before prostatectomy. By using a scale of 1-5 (score 1, definitely no tumor; score 5, definitely tumor), two radiologists independently scored likelihood of tumor per sextant on T2-weighted images. Two spectroscopists jointly recorded locations of lesions with metabolic features consistent with tumor on MR spectroscopic images. Whole-mount step-section histopathologic analysis constituted the reference standard. Diagnostic performance at sextant level (T2-weighted imaging) and detection sensitivities (T2-weighted imaging and MR spectroscopic imaging) for lesions of 0.5 cm3 or larger were calculated. RESULTS For T2-weighted imaging, areas under the receiver operating characteristic curves for sextant-level detection were 0.77 (reader 1) and 0.82 (reader 2). For lesions of ≥0.5 cm3 and, 1<cm3, sensitivities were significantly lower when the lesion Gleason score was ≤6 (0.44 [reader 1] and 0.61 [reader 2]) rather than when the Gleason score was ≥7 (0.73, P=.02 [reader 1]; and 0.84, P=.05 [reader 2]). For lesions of ≥1 cm3, lesion Gleason score did not significantly affect sensitivity (0.83 [reader 1] and 1.00 [reader 2] for Gleason score≤6 vs 0.82 and 0.92 for Gleason score≥7; P≥.07). MR spectroscopic imaging sensitivity was low and was not significantly affected by pathologic lesion volume or Gleason score. CONCLUSION In men with clinically low-risk prostate cancer, detection of lesions of <1 cm3 with T2-weighted imaging is significantly dependent on lesion Gleason score; detection of lesions of ≥1 cm3 is significantly better than detection of smaller lesions and is not affected by lesion Gleason score. The role of MR spectroscopic imaging alone in this population is limited.

Multiparametric Prostate MR Imaging with T2-weighted, Diffusion-weighted, and Dynamic Contrast-enhanced Sequences: Are All Pulse Sequences Necessary to Detect Locally Recurrent Prostate Cancer after Radiation Therapy?

PURPOSE To compare diagnostic accuracy of T2-weighted magnetic resonance (MR) imaging with that of multiparametric (MP) MR imaging combining T2-weighted imaging with diffusion-weighted (DW) MR imaging, dynamic contrast material-enhanced (DCE) MR imaging, or both in the detection of locally recurrent prostate cancer (PCa) after radiation therapy (RT). MATERIALS AND METHODS This retrospective HIPAA-compliant study was approved by the institutional review board; informed consent was waived. Fifty-three men (median age, 70 years) suspected of having post-RT recurrence of PCa underwent MP MR imaging, including DW and DCE sequences, within 6 months after biopsy. Two readers independently evaluated the likelihood of PCa with a five-point scale for T2-weighted imaging alone, T2-weighted imaging with DW imaging, T2-weighted imaging with DCE imaging, and T2-weighted imaging with DW and DCE imaging, with at least a 4-week interval between evaluations. Areas under the receiver operating characteristic curve (AUC) were calculated. Interreader agreement was assessed, and quantitative parameters (apparent diffusion coefficient [ADC], volume transfer constant [K(trans)], and rate constant [k(ep)]) were assessed at sextant- and patient-based levels with generalized estimating equations and the Wilcoxon rank sum test, respectively. RESULTS At biopsy, recurrence was present in 35 (66%) of 53 patients. In detection of recurrent PCa, T2-weighted imaging with DW imaging yielded higher AUCs (reader 1, 0.79-0.86; reader 2, 0.75-0.81) than T2-weighted imaging alone (reader 1, 0.63-0.67; reader 2, 0.46-0.49 [P ≤ .014 for all]). DCE sequences did not contribute significant incremental value to T2-weighted imaging with DW imaging (reader 1, P > .99; reader 2, P = .35). Interreader agreement was higher for combinations of MP MR imaging than for T2-weighted imaging alone (κ = 0.34-0.63 vs κ = 0.17-0.20). Medians of quantitative parameters differed significantly (P < .0001 to P = .0233) between benign tissue and PCa (ADC, 1.64 × 10(-3) mm(2)/sec vs 1.13 × 10(-3) mm(2)/sec; K(trans), 0.16 min(-1) vs 0.33 min(-1); k(ep), 0.36 min(-1) vs 0.62 min(-1)). CONCLUSION MP MR imaging has greater accuracy in the detection of recurrent PCa after RT than T2-weighted imaging alone, with no additional benefit if DCE is added to T2-weighted imaging and DW imaging.