Phase I study of dose escalation to dominant intraprostatic lesions using high-dose-rate brachytherapy.

PurposeRadiation dose escalation for prostate cancer improves biochemical control but is limited by toxicity. Magnetic resonance spectroscopic imaging (MRSI) can define dominant intraprostatic lesions (DIL). This phase I study evaluated dose escalation to MRSI-defined DIL using high-dose-rate (HDR) brachytherapy.Material and methodsEnrollment was closed early due to low accrual. Ten patients with prostate cancer (T2a-3b, Gleason 6-9, PSA < 20) underwent pre-treatment MRSI, and eight patients had one to three DIL identified. The eight enrolled patients received external beam radiation therapy to 45 Gy and HDR brachytherapy boost to the prostate of 19 Gy in 2 fractions. MRSI images were registered to planning CT images and DIL dose-escalated up to 150% of prescription dose while maintaining normal tissue constraints. The primary endpoint was genitourinary (GU) toxicity.ResultsThe median total DIL volume was 1.31 ml (range, 0.67-6.33 ml). Median DIL boost was 130% of prescription dose (range, 110-150%). Median urethra V120 was 0.15 ml (range, 0-0.4 ml) and median rectum V75 was 0.74 ml (range, 0.1-1.0 ml). Three patients had acute grade 2 GU toxicity, and two patients had late grade 2 GU toxicity. No patients had grade 2 or higher gastrointestinal toxicity, and no grade 3 or higher toxicities were noted. There were no biochemical failures with median follow-up of 4.9 years (range, 2-8.5 years).ConclusionsDose escalation to MRSI-defined DIL is feasible. Toxicity was low but incompletely assessed due to limited patients' enrollment

Prostate cancer lesion detection, volume quantification and high-grade cancer differentiation using cancer risk maps derived from multiparametric MRI with histopathology as the reference standard

Multi-parametric MRI (mpMRI) has proven itself a clinically useful tool to assess prostate cancer (PCa). Our objective was to generate PCa risk maps to quantify the volume and location of both all PCa and high grade (Gleason grade group ≥ 3) PCa. Such capabilities would aid physicians and patients in treatment decisions, targeting biopsy, and planning focal therapy. A cohort of men with biopsy proven prostate cancer and pre-prostatectomy mpMRI were studied. PCa and benign ROIs (1524) were identified on mpMRI and histopathology with histopathology serving as the reference standard. Logistic regression models were created to differentiate PCa from benign tissues. The MRI images were registered to ensure correct overlay. The cancer models were applied to each image voxel within prostates to create probability maps of cancer and of high-grade cancer. Use of an optimum probability threshold quantified PCa volume for all lesions >0.1 cc. Accuracies were calculated using area under the curve (AUC) for the receiver operating characteristic (ROC). The PCa models utilized apparent diffusion coefficient (ADC), T2 weighted (T2W), dynamic contrast-enhanced MRI (DCE MRI) enhancement slope, and DCE MRI washout as the statistically significant MRI scans. Application of the PCa maps method provided total PCa volume and individual lesion volumes. The AUCs derived from lesion analysis were 0.91 for all PCa and 0.73 for high-grade PCa. At the optimum threshold, the PCa maps detected 135 / 150 (90%) histopathological lesions >0.1 cc. This study showed the feasibility of cancer risk maps, created from pre-prostatectomy, mpMR images validated with histopathology, to detect PCa lesions >0.1 cc. The method quantified the volume of cancer within the prostate. Method improvements were identified by determining root causes for over and underestimation of cancer volumes. The maps have the potential for improved non-invasive capability in quantitative detection, localization, volume estimation, and MRI characterization of PCa

Reduced-FOV excitation decreases susceptibility artifact in diffusion-weighted MRI with endorectal coil for prostate cancer detection

The purposes of this study were to determine if image distortion is less in prostate MR apparent diffusion coefficient (ADC) maps generated from a reduced-field-of-view (rFOV) diffusion-weighted-imaging (DWI) technique than from a conventional DWI sequence (CONV), and to determine if the rFOV ADC tumor contrast is as high as or better than that of the CONV sequence. Fifty patients underwent a 3T MRI exam. CONV and rFOV (utilizing a 2D, echo-planar, rectangularly-selective RF pulse) sequences were acquired using b=600, 0s/mm(2). Distortion was visually scored 0-4 by three independent observers and quantitatively measured using the difference in rectal wall curvature between the ADC maps and T2-weighted images. Distortion scores were lower with the rFOV sequence (p<0.012, Wilcoxon Signed-Rank Test, n=50), and difference in distortion scores did not differ significantly among observers (p=0.99, Kruskal-Wallis Rank Sum Test). The difference in rectal curvature was less with rFOV ADC maps (26%±10%) than CONV ADC maps (34%±13%) (p<0.011, Student's t-test). In seventeen patients with untreated, biopsy confirmed prostate cancer, the rFOV sequence afforded significantly higher ADC tumor contrast (44.0%) than the CONV sequence (35.9%), (p<0.0012, Student's t-test). The rFOV sequence yielded significantly decreased susceptibility artifact and significantly higher contrast between tumor and healthy tissue

Liver Steatosis: Concordance of MR Imaging and MR Spectroscopic Data with Histologic Grade

PurposeTo determine if the concordance of magnetic resonance (MR) imaging and MR spectroscopic data with histologic measures of steatosis is affected by histologic magnification level, tissue heterogeneity, or assessment of tissue area versus that of hepatocytes.Materials and methodsThis study was institutional review board approved and HIPAA compliant. Written informed consent was obtained. In- and out-of-phase MR imaging and MR spectroscopic measures of steatosis were compared in 33 patients with nonalcoholic fatty liver disease and in 15 healthy volunteers. Concordance of MR imaging and MR spectroscopic data with histologic findings was assessed for (a) histologic examination at standard (×40 and ×100) versus high magnification (×200 and ×400), (b) heterogeneity and homogeneity of livers, and (c) percentage of tissue and hepatocytes that contained lipids. Evaluations included linear regression and Fisher exact tests.ResultsIn- and out-of-phase MR imaging and MR spectroscopic data were well correlated (R2=0.93) and generally concordant with histologic measures. Patients in whom MR fat fractions were higher than expected compared with steatosis grades at standard magnification histologic examination were upgraded significantly more often when high magnification was used than were the remaining patients (100% [10 of 10] vs 47% [7 of 15], P<.01). MR imaging and MR spectroscopic data of homogeneous livers were significantly more likely than those of heterogeneous livers to be concordant with steatosis grades when high magnification was used (81% [13 of 16] vs 47% [8 of 17], P<.05). For all patients, percentage of fat in tissue was lower than that in hepatocytes, which affected individual patients, but not the overall correlation.ConclusionMR imaging and MR spectroscopic data were generally concordant with histologic measures of steatosis. Discordance between them may reflect differences in magnification at histologic examination and in liver heterogeneity

Liver Steatosis: Concordance of MR Imaging and MR Spectroscopic Data with Histologic Grade

PURPOSE: To determine if the concordance of magnetic resonance (MR) imaging and MR spectroscopic data with histologic measures of steatosis is affected by histologic magnification level, tissue heterogeneity, or assessment of tissue area versus that of hepatocytes. MATERIALS AND METHODS: This study was institutional review board approved and HIPAA compliant. Written informed consent was obtained. In- and out-of-phase MR imaging and MR spectroscopic measures of steatosis were compared in 33 patients with nonalcoholic fatty liver disease and in 15 healthy volunteers. Concordance of MR imaging and MR spectroscopic data with histologic findings was assessed for (a) histologic examination at standard (×40 and ×100) versus high magnification (×200 and ×400), (b) heterogeneity and homogeneity of livers, and (c) percentage of tissue and hepatocytes that contained lipids. Evaluations included linear regression and Fisher exact tests. RESULTS: In- and out-of-phase MR imaging and MR spectroscopic data were well correlated (R(2) = 0.93) and generally concordant with histologic measures. Patients in whom MR fat fractions were higher than expected compared with steatosis grades at standard magnification histologic examination were upgraded significantly more often when high magnification was used than were the remaining patients (100% [10 of 10] vs 47% [7 of 15], P < .01). MR imaging and MR spectroscopic data of homogeneous livers were significantly more likely than those of heterogeneous livers to be concordant with steatosis grades when high magnification was used (81% [13 of 16] vs 47% [8 of 17], P < .05). For all patients, percentage of fat in tissue was lower than that in hepatocytes, which affected individual patients, but not the overall correlation. CONCLUSION: MR imaging and MR spectroscopic data were generally concordant with histologic measures of steatosis. Discordance between them may reflect differences in magnification at histologic examination and in liver heterogeneity. © RSNA, 201

Interactive, multi-modality image registrations for combined MRI/MRSI-planned HDR prostate brachytherapy

Purpose: This study presents the steps and criteria involved in the series of image registrations used clinically during the planning and dose delivery of focal high dose-rate (HDR) brachytherapy of the prostate. Material and methods: Three imaging modalities – Magnetic Resonance Imaging (MRI), Magnetic Resonance Spectroscopic Imaging (MRSI), and Computed Tomography (CT) – were used at different steps during the process. MRSI is used for identification of dominant intraprosatic lesions (DIL). A series of rigid and nonrigid transformations were applied to the data to correct for endorectal-coil-induced deformations and for alignment with the planning CT. Mutual information was calculated as a morphing metric. An inverse planning optimization algorithm was applied to boost dose to the DIL while providing protection to the urethra, penile bulb, rectum, and bladder. Six prostate cancer patients were treated using this protocol. Results: The morphing algorithm successfully modeled the probe-induced prostatic distortion. Mutual information calculated between the morphed images and images acquired without the endorectal probe showed a significant (p = 0.0071) increase to that calculated between the unmorphed images and images acquired without the endorectal probe. Both mutual information and visual inspection serve as effective diagnostics of image morphing. The entire procedure adds less than thirty minutes to the treatment planning. Conclusion: This work demonstrates the utility of image transformations and registrations to HDR brachytherapy of prostate cancer