Automatic Detection of Prostate Tumor Habitats using Diffusion MRI.

A procedure for identification of optimal Apparent Diffusion Coefficient (ADC) thresholds for automatic delineation of prostatic lesions with restricted diffusion at differing risk for cancer was developed. The relationship between the size of the identified Volumes of Interest (VOIs) and Gleason Score (GS) was evaluated. Patients with multiparametric (mp)MRI, acquired prior to radical prostatectomy (RP) (n = 18), mpMRI-ultrasound fused (MRI-US) (n = 21) or template biopsies (n = 139) were analyzed. A search algorithm, spanning ADC thresholds in 50 µm2/s increments, determined VOIs that were matched to RP tumor nodules. Three ADC thresholds for both peripheral zone (PZ) and transition zone (TZ) were identified for estimation of VOIs at low, intermediate, and high risk of prostate cancer. The determined ADC thresholds for low, intermediate and high risk in PZ/TZ were: 900/800; 1100/850; and 1300/1050 µm2/s. The correlation coefficients between the size of the high/intermediate/low risk VOIs and GS in the three cohorts were 0.771/0.778/0.369, 0.561/0.457/0.355 and 0.423/0.441/0.36 (p < 0.05). Low risk VOIs mapped all RP lesions; area under the curve (AUC) for intermediate risk VOIs to discriminate GS6 vs GS ≥ 7 was 0.852; for high risk VOIs to discriminate GS6,7 vs GS ≥ 8 was 0.952. In conclusion, the automatically delineated volumes in the prostate with restricted diffusion were found to strongly correlate with cancer aggressiveness.

Classification of suspicious lesions on prostate multiparametric MRI using machine learning.

We present a radiomics-based approach developed for the SPIE-AAPM-NCI PROSTATEx challenge. The task was to classify clinically significant prostate cancer in multiparametric (mp) MRI. Data consisted of a "training dataset" (330 suspected lesions from 204 patients) and a "test dataset" (208 lesions/140 patients). All studies included T2-weighted (T2-W), proton density-weighted, dynamic contrast enhanced, and diffusion-weighted imaging. Analysis of the images was performed using the MIM imaging platform (MIM Software, Cleveland, Ohio). Prostate and peripheral zone contours were manually outlined on the T2-W images. A workflow for rigid fusion of the aforementioned images to T2-W was created in MIM. The suspicious lesion was outlined using the high b-value image. Intensity and texture features were extracted on four imaging modalities and characterized using nine histogram descriptors: 10%, 25%, 50%, 75%, 90%, mean, standard deviation, kurtosis, and skewness (216 features). Three classification methods were used: classification and regression trees (CART), random forests, and adaptive least absolute shrinkage and selection operator (LASSO). In the held out by the organizers test dataset, the areas under the curve (AUCs) were: 0.82 (random forests), 0.76 (CART), and 0.76 (adaptive LASSO). AUC of 0.82 was the fourth-highest score of 71 entries (32 teams) and the highest for feature-based methods.

An Automated Multiparametric MRI Quantitative Imaging Prostate Habitat Risk Scoring System for Defining External Beam Radiation Therapy Boost Volumes.

PURPOSE: To develop a prostate tumor habitat risk scoring (HRS) system based on multiparametric magnetic resonance imaging (mpMRI) referenced to prostatectomy Gleason score (GS) for automatic delineation of gross tumor volumes. A workflow for integration of HRS into radiation therapy boost volume dose escalation was developed in the framework of a phase 2 randomized clinical trial (BLaStM). METHODS AND MATERIALS: An automated quantitative mpMRI-based 10-point pixel-by-pixel method was optimized to prostatectomy GSs and volumes using referenced dynamic contrast-enhanced and apparent diffusion coefficient sequences. The HRS contours were migrated to the planning computed tomography scan for boost volume generation. RESULTS: There were 51 regions of interest in 12 patients who underwent radical prostatectomy (26 with GS ≥7 and 25 with GS 6). The resultant heat maps showed inter- and intratumoral heterogeneity. The HRS6 level was significantly associated with radical prostatectomy regions of interest (slope 1.09, r = 0.767; P < .0001). For predicting the likelihood of cancer, GS ≥7 and GS ≥8 HRS6 area under the curve was 0.718, 0.802, and 0.897, respectively. HRS was superior to the Prostate Imaging, Reporting and Diagnosis System 4/5 classification, wherein the area under the curve was 0.62, 0.64, and 0.617, respectively (difference with HR6, P < .0001). HRS maps were created for the first 37 assessable patients on the BLaStM trial. There were an average of 1.38 habitat boost volumes per patient at a total boost volume average of 3.6 cm3. CONCLUSIONS: An automated quantitative mpMRI-based method was developed to objectively guide dose escalation to high-risk habitat volumes based on prostatectomy GS.

Delineation of Tumor Habitats based on Dynamic Contrast Enhanced MRI.

Tumor heterogeneity can be elucidated by mapping subregions of the lesion with differential imaging characteristics, called habitats. Dynamic Contrast Enhanced (DCE-)MRI can depict the tumor microenvironments by identifying areas with variable perfusion and vascular permeability, since individual tumor habitats vary in the rate and magnitude of the contrast uptake and washout. Of particular interest is identifying areas of hypoxia, characterized by inadequate perfusion and hyper-permeable vasculature. An automatic procedure for delineation of tumor habitats from DCE-MRI was developed as a two-part process involving: (1) statistical testing in order to determine the number of the underlying habitats; and (2) an unsupervised pattern recognition technique to recover the temporal contrast patterns and locations of the associated habitats. The technique is examined on simulated data and DCE-MRI, obtained from prostate and brain pre-clinical cancer models, as well as clinical data from sarcoma and prostate cancer patients. The procedure successfully identified habitats previously associated with well-perfused, hypoxic and/or necrotic tumor compartments. Given the association of tumor hypoxia with more aggressive tumor phenotypes, the obtained in vivo information could impact management of cancer patients considerably.

Prostate cancer radiomics and the promise of radiogenomics.

Prostate cancer exhibits intra-tumoral heterogeneity that we hypothesize to be the leading confounding factor contributing to the underperformance of the current pre-treatment clinical-pathological and genomic assessment. These limitations impose an urgent need to develop better computational tools to identify men with low risk of prostate cancer versus others that may be at risk for developing metastatic cancer. The patient stratification will directly translate to patient treatments, wherein decisions regarding active surveillance or intensified therapy are made. Multiparametric MRI (mpMRI) provides the platform to investigate tumor heterogeneity by mapping the individual tumor habitats. We hypothesize that quantitative assessment (radiomics) of these habitats results in distinct combinations of descriptors that reveal regions with different physiologies and phenotypes. Radiogenomics, a discipline connecting tumor morphology described by radiomic and its genome described by the genomic data, has the potential to derive "radio phenotypes" that both correlate to and complement existing validated genomic risk stratification biomarkers. In this article we first describe the radiomic pipeline, tailored for analysis of prostate mpMRI, and in the process we introduce our particular implementations of radiomics modules. We also summarize the efforts in the radiomics field related to prostate cancer diagnosis and assessment of aggressiveness. Finally, we describe our results from radiogenomic analysis, based on mpMRI-Ultrasound (MRI-US) biopsies and discuss the potential of future applications of this technique. The mpMRI radiomics data indicate that the platform would significantly improve the biopsy targeting of prostate habitats through better recognition of indolent versus aggressive disease, thereby facilitating a more personalized approach to prostate cancer management. The expectation to non-invasively identify habitats with high probability of housing aggressive cancers would result in directed biopsies that are more informative and actionable. Conversely, providing evidence for lack of disease would reduce the incidence of non-informative biopsies. In radiotherapy of prostate cancer, dose escalation has been shown to reduce biochemical failure. Dose escalation only to determinate prostate habitats has the potential to improve tumor control with less toxicity than when the entire prostate is dose escalated.