Validation of Multiparametric Magnetic Resonance Imaging Techniques for Evaluating the Prostate

Prostate cancer is extremely common. With recent advancements in cancer detection, an increasing number of men at a younger age face the difficult choice between delaying potentially life-saving interventions and seeking curative treatments, which are typically accompanied by a host of side effects. Non-invasive disease characterization is a promising step toward identifying patient-specific cancer management strategies. Due to the excellent performance of anatomic imaging and the ability to characterize physiologic properties via functional imaging modalities, multiparametic magnetic resonance imaging (mpMRI) has the potential to make a significant impact on the way prostate cancer is viewed by both patients and clinicians. This thesis will introduce multiparametric MR imaging in the context of prostate anatomy. It will address the issues of aligning MR imaging to the whole-mount histopathology images (commonly regarded as a reference standard) and discuss characterization and stratification of prostatic lesions based on mpMR imaging. This work will also introduce a semi-automatic approach to lesion segmentation on histopathology and report on the prostate cancer composition in the radical prostatectomy population. Furthermore, this thesis will investigate the prevalence of “sparse” prostatic lesions, discussing their clinical significance and exploring mpMRI capabilities to detect these cancers. Finally, this work will examine the influence of prostate treatments, specifically 5-alpha reductase inhibitors (often used to treat benign prostatic hyperplasia), on the structure of prostatic tissues, their effect on the appearance of prostatic tissues on mpMRI, and what role such treatments play in our ability to properly detect malignancies post treatment

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

Identification of prostate cancer using multiparametric MR imaging characteristics of prostate tissues referenced to whole mount histopathology.

In this study, the objective was to characterize the MR signatures of the various benign prostate tissues and to differentiate them from cancer. Data was from seventy prostate cancer patients who underwent multiparametric MRI (mpMRI) and subsequent prostatectomy. The scans included T2-weighted imaging (T2W), diffusion weighted imaging, dynamic contrast-enhanced MRI (DCE MRI), and MR spectroscopic imaging. Histopathology tissue information was translated to MRI images. The mpMRI parameters were characterized separately per zone and by tissue type. The tissues were ordered according to trends in tissue parameter means. The peripheral zone tissue order was cystic atrophy, high grade prostatic intraepithelial neoplasia (HGPIN), normal, atrophy, inflammation, and cancer. Decreasing values for tissue order were exhibited by ADC (1.8 10-3 mm2/s to 1.2 10-3 mm2/s) and T2W intensity (3447 to 2576). Increasing values occurred for DCE MRI peak (143% to 157%), DCE MRI slope (101%/min to 169%/min), fractional anisotropy (FA) (0.16 to 0.19), choline (7.2 to 12.2), and choline / citrate (0.3 to 0.9). The transition zone tissue order was cystic atrophy, mixed benign prostatic hyperplasia (BPH), normal, atrophy, inflammation, stroma, anterior fibromuscular stroma, and cancer. Decreasing values occurred for ADC (1.6 10-3 mm2/s to 1.1 10-3 mm2/s) and T2W intensity (2863 to 2001). Increasing values occurred for DCE MRI peak (143% to 150%), DCE MRI slope (101%/min to 137%/min), FA (0.18 to 0.25), choline (7.9 to 11.7), and choline / citrate (0.3 to 0.7). Logistic regression was used to create parameter model fits to differentiate cancer from benign prostate tissues. The fits achieved AUCs ≥0.91. This study quantified the mpMRI characteristics of benign prostate tissues and demonstrated the capability of mpMRI to discriminate among benign as well as cancer tissues, potentially aiding future discrimination of cancer from benign confounders

Practical aspects of prostate MRI: hardware and software considerations, protocols, and patient preparation.

The use of multiparametric MRI scans for the evaluation of men with prostate cancer has increased dramatically and is likely to continue expanding as new developments come to practice. However, it has not yet gained the same level of acceptance of other imaging tests. Partly, this is because of the use of suboptimal protocols, lack of standardization, and inadequate patient preparation. In this manuscript, we describe several practical aspects of prostate MRI that may facilitate the implementation of new prostate imaging programs or the expansion of existing ones

Semiautomatic registration of digital histopathology images to in vivo MR images in molded and unmolded prostates

PurposeTo evaluate a semiautomatic software-based method of registering in vivo prostate MR images to digital histopathology images using two approaches: (i) in which the prostates were molded to simulate distortion due to the endorectal imaging coil before fixation, and (ii) in which the prostates were not molded.Materials and methodsT2-weighted MR images and digitized whole-mount histopathology images were acquired for 26 patients with biopsy-confirmed prostate cancer who underwent radical prostatectomy. Ten excised prostates were molded before fixation. A semiautomatic method was used to align MR images to histopathology. Percent overlap between MR and histopathology images, as well as distances between corresponding anatomical landmarks were calculated and used to evaluate the registration technique for molded and unmolded cases.ResultsThe software successfully morphed histology-based prostate images into corresponding MR images. Percent overlap improved from 80.4 ± 5.8% before morphing to 99.7 ± 0.62% post morphing. Molded prostates had a smaller distance between landmarks (1.91 ± 0.75 mm) versus unmolded (2.34 ± 0.68 mm), P < 0.08.ConclusionMolding a prostate before fixation provided a better alignment of internal structures within the prostate, but this did not reach statistical significance. Software-based morphing allowed for nearly complete overlap between the pathology slides and the MR images

IMECE2008-68973 COMPLEXITY AND FRAILTY: MULTISCALE ENTROPYOF BALANCE DYNAMICS DURING QUIET STANDING AND DUAL-TASK: THE MOBILIZE BOSTON STUDY

ABSTRACT Balance control during standing is attributable to the complex, nonlinear interactions of multiple postural control systems, manifested as the highly irregular displacements in center of pressure (COP) during standing. Aging and associated frailty may result in the degradation of these complex interactions and manifest as a loss of complexity in COP dynamics. Furthermore, frail individuals may not be able to adapt to a superimposed stress that challenges balance, leading to falls. To test these hypotheses, data were analyzed from the MOBILIZE Boston Study, an ongoing population-based study of community-dwelling older adults. Each participant's frailty phenotype (not frail, pre-frail, frail) was determined using the Fried et al. 2001 definition. 551 participants (age 77.9±5.5) stood on a balance platform, with or without concurrently performing serial subtractions. Complexity of balance dynamics over multiple time scales was quantified using multiscale entropy (MSE), a more sensitive measure of physiologic health than variance. Of the participants, 39% were pre-frail and 6% were frail. Baseline MSE was lower with each successive frailty condition (p<0.002). When performing the cognitive task, MSE was lowered similarly in all groups (p<0.001). Frailty was associated with a loss of complexity in the dynamics of postural sway, which may be due to the degradation of integrated postural control networks that enable upright stance. Performance of a dual-task further reduced this complexity. Cognitive distractions during standing may further compromise balance control in frail individuals, which may explain their increased fall risk