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Brigham & Women's Hospital, Harvard University

Quantitative MRI of prostate cancer as a biomarker and guide for treatment.
Fiona Fennessy, MB, PhD 
ffennessy@partners.org
Brigham and Women's Hospital, Boston, MA
Grant Number: U01 CA151261

Brigham and Women's Hospital has established a multidisciplinary team in consortium with industry, supported by the Quantitative Imaging Network to address prostate cancer, the most common malignancy and third leading cause of cancer-related mortality in American men. Due to the ageing "baby boomers", the number of men with localized prostate cancer will increase, as will the need for an accurate non-invasive imaging tool. Magnetic Resonance (MR) imaging has the ability to deliver precise anatomical mapping of tumor. Newer MR techniques allow for pharmacokinetic (PK) evaluation of prostate tissue. This functional aspect of MR imaging could contribute greatly to the accuracy of tumor detection and localization, and potentially serve as a guide for focal ablative therapy, or non-invasively assess functional aspects of prostate tissue microcirculation in response to neoadjuvant treatment. The objective of this study is therefore to determine if optimized MR analysis tools and algorithms can be used as a biomarker guide for targeted therapy and as a surrogate for disease recurrence in prostate cancer. The investigators plan to achieve their objective through four specific aims: 1. To develop and implement imaging methodology and analysis tools for automated, robust quantitative assessment of prostate tumor volumetry and assessment of the functional properties (vascularity and permeability) using quantitative multi-parametric MR imaging (mpMRI). 2. To clinically validate the prostate mpMRi quantitative analysis tools described in Aim 1. They will perform a multivariate analysis of the results of the analyses tools, and patient-specific parameter maps for tumor localization (a summary statistic display) will be obtained and correlated with pathology at prostatectomy. 3. To determine the clinical use of the analysis tools as a biomarker guide for targeted therapy and as a surrogate for disease recurrence in low-risk prostate cancer patients. They will obtain mpMRI maps, detailing the index lesion and its margins, and register them with focal ablative therapy treatment planning images. Follow up mpMRI maps will be registered the pre-treatment maps to detect changes, and will be correlated with PSA to determine the "expected" treatment margin and untreated prostate mpMRI characteristics. 4. To determine the clinical use of the analysis tools in evaluating tumor response to treatment with neoadjuvant androgen deprivation therapy (ADT) in patients with high-risk prostate cancer. They will assess the changes in mpMRI maps after 12 weeks of ADT to determine if prostate tumor vascular permeability changes may be a suitable predictor of pathological response, by correlation with prostatectomy specimens.

The investigators will determine if new non-invasive quantitative MRI techniques can accurately detect and characterize tumor in patients with localized prostate cancer, a common diagnosis (and treatment dilemma) in American men. We will also investigate a role for these MRI techniques as a guide for targeting prostate cancer with focal therapy (thereby sparing normal healthy prostate tissue), as a marker for response to neoadjuvant therapy in those with high-risk prostate cancer, and as a marker for disease recurrence post-therapy.

The specific aims being addressed by the investigators include:
Aim 1.  To optimize prostate MR analysis tools,
Aim 2.  To clinically validate prostate MR quantitative analysis tools,
Aim 3.  To determine the clinical use of the analysis tools as a biomarker guide for targeted therapy and as a surrogate for disease recurrence In low-risk prostate cancer patients, and
Aim 4. To determine the clinical use of the analysis tools in evaluating tumor response to treatment with neoadjuvant androgen deprivation therapy (ADT) in patients with high-risk prostate cancer.