U01CA151261

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Background

Grant Number: 1U01CA151261-01
PI Name: Fiona M. Fennessy, MD
PI Email: ffennessy@partners.org
Project Title: QUANTITIATIVE MRI OF PROSTATE CANCER AS A BIOMARKER AND GUIDE FOR TREATMENT
Project Start: 01-JULY-2010
Project End: 31-JULY-2015
Grant Text:


The fiscal year for this grant is July 1 to June 30.

Abstract Prostate cancer is 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. We plan to achieve our objective through 4 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. We 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. We 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. We 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.

Specific Aims

new page for each SA, populate, maintain tasks and progress -- andrey todo

SA1: To optimize prostate MR analysis tools We will develop and implement imaging methodology and analysis tools for quantitative assessment of prostate tumor volumetry and functional properties using multi-parametric MR imaging (mpMRI). In this task, we will optimize MR imaging methods on standard clinical equipment, and develop tools that allow automated and robust measurement of tumor size and functional characterization of its angiogenic properties (vascularity and permeability) using quantitative MR imaging. The mpMRI protocol will include T2-weighted FSE, diffusion weighted imaging, dynamic contrast enhanced imaging, and MR spectroscopic imaging. We will develop techniques for combined analysis of tumor pathophysiology from this multi-parametric data.

SA2: To clinically validate prostate MR quantitative analysis tools We will use the optimized multiparametric prostate MR analysis tools to extract quantitative metrics for prostate tumor detection and tumor volumetrics. We will also use these tools for automated functional characterization of the tumor and its margins, such as vascularity and permeability. We will perform a multivariate analysis of the results of the analyses tools, and patient specific multiparametric maps for tumor localization (a summary statistic display) will be obtained. All clinical data including serum Prostate Specific Antigen (PSA), biopsy Gleason scores, and all pathological markers at radical prostatectomy will be recorded. Non-rigid registration of the multiparametric maps to pathology imaging will be performed, allowing for the determination of the accuracy of multiparametric tumor mapping. We will validate the analyses tools by determining the sensitivity and specificity of these tools for mapping an index prostate lesion and its margins, as defined by the pathology specimen.

SA3: 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 Using the above-described analyses tools for tumor definition and characterization, we will identify discrete tumor within the prostate, in low-risk prostate cancer patients, that will be treated with either dose escalated external beam radiation therapy (EBRT), or with focal ablative therapy with Magnetic Resonance guided Focused Ultrasound Surgery (MRgFUS). We will obtain multi-parametric maps, that will detail the index lesion and its margins, which will be registered with the index lesion treatment planning images for focal ablative therapy using a non-rigid image registration tool. We will test our hypothesis that patient-specific multiparametric maps obtained will be valuable to the physician performing the focal ablative therapy. After treatment, PSA will be collected at 1, 3, 6, and 12 months post focal therapy, and follow-up mpMRI exams will be obtained immediately, 6 months and 12 months after therapy. The multiparametric map of the treated index lesion, its margins, and the benign untreated gland at all follow-up time points will be registered with the pre-treatment multiparametric map to detect any changes, and will be correlated with PSA to determine what the “expected” treatment margin and untreated prostate mpMRI characteristics are. We will test our hypothesis that differentiation of residual tumor from peri-ablation enhancement is possible using mp mapping, thus improving the safety and effectiveness of focal therapy by providing quantitative information before and after treatment.

SA4: 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 Using the optimized analyses tools for tumor definition and characterization, we will assess the changes in mpMRI, specifically focusing on pharmacodynamic modeling of DCE-MRI/Diffusion, after 12 weeks of androgen deprivation therapy (ADT) with abiraterone acetate or leuprolide acetate, to determine if prostate tumor vascular permeability changes may be a suitable predictor of pathological response. Vascular permeability changes will also be correlated with other multiparametric MR findings, and with histopathology provided by prostate biopsy after 12 weeks of ADT, and with whole mount histopathology and molecular markers at radical prostatectomy after 24 weeks of ADT, to determine which MR parameters better assess response to treatment.

Timeline

  • Year 1
    • July
    • August
    • September
    • October -- QIN meeting at NIH on 10/18-10/19(Fiona, Bob, Sandeep, ???)
    • November -- ISMRM abstract deadline. RSNA conference
    • December
    • January
    • February
    • March
    • April -- RSNA abstract deadline
    • May -- ISMRM
    • June

Key Personnel

  • Fiona Fennessy, MD, PhD (PI) (FFENNESSY@PARTNERS.ORG)
  • Clare Tempany, MD (ctempany@bwh.harvard.edu)
  • Robert Mulkern, PhD
  • Yi Tang, MD
  • Ehud Schmidt, PhD
  • Sandeep Gupta (GE)
  • Andriy Fedorov, PhD

Progress Reports

File:U01CA151261 QIN Progress report Year1.doc (this is different from progress report, need to add here all reports -- andrey todo)

Meetings

BWH QIN group communicates by means of weekly tcons and meetings as necessary. There are monthly tcons for various working groups of QIN, and regular face-to-face meetings at NIH. Follow this link to the dedicated page.

Shortcuts:

Abstracts and Talks

  • ISMRM 2012 Accepted Abstracts
    1. F.Fennessy, A.Fedorov, S.Gupta, W.M.Wells, R.Mulkern, C.Tempany. Assessment of abnormal ADC matched voxels with DCE parameters for characterization of prostate cancer at 3T. Media:Fennessy_ISMRM2012.pdfOral presentation.May 10th 11:18am. Session;Prostate Cancer, Room:210-211. Slides: PPT, PDF
    2. S.Gupta, E.Schmidt, R.Mulkern, A.Fedorov, I.Hancu, Y.Zhu, C.Tempany, F.Fennessy. A Method for Correcting T1 maps of Prostate at 3T Obtained by Variable Flip Angle Imaging. Media:Gupta_ISMRM2012.pdfTraditional poster. May 9th 13:30. Session; Prostate.
    3. K.Tuncali, A.Fedorov, F.Fennessy, S.Gupta, J.Tokuda, S.Song, N.Hata, R.Mulkern, C.Tempany. Predictive Value of 3T mpMRI: Correlation with MRI-guided Transperineal Targeted Prostate Biopsy Outcomes Media:Tuncali_ISMRM2012.pdf E-poster. Session: Prostate & Breast. Day/Date: 7 May 2012. Session Time: 15:15. Program number: 2992. Computer number: 53. Slides: PPT
    4. A.Fedorov, L.Ibanez, K.Tuncali, R.Mulkern, W.M.Wells, C.Tempany, F.Fennessy. Deformable Registration for Recovering Image Distortions in DWI MRI of the Prostate at 3T Abstract PDF Traditional poster. May 9th 10:00-12:00am. Program number 1503. Session; Prostate. Poster PDF
    5. M. Moradi, A. Fedorov, W. M. Wells, K. Tuncali, S. N. Gupta, F. M Fennessy, C. M. Tempany. Machine learning for target selection in MR-guided prostate biopsy: A preliminary study Moradi_ISMRM2012(Traditional poster) Session: Prostate Day/Date: 9 May 2012 Session Time: 10:00 (Mehdi will not be attending, Clare and Bob will coordinate who will present this). The poster in PDF format is here: File:ISMRM2012 MM 1509.pdf
  • ISMRM 2011 Accepted Abstracts
    1. (NCIGT Prostate, Computation, Guidance) A. Fedorov, K. Tuncali, F. Fennessy, J. Tokuda, N. Hata, S.W. Wells, R. Kikinis, and C.M. Tempany. Hierarchical Image Registration for Improved Sampling during 3T MRI-guided Transperineal Targeted Prostate Biopsy media:2011_ISMRM_Fedorov.pdf Session: Prostate Cancer (Clinical Studies)Computer Assignment: 8Day/Date: Thursday, Thursday, May 12th Session Start Time: 13:30 Slides: Media:2011_ISMRM_Fedorov_slides.ppt
    2. (NCIGT Prostate, Guidance) J Tokuda, K. Tuncali, I. Iordachita, S-E. Song, A. Fedorov, S. Oguro, A. Lasso, F. M. Fennessy, Y. Tang, C. M. Tempany, and N. Hata. Preliminary Accuracy Evaluation of 3T MRI-guided Transperineal Prostate Biopsy with Grid Template. media:2011_ISMRM_Tokuda.pdf Session: Interventional MRI: Instrument Visualization, Guidance & Interfaces Computer Assignment:121 Day/Date: Thursday, May 12th Session Start Time: 13:30
    3. (NCIGT Prostate, Imaging) FM Fennessy, SN Gupta, A Fedorov, R Mulkern, Y Tang, F Franco, K Tuncali1, E Schmidt, C Tempany. A comparison between arterial input function approaches for high temporal resolution pharmacokinetic analysis of prostate cancer at 3.0T.media:2011_ISMRM_fennessy.pdf Session: Prostate Cancer (Clinical Studies) II Computer Assignment: 9 Day/Date: Tuesday, May 10th Session Start Time: 13:30 Slides: Media:2011_ISMRM_Fennessy_slides.ppt
    4. (NCIGT Prostate, Guidance) K. Tuncali, J. Tokuda, A. Fedorov, I. Iordachita, S. Song, S. Oguro, A. Lasso, F. M. Fennessy, Y. Tang, N. Hata, and C. M. Tempany. 3T MRI-guided Transperineal Targeted Prostate Biopsy: Clinical Feasibility, Safety, and Early Results. media:2011_ISMRM_Tuncali.pdf Session: Prostate Cancer (Clinical Studies) II Computer Assignment: Day/Date: Monday, May 9th Session Start Time: 11:00
    5. (NCIGT Prostate) F.Franco, F. Fennessy, A. Fedorov, K. Tuncali, J. Tokuda, S. Gupta and C. Tempany Correlation of Histology from MR-guided Transperineal Prostate biopsy with Multiparametric MR Imaging: A Feasibility Study media:2011_ISMRM_Franco.pdf Session: Prostate Cancer (Clinical Studies) Computer Assignment: Day/Date: Tuesday, May 10th Session Start Time: 13:30 File:2011 ISMRM Franco poster.pdf
    6. Y.Zhu, M.-C.Chang, F.Fennessy, S.N.Gupta Automatic Arterial Input Function Detection for Prostate Dynamic Contrast Enhanced MRI. Media:2011_ISMRM_Zhu.doc

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