High Resolution MRI Study for Prostate Cancer

2.0 BACKGROUND AND RATIONALE

Multiparametric MRI Multiparametric MRI combining T2-weighted, diffusion-weighted, and
dynamic contrast enhanced (DCE) images is commonly employed for detection and localization of
prostate lesions. Diffusion-weighted imaging (DWI) is sensitive to the diffusion of water
molecules interacting with surrounding macromolecules. DWI, which provides a quantitative
biological parameter called apparent diffusion coefficient (ADC) value, is a robust MRI
parameter for differentiating benign and malignant prostate tissue. In fact, the latest
version of the Prostate Imaging-Reporting and Data System (PI-RADS) scoring system relies
almost exclusively on DWI to identify tumors in the peripheral zone, which is where the vast
majority of prostate cancers form. Findings on T2 images are not used to identify cancer, and
DCE images are only used to differentiate between some PI-RADS 3 and 4 lesions. In a pilot
study of prostate cancer AS, DW-MRI was useful for detecting progression of Gleason score
based on changes in ADC value. Tumor size is another important clinical criterion for
defining low risk prostate cancer, and tumor size based on DWI has been shown to crudely
predict low risk prostate cancer. However, conventional DWI using single-shot echo-planar
imaging is unable to detect small tumors, low grade tumors, or small changes in tumor size on
serial imaging. Approximately 20% of small, low grade tumors found in men on AS are detected
on modern prostate MRI.

High Resolution MRI Investigators introduce a new three-dimensional (3D) high-resolution
diffusion-weighted imaging sequence (HR-DWI), which improves image quality while conferring
at least a 5-fold improvement in resolution when compared to standard two-dimensional (2D)
DWI (S-DWI). This novel 3D DWI technique has been developed by our team and can be applied on
existing 1.5T or 3T MRI systems. S-DWI suffers from two important limitations. a) It uses
single-shot echo-planar imaging (EPI) for data acquisition, which produces magnetic
susceptibility induced streaking artifacts and geometric distortions so that round objects
may appear oval. b) The relatively low signal-to-noise ratio and 2D image acquisition with
S-DWI limit spatial resolution, which is defined by the minimum distance between two objects
required to resolve them uniquely. Our HR-DWI overcomes these limitations by using
magnetization prepared, multi-shot, turbo-spin-echo acquisition, which improves
signal-to-noise ratio (SNR), spatial resolution, and image quality, and eliminates geometric
distortions and streaking artifacts associated with EPI.

Preliminary studies

In preliminary studies assessing the performance of our HR-DWI in a prospective pilot trial
of prostate cancer AS patients, the technique could detect tumors not seen on S-DWI and
measure ADC, which correlates with grade. This is important because the long-term natural
history of small prostate cancers invisible to S-DWI has never been prospectively defined, in
part due to lack of adequate imaging technology. In the era of molecular diagnostics and
next-generation sequencing, an important step in understanding the biology of these lesions
is to develop technologies to image and characterize these lesions. Importance of HR-DWI
includes:

- Better imaging will allow these lesions to be monitored serially and targeted for
biopsy, providing tissue for both histologic and molecular characterization.

- Higher resolution imaging will better delineate tumor boundaries, which can improve
tumor staging and identify margins during partial-gland ablation by cryotherapy or high
intensity focused ultrasound (HIFU), which was approved in 2015 by the U.S. FDA.

- Improved imaging resolution will allow for more accurate measurement of tumor size and
ADC, and detection of small changes in size or grade over time. Standard prostate DWI
has poor resolution; therefore, tumor growth kinetics have never been accepted as
clinical criteria for cancer progression while on AS. If tumor growth kinetics or
changes in grade determined by ADC prove prognostic, AS can rely less on serial
transrectal biopsies, which can lead to serious complications.

Inclusion Criteria:

- Age over 18 years

- Patients diagnosed with clinically localized prostate cancer

- Low or Low-intermediate Risk Prostate cancer1 defined as:

- Pre-operative PSA ≤ 20.0 ng/ml

- Clinical stage cT1 or cT2

- Gleason score 3+3 or 3+4

- Patients choosing AS or already on AS as primary management strategy

- No previous treatment for prostate cancer with radiotherapy, chemotherapy, or hormonal
therapy

- No contraindications for gadolinium enhanced MRI

Exclusion Criteria:

- No exclusion criteria