Characterization of Prostate Cancer With 3T MR

In our laboratory we have combined the use of new 3T clinical magnetic resonance (MR)
technology, dynamic-contrast enhancement (DCE), and a unique endorectal-coil (ERC) probe in
order to non-invasively obtain images of the prostate gland with higher signal-to-noise
resolution and better spectral dispersion than has been previously achieved. This imaging
strategy acquires higher-resolution images with smaller voxel sizes than has been possible
with prior MR technology and more comprehensive tissue sampling compared to other
pre-surgical assessments. This methodology should make it feasible to assess prostate-tissue
morphology and additional features of prostate cancer such as tissue metabolism, tissue
kinetics, and the vascular microenvironment, and thus provide a non-invasive tool to: 1)
detect extra-capsular spread, 2) detect specific areas within the prostate that harbor
cancer, 3) determine the aggressiveness of the cancer and 4) direct biopsy and treatment
specifically to diseased areas.

In order to prospectively validate these goals we will recruit successive patients who have
been scheduled for prostate removal to participate to our protocol. Each patient will be
studied with an ERC MRI at 3T using T2-weighted (T2W) imaging, DCE 3D T1-weighted imaging and
MR spectroscopy (MRS). A pathologist using whole mount preparations will independently
analyze each patient's prostate specimen. The whole mount data will be used as the standard
against which we will compare the observations and data obtained from the 3T MRI findings.

Aim 1: To evaluate the accuracy of T2W MRI, DCE-MRI and their combined data for staging
prostate cancer.

Supplementing T2W imaging with the high-resolution capability of 3TMR, we will apply standard
morphologic criteria used at 1.5T to determine the presence or absence of extracapsular
extension (ECE) of disease. The possible incremental value of high spatial resolution,
dynamic contrast-enhanced data will be investigated. MRI results will be compared to ECE
determination at whole-mount pathology.

Aim 2: To evaluate the accuracy of MRI in determining tumor volume in the prostate gland.

Using dynamic-contrast enhanced MRI with parametric analyses and T2-weighted images, both at
smaller voxel sizes than have been used previously, will be our approach. Tumor volumes
determined with MRI will be compared to those determined at pathology.

Aim 3: To evaluate the accuracy of MRI in grading prostate cancer.

The enhanced resolution available at 3T offers new opportunities to compare Gleason grades
with independent and combined assessments of tissue kinetics and metabolism. Pixel by pixel
parametric analyses will be obtained. Furthermore, choline to citrate and choline plus
creatine to citrate ratios determined using MRS techniques will be obtained. Single voxel
techniques will first be employed, followed by 3D chemical shift imaging, when the latter
becomes available at 3T. DCE and MRS data will be compared both separately and in combination
to the histologic Gleason scores of the comparable tumor identified at whole mount pathology.

Inclusion Criteria

1. Biopsy-proven adenocarcinoma of the prostate.

2. Written documentation from the urologist stating the anticipation that the patient
will undergo radical prostatectomy or biopsy of the prostate within six months of MRI.

3. The interval between biopsy and protocol MRI must not be less than 2 weeks.

4. Pathologic specimens from radical prostatectomy must be provided for whole mount
analysis.

5. Patients will sign a study-specific consent prior to study entry.

6. Men above the age of 40 years old

Exclusion Criteria

1. Patients who because of age, general medical or psychiatric condition, or physiologic
status unrelated to the presence of prostate cancer cannot give valid informed
consent.

2. Patients unwilling or unable to undergo MRI including patients with contra-indications
to MRI such as the presence of cardiac pacemakers or non-compatible intracranial
vascular clips.

3. Patients who cannot tolerate or have contra-indications to ERC insertion; for example,
patients who have had a prior abdominoperineal resection of the rectum or have Crohn's
disease.

4. Patients with an allergic reaction to latex.

5. Cryosurgery, surgery for prostate cancer including TURP, prostatic radiotherapy,
including bradiotherapy for rectal cancer, androgen deprivation therapy, rectal
surgery, or alternative medicine prior to radical prostatectomy.

6. Any metallic implant (e.g. hip) or device that might distort local magnetic field and
compromise quality of MRI.

7. Radical prostatectomy or biopsy of the prostate not planned to be performed within six
(6) months of protocol MRI.

8. Patients who have undergone BCG for bladder cancer.

9. Patients with severe motion artifacts rendering the data unusable.

10. Patients who have an allergic history to gadopentetate dimeglumine administration.

11. Patients with a contraindication to the administration of glucagon (pheochromocytoma,
islet pancreatic tumor, or insulin-dependent diabetes) or a prior history of allergic
reaction following glucagon administration.