“Men need to learn to fight like women, the incidence and mortality rates are very comparable between breast and prostate cancer.”~ Dr. Princenthal Prostate MRI in conjunction with prostate-specific antigen (PSA) screening and digital rectal exam provides a better pathway to triage men for consideration of biopsy. Fewer needles and less harm is the goal. This approach opens the door for tailored focal therapy. Prostate MRI is now at an inflection point, having gained recognition from the American Urologic Association based on data provided by the Promis and Precision trials, resulting in greater utilization.

Clinical Case Report: Prostate Cancer Detection on 1.2T Open Oasis MRI System

W H I T E PA P E R

Robert Princenthal, M.D.February 2020

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2 Clinical Case Report: Prostate Cancer Detection on 1.2T Open Oasis MRI System

Author’s BioRobert Princenthal, M.D., is a board-certified radiologist with more than 25 years of expertise in diagnostic medical imaging and serves as the medical co-director for RadNet’s Prostate MRI Program. Dr. Princenthal attended medical school at Penn State College of Medicine at the Milton S. Hershey Medical Center, completing his internship at Hartford Hospital in Hartford, Connecticut. He completed a diagnostic radiology residency at Yale University School of Medicine at New Haven Hospital and a fellowship in body imaging and interventional radiology at the University of California, San Diego.

Dr. Princenthal has a range of responsibilities as President of Rolling Oaks Radiology in Thousand Oaks, CA. As Director of Prostate Imaging for Radnet, Inc for Southern California and with his involvement in Women’s health, he has seen the difference in patient outcomes that early, accurate diagnosis of cancer provides. This is why he has been instrumental in bringing some of the most advanced cancer detecting technologies, including prostate MRI, to Ventura County’s patients and referring physicians. His experience in early detection for various cancers encouraged him to explore improved imaging options to detect cancer unique to men. Dr. Princenthal started his training in prostate MRI with the mentoring of Drs. Peter Choyke of NIH, and Jelle Barentsz (Holland) in 2009. He has gained tremendous experience; his practice performed over 6,000 prostate MRI’s in 2019, and he has interpreted close to 10,000 exams. Additionally, he was a beta evaluator for Dynatrim (Invivo Medical) in-bore MRI guided biopsy.

Dr. Princenthal is a consultant for Ezra Health and Profound Medical. He has been an invited lecturer sponsored by GE Medical and Philips Medical, and has also published several articles on prostate MRI.

OverviewProstate cancer is the most commonly diagnosed cancer in men and the second leading cause of cancer-associated death among men in the United States. Trying to distinguish high-risk from low-risk prostate cancer remains difficult, leading to overdiagnosis and unnecessary invasive treatments and treatment-associated morbidity. Tests that can detect clinically significant prostate cancer while reducing overdiagnosis of low-risk disease continue to be an unmet need in the clinical setting.

Enter prebiopsy multiparametric MRI, commonly referred to as mpMRI. In one study, this examination reduced unnecessary biopsies by more than one third, and increased the detection of clinically significant disease by more than 50%. Prebiopsy mpMRI combined with targeted biopsy is associated with the improved detection of clinically significant prostate cancers, a reduction in the number of biopsy cores per procedure, and the potential to avoid unnecessary biopsies1. Imaging offers the greatest potential means of differentiating indolent disease from more aggressive, lethal cancers, while the improvements in MRI techniques enable radiologists to play a key role in the risk stratification and management of patients. Prebiopsy MRI has the added advantage of avoiding biopsy-related hemorrhage, which can hinder interpretation. Transrectal ultrasound (TRUS) biopsy guides the needle to the prostate, but not necessarily to the cancer, and is prone to sampling errors. TRUS biopsies miss cancer in up to half of all cases, and have consistently been shown to underestimate the aggressiveness of prostate cancer in one third of cases. MR is often recommended for patients with negative biopsies, if warranted based on clinical suspicion, implying that many patients requiring a TRUS biopsy will undergo mpMRI at some stage in their clinical pathway2.

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Patient’s HistoryThe patient was a biopsy-naïve 76-year-old male, who presented with a rising PSA, and symptoms of benign prostatic hypertrophy (BPH). At the time of biopsy, the PSA was 6.37ng/mL. Physical examination revealed firmness in the right apex and left base of the prostate. The patient’s past medical history was positive for squamous cell carcinoma, which was treated with surgery and radiation therapy. A staging PET (positron emission tomography) scan performed 4 months prior to prostate MRI showed a possible hypermetabolic focus in the left lobe of the prostate.

MR Imaging TechniqueMultiparametric MRI (mpMRI) was performed on a 1.2T Open MRI system (Oasis, Hitachi Healthcare Americas). Multiparametric imaging includes any functional form of imaging used to supplement standard anatomical T1- and T2-weighted imaging. The functional sequences of choice are dynamic contrast-enhanced MR and diffusion-weighted imaging (DWI), including the calculation of apparent diffusion co-efficient (ADC) maps2. The protocol used in this case included high resolution, small field-of-view T2-weighted imaging in the axial, coronal, and sagittal planes. Diffusion weighted imaging utilized a high b-value of 1200 to allow for enough signal-to-noise for diagnostic image quality. When performing the dynamic contrast-enhanced images, data was acquired every 5 seconds over a 4-minute time period. Post-processing was performed on an Invivo® DynaCAD® workstation.

Acquisition Plane TR (msec) TE (msec) Thick (mm) FOV (cm) Matrix Other Settings Scan Time

FSE - T2

Sagittal 6500 96 4.0 20 288x448 RADAR 4:59

Coronal 4300 96 4.0 20 288x448 RADAR 3:17

Axial 4385 96 4.0 20 288x448 RADAR 6:43

FSE - T1 Axial 460 4.0 20 256x192 3:57

DWI Axial 4200 70 4.0 22 96x96 Fat Saturation 8:03

3D DCE - T1 Axial 4.0 2.0 3.5 24 96x96 Fat Saturation9.9s x 30

(4:47 total)

PI-RADS® V2.1The radiologist’s report on MR imaging findings includes PI-RADS® scores. PI-RADS® stands for Prostate Imaging-Reporting and Data System, which is currently on Version 2.1. This latest version was designed to improve detection, localization, characterization, and risk stratification in patients with suspected cancer in treatment naïve prostate glands. The overall objective is to improve outcomes for patients.

4 Clinical Case Report: Prostate Cancer Detection on 1.2T Open Oasis MRI System

The specific aims of PI-RADS® V2.1 include:• Establish minimum acceptable technical parameters for prostate mpMRI• Simplify and standardize the terminology and content of radiology reports• Facilitate the use of MRI data for targeted biopsy• Develop assessment categories that summarize levels of suspicion or risk and can be used

to select patients for biopsies and management (e.g., observation strategy vs. immediate intervention)

• Enable data collection and outcome monitoring• Educate radiologists on prostate MRI reporting and reduce variability in imaging interpretation• Enhance interdisciplinary communications with referring clinicians

The PI-RADS® v2.1 Assessment Categories include:• PIRADS 1 – Very low (clinically significant cancer is highly unlikely to be present)• PIRADS 2 – Low (clinically significant cancer is unlikely to be present) • PIRADS 3 – Intermediate (the presence of clinically significant cancer is equivocal) • PIRADS 4 – High (clinically significant cancer is likely to be present) • PIRADS 5 – Very high (clinically significant cancer is highly likely to be present)3

MR Imaging FindingsThe prostate gland had a calculated volume of 61cc, and a normal PSA density of 0.10. The transition zone showed a benign stromal nodule in the left mid gland ventrally. Evidence of a prior TURP (transurethral resection of the prostate) defect was seen at the base of the gland.

In the peripheral zone, lesion 1 was located at the 4:00-6:00 gland location at the lateral apex. This lesion measured 15 x 10 x 13mm, and displayed as an area of decreased T2 signal on the MR images. It was given a PI-RADS score of 5, which indicated that it was most likely malignant. This area showed restricted diffusion, with a mean ADC of 650, and corresponding high signal intensity on the high b-value images. These factors also indicate that it is most likely malignant, with another PI-RADS score of 5. Rapid early enhancement was demonstrated. The lesion had broad based capsular involvement, without gross extra prostatic extension.

Figure 1: Axial T2-weighted prostate image show left index lesion (yellow arrow)

Figure 2: Image from Figure 1 with index lesion measurements

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The right lobe revealed a mild decrease in T2 signal in the right apex, without significant diffusion changes. However, it did exhibit mild early enhancement. This area had a smaller volume (15mm) and was given PI-RADS scores of 4 and 5.

Mild left neuro-vascular bundle involvement was noted, but no seminal vesicle change was seen. No abnormal bony or nodal disease was identified. Incidental findings revealed mild free fluid in the cul-de-sac. Moderate bladder mucosal trabeculation from BPH was noted.

Based on imaging findings and the ADC score, a prediction of at least intermediate grade clinically significant prostate cancer was suggested.

Gleason Scores and Grade GroupsIn order to better understand the TRUS biopsy findings below, a review of Gleason Scores and Grade Groups may be in order. When examining biopsy specimens under the microscope, pathologists grade prostate cancers using numbers from 1 to 5, based on how much the cells in the cancerous tissue look like normal prostate tissue, as defined below:

• Gleason Score 1- Cancerous tissue looks very much like normal prostate cells• Gleason Score 2-4- Some cells look like normal prostate cells, other cells do not; patterns of

cells in these grades vary• Gleason Score 5- Cells appear abnormal and do not look like normal prostate cells; abnormal

cells appear to be scattered haphazardly throughout the prostate4

Figure 3: Image on left shows high signal intensity using b-value 1200; image on right demonstrates early enhancement of left apex, and small area of enhancement in right apex

Figure 4: Low grade lesion in right apex; image on right again shows positive dynamic enhancement revealing lesions in right apex and left apex

Figure 5: Image shows positive dynamic enhancement revealing lesions in right and left apices

6 Clinical Case Report: Prostate Cancer Detection on 1.2T Open Oasis MRI System

Grades are assigned to the two areas that make up most of the cancer, and the two grades are added to yield the Gleason Score. The first number assigned is the grade that is most common in the tumor (e.g., a score of 3+4=7 means that most of the tumor is grade 3, and less is grade 4). If the tumor is all the same grade (e.g., grade 3), the Gleason Score is reported as 3+3=6. Grades 1 and 2 are not often used for biopsies, so the lowest Gleason Score of a cancer found on a prostate biopsy is 6. A Gleason Score of 7 can result from a cancer that is 3+4=7 or 4+3=7; a 4+3=7 cancer is more likely to grow and spread than a 3+4=7 cancer, but not as likely as a Gleason Score 8 cancer. Gleason scores are often only divided into 3 main groups, which are totals scores of 6, 7, and 8-10.

A new way to grade prostate cancer that addresses some of the issues with the Gleason grading system uses Grade Groups. They range from 1 to 5, with group 1 being most favorable, and group 5 being least favorable. Grade Groups include:

• Grade Group 1- Gleason 6 (or less)• Grade Group 2- Gleason 3+4=7• Grade Group 3- Gleason 4+3=7• Grade Group 4- Gleason 8• Grade Group 5- Gleason 9-10

Although the Grade Group system may eventually replace the Gleason Score system, the two systems are currently reported side-by-side5, as in this case report.

TRUS Biopsy FindingsThe patient underwent a combined standard 12 core TRUS guided biopsy, with fusion targets of index lesions. Index lesions are defined as any lesions bearing the highest prostate cancer suspicion scores based on the patient’s initial multiparametric MRI, irrespective of lesion size6.

Pathology reports revealed an index lesion in the left apex with a Gleason Score of 4+3=7, 20% core involvement, and Grade Group 3. The left medial mid sample also revealed an index lesion, with a Gleason Score of 3+4=7, 52% core involvement, and Grade Group 2. In the right lateral apex, a 5mm lesion had a Gleason Score of 3+3=6, and Grade Group 1. The right medial mid sample revealed high grade prostatic intraepithelial neoplasia. Perineural invasion was not identified.

Figure 6: Examples of TRUS biopsy specimens, all with Gleason score of 7

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SummaryThis case demonstrates a high degree of tumor detection, and good correlation with pathology outcomes from a 1.2T high field open magnet. PI-RADS v2.1 has not yet determined the clinical validity of prostate cancer detection at MRI field strengths below 1.5T, as there is insufficient data to recommend its use3.

We obtain diagnostic prostate exams on the Oasis and direct our large patients to this platform. We also prefer to have our prostate exams with hip replacements scanned on the Oasis; the slightly lower field strength frequently allows more diagnostic-quality exams with reduced metal susceptibility artifacts on the diffusion sequence compared to a 3T magnet. While the current technical parameters described in PI-RADS v2.1 focus on optimal technique for 1.5T and 3T magnets, we hope that we can provide enough validated data to allow multiparametric prostate MRI on the Oasis 1.2T platform to be incorporated in newer PI-RADS guidelines, under certain conditions. The outstanding results for the patient in this case strongly suggest that cancer detection can be identified at 1.2T using the Hitachi Oasis scanner, with careful protocol implementation and rigorous attention to detail.

References1. Yee, Kate Madden. (9August2019). mpMRI reduces unnecessary prostate biopsies. Retrieved from

https://www.auntminnie.com/index.aspx?sec=sup&sub=mri&pag=dis&ItemID=126214

2. Barrett, Tristan. (2015). What is multiparametric-MRI of the prostate and why do we need it? Retrieved from https://www.openaccessjournals.com/articles/what-is-multiparametricmri-of-the-prostate-and-why-do-we-need-it.pdf

3. American College of Radiology. (2019) PI-RADS® Prostate Imaging-Reporting and Data System Version 2.1. Retrieved from https://www.acr.org/-/media/ACR/Files/RADS/Pi-RADS/PIRADS-V2-1.pdf?la=en

4. Prostate Cancer Free Foundation. (2017). Prostate Cancer Gleason Score. Retrieved from https://prostatecancerfree.org/prostate-cancer-gleason-score/

5. American Cancer Society. (2019). Understanding Your Pathology Report: Prostate Cancer. Retrieved from https://www.cancer.org/treatment/understanding-your-diagnosis/tests/understanding-your-pathology-report/prostate-pathology/prostate-cancer-pathology.html

6. Rais-Bahrami, Soroush, et.al. (30April2014). Natural history of small index lesions suspicious for prostate cancer on multiparametric MRI: recommendations for interval imaging follow-up. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463272/

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