Clinical assessment of the extent of prostate cancer (PC) is often difficult because of the inaccessible location of the gland deep within the pelvis. Traditionally, the extent of PC was evaluated by digital rectal examination. Increased awareness of limitations of traditional methods for diagnosis and staging of PC has mobilized the development and application of new imaging modalities for its assessment. Several new non-invasive imaging studies, such as CT scan, transrectal ultrasound of the prostate (TRUSP), and magnetic resonance imaging (MRI) have been developed to aid in this evaluation. However, each of these modalities has limitations and no one technique can consistently provide all the information needed by physicians.

While many different methods have been added to the number of diagnostic tests in PC assessment, this review will focus only on combined use of magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging (MRSI).

Both MRI and MRSI examinations are FDA approved. However the accuracy of the combined MRI/MRSI exam for assessing the presence and spatial extent of PC prior to, during and after therapy is still undergoing clinical investigation.

MRI emerged in 1980 as an outgrowth of the use of nuclear magnetic resonance to study the structure of chemical compounds. MRI imaging has several advantages over conventional radiography:

However, even with all of these advantages, the MRI has limitations:

Endorectal MRI uses five receiver coils (endorectal coil combined with four external coils) to acquire images simultaneously. This approach provides the sensitivity to acquire anatomic images with much higher resolution than previously possible. Furthermore, the use of endorectal MRI allows simultaneous acquisition of spectroscopic imaging. The endorectal coil provides the necessary sensitivity to focus on the prostate and surrounding structures. The pelvic phased array (4 external coils) allows a large enough field-of-view to also assess pelvic lymph nodes and the pelvic bones for metastatic disease. Variability in image quality (due to the fact that image intensity dramatically decreases with distance from the surface coil) and subsequent difficulties in interpretation, however, may present a problem. To correct for this obstacle, the University of California San Francisco MR Research Team has developed computer post-processing to create uniform images, greatly improving interpretation. Additionally, improved MR technology has provided reduction in the time required for MR examination making it more feasible to add MRSI to the staging examination.

The recent developments of MR spectroscopic imaging (MRSI) expand the diagnostic assessment beyond the anatomic information provided by MRI.^6-8 As with MRI, MRSI users a strong magnetic field and radiowaves to noninvasively obtain metabolic pictures (spectra) based on the relative concentrations of cellular chemicals (metabolites). MRSI therefore provides metabolic information specific to the prostate through detection of the cellular metabolites citrate, creatine, and choline.

The combined MRI/MRSI study provides high-resolution anatomic imaging (MRI) and nuclear magnetic resonance spectroscopy data that was previously used to study the structure of chemical compounds in the laboratory. The result is that one can observe specific resonances (peaks) for citrate, choline and creatine from small volumes throughout the gland. The area under these peaks is related to the concentration of these metabolites and changes in these concentrations can be used to identify cancer.

In a preliminary study of 85 PC patients who had combined MRI/MRSI evaluation prior to radical prostatectomy (RP), significantly higher choline levels and significantly lower citrate levels were observed in regions of cancer as compared to BPH and normal prostatic tissues. The ratio of these metabolites (choline/citrate) in regions of cancer had minimal overlap with normal prostate tissue and BPH values.⁷ In addition, a pilot study from our laboratory suggests that the metabolic information obtained from MRSI may also allow an expanded assessment of tumor aggressiveness and disease progression. In a study of 62 patients undergoing MRI/MRSI evaluation prior to RP with step-section histopathology, it was demonstrated that PC could be localized to a sextant of the prostate (i.e. left/right base, midgland and apex) with a specificity of up to 91% when both MRI and MRSI were positive for cancer and a sensitivity of up to 95% when either MRI or MRSI were positive for cancer. In a separate review, the data suggest that the addition of MRSI to MRI can improve both staging and localization of PC within the gland, prior to and after therapy. ⁹

¹ Sensitivity = True Positives ¸ [True Positives + False Negatives]

² Specificity = True Negatives ¸ [True Negatives + False Positives]

A study of high sensitivity is associated with few patients being told they don’t have PC when in fact they do have PC (false negative result)

A study of high specificity is associated with few patients being told they do have PC when in fact they don’t have PC (false positive result)

MRSI will probably have its greatest impact on the assessment of PC therapy and on the selection of additional therapy. Recent studies have indicated that residual or recurrent PC can be discriminated from normal and necrotic tissue after cryosurgery.^6,10 There is also evidence that the same is true for other therapies such as androgen deprivation therapy (ADT), radiation therapy (RT), and chemotherapy. The role of MRI/MRSI in detection of residual cancer in the prostate bed after RP is, at present, unknown. MRI cannot be safely used after RP due to the metallic clips used at the time of RP and the disruption of these clips due to the powerful magnets used in the MRI.

Additionally, MRI/MRSI data are useful in guiding biopsies in patients with consistently rising PSA tests but negative biopsies. The advantage of covering the entire gland is critical since biopsies sample only a small fraction of the gland and may miss PC. Post-biopsy hemorrhage, a major impediment to MRI interpretation, occurs frequently in PC patients. Post-biopsy hemorrhage occurred in 28% of all patients studied and was extensive (involving greater than 50% of the sites sampled) in 63% of these patients. The addition of an MRSI sequence to an MRI staging exam significantly increased specificity and accuracy of tumor detection in the presence of post-biopsy hemorrhage.¹¹

There are two main reasons why PC patients may opt for MRI/MRSI study:

A team of researchers at the Department of Radiology, UCSF, (Hedvig Hricak, Ph.D., MD, John Kurhanewicz, Ph.D., Ryan Males, Ph.D., Sarah Nelson, Ph.D., Kyle Yu, M.D. and Daniel Vigneron, Ph.D.), are currently adding an MRSI sequence to all patients receiving a high resolution MRI staging exam for PC. The official radiology report includes information from both MRI and MRSI. To date, over 1,000 PC patients have been studied using this combined examination. The time for the combined MRI/MRSI study is 50 minutes: one hour including patient positioning and coil placement.

To make an appointment to obtain the MRI/MRSI study, contact the UCSF Imaging Center, telephone (415) 476-2573. If you want to talk to a patient who had undergone this test, contact _______________ (Patient permission obtained and is on file.)

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