MR spectroscopy may be superior for determining prostate cancer prognosis

April 17, 2005. PSA Rising. Magnetic resonance spectroscopic imaging (MRSI) is a noninvasive method of detecting small molecular markers (such as the metabolites choline and citrate) within prostate tissue. It is performed in conjunction with high-resolution anatomic imaging.

As a computerized numerical method, it can be more accurate than human eyeballing of biopsy slides.

Recent studies in patients preparing for prostate surgery indicate that the metabolic information provided by MRSI combined with the anatomical information provided by MRI can significantly improve the assessment of cancer location and extent within the prostate, extracapsular spread, and cancer aggressiveness.

A special technique in magnetic resonance (MR) spectroscopy calledHigh-resolution magic angle spinning (Hr-MAS) may develop into a new diagnostic tool for studying intact tissue samples, and several types of cancer have been investigated with promising results.

Using this method, which offers detailed information on the chemical make-up of tissue samples, scientists at Massachusetts General Hospital (MGH) have shown that chemical profiles of prostate tissue can tell more about a tumor than standard pathological studies do. The report appears in the April 15 issue ofCancer Research.

"Our study indicates that analyzing prostate tissue's metabolic profile may give clinicians additional information about the biologic status of the disease that could allow them, in consultation with their patients, to make better-informed decisions on the next steps to take," says Leo L. Cheng, PhD, of the MGHRadiology andPathology Departments, the report's lead author.

Why it is needed

Since the prostate-specific antigen (PSA) test became widely used to screen for prostate cancer, tumor detection rates have increased dramatically, particularly among those at early stages of the disease. But increased detection has led to a clinical dilemma, since standard histologic evaluation, based on a biopsy sample's appearance under a microscope, often cannot distinguish which tumors are going to spread and which are not.

Many men live for years with slow-growing prostate tumors before they die of unrelated causes, and treating such patients could cause more harm than benefit, Cheng notes. So finding a better way to determine which patients need aggressive treatment and which can try watchful waiting has been a major challenge.

Another problem is that a biopsy sample from one area of the prostate may miss malignant cells elsewhere in the gland. Removal of the entire prostate can give a more definitive diagnosis, but if the tumor is a slow-growing one, the patient would have undergone unnecessary surgery. Surgery also is not appropriate when cancer has already spread beyond the prostate, since that situation requires other therapeutic approaches such as chemotherapy or drugs that block testosterone's action.

How it works

Although MR spectroscopy has been used for many years to measure the chemical composition of materials, including biological samples, it has not been useful for analyzing tumor specimens.

In recent years, Cheng and his colleagues have been developing a spectroscopic technique called high-resolution magic angle spinning that provides detailed analysis of a sample's components without destroying its cellular structure.

The current study was designed to evaluate the technique's potential for providing information useful for clinical decision-making in prostate cancer.

The researchers used MR spectroscopy to analyze tissue samples from 82 patients in whom prostate cancer had been confirmed by prostatectomy. Almost 200 separate samples were studied, including many that appeared benign to standard histological examination. They then compared the spectroscopy results - detailed profiles of each sample's chemical components - with the information gathered from pathological analyses of the removed glands and the patients' clinical outcomes.

Several chemical components of the tissue samples were found to correlate with the tumors' invasiveness and aggressiveness, supporting the potential of these metabolic profiles to provide valuable clinical information. Perhaps most significantly, even samples of apparently benign tissue had components that could successfully identify more and less aggressive tumors elsewhere in the prostate.

"Not only are the spectroscopy studies as good as histopathology in differentiating cancer cells from benign cells, they may be even better if they can find these metabolic differences in tissues that look benign," says Cheng. "We need to do a larger scale, more systematic study of this technique before it can be applied to clinical practice. And we hope to collaborate with other institutions to identify different metabolic profiles that could provide additional information." Cheng is an assistant professor of Radiology and Pathology at Harvard Medical School.

Leo L. Cheng, PhD is Assistant Professor of Radiology. The study's co-authors are Melissa Burns, Jennifer Taylor, Chin-Lee Wu, MD, PhD, and Wenlei He, MD, PhD, of MGH Pathology; Elkan Halpern, PhD, MGH Radiology; and Scott McDougal, MD, chief of MGH Urology. The study was supported by grants from the National Institutes of Health and the U.S. Department of Defense.

Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $450 million and major research centers in AIDS, cardiovascular research, cancer, cutaneous biology, medical imaging, neurodegenerative disorders, transplantation biology and photomedicine.

From Glossary at websitespectroscopyNOW:

hr-MAS High Resolution Magic Angle Spinning:  "The sample is spun at a high speed at a well-defined angle to the main magnetic field.....The appeal of hr-MAS is that it allows the study of systems that were previously not accessible with NMR. Some particularly interesting recent applications of this technology include the study of biological tissues and combinatorial chemistry samples that have been isolated on polymer beads.  (Aileen Constans "Taking It Higher: State-of-the-Art NMR technology offers answers for the solution and solid states" Scientist 14 (21): 26, Oct. 30, 2000)  Broader term:MAS Magic Angle Spinning.