Introduction: Diagnosing and treating space-occupying tumors of the brain presents special challenges due to the similarities of tumors to other pathologic entities on conventional imaging, the similarities of individual tumor cell types on conventional imaging, the inaccessibility of these lesions, and their proximity to complex brain structures. A non-invasive technique that could provide information about the chemical and histologic composition of brain tissue could greatly aid diagnosis and treatment of brain tumors by helping to avoid unnecessary biopsies, by helping to guide biopsies, and by providing additional information for improving treatment. The Centers for Medicare & Medicaid Services (CMS) requested a technology assessment by the Agency for Healthcare Research and Quality (AHRQ) to assess the value of Magnetic Resonance Spectroscopy (MRS) for diagnostic evaluation, surgical planning, and patient management of space-occupying brain tumors. The Tufts-New England Medical Center Evidence-based Practice Center was asked to conduct an assessment of this technology.
Methods: An OVID search of the MEDLINE® database was conducted on November 6, 2002. Filters and limitations were used to eliminate inappropriate publications, with inclusion and exclusion criteria developed to identify articles to be reviewed. The search used applicable MeSH headings and textwords with appropriate Boolean operators. After filtering irrelevant publication types (such as publications not containing original clinical data), the search resulted in 959 citations for download and screening. Hand screening of the abstracts resulted in accepting 137 citations for complete article retrieval. All abstracts were reviewed to identify full articles that met the criteria. In addition, abstracts from the following relevant professional society proceedings for the years 2001 and 2002 were reviewed and included in the analyses: American Society of Neuroradiology (ASNR), Radiological Society of North America (RSNA), and the International Society for Magnetic Resonance in Medicine (ISMRM).
Results: Ninety-six articles met our inclusion criteria for evaluation, and 85 of these only provided information about technical feasibility. Eleven of the articles provided information beyond the level of technical feasibility. Eight articles evaluated the test performance of MRS in various settings. Three articles addressed the impact of MRS on diagnostic thinking and therapeutic decision making. No article was found that addressed improvement of patient outcome.
Cho/Cr (choline/creatine) is the only metabolite ratio that has been found to be useful in differentiating neoplasm and non-neoplasm and supported by several studies. Among all the full articles examined in this technology assessment only one provided the most complete reporting of the metabolite signal intensities and ratios for each type of tumor found in their study population. However, no single metabolite or ratio, other than perhaps a very high Cho/Cr ratio to diagnose peripheral neuroectodermal tumors (PNET), by itself could differentiate among different neoplasms, among different tumor grades, or between neoplastic and non-neoplastic lesions.
The only study that addressed the incremental gain in the proportion of diagnostic tissue obtained demonstrated that MRS added to conventional MRI improved the number of correct diagnoses and reduced the number of incorrect or equivocal diagnoses.
Three studies addressed the potential impact of MRS results on diagnostic thinking or therapeutic decision making. Conclusions that can be drawn from these studies are severely limited due to the fact that the two prospective studies had only 15 and 17 patients, respectively, and the only large study was a retrospective analysis of medical records to identify potential opportunities of MRS to influence diagnostic thinking. No study explicitly evaluated the impact of voxel position on the accuracy of MRS. No study commented on the potential impact of operator error in placement of the voxel.
Conclusion: Human studies conducted on the use of MRS for brain tumors demonstrate that this non-invasive method is technically feasible and suggest potential benefits for some of the proposed indications. However, there is a paucity of high quality direct evidence demonstrating the impact on diagnostic thinking and therapeutic decision making. In addition, the techniques of acquiring the MRS spectra and interpreting the results are not well standardized. In summary, while there are a large number of studies that confirm MRS’ technical feasibility, there are very few published studies to evaluate its diagnostic accuracy and whether it can positively affect diagnostic thinking and therapeutic choice. Those studies that do address these areas often have significant design flaws including inadequate sample size, retrospective design and other limitations that could bias the results.