© 2000 by Society
© 2000 by the Society forNeuro-Oncology
Quantification of microheterogeneity in glioblastoma multiforme with exvivo high-resolution magic-angle spinning (HRMAS) proton magnetic resonancespectroscopy
Department of Pathology [L.L.C.], NMR Center andDivision of Neuroradiology, Department of Radiology[A.R.C., R.G.G.], Massachusetts General Hospital, Boston, MA 02129; Department of Pathology [D.C.A.], Department of Radiology [A.A.T.], Department of Neurosurgery [P.M.B.], Children's Hospital,Boston, MA 02115; Department of Pathology[D.C.A.], Department of Neurosurgery [P.M.B.], Brighamand Women's Hospital; and Harvard Medical School, Boston, MA 02115
2 Address correspondence and reprint requests to Leo L. Cheng, PathologyResearch, MGH CNY-7, 149 13th St., Charlestown, MA 02129.
Microheterogeneity is a routinely observed neuropathologic characteristicin brain tumor pathology. Although microheterogeneity is readily documented byroutine histologic techniques, these techniques only measure tumor status atthe time of biopsy or surgery and do not indicate likely tumor progression. Abiochemical screening technique calibrated against pathologic standards wouldgreatly assist in predicting tumor progression from its biological activity.Here we demonstrate for the first time that proton magnetic resonancespectroscopy (1H MRS) with high-resolution magic-angle spinning(HRMAS), a technique introduced in 1997, can preserve tissue histopathologicfeatures while producing well-resolved spectra of cellular metabolites in theidentical intact tissue specimens. Observed biochemical alterations and tumorhistopathologic characteristics can thus be correlated for the same surgicalspecimen, obviating the problems caused by tumor microheterogeneity. Weanalyzed multiple specimens of a single human glioblastoma multiformesurgically removed from a 44-year-old patient. Each specimen was firstmeasured with HRMAS 1H MRS to determine tumor metabolites, thenevaluated by quantitative histopathology. The concentrations of lactate andmobile lipids measured with HRMAS linearly reflected the percentage of tumornecrosis. Moreover, metabolic ratios of phosphorylcholine to cholinecorrelated linearly with the percentage of the highly cellular malignantglioma. The quantification of tumor metabolic changes with HRMAS 1HMRS, in conjunction with subsequent histopathology of the same tumor specimen,has the potential to further our knowledge of the biochemistry of tumorheterogeneity during development, and thus ultimately to improve our accuracyin diagnosing, characterizing, and evaluating tumor progression.
Received September 3, 1999; Accepted December 16, 1999
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