Correlations between Magnetic Resonance Spectroscopy and Image-guided Histopathology, with Special Attention to Radiation Necrosis

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Abstract
The differentiation of tumor recurrence from radiation necrosis in patients with malignant gliomas who have been treated previously remains a challenge. Magnetic resonance imaging, single-photon emission computed tomography, and positron emission tomography cannot provide definitive histopathological insight. Multivoxel proton magnetic resonance spectroscopic imaging (1H MRSI) may be reliable in guiding the clinical management of untreated patients; however, its value in managing previously treated patients remains unclear. Twenty-seven patients who had been treated previously with surgery, radiotherapy, and chemotherapy and reoperated for clinical and/or radiographic signs that caused suspicion for recurrent disease were studied. Tissues were categorized into four groups: spectroscopically normal, pure tumor, mixed tumor and radiation necrosis, and pure radiation necrosis. Spectral data for choline (Cho), lipid-lactate (Lip-Lac), N-acetylaspartate, and creatine (Cr) were analyzed as Cho/normal Cr (nCr), Lip-Lac/Cho, Lip-Lac/nCr, N-acetylaspartate/Cho, N-acetylaspartate/nCr, and Cho/normal Cho (nCho). Stereotactic biopsies were obtained within 48 hours of 1H MRSI and were directly correlated digitally with 1H MRSI data. Logistic regression analysis was performed on the basis of data obtained from 99 1H MRSI observations to determine whether the 1H MRSI ratios varied according to tissue category. 1H MRSI ratios were found to distinguish pure tumor from pure necrosis. The odds of a biopsy's being pure tumor and having either a Cho/nCr value greater than 1.79 or a Lip-Lac/Cho value less than 0.75 are seven times the odds of that biopsy's being pure necrosis (odds ratio, 7.00;P = 0.0136). The odds of a biopsy's being pure necrosis and having either a Cho/nCr value less than 0.89 or a Cho/nCho value less than 0.66 are six times the odds of that biopsy's being pure tumor (odds ratio, 5.71;P = 0.0329). The odds of a biopsy's being pure necrosis and having either a Lip-Lac/Cho value greater than 1.36 or a Lip-Lac/nCr value greater than 2.84 are more than five times the odds of the biopsy's being pure tumor (odds ratio, 5.25;P = 0.0322). In addition, although only marginally significant, Lip-Lac/Cho and Lip-Lac/nCr ratios distinguish pure tumor from pure necrosis. No values suggested that mixed specimens could be distinguished in a statistically significant way from either pure tumor or pure necrosis. The data that we gathered suggest that metabolite ratios derived on the basis of 1H MRSI spectral patterns do allow reliable differential diagnostic statements to be made when the tissues are composed of either pure tumor or pure necrosis, but the spectral patterns are less definitive when tissues composed of varying degrees of mixed tumor and necrosis are examined.

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