Correlation of magnetic resonance spectroscopic and growth characteristics within Grades II and III gliomas

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Object

The accurate diagnosis of World Health Organization Grades II and III gliomas is crucial for the effective treatment of patients with such lesions. Increased cell density and mitotic activity are histological features that distinguish Grade III from Grade II gliomas. Because increased cellular proliferation and density both contribute to the in vivo magnetic resonance (MR) spectroscopic peak corresponding to choline-containing compounds (Cho), the authors hypothesized that multivoxel MR spectroscopy might help identify the tumor regions with the most aggressive growth characteristics, which would be optimal locations for biopsy. They investigated the ability to use one or more MR spectroscopic parameters to predict the MIB-1 cell proliferation index (PI), the terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling cell death index (DI), the cell density, and the ratio of proliferation to cell death (PI/DI) within different regions of the same tumor.

Methods

Patients with presumed Grades II or III glioma underwent 3D MR spectroscopic imaging prior to surgery, and two or three regions within the tumor were targeted for biopsy retrieval based on their spectroscopic features. Biopsy specimens were extracted from the tumor during image-guided resection, and the PI, DI, and cell density were assessed in the specimens using immunohistochemical methods.

Conclusions

The authors found that the relative levels of Cho and N-acetylaspartate (NAA) correlated with the cell density, PI, and PI/DI ratio within different regions of the same tumor and that the association held for the subpopulation of nonenhancing tumors. The association was stronger in tumors with large ranges of Cho/NAA values, irrespective of the presence of contrast enhancement. The findings demonstrate the validity of using MR spectroscopy to identify regions of aggressive growth in presumed Grade II or III gliomas that would be suitable targets for retrieving diagnostic biopsy specimens.

Abbreviations used in this paper:CCI = Cho-to-creatine index; Cho = choline-containing compounds; CNI = Cho-to-N-acetylaspar-tate index; Cr = creatine and phosphocreatinine; DI = cell death index; FOV = field of view; LL = lactate and/or lipid; MR = magnetic resonance; NAA = N-acetylaspartate; PI = cell proliferation index; TUNEL = terminal deoxynucleotidyl transferase–mediated deoxy-uridine triphosphate nick-end labeling; WHO = World Health Organization.

Article Information

Address reprint requests to: Tracy McKnight, Ph.D., 185 Berry Street, Suite 350, Center for Molecular and Functional Imaging, University of California, San Francisco, California 94107. email: mcknight@mrsc.ucsf.edu.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    Contrast-enhanced T1-weighted MR image and corresponding MR spectroscopic array (upper) obtained in a patient with a Grade III astrocytoma. The spectrum from the enhancing tumor (lower right) shows elevated peaks corresponding to Cho and LL and decreased peaks corresponding to Cr (Cre) and NAA relative to the spectrum from contralateral healthy-appearing brain (lower left).

  • View in gallery

    Magnetic resonance spectroscopic and immunohistochemical data corresponding to two different biopsies obtained in a patient harboring a Grade III astrocytoma. MIB-1 (center) and TUNEL (lower). Orginial magnifications ×200. CD = cell density; nCho = normalized Cho; nCre = normalized Cr; nNAA = normalized NAA.

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