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Precise ex vivo histological validation of heightened cellularity and diffusion-restricted necrosis in regions of dark apparent diffusion coefficient in 7 cases of high-grade glioma. Neuro Oncol 2014 Dec;16(12):1599-606



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Pubmed Central ID




Scopus ID

2-s2.0-84938693563   53 Citations


BACKGROUND: Recent conflicting reports have found both brain tumor hypercellularity and necrosis in regions of restricted diffusion on MRI-derived apparent diffusion coefficient (ADC) images. This study precisely compares ADC and cell density voxel by voxel using postmortem human whole brain samples.

METHODS: Patients with meningioma were evaluated to determine a normative ADC distribution within benign fluid attenuated inversion recovery (FLAIR) T2/hyperintensity surrounding tumor. This distribution was used to calculate a minimum ADC threshold to define regions of ADC-FLAIR mismatch (AFMM), where restricted diffusion presented in conjunction with T2/FLAIR hyperintensity. Contrast-enhancing voxels were excluded from this analysis. AFMM maps were generated using imaging acquired prior to death in 7 patients with high-grade glioma who eventually donated their brains upon death. Histological samples were taken from numerous regions of abnormal FLAIR and AFMM. Each sample was computationally processed to determine cell density. Custom software was then used to downsample coregistered microscopic histology to the more coarse MRI resolution. A voxel-by-voxel evaluation comparing ADC and cellularity was then performed.

RESULTS: An ADC threshold of 0.929 × 10(-3) mm(2)/s was calculated from meningioma-induced edema and was used to define AFMM. Regions of AFMM showed significantly greater cell density in 6 of 7 high-grade glioma cases compared with regions of hyperintense FLAIR alone (P < .0001). Two patients had small regions of diffusion-restricted necrosis that had significantly lower ADC than nearby hypercellularity.

CONCLUSIONS: Regions of AFMM contain hypercellularity except for regions with extremely restricted diffusion, where necrosis is present.

Author List

LaViolette PS, Mickevicius NJ, Cochran EJ, Rand SD, Connelly J, Bovi JA, Malkin MG, Mueller WM, Schmainda KM


Joseph A. Bovi MD Professor in the Radiation Oncology department at Medical College of Wisconsin
Jennifer M. Connelly MD Professor in the Neurology department at Medical College of Wisconsin
Peter LaViolette PhD Associate Professor in the Radiology department at Medical College of Wisconsin
Nikolai J. Mickevicius PhD Assistant Professor in the Radiology department at Medical College of Wisconsin
Wade M. Mueller MD Professor in the Neurosurgery department at Medical College of Wisconsin
Kathleen M. Schmainda PhD Professor in the Biophysics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aged, 80 and over
Brain Edema
Diffusion Magnetic Resonance Imaging
Meningeal Neoplasms
Middle Aged