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Spatially quantifying microscopic tumor invasion and proliferation using a voxel-wise solution to a glioma growth model and serial diffusion MRI. Magn Reson Med 2011 Apr;65(4):1131-43



Pubmed ID


Pubmed Central ID




Scopus ID

2-s2.0-79952781642   37 Citations


The purpose of this study was to develop a voxel-wise analytical solution to a glioma growth model using serial diffusion MRI. These cell invasion, motility, and proliferation level estimates (CIMPLE maps) provide quantitative estimates of microscopic tumor growth dynamics. After an analytical solution was found, noise simulations were performed to predict the effects that perturbations in apparent diffusion coefficient values and the time between apparent diffusion coefficient map acquisitions would have on the accuracy of CIMPLE maps. CIMPLE maps were then created for 53 patients with gliomas with WHO grades of II-IV. MR spectroscopy estimates of the choline-to-N-acetylaspartate ratio were compared to cell proliferation estimates in CIMPLE maps using Pearson's correlation analysis. Median differences in cell proliferation and diffusion rates between WHO grades were compared. A strong correlation (R(2) = 0.9714) and good spatial correspondence were observed between MR spectroscopy measurements of the choline-to-N-acetylaspartate ratio and CIMPLE map cell proliferation rate estimates. Estimates of cell proliferation and diffusion rates appear to be significantly different between low- (WHO II) and high-grade (WHO III-IV) gliomas. Cell diffusion rate (motility) estimates are highly dependent on the time interval between apparent diffusion coefficient map acquisitions, whereas cell proliferation rate estimates are additionally influenced by the level of noise present in apparent diffusion coefficient maps.

Author List

Ellingson BM, LaViolette PS, Rand SD, Malkin MG, Connelly JM, Mueller WM, Prost RW, Schmainda KM


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
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

Brain Neoplasms
Cell Proliferation
Computer Simulation
Diffusion Magnetic Resonance Imaging
Image Enhancement
Image Interpretation, Computer-Assisted
Imaging, Three-Dimensional
Models, Biological
Neoplasm Invasiveness
Reproducibility of Results
Sensitivity and Specificity