Advanced magnetic resonance imaging of the physical processes in human glioblastoma

Abstract

The most common malignant primary brain tumor, glioblastoma multiforme (GBM) is a devastating disease with a grim prognosis. Patient survival is typically less than two years and fewer than 10% of patients survive more than five years. Magnetic resonance imaging (MRI) can have great utility in the diagnosis, grading, and management of patients with GBM as many of the physical manifestations of the pathologic processes in GBM can be visualized and quantified using MRI. Newer MRI techniques such as dynamic contrast enhanced and dynamic susceptibility contrast MRI provide functional information about the tumor hemodynamic status. Diffusion MRI can shed light on tumor cellularity and the disruption of white matter tracts in the proximity of tumors. MR spectroscopy can be used to study new tumor tissue markers such as IDH mutations. MRI is helping to noninvasively explore the link between the molecular basis of gliomas and the imaging characteristics of their physical processes. We, here, review several approaches to MR-based imaging and discuss the potential for these techniques to quantify the physical processes in glioblastoma, including tumor cellularity and vascularity, metabolite expression, and patterns of tumor growth and recurrence. We conclude with challenges and opportunities for further research in applying physical principles to better understand the biologic process in this deadly disease. See all articles in this Cancer Research section, "Physics in Cancer Research."

Figure 1

Tumor vasculature a. The healthy blood–brain barrier protects the brain through a network of astrocytes, pericytes, endothelial cells, and neurons that form tight, impermeable junctions, which exclude large cells, marcomolecules, and excess fluid from the central nervous system. The disruptions in the BBB that occur in brain tumors result in a thickened and disrupted basement membrane and widened junctions that allowing passage of macromolecules and fluid (to be adapted from Gerstner et al (2009), VEGF inhibitors in the treatment of cerebral edema in patients with brain cancer Nature Reviews Clinical Oncology 6, 229-236 (April 2009). b. Vascular normalization hypothesis. Schematic of the effects of antiangenic therapy (To be adapted from: Sorensen et al, Increased Survival of Glioblastoma Patients Who Respond to Antiangiogenic Therapy with Elevated Blood Perfusion, Cancer Res; 72(2) January 15, 2012)

Figure 2

DCE imaging a. Schematic of DCE compartments including the vascular bed, cells and EES (adapted from Parker et al (37)) b. DCE signal in the contrast-enhancing tumor region of interest c. Example post-contrast T1 image highlights tumor due to contrast agent extravasation d. Ktrans map created by fitting the “Tofts” model to the DCE-MRI signal.

Figure 3

DSC imaging a. Example DSC signal (T2*) in GBM shows the drop in signal intensity as the bolus of contrast agent passes through b. T1-post contrast image shows areas of contrast enhancing tumor c. FLAIR image shows areas of edema d. Color map of rCBF created using DSC analysis e. Color map of rCBV created using DSC analysis f. Color map of vessel size imaging created using DSC analysis

Figure 4

Diffusion imaging a. Diffusion weighted images acquired at different B-values show an exponential attenuation of the signal. The ADC can be estimated from this curve b. FLAIR image allows the visualization of edema c. Enhancing tumor seen on post-contrast T1-weighted image d. Diffusion weighted image e. ADC map shows increased ADC in areas of edema and areas of low ADC in areas of contrast-enhancing tumor f. Color FA map showing the loss of white matter tracts in areas of peritumoral edema

Figure 5

Grading tumors using DSC-MRI: (L-R) Post Contrast T1, T2, rCBF, rCBV images of a grade II (top row), grade III (middle row) and grade IV (bottom row) tumors generated using DSC-MRI. Note the absence of contrast enhancement in the grade II and grade III tumors. Also, note the elevated rCBV and rCBF in the grade IV tumors

Figure 6

3D imaging of 2HG in a glioma patient with IDH1 mutation. The 2HG map is overlaid on FLAIR anatomical imaging. High 2HG is found in a limited region around the postsurgical cavity. Note that edema in FLAIR image extend beyond the high 2HG area. Examples of difference MEGA-LASER (121) edited spectra from a voxel in a tumor (right) and a voxel in the contralateral hemisphere are shown.