How do you tell when a low-grade glioma will turn into an aggressive high-grade glioma, before its too late? It just so happens that a specialized kind of magnetic resonance imaging (MRI) can predict cancerous transformation of brain tumors up to a year prior to when the malignancy would be visible on regular contrast-enhanced MRI, according to a new study.
A glioma is a central nervous system tumor that forms from glial cells. They can affect the spinal cord, or any other part of the CNS, such as optic nerves, however, they most often are seen in the brain.
Low-grade gliomas are primary brain tumors that grow slowly over several years. Eventually, almost all low-grade gliomas progress to high-grade gliomas, which carry a poor prognosis. Blood volume in the brain was found to increase significantly in the months prior to malignant transformation of brain tumors.
“Patients with low-grade gliomas are often young and may remain clinically well for many years but, at an unpredictable time their tumor will transform to an aggressively high-grade glioma,” said study co-author, Adam Waldman, Ph.D, Imperial College and University College, London.
Brain tumors can bring about the formation of new blood vessels, a process known as angiogenesis. These vessels are abnormal and lead to changes in blood volume and flow. Using perfusion MRI, radiologists can detect these changes well before they become apparent on contrast-enhanced MR images. By measuring changes in cerebral blood volume with perfusion MRI, radiologists may be able to identify patients most likely to benefit from earlier or more aggressive treatment.
Because perfusion MRI is highly sensitive to microscopic changes in blood flow, it is therefore extremely sensitive to early changes in the brain resulting from ischemia, or abnormally low blood flow, such as changes which follow stroke. Magnetic resonance perfusion imaging uses an injected dye in order to see blood flow through tissues.
The patients underwent perfusion MRI and contrast-enhanced MRI every six months for up to three years. Seven patients progressed to high-grade, malignant gliomas between six and 36 months. In the six patients whose disease remained stable, regional cerebral blood volumes (rCBV) remained relatively stable, increasing from a mean level of 1.31 at the beginning of the study to 1.52 over the follow-up period.
However, in the patients exhibiting tumor transformation, mean rCBV increased progressively from 1.94 at study entry to 3.14 twelve months prior to transformation, to 3.65 six months prior to transformation and to 5.36 at the time transformation was diagnosed.
These findings suggest that significant changes in rCBV represent an important marker of malignant change in gliomas and reflect the earliest stages of the transformation process. Further, the data support the likelihood that the cellular processes underlying malignant transformation may occur 12 months or more before visible on contrast MRI.
“We have shown that perfusion MRI provides a noninvasive means of assessing the risk of transformation in individual patients,” Dr. Waldman said. “Increasing perfusion can be regarded as an early warning sign of impending malignant transformation that can assist radiologists in identifying those patients most likely to benefit from earlier or more aggressive treatment.”
1. “Low-Grade Gliomas: Do Changes in rCBV Measurements at Longitudinal Perfusion-weighted MR Imaging Predict Malignant Transformation?” Collaborating with Dr. Waldman were Nasuda Danchaivijitr, M.D., Daniel J. Tozer, Ph.D., Christopher E. Benton, B.Sc., Gisele Brasil Caseiras, M.D., Paul S. Tofts, Ph.D., Jeremy H. Rees, Ph.D., F.R.C.P., and H. Rolf JÃƒÂ¤ger, M.D., F.R.C.R. Radiology, Apr-01-2008 246
2. Mamelak A.N., and Jacoby, D.B. Targeted delivery of antitumoral therapy to glioma and other malignancies with synthetic chlorotoxin (TM-601) Expert Opin. Drug Drliv. (2007) 4(2):175-186
3. American Heritage Stedman’s Medical Dictionary,2002
Image: courtesy Wellcome Images, Creative Commons