Currently, the imaging characterization of GBM is provided primarily by contrast-enhanced MRI, which is a sensitive means of delineating anatomic and structural features of brain tumors. This technology, however, has not been used to detect subtle tumor infiltration beyond the contrast-enhancing margin of the tumor or to differentiate active tumor from therapy-related brain injury. The use of physiologic and metabolic MRI techniques - such as diffusion-weighted imaging and perfusion MRI, which are not based primarily on anatomic signals but rather on distinct physiologic or metabolic properties - permits the study of tumor biology such as cellularity and angiogensis, both quantitatively and noninvasively. The BTRC laboratory of Soonmee Cha, MD, studies these sequences extensively to validate their relationship with pathology and attempt to determine what they can tell us about GBM biology. By approaching this research in a multidisciplinary fashion, Cha and her colleagues hope to explore the potential of anatomic and physiologic MRI as useful tools for a variety of clinical applications, including GBM classification, therapy monitoring, and surgery planning.
Current Research Projects
Neuroimaging as a Clnical Trial Endpoint
A major aim of the Cha laboratory is to validate the usefulness of MRI as a tool for brain tumor therapy monitoring and identifying therapy endpoints. Dr. Cha and her colleagues in the BTRC have been involved in multiple clinical trials, primarily exploring the importance of two physiologic MRI sequences within the GBM population: dynamic contrast-enhanced (DCE) MRI and diffusion MRI. DCE MRI is as noninvasive tool used to estimate the degree of alteration in vascular permeability, which is represented by the endothelial permeability surface area product, ktrans. Endothelial permeability of vessels in brain tumors provides valuable information about blood-brain barrier integrity, vascular morphology, and response to anti-angiogenic therapy. Meanwhile, changes in cellularity quantitatively estimated by apparent diffusion coefficient (ADC) derived from with diffusion-weighted imaging are useful in assessing for potential biological change in tumors in response to therapy. DCE MRI and ADC are then related to clinical outcomes to establish correlations between imaging and clinical endpoints. The goal of this research is to validate both anatomic and physiologic MRI as important tools for monitoring brain-tumor therapy.
Correlating Neuroimaging with Histology
To validate physiologic MRI it is critical to establish direct correlations between quantitative variables and histopathology. For this reason, current imaging research in the BTRC has taken an emphasis on validating physiologic MRI variables by directly correlating them with histopathologic findings of the tumor specimen obtained through image-guided stereotactic biopsy (IGSB). Dr. Cha is currently working to analyze histopathologic features of IGSB specimens from patients with GBM and to correlate the histological findings with the anatomic and perfusion MRI characteristics of the site where the biopsy was taken.
Correlating MRI with Genetic Profiles of Brain Tumors
The Cha laboratory is exploring the potential for combining imaging with genetic analysis of GBM. It has been suggested that neural stem cells with astrocyte-like characteristics existing in the subventricular zone of the human brain are the cellular origin of GBM. To explore this hypothesis, the MRI features of GBMs in specific relation to the SVZ have been analyzed, and this research will be continued with the analysis of genetic markers, such as methylation and mRNA.