Advanced dynamic vascular imaging for high-grade gliomas
Malignant glioma is one of the most virulent neoplastic diseases in humans. The median survival remains in the 10 to 12 month range despite aggressive surgery, radiation, and chemotherapy. Although there are improvements in molecular characterization of high-grade glioma, in targeted therapeutic approaches and in refined radiological methods, the average life span of an afflicted individual has not been significantly prolonged, due to recurrent refractory disease. The tumor stimulates the formation of new blood vessels which are structurally and functionally abnormal, impairs effective delivery of therapeutic agents and hence reduces the effectiveness of radiation and chemotherapy. Angiogenic therapies
: The tight correlation between angiogenic processes and prognosis have lead, during recent years, to propose new strategies which utilize combinations of antiangiogenic and chemo therapies. Such drugs, when used judiciously, have the potential to normalize structurally and functionally abnormal tumor vasculature, reduce the risk of hemorrhage, enhance the penetration of concurrently administered chemotherapeutic and improve the efficacy of cytotoxic drugs and radiation by alleviating hypoxia. Moreover, such regimens decrease microvessel density, new vessel evolution and interstitial pressure. Yet, improvement is limited and the exact patho-physiologic processes of the therapeutic effects are not fully understood. The first aim of this study
is to improve understanding of the patho-physiological processes of glioma in relation to the clinical course and to pathological parameters, prior to and following therapeutic intervention. This knowledge regarding the tumor response at the system level will be achieved using animal models.
MRI is the method-of-choice for noninvasive whole brain assessment of gliomas, and has an essential role in classification and grading, preoperative evaluation, follow-up and therapeutic management. MRI can provide structural, biochemical and functional information regarding the tumor and its surrounding parenchyma. With the development of advanced MR methods, an increase in sensitivity along with improvement of reliability and specificity in the diagnosis of tumors has been achieved. However, more sensitive tissue differentiation, such as compartmentalization of the tumor into several regions differing in vessel density, diameter and in necrosis is needed. In addition, correlation to pathology, i.e. the micro characterization of the tumor like blood vessel density and morphology, is desired. One major problem is the reliability of the existing diagnostic criteria for assessing treatment response, which is questionable and can sometimes be misleading. Advanced imaging methods
provide additional information regarding vascularization which determines one of the pathophysiological characteristics of the tumor and its potential response to therapy. Density, permeability and blood brain barrier (BBB) breakdown are some aspects of the tumor vasculature that can provide valuable information for tumor prognosis and response to therapy. However, noninvasive methods for quantification and detecting vascularization are currently limited. We have previously presented a novel fMRI method using hyperoxia and hypercapnia (hemodynamic response imaging