BRAIN TUMOR ANALYSIS LAB

Division of Neuro-Oncology, Department of Neurology

 

Assessment of Brain Tumor Angiogenesis and Angiogenesis inhibiting drugs using Perfusion MRI

N. Shastry Akella, L. Burt Nabors, Donald B. Twieg, Joel K Cure, Glenn H. Roberson

Synopsis Several Magnetic Resonance Imaging (MRI) techniques have been successfully devised to study brain tumors in a clinical setting, ranging from radiological diagnosis to tumor characterization, from size and volume computations to measurement of bio-chemical information. The chief advantage of using MRI over other imaging modalities is the excellent tissue contrast it affords coupled with very good resolution and sensitivity. The image on the right shows an MRI of a patient with an Anaplastic Astrocytoma (WHO grade III). We investigate angiogenesis in primary malignant brain tumors using a combination of perfusion MR imaging and spectroscopy, towards a better radiological understanding of the underlying tumor physiology and metabolism. We deal primarily with anaplastic astrocytomas and Glioblastoma Multiforme (GBM). The emphasis of research in our lab is on non-invasively assessing the response of angiogenesis-inhibiting drugs and correlating the MR imaging studies with clinical outcomes.

Perfusion is the steady state delivery of blood to tissue parenchyma through the capillaries, representing the microscopic coherent motion of water and cellular material. We use perfusion imaging to correlate angiogenesis and kinetic parameters reflecting tumor vasculature changes. The image on the left shows a parametric map of the relative cerebral blood volume in a patient with a diagnosis of Anaplastic Astrocytoma.

Dynamic Susceptibility Contrast enhanced MRI (DSC-MRI) is a functional perfusion imaging technique where a patient is injected with a contrast agents which alters the magnetic suscpetibility of the imaging volume, allowing the variation to be measured. A typical MR signal curve exhibiting a susceptibility induced drop is shown on the right. The validation of such techniques for assessment of anti-angiogenic response in brain tumors will be required to move novel brain tumor therapy to comparative trial testing.

As evidence mounts that techniques like DSC-MRI can be used to aid clinical diagnosis and interpretation of human brain tumors, more focus is being placed on understanding the basic molecular pathways and cellular processes involved. Towards this end, understanding angiogenesis, i.e. the process of vascularization of tissue involving the development of new capillary blood-vessels, is very important. An understanding of the dynamics of angiogenesis cannot be achieved without an integrated analysis of morphological, functional, and molecular approaches that shed light on changes in tissues. Functional characterization of the tumor neovasculature by imaging will be important for the evaluation of patients receiving anti-angiogenic therapy. Interest in imaging techniques that can provide early indicators of effectiveness at a functional or molecular level has therefore increased. Tumor response to treatment can be detected by functional imaging techniques that are capable of monitoring changes such as perfusion, blood volume, or micro-vessel permeability. Magnetic resonance imaging can measure both blood volume and blood vessel permeability using dynamic enhancement with extra-cellular or blood pool contrast agents. Contrast-enhanced MRI can distinguish between normal and malignant tissues reflecting the hyperpermeable tumor vasculature. Contrast uptake correlates with micro-vessel density in human and animal experimental tumors. This is the basis for attempting to understand and track angiogenesis using non-invasive imaging techniques like perfusion imaging.