2-Jun-2009, TAU-MR club, Tel Aviv University
fMRI a non-invasive tool for monitoring angiogenesis and hemodynamical changes in pathology
Rinat Abramovitch, Goldyne Savad Institute of Gene Therapy,  the Hadassah University Hospital

Abstract:

---

Analysis of vascular remodeling in vivo is a major challenge both for the study of the regulatory mechanisms of its initiation and inhibition, and for the clinical evaluation of pathological processes. Angiogenesis is being assessed today by immunohistological staining of biopsy specimens, an invasive procedure that gives only local information. Application of MRI as a noninvasive detection tool can provide a full 3-dimensional information about vessel density, functionality and maturation. Most of the previous approaches for the study of angiogenesis by MRI relied on the use of exogenous contrast agents. In my work, vascular development is followed by gradient echo (GE) MRI using the intrinsic contrast originating from deoxyhemoglobin (Blood Oxygenation Level Dependent (BOLD) contrast).
Patients with malignant primary and metastatic brain and liver tumors have a poor prognosis, despite developments in diagnostic and therapeutic modalities. The inhibition of angiogenesis is currently one of the promising approaches as a therapy for cancer. However, most studies with anti-angiogenic compounds have been carried out in subcutaneous models. Since brain and liver tumors, tend to migrate over long distances, any experimental strategy should be assessed in orthotopic models. Previously, when we treated brain metastases with two anti-angiogenic therapies, the therapies increased vessel cooption- tumor cells growing along preexisting blood vessels. One goal of my research is to study the effects of anti-angiogenic therapies in brain and in liver tumor models, and to try to reveal the mechanism that is involved in the vessel-cooption phenotype. By using MRI, a non-invasive technique, we can study tumor vessel properties (functionality, maturation, permeability) in treated vs. non-treated animals. Additionally, we have recently utilized fMRI combined with hypercapnia and hyperoxia for monitoring changes in liver perfusion and hemodynamics. We expect that our new fMRI method will provide functional information that may reveal treatment efficacy as well as growth kinetics. Since anti-angiogenic therapy is a major approach for treating cancer, it is crucial to understand and reveal the vessel cooption phenomenon in order to improve treatment.