Magnetic Resonance imaging Assessment of Tumor Microvessels and Response to Antiangiogenesis Therapy

Magnetic resonance Imaging (MRI) is a diagnostic modality with high inherent contrast resolution and multiplanar imaging capability. Advances in MR technology and image processing have increased the utility and availability of this technique in the past two decades. MRI has become one of the leading modalities in current diagnostic imaging, combining soft tissue contrast with high anatomic and temporal resolution. MRI is now a widely employed diagnostic method for the clinical evaluation of tumors. One of the most recent applications of MRI is the investigation of angiogenesis using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). DCE-MRI represents the acquisition of serial MR images before, during, and after the administration of an intravenous contrast agent. The use of contrast enhancement in conjunction with magnetic resonance imaging provides a means to evaluate tissue function, as well as morphology. Tissue blood volume, blood flow, perfusion and capillary permeability represent indicators of the status of the vasculature that can be investigated with DCE-MRI. Use of such quantitation potentially allows tumors to be characterized in terms of pathophysiology and to be monitored over time, during the course of therapeutic interventions. The understanding of the angiogenesis process and the evaluation of new drugs that inhibit or stimulate angiogenesis are directly related to the development of an imaging assay of angiogenic activity. This method should provide functionally relevant and quantitative images, should be high in spatial resolution, should sample the entire tumor and could be repeated at frequent intervals. DCE-MRI has grown in importance with the development of antiangiogenic and neoadjuvant strategies for tumor therapy. Dedicated software makes it possible to interpret imaging pharmacokinetics and aid the assessment of physiological parameters such as capillary permeability and tissue perfusion. For instance, the permeability of functional tumor microvessels can be assessed noninvasively by dynamic MRI of contrast agent uptake in the tumor tissue (1-4). The analysis of contrast kinetics can be applied to differentiate between a malignant and a benign lesion and to determine whether a tumor is responding to treatment (5). It has been demonstrated that the permeability of blood vessels correlates with the ability of the tumor to metastasize, and with its response to treatment (6, 7). Thus, information concerning the status of vascular permeability might help assessing the metastatic potential of tumors and predict the sensitivity to chemotherapy or to antiangiogenic treatment.