Monitoring Gliomas In Vivo Using Diffusion-Weighted MRI During Gene Therapy-Induced Apoptosis

Abstract

Diffusion as detected by magnetic resonance imaging is typically self diffusion of water in biological samples or in vivo. Diffusion MRI has been widely studied and applied in clinical settings including detection of therapy responses in cancers. Malignant brain tumors especially gliomas are significant cause of cancer related deaths even though they are a reasonably rare type of cancer. Different kinds of therapies comprising of surgery, radiation-, chemotherapy or combined therapies have been applied routinely for treatment of these malignancies. Despite the developed therapy methods, the prognosis for the patients with malignant gliomas remains poor. Recently, gene therapy methods have also been developed for the treatment of the malignant glioma. When gene therapy becomes more widely available, the value of the imaging methods to detect treatment response will increase. Changes in the diffusion of water and metabolites, as measured with MRI and MRS, have been shown to serve as marker for positive treatment response in experimental settings. The main but simplified results from these studies in cell suspensions and in vivo are: water diffusion increases as a result of excessive cell loss and increase in extracellular water, and the diffusion of intracellular metabolites (total choline) decreases most likely due to cell shrinkage. The clinical studies are limited to chemotherapy and radiation therapy responses, which show similar responses as gene therapy in experimental models. As a conclusion, amongst the magnetic resonance markers water diffusion is one of the most extensively studied and it has been found to be sensitive to treatment response in several tumor treatment protocols, including gene therapy approaches.