Functional and metabolic magnetic resonance imaging (MRI) techniques have been rapidly evolving and have tremendous potential for clinical brain disorders research. Clinical activation functional MRI (fMRI) studies are performed at 1.5 Tesla using blood oxygenation level dependent (BOLD) contrast method and arterial spin tagging (AST) techniques. We have examined healthy controls, patients with schizophrenia, and their siblings using motor tasks of varying complexity and cognitive tasks of increasing working memory load. BOLD fMRI studies on patients with primary brain tumors were facilitated by using a newly developed real-time analysis package for fMRI and dynamic contrast studies. This new real-time analysis system allows for an interactive fMRI-based physiological interview. The investigator can review activation maps within 20 seconds after the completion of the fMRI acquisition while the subject is in the scanner in order to take advantage of the experimental conditions. Comparison of fMRI activation studies with intraoperative infrared recording of cortical surface in patients with brain tumors demonstrated good correlation between areas of increased blood flow to fMRI activation. These studies are providing valuable guidance to neurosurgeons in planning surgical approaches as well as information regarding the physiological mechanisms associated with the signal intensity changes on BOLD fMRI examinations. Multislice proton MR spectroscopic imaging (MRSI) studies that were performed in patients with schizophrenia have continued to show low N-acetyl aspartate (NAA) concentrations in the dorsolateral prefrontal cortex and are predictive of higher D-2 binding potential in the basal ganglia. Patients with schizophrenia and their siblings also had significant reductions in hippocampal NAA as compared with controls. These results may suggest that this pattern of neurochemical abnormality may represent a brain phenotype associated with schizophrenia. Proton MRSI studies performed in pediatric patients with recurrent primary brain tumor were performed in collaboration with the Pediatric Oncology Branch at the National Cancer Institute. With the worse voxel analysis method, patients could be segregated by individuals with choline to NAA ratios greater than 4.5 or less than 4.5. Patients whose tumors had choline/NAA ratios greater than 4.5 were all dead by 62 weeks, while patients whose tumors had choline/NAA less than 4.5 did not reach median survival of 120 weeks. These results indicated that the choline to NAA ratio in recurrent pediatric brain tumors might provide valuable information regarding patient survival. Thus, proton MRSI can be incorporated into new early phase treatment trials as a secondary outcome measure. Multi-institutional trials are being planned to further evaluate these MRSI findings in both primary and recurrent pediatric paients with primary brain tumors.
