NemoImage 11, Number 5, 2000, Part 2 of 2 Parts 1 BE al@ Differences in regional blood volume in schizophrenia and bipolar disorder METHODS - ANALYSIS Jadwiga Rogowska*f$$, Staci Gruber*$& Deborah Yurgelun-Todd*$&! *Cognitive Neuroimuging Laboratory TBrain Imaging Center $McLean Hospital DHarvard Medical School Introduction Two cortical areas that have consistently been implicated in the pathogenesis of schizophrenia and bipolar disorder are the prefrontal cortex and temporal lobe (1,2). These two regions belong to a larger neural network responsible for a variety of cognitive and emotional processes. Many neuroimaging studies utilize task activation paradigms which compare changes in “resting” and activated states,to define neurobiologic changes associated with these disorders. However, the interpretation of activation studies is dependent on the characteristics of resting state blood volume. In an attempt to better understand possible differences in blood volume resting states in patients with psychiatric disorders, we studied patients with schizophrenia, bipolar disorder, and normal controls with dynamic susceptibility contrast magnetic resonance imaging (DSCMRI). We hypothesized that no differences in the regional blood volume would be present in frontal and temporal regions between the study groups. Methods Nine subjects with schizophrenia, 8 subjects with bipolar disorder, and 8 healthy comparison subjects were included in this study. Images were acquired with a 1.5-T GE Signa scanner retrofit with an Advanced NMR Systems whole-body echo planar imaging coil. A spin-echo planar imaging sequence was used (TR= 1 s, TE= 100 ms) with a 1.5 mm x 1.5 mm in-plane resolution and a 7 mm slice thickness with a 3 mm gap. All scans were made following a bolus of gadolinium contrast agent (0.2 meq/kg) injected over 6 s through an 18-G angiocatheter in an antecubital vein. The functional and Tl*-weighted matched structural images were collected for each subject. Correlation values for all time-intensity curves were calculated using a software program that provides tools for drawing multiple regions within each image slice and displays the correlation maps (3). The four regions of interest included the left and right inferior frontal gyms, and left and right superior temporal gyrus, which were drawn by an experienced neuroanatomist. Results Reference time-intensity curves were derived from the parietal area of all subjects’ brains. The average percent signal change in the parietal area for 21 time points (centered at the minimum at 1lth time point) for all subjects are shown on Fig. 1. For each subject, the correlation values were calculated for alI frontal and temporal regions with the 21-point reference drawn in the parietal region. Statistical differences between schizophrenic patients and controls (p=O.O20) and between bipolar patients and controls (p=O.O13) were evident when measures from all four brain regions (left and tight inferior frontal gyms, left and right superior temporal gyrus) were considered. The significant effect between schizophrenic patients and controls was due predominantly to differences in the left hemisphere, whereasthe effect between bipolar patients and controls was due predominantly to differences in the right hemisphere. Tests between correlation values for left versus right brain regions did not show any statistical differences for schizophrenic, bipolar, or control subjects. Conclusion In sum, these findings suggest laterahzed resting state blood volume differences between healthy control subjects and both patients with schizophrenia and bipolar disorder. The changes identified for the schizophrenic patient exist predominantly in the left hemisphere, particularly in the area of the inferior temporal gyrus. In contrast, the significant differences identified for bipolar patients were found in the right hemisphere, and appear to be predominantly in the superior temporal gyrus. Further research is needed to ctarify the meaning of these preliminary findings and to determine, for example, whether these changes may be related to temporal delay in regional blood flow or to the changes in the magnitude of the regional blood volume. These. results are consistent with previous investigations which describe non-dominant hemisphere dysfunction in bipolar disorder and dominant hemisphere dysfunction in patients with schizophrenia (4). In addition, the presence of resting state blood volume changes suggests that studies examining relative changes in activation, such as the fMR1 BOLD technique, should interpret between group differences cautiously. References 1. Andreasen NC, Paradiso S, O’Leary DS. Schiz Bull. 1998; 24(2): 203-18. 2. Yurgelun-Todd D, Watemaux CM, Cohen B, et al. Am J Psychiatry. 1996; 153(2): 200-205. 3. Rogowska J, Preston K, Hunter G, et al. IEEE Trans on Med Imaging. 1995; 14(3): 480-486. 4. Gruzelier .I, Seymour K, Wilson L et al. Arch Gen Psychiatry. 1988;45(7): 623-629. 5670