Regional Xenon 133 Cerebral Blood Flow and Cerebral Technetium 99m HMPAO Uptake in Unmedicated Patients With Obsessive-Compulsive Disorder and Matched Normal Control Subjects

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Abstract
• We measured regional cerebral blood flow (rCBF) with the xenon 133 (133Xe) inhalation method and with regional cerebral uptake of technetium 99md,l—hexamethyl propyleneamine oxime (99mTc-HMPAO) by single-photon emission computed tomography in 10 adult male patients with obsessive-compulsive disorder (OCD) and in 10 agematched adult male normal controls. With the133Xe method, there were no significant differences in cortical or basal ganglia blood flow between the patients with OCD and their matched controls. In the patients, there was a positive relationship between rCBF and the severity of both obsessive and compulsive symptoms (averager=.48). These rCBF findings were consistent with those of earlier reports of increased rCBF in patients with OCD who were undergoing imaginal flooding and who had exacerbation of symptoms following m-CPP administration.99mTc-HMPAO is a lipophilic molecule that crosses the blood-brain barrier and is converted to a hydrophilic form that is trapped in the brain. The amount that is trapped is determined primarily by blood flow, but also by membrane permeability and kinetics of conversion of the99MTc-HMPAO to the hydro- philic form. Compared with their matched controls, the patients with OCD had significantly increased99mTcHMPAO uptake in the high dorsal parietal cortex bilaterally, in the left posterofrontal cortex, and in the orbital frontal cortex bilaterally. Possible explanations include (1) increased rCBF that was not detected with133Xe, (2) increased permeability of the blood-brain barrier and/or cell membranes, and (3) increased conversion and trapping of the lipophilic, injected form of99mTc-HMPAO in these regions. This finding is consistent with those findings from earlier reports of increased uptake of fluorodeoxyglucose in the orbital frontal regions of patients with OCD, as determined by positron emission tomography. The patients also had significantly reduced99mTc-HMPAO uptake in the head of the caudate nucleus bilaterally, but not in the putamen or thalamus, consistent with the hypothesized reduction of caudate nucleus activity in OCD. The results of our study provide additional support for the involvement of specific cortical areas in the pathophysiology of this disorder.