Karim Rezai

II. PET Studies of Memory: Novel versus Practiced Free Recall of Word Lists

Positron emission tomography (PET) with the tracer H215O was used to measure regional cerebral blood flow in 13 healthy volunteers while they engaged in free recall of 15-item word lists from the Rey Auditory Verbal Learning task. The study was designed so that recall of well-practiced versus novel material could be compared. One week before the PET study, subjects were trained to perfect recall of List A, while they were exposed to list B only 60 s prior to PET data acquisition. As in the companion study of free recall of complex narratives, we observed that practice tended to decrease the size of activations in regions involved in the memory component of the task; we also observed that the novel recall task produced greater activation in left frontal regions, probably due to active encoding. A commonality of other regions observed in this pair of studies, as well as other studies of memory in the literature, suggests that the human brain may contain a distributed multinodal general memory system. Nodes on this network include the frontal, parietal, and temporal cortices, the thalamus, the anterior and posterior cingulate, the precuneus, and the cerebellum. There appears to be a commonality of components across tasks (e.g., retrieval, encoding) that is independent of content, as well as differentiation of some components that may be content-specific or tasks-specific. In addition, these results support a significant role for the cerebellum in cognitive functions such as memory.

Regional Cerebral Blood Flow in Normal Pressure Hydrocephalus

Regional cerebral blood flow (rcbf) was studied preoperatively and at 2 and 6 months postoperatively in 22 normal pressure hydrocephalus patients using xenon-133 inhalation and single photon emission computed tomography. Sixteen of the 22 patients improved (improved group) and six did not (unimproved group). The following comparisons were made: (1) preoperative rcbf in the improved group, to 14 normal elderly volunteers and to that in 59 SDAT (senile dementia of the Alzheimer type) patients; (2) preoperative rcbf in the improved and unimproved groups to determine if rcbf could predict surgical outcome; (3) pre- to postoperative rcbf in the improved group to see if increased cbf accounted for clinical improvement. The findings were: (1) preoperative rcbf in the improved group was lower than that in normal controls but was the same as that in SDAT; however, the ratios of rcbf values in anterior and posterior brain regions were significantly different between improved group and SDAT (p = 0.02); (2) an anterior/posterior ratio of 1.05 correctly classified surgical outcome in 19/22 patients; five of six in the unimproved group were above this cut off while 14/16 in the improved group were below; (3) in the improved group rcbf increased at 2 but not at 6 months after surgery without a corresponding reduction of clinical signs, supporting the notion that increase in cbf probably does not account for clinical improvement in normal pressure hydrocephalus.

The effect of antipsychotic medication on relative cerebral blood perfusion in schizophrenia: Assessment with technetium-99m hexamethyl-propyleneamine oxime single photon emission computed tomography

Functional neuroimaging studies in schizophrenia have often been confounded by various factors including medication status. To explore the effects of antipsychotic medications on relative regional cerebral perfusion, we scanned a group of 33 persons with schizophrenia twice, while receiving a stable dose of antipsychotic and after being off antipsychotics for 3 weeks, using technetium-99m hexamethyl-propyleneamine oxime single photon emission computed tomography (Tc-99m HMPAO-SPECT. We found that antipsychotic significantly increased the mean relative cerebral perfusion in the left basal ganglia. Additionally, patients receiving thiothixene (n = 9) had a significantly greater increase in relative cerebral perfusion in the basal ganglia than patients receiving haloperidol (n = 12). These findings indicate that antipsychotics lead to regional increases in cerebral perfusion and that antipsychotic status must be controlled for in functional neuroimaging studies. Functional neuroimaging techniques such as SPECT may be useful in furthering our understanding of the mechanism of antipsychotics.

Coronary artery disease and cardiac events with asymptomatic and symptomatic cerebrovascular disease.

Background and Purpose The purpose of this study was to evaluate the prevalence of coronary artery disease and coronary events during follow-up in patients with asymptomatic carotid stenosis, transient ischemic attacks, or small strokes. Methods We prospectively studied 60 consecutive patients with thallium-201 scintigraphy followed by coronary arteriography according to an established protocol. Results The 201TI testing was abnormal in seven of 15 patients (47%) with asymptomatic carotid stenosis and in 19 of 44 patients (43%) with transient ischemic attacks or small strokes (p>0.05). In 33 patients with no history of coronary artery disease, 11 (33%) had reversible 201TI defects. In 26 patients with a history of coronary artery disease, 15 (58%) had reversible and/or fixed defects (p=0.054 compared with patients with no history). A history of peripheral vascular disease was the only risk factor significantly associated with an abnormal 201TI test (p=0.032). Coronary artery stenosis of greater than 50% was identified in one or more vessels in 14 of 15 patients undergoing coronary arteriography. Over a mean follow-up period of 311 days, four patients (7%) developed new onset of angina. There were four coronary events among 14 patients (29%) with both a reversible area on the 201TI and abnormal coronary arteriography. In comparison, there were only four coronary events among 46 patients (9%) without reversible defects on the 201TI studies (p=0.055). Conclusions Our study demonstrates that one third of patients with no history of coronary artery disease had an abnormal 201TI test and that nearly one half of patients with either symptomatic or asymptomatic cerebrovascular disease had abnormal 201TI tests. Patients with a reversible 201TI defect and significant stenosis by coronary arteriography were at higher risk for subsequent cardiac events. These findings demonstrate the utility of screening patients with asymptomatic and symptomatic cerebrovascular disease for cardiac disease.

Quantification of left ventricular function with an automated border detection system and comparison with radionuclide ventriculography

Quantification of 2-dimensional echocardiograms with a recently developed automated border detection (ABD) system provides on-line estimation of left ventricular (LV) function. Previous studies showed that short-axis cavity area measurements with the ABD system approximate manually traced cavity areas obtained with conventional 2-dimensional echocardiography. Further clinical validation needs a comparison of LV function between the ABD system and established methods. Fractional area change and ejection fraction measured by the ABD system were compared with ejection fraction measured by radionuclide ventriculography. Echocardiographic measurements were obtained from LV short-axis views at the level of the papillary muscles. Calculation of ejection fraction by the ABD system was based on an algorithm using a modified ellipsoid model. Forty-six patients underwent echocardiography on the same day as radionuclide ventriculography. Patients were included in the study if > or = 75% of the endocardium was visualized with conventional 2-dimensional echocardiography. Twenty-seven of 46 patients (59%) had a technically adequate, conventional echocardiogram. Fractional area change with the ABD system was highly correlated with ejection fraction from radionuclide ventriculography (r = 0.92; SEE 8.4%). Ejection fraction determined by the ABD system and radionuclide ventriculography also showed a strong linear relation in the 23 patients without severe wall motion abnormality (r = 0.90; SEE 9.5%). It is concluded that LV function measurements by the ABD system and radionuclide ventriculography have a strong linear relation.

Evaluation Of Diabetic Patients For Renal And Pancreas Transplantation: Noninvasive Screening for Coronary Artery Disease Using Radionuclide Methods

Pharmacologic stress thallium scintigraphy is commonly performed in the risk assessment of diabetic patients with nephropathy before kidney and/or pancreas transplantation; however, controversy exists regarding the tests accuracy in detecting coronary artery disease. Our purpose was to compare pharmacologic stress thallium scintigraphy and also exercise radionuclide ventriculography with coronary angiography in diabetic patients undergoing evaluation for transplantation. In addition, we also determined the association of the test results with outcome after transplantation. The medical records of 47 patients (mean age, 37+/-9 years) without clinical evidence of coronary artery disease were reviewed. Forty-one patients had pharmacologic stress thallium scintigraphy performed during their evaluation. Sensitivity was 62% and specificity was 76% for detecting > or = 75% coronary artery stenosis (sensitivity was 53% and specificity was 73% for > or = 50% stenosis). Thirty-five patients had exercise radionuclide ventriculography performed. Sensitivity was 50% and specificity was 67% for detecting > or = 75% coronary artery stenosis (sensitivity was 44% and specificity was 63% for > or = 50% stenosis). Thirty patients had both pharmacologic stress thallium scintigraphy and exercise radionuclide ventriculography performed; when either test was abnormal, sensitivity in the detection of > or = 50% or > or = 75% stenosis tended to increase compared with pharmacologic stress thallium scintigraphy alone (0.05<P<0.10), whereas specificity decreased (P<0.01). The incidence of adverse cardiac outcomes was identical for patients with abnormal thallium scintigrams and undergoing transplantation (2/11) compared with patients with normal scintigrams and undergoing transplantation (4/22). We conclude that: (1) pharmacologic stress thallium scintigraphy and exercise radionuclide ventriculography are suboptimal screening tests for coronary artery disease in diabetic patients awaiting kidney and/or pancreas transplantation; (2) using the two radionuclide tests in combination results in a decrease in specificity; and (3) patients with abnormal thallium scintigrams can receive transplants with outcomes similar to those for patients with normal thallium scintigrams.

Cerebral infarction due to moyamoya disease in young adults.

Moyamoya disease was diagnosed as the cause of cerebral infarction in eight young adults (seven women, one man), aged 17-40 (mean 33) years. All had angiographic abnormalities characteristic of moyamoya disease. Single-photon emission tomography showed bilateral carotid circulation hypoperfusion and posterior circulation hyperemia in all seven patients with regional cerebral blood flow studies. All seven women had used oral contraceptives before cerebral infarction. Four patients were treated medically; one died of a second cerebral infarction 9 months after diagnosis. Four patients underwent superficial temporal-to-middle cerebral artery anastomosis; they did well. Moyamoya disease should be included in the differential diagnosis of cerebral infarction as well as intracranial hemorrhage in young adults, particularly women. A possible relation between moyamoya disease and oral contraceptive use deserves investigation.

Patterns of regional diastolic function in the normal human left ventricle: An ultrafast computed tomographic study

The detailed evaluation of regional diastolic filling at multiple ventricular levels in the normal human left ventricle has not previously been reported. Ultrafast computed tomography was used to characterize global and regional early diastolic filling in the left ventricle of 11 normal male volunteers. Regional early diastolic filling data from six distinct ventricular levels (apex to base) were fit to a third-order polynomial curve, and the peak rate of diastolic filling and time of peak filling were determined. Peak filling rate was 259 +/- 17 ml/s (+/- SEM) as a global average, where peak filling rate referenced to end-diastolic volume and stroke volume across the levels examined was 3.78 +/- 0.17 s-1 and 4.83 +/- 0.20 s-1, respectively. Average filling fraction was 39 +/- 1%, and time to peak filling from end-systole was 145 +/- 5 ms. Regional (tomographic) peak filling rates, except for the most apical level examined, were not statistically different across the ventricle. Filling fraction and time to peak filling were remarkably constant from one level to another. However, reference of regional peak filling rate to regional end-diastolic volume demonstrated significant nonuniformity from apex (120% of average for all levels) to base (87% of average for all levels). Peak filling rate referenced to tomographic stroke volume was less variable and not statistically different across the ventricle as a whole.(ABSTRACT TRUNCATED AT 250 WORDS)

NeuroSPECT correlates of disabling mild head injury: Preliminary findings

Objective: To study mild head injury patients with poor psychosocial and vocational outcomes using neurological single photon emission computed tomography (neuroSPECT) imaging. Design: Case‐comparison study. Setting: VA Medical Center, outpatient clinics. Patients: Fourteen mild head injury patients with normal computed tomography (CT) and/or magnetic resonance imaging (MRI) scans and five normal controls. Head‐injured patients were selected because they had obtained and maintained highly responsible employment prior to injury, but were unable to sustain any occupation despite multiple attempts over a number of years after injury. Intervention: NeuroSPECT with technetium Tc 99m hexamethylpropyleneamine oxime. Main Outcome Measure: Regional abnormalities in cerebral perfusion as indicated by neuroSPECT. Results: This carefully preselected population consistently showed anterior mesial temporal hypoperfusion. By contrast, posterior temporal abnormalities were very infrequent. NeuroSPECT findings with regard to orbitofrontal damage were not as striking, but were statistically significant on the left and were sufficient to raise the question of dysfunction in this area as well. Conclusions: Findings indicate that some “mild” head injuries with unusually catastrophic psychosocial consequences can produce regional abnormalities in cerebral perfusion that are apparent with neuroSPECT, even in the absence of abnormalities seen on CT or MRI.

Dual isotope brain SPECT imaging for monitoring cognitive activation: initial studies in humans

A dual isotope, single photon emission tomography (SPECT) technique using 99Tcm-hexamethylpropyleneamine oxime (HMPAO) and 123I-iodoamphetamine (IMP) was investigated to determine its suitability for assessing regional cerebral blood flow (rCBF) changes resulting from cognitive activation. The similarity of the 123I-IMP and 99Tcm-HMPAO distributions under the same physiological conditions was first investigated by administering the two agents to human subjects (n = 8) either simultaneously or at different times but during the performance of the same task. Normalized ratio images generated from the 99Tcm and 123I data showed that the two tracers distributed similarly in the left and right cerebral hemispheres when administered under similar physiological conditions. There was, however, a significant anterior/posterior gradient that appears to be the result of partial volume effects due to small differences in spatial resolution of the two agents. In two subjects, 99Tcm-HMPAO was administered during a resting period with eyes-closed and 123I-IMP was injected later during visual checkerboard stimulation. Ratio images showed a localized increase in the occipital lobes during the visual stimulation consistent with the expected increase in rCBF. The dual isotope strategy appears promising for study of changes in rCBF due to cognitive activation.