Changes in regional cerebral blood flow in hexamethylpropylenaminoxim (HMPAO)-SPECT during and after brain irradiation — preliminary results of a prospective study

In a prospective study of changes in regional cerebral blood flow (rCBF) using HMPAO-SPECT during and after brain irradiation. 54 patients were compared to a base line study before irradiation. Follow up studies were performed in 49 patients. An increase in rCBF during irradiation was found in 36 patients, 5 of whom normalised at the end of radiation therapy. The other 20 patients normalised within 6 months. A total of 8 patients had a decrease in rCBF during irradiation, 4 patients returning to pre-irradiation levels 0–1 month after therapy. Five patients showed no immediate changes in rCBF. Late changes have not yet been seen and are only discussed in patients examined due to neurological symptoms apparent 2 years after therapy. Further follow up is required in this ongoing study. Correspondence to: Z. Lapukins     

Judo and choking: EEG and regional cerebral blood flow findings.

Ten judoka were examined at rest by EEG and regional Cerebral Blood Flow (rCBF) (133-Xenon inhalation method); in seven of them a syncope was induced by choking and EEG was recorded during the loss of consciousness while rCBF was measured immediately after recovery. Baseline EEG and rCBF examinations were normal. During choking, EEG showed diffuse 2-3 Hz. high voltage waves, predominantly in the anterior regions, then the EEG gradually recovered to normal. After choking, rCBF decreased in all but one subject, slightly in four and more markedly in two. Our findings suggest that there is no evidence of permanent CNS functional changes due to judo practice and choking. The variable rCBF features soon after choking-induced syncope may reflect a different timing of recovery from cerebral ischemia for each subject.     

Patterns of regional cerebral blood flow in Alzheimer's disease.

Regional cerebral blood flow was assessed in 35 patients with Alzheimer's disease and the same number of matched normal volunteers. Images were scored for regional perfusion deficits. Mildly demented patients had parietal and temporal perfusion deficits, often unilateral. Moderate to severely demented patients had bilateral temporal and parietal perfusion deficits. All severely demented patients also had involvement of both occipital regions. Frontal lobe deficits were seen in 14 patients. Left cortical perfusion deficits were more severe than the right cortical perfusion deficits in general. Patients with early onset of the disease showed left frontal deficits, more often, however, the total perfusion deficit scores in early and late onset groups were not statistically significant. Also, the cognitive performance scores were not statistically significant in these two groups. These results suggest a stage-dependent reduction in regional cerebral blood flow in patients with Alzheimer's disease.     

Evaluation of regional cerebral blood flow in fahr disease with schizophrenia-like psychosis: a case report

We report the case of a patient with Fahr disease presenting with schizophrenia-like psychosis for whom a technetium Tc99 methyl cysteinate dimmer brain study was used to evaluate regional blood flow. A brain single photon-emission CT study showed increased cerebral blood flow to the bilateral temporal lobes. Such perfusion abnormalities may reflect psychotic symptoms, including auditory hallucinations and delusions, which suggests a disruption of the cortico-subcortical neural circuits in psychosis.     

Influence of diabetes mellitus on regional cerebral glucose metabolism and regional cerebral blood flow

Previous studies have shown both increased and decreased regional cerebral glucose metabolism-blood flow (rMRGlu-rCBF) values in diabetes. We sought to elucidate the influence of diabetes on rMRGlu-rCBF in 57 patients with pure cerebral microangiopathy. Sixteen of 57 patients had diabetes requiring therapy (11 NIDDM, 5 IDDM). Using a special head-holder for exact repositioning, rMRGlu (PET) and rCBF (SPET) were imaged and measured in slices, followed by MRI. White matter and cortex were defined within regions of interest taken topographically from MRI (overlay). Diabetic and non-diabetic microangiopathy patients were compared to 19 age-matched controls. The diabetic patients showed significantly lower rMRGlu-rCBF values in all regions than controls, whereas non-diabetic patients did not. There were no significant NIDDM-IDDM differences. rMRGlu-rCBF did not depend on venous blood glucose levels at the time of the PET examination. However, analysis of variance with the factors diabetes, atrophy and morphological severity of microangiopathy showed that lowered rMRGlu-rCBF in the diabetic group was due to concomitant atrophy only (P < 0.005), while neither diabetes nor microangiopathy had any influence on rMRGlu-rCBF (all P > 0.2). These results were confirmed by multivariate factor analysis. It can thus be concluded that a supposed decrease in rMRGlu-rCBF in diabetes mellitus is in fact only an artefact produced by the concomitant atrophy. All previous studies failed to correct for atrophy, and a critical reappraisal is required.     

Changes in regional cerebral blood flow during brain maturation in children and adolescents.

Regional cerebral blood flow (rCBF) was studied by SPECT using 133Xe in 42 children, aged 2 days to 19 years, considered as neurologically normal. rCBF was measured on cortical regions and on the cerebellum and thalamus. Curves for reference values and standard deviation were defined for each region. At birth, cortical rCBFs were lower than those for adults; after birth they increased until 5 or 6 yr of age to values 50%-85% higher than those for adults and thereafter decreased, reaching adult levels between 15 and 19 yr. Neonatal values of rCBF on cerebellum and thalamus were slightly higher than adult level, but not significantly; after age 1, they followed the common pattern for cortical curves. When rCBFs were expressed in percent global CBF, they were lower at birth than adult levels in the cortex, then increased and reached a plateau corresponding to the adult value before the second year of age. The time needed to reach normal adult values differed for each cortical region. The shortest time was found on the primary cortex and the longest on the associative cortex. Cognitive development of the child seems to be related to changes in blood flow of the corresponding brain regions.     

Pitfalls of regional cerebral blood flow analysis in cerebrovascular disease

In 20 patients with unilateral cerebrovascular disease, regional cerebral blood flow (rCBF) was measured by F-18-fluoromethane inhalation and positron emission tomography (PET). The purpose was to study various strategies of rCBF data analysis that are currently used in SPECT and PET. Methods of quantitative data analysis standardize rCBF values relative to an intraindividual reference, and thus create ratios as estimators of rCBF in the ischemic regions-of-interest (ROI). These ratios were compared as well as the absolute rCBF values in the ischemic ROI graphically and by Spearman's rank correlation coefficient (r). The results demonstrated that previously reported methods of data analysis failed to represent rCBF in the ischemic ROI; r values were 0.467, -0.406, -0.453, and 0.329, respectively (N.S.). This failure was due to a more widespread reduction of rCBF even in patients with minimal ischemic deficits. In conclusion, previously reported strategies of rCBF analysis based on intraindividual standardization should not be used in patients with cerebrovascular disease since they may produce misleading results.     

SPECT study of regional cerebral blood flow in Alzheimer disease

A common cause of dementia in late midlife and old age is Alzheimer disease (AD), which affects more than one in 20 individuals over the age of 65. Past studies of regional cerebral blood flow (rCBF) in patients with AD here suggested blood flow abnormalities, but findings have differed. We have studied 37 patients diagnosed as having AD with inhalation and washout of 133Xe and single-photon emission computed tomography (SPECT), obtaining evidence of abnormal rCBF patterns in 19. Flow reductions were most common in the temporoparietal regions and were occasionally found in the frontal areas. Investigators using positron-emission tomography (PET) have identified similar findings with respect to rCBF and regional oxygen, glucose, and protein metabolism. The SPECT determination of rCBF, which gives information similar to that provided by PET, may assume importance in the diagnosis of AD and in the differential diagnosis of the dementias.     

Single-photon tomographic determination of regional cerebral blood flow in epilepsy

Using a single-photon emission computed tomographic scanner (SPECT) the authors determined regional cerebral blood flow (rCBF) with inhaled xenon-133, a noninvasive procedure. Studies were performed in 40 normal individuals, and these were compared with rCBF determinations in 51 patients with seizure disorders. Although positive results were obtained in 15 of 16 patients with mass lesions, the group of principal interest comprised 25 patients suffering from "temporal lobe" epilepsy. Only one of these had a positive x-ray computed tomogram, but 16 had positive findings on rCBF study. These findings included increased local blood flow in the ictal state and reduced flow interictally.     

Noninvasive determination of regional cerebral blood flow in rats using dynamic imaging with Gd(DTPA)

A method for the noninvasive, quantitative determination of regional cerebral blood flow (rCBF) in small laboratory animals, such as the rat, is described. The change in magnetic susceptibility in the vicinity of brain capillaries evoked by iv infusion of Gd(DTPA), a paramagnetic agent not crossing the blood-brain barrier, is detected as an attenuation of the 1H signal in T2-weighted MRI sequences. The reduction of the MR signal intensity after 1 or 2 min of Gd(DTPA) infusion correlates well (r greater than 0.95) with the rCBF values obtained using the well-established [14C]iodoantipyrine method. At a slice thickness of 3 mm, the pixel size typically is 0.15 x 0.5 mm2. The clearance rate of Gd(DTPA) from blood allows repeated measurements of CBF to be made using this technique approximately every 30 min. The experimental results obtained in normal and ischemic rat brain have been rationalized within the frame of a two-compartment model, allowing the definition of optimal experimental conditions for a given CBF: for normal and reduced CBF values (less than 150 ml/100 g/min) the reduction in MR signal intensity, measured after 1 or 2 min of Gd (DTPA) infusion, correlates closely with the CBF. However, for CBF values greater than 150 ml/100 g/min, a more reliable parameter would be the time constant of the MR signal attenuation during the infusion.     

Quantitative measurement of regional cerebral blood flow using N-isopropyl-(iodine-123)p-iodoamphetamine and single-photon emission computed tomography.

We have developed a quantitative method of measuring regional cerebral blood flow (rCBF) by using N-isopropyl-(iodine-123)p-iodoamphetamine and single-photon emission computed tomography (SPECT). Twenty-five dynamic SPECT images (24 sec/scan) were collected immediately after tracer injection using a ring-type SPECT system and the accumulation curve (C(t)) was obtained. The time-activity curve corresponding to the arterial blood activity curve was used as B(t). The latter curve was calculated from the lung time-activity curve monitored during scanning and corrected by the actual activity obtained by one-point blood sampling 5 min after tracer injection. The octanol extraction ratio during scanning was considered to be constant and taken as the value measured 5 min after tracer injection (E). The uptake constant (K) per pixel was calculated by the least squares fitting method as the slope of the linear relationship in which C(t)/E x B(t) was plotted against E x integral of t(o)B(tau)d tau/E x B(t). Functional maps of rCBF values were obtained on a 64 x 64 matrix by calculating the uptake constant per pixel and the cross calibration factor (CF) between the SPECT system and a well counter (rCBF = K.CF x 100).     

Donepezil hydrochloride preserves regional cerebral blood flow in patients with Alzheimer's disease.

The aim of this SPECT study was to investigate the effects of donepezil on regional cerebral blood flow (rCBF) in patients with mild to moderate Alzheimer's disease (AD) using statistical parametric mapping. METHODS: rCBF was noninvasively measured using (99m)Tc-ethyl cysteinate dimer in 35 AD patients with a Mini-Mental State Examination score > 16 on initial evaluation. Baseline and follow-up SPECT studies with a mean interval of 12 mo were performed on these patients. We used the adjusted rCBF images in the relative flow distribution (normalization of global cerebral blood flow for each patient to 50 mL/100 g/min with proportional scaling) to compare these groups through statistical parametric mapping. RESULTS: In the follow-up study, the adjusted rCBF was significantly preserved in the right and left anterior cingulate gyri, right middle temporal gyrus, right inferior parietal lobules, and prefrontal cortex of donepezil-treated AD patients, compared with placebo-treated AD patients. CONCLUSION: Treatment with donepezil for 1 y appears to reduce the decline in rCBF, suggesting preservation of functional brain activity.     

Educational level influences regional cerebral blood flow in patients with Alzheimer's disease.

We tested the hypothesis that educational level influences regional cerebral blood flow (rCBF) in Alzheimer's disease (AD) patients. METHODS: The severity of AD was measured with the Cognitive Ability Screening Instrument (age and education adjusted). rCBF was assessed using (99m)Tc-hexamethylpropyleneamine oxime brain SPECT; differences in rCBF between groups with different educational levels were determined using statistical parametric mapping (SPM). RESULTS: In matched low-education (< or =6 y; n = 29) and high-education (>6 y; n = 29) groups, SPM revealed 2 statistically significant clusters of voxels with higher rCBF in the high-education group: one in the left lateral inferior, middle, and superior temporal gyrus; another in the left medial temporal area to the left inferior frontal gyrus. CONCLUSION: We provide biologic evidence that education may lead to relatively higher rCBF in specific areas in AD patients, which may explain the effects of education on clinical manifestations of AD.