A quantitative study of regional cerebral blood flow in childhood using 123I-IMP-SPECT: with emphasis on age-related changes

Single photon emission computed tomography (SPECT), using N-isopropyl-p-[123I] iodoamphetamine (123I-IMP) was used for quantitative analysis of regional cerebral blood flow (rCBF) on 26 individuals between 0 and 19 years of age. The rCBF showed age-related changes; it was low in early infancy, increased in late infancy through early childhood, and decreased and remained constant after puberty. The rCBF through cerebral cortex varied more greatly than through thalamus and cerebellum, and seemed to depend more closely on age. In the case of 4 months of age rCBF was very low at the frontal region and was very high at the occipital region. In more older cases, rCBF in the cerebral cortex was higher than in the thalamus. In childhood, rCBF was very inconsistent and showed a great inter-individual variance.     

Nigral glutathione deficiency is not specific for idiopathic Parkinson's disease

The consistent findings of decreased levels of the major antioxidant glutathione in substantia nigra of patients with idiopathic Parkinson's disease (PD) has provided most of the basis for the oxidative stress hypothesis of the etiology of PD. To establish whether a nigral glutathione deficiency is unique to PD, as is generally assumed, or is present in other Parkinsonian conditions associated with nigral damage, we compared levels of reduced glutathione (GSH) in postmortem brain of patients with PD to those with progressive supranuclear palsy (PSP) and multiple system atrophy (MSA). As compared with the controls, nigral GSH levels were decreased in the PD and PSP patient groups (P < 0.05 for PD [-30%], PSP [-21%]), whereas a similar decrease in the MSA patient group did not reach statistical significance (P = 0.078, MSA [-20%]). GSH levels were normal in all examined normal and degenerating extra-nigral brain areas in PSP and MSA. A trend for decreased levels of uric acid (antioxidant and product of purine catabolism) also was observed in nigra of all patient groups (-19 to -30%). These data suggest that glutathione depletion, possibly consequent to overutilisation in oxidative stress reactions, could play a causal role in nigral degeneration in all nigrostriatal dopamine deficiency disorders, and that antioxidant therapeutic approaches should not be restricted to PD.     

Regional cerebral blood flow in pediatric moyamoya disease: age-dependent decline in specific regions

Thirteen pediatric patients (ages 4-13 years) who underwent surgical treatment were examined regarding their rCBF in the preoperative periods. The postoperative rCBF was measured 39 times in these 13 patients. Thirteen healthy normal subjects (ages from 6 to 21 years) were also examined. The rCBF in the operculum and in the frontal, parietal, and occipital lobes was measured with 133Xe inhalation method and single photon emission computed tomography. In the parietal and occipital lobes, the preoperative rCBF had a negative and significant correlation with their ages, but not in the operculum or frontal lobe. However, subsequent to the surgical treatment, the rCBF increased significantly in the patients 5 years old or less, and then post-operative rCBF values had significant negative correlations with age in each region.     

Effect of early pregnancy on maternal regional cerebral blood flow

OBJECTIVE: The purpose of this study was to assess the effect of early pregnancy on maternal regional cerebral blood flow. STUDY DESIGN: We studied 10 pregnant women at 7 to 19 weeks' gestation by the xenon 133 washout technique by means of single-photon emission computed tomography the day before the abortion was induced and then again at a mean of 42.8 days after the abortion. RESULTS: Blood flow in the cerebral hemispheres decreased after the abortion, with a decline of 8.1% (p < 0.001). Each regional decrease was as follows: 7.6% (p < 0.01) in the frontal lobe, 9.1% (p < 0.01) in the temporal lobe, 12.9% (p < 0.001) in the parietal lobe, 9.8% (p < 0.01) in the basal ganglia, and 16.7% (p < 0.001) in the cerebellum. There was no significant difference in blood flow in the occipital lobe before versus after the abortion. CONCLUSION: Maternal regional cerebral blood flow was increased in early pregnancy compared with the nonpregnant state, except in the occipital lobe.     

Fear conditioning and brain activity: A positron emission tomography study in humans.

Regional cerebral blood flow (rCBF) was measured with H? 1?O positron emission tomography in 8 healthy women before and after fear conditioning (i.e., paired shocks) and unpaired shocks to videotape cues. Conditioning was supported by enhanced peripheral nervous system recordings and subjective ratings. Fear conditioning increased rCBF in the central gray of the midbrain; bilaterally in the hypothalamus, the thalamus, and the left striatum; and in the right and left anterior cingulate and right prefrontal cortices. Regional CBF was attenuated bilaterally in the right and left prefrontal, temporal (including the amygdala), parietal, and occipital cortices, and in the left orbitofrontal cortex. When compared with unpaired shock presentations, fear conditioning resulted in elevated rCBF in the left cerebellum. Hence, in the present paradigm, only neural activity in the left cerebellum solely reflected processes associated with true Pavlovian conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cerebral blood flow relationships associated with a difficult tone recognition task in trained normal volunteers

Tone recognition is partially subserved by neural activity in the right frontal and primary auditory cortices. First we determined the brain areas associated with tone perception and recognition. This study then examined how regional cerebral blood flow (rCBF) in these and other brain regions correlates with the behavioral characteristics of a difficult tone recognition task. rCBF changes were assessed using H2(15)O positron emission tomography. Subtraction procedures were used to localize significant change regions and correlational analyses were applied to determine how response times (RT) predicted rCBF patterns. Twelve trained normal volunteers were studied in three conditions: REST, sensory motor control (SMC) and decision (DEC). The SMC-REST contrast revealed bilateral activation of primary auditory cortices, cerebellum and bilateral inferior frontal gyri. DEC-SMC produced significant clusters in the right middle and inferior frontal gyri, insula and claustrum; the anterior cingulate gyrus and supplementary motor area; the left insula/claustrum; and the left cerebellum. Correlational analyses, RT versus rCBF from DEC scans, showed a positive correlation in right inferior and middle frontal cortex; rCBF in bilateral auditory cortices and cerebellum exhibited significant negative correlations with RT These changes suggest that neural activity in the right frontal, superior temporal and cerebellar regions shifts back and forth in magnitude depending on whether tone recognition RT is relatively fast or slow, during a difficult, accurate assessment.     

The resting and activation issue of hypofrontality: a single photon emission computed tomography study in neuroleptic-naive and neuroleptic-free schizophrenic female patients

BACKGROUND: Functional neuroimaging findings of "hypofrontality" in schizophrenic patients is still controversial, due to the heterogeneity of methods and patient samples. This study tries to prevent some of these concerns by studying neuroleptic-naive (NN) and neuroleptic-free (NF) young female patients both in resting conditions and during a frontal cognitive activation task. METHODS: Regional cerebral blood flow (rCBF) was studied at rest and during the Wisconsin Card Sorting Test (WCST) in 25 young acute unmedicated schizophrenic female patients (14 NN and 11 NF) and 15 female controls, using single photon emission computed tomography. RESULTS: The schizophrenic and control groups did not differ in rCBF during the baseline condition, but the schizophrenic group failed to activate the frontal lobe during the WCST condition. In addition, the left anterior temporal rCBF at rest correlated with the Scale for the Assessment of Positive Symptoms total score. CONCLUSIONS: The results suggest that hypofrontality in young acute unmedicated schizophrenic patients is a result of an inability to activate frontal regions during cognition, rather than a baseline decrease in frontal activity. Furthermore, positive symptoms seem to be associated with left temporal cortex activity.     

Neuroradiological findings on cerebral blood flow and metabolism of a case of adult onset sialidosis

We examined a patient with adult onset sialidosis using N-isopropyl-p-123I-iodoamphetamine single photon emission computed tomography (SPECT) and 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (PET). A 41-year-old [correction of 47] man was admitted to our hospital because of the involuntary movement of his extremities and gait disturbance. On admission, he exhibited action myoclonus in his face and extremities with cerebellar ataxia. Ophthalmoscopy revealed cherry-red spots on his retina. Enzymological analysis of his leucocytes and skin fibroblasts revealed primary sialidase deficit. Brain MRI showed no abnormal findings. Brain SPECT showed decreased cerebral blood flow in the cortex of bilateral occipital lobes, and PET study revealed decreased glucose metabolism in the cortex of bilateral occipital lobes. This case is the thirteenth patient of adult onset sialidosis in Japan. As far as we know, there are no previous reports of SPECT or PET on sialidosis patients. Why the cerebral blood flow and glucose metabolism was decreased in the occipital lobe region remains obscure. From the literatures, we suppose that the onset time of neuronal tissue degeneration or the sensitivity to cumulative metabolites in the occipital region may be different from those in other regions. Further studies are required to confirm abnormalities of cerebral blood flow and metabolism in sialidosis.     

Differential distribution of striatal [123I]beta-CIT in Parkinson's disease and progressive supranuclear palsy, evaluated with single-photon emission tomography

Functional imaging of the presynaptic dopaminergic activity using single-photon emission tomography (SPET) and iodine-123 labelled 2-beta-carboxymethoxy-3-beta-(4-iodophenyl)tropane ([123I]beta-CIT) is important for the assessment of disease severity and progression in patients with Parkinson's disease (PD). However, its capability to discriminate between different extrapyramidal disorders has not yet been assessed. The aim of this study was to evaluate the possibility of differentiating patients with PD and with progressive supranuclear palsy (PSP) by means of this method. The distribution of [123I]beta-CIT in the basal ganglia was assessed in six normal subjects, 13 petients with PD and five patients with PSP in whom the disease was mild. SPET images were obtained 24+/-2 h after i.v. injection of the tracer using a brain-dedicated system (CERASPECT). MR and SPET images were co-registered in four normal subjects and used to define a standard set of 16 circular regions of interest (ROIs) on the slice showing the highest striatal activity. The basal ganglia ROIs corresponded to (1) the head of caudate, (2) a region of transition between the head of caudate and the anterior putamen, (3) the anterior putamen and (4) the posterior putamen. A ratio of specific to non-displaceable striatal uptake was calculated normalising the activity of the basal ganglia ROIs to that of the occipital cortex (V3"). ANOVA revealed a global reduction of V3" in all ROIs of PD and PSP patients compared with normal controls (P<0. 0001). A Mann-Whitney U test showed that the difference between PD and PSP patients was statistically significant for the caudate region only (Z value: 2.6; P<0.01). By subtracting V3" caudate values from those of the putamen, differentiation from PSP was possible in 10/13 PD patients. In conclusion, analysis of [123I]beta-CIT distribution in discrete striatal areas provides information on the relative caudate-putamen damage, with different values being obtained in patients clinically diagnosed as having either PD or PSP.     

In vivo mapping of cholinergic terminals in normal aging, Alzheimer's disease, and Parkinson's disease

To map presynaptic cholinergic terminal densities in normal aging (n = 36), Alzheimer's disease (AD) (n = 22), and Parkinson's disease (PD) (n = 15), we performed single-photon emission computed tomography using [123I]iodobenzovesamicol (IBVM), an in vivo marker of the vesicular acetylcholine transporter. We used coregistered positron emission tomography with [18F]fluorodeoxyglucose for metabolic assessment and coregistered magnetic resonance imaging for atrophy assessment. In controls (age, 22-91 years), cortical IBVM binding declined only 3.7% per decade. In AD, cortical binding correlated inversely with dementia severity. In mild dementia, binding differed according to age of onset, but metabolism did not. With an onset age of less than 65 years, binding was reduced severely throughout the entire cerebral cortex and hippocampus (about 30%), but with an onset age of 65 years or more, binding reductions were restricted to temporal cortex and hippocampus. In PD without dementia, binding was reduced only in parietal and occipital cortex, but demented PD subjects had extensive cortical binding decreases similar to early-onset AD. We conclude that cholinergic neuron integrity can be monitored in living AD and PD patients, and that it is not so devastated in vivo as suggested by postmortem choline acetyltransferase activity (50-80%).     

PET study of human voluntary saccadic eye movements in darkness: effect of task repetition on the activation pattern

Using H2(15)O 3D Positron Emission Tomography (PET), regional cerebral blood flow (rCBF) was measured in six human subjects under two different conditions: at rest and while performing self-paced horizontal saccadic eye movements in darkness. These two conditions were repeated four times each. First, the comparison between the four saccadic and four resting conditions was investigated in a group and a single subject analysis. Saccades elicited bilateral rCBF increases in the medial part of the superior frontal gyrus (supplementary eye field), precentral gyrus (frontal eye field), superior parietal lobule, anterior medial part of the occipital lobe involving striate and extrastriate cortex (lingual gyrus and cuneus), and in the right inferior parietal lobule. At the subcortical level, activations were found in the left putamen. These results mainly replicate previous PET findings on saccadic control. Second, the interaction between the experimental conditions and their repetition was examined. When activations throughout repetition of the same saccadic task are compared, the supplementary eye fields show a progressive increase of activation. On the contrary, the activation in the cerebellum, left superior parietal lobule and left occipital cortex progressively decreases during the scanning session. Given the existence of such an interaction, the pattern of activations must be interpreted as a function of task repetition. This may be a factor explaining some apparent mismatch between different studies.     

Correlation of positive symptoms exclusively to hyperperfusion or hypoperfusion of cerebral cortex in never-treated schizophrenics

BACKGROUND: Studies of schizophrenia by single photon emission computed tomography (SPECT) and positron emission tomography (PET) have shown both regional cerebral hyperperfusion and hypoperfusion. The aim of this study was to examine the inter-relations between regional cerebral blood flow (rCBF), psychopathology, and effects of neuroleptic therapy. METHODS: 24 never-treated patients with acute schizophrenia were examined with hexamethylpropyleneamine-oxime brain SPECT and assessed psychopathologically according to the positive and negative syndrome scale; they were studied again after neuroleptic treatment and psychopathological remission. rCBF values that deviated from those of 20 controls by more than 2 SD were regarded as abnormal. FINDINGS: Both hyperperfused and hypoperfused patterns were found among schizophrenia patients during acute illness. The seven positive symptoms on the symptom scale showed different correlations with rCBF: formal thought disorders and grandiosity correlated positively (and strongly) with bifrontal and bitemporal rCBF; delusions, hallucinations, and distrust correlated negatively (and strongly) with cingulate, left thalamic, left frontal, and left temporal rCBF. Stereotyped ideas as a negative symptom correlated negatively (and strongly) with left frontal, cingulate, left temporal, and left parietal rCBF. After neuroleptic treatment (and reduction of positive symptoms), only negative symptoms correlated exclusively with bifrontal, bitemporal, cingulate, basal ganglia, and thalamic hypoperfusion. INTERPRETATION: Different positive symptoms are accompanied by different rCBF values--some related to hyperperfusion, others to hypoperfusion. This finding may help to explain observed inconsistencies of perfusion patterns in drug-na?ve schizophrenics.     

Relations between neuropsychological findings and lateral asymmetries of cerebral blood flow measured by SPECT in dementia of Alzheimer type

We studied 16 right-handed patients clinically diagnosed as dementia of Alzheimer type (6 men, 10 women; aged 63-85, mean 72.8 years). The average duration of symptoms was 2.7 years. Dementia ranged from mild to moderately severe. None had clinical or laboratory evidence of cerebrovascular disease (Hachinski ischemic scores for all patients were 4 or below 4). All received the Wechsler Adult Intelligence Scale (WAIS), Mini-mental State Test (MMS) and Western Aphasia Battery (WAB, First Japanese edition, 1986). Regional cerebral blood flow (rCBF) was evaluated by single photon emission CT (SPECT) with 123I-N-isopropyl-p-iodoamphetamine (123I-IMP), using the Matsuda's quantitative method (Am J Physiol Imag 1: 186, 1986). Regional tracer uptake was measured in regions of interests (ROIs) over right and left frontal, temporal, parietal and occipital cortical regions; basal ganglia; and cerebellar hemispheres. The subjects were divided into three groups on the basis of lateral asymmetries in the temporal and parietal cortexes of rCBF (left < right, n = 5; right < left, n = 3; left = right, n = 8). We decided that lateral asymmetry was present when rCBF for each ROI between left and right sides differs by more than 10%. General score (MMS, T-IQ) was not correlated with asymmetry of cerebral blood flow. Verbal IQ in patients with predominant hypoperfusion of left temporal and parietal lobe was significantly lower than other group, while performance IQ and WAB constructive scores were lower in those with right hemispheric hypoperfusion (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Functional anatomy of pointing and grasping in humans

The functional anatomy of reaching and grasping simple objects was determined in nine healthy subjects with positron emission tomography imaging of regional cerebral blood flow (rCBF). In a prehension (grasping) task, subjects reached and grasped illuminated cylindrical objects with their right hand. In a pointing task, subjects reached and pointed over the same targets. In a control condition subjects looked at the targets. Both movement tasks increased activity in a distributed set of cortical and subcortical sites: contralateral motor, premotor, ventral supplementary motor area (SMA), cingulate, superior parietal, and dorsal occipital cortex. Cortical areas including cuneate and dorsal occipital cortex were more extensively activated than ventral occipital or temporal pathways. The left parietal operculum (putative SII) was recruited during grasping but not pointing. Blood flow changes were individually localized with respect to local cortical anatomy using sulcal landmarks. Consistent anatomic landmarks from MRI scans could be identified to locate sensorimotor, ventral SMA, and SII blood flow increases. The time required to complete individual movements and the amount of movement made during imaging correlated positively with the magnitude of rCBF increases during grasping in the contralateral inferior sensorimotor, cingulate, and ipsilateral inferior temporal cortex, and bilateral anterior cerebellum. This functional-anatomic study defines a cortical system for "pragmatic' manipulation of simple neutral objects.     

Regional cerebral blood flow during the Wisconsin Card Sorting Test in normal subjects studied by xenon-133 dynamic SPECT: comparison of absolute values, percent distribution values, and covariance analysis

We studied regional cerebral blood flow (rCBF) by xenon-133 dynamic single photon emission computed tomography (SPECT) in 17 normal volunteers who were performing the Wisconsin Card Sorting Test (WCST), a task that is particularly sensitive to disturbance of the prefrontal cortex, and a simple matching-to-sample task (BAR) as a sensorimotor control. Three methods for statistical analysis of regional "subtraction" data were used: absolute rCBF values, percent distribution values, and means adjusted for global CBF changes (covariance analysis). The absolute values had high variance, due to the combination of interindividual differences in global flow and intra-individual variation, and showed no statistically significant regional changes. This variation was greatly reduced by percent values and covariance analysis, which had quite similar outcomes. With both methods, significant increases of rCBF during the WCST as compared with the BAR were seen in the right anterior dorsolateral prefrontal and left occipital cortices, and reduction of rCBF in the left pararolandic region. Moreover, significant correlations with performance were found in the medial regions of the frontal lobes, with opposite trends for the right and left hemisphere. The posterior dorsolateral prefrontal region showed a negative correlation with sensory-motor frequency, an index related to the task's difficulty. These results are consistent with previous findings using other rCBF techniques and confirm the statistical advantage of normalization and covariance methods, which yield practically identical results, at least in this analysis based on regions of interest.     

Decrease of medullary catecholaminergic neurons in multiple system atrophy and Parkinson's disease and their preservation in amyotrophic lateral sclerosis

We investigated the number of tyrosine hydroxylase (TH)-immunoreactive neurons in the C1 and A2 regions of the medulla, the sites of the baroreflex arc, in 7 patients with multiple system atrophy (MSA), 8 with Parkinson's disease (PD), 9 with amyotrophic lateral sclerosis (ALS), and 12 age-matched normal subjects to analyze the relationship between cardiovascular dysfunction and medullary catecholaminergic neurons. Orthostatic hypotension (OH) was marked in all the MSA patients and moderate in three PD patients. Three of the five ALS patients who had been on respirators showed lability of blood pressure; paroxysmal hypertension and nocturnal hypotension without compensatory tachycardia. All the MSA patients showed extremely marked decrease of TH-immunoreactive neurons in both the C1 and A2 regions. In the patients with Parkinson's disease, numerous TH-immunoreactive neurons contained Lewy bodies that were immunostained by antibody to TH. TH-immunoreactive neurons were decreased very markedly in the A2 regions of two patients with OH, and three patients without OH showed fairly marked decreases in the C1 or A2 region. In contrast, the number of TH-immunoreactive neurons in ALS was the same as in normal subjects. In MSA and some PD patients, orthostatic hypotension may partly be due to the involvement of the medullary catecholaminergic neurons. The lability of blood pressure in ALS probably is not related to the medullary catecholaminergic neurons.     

Neuropsychological dysfunction in depression: the relationship to regional cerebral blood flow

The relationship between neuropsychological test performance and regional cerebral blood flow (rCBF) was examined in 29 patients meeting Research Diagnostic Criteria (RDC) for major depression. Following a comprehensive neuropsychological assessment two subsets of tests, comprising tests that discriminated between patients and controls or between patients with varying degrees of global cognitive impairment, were selected. These subtests were entered into a principal components analysis (PCA) which generated a two-factor solution, accounting for 50% of the overall variance in test scores. Individual patient loadings on each of these factors were subsequently correlated with regional cerebral blood flow (rCBF), as measured by positron emission tomography (PET). Both factors demonstrated significant correlations with rCBF in the medial prefrontal cortex and frontal polar cortex while for each factor there were also unique patterns of correlations with posterior brain regions. The findings provide additional evidence that neuropsychological deficits in depression are associated with abnormalities in regional brain function and in particular with the function of the medial prefrontal cortex.     

Neural activation of the brain with hemodynamic insufficiency

Little is known about how ischemia affects hemodynamic responses to neural activation in the brain. We compare the effects of a motor activation task and a cerebral vasodilating agent, acetazolamide (ACZ), on regional cerebral blood flow (rCBF) in primary sensorimotor cortex (PSM) in six patients with major cerebral artery steno-occlusive lesions without paresis of the upper extremities. Quantitative rCBF was measured in all patients using H2(15)O autoradiographic method and positron emission tomography. The CBF was determined at rest, during a bimanual motor activation task, and 10 minutes after ACZ administration. With bimanual motor activation, rCBF increased significantly in both PSM compared with at rest (P < 0.01 on lesion side, and P < 0.02 on contralateral side). However, rCBF did not increase after ACZ injection in the PSM on the lesion side, whereas rCBF increased significantly in the contralateral PSM after ACZ injection compared with the level at rest. This result suggests that despite a decreased hemodynamic reserve, there is a nearly normal flow response to neural activation, indicating that the mechanism of vasodilation responsible for perfusion change is different for acetazolamide and neural activation. The relations among neural activation, hemodynamic status, and cerebral metabolism in the ischemic stroke patients are discussed.     

Effect of rebamipide, a novel antiulcer agent, on Helicobacter pylori adhesion to gastric epithelial cells

We examined regional cerebral blood flow (rCBF) during a long-term recognition memory task for words in schizophrenic patients and in healthy subjects using positron emission tomography (PET). The task was designed so that performance scores were similar in the patient and control subjects. This memory retrieval task did not increase rCBF in the patients' prefrontal cortex, precuneus and cerebellum as much as it did in the control group. These results point to a dysfunctional corticocerebellar circuit leading to poorly coordinated mental activity ('cognitive dysmetria'), which could explain the broad range of schizophrenic symptoms. In addition, other brain areas were more activated by the task in the patient group than in the control group and may form a compensatory network performing the memory retrieval task by assisting or replacing the dysfunctional cortico-cerebellar circuit.     

Superantigen-induced stromelysin production from rheumatoid synovial cells

Positron emission topographic studies on local cerebral glucose metabolism in Parkinson's disease (PD) including our own data were reviewed. In our 18F-FDG PET studies, local or global metabolic change was not found in 9 patients with non-demented PD, with respect to 5 normal controls. Moreover, there was not an apparent difference between severe PD group (Hoehn-Yahr III-IV) and mild PD group (Hoehn-Yahr I-II). In other PD patients with dementia or autonomic failure, parietal dominant hypometabolism was found likely to those of Alzheimer disease, but lenticular nucleus was well preserved. Furthermore 18F-FDG PET findings of atypical parkinsonian syndromes, such as SND and PSP were reviewed. They showed relative hypometabolism in the basal ganglia in PET images. PET study with FDG provides a clue to differential diagnosis of parkinsonian patients.