Single-subject statistical mapping of acute brain hypoxia in the rat following middle cerebral artery occlusion: a microPET study.

No study so far has attempted to map the 3D topography of brain hypoxia in the individual rat in vivo following middle cerebral artery occlusion (MCAo). In a previous microPET study, we reported that (18)F-fluoromisonidazole ((18)F-MISO) trapping in the brain after MCAo was specific for the hypoxic viable tissue. Here, we used (18)F-MISO microPET to map the 3D topography of brain hypoxia in the acute stage of permanent distal MCAo in individual spontaneously hypertensive rats. Normal rats were also studied. (18)F-MISO was intravenously injected approximately 1 h after clip placement and PET data were acquired for 2 hours. Animals were sacrificed and the brains harvested 48 h later for infarct mapping using standard histopathology. As expected, continuous (18)F-MISO trapping was found over the affected relative to unaffected and control MCA cortex. Using single-subject voxel-based statistical mapping, tracer accumulation 90-120 min after injection was consistently significantly higher in the anterior MCA cortex (proximal relative to clip site) and gradually decreased towards posterior areas, a pattern consistent with the classic penumbra concept. The data also suggested that (i) a portion of the significant (18)F-MISO trapping area may sit outside the contours of the final infarct despite the permanent MCAo, suggesting that (18)F-MISO may be a marker not only of severe (penumbral) but also of milder (oligemic) hypoxia, and (ii) small portions of the final infarct may not exhibit early tracer trapping, suggesting that by the time the tracer was administered this tissue had already progressed to irreversible damage. This study shows the feasibility of single-subject mapping of brain hypoxia following MCAo in the rat, which has potential applications in pathophysiological investigations.

Uncoupling of flow and metabolism by chloral hydrate: a rat in-vivo autoradiographic study.

General anesthesia is commonly used in experiments; however, its effects on cerebral circulation remain unknown. We measured cerebral blood flow using N-isopropyl[methyl 1,3-14C] p-iodoamphetamine (14C-IMP) and glucose utilization using 2-[1-14C] deoxy-D-glucose during general anesthesia with pentobarbital and chloral hydrate as well as conscious controls using rats and in-vivo autoradiography. Although a substantial reduction in 14C-IMP uptake was seen in the pentobarbital group, there was a significant increase in the chloral hydrate group. The ratio of cerebral blood flow against cerebral glucose utilization was 0.58 over all regions in the pentobarbital group, similar to the value for the controls, whereas this value was significantly high (over 1.5) in the chloral hydrate group. This decoupling effect should be considered when extrapolating experimental study data to normal physiology.

Statistical parametric analysis of cerebral blood flow in vascular dementia with small-vessel disease using Tc-HMPAO SPECT.

BACKGROUND: Subcortical ischemic vascular dementia (SVD) caused by small-artery disease is a major cause of dementia. It still remains unclear, however, whether SVD may present with localized regional cerebral blood flow (rCBF) changes. We aimed to clarify the local rCBF changes associated with dementia in patients with early-stage SVD. METHODS: The subjects consisted of 15 patients with early-stage SVD [Mini Mental State Examination (MMSE) score: 20 +/- 3.5] without apparent brain atrophy (SVD group), 11 patients without dementia with white matter lesions (non-dementia-WML group) and 16 age-matched controls. All the subjects were right-handed and underwent brain perfusion single photon emission computed tomography (SPECT), magnetic resonance imaging and cognitive function testing. Statistical analysis of the differences in the SPECT rCBF was performed by SPM2. The degree of severity of the WMLs was evaluated based on the Scheltens rating scale. RESULTS: The results of SPM analysis revealed that the rCBF in the SVD group was significantly decreased in the pulvinar nuclei of the thalamus of both sides as compared with that in the controls, and in the left pulvinar nucleus as compared with that in the non-dementia-WML group. On the other hand, SPM analysis revealed no significant reduction in rCBF in the non-dementia-WML group as compared with that in the controls. The WMLs in the left parietal region were severer in the SVD group than in the non-dementia-WML group. CONCLUSIONS: In patients with early-stage SVD without apparent brain atrophy, significant rCBF reduction in the bilateral pulvinar nuclei as compared with that in normal controls, and in the left pulvinar nucleus as compared with that in patients without dementia with WMLs was found.

Applications of nitroimidazole in vivo hypoxia imaging in ischemic stroke.

BACKGROUND AND PURPOSE: Nitroimidazole imaging is a promising contender for noninvasive in vivo mapping of brain hypoxia after stroke. However, there is a dearth of knowledge about the behavior of these compounds in the various pathophysiologic situations encountered in ischemic stroke. In this article we report the findings from a systematic review of the literature on the use of the nitroimidazoles to map hypoxia after stroke. SUMMARY OF REVIEW: We describe the characteristics of nitroimidazoles as imaging tracers, their pharmacology, and results of both animal and clinical studies during and after focal cerebral ischemia. Findings in brain tumors are also presented to the extent that they enlighten results in stroke. Early results from application of kinetic modeling for quantitative measurement of tracer binding are briefly discussed. CONCLUSIONS: Based on this literature review, nitroimidazole hypoxia imaging agents are of considerable interest in stroke because they appear, both in animal models and in humans, to specifically detect the severely hypoxic viable tissue, but not the reperfused nor the necrotic tissue. To fully realize this potential in stroke, however, formal validation by concurrent measurement of tissue oxygen tension, together with development of novel ligands with faster distribution kinetics, faster clearance from normal tissue, and well-defined trapping mechanisms, are important goals for future investigations.

How reliable is perfusion MR in acute stroke? Validation and determination of the penumbra threshold against quantitative PET.

BACKGROUND AND PURPOSE: Perfusion magnetic resonance imaging (pMR) is increasingly used in acute stroke, but its physiologic significance is still debated. A reasonably good correlation between pMR and positron emission tomography (PET) has been reported in normal subjects and chronic cerebrovascular disease, but corresponding validation in acute stroke is still lacking. METHODS: We compared the cerebral blood flow (CBF), cerebral blood volume, and mean transit time (MTT) maps generated by pMR (deconvolution method) and PET ((15)O steady-state method) in 5 patients studied back-to-back with the 2 modalities at a mean of 16 hours (range, 7 to 21 hours) after stroke onset. We also determined the penumbra thresholds for pMR-derived MTT, time to peak (TTP), and Tmax against the previously validated probabilistic PET penumbra thresholds. RESULTS: In all patients, the PET and pMR relative distribution images were remarkably similar, especially for CBF and MTT. Within-patient correlations between pMR and PET were strong for absolute CBF (average r(2)=0.45) and good for MTT (r(2)=0.35) but less robust for cerebral blood volume (r(2)=0.24). However, pMR overestimated absolute CBF and underestimated MTT, with substantial variability in individual slopes. Removing individual differences by normalization to the mean resulted in much stronger between-patient correlations. Penumbra thresholds of approximately 6, 4.8, and 5.5 seconds were obtained for MTT delay, TTP delay, and Tmax, respectively. CONCLUSIONS: Although derived from a small sample studied relatively late after stroke onset, our data show that pMR tends to overestimate absolute CBF and underestimate MTT, but the relative distribution of the perfusion variables was remarkably similar between pMR and PET. pMR appears sufficiently reliable for clinical purposes and affords reliable detection of the penumbra from normalized time-based thresholds.

Differential brain processing of audiovisual sexual stimuli in men: comparative positron emission tomography study of the initiation and maintenance of penile erection during sexual arousal.

The human male psychosexual cycle consists of four phases: excitation, plateau, orgasm, and resolution. Identification of the specific neural substrates of each phase may provide information regarding the brain's pathophysiology of sexual dysfunction. We previously analyzed regional cerebral blood flow (rCBF) with H(2)15O-positron emission tomography (PET) during the excitation phase (initiation of penile erection) induced by audiovisual sexual stimuli (AVSS) and identified activation of the cerebellar vermis, the bilateral extrastriate cortex, and right orbitofrontal cortex, suggesting a role of cognition/emotion in the excitement phase. In the present study, we analyzed rCBF of the same six healthy volunteers during the plateau phase (maintenance of penile erection) induced by AVSS and compared the results with those of the excitation phase. Penile rigidity was monitored in real time with RigiScan Plus during PET scanning. Images were analyzed by statistical parametric mapping (SPM) software, and rCBF in the amygdala, hypothalamus, anterior cingulate, and insula was measured. During the plateau phase, primary subcortical activation was noted in the right ventral putamen, indicating motivational factors in the sexual response via the limbic reward circuit. A significant increase in rCBF in the left hypothalamus was also observed during the plateau phase. The right anterior cingulate and left insula were specifically activated during the excitation phase but not during the plateau phase. These results indicate a significant role of the ventral putamen and the hypothalamus in the plateau phase and confirm that paralimbic and limbic components of the human brain differentially coordinate the sexual response in a psychosexual phase-dependent manner.

Deterioration of hemiparesis after recurrent stroke in the unaffected hemisphere: Three further cases with possible interpretation.

BACKGROUND: The concept of neural reorganization after brain damage is already well established, and many previous studies have successfully reported the translocation of the neural activation in the motor-related cortices during motor tasks using functional imaging modalities. Several primate and human studies have suggested the formation of newly reorganized tracts in the ipsilesional or contralesional hemisphere, but the mechanism for the formation of these tracts is still largely unknown. METHODS: Three acute stroke patients who presented with abrupt deterioration of their right-sided hemiparesis due to the infarcts following a recurrent stroke in the originally unaffected hemisphere were studied using magnetic resonance imaging (MRI), MR angiography and single-photon emission CT. The relationship between the neurological symptom on admission and the precise location of the new infarct was carefully investigated from the perspective of reorganization. RESULTS: Diffusion-weighted MRI showed a new subcortical infarct in the right hemisphere contralateral to the initial stroke in all patients. These new lesions involved the thalamus, globus pallidus or corona radiata, sparing the area of the internal capsule. T2-weighed MRI on admission showed an old infarct in the left middle cerebral artery territory, which had caused the original right-sided hemiparesis. CONCLUSION: It is proposed that the 'extrapyramidal' motor pathway in the unaffected hemisphere is associated with poststroke neural reorganization.

Imaging of brain hypoxia in permanent and temporary middle cerebral artery occlusion in the rat using 18F-fluoromisonidazole and positron emission tomography: a pilot study.

In acute stroke, the target of therapy is the severely hypoxic but salvageable tissue. Previous human studies using 18F-fluoromisonidazole and positron emission tomography (18F-FMISO PET) have shown high tracer retention indicative of tissue hypoxia, which had normalized at repeat scan >48 h later. In the only validation study of 18F-FMISO, using ex vivo autoradiography in thread middle cerebral artery occluded (MCAo) rats, there was unexpected high uptake as late as 22 h after reperfusion, raising questions about the use of 18F-FMISO as a hypoxia tracer. Here we report a pilot study of 18F-FMISO PET in experimental stroke. Spontaneous hypertensive rats were subjected to distal clip MCAo. Three-hour dynamic PET was performed in 7 rats: 3 normals, 1 with permanent MCAo (two sessions: 30 mins and 48 h after clip), and 3 with temporary MCAo (45 mins, n=1; 120 mins, n=2; scanning started 30 mins after clip removal). Experiments were terminated by perfusion-fixation for standard histopathology. Late tracer retention was assessed by both compartmental modelling and simple side-to-side ratios. In the initial PET session of the permanent MCAo rat, striking trapping of 18F-FMISO was observed in the affected cortex, which had normalized 48 h later; histopathology revealed pannecrosis. In contrast, there was no demonstrable tracer retention in either temporary MCAo models, and histopathology showed ischemic changes only. These results document elevated 18F-FMISO uptake in the stroke area only in the early phase of MCAo, but not after early reperfusion nor when tissue necrosis has developed. These findings strongly support the validity of 18F-FMISO as a marker of viable hypoxic tissue/penumbra after stroke.

Effect of linearization correction on statistical parametric mapping (SPM): a 99mTc-HMPAO brain perfusion SPECT study in mild Alzheimer's disease.

OBJECTIVE: Statistical parametric mapping (SPM) was employed to investigate the regional decline in cerebral blood flow (rCBF) as measured by 99mTc-hexamethyl propylene amine oxime (HMPAO) single photon emission computed tomography (SPECT) in mild Alzheimer's disease (AD). However, the role of the post reconstruction image processing on the interpretation of SPM, which detects rCBF pattern, has not been precisely studied. We performed 99mTc-HMPAO SPECT in mild AD patients and analyzed the effect of linearization correction for washout of the tracer on the detectability of abnormal perfusion. METHODS: Eleven mild AD (NINCDS-ADRDA, male/female, 5/6; mean+/-SD age, 70.6+/-6.2 years; mean+/-SD mini-mental state examination score, 23.9+/-3.41; clinical dementia rating score, 1) and eleven normal control subjects (male/female, 4/7; mean+/-SD age, 66.8+/-8.4 years) were enrolled in this study. 99mTc-HMPAO SPECT was performed with a four-head rotating gamma camera. We employed linearization uncorrected (LU) and linearization corrected (LC) images for the patients and controls. The pattern of hypoperfusion in mild AD on LU and LC images was detected by SPM99 applying the same image standardization and analytical parameters. A statistical inter image-group analysis (LU vs. LC) was also performed. RESULTS: Clear differences were observed between the interpretation of SPM with LU and LC images. Significant hypoperfusion in mild AD was found on the LU images in the left posterior cingulate gyrus, right precuneus, left hippocampus, left uncus, and left superior temporal gyrus (cluster level, corrected p < 0.005). With the LC images, significant hypoperfusion in AD was found only in the bilateral posterior cingulate gyrus and left precuneus (cluster level, corrected p < 0.005). A pattern of greater rCBF distribution at the high flow cortices and low flow cortices was observed on LC and LU images, respectively, in the case of both controls and mild AD patients. CONCLUSION: Hippocampal hypoperfusion could be detected by means of SPM in the LU images but not in the LC images. The results of SPM may vary in 99mTc-HMPAO SPECT with or without linearization correction, which should be carefully evaluated when interpreting the pattern of rCBF changes in mild Alzheimer's disease.

Brain processing of audiovisual sexual stimuli inducing penile erection: a positron emission tomography study.

PURPOSE: Penile erection is dependent on commands from the central nervous system. Although basic studies of animals and neuroimaging studies of humans have been conducted to identify key brain regions associated with sexual arousal, to our knowledge no reliable studies of the first excitation phase of sexual arousal leading to penile erection have been reported. MATERIALS AND METHODS: We used H(2)(15)O-positron emission tomography to analyze regional cerebral blood flow just before penile erection in heterosexual volunteers. The subjects viewed 3 different types of audiovisual materials-sexually explicit clips, nonsexual neutral clips and dynamic mosaic image control clips-presented in random order, and penile rigidity was monitored in real time with a RigiScan(R) Plus device. Positron emission tomography scanning was initiated simultaneously when each clip was started, and images obtained when the subjects showed appropriate penile response were analyzed and compared. RESULTS: The advanced audiovisual cortices and cerebellar vermis in the right hemisphere were activated for sexually explicit-dynamic mosaic image control clip contrast, and only the right middle frontal gyrus was activated for sexually explicit- nonsexual neutral clip contrast. Several primary visual and audio regions were activated for dynamic mosaic image control-sexually explicit clip contrast and nonsexual neutral-sexually explicit clip contrast. CONCLUSIONS: We speculate that advanced audiovisual activity with imagination, not primary visual and audio activity, occurs when men experience sexual arousal inducing penile erection. Furthermore, the cerebellar vermis may be a key region for induction of penile erection in humans.

Diastolic blood pressure influences cerebrovascular reactivity measured by means of 123I-iodoamphetamine brain single photon emission computed tomography in medically treated patients with occlusive carotid or middle cerebral artery disease.

OBJECTIVE: Impaired cerebrovascular reactivity (CVR) to vasodilating agents is a predictor of the onset and prognosis of ischemic stroke. It is realized that the CVR improves or worsens when measured periodically during the clinical course in medically treated patients with occlusive cerebrovascular disease. In these patients, we investigated the possible relationship between the interval change in CVR and that in systemic blood pressure (BP). METHODS: Forty-two patients (14 females and 28 males, mean age +/- SD: 65.3 +/- 8.8 years) with severe stenosis or occlusion of the common carotid, internal carotid, or middle cerebral arteries repeatedly underwent single photon emission computed tomography (SPECT) studies using 123I-iodoamphetamine to measure cerebral blood flow (CBF) distribution and CVR at a more-than-6-month interval (mean +/- SD: 18.5 +/- 8.8 months). The CVR was separately estimated in cerebral hemispheres ipsilateral and contralateral to the most severe vascular lesion as the % increase in CBF after acetazolamide loading to CBF at rest. Systemic BP was measured four times at enrollment and the follow-up SPECT studies during resting and acetazolamide loading. Average BP at each SPECT study was an average of BP measurements during resting and acetazolamide loading. Interval changes in CVR were correlated with those in average systolic BP, average diastolic BP, and average mean arterial BP. RESULTS: The interval changes in CVR were significantly correlated with those in average diastolic BP in the ipsilateral hemisphere (y = 0.71x + 1.43, r2 = 0.11, p < 0.05) and in the contralateral hemisphere (y = 0.88x - 0.46, r2 = 0.16, p < 0.05) but not with those in average systolic BP or average mean arterial BP. CONCLUSIONS: In medically treated patients with steno-occlusive carotid artery or middle cerebral artery lesions, the interval change in CVR to acetazolamide by means of 123I-IMP SPECT was influenced by the diastolic BP at the SPECT studies. Monitoring diastolic BP is important to evaluate interval change in CVR.

Neural mechanism of residual inhibition of tinnitus in cochlear implant users.

Residual inhibition is a transient suppression of tinnitus after auditory stimulation has stopped. We used positron emission tomography to study brain regions underlying residual inhibition in three tinnitus patients with cochlear implants and six normal hearing controls. Regional cerebral blood flow was measured and compared under two conditions: with tinnitus and during the residual inhibition of tinnitus. The right anterior middle and superior temporal gyri (Brodmann areas 21 and 38) were activated during residual inhibition, while the right cerebellum was activated during tinnitus perception in the tinnitus patients. No significant activation was observed in the normal controls. Our results suggest that tinnitus and residual inhibition are related to cortical networks of auditory higher-order processing, memory and attention.

Hemodynamic influences of losartan on the brain in hypertensive patients.

The effects of angiotensin II receptor blockers on cerebral hemodynamics in humans have not been well elucidated. The present study evaluated the effects of losartan on cerebral hemodynamics in hypertensive patients using positron emission tomography. Ten patients with essential hypertension (mean age, 60.8 years) were examined. In each patient, regional cerebral blood flow was measured by [O-15] labeled water positron emission tomography before and after the oral administration of losartan for 8 to 23 weeks. In 8 patients, the baseline regional cerebral blood flow measurement was followed by 1,000 mg of acetazolamide challenge to measure the cerebral perfusion reserve. Systemic blood pressures before and after treatment were 153.8 +/- 10.8/96.0 +/- 6.5 mmHg (systolic mean +/- SD/diastolic mean +/- SD) and 133.4 +/- 11.2/83.6 +/- 6.5 mmHg, respectively; this difference was significant. The baseline global cerebral blood flow values before and after treatment were 38.4 +/- 6.9 ml/min/100 g and 38.2 +/- 8.2 ml/min/100 g, respectively; this difference was not significant. The results of the global cerebral blood flow response to the acetazolamide challenges were not statistically different before and after treatment. A regional analysis showed no statistical difference in regional cerebral blood flow or cerebral perfusion reserve throughout the brain before and after treatment. Losartan's effect on reducing the blood pressure did not affect either the baseline regional cerebral blood flow or the cerebral perfusion reserve in patients with mild to moderate hypertension. The inclusion of losartan in anti-hypertensive regimens could be advantageous for cerebral circulation in patients with essential hypertension.

The effect of tapping finger and mode differences on cortical and subcortical activities: a PET study.

Using positron emission tomography (PET), the brain regions recruited for the tapping movement by different fingers and different tapping modes were investigated in ten young healthy volunteers without specific finger training. Auditory-paced (2 Hz) tapping movements were performed by the index (I) or ring (R) finger alone (single-finger tapping) and by the alternate use of the I and middle (M) fingers or the R and little (L) fingers (double-finger tapping). Each subject also provided subjective rankings of perceived task difficulty, as well as muscular fatigue, among the tapping tasks. The activated areas of the brain during tapping by the R finger were more extensive in the frontal and temporal areas, as well as the cerebellum, than during tapping by the I finger. A similar result was revealed for the comparison of the RL and IM finger pairs. The perceived task difficulty, as well as muscular fatigue, was also higher for the R finger or RL finger pair than the I finger or IM finger pair. These results indicate that movement of individual fingers or finger pairs with different levels of task difficulty is represented differently in the structures of cortical and subcortical systems. A comparison of the single- and double-finger modes revealed that in addition to the brain areas activated during single-finger mode, the bilateral dorsal premotor and left primary motor/sensory areas and the right anterior cerebellum were also activated during the double-finger mode. These additional areas could be essential structures for the execution and motor sequence operation of the two fingers.

Clinical significance of cerebrovascular reserve in acetazolamide challenge -comparison with acetazolamide challenge H2O-PET and Gas-PET.

OBJECTIVE: The response of cerebral blood flow (CBF) to acetazolamide (ACZ) challenge is frequently determined in clinical settings to evaluate cerebrovascular reserve (CVR). A reduced CVR can indicate patients with occlusive cerebrovascular disease and compromised hemodynamics who may be at increased risk of cerebral ischemia. However, how precisely ACZ reflects cerebral hemodynamic impairment remains obscure. The present study aims to clarify the pathological significance of CVR in patients with occluded carotid arteries. METHODS: We recruited seventeen patients with occlusive lesions in the internal carotid artery (ICA) or middle cerebral artery (MCA). We assessed these patients in terms of resting cerebral blood flow (CBF) and the CVR response to ACZ challenge using H20 positron emission tomography (PET). In addition, we evaluated hemodynamic parameters including oxygen extraction fraction (OEF) using Gas-PET. RESULTS: We identified a significant negative correlation between the CVR and OEF or the cerebral blood volume (CBV)/CBF ratio, as a potential index of cerebral perfusion pressure. Although the CVR values were reduced in all regions with elevated OEF (Stage II), these values were highly variable regardless of the CBV/CBF ratios. The cut-off value of CVR alone could not detect Stage II, but when combined with resting CBF, misery perfusion accompanied by increased OEF was detected with high sensitivity (6/7) and specificity (61/62). CONCLUSION: CVR could be applied as an index reflecting both autoregulatory capacity and OEF. The present study also supported the notion that SPECT with ACZ challenge can be clinically applied to detect misery perfusion.

Spectral analysis of 99mTc-HMPAO for estimating cerebral blood flow: a comparison with H2(15)O PET.

Cerebral blood flow (CBF) can be quantified non-invasively using the brain perfusion index (BPI), which is determined using radionuclide angiographic data obtained through the use of technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO). The BPI is generally calculated using graphical analysis (GA). In this study, BPI was measured using spectral analysis (SA), and the usefulness of SA was compared with that of GA. Thirteen patients with various brain diseases and four healthy male volunteers were examined using radionuclide angiography with 99mTc-HMPAO. The BPI was measured for each subject using both SA and GA. In the four healthy volunteers, the BPI was examined at rest and after the intravenous administration of 1 g of acetazolamide (ACZ). An H2(15)O PET examination was also performed in the 13 patients; the BPIS and BPIG values were compared with the CBF measurements obtained using H2(15)O PET (CBFPET). The BPI values obtained by SA (BPIS) (x) and by GA (BPIG) (y) were correlated (y = 0.568x + 0.055, r = 0.901) in the 13 patients and four healthy volunteers at rest, although the BPIG values were underestimated by 36.1 +/- 7.5% (mean +/- SD) compared with the BPIS values. The degree of underestimation tended to increase with increasing BPIS values. The increase in the BPIS was 32.1 +/- 8.0% after the intravenous administration of ACZ, while the increase in BPIG was only 8.1 +/- 2.8%. This discrepancy was considered to be the result of the BPIG values being affected by the first-pass extraction fraction of the tracer. Although both BPIS and BPIG values were significantly correlated with the CBFPET values, the correlation coefficient for BPIS was higher than that for BPIG (BPIS: r = 0.881; BPIG: r = 0.832). These results suggest that SA produces a more reliable BPI for quantifying CBF using 99mTc-HMPAO than the conventional method using GA. The SA method should be especially useful for activation studies involving pharmacological intervention and/or clinical cases with an increased CBF.

Cerebral hemodynamics and metabolism in adult moyamoya disease: comparison of angiographic collateral circulation.

PURPOSE: The extent of the hemodynamic and metabolic impairments in adult patients with moyamoya disease is still controversial. The aim of the present study was to evaluate the hemodynamic and metabolic status in relation to the development of basal moyamoya vessels (BMVs). METHODS: The cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF), and cerebral blood volume (CBV) were measured using PET in ten patients with ischemic adult moyamoya disease (mean age, 36.6 years) and six age-matched normal controls (mean age, 33.3 years). The cerebrovascular reserve (CVR) after acetazolamide (ACZ) loading was also estimated using iodine-123 N-isopropyl-p-iodo amphetamine single photon emission computed tomography (123I-IMP SPECT). RESULTS: Based on the angiographic findings, eleven cerebral hemispheres with well-developed BMV (extensive BMV hemispheres) and nine cerebral hemispheres with diminished BMV (diminished BMV hemispheres) were identified. The main routes of collateral circulation in extensive BMV hemispheres were BMVs and leptomeningeal anastomoses. On the other hand, in diminished BMV hemispheres, transdural anastomosis was predominant, and leptomeningeal anastomoses were less developed. In cortices distal to the occluded internal carotid artery, the extensive BMV hemispheres exhibited a significantly lower CBF, CMRO2, CBF/CBV, and CVR (p < 0.05) and a significantly higher CBV and OEF than in diminished BMV hemispheres and controls (p < 0.05). Except for the CBF in the white matter, the mean hemodynamic and metabolic parameters of the diminished BMV hemispheres were not significantly different from those of the controls. CONCLUSION: The extensive development of basal moyamoya vessels is a sign of severe hemodynamic impairment in adult patients with ischemic moyamoya disease. The results may not apply to adults with hemorrhagic onset.

Cortical processing of tactile language in a postlingually deaf-blind subject.

We compared neural activation detected by magnetoencephalography (MEG) during tactile presentation of words and non-words in a postlingually deaf-blind subject and six normal volunteers. The left postcentral gyrus, bilateral inferior frontal gyri, left posterior temporal lobe, right anterior temporal lobe, bilateral middle occipital gyri were activated when tactile words were presented to the right hand of the deaf-blind subject. This set of activated regions was not observed in the normal volunteers, although activation of several combinations of these regions was detected. Positron emission tomography confirmed the location of the MEG-activated areas in the deaf-blind subject. Our results demonstrated that the deaf-blind subject is heavily involved in interpreting tactile language by enhancing cortical activation of cognitive and semantic processing.

Extraction of arterial input function for measurement of brain perfusion index with 99mTc compounds using fuzzy clustering.

Cerebral blood flow (CBF) can be quantified non-invasively using the brain perfusion index (BPI) determined from radionuclide angiographic data generated with 99mTc-hexamethylpropylene amine oxime (99mTc-HMPAO). When measuring the BPI, manual drawing of regions of interest (ROIs) (manual ROI method) for the extraction of the arterial input function (AIF) can lead to serious individual differences. The purpose of this study was to apply the fuzzy c-means (FCM) clustering method to determine AIF, and to investigate its usefulness in comparison with the manual ROI method. Radionuclide angiography was performed using a bolus injection of about 555 MBq of 99mTc-HMPAO, followed by sequential imaging (1 sec/frame x 120 s) using a solid-state gamma camera, and the BPI values were calculated using spectral analysis. To investigate the dependence of BPI on the ROI size, we drew five ROIs with different sizes over the aortic arch, and calculated the BPI using the manual ROI method [BPI(manual)] and the FCM clustering method [BPI(FCM)]. Furthermore, we asked 10 individuals to draw ROIs to investigate the inter-operator variability of the two methods. The mean and standard deviation (SD) of BPI(manual) increased with increasing ROI size, whereas the mean of BPI(FCM) was almost constant regardless of the ROI size; the SD of BPI(FCM) was smaller than that of BPI(manual). The inter-operator variability of the FCM clustering method was smaller than that of the manual ROI method. These results suggest that the FCM clustering method appears to be useful for the measurement of BPI, because it allows a reliable and objective determination of AIF.

Cerebral and cerebellar activation in power and precision grip movements: an H2 15O positron emission tomography study.

SUMMARY: Most human manual grip movements can be divided into power gripping and precision gripping, but central neural control during these tasks remains unclear. We investigated activation of the whole brain to analyze how simple hand movements are performed. The cerebral blood flow of seven healthy right-handed volunteers was measured by H2 15O positron emission tomography during right grip tasks without gripping a target object. Auditory-cued, repetitive power grips (i.e., fist making) and repetitive precision grips (i.e., opposition of the tip of the index finger and the tip of the thumb) were performed at 1.26 Hz. The areas activated during both tasks were the left primary sensorimotor cortex, caudal portion of the dorsal premotor, caudal portion of the supplementary motor area, cingulate motor area, and the right spinocerebellum and intermediate region of the cerebrocerebellum in comparison with the rest state. The analysis of power grip-precision grip tasks showed the activated peaks in the upper portion of the left sensorimotor area and right cerebellar vermis, but these areas were activated in both the tasks [(power grip-rest) and (precision grip-rest)] with uncorrected P < 0.001 as the statistical criterion. With P < 0.05 corrected as the statistical criterion, the results showed no significant activated peaks in regional cerebral blood flow. Our findings indicate no difference in brain activation between the acts of power grip and precision grip without a target object.