Regional cerebral blood flow,blood volume,oxygen extraction fraction,and oxygen utilization rate in normal volunteers measured by the autoradiographic technique and the single breath inhalation method

By means of a high resolution PET scanner, the regional cerebral blood flow (rCBF), cerebral blood volume (rCBV), oxygen extraction fraction (rOEF), and metabolic rate of oxygen (rCMRO₂) for major cerebral gyri and deep brain structures were studied in eleven normal volunteers during an eye-covered and ear-unplugged resting condition. Regional CBF was measured by the auto-radiographic method after intravenous administration of H₂ ¹⁵O. Regional OEF and rCMRO₂ were measured by the single inhalation of¹⁵O₂. With MR T₁-weighted images as an anatomical reference, thirteen major cerebral gyri, caudate nucleus, lentiform nucleus, thalamus, midbrain, pons, cerebellum and vermis were defined on the CMRO₂ images. Values were read by using circular regions of interest 16 mm in diameter. The posterior part of the cingulate gyri had the highest rCBF and rCMRO₂ values among brain structures, followed by the lentiform nucleus, the cerebellum, the caudate nucleus, and the thalamus. Parahippocampal gyri had the lowest rCBF and rCMRO₂ values amongthe cortical gyri.RegionalOEFforthepontinenuclei (0.34 ± 0.04), the midbrain (0.35 ± 0.05), the parahippocampal gyri (0.35 ± 0.04 for the right and 0.37 ± 0.05 for the left), and the thalami (0.37 ± 0.05 for the right and 0.36 ± 0.04 for the left) were significantly lower than the mean OEF for the cerebral cortices (0.42 ± 0.04) (p < 0.05 or less). The global CBF and CMRO₂ were consistent with those obtained by the Kety-Schmidt method. Although several limitations to the quantification derived from an inadequate spacial resolution remain unsolved, the performance of the present PET scanner and the method for the quantification employed provide regional estimates of brain circulation and oxygen metabolism more acurately than the PET system and the steady state method previously used.     

CT灌注成像对脑肿瘤瘤周水肿的评价

目的　应用CT灌注成像半定量估计脑肿瘤瘤周水肿的灌注状况。方法　应用SomatomPlus4螺旋CT机,对21例脑肿瘤瘤周水肿患者[脑膜瘤4例,胶质瘤(Ⅲ~Ⅳ级)7例、转移瘤10例]进行CT灌注成像,经灌注软件处理分别计算瘤周水肿区局部脑血流量(rCBF)、局部脑血容量(rCBV)、对比剂平均通过时间(MTT),并与对侧脑白质和不同肿瘤瘤周水肿间的灌注参数进行比较。结果　脑膜瘤和转移瘤瘤周水肿的rCBF和rCBV明显低于对侧脑白质(rCBF:t=2 .92和3 .82,P值均<0. 05, 0. 005;rCBV:t=2 .42和3. 53, P<0 .05, 0 .01),胶质瘤瘤周水肿的rCBF和rCBV与正常脑白质无明显差别(t=1 .00和1 .33, P值均>0 .05)。瘤周水肿区与对侧正常脑白质rCBF、rCBV比值,脑膜瘤和转移瘤之间差异无统计学意义(t=0 .23和0. 73, P值均>0 .05),胶质瘤明显大于脑膜瘤和转移瘤(t=3 .05和3. 37, P<0 .01, 0 .005)。结论　脑膜瘤和转移瘤瘤周水肿区的rCBF、rCBV显著降低,而胶质瘤瘤周水肿区接近或高于对侧脑白质,CT灌注能定量脑肿瘤瘤周水肿血流灌注状况,有助于肿瘤的鉴别和随访。     

Asymmetry of cerebral blood flow in patients with senile dementia of Alzheimer type by SPECT using I-123 IMP

Regional cerebral blood flow (rCBF) was determined by single photon emission CT (SPECT) with N-isopropyl-p-[123I]iodoamphetamine in 22 patients with clinically diagnosed senile dementia of Alzheimer type (SDAT) and in 18 age matched controls. We calculated asymmetry indices (AIs) of rCBF for matched right-left regions of interest. rCBF of parietal lobe in SDAT patients was significantly most laterally asymmetrical, but the least in occipital lobe. Lateral asymmetry of rCBF in SDAT patients correlated with asymmetry of language and visuospatial functions; decreased rCBF in the left parietal lobe was associated with language dysfunction, and that in the right parietal lobe, with visuospatial dysfunction. Furthermore cerebellar AIs correlated negatively with those of the cerebral hemisphere and lower frontal region in SDAT patients. The results demonstrate that rCBF measurement by 123I-IMP SPECT is useful to detect lateral asymmetry in reduction of rCBF in SDAT.     

Regional cerebral blood flow and blood volume in patients with subcortical arteriosclerotic encephalopathy (SAE)

The aim of the present study was a detailed analysis of the regional cerebral blood flow and blood volume in patients with subcortical arteriosclerotic encephalopathy (SAE) by means of functional magnetic resonance imaging (MRI). A group of 26 patients with SAE and a group of 16 age-matched healthy volunteers were examined. Using a well-established dynamic susceptibility contrast-enhanced MRI method, the regional cerebral blood flow (rCBF) and blood volume (rCBV) were quantified for each subject in 12 different regions in the brain parenchyma. As compared to healthy volunteers, patients with SAE showed significantly reduced rCBF and rCBV values in white matter regions and in the occipital cortex. Regions containing predominantly grey matter show almost normal rCBF and rCBV values. In conclusion, quantitative analysis of rCBF and rCBV values demonstrates clearly that SAE is a disease that is associated with a reduced microcirculation predominantly in white matter.     

Principal component and volume of interest analyses in depressed patients imaged by 99mTc-HMPAO SPET: a methodological comparison

Previous regional cerebral blood flow (rCBF) studies on patients with unipolar major depressive disorder (MDD) have analysed clusters of voxels or single regions and yielded conflicting results, showing either higher or lower rCBF in MDD as compared to normal controls (CTR). The aim of this study was to assess rCBF distribution changes in 68 MDD patients, investigating the data set with both volume of interest (VOI) analysis and principal component analysis (PCA). The rCBF distribution in 68 MDD and 66 CTR, at rest, was compared. Technetium-99m d,l-hexamethylpropylene amine oxime single-photon emission tomography was performed and the uptake in 27 VOIs, bilaterally, was assessed using a standardising brain atlas. Data were then grouped into factors by means of PCA performed on rCBF of all 134 subjects and based on all 54 VOIs. VOI analysis showed a significant group × VOI × hemisphere interaction (P<0.001). rCBF in eight VOIs (in the prefrontal, temporal, occipital and central structures) differed significantly between groups at the P<0.05 level. PCA identified 11 anatomo-functional regions that interacted with groups (P<0.001). As compared to CTR, MDD rCBF was relatively higher in right associative temporo-parietal-occipital cortex (P<0.01) and bilaterally in prefrontal (P<0.005) and frontal cortex (P<0.025), anterior temporal cortex and central structures (P<0.05 and P<0.001 respectively). Higher rCBF in a selected group of MDD as compared to CTR at rest was found using PCA in five clusters of regions sharing close anatomical and functional relationships. At the single VOI level, all eight regions showing group differences were included in such clusters. PCA is a data-driven method for recasting VOIs to be used for group evaluation and comparison. The appearance of significant differences absent at the VOI level emphasises the value of analysing the relationships among brain regions for the investigation of psychiatric disease.     

Developmental changes of cerebral blood flow and oxygen metabolism in children.

BACKGROUND AND PURPOSE: Normal values for cerebral blood flow (CBF) and metabolism in adults are well established, but not for children. Our goal, therefore, was to clarify functional developmental changes of the brain in children in relation to CBF and oxygen metabolism. METHODS: We measured regional CBF (rCBF), regional cerebral metabolic rate for oxygen (rCMRO2), and regional oxygen extraction fraction (rOEF), using positron emission tomography (PET). We performed 30 PET studies in 24 children ages 10 days to 16 years (nine boys, 15 girls), using a steady inhalation method with C(15)O2, (15)O2, and 15CO in order to measure rCBF, rCMRO2, and rOEF, respectively. Regions of interest were set in the primary cerebral areas (sensorimotor, visual, temporal, and parietal cortex), cerebral association areas (frontal and visual association), basal ganglia (lenticular and thalamus), and posterior fossa (brain stem and cerebellar cortex). Subjects were grouped by age (< 1, 1 to < 3, 3 to < 8, and > or = 8 years), and the absolute values of the parameters were compared with those obtained from 10 healthy adults. RESULTS: rCBF and rCMRO2 were lower in the neonatal period than in older children and adults, and increased significantly during early childhood. rCBF was higher as compared with adults, peaking around age 7, whereas rCMRO2 was relatively high, with the last area to increase being the frontal association cortex. Both rCBF and rCMRO2 reached adult values during adolescence. No difference in rCBF was observed between the basal ganglia and the primary cerebral cortex; however, it was prominent in the occipital lobe in every age bracket. No significant changes in rOEF were found during childhood. CONCLUSION: The dynamic changes of rCBF and rCMRO2 observed in children probably reflect the physiologic developmental state within anatomic areas of the brain.     

脑膜瘤瘤周水肿的64层螺旋CT灌注成像定量研究

目的:应用64层螺旋CT灌注成像定量估计脑膜瘤瘤周水肿的灌注状况.方法:对15例脑肿膜瘤伴瘤周水肿患者进行MSCT灌注成像,经灌注软件处理分别计算近瘤周水肿区及远瘤周水肿区局部脑血流量(rCBF)、局部脑血容量(rCBV)、表面通透性(PS),并与对侧脑白质灌注参数进行比较;测量并计算水肿指数EI[(V水肿+V肿瘤)/V肿瘤],并与rrCBV(rCBV水肿平均/rCBV对侧脑白质)的进行相关性分析.结果:脑膜瘤近瘤周水肿区、远瘤周水肿区的rCBF和rCBV明显低于对侧脑白质(rCBF:t=5.78和4.34,P=0.001,0.005; rCBV:t=6.46和8.46,P=0.001,0.003),近瘤周水肿区的rCBF和rCBV低于远瘤周水肿区(rCBF:t=3.49,P=0.013;rCBV:t=4.10,P=0.006),三组间PS值的差异均没有统计学意义(P值均＞0.05);水肿指数跟瘤周水肿区的rrCBV值呈负相关(r=-0.72,P＜0.01);2例恶性脑膜瘤近瘤周水肿区的rCBV、rCBF、PS值的均数明显高于良性脑膜瘤近瘤周水肿区.结论:脑膜瘤瘤周水肿区的灌注具有一定特征,有助于鉴别肿瘤良恶性,优化手术方案及相关辅助治疗、评价手术疗效、鉴别肿瘤复发和坏死.     

Long term evaluation of brain perfusion with magnetic resonance in high flow extracranial-intracranial saphenous graft bypass

Assessment was made of the cerebral vascular haemodynamic parameters in patients with a high-flow extra-intracranial (EC-IC) bypass performed for therapeutic occlusion of the internal carotid artery (ICA). Sixteen patients with ICA occlusion and EC-IC bypass (time interval from surgery 1–6 years) underwent MRI. Perfusion-weighted magnetic resonance imaging (PW-MRI) sequences were performed without the use of an arterial input function. The relative cerebral blood volume (rCBV), mean transit time (MTT) and relative cerebral blood flow (rCBF) were evaluated in all patients at the level of the basal ganglia, centrum semiovale and cortex in both hemispheres. Statistically significant differences (P<0.005) were observed in the haemodynamic parameters, indicating increased rCBV in the basal ganglia and decreased rCBF and rCBV in the cortex of the hemisphere supplied by the graft with respect to the contralateral. Patients with occlusion of the ICA and high flow EC-IC bypass do have altered vascular haemodynamic status between the hemispheres. In particular, rCBF is impaired in the surgical hemisphere at the level of the cortex. These patients should be followed-up to rule out chronic ischemia.     

Clinical significance of reduced cerebral metabolism in multiple sclerosis: A combined PET and MRI study

Magnetic resonance imaging (MRI) in patients with multiple sclerosis (MS) has provided major insights into the disease’s natural history, and many studies have focussed on possible correlations between MRI findings and the clinical manifestations of MS. In contrast, there are few reports on possible relationships between functional imaging data and cognitive function. The present study assessed the relationship between clinical presentation and combined anatomical and functional imaging data in MS. Twenty patients with definite MS underwent MRI and positron emission tomography (PET) to evaluate cerebral blood flow (rCBF) and oxygen metabolism (rCMRO₂). The relationships between these neuroimaging findings and clinical data, including the Expanded Disability Status Scale (EDSS), Mini-mental status scale, Hasegawa Dementia Scale and relapse time, were evaluated with Spearman’s rank correlation coefficients. A general reduction in rCBF and rCMRO₂ in the gray and white matter were found in the MS patients. EDSS was correlated with the number and size of the lesions on MRI and was negatively correlated with rCMRO₂. A correlation between the decrease in rCMRO₂ and the level of cognitive impairment was also found. The severity of cerebral hypometabolism was also related to the number of relapses. Morphological and functional findings obtained by MRI and PET are closely related to the clinical status in MS. Our results suggest that measurement of cerebral metabolism in MS has the potential to be an objective marker for monitoring disease activity and to provide prognostic information.     

Evaluation of brain perfusion with technetium-99m bicisate single-photon emission tomography in patients with depressive disorder before and after drug treatment

Depression is one of the most common psychiatric illnesses. Its influence on brain perfusion has been demonstrated, but conflicting data exist on follow-up after drug treatment. The aim of our study was to evaluate the effects of antidepressant drugs on regional cerebral blood flow (rCBF) in patients with depression after 3 weeks and 6 months of drug therapy. Clinical criteria for depression without psychosis were met according to psychiatric evaluation. Severity of depression was evaluated with the Hamilton Depression Rating Scale (HAMD) before every scintigraphic study. rCBF was assessed using technetium-99m bicisate (Neurolite) brain single-photon emission tomography in nine patients with severe depression before the beginning of antidepressant drug therapy and 3 weeks and six months after initiation of therapy. Only patients with no change in antidepressant medication during the study were included. No antipsychotic drugs were used. Cerebellum was used as the reference region. rCBF was evaluated for eight regions in each study in three consecutive transversal slices. Follow-up studies were compared with the baseline study. The mean HAMD score was 25.5 points initially, 16 at the second examination and 8.8 after 6 months. Global CBF was decreased compared with the reference region in drug-free patients. Perfusion of left frontal and temporal regions was significantly lower (P<0.005) in comparison with the contralateral side. After therapy, a moderate decrease in perfusion was seen in the right frontal region (P<0.05). Perfusion decreased further after 6 months in the right frontal (P<0.005) and temporal regions (P<0.01). The highly significant asymmetry in perfusion between the left and right frontal and temporal lobes almost disappeared during treatment. Our findings implicate dysfunction of the frontal and temporal cortex in clinically depressed patients before specific drug treatment. Clinical improvement and decreases in HAMD score after 3 weeks and after 6 months reflect the treatment effect on mood-related rCBF changes. Received 1 May and in revised form 24 June 1998     

Contrast-to-noise ratio in functional MRI of relative cerebral blood volume with sprodiamide injection

The purpose of this study was to investigate the dependence of contrast-to-noise ratio (CNR) on the dose and rate of sprodiamide injection in magnetic resonance relative cerebral blood volume (rCBV) imaging. rCBV maps for 35 normal volunteers were constructed from dynamic MR image sets acquired with echo-planar spin-echo imaging after intravenous injection of sprodiamide. Doses of .1, .2, and .3 mmol/kg, at rates of 2 ml/second and 5 ml/second, were tested. CNRs and blood/volume ratios of gray to white matter were computed. CNR depended on dose (P < .0001) but was independent of injection rate (P < .69). rCBV ratios of gray to white matter were dose independent (P < .38) and rate independent (P < .97). The dependence of CNR on dose, but not injection rate, has practical implications in optimal protocol design. The independence of gray/white ratios supports the theory underlying the generation of rCBV maps.     

Regional cerebral blood flow pattern in normal young and aged volunteers: a99mTc-HMPAO SPET study

The aim of this study was to investigate the normal pattern of regional cerebral blood flow (rCBF) distribution in normal young and aged volunteers using technetium-99m hexamethylpropylene amine oxime (^99m-Te-HMPAO) as a tracer. The region brain perfusion of young and aged subjects was compared, especially regarding rCBF differences due to age and gender, and interhemispheric rCBF asymmetries. Sixty-eight right-handed normal volunteers — 40 young (mean age 29.5±6.3 years) and 28 aged (mean age 71.2±4.3 years) — were included in the study. rCBF was estimated on the basis of a semiquantitative approach by means of a left/right index and two region/reference ratios, using the cerebellum and the whole brain activity as references. A good correlation between these two region/reference ratios was found (P<0.005 in all cerebral regions). The highest rCBF ratios corresponded to the cerebellum, followed by the occipital lobe. The remaining cortical regions (temporal, parietal, frontal and basal ganglia) showed slightly lower values. The white matter showed rCBF ratios substantially lower than the grey matter. In neither young nor aged subjects were significant rCBF differences between the genders found in any of the two region/reference indices employed. Aged subjects showed significantly lower rCBF ratios than young subjects in the left frontal lobe and in the posterior region of the left temporal lobe. In both young and aged subjects, lower perfusion was found in the left hemisphere, except for the white matter region in both age groups and the frontal lobe in the young subjects. Aged subjects presented a slightly higher interhemispheric asymmetry in the frontal lobe. However, interhemispheric asymmetry was minimal (–1.01% to 3.14%). Consequently, a symmetrical rCBF distribution can be assumed between homologous regions, independent of age.     

Haemodynamic assessment in patients with dural arteriovenous fistulae: dynamic susceptibility contrast-enhanced MRI

Cerebral haemodynamics in patients with dural arteriovenous fistulae (DAVF) have not been fully investigated and their effects are not clear. Our purpose was to assess impaired haemodynamics in patients with DAVF using dynamic susceptibility contrast-enhanced MRI (DSC-MRI). We used this technique in eight control subjects (group I) and 17 patients with DAVF who were scheduled to undergo or had already undergone endovascular embolisation and/or surgical excision. There were seven patients with cavernous sinus DAVF (CSDAVF) and the other ten had unilateral transverse/sigmoid sinus DAVF. All patients with CSDAVF underwent DSC-MRI preoperatively (group II) and those with transverse/sigmoid sinus DAVF underwent preoperative DSC-MRI (group III) and postoperative (group IV) assessment. The ratios of relative cerebral blood volume (rCBV), cerebral blood flow (rCBF) and mean transit time (rMTT) were calculated relative to contralateral values. Patients in group II had no significant haemodynamic impairment in grey (GM) or white matter (WM), but cerebellar rMTT were significantly prolonged ( P<0.05). Group III showed haemodynamic impairment characterised by significant increase in rCBV, prolongation of rMTT and decrease in rCBF in GM ( P<0.05). Significantly increased rCBV and prolonged rMTT in the GM ( P<0.05) were obvious in group III patients irrespective of retrograde leptomeningeal venous drainage (RLVD). In group IV, rCBV and rCBF returned to normal values, whereas rMTT was still significantly prolonged in GM ( P<0.05). Our study indicates that patients with CSDAVF may have impaired cerebellar perfusion, and that those with transverse/sigmoid sinus DVAF can have disturbed cerebral haemodynamics, even in the absence of RLVD.     

Functioning heterotopic grey matter? Increased blood flow with voluntary movement and sensory stimulation

A 66-year-old woman with a right hemiplegia due to cerebral haemorrhage was found to have heterotopic grey matter in the left frontal and right frontal and parietal lobes. She had no neurological disturbance prior to the haemorrhage. Regional cerebral blood flow (rCBF) was measured by xenon-CT (Xe-CT) in the zones of heterotopic grey matter during voluntary movement and sensory stimulation of her left limbs. During voluntary movement, rCBF increased markedly in the heterotopic grey matter of the frontal lobes and the overlying cortex. During sensory stimulation, rCBF increased in the right parietal heterotopic grey matter and the overlying cortex. This strongly suggests that the heterotopic grey matter is functional.     

Detection of dopaminergic neurotransmitter activity using pharmacologic MRI: Correlation with PET,microdialysis, and behavioral data

The metabolic activation resulting from direct dopaminergic stimulation can be detected using auto-radiography, positron emission tomography (PET) or, potentially, fMRI techniques. To establish the validity of the latter possibility, we have performed a number of experiments. We measured the regional selectivity of two different dopaminergic ligands: the dopamine release compound D-amphetamine and the dopamine transporter antagonist 2β-carbomethoxy-3β-(4-fluoropheny) tropane (CFT). Both compounds led to increased signal intensity in gradient echo images in regions of the brain with high dopamine receptor density (frontal cortex, striatum, cingulate cortex ? parietal cortex). Lesioning the animals with unilaterally administered 6-hydroxydopamine (6-OHDA) led to ablation of the phMRI response on the ipsilateral side; control measurements of rCBV and rCBF using bolus injections of Gd,-DTPA showed that the baseline rCBV and rCBF values weire intact on the lesioned side. The time course of the BOLD signal changes paralleled the changes observed by microdialyisis measurements of dopamine release in the striatum for both amphetamine and CFT; peaking at 20–40 min after injection and returning to baseline at about 70–90 min. Signal changes were not correlated with either heart rate, blood pressure or pCO₂. Measurement of PET binding in the same animals showed an excellent correlation with the phMRI data when compared by either measurements of the number of pixels activated or percent signal change in a given region. The time course for the behavioral measurements of rotation in the 6-OHDA lesioned animals correlated with the phMRI. These experiments demonstrate that phMRI will become a valuable, noninvasive tool for investigation of neurotransmitter activity in vivo. Key words: fMRI; dopamine; amphetamine; CFT.     

High-grade and low-grade gliomas: differentiation by using perfusion MR imaging

AIM: Relative cerebral blood volume (rCBV) is a commonly used perfusion magnetic resonance imaging (MRI) technique for the evaluation of tumour grade. Relative cerebral blood flow (rCBF) has been less studied. The goal of our study was to determine the usefulness of these parameters in evaluating the histopathological grade of the cerebral gliomas. METHODS: This study involved 33 patients (22 high-grade and 11 low-grade glioma cases). MRI was performed for all tumours by using a first-passage gadopentetate dimeglumine T2*-weighted gradient-echo single-shot echo-planar sequence followed by conventional MRI. The rCBV and rCBF were calculated by deconvolution of an arterial input function. The rCBV and rCBF ratios of the lesions were obtained by dividing the values obtained from the normal white matter of the contralateral hemisphere. For statistical analysis Mann-Whitney testing was carried out. A p value of less than 0.05 indicated a statistically significant difference. Receiver operating characteristic curve (ROC) analysis was performed to assess the relationship between the rCBV and rCBF ratios and grade of gliomas. Their cut-off value permitting discrimination was calculated. The correlation between rCBV and CBF ratios and glioma grade was assessed using Pearson correlation analysis. RESULTS: In high-grade gliomas, rCBV and rCBF ratios were measured as 6.50+/-4.29 and 3.32+/-1.87 (mean+/-SD), respectively. In low-grade gliomas, rCBV and rCBF ratios were 1.69+/-0.51 and 1.16+/-0.38, respectively. The rCBV and rCBF ratios for high-grade gliomas were statistically different from those of low-grade gliomas (p < 0.001). The rCBV and CBF ratios were significantly matched with respect to grade, but difference between the two areas was not significant (ROC analysis, p > 0.05). The cut-off value was taken as 1.98 in the rCBV ratio and 1.25 in the rCBF ratio. There was a strong correlation between the rCBV and CBF ratios (Pearson correlation = 0.830, p < 0.05). CONCLUSION: Perfusion MRI is useful in the preoperative assessment of the histopathologicalal grade of gliomas; the rCBF ratio in addition to the rCBV ratio can be incorporated in MR perfusion analysis for the evaluation.     

Measurement of temporal regional cerebral perfusion with single-photon emission tomography predicts rate of decline in language function and survival in early Alzheimer’s disease

We determined the relationship between regional cerebral blood flow (rCBF) measured with single-photon emission tomography (SPET) and decline in cognitive function and survival in Alzheimer’s disease. In a prospective follow-up study, 69 consecutively referred patients with early probable Alzheimer’s disease (NINCDS/ADRDA criteria) underwent SPET performed at the time of initial diagnosis using technetium-99m-labelled hexamethylpropylene amine oxime. Neuropsychological function was assessed at baseline and after 6 months and survival data were available on all patients, extending to 5.5 years of follow-up. Lower left temporal (P<0.01) and lower left parietal (P<0.01) rCBF were statistically significantly related to decline in language function after 6 months. The association between left temporal rCBF and survival was also statistically significant (P<0.05) using Cox proportional hazards regression analysis. Performing analysis with quartiles of the distribution, we found a threshold effect for low left temporal rCBF (rCBF<73.7%, P<0.01) and high risk of mortality. In this lowest quartile, median survival time was 2.7 years (follow-up to 5.2 years), compared with 4.4 years in the other quartiles (follow-up to 5.5 years). Kaplan-Meier survival curves showed statistically significant (P<0.05, log rank test) survival curves for the lowest versus other quartiles of left temporal rCBF. All results were unaffected by adjustment for age, sex, dementia severity, duration of symptoms, education and ratings of local cortical atrophy. We conclude that left temporal rCBF predicts decline in language function and survival in patients with early probable Alzheimer’s disease, with a threshold effect of low rCBF and high risk of mortality. Received 1 June and in revised form 6 November 1998     

Differences in resting state regional cerebral blood flow assessed with 99mTc-HMPAO SPECT and brain atlas matching between depressed patients with and without tinnitus

An increased occurrence of major depressive disorder has been reported in tinnitus patients, and of tinnitus in depressive patients. Involvement of several Brodmann areas (BAs) has been reported in tinnitus perception. The aim of this study was to assess the regional cerebral blood flow (rCBF) changes in depressed patients with and without tinnitus. The rCBF distribution at rest was compared among 45 patients with a lifetime prevalence of major depressive disorder, of whom 27 had severe tinnitus, and 26 normal healthy subjects. 99mTc-hexamethylenepropylene amine oxime (99mTc-HMPAO) single photon emission computed tomography (SPECT), using a three-headed gamma camera, was performed and the uptake in 34 functional sub-volumes of the brain bilaterally was assessed by a computerized brain atlas. Decreased rCBF in right frontal lobe BA 45 (P<0.05), the left parietal lobe BA 39 (P<0.00) and the left visual association cortex BA 18 (P<0.05) was found in tinnitus patients compared with non-tinnitus patients. The proportion of tinnitus patients with pronounced rCBF alterations in one or more of the temporal lobe BAs 41+21+22 was increased compared to gender matched controls (P<0.00) and patients without tinnitus (P<0.05). Positive correlations were found between trait anxiety scales from the Karolinska Scales of Personality and rCBF in tinnitus patients only in three limbic BAs (P<0.01), and inverse correlations in non-tinnitus patients only in five BAs subserving auditory perception and processing (P<0.05). rCBF differences between healthy controls and depressed patients with and without tinnitus were found in this study. The rCBF alterations were distributed in the cortex and were particularly specific in the auditory cortex. These findings suggest that taking audiological symptoms into account may yield more consistent results between rCBF studies of depression.     

Regional cerebral blood flow in normal pressure hydrocephalus: diagnostic and prognostic aspects

Relative regional cerebral blood flow (rrCBF) was measured by single-photon emission tomography (SPET), using technetium-^99m-d,l-hexamethylpropylene amine oxime (HMPAO) as flow tracer, in 23 patients with normal pressure hydrocephalus (NPH). 1000 MBq ^99mTc-HMPAO was given intravenously and the rrCBF calculated as regional/cerebellar count level ratios. The patients were examined before and 3–12 months after ventriculoperitoneal shunt surgery. rrCBF was also determined in ten healthy aged matched volunteers who served as controls. The NPH patients had decreased rrCBF in the hippocampal regions and in the frontal and parietal white matter as compared to the controls. The frontal/parietal rrCBF ratio correlated with both psychiatric disability and the preoperative degree of incontinence. Decreased flow in frontal white matter, frontoparietal and hippocampal grey matter and a low frontalparietal grey matter flow ratio preoperatively correlated with improvement in both Mini Mental State score and psychiatric disability after shunt surgery. After shunt surgery the rrCBF increased in the mesencephalon, frontal grey and white matter, parietal white matter and hippocampus. The flow increase in hippocampal regions and frontal white matter correlated with improvement in psychiatric symptomatology. The results of this study regarding the frontal and hippocampal rrCBF patterns, and the clinical correlation, support the hypothesis that CBF changes in these regions are of patohphysiological and prognostic importance in NPH. Correspondence to: A. Larsson     

Disease-related patterns of in vivo pathology in Corticobasal syndrome

Purpose

To assess disease-related patterns of in vivo pathology in 11 patients with Corticobasal Syndrome (CBS) compared to 20 healthy controls and 33 mild cognitive impairment (MCI) patients due to Alzheimer’s disease.

Methods

We assessed tau aggregates with [¹⁸F]AV1451 PET, amyloid-β depositions with [¹⁸F]AV45 PET, and volumetric microstructural changes with MRI. We validated for [¹⁸F]AV1451 standardised uptake value ratio (SUVRs) against input functions from arterial metabolites and found that SUVRs and arterial-derived distribution volume ratio (DVRs) provide equally robust measures of [¹⁸F]AV1451 binding.

Results

CBS patients showed increases in [¹⁸F]AV1451 SUVRs in parietal (P?<?0.05) and frontal (P?<?0.05) cortices in the affected hemisphere compared to healthy controls and in precentral (P?=?0.008) and postcentral (P?=?0.034) gyrus in the affected hemisphere compared to MCI patients. Our data were confirmed at the histopathological level in one CBS patient who underwent brain biopsy and showed sparse tau pathology in the parietal cortex co-localizing with increased [¹⁸F]AV1451 signal. Cortical and subcortical [¹⁸F]AV45 uptake was within normal levels in CBS patients. In parietal and frontal cortices of the most affected hemisphere we found also grey matter loss (P?<?0.05), increased mean diffusivity (P?<?0.05) and decreased fractional anisotropy (P?<?0.05) in CBS patients compared to healthy controls and MCI patients. Grey matter loss and white matter changes in the precentral gyrus of CBS patients were associated with worse motor symptoms.

Conclusions

Our findings demonstrate disease-related patterns of in vivo tau and microstructural pathology in the absence of amyloid-β, which distinguish CBS from non-affected individuals and MCI patients.