Expression of neuronal type nitric oxide synthase and renin in the juxtaglomerular apparatus of angiotensin type-1a receptor gene-knockout mice

OBJECTIVE: To determine whether the hypometabolism observed in PET images of patients with Alzheimer's disease (AD) is due entirely to brain atrophy. BACKGROUND: Reduced brain glucose metabolism in AD patients measured using PET has been reported by numerous authors. Actual glucose metabolic values in AD may be reduced artificially because of brain atrophy, which accentuates the partial volume effect (PVE) on data collected by PET. METHODS: Using segmented MR images, we corrected regional cerebral metabolic rates for glucose for PVEs to evaluate the effect of atrophy on uncorrected values for brain metabolism in AD patients and healthy control subjects. RESULTS: Global glucose metabolism was reduced significantly before and after correction in AD patients compared with controls. Before PVE correction, glucose metabolic values in patients were lower than in control subjects in the inferior parietal, frontal, and lateral temporal cortex; in the posterior cingulate; and in the precuneus. These reductions remained significantly lower after PVE correction, although in the posterior cingulate the difference in metabolism between AD patients and control subjects lessened. Regional glucose metabolism of these areas with PVE correction was lower in moderately-severely demented patients than in mildly demented patients. CONCLUSION: Reduced glucose metabolism measured by PET in AD is not simply an artifact due to an increase in CSF space induced by atrophy, but reflects a true metabolic reduction per gram of tissue.     

Effect of chronic hypoxia on adrenoceptor responses of ovine foetal umbilical vessels

OBJECTIVE: To evaluate the relevance of hypometabolism in the hippocampal head to the pathophysiology of memory impairment. BACKGROUND: Neurofunctional imaging studies with an image reslicing technique provided by using software suggest that dysfunction of the amygdalohippocampal system causes memory impairment. However, metabolic and morphologic profiles of the whole hippocampal formation have not been evaluated in detail. METHODS: By tilting the gantry of a high-resolution PET scanner in a plane parallel to the hippocampal longitudinal axis determined beforehand by MRI, we performed quantitative measurement of glucose metabolism in the subdivisions of the hippocampal formation (head, body, tail) in 10 patients of normal intelligence with pure amnesia, in eight patients with AD, and in eight normal subjects. RESULTS: Although the volumes of the amygdala and hippocampal formation in pure amnesics were not different significantly from those of normal subjects, glucose metabolism in the head of the hippocampus was significantly lower in pure amnesics. In patients with AD, marked hypometabolism was found extending to the amygdala, the hippocampal head, and the parietotemporal cortex, along with amygdalohippocampal atrophy. CONCLUSION: Hippocampal head dysfunction plays an important role in memory impairment in amnesic patients. Further metabolic impairment over the amygdalohippocampal system and the surrounding association cortex reflects the pathophysiology of AD.     

18F-labeled 2-deoxy-2-fluoro-D-glucose positron-emission tomography scans for the localization of the epileptogenic foci

The localization of epileptogenic foci that are amenable to curative epilepsy surgery may be accomplished by noninvasive surface electroencephalogram (EEG) recordings, clinical observations, computed tomography (CT), magnetic resonance imaging (MRI), and neuropsychologic tests. Other tests, such as invasive EEG, 18F-fluoro-deoxyglucose-positron-emission tomography (FDG-PET or PET) scans, and single-photon-emission computed tomography (SPECT) scans, have also been used at various epilepsy centers to help identify candidates who might benefit from such surgery. Interictal PET scans have demonstrated hypometabolism in areas concordant with the epileptogenic foci indicated by other diagnostic tests such as EEG and MRI. However, PET scans have also shown no abnormality in many patients with EEG-indicated epileptogenic foci; in others, the scans have shown abnormal metabolism in areas that were discordant with the epileptogenic foci. Although substitution of the noninvasive PET scan for the invasive EEG recordings would be desirable, the available data were insufficient to determine whether PET scans might serve as a reliable substitute for EEG. A positive PET scan might contribute independent information for identifying the epileptogenic site but could be noncontributory or confusing when hypometabolism is not seen or is seen in presumably normal brain areas. It is not evident from the data in the literature to what extent confirmatory PET scan findings might contribute to the management of patients with complex partial seizures.     

A technique utilizing positron emission tomography and magnetic resonance/computed tomography image fusion to aid in surgical navigation and tumor volume determination

Brain tumors are histologically heterogeneous. A technique for three-dimensional fusing of computed tomography (CT) or magnetic resonance images (MRI) with positron emission tomography (PET) images is described. This allows the anatomic detail provided by CT or MRI scans to be combined with the information about metabolic activity provided by PET scans. The fused images allowed selection of the most metabolically active portions of tumors. Fusion of CT and MRI images with PET scans has allowed first-pass diagnostic yield by providing the surgeon with a map of anatomical as well as functional (metabolic) detail. We describe a technique to allow routine fusion of MRI, CT, and PET information to help guide the neurosurgeon.     

Correlations of Regional Cerebral Metabolism With Memory Performance and Executive Function in Patients With Herpes Encephalitis or Frontal Lobe Lesions.

Cerebral [1?F]fluorodeoxyglucose positron emission tomography (1?FDG-PET) data from patients suffering amnesia following herpes encephalitis (n = 7) or frontal lobe pathology (n = 14) were compared with data from age-matched nonamnesic subjects (n = 10). All subjects received structural MRI, resting 1?FDG-PET scans, and neuropsychological evaluation. PET data were analyzed using complementary statistical parametric mapping and region-of-interest methods. Differential patterns of hypometabolism were found in patients relative to healthy controls. Factor analysis of the neuropsychological data revealed that memory performance was associated with retrosplenial and medial temporal metabolism, and executive function was associated with dorsolateral frontal metabolism. The association between memory performance and retrosplenial metabolism remained statistically significant after accounting for measures of cerebral atrophy using MRI. The significance of the retrosplenium as a major relay station between the thalamus and the medial temporal and frontal lobes--sensitive to changes in either--is discussed in the light of the findings. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

FDG-PET and volumetric MRI in the evaluation of patients with partial epilepsy

We performed interictal FDG-PET- and MRI-based hippocampal volumetric measurements on 18 adult patients with complex partial epilepsy of temporal lobe origin in whom we had identified their ictal focus by video-telemetry EEG. Sixteen patients (89%) had regional hypometabolism, 11 (61%) had focal 1.5-tesla T2-weighted MRI (two structural abnormalities, nine hippocampal formation [HF] increased T2 signal), and nine (50%) had absolute HF atrophy ipsilateral to the temporal ictal focus. Ten (55%) had abnormal L/R HF ratios, nine ipsilateral to the EEG focus. All patients with abnormal MRI volumetric studies had focal PET abnormalities. Only seven had both abnormal HF volume ratios and T2 MRI (all increased HF T2 signal). There was a significant correlation between hippocampal volume and inferior mesial and lateral temporal lobe cerebral metabolic rate of glucose asymmetry index (p < 0.01), suggesting that hypometabolism may reflect hippocampal atrophy. PET is more sensitive than MRI volumetry in identifying the ictal focus but does not provide additional information when HF atrophy is present.     

Regional cerebral glucose metabolism and postmortem pathology in Alzheimer's disease

In four patients with an antemortem diagnosis of probable Alzheimer's disease (AD) regional cerebral glucose metabolism (rCMRGl) was studied prospectively by positron emission tomography (PET) and compared with postmortem semiquantitative neuropathology. The interval between the last PET study and autopsy was 1.3 +/- 0.8 years. In comparison with age-matched controls, the AD patients showed predominant temporoparietal hypometabolism spreading to other cortical and subcortical regions during serial PET scans. All patients had neuropathological findings typical for AD. There was a significant relationship between rCMRGl and density of senile plaques (SP) in one patient (tau b = -0.86, P < 0.05). SP were distributed quite homogeneously in all regions examined. Neurofibrillary tangles (NFT) were concentrated focally in the hippocampus-amygdala-entorhinal complex. In the context of widespread developing cortical hypometabolism, the predilection of NFT for involvement in limbic areas suggests a disruption of projection neurons as the pathogenetic process of cortical dysfunction.     

Cerebral positron emission tomographic study in systemic lupus erythematosus

The cerebral glucose metabolism in eight patients with systemic lupus erythematosus (SLE) and in five healthy controls were examined by positron emission tomography (PET) using 18-F-labeled deoxy-glucose (FDG) as tracer. One of the eight patients had no abnormality by magnetic resonance imaging (MRI), three of them had cerebral atrophy and four patients had multiple white matter hyperintensities and vascular infarcts in the striatum as assessed by MRI. With FDG-PET, inhomogeneous multifocal cerebral glucose hypometabolism was detected, more frequently in the temporal lobe of right hemisphere. The PET findings did not correlate always with the neurological symptoms. Abnormalities in brain metabolism can be detected more frequently by PET, than morphological changes by MRI, indicating the involvement of the central nervous system.     

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.     

Assessment of the biodistribution and metabolism of 5-fluorouracil as monitored by 18F PET and 19F MRI: a comparative animal study

The effective clinical use of the anticancer drug 5-fluorouracil (5-FU) requires the non-invasive assessment of its transport and metabolism, particularly in the tumor and the liver, where the drug is catabolized to alpha-fluoro-beta-alanine (FBAL). In this study, the potentials and limitations of dynamic 18F PET and metabolic 19F MRI examinations for noninvasive 5-FU monitoring were investigated in ACI and Buffalo rats with transplanted MH3924A and TC5123 Morris hepatomas, respectively. Selective 5-[19F]FU and [19F]FBAL MR images were acquired 5 and 70 min after 5-FU injection using a CHESS MRI sequence. After administration of 5-[18F]FU, the kinetics of the regional 5-[18F]FU uptake were measured by dynamic PET scanning over 120 min. To allow a comparison between PET and MRI data, standardized uptake values (SUV) were computed at the same points in time. The TC5123 hepatoma showed a significantly (p < 0.002) higher mean SUV at 5 and 70 min post-5-FU injection than the MH3924A cell lines, whereas there were no significant differences between the mean SUV measured in the liver of both animal populations. In contrast to the PET data, no significant differences in the mean 5-[19F]FU and [19F]FBAL MR signal values in the tumor of both models were observed. The MR images, however, yielded the additional information that 5-FU is converted to FBAL only in the liver and not in the hepatomas.     

Normal and pathological aging--findings of positron-emission-tomography

Normal aging of the brain is predominantly characterized by metabolic changes in the prefrontal cortex. While in middle age there is a trend to hyperfrontality, PET demonstrates in old age a decline of regional cerebral glucose metabolism in frontal areas. In progeric diseases, clinically apparent as premature aging, the metabolic pattern is similar like in normal aging but qualitatively more severe. In patients with the diagnosis of probable Alzheimer's disease (AD) hypometabolism in early dementia is typically present in heteromodal association areas. Hypometabolism then spreads to other cortical and subcortical regions suggesting a characteristic pattern of degeneration that reflects selective vulnerability within limbic-cortical networks. Synaptic plasticity, clinically apparent as cognitive reserve capacity, can be assessed by PET under specific cognitive activation. In AD it is reduced in comparison to age-matched normals and may be influenced by drugs giving trophic support to neurochemical systems.     

Anterior cingulate gyrus volume and glucose metabolism in autistic disorder

OBJECTIVE: This study reports the first paired measurements of glucose metabolism and volume of the anterior cingulate gyrus in autism. METHOD: Magnetic resonance imaging (MRI) and positron emission tomography (PET) scans of seven high-functioning autistic patients and seven sex- and age-matched normal volunteers were coregistered. After the anterior cingulate gyri were outlined on the MRI images, the volumes of the structures were measured and corrected for brain volume. The volumes were then applied to the PET images and metabolic maps were obtained. RESULTS: Right anterior cingulate area 24' was significantly smaller in relative volume, and both area 24 and area 24' were metabolically less active, in the autistic patients than in the normal subjects. CONCLUSIONS: Autism may be characterized by structural and functional alterations in the anterior cingulate gyrus.     

Transmission scanning in emission tomography

Attenuation correction in single-photon (SPET) and positron emission (PET) tomography is now accepted as a vital component for the production of artefact-free, quantitative data. The most accurate attenuation correction methods are based on measured transmission scans acquired before, during, or after the emission scan. Alternative methods use segmented images, assumed attenuation coefficients or consistency criteria to compensate for photon attenuation in reconstructed images. This review examines the methods of acquiring transmission scans in both SPET and PET and the manner in which these data are used. While attenuation correction gives an exact correction in PET, as opposed to an approximate one in SPET, the magnitude of the correction factors required in PET is far greater than in SPET. Transmission scans also have a number of other potential applications in emission tomography apart from attenuation correction, such as scatter correction, inter-study spatial co-registration and alignment, and motion detection and correction. The ability to acquire high-quality transmission data in a practical clinical protocol is now an essential part of the practice of nuclear medicine.     

Estrogen and cancellous bone loss in the fowl

Long-term follow-up study with positron emission tomography (PET) has been conducted in a patient with superficial siderosis for ten years. A 63-year-old right-handed woman began to exhibit a cerebellar ataxia when she was 52 years old. Thereafter she has been exhibiting a slowly progressive course of pyramidal signs, hearing loss, anosmia, bilateral sciatica and memory disturbance in addition to the cerebellar ataxia. Series of x-ray CT and MRI disclosed a progressive atrophy of the cerebellum, specifically in the superior vermis, and a mild diffuse atrophy in the cerebral hemispheres, whereas no significant atrophy was seen in the brainstem. A marked hypointensity was seen along the rim of the brain structures including brainstem, cerebellum, sylvian fissures and the medial temporal lobes on MR T 2-weighted images. This hypointensity was also found at the edges of the third and fourth ventricles. These findings were regarded as haemosiderin deposit. By using oxygen-15, PET was carried out repeatedly with ten-year interval. In the initial PET study, both cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were mildly decreased in the cerebellar hemispheres and the occipital cortices. The follow-up PET study revealed a progressive reduction of CMRO2 in the brainstem, cerebellar hemispheres and temporal cortices including the hippocampus in which the haemosiderin deposition was marked on MRI, whereas the reduction of CBF was not advanced as compared with CMRO2. It was suggested that the progressive reduction of CMRO2 in the brain sites where the haemosiderin deposition was observed on MRI reflected the clinical course of neurological deterioration.     

Positron emission tomography in diagnosing brainstem vascular lesions that cause abnormal eye movements

PURPOSE: To evaluate the efficacy of positron emission tomography (PET) in aiding in the diagnosis of brainstem infarctions that cause abnormal eye movements. METHOD: Cerebral glucose metabolism was examined by PET with 18F-fluorodeoxyglucose as a tracer in five normal control subjects and six patients with abnormal eye movements. The PET images were registered to and superimposed on magnetic resonance images (MRIs). RESULTS: All control subjects showed little asymmetry of glucose metabolism in the brainstem, whereas all six patients demonstrated areas of low glucose metabolism in the brainstem. Areas of low metabolism seen by PET were wider than they appeared to be by MRI; MRIs even appeared normal in some patients. Asymmetry index measurements at the level of the ischemic lesion ranged between 19% and 45%. CONCLUSIONS: Positron emission tomography detected metabolic abnormality in patients with brainstem lesions that caused abnormal eye movements. Superimposing PET images on MRIs accurately localized abnormally low metabolism in the brainstem. Combined imaging with PET and MRI can be used to diagnose ischemic lesions in the brainstem from functional (PET) and morphologic (MRI) viewpoints.     

Changes in cerebral blood flow and oxygen metabolism related to magnetic resonance imaging white matter hyperintensities in Alzheimer's disease

We studied changes in cerebral perfusion and oxygen metabolism to elucidate the pathophysiological nature and clinical significance of white matter hyperintensities in Alzheimer's disease (AD). METHODS: Sixteen AD patients (age 71.6 +/- 3.1 yr) whose T2-weighted MR images showed white matter hyperintensities, and 16 age-matched AD patients (age 71.0 +/- 4.3 yr) without white matter hyperintensities were compared. Regional cerebral blood flow (CBF), oxygen metabolism (CMRO2) and oxygen extraction fraction (OEF) were measured by using (15)O steady-state method and PET. RESULTS: There was no significant difference in cognitive impairment between the two groups. Compared to the patients without white matter hyperintensities, those with them had significantly low CBF values and significantly high OEF values in all cortical and white matter regions. However, there were no significant differences in CMRO2 values between the two groups. Severity of white matter hyperintensities correlated with the mean cortical and mean white matter OEF. CONCLUSION: In AD patients, white matter hyperintensities on T2-weighted MR images represent ischemic changes in which oxygen metabolism and function are fairly compensated. These changes are not disease-specific but are age-associated coincidences, as in normal aging with or without vascular risk factors.     

Abnormal brain glucose metabolism in the delusional misidentification syndromes: a positron emission tomography study in Alzheimer disease

Brain lesions have been reported with increasing frequency in the delusional misidentification syndromes (DMS). This is the first controlled study to describe DMS regional cerebral metabolic rates of glucose (rCMRglc). We compared rCMRglc (using positron emission tomography) and neuropsychological data in 9 patients with DMS and Alzheimer dementia (AD), 15 AD patients without DMS, and 17 healthy controls. The DMS group differed from the AD group without DMS in having significant hypometabolism in paralimbic (orbitofrontal and cingulate areas bilaterally) and left medial temporal areas, and significant bilateral normalized hypermetabolism in sensory association cortices (superior temporal and inferior parietal) without right left asymmetry. Compared to healthy controls, both AD groups had significant dorso lateral frontal hypometabolism bilaterally. No specific DMS neuropsychological profile was identified. Dysfunctional connections among multimodal association areas, paralimbic structures, and dorsolateral frontal cortex are proposed as the predisposing neural deficit underlying DMS, causing cognitive-perceptual-affective dissonance, which under specific conditions results in "positive" delusion formation.     

Large colon resection

Early motor manifestations are the main components of focal seizures involving the frontal lobe. We examined the relationship between the initial ictal motor manifestations and interictal abnormalities of cerebral glucose consumption (rCMRGlc) as assessed by PET in 48 consecutive patients with focal seizures of neocortical origin. Group data analysis revealed that patients with predominantly unilateral clonic seizures had a significant contralateral perirolandic hypometabolism and to a lesser degree a contralateral frontomesial hypometabolism. Patients with predominantly focal tonic manifestations showed a hypometabolism within the frontomesial and perirolandic regions that was unilateral in all patients with lateralized tonic seizures. Patients with versive seizures had mainly contralateral metabolic depressions without a consistent regional pattern. Patients with hypermotor seizures had metabolic depressions involving frontomesial, anterior cingulate, perirolandic, and anterior insular/frontal operculum areas. In all patient groups, bilateral and symmetric hypometabolism of the thalamus and cerebellum was observed. We propose that this pattern of distinctly abnormal metabolic brain regions demonstrates not only possible epileptogenic zones but also symptomatogenic brain regions as shown by the associations between clinical manifestations and sets of abnormal brain regions, particularly if epileptogenic zones are in a clinically silent neocortical brain region. The detection and possible differentiation of symptomatogenic and epileptogenic zones might improve the effectiveness of presurgical noninvasive studies.     

Enhancement of the anti-tumor immune response using a combination of interferon-gamma and B7 expression in an experimental mammary carcinoma

BACKGROUND: An extensive literature describes structural lesions in apraxia, but few studies have used functional neuroimaging. We used positron emission tomography (PET) to characterize relative cerebral glucose metabolism in a 65-year-old, right-handed woman with progressive decline in ability to manipulate objects, write, and articulate speech. OBJECTIVE: To characterize functional brain organization in apraxia. DESIGN AND METHODS: The patient underwent a neurological examination, neuropsychological testing, magnetic resonance imaging, and fludeoxyglucose F 18 PET. The patient's magnetic resonance image was coregistered to her PET image, which was compared with the PET images of 7 right-handed, healthy controls. Hemispheric regions of interest were normalized by calcrine cortex. RESULTS: Except for apraxia and mild grip weakness, results of the neurological examination were normal. There was ideomotor apraxia of both hands (command, imitation, and object) and buccofacial apraxia. The patient could recognize meaningful gestures performed by the examiner and discriminate between his accurate and awkward pantomime. The magnetic resonance image showed moderate generalized atrophy and mild ischemic changes. Positron emission tomographic scans showed abnormal fludeoxyglucose F 18 uptake in the posterior frontal, supplementary motor, and parietal regions, the left affected more than the right. Focal metabolic deficit was present in the angular gyrus, an area hypothesized to store conceptual knowledge of skilled movement. CONCLUSIONS: Greater parietal than frontal physiological dysfunction and preserved gesture recognition are not consistent with the theory that knowledge of limb praxis is stored in the dominant parietal cortex. Gesture comprehension may be more diffusely distributed.     

Widespread functional deficits in perception-related networks demonstrated by PET in a case with simple visual seizures

PURPOSE: To study benzodiazepine receptor (BZR) density and functional deficits in occipital lobe epilepsy. METHODS: A 39-year-old man who had simple partial visual seizures after neurosurgical transtentorial extirpation of a pinealoma was studied by EEG, magnetic resonance imaging (MRI), and positron emission tomography (PET) of [18F]2-fluoro-2-deoxy-D-glucose (FDG) at rest and during visual activation task and[11C]flumazenil (FMZ). RESULTS: Electroencephalographic recordings were nonspecific, and MRI did not reveal any morphologic anomaly in the occipital lobe. Flumazenil-PET demonstrated a small epileptogenic region in the right visual association cortex and FDG-PET showed hypometabolism in a corresponding location and thalamic diaschisis. Stimulation of occipital metabolism by a continuous visual recognition task improved significantly the contrast between the dysfunctional zone and its surround. CONCLUSIONS: As BZR deficits are restricted to a small region, widespread hypometabolism in networks involved in visual information processing indicates an extensive functional deactivation by the epileptogenic focus.