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Biomedical subjects

R Harrop

Publications and source records attributed to R Harrop.

16 recordsLinked to original sources

Full data utilization in PVI using the 3D radon transform.

An algorithm is described for three-dimensional (3D) image reconstruction in positron volume imaging (PVI) using the inversion of the 3D radon transform (RT) for a truncated cylindrical detector geometry. A discrete version of the 3D RT is formed in a 3D histogram from the event-line coordinates of the detected events. The histogram entries represent the plane integrals of the activity in the field of view. Conventional inversion of the x-ray transform (XT) excludes oblique events in non-iterative reconstruction methods. by employing a spatially varying angular acceptance of events into the histogrammed plane integrals of the 3D RT, it is possible to include most of the detected oblique events in the reconstruction of the image using the standard 3D RT inversion formula. the oblique events are added to the histogram with a partial weight compared to those in complete (XT) projections. This single-pass reconstruction image has better statistical noise properties than images formed by RT inversion from complete XT projections, but only for some detector geometries is it significantly better. Monte Carlo simulations were used to study the statistical noise in images reconstructed using the new algorithm. The inherent difference in the axial versus the transaxial statistical noise in images reconstructed from truncated detectors is noted and is found to increase by including oblique events with this new algorithm.

Algorithms

Correlations of regional postmortem enzyme activities with premortem local glucose metabolic rates in Alzheimer's disease.

Correlations were sought between local cerebral metabolic rates (LCMRs) for glucose in various regions of the cortex, determined in premortem PET scans, with the regional activities of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), beta-glucuronidase (Gluc, a probable index of reactive gliosis), and phosphate-activated glutaminase (PAG, a possible indice of the large pyramidal neurons) measured on postmortem tissue. Significant negative correlations between LCMRs and Gluc activities were found in 6 PET-scanned cases of Alzheimer disease (AD), and positive correlations of LCMRs with PAG were found in 5. By contrast, a positive correlation with ChAT and AChE was found in only 1. The results are consistent with the metabolic deficits in AD being primarily a reflection of local neuronal loss and gliosis. Similar data on two cases of Huntington's disease showed no significant correlations, while 1 patient with Parkinson dementia showed a significant (negative) correlation only with Gluc.

Aged

18Fluorodeoxyglucose positron emission tomography studies in presumed Alzheimer cases, including 13 serial scans.

Positron emission tomographic (PET) data on local cerebral metabolic rates for glucose (LCMR) are reported for 32 regions of interest (ROI)s in cross-sectional studies on 57 patients with clinically diagnosed Alzheimer's disease (AD) and 20 neurologically normal controls, and in serial studies on 13 of the AD cases, including a familial, young-onset case where the diagnosis has been confirmed at autopsy. Extensive psychological testing was done on all the AD cases. Almost all cortical regions showed a significant decline in LCMR with age in the control subjects. There were the expected cortical metabolic deficits in AD and the serial studies showed a general increase in such deficits over time in 12 of the 13 cases. The regions showing the greatest declines with time in serial studies are the same as those showing the most severe deficiencies in cross-sectional studies. The young-onset case did not show a greater rate of metabolic decline than many of the older cases studied. Results on individual psychological tests tended to correlate with metabolic rates in multiple, rather than single, cortical regions, suggesting intact neuronal networks are required for good performance. The correlations with cortical metabolic activity found were of a sign indicating that the higher the metabolic rates and the better the left:right asymmetry index, the better was the performance.

Aged

Cortical glutaminase, beta-glucuronidase and glucose utilization in Alzheimer's disease.

Large pyramidal neurons of rat and human neocortex stain immunohistochemically for phosphate-activated glutaminase (PAG). In a limited number of postmortem brains, we find large reductions in cortical PAG activity in Alzheimer's disease (AD). This finding is consistent with histological evidence that pyramidal neurons are affected in AD. The reductions are greater than those found in the same samples in choline acetyltransferase (ChAT) but the possible deleterious effects of coma and similar premortem factors on human PAG activity have yet to be assessed. The activity of beta-glucuronidase, a lysosomal enzyme which occurs in reactive astrocytes, is elevated in the same samples. Positron emission tomography (PET) studies, using 18F-fluorodeoxyglucose (FDG), have demonstrated significant deficiencies in glucose metabolism in the cortex in AD, with the parietal, temporal and some frontal areas being particularly affected. We found in serial scans of 13 AD cases, including one relatively young (44-46 year old) familial case, an exacerbation of the defect over time in most cases. We have found a negative correlation between the regional metabolic rates for glucose (LCMR(s] measured premortem and the beta-glucuronidase activities measured postmortem on a few AD cases that have come to autopsy. The correlations between LCMR(s) and PAG and ChAT activities tend to be positive. The results are consistent with previous suggestions that decreased LCMR(s) in AD reflect local neuronal loss and gliosis.

Adult

Crossed cerebellar and uncrossed basal ganglia and thalamic diaschisis in Alzheimer's disease.

We detected crossed cerebellar as well as uncrossed basal ganglia and thalamic diaschisis in Alzheimer's disease by positron emission tomography (PET) using 18F-fluorodeoxyglucose. We studied a series of 26 consecutive, clinically diagnosed Alzheimer cases, including 6 proven by later autopsy, and compared them with 9 age-matched controls. We calculated asymmetry indices (AIs) of cerebral metabolic rate for matched left-right regions of interest (ROIs) and determined the extent of diaschisis by correlative analyses. For the Alzheimer group, we found cerebellar AIs correlated negatively, and thalamic AIs positively, with those of the cerebral hemisphere and frontal, temporal, parietal, and angular cortices, while basal ganglia AIs correlated positively with frontal cortical AIs. The only significant correlation of AIs for normal subjects was between the thalamus and cerebral hemisphere. These data indicate that PET is a sensitive technique for detecting diaschisis.

Alzheimer Disease

Regional cerebral glucose metabolism in identical twins.

The present study reports on the degree of similarity in regional cerebral glucose metabolism in seven sets of female identical twins. All scans were done with subjects at rest. Glucose metabolism was measured with positron emission tomography (PET). Significant intraclass correlations were found for the orbital and prefrontal cortex as well as the basal ganglia (caudate/putamen). It is suggested that these correlations reflect the functional aspects of these areas, namely attention and posturing movements.

Adult

Positron emission tomography and histopathology in Pick's disease.

PET using 18F-2-fluoro-2-deoxyglucose was carried out on a case of Pick's disease established by necropsy. A sharply decreased cortical metabolic rate for glucose was obtained in specific gyri, especially in the frontal lobes, where there was extensive gliosis and neuronal loss. More moderate decreases were found in areas with numerous Pick bodies and inflated neurons but less gliosis. The PET pattern was sufficiently distinctive to suggest that it might be possible to distinguish Pick's from Alzheimer's disease premortem.

Aged

Positron emission tomography in patients with clinically diagnosed Alzheimer's disease.

Fourteen patients who had clinically diagnosed Alzheimer's disease with mild to severe dementia (mean age 69.1 years) were evaluated by calculation of local cerebral metabolic rate for glucose (LCMR-gl) based on uptake of 18F-2-fluoro-2-deoxyglucose (FDG) detected with positron emission tomography (PET). PET scanning showed that the patients had significantly lower LCMR-gl values than 11 age-matched neurologically normal volunteers (mean age 66.3 years). The differences were most marked in the temporal cortex, followed by the frontal, parietal and occipital cortex. In each case the LCMR-gl value was below the lowest control value in at least one cortical area and usually in several; the reduction in LCMR-gl and the number of regions involved in the patients increased with the severity of the dementia. Deficits noted in neuropsychologic testing generally correlated with those predicted from loss of regional cortical metabolism. The patients with Alzheimer's disease were also examined with magnetic resonance imaging, computed tomography or both; the degree of atrophy found showed only a poor correlation with the neuropsychologic deficit. Significant atrophy was also noted in some of the controls. A detailed analysis of LCMR-gl values in selected cerebral regions of various sizes refuted the hypothesis that the reduction in cortical glucose metabolism in Alzheimer's disease is due to the filling by metabolically inert cerebrospinal fluid of space created by tissue atrophy.

Aged

Cortical metabolism, acetylcholinesterase staining and pathological changes in Alzheimer's disease.

The local cerebral metabolic rate for glucose (LCMRgl) was determined by positron emission tomography (PET) using the 18F-fluorodeoxyglucose method in a series of Alzheimer patients and normal controls. The LCMRgl declined in the cerebral cortex with age, but the decrement was significantly greater in the clinically diagnosed Alzheimer's cases. Comparison of PET and psychological data indicated that, as the disease progressed clinically, the reduction in cortical LCMRgl and the number of cortical regions involved also increased. Variable regions of cortex were involved in the early stages but the temporal, parietal and frontal regions were most typically affected. One case coming to autopsy showed that the severity of the LCMRgl decline paralleled loss of neurons in the cortex and their replacement with astroglia. A case of Pick's disease coming to autopsy had shown a different and highly characteristic pattern of cortical metabolic defect. In this case also a poor metabolic rate was associated with extensive gliosis. Acetylcholinesterase (AChE) staining of the cerebral cortex in elderly normals and Alzheimer's disease cases with a new, highly sensitive method showed that in Alzheimer's disease there was an extensive loss of AChE-positive fibers with senile plaques frequently incorporating AChE-positive fiber debris. AChE staining of the substantia innominata area, where the cells giving rise to these neocortical fibers are presumably located, also showed evidence of degenerating cells and fibers.

Acetylcholinesterase

Design of an efficient position sensitive gamma ray detector for nuclear medicine.

The shortcomings of conventional scintillation cameras are analysed theoretically with a view towards improving performance at gamma ray energies above 140 keV. A camera design is proposed which incorporates several new features to obtain good spatial resolution from thicker crystals of sodium iodide. Computer simulations show that in addition to having good efficiency and spatial resolution, the new design allows parallax error correction and (possibly) Compton scattering correction at gamma energies up to 511 keV.

Computer Simulation

Comparison of PET, MRI, and CT with pathology in a proven case of Alzheimer's disease.

Positron emission tomography (PET) with fluorodeoxyglucose (FDG), magnetic resonance imaging (MRI), and CT were carried out in a patient with Alzheimer's disease 16 months before he died. At autopsy, the gross appearance of the brain correlated with MRI and CT, which showed some regional atrophy. These were much less revealing than PET, which correlated with microscopic findings of neuronal loss and proliferation of glia. In areas of moderately impaired local cerebral metabolic rate of glucose, as revealed by reduced FDG uptake, there was some gliosis, primarily around the numerous senile plaques. In areas of severe metabolic impairment, there was a profound loss of neurons, extensive gliosis, and a diminished appearance of plaques. PET-FDG is a better measure of the severity of Alzheimer's disease than MRI or CT, because it reflects the degree of neuronal pathology.

Aged

PET studies of cerebral glucose metabolism in idiopathic torticollis.

Regional cerebral glucose metabolism was studied in 16 patients with idiopathic torticollis, using positron emission tomography. Analysis of subcortical regions revealed no consistent focal abnormality of cerebral metabolic rate for glucose, but there was a bilateral breakdown of the normal relationships between the thalamus and basal ganglia. The findings suggest disruption of the pallidothalamic projections in this focal dystonia and may imply a disturbance of GABA.

Adult

Positron emission tomography in the early diagnosis of Huntington's disease.

We studied 10 patients with early Huntington's disease and 7 normal age-matched controls with positron emission tomography (PET) using fluorodeoxyglucose. Subjects had little or no caudate nucleus atrophy and had not received any medications. The results demonstrated that hypometabolism of glucose preceded tissue loss. Furthermore, patients with minimal neurologic or psychiatric symptoms and no obvious CT changes may be differentiated from normal persons with high accuracy by PET. PET is helpful in the early diagnosis of Huntington's disease irrespective of the mode of presentation. PET may also be useful for preclinical detection and may supplement information from DNA studies.

Adolescent

The magnetoencephalographic localisation of source-systems in the brain: early and late components of event related potentials.

The application of magnetoencephalography (MEG) to the analysis of sources in the brain responsible for early and late components of evoked potentials is discussed. Representative data are presented and discussed which demonstrate localisation of sources assuming single equivalent dipoles. Distributed systems as sources for some steady-state responses are discussed in relation to the broader issue of the usefulness of equivalent single dipole models. These issues are related to the use of MEG for the analysis of source systems influenced by alcohol and other drugs.

Animals