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ABSTRACT: Nicotinic acetylcholine receptors (nAChRs) have been implicated in a number of neurological disorders. 5-Iodo-3-[2(S)-2-azetidinylmethoxy]pyridine (5-I-A-85380) is a novel nAChR marker, binding predominantly to the alpha4beta2 subtype. This in vitro autoradiography study describes the distribution of 5-[(125)I]-A-85380 binding in post-mortem brain tissue from normal elderly individuals and from cases with age-associated dementias of both neurodegenerative and vascular types. The binding distribution of 5-[(125)I]-A-85380 in normal brain tissue was found to be consistent with the reported distribution of other high-affinity nicotinic ligands. In addition to high thalamic and moderate striatal and temporal cortex density, moderate 5-[(125)I]-A-85380 binding was also seen in white matter tracts in cingulate, occipital, and temporal areas, indicating the presence of nAChRs along nerve fiber tracts, which has not been reported in other high-affinity nicotinic agonist distribution studies. In Parkinson's disease (PD), loss of striatal 5-[(125)I]-A-85380 binding closely parallels the loss of nigrostriatal dopaminergic markers previously observed. In dementia with Lewy bodies (DLB) reduced striatal 5-[(125)I]-A-85380 binding density, comparable to that in PD, may be a marker of early degeneration in nigrostriatal inputs, while in Alzheimer's disease (AD) reduced striatal 5-[(125)I]-A-85380 binding could be related to reduced cortical inputs. The reductions of nAChRs seen in AD, DLB, and PD were not apparent in vascular dementia (VaD). In conclusion, 5-I-A-85380 is clearly a useful ligand for both in vitro and in vivo single photon emission tomography human studies investigating disease symptoms and progression, response to acetylcholinesterase-inhibiting drugs and in differentiating primary degenerative dementia from VaD.
Neuropsychopharmacology 02/2004; 29(1):108-16. · 7.99 Impact Factor
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ABSTRACT: In this study standard patterns of cerebral perfusion based on classifications described in the literature have been chosen and the ability of experienced imaging specialists to categorise the 99m Tc HMPAO SPECT scans of patients referred to the department for investigation of dementia has been compared before and after the calculation of Statistical Parametric Maps (SPM - Wellcome Dept of Cognitive Neurology). The primary aim was to investigate whether SPM is an effective decision aid and whether it impacts on the confidence of image reporting. The secondary aim was to examine the influence of SPM on the agreement between image reporting and clinical diagnosis. The results showed that there was a slight decrease in agreement between the imaging specialists after the introduction of additional information from SPM (K=0.57 to K=0.5) and that agreement between imaging reporting (including information from SPM) and clinical diagnosis was moderate (K=0.28). This study was able to confirm that SPM is capable of producing meaningful significance maps of individual patients in a routine clinical environment. However, there was no overwhelming evidence that SPM was able to resolve many of the dilemmas associated with the use of SPECT for the differential diagnosis of dementia. In particular, interpretation of SPECT perfusion patterns in dementia is a bigger problem than the initial identification of abnormalities.
Behavioural neurology 02/2000; 12(1-2):77-86. · 1.77 Impact Factor
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ABSTRACT: There is evidence for the involvement of the cingulate gyrus in schizophrenia. We present details of a Statistical Parametric Mapping (SPM) analysis of SPECT data from the largest study (N = 39) of drug naive schizophrenic patients. The main findings are that there is decreased perfusion in the anterior cingulate during verbal fluency when patients are compared to controls (matched individually by age, gender and father's social class as determined by occupation) and also that PANSS negative scores correlate negatively with regional cerebral blood flow in the cingulate gyrus (Pearson's Correlation coefficient of r = - 0.49 and significance p< 0.005). This suggests that measurement of change of perfusion in this region could be a useful biological marker in assessing the effect of neuroleptics on negative symptoms.
Behavioural neurology 02/2000; 12(1-2):93-101. · 1.77 Impact Factor
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ABSTRACT: We investigated whether SPET studies of neuroactivation might benefit from a similar approach used in PET; that is, increase the number of scans per task and accept poorer individual scan quality. Different study paradigms were simulated by varying the scanning parameters: (1) administered radiation activity per scan, (2) number of scans per task and (3) scan acquisition time. The maximum total dose received by each simulated subject remained the same. Areas of activation of varying signal strength were added to the scans using a customized graphics package. To establish the statistical benefits of a replication paradigm versus a non-replication paradigm, the datasets were analysed using SPM95 statistics software. This simulation was able to show that, when an SPM investigation is used for data analysis, study replication is more important than the individual image quality typically available from a high-performance SPET system.
Nuclear Medicine Communications 01/1998; 18(12):1155-60. · 1.40 Impact Factor
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ABSTRACT: Although much has been published concerning the various safety risks associated with magnetic resonance (MR) imaging, little mention is made of the acoustic noise generated during scanning. The existing data are now out of date with regard to currently used imaging protocols and technology. Out of concern for patient safety, measurements were made of the acoustic noise generated during various scan protocols on a high field (1.5 T) Siemens MR imager. These data were compared with published data. The data show that for certain protocols, the exposure to acoustic noise falls outside safety guidelines unless ear protection is used.
British Journal of Radiology 05/1994; 67(796):413-5. · 1.31 Impact Factor
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ABSTRACT: The pattern of abnormal distribution of the single photon emission computed tomography (SPECT) cerebral blood flow tracer 99m-technetium-hexamethylpropyleneamine oxime (99Tcm-HMPAO) was investigated in 14 patients with clinically diagnosed Alzheimer's disease (AD) who subsequently had post-mortem confirmation of the disease and also in 14 elderly control subjects. These abnormalities were compared with computed tomography (CT) scans to investigate the degree to which the focal SPECT deficits were due to atrophy. The results show that SPECT imaging with 99Tcm-HMPAO and CT scanning both have a higher incidence of abnormality in AD patients than in controls and that the difference between patients and controls is greater with SPECT than with CT. Frontal SPECT and CT abnormalities in moderate/severe Alzheimer's disease occur as frequently as temporal/occipital abnormalities but the latter are rare in control subjects. Around 50% of the SPECT deficits occur in CT normal brain regions, showing that atrophy is not the sole cause of SPECT deficits.
British Journal of Radiology 02/1993; 66(781):23-7. · 1.31 Impact Factor
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ABSTRACT: Focal post traumatic mass lesions such as contusions and intracerebral haematomas are common, and often difficult for neurosurgeons to manage, because little is known of their pathophysiology. We have mapped cerebral blood flow, and studied small vessel ultrastructure at different time points within the first three weeks of head injury, in patients with these lesions. A zone of ischaemic brain is always present around these lesions, and persists for weeks or months. This accords with astrocyte swelling and microvascular compression seen on electron microscopy. Focal zones of hyperaemia were also present in 42% of patients, within the first two weeks of injury, and this appeared only within apparently normal tissue as judged by late MRI or CT.
Acta neurochirurgica. Supplement 02/1992; 55:14-7.
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ABSTRACT: Uptake of 99mTc-Exametazime, a marker of relative regional cerebral blood flow has been determined with Single Photon Emission Tomography (SPET or SPECT) in 20 healthy, elderly female subjects during neuropsychological challenge. Each subject was studied under basal conditions after injection of 125 MBq 99mTc-Exametazime. Without moving the head of the subject, they were scanned again after injection of 375 MBq 99mTc-Exametazime. The second injection was made in 10 subjects during a test of verbal fluency, usually regarded as a test of the integrity of function of the left frontal cortex. In the other 10 subjects the second injection was made during simple verbalization (counting). This method of splitting the normal full dose of 99mTc-Exametazime allows a novel comparison between basal and active conditions for different brain regions. Verbal fluency was associated with reduced uptake bilaterally in the region of the basal ganglia and in left temporal (peri-sylvian) cortex when compared with calcarine cortex, an unstimulated reference sensory area. By contrast, counting produced relative activation, greatest in frontal and parietal areas. Thus, a clinically relevant neuropsychological test can be characterized metabolically by a pattern of regional brain activity, whose localization cannot readily be predicted from classical studies of brain lesions. Reduction of regional uptake may suggest an important role for deactivation or inhibition of function in human cognition. The involvement of basal ganglia and temporal areas is of particular interest in relation to the investigation of functional psychiatric illness.
Psychological Medicine 09/1991; 21(3):687-96. · 6.16 Impact Factor
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ABSTRACT: Single photon emission computed tomography (SPECT) with 99mTc-HMPAO was used to image 26 patients with dementia of the Alzheimer type (DAT) and 10 healthy controls. Regional cerebral blood flow (rCBF) data indicated a relative sparing of the occipital regions in DAT. Normalisation to occipital flow illustrated highly significant CBF deficits in a number of cortical regions, particularly in the left and right posterior--temporal cortex in DAT compared to controls. The cognitive performance of DAT patients was measured using a clinical cognitive assessment procedure (CAMCOG) and numerous correlations between these scores and rCBF were obtained. The implications and value of this investigative technique are discussed.
Journal of Neurology Neurosurgery & Psychiatry 02/1990; 53(1):33-8. · 4.76 Impact Factor
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ABSTRACT: We have tomographically mapped changes in the blood brain barrier (BBB) (99 mTc Pertechnetate) in 20 patients with acute contusions, and four with acute subdural haematomas in situ. The changes were related to regional CBF, (99 mTc HMPAO SPECT) T2 weighted MRI scans, CT abnormalities and the clinical features. Seventy-five percent of contusions were accompanied by a BBB abnormality, usually a "halo" around the lesion, which was more common in scans made after the second day. All contusions demonstrated "oedema" as a zone of "T2" signal on MRI or a zone of lucency on CT, and all were accompanied by a focal zone of low CBF on SPECT. Early contusional oedema appears to be cytotoxic but in certain cases, delayed blood brain barrier lesions develop, suggesting a vasogenic component.
Acta neurochirurgica. Supplement 02/1990; 51:286-8.
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ABSTRACT: Single photon emission tomography (SPET) with the lipophilic blood flow marker 99mTc-hexamethyl propyleneamine oxime (99mTc-HMPAO) has been used to determine regional uptake of radiolabel into brain regions of patients with presenile Alzheimer's disease and Korsakoff's psychosis, and age-matched controls. Using occipital cortical uptake as reference area, the pattern of relative regional cerebral blood flow (rCBF) was determined in other cortical areas and basal ganglia. In Alzheimer's disease, reduction in rCBF occurred most strikingly in posterior temporal and parietal areas. By contrast, in Korsakoff's psychosis, posterior temporal rCBF was maintained, although there was a trend to reduced tracer uptake in other cortical areas. These impairments of flow were correlated with impairments of neuropsychological function. In Alzheimer's disease, left posterior temporal and left parietal regions in particular showed rCBF to be strongly correlated with most aspects of cognitive function. In Korsakoff's psychosis, however, impaired flow in frontal regions was correlated with impaired performance on tests of memory and orientation. The findings in Alzheimer's disease show quantitative parallels with those from studies using Positron Emission Tomography (PET), and extend our understanding of the relationship between cognition and regional brain function in dementia. The findings in Korsakoff's psychosis offer the first direct evidence linking frontal lobe dysfunction with the cognitive impairment seen in the disorder.
Psychological Medicine 12/1989; 19(4):847-55. · 6.16 Impact Factor
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ABSTRACT: Investigated 16 patients with diffuse or contusional brain damage and 8 patients with focal lesions 5–22 mo postinjury, using single proton emission computed tomography (SPECT) cerebral blood flow (CBF) measurements and neuropsychological examination. All Ss were aged 16–64 yrs. Compared with 16 controls, the diffuse group showed significant differences on 13 of 24 measures after correction for premorbid differences, whereas the focal group was significantly impaired on only 3 tests after correction. SPECT apparently identified abnormalities not demonstrated on magnetic resonance (MR) imaging and vice versa. Abnormal regional CBF seemed to be related to neuropsychological defects. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Neuropsychology 10/1989; 3(4):267-281. · 3.82 Impact Factor
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The Lancet 02/1989; 1(8631):214. · 38.28 Impact Factor
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ABSTRACT: Cranial CSF volumes, for the first time including CSF in the subarachnoid space, can be measured by Magnetic Resonance Imaging (MRI). The MRI sequence causes signal from the grey matter and white matter to cancel producing a contrast of 200: 1 between a unit of CSF and a unit of brain. We have assessed the variations between normal individuals and investigated some of the physiological factors that might influence cranial CSF volumes. Total CSF volumes were measured in 64 normal subjects, aged from 18-64 years (mean 38 years). Ventricular, cortical sulcal and posterior fossa volumes were also calculated separately. In 20 females with a normal menstrual cycle, CSF volumes were measured mid cycle and premenstrually; 10 post menopausal females and 10 males were rescanned after an interval of 2 weeks. Total cranial CSF volume were calculated before and during inhalation of 7% CO2 and before and during hyperventilation while breathing 60% O2, in 12 normal subjects. Total intracranial CSF volume ranged from 57.1-286.5 ml. Total intracranial and cortical sulcal CSF volumes increased more steeply with age than ventricular or posterior fossa CSF volumes. Males had more cranial CSF than females. Total CSF volume increased premenstrually in 19 females. Males and post-menopausal females did not have a significant change in CSF volume, on repeat examination. CO2 inhalation produced a mean increase of paCO2 of 17.2 mmHg and CSF volume decreased in all subjects (mean 9.4 ml). Cranial CSF volume increased in 11 subjects during O2 inhalation (range -0.5 to +26.7 ml mean 10.9 ml).(ABSTRACT TRUNCATED AT 250 WORDS)
Acta neurochirurgica. Supplement 02/1988; 42:230-5.
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British Journal of Radiology 02/1987; 60(709):83-7. · 1.31 Impact Factor
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ABSTRACT: Magnetic resonance imaging was used to measure intracranial extraventricular and ventricular cerebrospinal fluid (CSF) volume. In 10 normal subjects lateral ventricular and extraventricular intracranial CSF volumes were 25.3 +/- 4.6 ml (mean +/- SD) and 97.6 +/- 6.6 ml, respectively (total 122.8 +/- 38.7). These volumes were measured in 4 patients and the results were: 11.0 ml ventricular volume, 68.7 ml total cranial CSF in the patient with benign intracranial hypertension; 606.6 ml ventricular, 174.1 ml total in the patient with hydrocephalus due to a blocked ventriculo-peritoneal (V-P) shunt; 83.4 ml ventricular, 108.5 ml total in the patient with normal pressure hydrocephalus; and 52.7 ml ventricular, 181.0 ml total in the patient with cerebral atrophy due to Alzheimer's disease. The technique gave highly reproducible results (SD less than 5.7% of mean value). It may be useful in differential diagnosis and as an objective means of monitoring therapy or progress in conditions such as cerebral atrophy, hydrocephalus, and benign intracranial hypertension.
The Lancet 07/1986; 1(8494):1355-7. · 38.28 Impact Factor
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ABSTRACT: The response of cerebral blood flow (CBF) to drug-induced hypotension was measured in 20 patients who underwent craniotomy for clipping of a cerebral aneurysm following subarachnoid hemorrhage. A modified intravenous xenon-133 injection technique was used to monitor CBF. In 15 patients, CBF increased significantly with hypotension, and only one developed a late neurological deficit. In five patients, CBF fell with halothane-induced hypotension, and four developed delayed neurological deficits. Measurement of the intraoperative CBF response to halothane-induced hypotension may reveal those patients at greatest risk of developing late neurological deficits and who require more intensive postoperative monitoring and early use of the induced hypertension technique.
Journal of Neurosurgery 10/1980; 53(3):305-8. · 2.96 Impact Factor
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ABSTRACT: A review of 15 recent publications purporting to provide the relaxation times of CSF reveals a considerable disparity in the quoted results, by a factor of five in terms of T1 (range 1,000 to 5,500 ms) and by a factor of 16 for T2 (range 166 to 2,640 ms). In this article measurements are performed independently on both a spectrometer and an imager. The results indicate that for CSF T1 is greater than 3,000 ms and T2 is approximately 2,000 ms at 6 MHz. The vast differences in relaxation behaviour between CSF and other body tissues have considerable clinical implications and present profound diagnostic opportunities. The application of this knowledge to ventriculography, myelography, and image contrast methodology is discussed.
Journal of Computer Assisted Tomography 11(2):203-7. · 1.22 Impact Factor
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