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M J Fulham

Publications and source records attributed to M J Fulham.

At least 19 recordsLinked to original sources
PubMed2001

In vivo imaging of nicotinic receptor upregulation following chronic (-)-nicotine treatment in baboon using SPECT.

To quantify changes in neuronal nAChR binding in vivo, quantitative dynamic SPECT studies were performed with 5-[(123)I]-iodo-A-85380 in baboons pre and post chronic treatment with (-)-nicotine or saline control. Infusion of (-)-nicotine at a dose of 2.0 mg/kg/24h for 14 days resulted in plasma (-)-nicotine levels of 27.3 ng/mL. This is equivalent to that found in an average human smoker (20 cigarettes a day). In the baboon brain the regional distribution of 5-[(123)I]-iodo-A-85380 was consistent with the known densities of nAChRs (thalamus > frontal cortex > cerebellum). Changes in nAChR binding were estimated from the volume of distribution (V(d) ) and binding potential (BP) derived from 3-compartment model fits. In the (-)-nicotine treated animal V(d) was significantly increased in the thalamus (52%) and cerebellum (50%) seven days post cessation of (-)-nicotine treatment, suggesting upregulation of nAChRs. The observed 33% increase in the frontal cortex failed to reach significance. A significant increase in BP was seen in the thalamus. In the saline control animal no changes were observed in V(d) or BP under any experimental conditions. In this preliminary study, we have demonstrated for the first time in vivo upregulation of neuronal nAChR binding following chronic (-)-nicotine treatment.

Animals↗
PubMed2001

The effects of mesial temporal and cerebellar hypometabolism on learning and memory.

The effects of mesial temporal (MT) and cerebellar hypometabolism were studied using measures of verbal, visual and motor skill learning. Twelve patients with refractory temporal lobe epilepsy who showed asymmetrical mesial temporal lobe hypometabolism on [18F] fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) were given tests involving 4 consecutive learning trials and a 30-min delayed recall trial. Delayed recognition was also assessed for the words and designs, and skill transfer was evaluated for mirror drawing. Compared to 9 normal control participants, patients with more marked MT hypometabolism on the left had impaired delayed recall of words and patients with more marked MT hypometabolism on the right showed impaired learning of novel designs, but normal retention over delay. Patients were not impaired in their mirror-drawing performance. The findings for MT hypometabolism correspond well to those obtained in other studies where patients have been classified on the basis of side of hippocampal atrophy or temporal lobe excision.

Adult↗
PubMed2001

Simultaneous estimation of physiological parameters and the input function--in vivo PET data.

Dynamic imaging with positron emission tomography (PET) is widely used for the in vivo measurement of regional cerebral metabolic rate for glucose (rCMRGlc) with [18F]fluorodeoxy-D-glucose (FDG) and is used for the clinical evaluation of neurological disease. However, in addition to the acquisition of dynamic images, continuous arterial blood sampling is the conventional method to obtain the tracer time-activity curve in blood (or plasma) for the numeric estimation of rCMRGlc in mg glucose/100-g tissue/min. The insertion of arterial lines and the subsequent collection and processing of multiple blood samples are impractical for clinical PET studies because it is invasive, has the remote, but real potential for producing limb ischemia, and it exposes personnel to additional radiation and risks associated with handling blood. In this paper, based on our previously proposed method for extracting kinetic parameters from dynamic PET images, we developed a modified version (post-estimation method) to improve the numerical identifiability of the parameter estimates when we deal with data obtained from clinical studies. We applied both methods to dynamic neurologic FDG PET studies in three adults. We found that the input function and parameter estimates obtained with our noninvasive methods agreed well with those estimated from the gold standard method of arterial blood sampling and that rCMRGlc estimates were highly correlated (r = 0.973). More importantly, no significant difference was found between rCMRGlc estimated by our methods and the gold standard method (P > 0.16). We suggest that our proposed noninvasive methods may offer an advance over existing methods.

Adult↗
PubMed2000

The influence of tomograph sensitivity on kinetic parameter estimation in positron emission tomography imaging studies of the rat brain.

We investigated the influence of tomograph sensitivity on reliability of parameter estimation in positron emission tomography studies of the rat brain. The kinetics of two tracers in rat striatum and cerebellum were simulated. A typical injected dose of 10 MBq and a reduced dose of 1 MBq were assumed. Kinetic parameters were estimated using a region of interest (ROI) analysis and two pixel-by-pixel analyses. Striatal binding potential was estimated as a function of effective tomograph sensitivity (S(eff)) using a simplified reference tissue model. A S(eff) value of > or =1% was required to ensure reliable parameter estimation for ROI analysis and a S(eff) of 3-6% was required for pixel-by-pixel analysis. We conclude that effective tomograph sensitivity of 3% may be an appropriate design goal for rat brain imaging.

Animals↗
PubMed2000

Progressive supranuclear palsy pathology caused by a novel silent mutation in exon 10 of the tau gene: expansion of the disease phenotype caused by tau gene mutations.

Genetic mutations in the tau gene on chromosome 17 are known to cause frontotemporal dementias. We have identified a novel silent mutation (S305S) in the tau gene in a subject without significant atrophy or cellular degeneration of the frontal and temporal cortices. Rather the cellular pathology was characteristic of progressive supranuclear palsy, with neurofibrillary tangles concentrating within the subcortical regions of the basal ganglia. Two affected family members presented with symptoms of dementia and later developed neurological deficits including abnormality of vertical gaze and extrapyramidal signs. The third presented with dystonia of the left arm and dysarthria, and later developed a supranuclear gaze palsy and falls. The mutation is located in exon 10 of the tau gene and forms part of a stem-loop structure at the 5' splice donor site. Although the mutation does not give rise to an amino acid change in the tau protein, functional exon-trapping experiments show that it results in a significant 4.8-fold increase in the splicing of exon 10, resulting in the presence of tau containing four microtubule-binding repeats. This study provides direct molecular evidence for a functional mutation that causes progressive supranuclear palsy pathology and demonstrates that mutations in the tau gene are pleiotropic.

Aged↗
PubMed1998

Pretreatment and posttreatment positron emission tomographic scan imaging in a 20-year-old patient with Wilson's disease.

Wilson's disease is an autosomal-recessive inherited disorder that results in predominantly hepatic and neurologic manifestations. Neurologic abnormalities include tremor, ataxia, bradykinesia, rigidity, chorea, and dystonia. We report the clinical, radiologic, and serial FDG PET findings in a 20-year-old woman who presented with an asymmetric upper limb tremor caused by Wilson's disease. Reduced striatal and cerebral cortical glucose metabolism was demonstrated on a FDG PET study performed before the commencement of D-penicillamine therapy. After 6 months of treatment, the patient had shown only minimal clinical improvement, despite an increase in striatal and cerebral cortical glucose metabolism on a repeat FDG PET study. After 14 months of treatment, however, a moderate clinical improvement was noted and there was further increase in glucose metabolism on FDG PET.

Adult↗
PubMed1998

Decreased brain glucose utilization in patients with Cushing's disease.

UNLABELLED: Glucocorticoid hormones affect glucose use in different tissues, and the results of several experimental studies have suggested that glucocorticoids have a central action on cerebral metabolism. PET, using the radiotracer 18F-fluorodeoxyglucose (FDG), permits the measurement of cerebral glucose metabolism. METHODS: To investigate whether cerebral glucose metabolism would be altered in patients with increased plasma glucocorticoid levels, we analyzed the FDG PET studies that were done on 13 patients with Cushing's disease and compared the results with those obtained in 13 age-matched normal control subjects. A second FDG PET scan was performed on 4 patients after surgical removal of the pituitary adenoma. RESULTS: Patients with Cushing's disease had a significant reduction in cerebral glucose metabolism compared with normal controls. In the patients on whom a second PET scan was performed, there was a trend toward increased glucose metabolism on the second scan when comparing pre- and postsurgery values for each patient. CONCLUSION: We suggest that the decreased cerebral glucose metabolism we observed in Cushing's disease is attributable to increased glucocorticoid levels, and we speculate that abnormal cerebral glucose metabolism might contribute to the cognitive and psychiatric abnormalities that are frequently observed in patients with Cushing's disease.

Brain↗
PubMed1997

Two novel (M233T and R278T) presenilin-1 mutations in early-onset Alzheimer's disease pedigrees and preliminary evidence for association of presenilin-1 mutations with a novel phenotype.

Eleven early-onset dementia families, all with affected individuals who have either presented clinical symptoms of early onset familial Alzheimer's disease (EOFAD) or have been confirmed to have EOFAD by autopsy, and two early onset cases with biopsy-confirmed AD pathology, were screened for missense mutations in the entire coding region of presenilin-1 (PS-1) and -2 (PS-2) genes. Missense mutations were detected by direct sequence analysis of PCR products amplified from genomic DNA templates of affected individuals. Three pedigrees were attributable to known mutations in the PS-1 gene: P264L, E280A and the splice acceptor site (G to T) mutation, which results in the deletion of residues 290-319 of PS-1 (PS-1 delta 290-319). In a fourth pedigree, a novel PS-1 mutation was identified in exon 7 (M233T), which is homologous to a pathogenic PS-2 mutation (M239V), and is characterized by a very early average age of onset (before the age of 35). In one early onset case, another novel PS-1 mutation was identified in exon 8 (R278T). Of the five remaining families and the other early onset case, none have missense mutations in the PS-1 or PS-2 genes, or in exon 16 and 17 of the APP gene. Moreover, two of the PS-1 mutations, PS-1 delta 290-319 and R278T, are associated with the co-presentation of familial spastic paraparesis (FSP) in some of the affected family members. Our data raise the possibility that the phenotypic spectrum associated with PS-1 mutations may extend beyond typical FAD to include FSP, a disease heretofore unsuspected to bear any relationship to FAD. In addition, our data suggest that other novel EOFAD loci, in addition to APP and the presenilin genes, are involved in the aetiology of up to 50% of EOFAD cases.

Adult↗
PubMed1997

Evaluation of two population-based input functions for quantitative neurological FDG PET studies.

The conventional measurement of the regional cerebral metabolic rate of glucose (rCMRGlc) with fluorodeoxyglucose (FDG) and positron emission tomography (PET) requires arterial or arterialised-venous (a-v) blood sampling at frequent intervals to obtain the plasma input function (IF). We evaluated the accuracy of rCMR-Glc measurements using population-based IFs that were calibrated with two a-v blood samples. Population-based IFs were derived from: (1) the average of a-v IFs from 26 patients (Standard IF) and (2) a published model of FDG plasma concentration (Feng IF). Values for rCMRGlc calculated from the population-based IFs were compared with values obtained with IFs derived from frequent a-v blood sampling in 20 non-diabetic and six diabetic patients. Values for rCMRGlc calculated with the different IFs were highly correlated for both patient groups (r > or = 0.992) and root mean square residuals about the regression line were less than 0.24 mg/min/100 g. The Feng IF tended to underestimate high rCMRGlc. Both population-based IFs simplify the measurement of rCMRGlc with minimal loss in accuracy and require only two a-v blood samples for calibration. The reduced blood sampling requirements markedly reduce radiation exposure to the blood sampler.

Adult↗
PubMed1996

Positron emission tomography in the detection and management of metastatic melanoma.

Initial reports suggest that positron emission tomography with [18F]fluorodeoxyglucose (FDG-PET) may offer greater diagnostic accuracy and versatility than conventional radiology in staging patients with metastatic melanoma. We reviewed the first 100 melanoma patients to have PET imaging at our institution. PET findings were correlated with all other available results, including plain X-ray, computed tomography (CT), magnetic resonance (MR) imaging, bone scintigraphy, clinical findings and histopathology. A total of 415 metastatic lesions were evaluated, 388 (93%) of which were detected by PET. In 20 patients, PET detected 24 metastases up to 6 months earlier than conventional imaging or physical examination. Selection of surgical or medical management was specifically influenced by PET findings in 22 patients, and PET was used to clarify another 12 cases where CT was inconclusive. In nine patients undergoing chemotherapy, PET was used to assess response to treatment. We conclude that FDG-PET can accurately detect metastatic melanoma with a single non-invasive scan, and can demonstrate some metastases months before conventional imaging techniques. PET can improve the selection of patients for surgery, has potential for monitoring response to treatment and may prove a cost-effective means of staging melanoma patients.

Adult↗
PubMed1996

Optimized sampling and parameter estimation for quantification in whole body PET.

Whole-body positron emission tomography (PET) has recently emerged as an important imaging tool for cancer detection and staging. Initial applications of the technique have been primarily qualitative. One of the major reasons is the limits imposed by kinetically undersampled data over the whole body, as opposed to the standard method of continuous dynamic sampling in one body location. In this paper, a new estimation method using weighted nonlinear least squares (WNLS) for the first bed position and Bayesian regression (BR) for subsequent positions is proposed. A general criterion for designing optimal sampling schedules which maximizes the measurement information with multiple bed positions is developed. The overall approach is illustrated with the problem of estimating the metabolic rate of glucose (MRGLu) in tumors at different axial positions (image bed positions) in the body by using computer simulations and patient data. The results show that estimates of MRGLu using sparse data and the optimized Bayesian approach are comparable with those obtained by standard methods and fully sampled data. This study demonstrates the potential of the technique described for quantification where several bed positions have to be used to image all the regions of interest (ROI).

Abdominal Muscles↗
PubMed1996

Validation of postinjection transmission measurements for attenuation correction in neurological FDG-PET studies.

UNLABELLED: Accurate estimation of local cerebral metabolic rate of glucose utilization (LCMRGlu) with PET requires a separate measurement of photon attenuation using a transmission source that extends study duration. The feasibility of postinjection transmission, (PIT) scanning has been demonstrated but not previously validated in humans. METHODS: Preinjection and postinjection transmission scans were performed in 26 patients undergoing routine [18F]fluorodeoxyglucose (FDG) neurological PET. The PIT data were processed with two methods: One estimated emission contamination using an independent emission scan (PITind); the other estimated the contamination directly from the PIT scan, using simultaneously acquired emission data for subtraction (PITsim). These methods were compared with measured attenuation correction (AC) using preinjection transmission data (ACpre) and calculated AC (ACcalc). After reconstruction, image data were reformatted to fit a standard brain atlas to facilitate analysis of the region of interest and to allow subtraction of datasets averaged over all subjects. RESULTS: The ratios of LCMRGlu values with respect to those obtained by the ACpre method ranged from 0.98 to 1.06 (mean +/- s.d., 1.01 +/- 0.02) for PITind, from 0.96 to 1.04 (mean 0.99 +/- 0.02) for PITsim and from 0.77 to 1.12 (mean 0.96 +/- 0.07) for ACcalc. Both PIT methods agreed well with the ACpre method, whereas ACcalc gave rise to appreciable bias in structures near thick bone or sinuses. CONCLUSION: Accurate quantitative estimates of LCMRGlu can be obtained using PIT measurements. The PIT methods shorten study duration and increase patient throughput. The PITsim method has the further advantage that it is not affected by tracer redistribution and can therefore be applied to tracers with relatively rapid kinetics in vivo.

Brain↗
PubMed1996

Automated interstudy image registration technique for SPECT and PET.

UNLABELLED: We report the extended application of an automated computer technique for three-dimensional spatial registration of SPECT and PET studies. METHODS: The technique iteratively reslices a misaligned data set until the sum of the absolute differences (SAD) from a reference data set is minimized. The registration accuracy was assessed in Hoffman brain phantom studies collected with known misalignments and transmission studies of a thorax phantom with fiducial markers. The SAD was compared with three other cost functions: stochastic sign change criterion, sum of products and standard deviation (s.d.) of ratios. In clinical neurological and myocardial perfusion studies, registration accuracy was estimated from the relative locations of landmarks in the reference and registered data sets. RESULTS: Registration accuracy in the Hoffman brain phantom studies was -0.07 +/- 0.46 mm (mean +/- s.d.) for translations and -0.01 +/- 0.20 degrees for rotations, with maximum translation and rotation errors of 1.2 mm and 0.8 degree, respectively. The SAD was the most accurate and reliable cost function. Registration errors in the thorax phantom were 3.1 +/- 1.7 mm. Mean accuracy in the neurological studies, estimated from landmark pairs, was 2.0 +/- 1.1 mm for SPECT to SPECT and 1.8 +/- 1.1 mm for PET to SPECT registrations. Average registration accuracy in 201Tl myocardial perfusion studies was 2.1 +/- 1.2 mm. CONCLUSION: Our registration method (a) provided accurate registrations for phantom and clinical SPECT and PET studies, (b) is fully automated, (c) simplifies comparison of data sets obtained at different times and with different modalities, and (d) can be applied retrospectively.

Algorithms↗
PubMed1995

Decreased cerebral glucose metabolism in patients with brain tumors: an effect of corticosteroids.

The authors measured cerebral glucose metabolism (CMRglu) using [18F]fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) in patients with brain tumors to evaluate the effect of exogenous corticosteroids (in this instance, dexamethasone) on glucose metabolism. Fifty-six FDG-PET studies obtained in 45 patients with unilateral supratentorial brain tumors were analyzed. Patients with brain tumors were divided into three groups: 1) patients with cushingoid symptoms, who had been treated with combinations of radiotherapy and chemotherapy taking oral dexamethasone; 2) patients not taking dexamethasone but treated with radiotherapy; and 3) patients not taking dexamethasone who had not been treated with radiotherapy. Serial FDG-PET scans were obtained in eight of the cushingoid patients. Glucose metabolism was measured in the contralateral cerebral and ipsilateral cerebellar hemispheres in patients and compared to measurements taken from 19 normal volunteers. The authors found that in the cushingoid brain tumor patients there was a marked reduction in CMRglu compared to normal volunteers and other brain tumor patients (Kruskal-Wallis test; p 0.001). In the majority of patients who had serial FDG-PET scans, there was a decline in glucose metabolism over time and in one patient, in whom dexamethasone was reduced in dosage, there was a subsequent increase in CMRglu. The authors conclude that there is a generalized reduction in CMRglu in brain tumor patients taking dexamethasone compared to other brain tumor patients and normal volunteers, and that this effect is independent of radiotherapy, concurrent anticonvulsant medication, and transhemispheric functional disconnection (transhemispheric diaschisis).

Adult↗
PubMed1995

Simultaneous emission and transmission measurements for attenuation correction in whole-body PET.

UNLABELLED: We describe a methodology for measuring and correcting for attenuation in whole-body PET using simultaneous emission and transmission (SET) measurements. METHODS: The main components of the methodology are: (a) sinogram windowing of low activity (< or = 50 MBq) rotating 68Ge/Ga rod sources, (b) segmented attenuation correction (SAC) and (c) maximum likelihood reconstruction using the ordered subsets EM (OS-EM) algorithm. The methods were implemented on a whole-body positron emission tomograph. Quantitative accuracy and the signal-to-noise ratio (SNR) were measured for a thorax-tumor phantom as functions of acquisition time (range: 2-20 min per position). RESULTS: When a typical rod source activity (200 MBq 68Ge/Ga) was used, emission SNR was 60% lower in simultaneous than in separate measurements. The difference was only 14% when the rods contained 45 MBq 68Ge/Ga. The SNR was further improved by SAC in conjunction with OS-EM reconstruction and the relative gain increased with increasing acquisition time. Quantitative estimates of tumor, liver and lung radioactivity agreed with values obtained from a separate high count measurement to within 8%, independent of acquisition time. CONCLUSION: Attenuation correction of whole-body PET images is feasible using SET measurements. There is good quantitative agreement with conventional methods and increased noise is offset by the use of SAC and OS-EM reconstruction.

Adult↗