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P K Marsden

Publications and source records attributed to P K Marsden.

At least 19 recordsLinked to original sources
PubMed2005

Differential changes in brain glucose metabolism during hypoglycaemia accompany loss of hypoglycaemia awareness in men with type 1 diabetes mellitus. An [11C]-3-O-methyl-D-glucose PET study.

AIMS/HYPOTHESIS: Hypoglycaemia unawareness in type 1 diabetes increases the risk of severe hypoglycaemia and impairs quality of life for people with diabetes. To explore the central mechanisms of hypoglycaemia awareness, we used [11C]-3-O-methyl-D-glucose (CMG) positron emission tomography (PET) to measure changes in global and regional brain glucose metabolism between euglycaemia and hypoglycaemia in aware and unaware diabetic subjects. MATERIALS AND METHODS: Twelve men with type 1 diabetes, of whom six were characterised as aware and six as unaware of hypoglycaemia, underwent two CMG-PET brain scans while plasma glucose was controlled by insulin and glucose infusion either at euglycaemia (5 mmol/l) or at hypoglycaemia (2.6 mmol/l) in random order. RESULTS: With hypoglycaemia, symptoms and sweating occurred only in the aware group. Brain glucose content fell in both groups (p=0.0002; aware, 1.18+/-0.45 to 0.02+/-0.2 mmol/l; unaware, 1.07+/-0.46 to 0.19+/-0.23 mmol/l), with a relative increase in tracer uptake in prefrontal cortical regions, including the anterior cingulate. No detectable differences were found between groups in global brain glucose transport parameters (K1, k2). The cerebral metabolic rate for glucose (CMRglc) showed a relative rise in the aware subjects (11.839+/-2.432 to 13.958+/-2.372) and a fall in the unaware subjects (from 12.457+/-1.938 to 10.16+/-0.801 micromol 100 g(-1) min(-1), p=0.043). CONCLUSIONS/INTERPRETATION: Hypoglycaemia is associated with reduced brain glucose content in aware and unaware subjects, with a relative preservation of metabolism in areas associated with sympathetic activation. The relative rise in global glucose metabolic rate seen in aware subjects during hypoglycaemia contrasted with the relative fall in the unaware subjects and suggests that cortical neuronal activation is a necessary correlate of the state of hypoglycaemia awareness.

3-O-Methylglucose↗
PubMed2003

An improved analytical detector response function model for multilayer small-diameter PET scanners.

The optimization of spatial resolution is a critical consideration in the design of small-diameter positron emission tomography (PET) scanners for animal imaging, and is often addressed with Monte Carlo simulations. As a faster and simpler solution, we have developed a new analytical model of the PET detector response function, and implemented the model for a small single-slice, multilayer PET scanner. The accuracy of the model has been assessed by comparison with both Monte Carlo simulations and experimental measurements published in the literature. Results from the analytical model agreed well with the Monte Carlo method, being noise free and two to three orders of magnitude faster. The only major discrepancy was a slight underestimation of the width of the point spread function by the analytical method as inter-crystal scatter is neglected. We observed good agreement between the predictions of the model and experimental measurements. For two large-diameter scanners additional discrepancies were seen due to photon acollinearity, which is not considered in the model. We have shown that the simple and fast analytical detector response function model can provide accurate estimates of spatial resolution for small-diameter PET scanners, and could be a useful tool for several applications, complementing or cross-validating other simulation methods.

Algorithms↗
PubMed2002

Quantification of skeletal kinetic indices in Paget's disease using dynamic 18F-fluoride positron emission tomography.

The purpose of this study was to quantify indices of regional bone metabolism in Paget's disease and to compare these indices with normal bone using dynamic 18F-fluoride positron emission tomography (PET). Seven patients with vertebral Paget's disease had 1 h dynamic 18F-fluoride PET scans performed. The scans included a diseased vertebra and an adjacent normal vertebra. Arterial plasma input functions were also measured. A three-compartment, four-parameter model was used with nonlinear regression analysis to estimate bone kinetic variables. Compared with normal bone, pagetic bone demonstrated higher values of plasma clearance to bone mineral (Ki; 1.03 x 10(-1) vs. 0.36 x 10(-1) ml/min per milliliter; p = 0.018) and clearance to total bone tissue (K1; 2.38 x 10(-1) vs. 1.25 x 10(-1) ml/min per milliliter; p = 0.018), reflecting increased mineralization and blood flow, respectively. Release of 18F-fluoride from bone mineral (k4) was lower in pagetic bone (p = 0.022), suggesting tighter binding of 18F-fluoride to bone mineral. The notional volume of the extravascular bone compartment (K1/k2) was greater in pagetic bone (p = 0.018). Although the unidirectional extraction efficiency from the extravascular space to bone mineral (Ki/K1) was greater in pagetic bone (p = 0.018), a lower pagetic value of k2 (p = 0.028), describing the rate of transfer from the bone extravascular compartment to plasma, suggests that the 18F-fluoride that enters the relatively fibrotic marrow space of pagetic bone may be less accessible for return to plasma. These findings confirm some of the known pathophysiology of Paget's disease, introduce some new observations, and show how dynamic 18F-fluoride PET may be of value in the measurement of regional metabolic parameters in focal bone disorders.

Aged↗
PubMed2001

Effect of corrections for blood glucose and body size on [18F]FDG PET standardised uptake values in lung cancer.

Standardised uptake values (SUVs) are commonly used as a semi-quantitative index of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) tracer uptake in positron emission tomography (PET). Studies have shown that SUVs may depend on body size and blood glucose concentration and corrections for these effects have been proposed in the literature. This retrospective study investigated the effect of the proposed corrections on SUVs from a group of 154 patients with lung cancer who had scans on a dedicated PET scanner. A total of 252 SUVs were requested as an aid to staging during consideration for surgical resection. SUVs were calculated normalised to body weight (SUVw), lean body mass (SUV(LBM)) and body surface area (SUV(BSA)). The following correlations were examined: SUV with height, weight and body surface area for the different body size normalisations; SUVw and SUVw x blood glucose (SUV(BG)) with blood glucose; SUVw with scan time post injection; and SUVw with apparent lesion diameter. Significant correlations were only observed between: SUV(LBM) and height (P=0.007); SUVw and scan time (P=0.007); SUVw and lesion diameter (P=0.0005); and SUV(BG) and blood glucose (P<0.00001). The correlation between SUV(LBM) and height suggests that lean body mass as a function of height alone should not be used to normalise SUVs; however, the lean body mass calculated from a height and weight nomogram did not show this effect. The strong correlation between SUV(BG) and blood glucose concentration suggests that for non-diabetic fasted patients, lung tumour SUVs should not be adjusted for blood glucose.

Adult↗
PubMed2001

Changes in regional brain (18)F-fluorodeoxyglucose uptake at hypoglycemia in type 1 diabetic men associated with hypoglycemia unawareness and counter-regulatory failure.

We examined the effects of acute moderate hypoglycemia and the condition of hypoglycemia unawareness on regional brain uptake of the labeled glucose analog [(18)F]fluorodeoxyglucose (FDG) using positron emission tomography (PET). FDG-PET was performed in diabetic patients with (n = 6) and without (n = 7) hypoglycemia awareness. Each patient was studied at plasma glucose levels of 5 and 2.6 mmol/l, applied by glucose clamp techniques, in random order. Hypoglycemia-unaware patients were asymptomatic during hypoglycemia, with marked attenuation of their epinephrine responses (mean [+/- SD] peak of 0.77 +/- 0.39 vs. 7.52 +/- 2.9 nmol/l; P < 0.0003) and a reduced global brain FDG uptake ([mean +/- SE] 2.592 +/- 0.188 vs. 2.018 +/- 0.174 at euglycemia; P = 0.027). Using statistical parametric mapping (SPM) to analyze images of FDG uptake, we identified a subthalamic brain region that exhibited significantly different behavior between the aware and unaware groups. In the aware group, there was little change in the normalized FDG uptake in this region in response to hypoglycemia ([mean +/- SE] 0.654 +/- 0.016 to 0.636 +/- 0.013; NS); however, in the unaware group, the uptake in this region fell from 0.715 +/- 0.015 to 0.623 +/- 0.012 (P = 0.001). Our data were consistent with the human hypoglycemia sensor being anatomically located in this brain region, and demonstrated for the first time a change in its metabolic function associated with the failure to trigger a counter-regulatory response.

Autonomic Nervous System↗
PubMed2000

A comparison of normalization effects on three whole-body cylindrical 3D PET systems.

Normalization coefficients in three-dimensional positron emission tomography (3D PET) are affected by parameters such as camera geometry and the design and arrangement of the block detectors. In this work, normalization components for three whole-body 3D-capable tomographs (the GE Advance, the Siemens/CTI962/HR+ and the Siemens/CTI951R) are compared by means of a series of scans using uniform cylindrical and rotating line sources. Where applicable, the manufacturers' normalization methods are validated, and it is shown that these methods can be improved upon by using previously published normalization protocols. Those architectural differences between the three tomographs that affect normalization are discussed with a view to drawing more general conclusions about the effect of machine architecture on normalization. The data presented suggest that uniformity of system response becomes easier to achieve as the uniformity of crystal response within the detector block is improved.

Humans↗
PubMed2000

Differences in skeletal kinetics between vertebral and humeral bone measured by 18F-fluoride positron emission tomography in postmenopausal women.

We have sought to investigate regional differences in skeletal kinetics between lumbar vertebrae and the humerus of postmenopausal women with 18F-fluoride positron emission tomography (PET). Twenty-six women, mean age 62 years, had dynamic PET scans of the lumbar spine and lower humerus after the injection of 180 MBq 18F-fluoride ion. Plasma arterial input functions (IFs) were calculated from a mean IF measured arterially from 10 women and scaled according to late individual venous activity. Vertebral and humeral time activity curves were measured by placing regions of interest (ROI) over lumbar vertebrae and the humeral shaft. Using a three-compartmental model and nonlinear regression analysis the macroconstant Ki, representing plasma clearance of fluoride to bone mineral, and the individual rate constants K1 (related to regional skeletal blood flow) and k2 to k4 describing transport between plasma, an extracellular fluid compartment and a bone mineral compartment, were measured. Mean vertebral Ki (3.47x10(-2) ml x min(-1) x ml(-1)) and K1 (1.08x10(-1) ml x min(-1) x ml(-1)) were found to be significantly greater than humeral Ki (1.64x10(-2) ml min(-1) ml(-1); P<0.0001) and K1 (3.90x10(-2) ml x min(-1) x ml(-1); P<0.0001) but no significant differences were found in k2, k3, and k4. These findings confirm differences in regional skeletal kinetics between lumbar vertebrae and the lower humerus. These observations may help increase our understanding of the regional differences in pathophysiology and response to treatment that have been observed in sites consisting predominantly of either trabecular or cortical bone. 18F-fluoride PET may prove to be a valuable technique in the noninvasive measurement of regional skeletal metabolism.

Adult↗
PubMed1999

A PET study of 18FDG uptake in soft tissue masses.

A study was performed with the aim of investigating some of the methodological factors affecting the ability of quantitative 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography to assess tumour malignancy. Twenty-nine patients with soft tissue masses were studied using a 6-hour scanning protocol and various indices of glucose metabolism were compared with histological grade. Significant differences were observed in the time-activity response of benign and high-grade tumours. High-grade sarcomas were found to reach a peak activity concentration approximately 4 h after injection whereas benign lesions reached a maximum within 30 min. This translated to improved differentiation between these two tumour types using a standard uptake value (SUV) derived from images acquired at later times. An SUV measured 4 h post-injection was found to be as useful an index of tumour malignancy as the metabolic rate of FDG determined using either Patlak or non-linear regression techniques. Each of these indices had a sensitivity and specificity of 100% and 76% respectively for the discrimination of high-grade sarcomas from benign tumours.

Case-Control Studies↗
PubMed1999

Are restrictions to behaviour of patients required following fluorine-18 fluorodeoxyglucose positron emission tomographic studies?

The clinical use of positron emission tomography (PET) is expanding rapidly in most European countries. It is likely therefore that patients receiving the tracer fluorine-18 fluorodeoxyglucose (18FDG) will be discharged to come into contact with family members, members of the public and ward staff. There are few direct measurements on which to base any recommendations with regard to radiation protection, and so we have measured the dose rates from patients undergoing clinical PET examinations in our centre. Seventy-five patients who underwent whole-body and brain 18FDG PET examinations were studied. Dose rates were measured at 0.1, 0.5, 1.0 and 2.0 m from the mid thorax on leaving the department. The median administered activity was 323 MBq with a 95th percentile value of 360 MBq. The median dose rates measured at the four distances were 90.0, 35.0, 14.0 and 5.0 microSv h-1 (the median dose rates per unit administered activity at 2 h post injection were 0.31, 0.11, 0.04 and 0.02 microSv h-1 MBq-1). The corresponding 95th percentile values were 174.0, 69.0, 29.0 and 7.5 microSv h-1 (0.43, 0.2, 0.08 and 0.03 microSv h-1 MBq-1). A number of social situations were modelled and an annual dose limit of 1 mSv was used to determine whether restrictive behavioural advice was required. In the case of nursing staff on wards a value of 6 mSv was regarded as the annual limit, which translates to a daily limit of approximately 24 microSv. There is no need for restrictive advice for patients travelling by public or private transport when they leave the department 2 h after the administration of 18FDG. Similarly, there is no need for restrictive advice with regard to their contact with partners, work colleagues or children of any age, although it should be stressed that children should not accompany the patient to the scanning department. The only possible area of concern is in an oncology ward, where patients may be regularly referred for PET investigations and other high activity radionuclide studies and are partially helpless. Even in this area, however, it is unlikely that a nurse would receive a daily dose of more than 24 microSv. We conclude that there is no need for restrictive advice for patients undergoing 18FDG PET studies given the current administered activities.

Adolescent↗
PubMed1999

Non-invasive assessment of skeletal kinetics using fluorine-18 fluoride positron emission tomography: evaluation of image and population-derived arterial input functions.

To measure regional skeletal kinetics using fluorine-18 fluoride positron emission tomography (PET) it is necessary to know the concentration of radioactive tracer being delivered to bone by arterial plasma with relation to time, the arterial input function (IFa). Methods by which IFa can be derived without arterial sampling are attractive because of their relative technical simplicity and the reduction in possible morbidity to the subject. We have compared the use of a scaled population input function (IFp) and a corrected image-derived input function from the aorta (IFi) with an IFa directly measured from a radial artery line in ten normal postmenopausal women. Both of the aforementioned methods rely only on a small number of discrete venous samples. Each subject had a dynamic PET acquisition of the lumbar spine performed after the intravenous injection of 180 MBq (18)F-fluoride. Both the IFp and the IFi were compared with the IFa in terms of the accuracy of determination of six parameters. These were: plasma clearance of fluoride to bone mineral (K(i)), unidirectional plasma clearance to total bone tissue (K(1)) and individual rate constants k(2), k(3) and k(4), calculated using non-linear regression with a three-compartment model, and the plasma clearance to bone mineral calculated using the Patlak method (K(pat)). For both the IFp and the IFi method the root mean square errors for K(pat) and K(i) were similar and small (<8.2%). The errors in determining K(1) and the rate constants k(2) to k(4) are larger by either method, but with a small advantage using the IFp method. It is concluded that the use of either non-invasive method for determining the arterial plasma input function is suitable for the measurement of the most important parameters, K(i) and K(pat), in these subjects.

Female↗
PubMed1999

Differential uptake of FDG and DG during post-ischaemic reperfusion in the isolated, perfused rat heart.

Fluorine-18 2-fluoro-2-deoxyglucose (FDG) and 2-deoxyglucose (DG) are widely used as tracers of glucose uptake in the myocardium. Although there is agreement that the two analogues behave similarly to glucose under control conditions, there is growing evidence that some interventions (e.g. insulin stimulation or ischaemia/reperfusion) cause differential changes in their behaviour. The addition of a two-surface coil nuclear magnetic resonance (NMR) probe and a dual-perfusion cannula to our recently developed PET and NMR dual-acquisition (PANDA) system allows us to collect PET (FDG) images and phosphorus-31 NMR (2-deoxyglucose-6-phosphate) spectra simultaneously from each independently perfused coronary bed of the heart. We have used this technique to study the effect of regional ischaemia/reperfusion on FDG and DG uptake in the isolated, perfused rat heart. During control perfusion, FDG uptake was almost identical in both coronary beds. When one coronary bed was made ischaemic, FDG uptake ceased on that side but continued on the control side. Reperfusion failed to restore FDG uptake. In contrast, NMR spectra showed that, during reperfusion, the uptake and phosphorylation of DG did not differ between the two coronary beds. The results thus demonstrate that regional myocardial ischaemia/reperfusion has different effects on the uptake of FDG and DG in the isolated, perfused rat heart.

Animals↗
PubMed1999

Prospective evaluation of soft tissue masses and sarcomas using fluorodeoxyglucose positron emission tomography.

BACKGROUND: The differentiation of soft tissue sarcoma (STS) from benign masses is difficult owing to their clinical and radiological similarities. Accurate staging is hindered by the large number of sites at which metastases may be found. This study examined the value of whole-body [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) in patients presenting with soft tissue masses. METHODS: Thirty patients with a soft tissue mass suspected to be malignant were evaluated with FDG PET. The images were evaluated qualitatively and quantitatively for uptake of FDG to determine whether benign lesions could be differentiated from malignant tumours, and for the presence of metastases. RESULTS: Thirty-one masses were removed from 30 patients; 12 were benign and 19 were malignant STSs. Using qualitative assessment of the FDG PET images, all the high-grade STSs (n = 12) were correctly identified, but low-grade STS (n = 7) could not be differentiated from a benign lesion. Using a quantification assessment, there was a 95 per cent sensitivity and a 75 per cent specificity in diagnosing STS. Three patients had metastases at presentation; two were correctly identified by FDG PET. CONCLUSION: FDG PET has a role in distinguishing high-grade STS from low-grade or benign STS and may have a role in staging malignant tumours.

Adolescent↗
PubMed1999

Developments in component-based normalization for 3D PET.

Normalization in positron emission tomography (PET) is the process of ensuring that all lines of response joining detectors in coincidence have the same effective sensitivity. In three-dimensional (3D) PET, normalization is complicated by the presence of a large proportion of scattered coincidences, and by the fact that cameras operating in 3D mode encounter a very wide range of count-rates. In this work a component-based normalization model is presented which separates the normalization of true and scattered coincidences and accounts for variations in normalization effects with count-rate. The effects of the individual components in the model on reconstructed images are investigated, and it is shown that only a subset of these components has a significant effect on reconstructed image quality.

Adult↗
PubMed1999

Randoms variance reduction in 3D PET.

In positron emission tomography (PET), random coincidence events must be removed from the measured signal in order to obtain quantitatively accurate data. The most widely implemented technique for estimating the number of random coincidences on a particular line of response is the delayed coincidence channel method. Estimates obtained in this way are subject to Poisson noise, which then propagates into the final image when the estimates are subtracted from the prompt signal. However, this noise may be reduced if variance reduction techniques similar to those used in normalization of PET detectors are applied to the randoms estimates prior to use. We have investigated the effects of randoms variance reduction on noise-equivalent count (NEC) rates on a whole-body PET camera operating in 3D mode. NEC rates were calculated using a range of phantoms representative of situations that might be encountered clinically. We have also investigated the properties of three randoms variance reduction methods (based on algorithms previously used for normalization) in terms of their systematic accuracy and their variance reduction efficacy, both in phantom studies and in vivo. Those algorithms investigated that do not make assumptions about the spatial distribution of random coincidences give the best estimates of the randoms distribution. With the camera used, which has a limited axial extent (10.8 cm) and a large ring diameter (102 cm), the gains in image signal-to-noise ratio obtained with this technique ranged from approximately 5% to approximately 15%, depending on object size, activity distribution and the amount of activity in the field of view. Larger gains would be expected if this technique were to be employed on cameras of greater axial extent and smaller ring diameter.

Algorithms↗
PubMed1999

A study of artefacts in simultaneous PET and MR imaging using a prototype MR compatible PET scanner.

We have assessed the possibility of artefacts that can arise in attempting to perform simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) using a small prototype MR compatible PET scanner (McPET). In these experiments, we examine MR images for any major artefacts or loss in image quality due to inhomogeneities in the magnetic field, radiofrequency interference or susceptibility effects caused by operation of the PET system inside the MR scanner. In addition, possible artefacts in the PET images caused by the static and time-varying magnetic fields or radiofrequency interference from the MR system were investigated. Biological tissue and a T2-weighted spin echo sequence were used to examine susceptibility artefacts due to components of the McPET scanner (scintillator, optical fibres) situated in the MR field of view. A range of commonly used MR pulse sequences was studied while acquiring PET data to look for possible artefacts in either the PET or MR images. Other than a small loss in signal-to-noise using gradient echo sequences, there was no significant interaction between the two imaging systems. Simultaneous PET and MR imaging of simple phantoms was also carried out in different MR systems with field strengths ranging from 0.2 to 4.7 T. The results of these studies demonstrate that it is possible to acquire PET and MR images simultaneously, without any significant artefacts or loss in image quality, using our prototype MR compatible PET scanner.

Artifacts↗
PubMed1998

A clinical evaluation of the quantitative accuracy of simultaneous emission/transmission scanning in whole-body positron emission tomography.

We present a clinical evaluation of the quantitative bias which is introduced during simultaneous emission/transmission (SET) acquisition for the application of whole-body positron emission tomography (PET) with fluorine-18 2-fluoro-2-deoxy-d-glucose. The quantitative accuracy of the SET technique was assessed by means of a clinical study involving 28 patients and a realistic phantom experiment. In the clinical study, SET overestimated the activity concentration in the tumours by a factor of approximately 1.10, but in the phantom study, where the tumours were smaller, the bias was found to increase to a value of 1.39. The bias in the soft tissue regions of the patient studies varied between 1.03 and 1.36, and close agreement was observed with the corresponding phantom results. The extent of the bias increased as the local activity concentration decreased and we attribute the effect to scattered photons from the transmission source which are detected in the emission window during SET.

Artifacts↗
PubMed1998

Algorithms for calculating detector efficiency normalization coefficients for true coincidences in 3D PET.

Accurate normalization of lines of response in 3D PET is a prerequisite for quantitative reconstruction. Most current methods are component based, calculating a series of geometric and intrinsic detector efficiency factors. We have reviewed the theory behind several existing algorithms for calculating detector efficiency factors in 2D and 3D PET, and have extended them to create a range of new algorithms. Three of the algorithms described are 'fully 3D' in that they make use of data from all detector rings for the calculation of the efficiencies of any one line of response. We have assessed the performance of the new and existing methods using simulated and real data, and have demonstrated that the fully 3D algorithms allow the rapid acquisition of crystal efficiency normalization data using low-activity sources. Such methods enable the use of scatter-free scanning line sources or the use of very short acquisitions of cylindrical sources for routine normalization.

Algorithms↗