Being equipped for clinical PET.
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Humans↗
Biomedical subjects
P K Marsden
Publications and source records attributed to P K Marsden.
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
Clinical value of "ictal" FDG-positron emission tomography and the routine use of simultaneous scalp EEG studies in patients with intractable partial epilepsies.
PURPOSE: EEG is widely used during positron emission tomography (PET) to confirm the interictal state of the patient and assist in scan interpretation when a seizure occurs. Ictal scans usually reflect mixed interictal-ictal-postictal metabolic activity as seizures are brief in comparison to the 30-min uptake period of the tracer. We wished to determine whether routine EEG is justified and if seizures commonly affect the diagnostic information of the PET scan. METHODS: We examined the PET scans of 6 of 236 outpatients with intractable epilepsy with clinical and electrical evidence of a seizure during tracer uptake. We performed semi-quantitative analysis in 2 patients who had "ictal" and control interictal scans. RESULTS: Patients with single seizures lasting 23 s to 4 min [four complex partial seizures (CPS) and one absence seizure (AS)] had focal hypometabolism concordant with results of other investigations. One patient with complex partial status had irregular cortical uptake and focal hypometabolism, but the site of the ictal focus could not be confirmed. CONCLUSIONS: In this group of patients, seizures occurred infrequently during tracer uptake. The interpretation of the PET scan when single seizures occurred did not appear to be influenced by the continuous scalp EEG (CSEEG) recordings. The value of routine CSEEG in outpatients treated with medication should be reappraised, with potential cost savings. In rare circumstances in which a true ictal study occurs (complex partial status, epilepsia partialis continua, and repetitive CPS), PET scanning may be inconclusive and repeat interictal scanning should be pursued.
Adolescent↗
PET and NMR dual acquisition (PANDA): applications to isolated, perfused rat hearts.
Positron emission tomography and nuclear magnetic resonance spectroscopy are non-invasive techniques that allow serial metabolic measurements to be obtained in a single subject. Significant advantages could be obtained if both types of scans could be acquired with a single machine. A small-scale PET scanner, designed to operate in a high magnetic field, was therefore constructed and inserted into the top half of a 7.3 cm bore, 9.4 T NMR magnet and its performance characterized. The magnetic field did not significantly affect either the sensitivity (approximately 3 kcps/MBq) or the spatial resolution (2.0 mm full width at half maximum, measured using a 0.25 mm diameter line source) of the scanner. However, the presence of the PET scanner resulted in a small decrease in field homogeneity. The first, simultaneous 31P NMR spectra (200, 80 degrees pulses collected at 6 s intervals) and PET images (transverse, mid-ventricular slices at the level of the mitral value) from isolated, perfused rat hearts were acquired using a specially designed NMR probe inserted into the bottom half of the magnet. The PET images were of excellent quality, enabling the left ventricular wall and interventricular septum to be clearly seen. In conclusion, we have demonstrated the simultaneous acquisition of PET and NMR data from perfused rat hearts; we believe that the combination of these two powerful techniques has tremendous potential in both the laboratory and the clinic.
Adenosine Triphosphate↗
Simultaneous PET and MR imaging.
We have developed a prototype PET detector which is compatible with a clinical MRI system to provide simultaneous PET and MR imaging. This single-slice PET system consists of 48 2 x 2 x 10 mm3 LSO crystals in a 38 mm diameter ring configuration that can be placed inside the receiver coil of the MRI system, coupled to three multi-channel photomultipliers housed outside the main magnetic field via 4 m long and 2 mm diameter optical fibres. The PET system exhibits 2 mm spatial resolution, 41% energy resolution at 511 keV and 20 ns timing resolution. Simultaneous PET and MR phantom images were successfully acquired.
Equipment Design↗
Adaptive and maladaptive behaviour in children with epileptic encephalopathies: correlation with cerebral glucose metabolism.
In the childhood epileptic encephalopathies mental impairment is common and severe. Traditional cognitive assessment is difficult because of the low level of performance, autistic features, and the unpredictable effect of seizures. An alternative is to measure adaptive and maladaptive behaviour using instruments administered to the caregivers. Adults with different types of dementia have characteristic patterns of cortical glucose hypometabolism. Thirty-two children were studied using visual and semiquantitative analysis of 18fluorodeoxyglucose positron emission tomographic (PET) scans. The Vineland Scales and the Conners' Questionnaires were used to assess adaptive and maladaptive behaviour. The mean adaptive behaviour composite score was 37.3+/-15.6; all but one subject had a low adaptive level. A profile of relative strength in socialisation and weakness in daily living skills emerged. Up to two-thirds of children had abnormal behaviour patterns, particularly attention-deficit disorders and hyperactivity. Adaptive and maladaptive behaviour was not related to the presence or absence of focal cortical PET abnormalities. However, adaptive behaviour scores showed an inverse correlation with the degree of metabolic abnormality in the frontal lobes.
Adaptation, Psychological↗
Cortical and subcortical glucose metabolism in childhood epileptic encephalopathies.
OBJECTIVES: Nearly one third of children with cryptogenic epileptic encephalopathies have been reported to have focal cortical defects on 18fluorodeoxyglucose (FDG) PET. As diffuse cortical dysfunction and involvement of subcortical structures, particularly the thalami, is postulated to underlie the propensity to seizures in these conditions, the aim was to determine the frequency of bilateral and diffuse cortical metabolic defects and of subcortical metabolic abnormalities in the same patients. METHODS: The interictal uptake of FDG was studied in 32 children with epileptic encephalopathies. Using a semiquantitative technique, the ratio of uptake in cortical regions and subcortical structures to that in the cerebellum was compared with that of age matched historical controls. Uptake more than 2 SD above ("hypermetabolic") or below ("hypometabolic") that of age matched controls was considered abnormal. RESULTS: Diffusely abnormal cortical up-take (nearly always hypometabolic) occurred in almost two thirds of patients; in all but two of the remaining patients at least one cortical region showed significantly decreased uptake bilaterally. When analysed as age cohorts, the mean cortical:cerebellar FDG uptake was significantly lower than that of controls in all cortical regions (P<0.005). Ninety per cent of patients had evidence of relative thalamic hypometabolism and in each age group there was a significant reduction in relative thalamic FDG uptake compared with that of controls (P<0.005). In nine out of 11 patients with unilateral cortical hypometabolic defects thalamic FDG up-take was lower ipsilateral to the cortical abnormality. CONCLUSIONS: Diffuse cortical dysfunction is common in the epileptic encephalopathies and may reflect the underlying cause of the condition or arise as a consequence of uncontrolled seizures. Altered thalamic glucose metabolism is further evidence of subcortical involvement in these conditions.
Cerebellum↗