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D L Bailey

Publications and source records attributed to D L Bailey.

At least 19 recordsLinked to original sources
PubMed2003

Scaling images using their background ratio. An application in statistical comparisons of images.

Comparison of two medical images often requires image scaling as a pre-processing step. This is usually done with the scaling-to-the-mean or scaling-to-the-maximum techniques which, under certain circumstances, in quantitative applications may contribute a significant amount of bias. In this paper, we present a simple scaling method which assumes only that the most predominant values in the corresponding images belong to their background structure. The ratio of the two images to be compared is calculated and its frequency histogram is plotted. The scaling factor is given by the position of the peak in this histogram which belongs to the background structure. The method was tested against the traditional scaling-to-the-mean technique on simulated planar gamma-camera images which were compared using pixelwise statistical parametric tests. Both sensitivity and specificity for each condition were measured over a range of different contrasts and sizes of inhomogeneity for the two scaling techniques. The new method was found to preserve sensitivity in all cases while the traditional technique resulted in significant degradation of sensitivity in certain cases.

Algorithms↗
PubMed2002

A comparison of the progression of early Parkinson's disease in patients started on ropinirole or L-dopa: an 18F-dopa PET study.

OBJECTIVE: To study the relative rates of progression of early Parkinson's disease (PD) in patients started on a dopamine agonist, ropinirole, or L-dopa. METHODS: A double-blind study of 45 early PD patients [mean age 61 +/- 9.8 SD and mean symptom duration, 26 +/- 16 SD months] randomized 2 : 1 (ropinirole : L-dopa). Supplementary L-dopa was allowed if, during the trial, there was lack of a therapeutic effect. (18)F-dopa PET scans were performed at baseline (n = 45) and 2 years (n = 37). RESULTS: At two years, the mean percentage reduction in putamen (18)F-dopa uptake (Ki(o)) was not significantly different between the two groups (13% ropinirole, n = 28 versus 18% L-dopa, n = 9). CONCLUSIONS: We found no significant overall difference in underlying PD progression, after two years treatment, between patients groups. In summary, (18)F-dopa PET can be employed to objectively evaluate the effect of potential neuroprotective agents on dopaminergic function.

Aged↗
PubMed2000

Diamino benzo[b]thiophene derivatives as a novel class of active site directed thrombin inhibitors. 5. Potency, efficacy, and pharmacokinetic properties of modified C-3 side chain derivatives.

A systematic investigation of the structure-activity relationships of the C-3 side chain of the screening hit 1a led to the identification of the potent thrombin inhibitors 23c, 28c, and 31c. Their activities (1240, 903, and 1271 x 10(6) L/mol, respectively) represent 2200- and 2900-fold increases in potency over the starting lead 1a. This activity enhancement was accomplished with an increase of thrombin selectivity. The in vitro anticoagulant profiles of derivatives 28c and 31c were determined, and they compare favorably with the clinical agent H-R-1-[4aS, 8aS]perhydroisoquinolyl-prolyl-arginyl aldehyde (D-Piq-Pro-Arg-H; 32). The more potent members of this series have been studied in an arterial/venous shunt (AV shunt) model of thrombosis and were found to be efficacious in reducing clot formation. However, their efficacy is currently limited by their rapid and extensive distribution following administration.

Animals↗
PubMed2000

Physical characteristics of the ECAT EXACT3D positron tomograph.

The 'EXACT3D' positron tomograph, which is now in routine clinical research use, was developed with the aim of achieving unprecedented sensitivity, high spatial and temporal resolution and simplicity of design using proven detector technology. It consists of six rings of standard detector blocks (CTI/Siemens EXACT HR+) with 4.39 mm x 4.05 mm x 30 mm elements, giving an axial field of view (FOV) of 23.4 cm. This extended FOV and the absence of interplane septa and retractable transmission rod sources has allowed greatly simplified gantry and detector cassette design. Operation in exclusive 3D mode requires an alternative to the conventional coincidence method for transmission scanning, and a single photon approach using a hydraulically driven 137Cs point source has been implemented. The tomograph has no other moving parts. A single time frame of data without any compression is very large (> 300 Mbyte) and two approaches are employed to overcome this difficulty: (a) adjacent sinograms can be summed automatically into different combinations and (b) listmode (event-by-event) acquisition has been instituted, which is both storage efficient (particularly for acquisition of sparse data sets) and maximizes temporal resolution. The high-speed I/O and computing hardware can maintain a sustained acquisition rate of about 4 million coincidence events per second. A disadvantage of the large axial FOV in 3D is the increased sensitivity to activity outside the coincidence FOV. However, this can be minimized by additional side shielding. The mean spatial resolution is 4.8 +/- 0.2 mm FWHM (transaxial, 1 cm off-axis) and 5.6 +/- 0.5 mm (axial, on-axis). Its absolute efficiency is 5.8% for a line source in air (just spanning the axial FOV) and 10% for a central point source (with thresholds of 350-650 keV). For a uniform 20 cm diameter cylinder, the efficiency is 69 kcps kBq(-1) ml(-1) (after subtraction of a scatter fraction of 42%). Sensitivity relative to the EXACT HR+ (with four rings of blocks) is 2.5 (3D) and 12 (2D) times respectively. The rate of random events in blood flow studies in the brain and body, using 15O-labelled water, can be controlled by limiting the administered dose and inserting additional side shielding.

Cesium Radioisotopes↗
PubMed2000

Regional mucociliary clearance in patients with cystic fibrosis.

This paper reports on a large retrospective analysis of mucociliary clearance (MCC) studies in a group of 59 patients with cystic fibrosis (CF) and 17 age-matched healthy subjects. As many of the CF patients were studied on multiple occasions, a total of 184 patient studies are presented. MCC was measured using a radioaerosol and gamma camera technique. In addition to whole lung clearance, MCC was measured from the central, intermediate, peripheral, basal, mid and apical regions of the lung. MCC was markedly decreased in the CF patient group. Not only was whole lung clearance (14.2 +/- 1.4% vs. 28.0 +/- 3.7%) impaired, but also clearance from the central (19.1 +/- 1.9% vs. 35.6 +/- 4.3%), intermediate (10.7 +/- 1.6% vs. 25.5 +/- 3.7%), apical (12.4 +/- 2.6% vs. 31.6 +/- 4.6%) and mid (14.0 +/- 1.9% vs. 30.4 +/- 4.0%) regions. Attempts were made to identify factors that may have influenced MCC in both the normal subjects and CF patients. Age, gender, body mass index, patient genotype, penetration index, spontaneous cough, and various lung function parameters were entered into a stepwise multiple regression model, but none of the factors proved to be statistically important in determining MCC. Both intrasubject repeatability and intersubject variability estimates are presented for the patients and normal subjects that had multiple studies. The values were found to be remarkably similar for both CF patients and normal subjects and for both intra- and intersubject repeatability. With marked deviation from normal ranges and good repeatability, the measurement of MCC in CF patients would seem to be a valuable outcome measure for clinical trials involving new pharmaceuticals and physical therapy designed to improve removal of secretions from the airways.

Adolescent↗
PubMed1999

Dibasic benzo[b]thiophene derivatives as a novel class of active site directed thrombin inhibitors: 2. Sidechain optimization and demonstration of in vivo efficacy.

Potent, subnanomolar thrombin inhibitors 4, 5, and 6 are developed through side chain optimization of novel, benzo[b]thiophene-based small organic entities 2 and 3 and through SAR additivity studies of the new structural elements identified. X-ray crystallographic studies of 4b-thrombin complex revealed a hydrophobic and an electrostatic interaction of these new elements with thrombin at the S2 and S3 binding sites. In vitro and in vivo pharmacological studies showed that 4, 5, and 6 are potent anticoagulants in human plasma with demonstrated antithrombotic efficacy in a rat model of thrombosis.

Animals↗
PubMed1999

A dimeric form of Escherichia coli succinyl-CoA synthetase produced by site-directed mutagenesis.

Succinyl-CoA synthetase (SCS) catalyzes the substrate-level phosphorylation step of the citric acid cycle. The enzyme from Escherichia coli is an (alphabeta)2-heterotetramer with two active sites, one in each alphabeta-dimer. To determine whether the two active sites could function independently, mutations were made to split the tetramer into alphabeta-dimers. Because two choices for the tetramer (I and II) were possible from the X-ray crystallographic analyses, mutations were made at two different interfaces. All mutations based on tetramer I resulted in an intact tetramer. Of the two mutants based on tetramer II, one was insoluble and the other, where M156beta, Y158beta, R161beta and E162beta were changed to D, D, E and R, respectively, was a dimer. This quaternary structure was confirmed by fast protein liquid chromatography, blue native PAGE and ultracentrifugation. The DDER mutant has kinetic parameters similar to the tetrameric E. coli enzyme. Like the tetrameric enzyme, it shows ATP-facilitated dethiophosphorylation, proving that this property is a single-site effect. The ATP-facilitated dethiophosphorylation is inhibited by phosphate. It is concluded that dimerization of alphabeta-dimers is not a prerequisite for catalytic competency nor for alternating sites cooperativity in the tetramer. The rationale behind the dimer-of-dimers in E. coli SCS is still not known, but increased solubility, increased stability and in vivo interactions of the tetramer with other proteins are still possibilities.

Amino Acid Sequence↗
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

Frontal, midbrain and striatal dopaminergic function in early and advanced Parkinson's disease A 3D [(18)F]dopa-PET study.

We have studied focal changes in dopaminergic function throughout the brain volume in early and advanced Parkinson's disease by applying statistical parametric mapping (SPM) to 3D [(18)F]dopa-PET. Data from seven early hemi-Parkinson's disease and seven advanced bilateral Parkinson's disease patients were compared with that from 12 normal controls. Parametric images of [(18)F]dopa influx rate constant (K(i)(o)) were generated for each subject from dynamic 3D [(18)F]dopa datasets and transformed into standard stereotactic space. Significant changes in mean voxel [(18)F]dopa K(i)(o) values between the normal control group and each Parkinson's disease group were localized with SPM. Conventional region of interest analysis was also applied to comparable regions on the untransformed image datasets. In early left hemi-Parkinson's disease, significant extrastriatal increases in [(18)F]dopa K(i)(o) were observed in the left anterior cingulate gyrus and the dorsal midbrain region (P < 0.05, corrected) along with decreases in striatal [(18)F]dopa K(i)(o). In advanced Parkinson's disease, significant extrastriatal decreases in [(18)F]dopa K(i)(o) were observed in the ventral and dorsal midbrain regions (P < 0.05, corrected). No significant changes in [(18)F]dopa K(i)(o) were observed in the anterior cingulate region. In a direct comparison between the early and late Parkinson's disease groups, we observed relative [(18)F]dopa K(i)(o) reductions in ventral and dorsal midbrain, and dorsal pontine regions along with striatal [(18)F]dopa K(i)(o) reductions. Similiar results were found with a region of interest approach, on non-transformed data, except for the focal midbrain [(18)F]dopa K(i)(o) increase seen in early Parkinson's disease. In conclusion, using SPM with [(18)F]dopa-PET, we have objectively localized changes in extrastriatal, pre-synaptic dopaminergic function in Parkinson's disease. The significance of the increased dopaminergic activity of anterior cingulate in early Parkinson's disease remains unclear, but may be compensatory. The [(18)F]dopa signal in dorsal midbrain and pontine regions suggests that [(18)F]dopa is taken up by serotonergic and noradrenergic neurons which also degenerate in advanced Parkinson's disease. This suggests, therefore, that Parkinson's disease is a monoaminergic neurodegenerative disorder.

Biological Transport↗
PubMed1999

Statistical parametric mapping with 18F-dopa PET shows bilaterally reduced striatal and nigral dopaminergic function in early Parkinson's disease.

OBJECTIVE: To apply statistical parametric mapping to 18F-dopa PET data sets, to examine the regional distribution of changes in dopaminergic metabolism in early asymmetric Parkinson's disease. METHODS: Thirteen normal volunteers (age 57.7 (SD 16.5) years; four women, nine men ) and six patients (age 50.3 (SD 13.5) years; three women, three men) with asymmetric (right sided) Parkinson's disease were studied. Images from each dynamic dopa PET dataset were aligned and parametric images of 18F-dopa influx (Ki) were created for each subject. The Ki images were transformed into standard stereotactic space. The Ki values of the caudate and putamen on spatially normalised images were compared with the Ki values before normalisation. The application of statistical parametric mapping (SPM) allowed statistical comparison of regional Ki values on a voxel by voxel basis between healthy volunteers and patients with Parkinson's disease. RESULTS: There was a strong correlation between the Ki values before and after spatial normalisation (r=0.898, p=0.0001). Significant decreases in the Ki values were found for the Parkinson's desease group throughout the entire left putamen (p< 0.001) and focally in the dorsal right putamen (p<0.001). Decreased Ki values were also shown bilaterally in the substantia nigra (p< 0.01). CONCLUSION: Using (SPM) and 18F-dopa PET, reductions in both striatal and nigral brain dopaminergic function could be demonstrated in early Parkinson's disease.

Adult↗
PubMed1998

Transmission scanning in emission tomography.

Attenuation correction in single-photon (SPET) and positron emission (PET) tomography is now accepted as a vital component for the production of artefact-free, quantitative data. The most accurate attenuation correction methods are based on measured transmission scans acquired before, during, or after the emission scan. Alternative methods use segmented images, assumed attenuation coefficients or consistency criteria to compensate for photon attenuation in reconstructed images. This review examines the methods of acquiring transmission scans in both SPET and PET and the manner in which these data are used. While attenuation correction gives an exact correction in PET, as opposed to an approximate one in SPET, the magnitude of the correction factors required in PET is far greater than in SPET. Transmission scans also have a number of other potential applications in emission tomography apart from attenuation correction, such as scatter correction, inter-study spatial co-registration and alignment, and motion detection and correction. The ability to acquire high-quality transmission data in a practical clinical protocol is now an essential part of the practice of nuclear medicine.

Algorithms↗
PubMed1998

Parametric image reconstruction using spectral analysis of PET projection data.

Spectral analysis is a general modelling approach that enables calculation of parametric images from reconstructed tracer kinetic data independent of an assumed compartmental structure. We investigated the validity of applying spectral analysis directly to projection data motivated by the advantages that: (i) the number of reconstructions is reduced by an order of magnitude and (ii) iterative reconstruction becomes practical which may improve signal-to-noise ratio (SNR). A dynamic software phantom with typical 2-[11C]thymidine kinetics was used to compare projection-based and image-based methods and to assess bias-variance trade-offs using iterative expectation maximization (EM) reconstruction. We found that the two approaches are not exactly equivalent due to properties of the non-negative least-squares algorithm. However, the differences are small (< 5%) and mainly affect parameters related to early and late time points on the impulse response function (K1 and, to a lesser extent, VD). The optimal number of EM iteration was 15-30 with up to a two-fold improvement in SNR over filtered back projection. We conclude that projection-based spectral analysis with EM reconstruction yields accurate parametric images with high SNR and has potential application to a wide range of positron emission tomography ligands.

Algorithms↗
PubMed1998

Experience with fully 3D PET and implications for future high-resolution 3D tomographs.

The aim of this paper is to report on experience with 3D positron emission tomography (PET) in our institute where we have three 3D scanners, of which two operate exclusively in 3D mode (ECAT ART, EXACT 3D). Fully 3D PET requires attention to a number of factors which are not as problematic in 2D PET. Firstly, 3D tomographs designed for whole-body acquisition suffer from a large single-photon field of view, extending well beyond the coincidence field of view. Single photons from outside the coincidence field of view increase the dead time and random coincidence rates, and contribute scattered events. For brain studies, we have extended the lead side shielding at the ends of the tomograph to mitigate against these effects, and this has dramatically improved the count rate performance. This approach is not as effective for whole-body scanning. In addition, operating in 3D without septa necessitates new approaches to transmission scanning, as measurements using positron emitters such as 68Ge/68Ga have the unfavourable characteristics of high dead time and high scatter. Both of our fully 3D scanners use 137Cs for single-photon transmission measurements, although the data are treated differently. On the ECAT ART, a combination of physical and electronic collimation effectively reduces transmission scatter to acceptable levels. On the EXACT 3D physical collimation is not as readily implemented and therefore segmentation and reassignment of the histogrammed attenuation (mu) values is employed to produce unbiased attenuation correction factors in 3D. Many of the lessons learnt with these BGO (bismuth germanate) based tomographs will be applicable to the next generation of systems using faster detectors such as lutetium oxyorthosilicate (LSO).

Brain↗
PubMed1998

The effect of activity outside the direct field of view in a 3D-only whole-body positron tomograph.

The ECAT EXACT3D (CTI/Siemens 966) 3D-only PET tomograph has unprecedented sensitivity due to the large BGO (bismuth germanate) detector volume. However, the consequences of a large (23.4 cm) axial field-of-view (FOV) and the need for a patient port diameter to accommodate body scanning make the device more sensitive to photons arising from activity outside the direct (coincidence) FOV. This leads to relatively higher deadtime and an increased registration of random and scatter (true) coincidences. The purpose of this study is to determine the influence of activity outside the FOV on (i) noise-equivalent counts (NEC) and (ii) the performance of a 'model-based' scatter correction algorithm, and to investigate the effect of side shielding additional to that supplied with the tomograph. Annular shielding designed for brain scanning increased the NEC for blood flow (H[2]15O) measurement (integrated over 120 s) by up to 25%. For 11C tracer studies, the increase is less than 5% over 120 min. Purpose-built additional body shielding, made to conform to the shape of a volunteer, reduced the randoms count rate in a heart blood flow measurement (H[2]15O) by about 30%. After scatter correction the discrepancy between ROI count ratios for compartments within the 20 cm diameter 'Utah' phantom differed by less than 5% from true (sampled) activity concentration ratios. This was so with or without activity outside the FOV and with or without additional side shielding. Count rate performance is thus improved by extra shielding but more improvement is seen in head than in body scanning. Measurement of heart blood flow using bolus injections of H(2)15O would benefit from the use of detectors with lower deadtime and superior timing resolution such as LSO (lutetium oxyorthosilicate).

Algorithms↗
PubMed1998

Measuring the rate of progression and estimating the preclinical period of Parkinson's disease with [18F]dopa PET.

OBJECTIVES: To measure the rate of progression in striatal [18F]dopa metabolism in a large group (n=32) of patients with Parkinson's disease, to estimate the average duration of preclinical period, and to examine the influence of the PET method on the assessment of rate of progression and preclinical period. METHODS: Thirty two patients with Parkinson's disease (mean age 58 (SD 13) years, mean duration 39 (SD 33) months) were assessed with [18F]dopa PET and UPDRS scoring on two occasions a mean of 18 (SD 6) months apart. PET data were sampled with separate caudate and putamen and total striatal regions of interest, and both graphical (Ki) and ratio methods of analysis. RESULTS: The mean annual rate of deterioration in [18F]dopa uptake varied according to structure and method of analysis, with putamen Ki showing the most rapid mean rate of progression (4.7% of normal mean per year). The group showed a significant deterioration (p<0.0004, paired two tailed t test) in UPDRS and in the putamen (p=0.008) and total striatal (p=0.012) [18F]dopa uptake measured using a graphical analysis, but no significant change in caudate or putamen uptake measured by a ratio approach. A study of sensitivity confirmed that putamen Ki was the most sensitive measure of disease progression, caudate ratio the least. Symptom onset in Parkinson's disease was estimated at a mean putamen [18F]dopa uptake (Ki) of 75% of normal and a mean caudate [18F]dopa uptake (Ki) of 91% of normal. CONCLUSIONS: Estimation of mean rate of progression varies according to the sensitivity of a functional imaging method to clinical severity. Sensitivity and reproducibility of method must be considered when designing studies of disease progression and neuroprotection. The mean preclinical period in Parkinson's disease is unlikely to be longer than seven years.

Aged↗
PubMed1997

A method for calibrating three-dimensional positron emission tomography without scatter correction.

Calibration for three-dimensional positron emission tomography (3D PET) using a uniform cylinder and cross-calibration with aliquots requires correction for scatter and attenuation. Thus the accuracy of the calibration is dependent on the scatter correction method, and on the applicability of the scatter correction for different regions of the body. A method has been developed which provides a calibration which does not require correction for scatter or attenuation, making it generally applicable and independent of the scatter correction. The method has been previously described for measurement of the absolute sensitivity of tomographic devices. This approach has been extended to give a calibration of the PET camera "in air" in units of kBq/pixel. The reconstructed images are multiplied by this factor to give accurate activity concentrations, after attenuation and scatter correction. The method has been used with a fully 3D filtered backprojection (reprojection) algorithm and iterative convolution-subtraction scatter correction on data from an ECAT 953B. Using this method 3D PET images have been calibrated to within +/-5% accuracy, but this is highly dependent on the accuracy of the scatter correction. The method described here is practical and provides a means of calibrating a 3D PET system without the need for correction for scatter or attenuation of the calibration data.

Algorithms↗