Dale L. Bailey

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 ttest) 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.

A convolution-subtraction scatter correction method for 3D PET

3D acquisition and reconstruction in positron emission tomography (PET) produce data with improved signal-to-noise ratios compared with conventional 2D slice-oriented methods. However, the sensitivity increase is accompanied by an increase in the number of scattered photons and random coincidences detected. This paper presents a scatter correction technique for 3D PET data where an estimate of the scattered photon distribution is subtracted from the data before reconstruction. The scatter distribution is estimated by iteratively convolving the photopeak projections with a mono-exponential kernel. The method accounts for the 3D acquisition geometry and nature of scatter by performing the scatter estimation on 2D projections. The assumptions of the method have been investigated by measuring the variation in the scatter fraction and the scatter function at different positions in a cylinder. Both parameters were found to vary by up to 50% from the centre to the edge of a large water-filled cylinder. Despite this, in a uniform cylinder containing water with different concentrations of radioactivity, scatter was reduced from 25% in a non-radioactive region to less than 5% using the convolution-subtraction method. In addition, the relative concentration of a cylinder containing an increased concentration, which was underestimated by almost 50% without scatter correction, was within 5% of the true concentration after correction.

Fully three-dimensional reconstruction for a PET camera with retractable septa

A fully 3-D reconstruction algorithm has been developed to reconstruct data from a 16 ring PET camera (a Siemens/CTI 953B) with automatically retractable septa. The tomograph is able to acquire coincidences between any pair of detector rings and septa retraction increases the total system count rate by a factor of 7.8 (including scatter) and 4.7 (scatter subtracted) for a uniform, 20 cm diameter cylinder. The reconstruction algorithm is based on 3-D filtered backprojection, expressed in a form suitable for the multi-angle sinogram data. Sinograms which are not measured due to the truncated cylindrical geometry of the tomograph, but which are required for a spatially invariant response function, are obtained by forward projection. After filtering, the complete set of sinograms is backprojected into a 3-D volume of 128*128*31 voxels using a voxel-driven procedure. The algorithm has been validated with simulation, and tested with both phantom and clinical data from the 953B. >

Positon emission tomography. Basic sciences

1. Positron Emission Tomography in Clinical Medicine Michael N Maisey 2. Physics and Instrumentation in PET Dale L Bailey, Joel S Karp and Suleman Surti 3. Data Acquisition and Performance Characterization in PET Dale L Bailey 4. Image Reconstruction Algorithms in PET Michel Defrise, Paul E Kinahan and Christian J Michel 5. Quantitative Techniques in PET Steven R Meikle and Ramsey D Badawi 6. Tracer Kinetic Modeling in PET Richard E Carson 7. Coregistration of Structural and Functional Images David J Hawkes, Derek LG Hill, Lucy Hallpike and Dale L Bailey 8. Anato-Molecular Imaging: Combining Structure and Function David W Townsend and Thomas Beyer 9. Radiohalogens for PET Imaging N Scott Mason and Chester A Mathis 10. Progress in 11C Radiochemistry Gunnar Antoni and Bengt Langstrom 11. Metal Radionuclides for PET Imaging Paul McQuade, Deborah W McCarthy and Michael J Welch 12. Radiation Dosimetry and Protection in PET Jocelyn EC Towson 13. Whole-Body PET Imaging Methods Paul D Shreve 14. Artefacts and Normal Variants in Whole-Body PET and PET/CT Imaging Gary J R Cook 15. The Technologists Perspective Bernadette F Cronin 16. PET Imaging in Oncology Andrew M Scott 17. The Use of Positron Emission Tomography in Drug Discovery and Development William C Eckelman 18. PET as a Tool in Multimodality Imaging of Gene Expression and Therapy Abhijit De and Sanjiv Sam Gambhir

Transmission scanning in emission tomography.

Abstract. 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.

Rigid-body transformation of list-mode projection data for respiratory motion correction in cardiac PET

Respiratory motion is a source of artefacts and quantification errors in cardiac imaging. Preliminary studies with retrospective respiratory gating in PET support the observation of other imaging modalities of a rigid-body motion of the heart during respiration. However, the use of gating techniques to eliminate motion may result in poor count statistics per reconstructed image. We have implemented a motion correction technique which applies rigid-body transformations on list-mode data event-by-event on the basis of a geometric model of intersection of the lines-of-response with the scanner. Pre-correction for detector efficiencies and photon attenuation before transformation are included in the process. Projection data are acquired together with physiological signal (every ms) from an inductive respiration monitor with an elasticised belt at chest level. Data are retrospectively sorted into separate respiratory gates on an off-line workstation. Transformation parameters relating the gated images, estimated by means of image registration, can be applied on the original list-mode data to obtain a single motion-corrected dataset. The accuracy of the technique was assessed with point source data and a good correlation between applied and measured transformations, estimated from the centroid of the source, was observed. The technique was applied on phantom data with simulated respiratory motion and on patient data with C/sup 15/O and /sup 18/FDG. Quantitative assessment of preliminary C/sup 15/O patient datasets showed at least 4.5% improvement in the recovery coefficient at the centre of the left ventricle.

An Evidence-Based Review of Quantitative SPECT Imaging and Potential Clinical Applications

SPECT has traditionally been regarded as nonquantitative. Advances in multimodality γ-cameras (SPECT/CT), algorithms for image reconstruction, and sophisticated compensation techniques to correct for photon attenuation and scattering have, however, now made quantitative SPECT viable in a manner similar to quantitative PET (i.e., kBq⋅cm−3, standardized uptake value). This review examines the evidence for quantitative SPECT and demonstrates clinical studies in which the accuracy of the reconstructed SPECT data has been assessed in vivo. SPECT reconstructions using CT-based compensation corrections readily achieve accuracy for 99mTc to within ±10% of the known concentration of the radiotracer in vivo. Quantification with other radionuclides is also being introduced. SPECT continues to suffer from poorer photon detection efficiency (sensitivity) and spatial resolution than PET; however, it has the benefit in some situations of longer radionuclide half-lives, which may better suit the biologic process under examination, as well as the ability to perform multitracer studies using pulse height spectroscopy to separate different radiolabels.

A method for measuring the absolute sensitivity of positron emission tomographic scanners

A need exists to measure the absolute sensitivity of a positron emission tomographic (PET) scanner in units of counts.s-1.MBq-1. At present sensitivity is generally determined by measurement of a radionuclide of known concentration distributed in a water-filled cylindrical phantom, usually 20 cm in diameter. The measurement is confounded by self-attenuation of the source and scatter within the cylinder and does not give a true absolute sensitivity measurement. Due to variations in the magnitude and treatment of these factors, meaningful comparison between different manufacturers scanners is difficult, as are comparisons between different acquisition geometries (e.g. with and without interplane septa present). A method has been developed in our laboratory that provides measurements of absolute sensitivity in air for a scanner independent of attenuation and scatter within the source. The method involves measurements of a thin-line source of fluorine 18 contained within an aluminium housing to which successive aluminium sleeves are added. The extrapolation of these measurements allows an effective counts.s-1.MBq-1 measurement to be made for zero thickness of aluminium. Measurements have yielded absolute sensitivities of 3926 +/- 61 counts.s-1.MBq-1 (0.39% efficiency), 5079 +/- 26 counts.s-1.MBq-1 (0.51%), and 32312 +/- 544 counts.s-1.MBq-1 (3.2%) for a whole-body PET scanner with interplane septa and for a NeuroPET operating with and without interplane septa, respectively.

ECAT ART — a continuously rotating PET camera: Performance characteristics, initial clinical studies, and installation considerations in a nuclear medicine department

Advances in fully three-dimensional (3D) image reconstruction techniques have permitted the development of a commercial, rotating, partial ring, fully 3D positron emission tomographic (PET) scanner, the ECAT ART. The system has less than one-half the number of bismuth germanate detectors compared with a full ring scanner with the equivalent field of view, resulting in reduced capital cost. The performance characteristics, implications for installation in a nuclear medicine department, and clinical utility of the scanner are presented in this report. The sensitivity (20 cm diameter×20 cm long cylindrical phantom, no scatter correction) is 11400 cps·kBq−1·ml−1. This compares with 5800 and 40500 cps·kBq−1·ml−1 in 2D and 3D respectively for the equivalent full ring scanner (ECAT EXACT). With an energy window of 350–650 keV the maximum noise equivalent count (NEC) rate was 27 kcps at a radioactivity concentration of ~15 kBq·ml−1 in the cylinder. Spatial resolution is ~6 mm full width at half maximum on axis degrading to just under 8 mm at a distance of 20 cm off axis. Installation and use within the nuclear medicine department does not appreciably increase background levels of radiation on gamma cameras in adjacent rooms and the dose rate to an operator in the same room is 2 µSv·h−1 for a typical fluorine-18 fluorodeoxyglucose (18F-FDG) study with an initial injected activity of 370 MBq. The scanner has been used for clinical imaging with18F-FDG for neurological and oncological applications. Its novel use for imaging iron-52 transferrin for localising erythropoietic activity demonstrates its sensitivity and resolution advantages over a conventional dual-headed gamma camera. The ECAT ART provides a viable alternative to conventional full ring PET scanners without compromising the performance required for clinical PET imaging.

The direct calculation of parametric images from dynamic PET data using maximum-likelihood iterative reconstruction.

The aim of this work is to calculate, directly from projection data, concise images characterizing the spatial and temporal distribution of labelled compounds from dynamic PET data. Conventionally, image reconstruction and the calculation of parametric images are performed sequentially. By combining the two processes, low-noise parametric images are obtained, using a computationally feasible parametric iterative reconstruction (PIR) algorithm. PIR is performed by restricting the pixel time-activity curves to a positive linear sum of predefined time characteristics. The weights in this sum are then calculated directly from the PET projection data, using an iterative algorithm based on a maximum-likelihood iterative algorithm commonly used for tomographic reconstruction. The ability of the algorithm to extract known kinetic components from the raw data is assessed, using data from both a phantom experiment and clinical studies. The calculated parametric images indicate differential kinetic behaviour and have been used to aid in the identification of tissues which exhibit differences in the handling of labelled compounds. These parametric images should be helpful in defining regions of interest with similar functional behaviour, and with FDG Patlak analysis.