Ronald H. Huesman

Regional Cerebral Metabolic Alterations in Dementia of the Alzheimer Type: Positron Emission Tomography with [1818] Fluorodeoxyglucose

Alzheimer disease is the most common cause of dementia in adults. Despite recent advances in our understanding of its anatomy and chemistry, we remain largely ignorant of its pathogenesis, physiology, diagnosis, and treatment. Dynamic positron emission tomography using [18F] fluorodeoxyglucose (FDG) was performed on the Donner 280-crystal ring in 10 subjects with dementia of the Alzheimer type and six healthy age-matched controls. Ratios comparing mean counts per resolution element in frontal, temporoparietal, and entire cortex regions in brain sections 10 mm thick obtained 40–70 min following FDG injection showed relatively less FDG uptake in the temporoparietal cortex bilaterally in all the Alzheimer subjects (p < 0.01). Left-right alterations were less prominent than the anteroposterior changes. This diminished uptake was due to lowered rates of FDG use and suggests that the metabolic effects of Alzheimer disease are most concentrated in the temporoparietal cortex. Positron emission tomography is a most powerful tool for the noninvasive in vivo assessment of cerebral pathophysiology in dementia.

Emission Computer Assisted Tomography with Single-Photon and Positron Annihilation Photon Emitters

Computed transverse section emission tomography using 99mTc with the Anger camera is compared to positron annihilation coincident detection using a ring of crystals and 68Ga. The single-photon system has a line spread function (LSF) of 9 mm full width at half maximum (FWHM) at the collimator and gives a transverse section reconstruction LSF of 11 mm FWHM with 144 views. The positron ring has a LSF of 6 mm at the center with a transverse section reconstruction LSF of 7.5 mm FWHM. Correction for uniformity of detector response and accurate center of rotation determination is essential in both techniques. The signal-to-noise ratio in a reconstruction is diminished by a factor of 1.2 x (number of resolution elements)1/4 over that expected from the average number of events per resolution element. Attenuation compensation causes more noise to appear in the center than the edge for both modes and an average increase in uncertainty of 30%. The effects of attenuation result in more loss of data for positron coincidence imaging than for single-photon imaging even at energies of 80 keV. For a 20-cm cylinder imaged in transverse section, only 20% of the positron annihilation events are not scattered; however, at 140 keV, 40% of the photons are not scattered. The relative crystal efficiency gives single-photon imaging an advantage of 5. On the other hand, the solid angle advantage of positron photon coincidence imaging is about 100 for the comparisons of this paper. Taking these factors into account, we find positron-computed section imaging has a tenfold increase in sensitivity over multiple-view imaging with the scintillation camera, which gives multiple sections but requires camera or patient rotation.

A new fast algorithm for the evaluation of regions of interest and statistical uncertainty in computed tomography

A new algorithm for region of interest evaluation in computed tomography has been developed. Region of interest evaluation is a technique used to improve quantitation of the tomographic imaging process by summing (or averaging) the reconstructed quantity throughout a volume of particular significance. An important application of this procedure arises in the analysis of dynamic emission computed tomographic data, in which the uptake and clearance of radiotracers are used to determine the blood flow and/or physiologic function of tissue within the significant volume. The new algorithm replaces the conventional technique of repeated image reconstructions with one in which projected regions are convolved and then used to form multiple vector inner products with the raw tomographic data sets. Quantitation of regions of interest is made without the need for reconstruction of tomographic images. The computational advantage of the new algorithm over conventional methods is between a factor of 20 and a factor of 500 for typical applications encountered in medical science studies. The greatest benefit of the new algorithm (and the motivation for its development) is the ease with which the statistical uncertainty of the result is computed. The entire covariance matrix for the evaluation of regions of interest can be calculated with relatively few operations.

An attenuated projector-backprojector for iterative SPECT reconstruction

A new ray-driven projector-backprojector which can easily be adapted for hardware implementation is described and simulated in software. The projector-backprojector discretely models the attenuated Radon transform of a source distributed within an attenuating medium as line integrals of discrete pixels, obtained using the standard sampling technique of averaging the emission source or attenuation distribution over small square regions. Attenuation factors are calculated for each pixel during the projection and backprojection operations instead of using precalculated values. The calculation of the factors requires a specification of the attenuation distribution, estimated either from an assumed constant distribution and an approximate body outline or from transmission measurements. The distribution of attenuation coefficients is stored in memory for efficient access during the projection and backprojection operations. The reconstruction of the source distribution is obtained by using a conjugate gradient or SIRT type iterative algorithm which requires one projection and one backprojection operation for each iteration.

List-mode maximum-likelihood reconstruction applied to positron emission mammography (PEM) with irregular sampling

Presents a preliminary study of list-mode likelihood reconstruction of images for a rectangular positron emission tomograph (PET) specifically designed to image the human breast. The prospective device consists of small arrays of scintillation crystals for which depth of interaction is estimated. Except in very rare instances, the number of annihilation events detected is expected to be far less than the number of distinguishable events. If one were to histogram the acquired data, most histogram bins would remain vacant. Therefore, it seems natural to investigate the efficacy of processing events one at a time rather than processing the data in histogram format. From a reconstruction perspective, the new tomograph presents a challenge in that the rectangular geometry leads to irregular radial and angular sampling, and the field of view extends completely to the detector faces. Simulations are presented that indicate that the proposed tomograph can detect 8-mm-diameter spherical tumors with a tumor-to-background tracer density ratio of 3:1 using realistic image acquisition parameters. Spherical tumors of 4-mm diameter are near the limit of detectability with the image acquisition parameters used. Expressions are presented to estimate the loss of image contrast due to Compton scattering.

Diminished Glucose Transport in Alzheimer's Disease: Dynamic PET Studies

Dynamic positron emission tomography with [18F]fluorodeoxyglucose was used in six patients with Alzheimers disease (AD) and seven healthy age-matched control subjects to estimate the kinetic parameters K1*, k2*, and k3* that describe glucose transport and phosphorylation. A high-resolution tomograph was used to acquire brain uptake data in one tomographic plane, and a radial artery catheter connected to a plastic scintillator was used to acquire arterial input data. A nonlinear iterative least-squares fitting procedure that included terms for the vascular fraction and time delay to the peripheral sampling site was used to fit a three-compartment model to the brain data. Regions studied included frontal, temporal, occipital, and the entire cortex and subcortical white matter. The values obtained for the individual rate constants and regional CMRglc (rCMRglc; calculated using regional values of the rate constants) were higher than those reported previously. A significant (p < 0.05) decrease was found in K1* in frontal and temporal cortex in the AD patients compared with the controls, with values of 0.157 and 0.161 ml/g/min in frontal and temporal cortex, respectively, of controls and 0.127 and 0.126 ml/ g/min in frontal and temporal cortex of the AD patients. rCMRglc was also significantly (p < 0.02) lower in the AD patients than controls in all cortical brain regions. Lower values of k3* were found in all brain regions in the AD patients, although these were not statistically significant. These findings provide evidence of an in vivo abnormality of forward glucose transport in AD. This transport defect, however, is probably not the cause of the diminution in glucose metabolism that has been widely found in AD patients, since a diminution of this magnitude should not lower intracerebral glucose content enough to alter rCMRglc.

THE EFFECTS OF A FINITE NUMBER OF PROJECTION ANGLES and FINITE LATERAL SAMPLING OF PROJECTIONS ON THE PROPAGATION OF STATISTICAL ERRORS IN TRANSVERSE SECTION RECONSTRUCTION

The dependence of noise amplification on the nuber of projection angles and on the lateral sampling interval of projections is presented. It is shown that about 1-5D/d angles and a sampling interval of about 0-5d are required in order that the data be efficiently utilized. D is the linear dimension of the reconstruction region and d is the linear dimension of the cells into which the reconstruction region is subdivided (resolution length). Values for noise amplification are given for various combinations of projection angles and lateral sampling intervals.

Real-time system for respiratory-cardiac gating in positron tomography

A Macintosh-based signal processing system has been developed to support simultaneous respiratory and cardiac gating on the ECAT EXACT HR PET scanner. Using the Lab-View real-time software environment, the system reads analog inputs from a pneumatic respiratory bellows and an ECG monitor to compute an appropriate histogram memory location for the PET data. Respiratory state is determined by the bellows signal amplitude; cardiac state is based on the time since the last R-wave. These two states are used in a 2D lookup table to determine a combined respiratory-cardiac state. A 4-bit address encoding the selected histogram is directed from the system to the ECAT scanner, which dynamically switches the destination of tomograph events as respiratory-cardiac state changes. To test the switching efficiency of the combined Macintosh/ECAT system, a rotating emission phantom was built. Acquisitions with 25 msec states while the phantom was rotating at 240 rpm demonstrate the system could effectively stop motion at this rate, with approximately 5 msec switching time between states.

Dynamic PET data analysis.

A general method for estimating the precision of parameters resulting from the use of various experimental designs (rate of injection and rate of tomographic data collection) in emission tomography studies is proposed. The sensitivity matrix of the study model and an estimate of the statistical uncertainty of the tomographic data are used to compute the covariance matrix of the parameters. The determinant of this covariance matrix (proportional to the total volume of uncertainty of the model parameters) serves as a criterion to be minimized. The method is applied to a three-compartment, three-transfer rate constant for glucose metabolism using dynamic positron emission tomography, and a comparison of various current protocols is made with simulated data. The results show that higher rates of injection and higher rates of tomographic data collection at early times lead to smaller statistical uncertainties for the estimates of rate constants. However, for the range of rate constants encountered in practice, differences are insignificant when an initial scan duration <30 s is used, without regarding the injection duration.

Non-rigid summing of gated PET via optical flow

A method for summing together datasets from gated cardiac PET acquisitions is described. Optical flow techniques are used to accurately model non-rigid motion present during the cardiac cycle so that a one-to-one mapping is found between each voxel of two gated volumes. Using this mapping, image summing can take place, producing a composite dataset with improved statistics and reduced motion-induced blur. Results using a data from a gated cardiac study on a dog are presented.