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Biomedical subjects

R H Huesman

Publications and source records attributed to R H Huesman.

16 recordsLinked to original sources

Simulation of compartmental models for kinetic data from a positron emission tomograph.

Linear compartmental models are used to describe the disposition of radio-labelled compounds in regions of interest in the mammalian body, based on a time sequence of measurements from a positron emission tomograph (PET). In this paper we show how closed form solutions for the model equations have been incorporated into a computer program for simulation and parameter estimation. A typical PET data example is included to illustrate the implementation and compare the closed form method with a numerical ode solution method.

Body Fluid Compartments

Generalized approach to inverse problems in tomography: image reconstruction for spatially variant systems using natural pixels.

A major limitation in tomographic inverse problems is inadequate computation speed, which frequently impedes the application of engineering ideas and principles in medical science more than in the physical and engineering sciences. Medical problems are computationally taxing because a minimum description of the system often involves 5 dimensions (3 space, 1 energy, 1 time), with the range of each space coordinate requiring up to 512 samples. The computational tasks for this problem can be simply expressed by posing the problem as one in which the tomograph system response function is spatially invariant, and the noise is additive and Gaussian. Under these assumptions, a number of reconstruction methods have been implemented with generally satisfactory results for general medical imaging purposes. However, if the system response function of the tomograph is assumed more realistically to be spatially variant and the noise to be Poisson, the computational problem becomes much more difficult. Some of the algorithms being studied to compensate for position-dependent resolution and statistical fluctuations in the data acquisition process, when expressed in canonical form, are not practical for clinical applications because the number of computations necessary exceeds the capabilities of high-performance computer systems currently available. Reconstruction methods based on natural pixels, specifically orthonormal natural pixels, preserve symmetries in the data acquisition process. Fast implementations of orthonormal natural pixel algorithms can achieve orders of magnitude speedup relative to general implementations. Thus, specialized thought in algorithm development can lead to more significant increases in performance than can be achieved through hardware improvements alone.

Algorithms

In vivo NMR spectral parameter estimation: a comparison between time and frequency domain methods.

We have compared various methods of in vivo NMR spectral parameter estimation, namely a nonlinear fit of the free induction decay signal in the time domain (NLTD), a nonlinear fit of the fast Fourier transform of the FID data in the frequency domain using either a continuous Lorentzian model (NLLM) or a Fourier-sampled model (NLFM), and a time-domain linear prediction method using singular value decomposition (LPSVD). Monte Carlo simulations of 31P and 13C in vivo experiments were used to assess the bias and statistical uncertainties of spectral parameters obtained with each method. In the 31P case, all methods appear to be equivalent except the LPSVD method that led to significantly biased peak amplitudes (up to 28%). In the 13C case, the only methods able to recover the glycogen peak were the NLTD method and its equivalent in the frequency domain (NLFM). In both the 31P and the 13C cases simulations demonstrated that 256 data points were sufficient. These results demonstrate the feasibility and the robustness of a nonlinear fit of the FID data in the time domain, and we illustrate this on 31P and 13C data sets obtained in humans.

Algorithms

Diminished glucose transport in Alzheimer's disease: dynamic PET studies.

Dynamic positron emission tomography with [18F]fluorodeoxyglucose was used in six patients with Alzheimer's 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 less than 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 less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Clinical evaluation of a high-resolution (2.6-mm) positron emission tomography.

The intrinsic resolution of the Donner 600-crystal positron emission tomograph (PET 600) is 2.6 mm full width at half maximum (FWHM) in-plane and 6 mm FWHM axially. More than 100 patients with glioma, radiation necrosis, Alzheimer disease, or epilepsy have been studied with this system. Approximately 1 million events are acquired in 15 minutes, starting 1 hour after injection of 10 mCi (370 MBq) of fluorine-18-fluorodeoxyglucose. Normal structures as small as the superior colliculi and the external capsule have been resolved. Improved separation of the cortical ribbon from adjacent white matter has allowed more accurate determination of cortical metabolic rate. In two of 15 patients undergoing evaluation for recurrent glioma, the PET 600 images showed tumor uptake that was not apparent on a lower-resolution study. A high-activity orbiting transmission source with electronic collimation allows accurate, short-duration transmission measurements to be made after radiopharmaceutical administration. The anatomic detail seen on the transmission images can be used for reproducible patient positioning with an accuracy of 1-2 mm perpendicular to the image plane. These findings demonstrate the practicality and clinical effectiveness of high-resolution positron emission tomography.

Alzheimer Disease

Regional cerebral glucose transport and utilization in Alzheimer's disease.

We performed dynamic positron emission tomographic (PET) studies of glucose utilization, using (18F) 2-fluoro-2-deoxy-D-glucose (FDG), in patients with probable Alzheimer's disease (AD) and healthy age-matched controls, to evaluate blood-brain-barrier glucose transport and glucose utilization rates in the disease. We found no significant differences in rate constants for glucose transport (k1 and k2) and phosphorylation (k3), nor for the vascular fraction (fv), between the 2 groups, although k3 and fv were relatively depressed in temporal cortex in AD. Absolute rates of glucose use were depressed in temporal and parietal cortex, and relative rCMRglc rates were lower in frontal, temporal, parietal, and occipital cortices. These data suggest that in AD bidirectional glucose transport is intact, and that temporal-parietal hypometabolism is present upon a background of widespread cortical metabolic impairment.

Aged

Kinetic data analysis with a noisy input function.

Methods of parameter estimation are proposed for the analysis of dynamic experiments in which the input function is noisy. Noise in the input function leads to uncertainties in the calculated model-predicted values, and therefore the covariance matrix of the residuals is a function of the model parameters. These statistical uncertainties in the model-predicted values significantly change the nature of the fitting process and the quality of the results. The proposed optimisation methods use weighted least-squares criteria, and three choices for the weighting matrix are considered. The proposed weighting matrices, in order of complexity are: (1) the identity matrix (no weighting), (2) the covariance matrix of the data (ignoring the noise in the input function), and (3) the full covariance matrix of the residuals (incorporating both the noise in the data and the noise in the input function). The methodology is applied to dynamic emission tomography studies of the heart, where the blood (input) and tissue tracer concentrations at each time are derived from two regions of interest in the same tomographic slice. Computer stimulations of compartmental systems show that parameters and their covariance matrix are more accurately estimated when the full covariance matrix of the residuals is used as a weighting matrix rather than either of the other two methods. For the practical example considered, parameter bias was increased by a factor of at least four when the noise in the input function was ignored, and one parameter had a bias of 24% when the unweighted least-squares criterion was used.

Computer Simulation

Methodologic factors affecting PET measurements of cerebral glucose metabolism.

Measurements of cerebral glucose utilization rates in similar populations of human subjects under similar conditions vary considerably because of methods used in data collection and analysis. Using data acquired in two patients, we evaluated the effects of time schedule of data collection, region of interest size, method of attenuation correction, and input function shape on LCMRglu determined by dynamic positron emission tomographic scanning and calculation of rate constants. These different strategies of data acquisition and analysis produced variations of 3 to 14% in calculated LCMRglu. These factors, in conjunction with the well described effects of instrument resolution and sensitivity may account for data discrepancies in the literature.

Brain

Dead time correction and counting statistics for positron tomography.

A correction for loss of events due to dead time in dynamic positron emission tomography (PET) is presented. The model employs a paralysing dead time to describe the behaviour of a tomograph over the range of event rates normally encountered in patient studies (up to 200 000 events/s per detector layer). The Donner 280-crystal positron tomograph has a dead time of 1.8 microseconds/event for observed count rates less than 200 000 events/s. The dead time correction factor is 1.8 at 180 000 events/s. The correction is applied to projection data and region of interest analysis of dynamic PET studies, and formulae for the covariances between corrected projection data and between counts in regions of interest in different images from the same dynamic study are established. At 180 000 events/s, the variance of the actual (corrected) number of events in a region containing 3.34 X 10(5) actual events is predicted from the model to be 3.86 X 10(6) (events)2, more than 10 times the variance that would be expected from a naive assumption of Poisson statistics. These statistical results are verified experimentally. An error of 25% is observed in myocardial flow if dead time compensation is not applied, showing the necessity for this correction.

Animals

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.

Heart

Quantitative potentials of dynamic emission computed tomography.

Statistical uncertainties in emission computed tomography were simulated in 60 computer studies involving various numbers of events and distributions of activity. Previous studies have shown that for a uniform disc of activity of rms percentage of uncertainty per resolution cell is: 120 X (number of resolution cells)1/4 X (number of events per resolution cell)- 1/2. In this work we examined the more general situation where one or two regions of uniform activity are surrounded by a uniform background, and found that for an equal number of recorded events the uncertainties were reduced when the activity was concentrated in a portion of the field. The empirical relation rms % uncertainty in nt = 120(N)1/4(nt)-3/4, where nt is the number of events in an average target (organ) resolution cell and N is the total number of events recorded, satisfactorily described the relationships between uncertainties, contrast, total number of detected events, and number of resolution cells for all 60 computer studies. By means of this relation, we show the theoretical possibility of gated cardiac imaging with 20% uncertainty in 1 cm X 1 cm regions, and of 1-sec cerebral blood-flow images with 20% uncertainty in 2 cm X 2 cm regions.

Computers

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.

Information Theory

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.

Elementary Particles

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 less than 30 s is used, without regarding the injection duration.

Deoxyglucose