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J R Votaw

Publications and source records attributed to J R Votaw.

At least 19 recordsLinked to original sources

Accelerated penalized weighted least-squares and maximum likelihood algorithms for reconstructing transmission images from PET transmission data.

We present penalized weighted least-squares (PWLS) and penalized maximum-likelihood (PML) methods for reconstructing transmission images from positron emission tomography transmission data. First, we view the problem of minimizing the weighted least-squares (WLS) and maximum likelihood objective functions as a sequence of nonnegative least-squares minimization problems. This viewpoint follows from using certain quadratic functions as surrogate functions for the WLS and maximum likelihood objective functions. Second, we construct surrogate functions for a class of penalty functions that yield closed form expressions for the iterates of the PWLS and PML algorithms. Due to the slow convergence of the PWLS and PML algorithms, accelerated versions of them are developed that are theoretically guaranteed to monotonically decrease their respective objective functions. In experiments using real phantom data, the PML images produced the most accurate attenuation correction factors. On the other hand, the PWLS images produced images with the highest levels of contrast for low-count data.

Algorithms↗

Self-administration of cocaine and the cocaine analog RTI-113: relationship to dopamine transporter occupancy determined by PET neuroimaging in rhesus monkeys.

Dopaminergic mechanisms are thought to play a central role in the reinforcing effects of cocaine. The present study examined the reinforcing effects of 3beta-(4-chlorophenyl)tropane-2beta-carboxylic acid phenyl ester (RTI-113), a long-acting, selective, high-affinity dopamine uptake inhibitor. Additionally, the effects of RTI-113 pretreatment on cocaine self-administration were determined. Monkeys were trained to respond under a second-order schedule for intravenous cocaine administration (0.10 or 0.17 mg/kg/infusion). When responding was stable, cocaine (0.0030-1.0 mg/kg/infusion) and RTI-113 (0.010-0.30 mg/kg/infusion) were substituted for the cocaine training dose. Cocaine and RTI-113 were equipotent for their reinforcing effects. However, cocaine maintained higher response rates in two of the three monkeys tested. When administered as a pretreatment, RTI-113 (0.10-0.30 mg/kg) dose-dependently reduced responding maintained by two doses of cocaine. Drug effects on behavior were related to dopamine transporter (DAT) occupancy in monkey striatum during neuroimaging with positron emission tomography. DAT occupancy was determined by displacement of 8-(2-[(18)F]fluroethyl)2beta-carbomethoxy-3beta-(4-chlorophenyl)nortropane (FECNT). DAT occupancy was between 65-76% and 94-99% for doses of cocaine and RTI-113 that maintained maximum response rates, respectively. DAT occupancy did not differ markedly across RTI-113 pretreatment doses and ranged between 72-84%. The results suggest that the pharmacokinetic profile of RTI-113 (i.e., long-acting) may influence its ability to maintain self-administration, and therefore its abuse liability. Additionally, high DAT occupancy is required for RTI-113 to reduce cocaine-maintained responding.

Animals↗

An apparatus and behavioral training protocol to conduct positron emission tomography (PET) neuroimaging in conscious rhesus monkeys.

Nonhuman primates offer a unique resource in neuroimaging research, providing the opportunity to manipulate appropriate biological and behavioral variables under well-controlled experimental conditions in an animal model that is closely related to humans, both functionally and neuroanatomically. The present report describes the development and standardization of PET neuroimaging protocols in conscious rhesus monkeys and their application to characterize the acute effects of cocaine on cerebral blood flow. Specific attention was devoted to the development of an effective and comfortable head restraint device to be used in the imaging of conscious monkeys. The restraint device was designed to attach to a standard primate chair to facilitate frequent immobilization. Subjects received extensive behavioral training prior to neuroimaging in order to ensure their comfort and minimize potential stress associated with the imaging protocols. Functional changes in cerebral blood flow were characterized in three subjects with the positron-emitting tracer 15O water following acute i.v. administration of cocaine. Regions of interest were defined on MRI scans with a high degree of accuracy. Cocaine caused pronounced increases in cerebral blood flow at 5 min postinjection that diminished markedly within 25 min. The results document the feasibility to conduct PET neuroimaging studies of cerebral blood flow in conscious nonhuman primates. Extension of the methodology to include brain activation during behavioral studies could contribute significantly to the growing discipline of behavioral neuroscience.

Animals↗

Biodistribution and radiation dosimetry of the dopamine transporter ligand.

UNLABELLED: 18F-labeled 2 beta-carbomethoxy-3beta-(4-chlorophenyl)-8-(-2-fluoroethyl)nortropane ([18F]FECNT) is a recently developed dopamine transporter ligand with potential applications in patients with Parkinson's disease and cocaine addiction. METHODS: Estimates of the effective dose equivalent and doses for specific organs were made using biodistribution data from 16 Sprague-Dawley rats and nine rhesus monkeys. PET images from two rhesus monkeys were used to calculate the residence time for the basal ganglia. The computer program MIRDOSE3 was used to calculate the dosimetry according to the methodology recommended by MIRD. RESULTS: The basal ganglia were the targeted tissues receiving the highest dose, 0.11 mGy/MBq (0.39 rad/mCi). The effective dose equivalent was 0.018 mSv/MBq (0.065 rem/mCi), and the effective dose was 0.016 mSv/MBq (0.058 rem/mCi). CONCLUSION: Our data show that a 185-MBq (5-mCi) injection of [18F]FECNT leads to an estimated effective dose of 3 mSv (0.3 rem) and an estimated dose to the target organ or tissue of 19.4 mGy (1.93 rad).

Animals↗

Comparison of 2-dimensional and 3-dimensional cardiac 82Rb PET studies.

UNLABELLED: Most new PET scanners have the capability to collect data in 3-dimensional (3D) (septa removed) mode. This allows many more detected events at the cost of increased random events and scatter. In the case of 82Rb imaging, the injected dose might have to be limited to avoid saturating the scanner. We present a comparison of 2-dimensional (2D) and 3D data collection for 82Rb cardiac studies using the ECAT EXACT scanner. METHODS: Resting 82Rb cardiac studies were collected in 2D and 3D modes for 33 consecutive patients. Four experienced physicians rated the images to determine if the different acquisition methods would lead to different patient care. A separate quantitative analysis was performed on data from multiple scans of a thoracic phantom filled to simulate cardiac and background radioactivity corresponding to 82Rb injections between 37 and 1740 MBQ: RESULTS: The 2D and 3D studies were significantly different, with the image quality being poorer in the 3D studies. The scanner collected data at near its maximal counting rate for either 1480-MBq 2D or 37-MBq 3D acquisitions. Because the data collection was counting rate limited in either mode, and there are more random and scatter events in 3D mode, the 2D acquisitions resulted in more detected true events and a better signal-to-noise ratio. CONCLUSION: Cardiac 82Rb studies should be performed in 2D mode when using the ECAT EXACT scanner.

Heart↗

Acute blood flow changes and efficacy of vagus nerve stimulation in partial epilepsy.

OBJECTIVE: To determine possible sites of therapeutic action of vagus nerve stimulation (VNS), by correlating acute VNS-induced regional cerebral blood flow (rCBF) alterations and chronic therapeutic responses. BACKGROUND: We previously found that VNS acutely induces rCBF alterations at sites that receive vagal afferents and higher-order projections, including dorsal medulla, somatosensory cortex (contralateral to stimulation), thalamus and cerebellum bilaterally, and several limbic structures (including hippocampus and amygdala bilaterally). METHODS: VNS-induced rCBF changes were measured by subtracting resting rCBF from rCBF during VNS, using [O-15]water and PET, immediately before ongoing VNS began, in 11 partial epilepsy patients. T-statistical mapping established relative rCBF increases and decreases for each patient. Percent changes in frequency of complex partial seizures (with or without secondary generalization) during three months of VNS compared with pre-VNS baseline, and T-thresholded rCBF changes (for each of the 25 regions of previously observed significant CBF change), were rank ordered across patients. Spearman rank correlation coefficients assessed associations of seizure-frequency change and t-thresholded rCBF change. RESULTS: Seizure-frequency changes ranged from 71% decrease to 12% increase during VNS. Only the right and left thalami showed significant associations of rCBF change with seizure-frequency change. Increased right and left thalamic CBF correlated with decreased seizures (p < 0.001). CONCLUSIONS: Increased thalamic synaptic activities probably mediate some antiseizure effects of VNS. Future studies should examine neurotransmitter-receptor alterations in reticular and specific thalamic nuclei during VNS.

Adult↗

A confrontational naming task produces congruent increases and decreases in PET and fMRI.

This work uses the well-established (by PET) confrontation naming task to compare PET and fMRI in a cognitive activation experiment. The signal changes from this task are much less than the changes caused by visual or motor activation tasks used in previous comparisons. ANOVA methods adjusted for multiple comparisons were used to determine significant changes in signal between confrontation naming and figure size discrimination tasks. All 17 significantly increased regions (confrontation naming signal greater) seen on one modality were increased on both modalities. Ten of 13 regions that were significantly decreased on one modality were decreased on the other. Three mismatched regions showed a significant decrease on one modality and a nonsignificant increase on the other. This study could not detect a consistent difference in activation site location between PET and fMRI.

Adult↗

Butanol is superior to water for performing positron emission tomography activation studies.

[15(O)]Butanol has been shown to be superior to [15(O)]water for measuring cerebral blood flow with positron emission tomography. This work demonstrates that it is also superior for performing activation studies. Data were collected under three conditions: a visual confrontation animal-naming task, nonsense figure size discrimination, and a nonvisual darkroom control task. Time-activity curves (TAC) were obtained for regions known to be activated by the confrontation naming task to compare absolute uptake and the different kinetics of the two tracers. Also, t statistic maps were calculated from the data of 10 subjects for both tracers and compared for magnitude of change and size of activated regions. Peak uptake in the whole-brain TAC were similar for the two tracers. For all regions and conditions, the washout rate of [15(O)]butanol was 41% greater than that of [15(O)]water. At a threshold of 0, the [15(O)]water and [15(O)]butanol percent difference (nonnormalized) and t statistic (global normalization) images are nearly identical, indicating that the same property is being measured with both tracers. The [15(O)]butanol parametric images displayed at a threshold of /t/ = 5 look similar to the [15(O)]water parametric maps displayed at a threshold of /t/ = 4, which is consistent with the observation that t statistic values in [15(O)]butanol images are generally greater. The t statistic values were equal when the [15(O)]butanol parametric map was created from any subset of 6 subjects and the [15(O)]water parametric map was created from all 10 subjects. Fewer subjects need to be studied with [15(O)]butanol to reach the same statistical power as an [15(O)]water-based study.

Adult↗

Compensatory recruitment of neural resources during overt rehearsal of word lists in Alzheimer's disease.

Functional neuroanatomical correlates subserving maintenance rehearsal relative to a reading control task were investigated with positron emission tomography imaging of cerebral blood flow in 6 healthy older participants and 6 patients with mild Alzheimer's disease (AD). Rehearsal and reading rates and number of unique words rehearsed did not differ significantly for the 2 groups. The right dorsolateral prefrontal cortex was activated in both groups during rehearsal, highlighting this region's role in short-term maintenance of verbal information. A shift in cortical processing resources to more anterior brain regions with increased rehearsal list length was seen, likely reflecting greater demands on frontal cortex as cognitive load grows. Whereas controls showed unilateral right frontal activation during rehearsal, AD patients demonstrated bilateral frontal activation, possibly reflecting compensatory recruitment of neural resources.

Adaptation, Physiological↗

Optimization of PET activation studies based on the SNR measured in the 3-D Hoffman brain phantom.

This work investigates the noise properties of O-15 water PET images in an attempt to increase the sensitivity of activation studies. A method for computing the amount of noise within a region of interest (ROI) from the uncertainty in the raw data was implemented for three-dimensional (3-D) positron emission tomography (PET). The method was used to study the signal-to-noise ratio (SNR) of regions-of-interest (ROI's) inside a 3-D Hoffman brain phantom. Saturation occurs at an activity concentration of 2.2 mCi/l which corresponds to a 75-mCi O-15 water injection into a normal person of average weight. This establishes the upper limit for injections for human brain studies using 3-D PET on the Siemens ECAT 921 EXACT scanner. Data from human brain activation studies on four normal volunteers using two-dimensional (2-D) PET were analyzed. The biological variation was found to be 5% in 1-ml ROI's. The variance for a complete activation study was calculated, for a variety of protocols, by combining the Poisson noise propagated from the raw data in the phantom experiments with the biological variation. A protocol that is predicted to maximize the SNR in dual-condition activation experiments while remaining below the radiation safety limit is: ten scans with 45 mCi per injection. The data should not be corrected for random or scatter events since they do not help in the identification of activation sites while they do add noise to the image. Due to the lower noise level of 3-D PET, the threshold for detecting a true change in activity concentration is 10%-20% lower than 2-D PET. Because of this, a 3-D activation experiment using the Siemens 921 scanner requires fewer subjects for equal statistical power.

Brain↗

Brain blood flow alterations induced by therapeutic vagus nerve stimulation in partial epilepsy: I. Acute effects at high and low levels of stimulation.

PURPOSE: Left cervical vagus nerve stimulation (VNS) decreases complex partial seizures (CPS) by unknown mechanisms of action. We hypothesized that therapeutic VNS alters synaptic activities at vagal afferent terminations and in sites that receive polysynaptic projections from these medullary nuclei. METHODS: Ten patients with partial epilepsy underwent positron emission tomographic (PET) measurements of cerebral blood flow (BF) three times before and three times during VNS. Parameters for VNS were at high levels for 5 patients and at low levels for 5. Resting BF measurements were subtracted from measurements during VNS in each subject. Subtraction data were averaged in each of 2 groups of 5 patients. t Tests were applied to BF changes in brain regions that receive vagal afferents and projections (significant at p < 0.05, corrected for repeated measures). RESULTS: In both the low- and high-stimulation groups during VNS, brain BF was (a) increased in the rostral, dorsal-central medulla; (b) increased in the right postcentral gyrus, (c) increased bilaterally in the hypothalami, thalami, and insular cortices, and in cerebellar hemispheres inferiorly; and (d) decreased bilaterally in hippocampus, amygdala, and posterior cingulate gyri. The high-stimulation group had greater volumes of activation and deactivation sites. CONCLUSIONS: Our findings suggest that left cervical VNS acutely increases synaptic activity in structures directly innervated by central vagal structures and areas that process left-sided somatosensory information, but VNS also acutely alters synaptic activity in multiple limbic system structures bilaterally. These findings may reflect sites of therapeutic actions of VNS.

Adult↗

Motor subcircuits mediating the control of movement velocity: a PET study.

The influence of changes in the mean velocity of movement on regional cerebral blood flow (rCBF) was studied using positron emission tomography (PET) in nine healthy right-handed adults while they performed a smooth pursuit visuomanual tracking task. Images of relative rCBF were obtained while subjects moved a hand-held joystick to track the movement of a target at three different rates of a sinusoidal displacement (0.1, 0.4, and 0.7 Hz). Significant changes in rCBF between task conditions were detected using analysis of variance and weighted linear contrasts. The kinematics of arm and eye movements indicated that subjects performed tasks in a similar manner, particularly during the faster two tracking conditions. Significant increases in rCBF during arm movement (relative to an eye tracking only control condition) were detected in a widespread network of areas known for their involvement in motor control. The activated areas included primary sensorimotor (M1S1), dorsal and mesial premotor, and dorsal parietal cortices in the left hemisphere and to a lesser extent the sensorimotor and superior parietal cortices in the right hemisphere. Subcortically, activations were found in the left putamen, globus pallidus (GP), and thalamus, in the right basal ganglia, and in the right anterior cerebellum. Within the cerebral volume activated with movement, three areas had changes in rCBF that correlated positively with the rate of movement: left M1S1, left GP, and right anterior cerebellum. No movement-related sites had rCBF that correlated negatively with the rate of movement. Regressions of mean percent change (MPC) in rCBF onto mean hand velocity yielded two nonoverlapping subpopulations of movement-related loci, the three sites with significant rate effects and regression slopes steeper than 0.17 MPC.cm-1.s-1 and all other sites with nonsignificant rate effects and regression slopes below 0.1 MPC.cm-1. s-1. Moreover, the effects of movement per se and of movement velocity varied in magnitude independently. These results confirm previous reports that movement-related activations of M1S1 and cerebellum are sensitive to movement frequency or some covarying parameter of movement. The activation of GP with increasing movement velocity, not described in previous functional-imaging studies, supports the hypothesis that the basal ganglia motor circuit may be involved preferentially in controlling or monitoring the scale and/or dynamics of arm movements. The remaining areas that were activated equally for all movement rates may be involved in controlling higher level aspects of motor control that are independent of movement dynamics.

Aged↗

Performance evaluation of the Pico-Count flow-through detector for use in cerebral blood flow PET studies.

UNLABELLED: This study evaluated the Pico-Count (Bioscan, Inc., Washington, DC) flow-through radioactivity detector, designed for use in PET studies of cerebral blood flow. METHODS: The Pico-Count detects the two 511-keV positron annihilation photons with two bismuth germanate detectors operating in coincidence. The detectors, photomultipliers and preamps are housed within a 12 cm x 9 cm x 22 cm box, which includes 16 mm of lead shielding, to allow placement of the detector within 15 cm of the sampling site. The counting electronics are housed in a remote box, which is connected to a laptop computer for process control. The dwell time per sample and the number of samples to collect are entered through the computer and can vary throughout the study. Approximately 22 cm of arterial tubing (which contains 0.11 ml of blood) is looped between the detectors. Typically, blood is withdrawn with a syringe pump at a rate of 2.75 ml/min, which corresponds to a flow rate in the tubing of 9.2 cm/sec. Dispersion within the arterial catheter is measured by observing the response to an input step function and is well-modeled as a monoexponential. RESULTS: The sensitivity is 270 Hz/(microCi/ml), which corresponds to detecting 6.9% of the positron decays occurring within the detector. The peak counting rate after a 12-mCi injection is approximately 2100 Hz, with the background being less than 0.2%. The dispersion time constant is 1.3 sec, and the delay between radioactivity present at the catheter tip and that measured by the detector is 4.1 sec. The cutoff in the power spectral density of typical human arterial blood time radioactivity curves is far less than the corresponding cutoff for the dispersion function. CONCLUSION: The Pico-Count is an excellent detector for continuously monitoring positron radioactivity in blood. Depending on the application, dispersion correction for the detection apparatus may not be needed.

Brain↗

Role of posterior parietal cortex in the recalibration of visually guided reaching.

Visually guided reaching requires complex neural transformations to link visual and proprioceptive inputs with appropriate motor outputs. Despite the complexity of these transformations, hand-eye coordination in humans is remarkably flexible, as demonstrated by the ease with which reaching can be adapted to distortions in visual feedback. If subjects attempt to reach to visual targets while wearing displacing prisms, they initially misreach in the direction of visual displacement. Given feedback about their reaching errors, however, they quickly adapt to the visual distortion. This is shown by the gradual resumption of accurate reaching while the prisms remain in place, and by the immediate onset of reaching errors in the opposite direction after the prisms have been removed. Despite an abundance of psychophysical data on adaptation to prisms, the functional localization of this form of sensorimotor adaptation is uncertain. Here we use positron emission tomography (PET) to localize changes in regional cerebral blood flow (rCBF) in subjects who performed a prism-adaptation task as well as a task that controlled for the sensory, motor and cognitive conditions of the adaptation experiment. Difference images that reflected the net effects of the adaptation process showed selective activation of posterior parietal cortex contralateral to the reaching limb.

Adaptation, Physiological↗

Analysis of PET neurofunctional mapping studies.

In this work, we present a method for analyzing positron emission tomography (PET) functional mapping experiments. The method is useful for identifying statistically significant differences between two PET data sets. First, uniform-variance Z-images are created and then the statistical uncertainty in region-of-interest values are calculated using a previously published method. The Z-images are calculated from the emission sinograms only--the calculation does not use scanner normalization and attenuation corrections and hence variance from these sources is eliminated, with no decrease in validity. Next, the Z-images are analyzed for activation sites using two separate techniques: a cluster analysis method and a change distribution analysis method. Both of these techniques are shown to be effective for objectively locating significantly activated regions from the Z-images. Two advantages of these methods are that they are objective and efficient; all of the parameters necessary in the calculations can be precomputed and stored since they depend only upon the geometry of the scanner.

Brain↗

The AAPM/RSNA physics tutorial for residents. Physics of PET.

Positron emission tomography (PET) is a coalition of physics, chemistry, physiology, and medicine united in an effort to measure physiologic parameters noninvasively. A PET study consists of producing radiotracers, synthesizing radiopharmaceuticals from the tracers, administering the radiopharmaceutical to a patient, measuring the resulting radioactivity distribution in an organ of interest, and interpreting the activity distribution as a function of physiologic parameters. Radiotracers are produced with medical accelerators that are characterized by the amount of time required to produce a set amount of radiotracer. Radiopharmaceutical production requires automated or remote synthesis modules that are characterized by their efficiency for incorporating the radiotracer into a radiopharmaceutical and the length of time and amount of human interaction required. Imaging protocols must consider sources of image artifacts, the method by which the images will be analyzed, and the uncertainty in the final result. Each of these areas has implications for the cost of the procedure, patient comfort, and the information obtainable from the study. This article gives an overview of these areas and defines the principles that can be used to distinguish between and the consequences of different approaches.

Humans↗

Nitrogen-13-ammonia and PET to detect allograft coronary artery disease after heart transplantation: comparison with coronary angiography.

UNLABELLED: The diffuse nature of allograft coronary artery disease (CAD) suggests that global myocardial blood flow (MBF) may decrease with time after transplantation; therefore the diagnosis of this disease remains problematic. METHODS: To investigate whether PET detects a fall in allograft MBF over time, PET scans (108) were obtained from 43 heart transplant recipients. Thirty-five patients underwent two serial PET scans 1 yr apart. MBF was measured by PET using 13N-ammonia as a tracer. Coronary angiography was performed parallel with PET imaging and compared with perfusion rates measured by PET scans. RESULTS: MBF measured by PET decreased sequentially with time. The mean MBF was 73 +/- 21, 56 +/- 13, 51 +/- 11 and 51 +/- 27 ml/min/100 g of tissue in patients surviving 3 mo, 1, 2 and 3 yr after transplantation, respectively. Significant MBF decrease occurred within 1 yr after transplantation. Sequential PET studies showed a decrease in MBF in 22 of 35 patients (63%). Mean MBF for the first and second scans was 65 +/- 18 and 54 +/- 16, respectively. MBF decrease was more profound in patients (n = 11) angiographic evidence of CAD. There was a trend towards increased rejection and CMV infection rates in patients with decreased MBF. CONCLUSION: With time, PET detects a decrease in MBF in cardiac allografts. The frequency of MBF decrease detected by PET is concordant with the true incidence of allograft CAD, suggesting that sequential PET is a more sensitive modality for monitoring allograft CAD than angiography.

Ammonia↗