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J S Perlmutter

Publications and source records attributed to J S Perlmutter.

82 records · Page 5Linked to original sources

Strategies for in vivo measurement of receptor binding using positron emission tomography.

Dopaminergic ligands labeled with positron-emitting radionuclides have been synthesized for quantitative evaluation of dopaminergic binding in vivo. Two different methods, the explicit method and an operationally simplified ratio method, have been proposed for analysis of these positron emission tomographic (PET) data. The basis for both methods is the same three-compartment model. The two methods differ in the assumptions necessary for practical implementation. We have compared these two approaches using PET data obtained in our laboratory. Sequential scans and serial arterial blood samples from a baboon following intravenous injection of [18F]spiroperidol were collected. Application of the two methods to the same data yielded different values for corresponding parameters. Values calculated by the ratio method for the specific rate constant describing receptor binding varied depending upon the time after tracer injection, thus demonstrating an internal inconsistency in this approach. Tracer metabolism markedly affected the binding measurements calculated with either method and thus cannot be ignored. Our results indicate that the adoption of simplifying assumptions for operational convenience can lead to substantial errors and must be done with caution. Alternatively, we present simple new analytical solutions of the tracer conservation equations describing the complete, unsimplified three-compartment model that vastly reduce the computations necessary to implement the explicit method.

Animals↗

Standardized mean regional method for calculating global positron emission tomographic measurements.

A new "mean regional" method for calculating global hemispheric values of blood flow, blood volume, and metabolism with positron emission tomography is presented. It is based on a standardized set of regions defined according to coordinates in a stereotactic atlas of the brain. Region locations in each individual scan were determined by a localization technique that is independent of the appearance of the physiological images. Measurements obtained with this mean regional method minimize contributions from nonbrain structures such as ventricles or venous sinuses and provide the necessary basis for comparisons among different subjects and laboratories.

Adult↗

Regional blood flow in hemiparkinsonism.

Positron emission tomography was used to measure global and local blood flow in 11 patients with hemiparkinsonism (before and after an acute oral dose of L-dopa) and in 26 normal subjects. Global hemispheric blood flow was not significantly different between the patients [45 +/- 11 ml/(min X 100 g)] and the controls [49 +/- 8 ml/(min X 100 g)]. After L-dopa, the patients' mean global hemispheric flow did not change. Measurements of local blood flow from specific, anatomically defined cortical and basal ganglia regions were performed using a newly developed stereotactic localization technique. Before L-dopa, mesocortical blood flow contralateral to the patients' symptoms was significantly less than controls (p less than 0.003), suggesting a specific abnormality in the cortical dopaminergic projection from the ventral tegmental area. In addition, right and left pallidal blood flow were significantly less tightly coupled in patients than controls (p = 0.0312). After L-dopa, the mesocortical blood flow remained below normal, whereas pallidal blood flow was no longer significantly different from controls (p greater than 0.05).

Adult↗

Pure hemidystonia with basal ganglion abnormalities on positron emission tomography.

We present a patient with hemidystonia and an abnormality of the contralateral basal ganglion seen only with positron emission tomography. A 50-year-old sinistral man suffered minor trauma to the right side of his head and neck. Within 20 minutes he developed paroxysmal intermittent dystonic posturing of his right face, forearm, hand, and foot, with weaker contractions of the left foot, lasting several seconds and recurring every few minutes. Neurological findings between spells were normal. The following were also normal: electrolyte, calcium, magnesium, and arterial blood gas levels, and findings of drug screen, cerebrospinal fluid examination, electroencephalography with nasopharyngeal leads, computed tomographic scanning (initially and four weeks later), and cerebral angiography. Positron emission tomographic scanning revealed abnormalities in the left basal ganglion region, including decreased oxygen metabolism, decreased oxygen extraction, increased blood volume, and increased blood flow.

Basal Ganglia↗

A stereotactic method of anatomical localization for positron emission tomography.

Extant methods for anatomical localization within a physiological image are inadequate for precise regional correlations between anatomy and physiology. We have developed a method for determining the location of any region of interest within a positron emission tomographic (PET) image by transformation of the tomographic location coordinates into coordinates within a stereotactic atlas of the human brain. The specific anatomical assumptions of this approach were identified and validated within groups of normal subjects by means of measurements made from lateral skull radiographs and nuclear magnetic resonance proton images. A high degree of accuracy and reproducibility was demonstrated when this technique was applied to groups of normal subjects by determining the anatomical location of two physiologically defined PET areas: the cavernous sinus and visually responsive cortex. This method is simple to implement and highly objective. Generalization of the localization procedure for use with structural tomography is readily accomplished.

Brain↗

A metric for testing the accuracy of cross-modality image registration: validation and application.

PURPOSE: Our goals were to (a) develop and validate a sensitive measure of image registration, applicable between as well as within imaging modalities; and (b) quantify the accuracy of the automated image registration (AIR) algorithm in retrospectively registering MR and PET images of baboon brain. METHOD: We studied five monkeys, each with a surgically implanted "cap" that was bolted to an acrylic headholder containing fiducial markers. Anatomic MRI and PET H2 15O blood flow images were aligned using AIR (ignoring the fiducials). RESULTS: (a) Fiducial points were localized to about one-tenth the voxel size. Distances computed from the fiducial points were correct to within 0.2% (MRI) and 1.4% (PET). (b) The mean error remaining after AIR, measured at the five fiducial points, varied from 2.9 to 5.3 mm. The average registration error within the brain was calculated to be 2.20 mm (maximum, 3.57 mm). This error was not primarily rotational about the center of the brain and was worsened by heavy smoothing of the PET images. CONCLUSION: (a) We have defined a reliable, sensitive metric that can stringently test the accuracy of various image registration techniques. (b) The AIR algorithm leaves modest error after aligning PET blood flow and anatomic MR images of baboon brain.

Algorithms↗

Baboon basal ganglia stereotaxy using internal MRI landmarks: validation and application to PET imaging.

PURPOSE: We report the residual anatomic error after a nine parameter visually guided registration of MR images with a baboon brain atlas to validate a stereotactic method for use in PET studies. METHOD: MPRAGE images of brain in six baboons and one nemestrina monkey were placed in atlas space using internal landmarks and proportional measurements. An expert noted the location of 23 subcortical test points in the transformed images and in the atlas. RESULTS: The average absolute error at the test points was 1.62 mm. At the extremes of the brain surface, there was more variability. PET images could be combined across animals in a common atlas space. CONCLUSION: There is minimal subcortical error attributable to anatomic variability after this method of transforming MR images of baboon to stereotactic space. This method provides a useful tool for intrasubject PET baboon studies as well as "bootstrapping" for more refined methods.

Animals↗

Efficacy and safety of a new bulk toxin of botulinum toxin in cervical dystonia: a blinded evaluation.

We investigated the efficacy and safety of botulinum toxin A (BTX) manufactured from a new bulk strain for the treatment of cervical dystonia. This was a single-blinded retrospective comparison of length of benefit, subjective improvement, and complications of treatment in 50 patients treated with the old form of toxin designated 79-11 and the new toxin strain BCB2024. The mean duration of benefit of the 79-11 strain and the BCB2024 strain were the same. Subjective efficacy, measured on a -4 to +4 scale, demonstrated no difference between the two strains. Dysphagia occurred in 12% of patients injected with the 79-11 strain and 14% of subjects injected with the BCB2024 strain. We also used a clinician's global assessment that incorporated the duration of benefit, subjective efficacy, and complications as a secondary analysis. There was no significant difference between the two forms of botulinum toxin A according to this scale. We conclude that the 79-11 strain and the BCB2024 strain offer similar peak efficacy duration of benefit, and adverse events.

Adult↗