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Biomedical subjects

J Markham

Publications and source records attributed to J Markham.

At least 55 records · Page 3Linked to original sources
PubMed1986

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↗
PubMed1985

Quantification of differences in frequency content of signal-averaged electrocardiograms in patients with compared to those without sustained ventricular tachycardia.

To quantify differences in the frequency content of signal-averaged electrocardiograms between patients with and without sustained ventricular tachycardia (VT), the energy spectra of the terminal QRS and ST segments of signal-averaged orthogonal ECGs were computed in 3 groups of patients by squaring the magnitude of the fast-Fourier transformed data. The terminal 40 ms of the QRS complex and ST segment were analyzed as a single unit to enhance frequency resolution. Group I comprised 23 patients with documented, remote myocardial infarction who had manifested subsequent episodes of sustained VT; group II comprised 53 patients with previous, remote infarction without subsequent sustained VT; and group III comprised 11 normal subjects. The terminal QRS and ST segments from patients with sustained VT contained a 10- to 100-fold greater proportion of components in the 20- to 50-Hz range compared with corresponding electrocardiographic segments in patients without VT. There were no significant differences in the peak frequencies among patient groups. However, the relative contribution of the magnitudes of these peak frequencies to the overall maximum magnitude of the spectral plot differed significantly (p less than 0.0001). No frequencies above 50 Hz contributed substantially to the energy spectra of the terminal QRS and ST segments in any group. Thus, differences in the energy spectra do not result from differences in the frequencies of components, but are attributable instead to differences in the amplitudes of components within a relatively narrow range of frequencies. The quantitative approach developed should provide objective indexes for assessing effects of antiarrhythmic interventions on abnormalities recognizable by frequency-domain analysis and improve noninvasive definition of risk for development of sustained VT.

Adult↗
PubMed1984

Quantification of regional myocardial blood flow in vivo with H215O.

Using H215O (half-life = 2.1 min) we demonstrated that a modification of the tissue autoradiographic approach permitted quantitation of myocardial blood flow in open-chest dogs by direct assay of myocardial tissue and that noninvasive estimation with positron-emission tomography (PET) delineated relative myocardial blood flow in intact dogs. In open-chest anesthetized dogs, the single-pass extraction fraction of H215O averaged 96 +/- 5% at flows of 80 to 100 ml/100 g/min. This high extraction fraction did not differ significantly over the range of 12 to 238 ml/100 g/min. Myocardial blood flow calculated after a 60 sec intravenous infusion of H215O and direct analysis of tissue correlated well with results obtained with microspheres (r = .94, n = 9 dogs). Subsequently the approach was adapted for preliminary use with PET. Estimation of myocardial content of radiolabeled H2O after intravenous infusion of 20 to 30 mCi of H215O was corrected for vascular pool radioactivity with the use of tomographic data obtained after administration of C15O by inhalation to label red blood cells. Tomograms obtained in vivo in six dogs with either normal or reduced regional blood flow correlated closely with the tomographically detectable distribution of 68Ga-labeled microspheres (r = .93) and with postmortem microsphere distribution (r = .95). The technique accurately reflects myocardial blood flow. With the use of PET, rapid sequential noninvasive estimation of relative regional myocardial blood flow has been demonstrated that should ultimately permit improved objective assessment of nutritional blood flow in patients in response to medical and surgical interventions designed to augment perfusion.

Animals↗
PubMed1983

Brain blood flow measured with intravenous H2(15)O. I. Theory and error analysis.

The tissue autoradiographic method for the measurement of regional cerebral blood flow (rCBF) in animals was adapted for use with positron emission tomography (PET). Because of the limited spatial resolution of PET, a region of interest will contain a mix of gray and white matter, inhomogeneous in flow and in tracer partition coefficient (lambda). The resultant error in rCBF, however, is less than 4%. Although the tissue autoradiographic method requires a monotonically increasing input function to ensure a unique solution for flow, the PET adaptation does not, because of an additional integration in the operational equation. Simulation showed that the model is accurate in the presence of ischemia or hyperemia of the gray matter. Inaccuracy in timing of the arterial input function will result in large errors in rCBF measurement. Propagation of errors in measurement of tissue activity is largely independent of flow, reflecting the nearly linear flow compared with activity relationship.

Cerebrovascular Circulation↗
PubMed1983

Brain blood flow measured with intravenous H2(15)O. II. Implementation and validation.

We have adapted the well-known tissue autoradiographic technique for the measurement of regional cerebral blood flow (CBF), originally proposed by Kety and his colleagues, for the measurement of CBF in human subjects using positron emission tomography (PET) and intravenously administered oxygen-15-labeled water. This report describes the steps necessary for the implementation of this PET/autoradiographic technique. In order to establish the accuracy of the method, we measured CBF with intravenously administered oxygen-15-labeled water and PET in anesthetized adult baboons and compared the results with blood flow measured by a standard tracer technique that uses residue detection of a bolus of oxygen-15-labeled water injected into the internal carotid artery. The correlation between CBF measured with PET and the true CBF for the same cerebral hemisphere was excellent. Over a blood-flow range of 10-63 ml/(min X 100 g), CBF (PET) = 0.90 CBF(true) + 0.40 (n = 23, r = 0.96, p less than 0.001). When blood flow exceeds 65 ml/(min X 100 g) CBF was progressively underestimated due to the known limitation of brain permeability to water.

Adult↗
PubMed1981

Photon time-of-flight-assisted positron emission tomography.

In positron emission tomography (PET), the annihilation radiation is usually detected as a coincidence occurrence that localizes the position of the annihilation event to a straight line joining the detectors. The measure of the difference between the time of flight (TOF) of the annihilation photons between their inception and their detection permits the localization of the position of the annihilation event along the coincidence line. The incorporation of TOF information into the PET reconstruction process improves the signal-to-noise ratio in the image obtained. The utilization of scintillation detectors utilizing cesium fluoride scintillators, fast photomultiplier tubes, and fast timing circuits allows sub-nanosecond coincidence timing resolution needed for the effective use of TOF in PET. Mathematical considerations and pilot experiments show that with state-of-the-art electronic components and through the application of proper reconstruction algorithms, the combination of TOF and PET positional data improves severalfold the signal-to-noise ratio with respect to conventional PET image reconstruction at the cost of increasing the amount of data to be processed. The construction of a TOF-assisted PET device is within the capability of state-of-the-art technology.

Electronics, Medical↗
PubMed1981

An introduction to the measurement of the cerebral oxygen uptake rate by inhalation of 15O2; analysis of the contribution of 15O2 and H2 15O in brain radioactivity.

This paper introduces a model for the computation of the regional cerebral metabolic rate of oxygen from the data of cerebral regional radioactivity collected after inhalation of 15O2. A method was devised for the differential determination of the respective contribution of radiooxygen and of radiowater in the inflow and the outflow of radioactivity in the brain after or during such on inhalation. The results demonstrate the feasability of such a model and outline some of the methodological to be taken into account in the numerical analysis of the data.

Animals↗
PubMed1981

Positron tomographic imaging of the liver: 68 Ga iron hydroxide colloid.

A new radiopharmaceutical, 68Ga ion hydroxide colloid, for hepatic imaging by positron emission tomography was prepared from the eluate of a 68Ge-68Ga solvent extraction generator. In rats, 84% of the administered dose of colloid localized in the liver and 4.6% accumulated in the spleen. Initial imaging studies in normal dogs showed close correspondence of the findings by positron tomography and transmission computed tomography. Emission tomography with 68Ga-colloid was performed in 10 patients with hepatic metastases demonstrated by conventional 99mTc sulfur colloid scintigraphy. All focal defects noted on the conventional scintigrams were easily identified and generally were seen more clearly by positron tomography. In one patient, additional lesions not identified on the initial 99mTc sulfur colloid images were demonstrated. The positron tomographic images were compared with those obtained by transmission computed tomography in seven patients; the two studies showed comparable findings in five patients, whereas positron tomography more clearly showed multiple lesions in two. Our results suggest that positron emission tomography is a suitable technique for obtaining high contrast, cross-sectional images of large abdominal organs.

Animals↗
PubMed1980

Feasibility of time-of-flight reconstruction in positron emission tomography.

A feasibility study was carried out to determine whether image quality can be improved by the use of time-of-flight (TOF) information in positron emission tomography (PET). The experiment used two fast cesium fluoride detectors followed by constant-fraction discriminators for coincidence-timing resolutions of 600 to 800 psec full width at half maximum, depending on the energy discrimination level. A point source was scanned to study the spatial response of the point spread function with and without the TOF information for nonfiltered back-projected data. Back-projected images of a simplified chest phantom, 42 cm in diameter and filled with relative activity concentrations of 1.0, and 5, are presented for the unfiltered data to demonstrate the improvement in image quality obtained with the use of TOF. Filtered and reconstructed images of this phantom are also presented to show the relative differences in the images obtained with PET and TOF-PET techniques for similar filter functions.

Physical Phenomena↗
PubMed1977

Atypical staphylococcal mastitis in a dairy herd.

A herd of cattle with a history of increased prevalence of clinical and nonclinical mastitis was investigated. Bacteriologic analysis of milk samples indicated approximately 50% of the herd was producing milk containing coagulase-positive staphylococci. Of these staphylococcal isolates, 55% had characteristics consistent with those of human strains of staphylococci, based on hemolysin production and phage patterns. Human beings in contact with the herd were nasal carriers of these staphylococci, which produced a granulartype coagulase reaction in bovine plasma, rather than the usually expected clot-type reaction. In the herd, the staphylococci caused mainly nonclinical mastitis, which was largely unresponsive to antibiotic therapy.

Animals↗
PubMed1975

Regional ventilation-perfusion relationships.

Regional ventilation-perfusion ratios have been determined in 12 healthy subjects, 16 patients with pulmonary embolism, and 22 patients with chronic obstructive lung disease. The ventilation-perfusion ratios were determined from xenon-133 ventilation studies and 99-tc-m-labeled particle perfusion scans, using either the fractional exchange of air or the relative distribution of tidal volume per unit volume as the numerator of the ratio. A comparison of these two methods showed comparable distributions of regional ventilation-perfusion relationships in the healthy subjects and patients with pulmonary embolism. However, in the patients with chronic obstructive pulmonary disease, the fractional exchange method clearly separated this group of patients from the others.

Chemotherapy, Cancer, Regional Perfusion↗
PubMed1975

Radionuclide angiocardiography. Improved diagnosis and quantitation of left-to-right shunts using area ratio techniques in children.

A comparison of several reported methods for detection and quantitation of left-to-right shunts by radionuclides was performed in 50 children. Count ratio (C2/C1) techniques were compared with the exponential extrapolation and gamma function area ratio techniques. C2/C1 ratios accurately detected shunts and could reliably separate shunts from normals, but there was a high rate of false positives in children with valvular heart disease. The area ratio methods provided more accurate shunt quantitation and a better separation of patients with valvular heart disease than did the C2/C1 ratio. The gamma function method showed a higher correlation with oximetry than the exponential method, but the difference was not statistically significant. For accurate shunt quantitation and a reliable separation of patients with valvular heart disease from those with shunts, area ratio calculations are preferable to the C2/C1 ratio.

Adolescent↗
PubMed1975

Metabolism in immunoreactive parathyroid hormone in the dog. The role of the kidney and the effects of chronic renal disease.

The role of the kidney in the metabolism of parathyroid hormone (PTH) was examined in the dog. Studies were performed in awake normal and uremic dogs after administration of bovine parathyroid hormone (b-PTH) or synthetic amino terminal tetratricontapeptide of b-PTH (syn b-PTH 1-34). The renal clearance of immunoreactive PTH was determined from the product of renal plasma flow and the percent extraction of PTH immunoreactivity by the kidney. Blood levels of circulating immunoreactive PTH were determined by radioimmunoassay. The normal dog kidney extracted 20 plus or minus 1% of the immunoreactive b-PTH delivered to it, and renal clearance (RC) of immunoreactivity was 60 ml/min. When RC was compared to an estimate of total metabolic clearance (MCR) of immunoreactivity, it accounted for 61% of the total. Both MCR and RC were markedly decreased in dogs with chronic renal disease. However, the percent extraction of immunoreactive PTH was unchanged in chronic renal disease, and the observed decrease in RC was due to changes in renal plasma flow. The largest portion of the reduction in total MCR was accounted for by the decrease in RC, and there was no compensation for the decrease in RC by extrarenal sites of PTH metabolism.

Animals↗