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Biomedical subjects

J L Lear

Publications and source records attributed to J L Lear.

47 records · Page 3Linked to original sources

Autoradiographic comparison of thallium-201 diethyldithiocarbamate, isopropyliodoamphetamine and iodoantipyrine as cerebral blood flow tracers.

We investigated [201Tl]diethyldithiocarbamate (DDC) as a tracer for local cerebral blood flow (LCBF). Awake male rats were given intravenous infusions of a mixture of DDC and reference tracer(s): [123I]isopropyliodoamphetamine (IMP) and/or [14C]iodoantipyrine (IAP). LCBF values for DDC, IMP, and IAP were measured using simultaneous multiple radionuclide autoradiography and quantitative digital image analysis. Patterns of local cerebral blood flow (LCBF) obtained with DDC were intermediate compared to IMP and IAP, although they were more similar to those of IMP. DDC and IMP underestimated LCBF in some white matter and adjacent structures, while IAP underestimated LCBF values in high flow regions. We conclude that DDC uptake generally reflects local cerebral blood flow and that it can therefore be used as a cerebral perfusion tracer in humans using SPECT imaging.

Amphetamines↗

Digital autoradiography: design, development, and evaluation of a solid-state image analyzer.

A digital image analyzer was developed for high spatial resolution analysis of autoradiograms. The system uses a linear array of charge-coupled devices operating under microcomputer control to scan and digitize autoradiograms into matrices of up to 1,500 X 2,000 pixels with 256 gray levels. The digitized images can be converted from gray scale to pseudo-color and displayed on a high resolution color monitor. Software was developed to facilitate quantitative analysis of autoradiograms produced in single and multiple tracer studies. Because of the high output linearity and accuracy of the solid-state detectors, the system was found to digitize autoradiograms significantly more precisely and accurately than previously described autoradiographic analyzers.

Autoradiography↗

High-performance digital image analyzer for quantitative autoradiography.

A digital image-processing system was developed for high-spatial resolution analysis of autoradiograms. The system uses a linear array of charge-coupled devices operating under computer control to scan and digitize autoradiograms into 512 X 512 matrices with 256 gray levels. Software was developed to facilitate quantitative analysis of autoradiograms produced in single- and multiple-tracer studies. Because of the high output, linearity, and accuracy of the solid-state detectors, the system was found to digitize autoradiograms significantly more precisely and accurately than previously described video camera- or photomultiplier tube-based scanning densitometers.

Autoradiography↗

Maximizing precision in quantitative autoradiographic determination of tissue tracer concentration using exposure optimization.

The relationships between tissue tracer concentrations, length of time of tissue contact with film, and the darkness of resulting autoradiographic images were explored. Operational equations were then developed relating ranges of film darkening to the ranges of tracer concentration contained within the sections. These equations were solved and used to define ranges of optical density that are optimal for precise determination of tracer concentration using digital image analyzers. The solutions indicated that optimal optical densities are a function of the range of tracer concentrations in the sections. For autoradiograms of typical cerebral blood flow and metabolism tracers, exposure should be controlled to produce images that are significantly less dark than what is generally considered pleasing to the eye.

Autoradiography↗

Effect of exercise position during stress testing on cardiac and pulmonary thallium kinetics and accuracy in evaluating coronary artery disease.

We compared the effects of symptom-limited upright and supine exercise on 201Tl distribution and kinetics in the heart and lungs of 100 consecutive patients. Our analysis was based on data obtained with a digital gamma camera in the 45 degrees left anterior oblique position at 5, 40, 240, and 275 min postadministration of [201Tl]chloride. We found significant differences in the results at the 5- and 40-min intervals; viz, higher cardiac and lower pulmonary thallium activity after upright exercise in 94 subjects at both intervals, and greater variability in total and regional cardiac thallium kinetics after supine exercise. With supine exercise, the relatively low initial cardiac activity, relatively high lung activity, and the greater variability in thallium kinetics combined to make interpretation of quantitative data and cardiac images difficult and less accurate with respect to detection of coronary artery disease. These observations have important implications for the interpreting physician when thallium stress tests are performed in the supine position.

Coronary Disease↗

Supine thallium 201 cardiac testing compared with treadmill testing.

Although thallium 201 stress testing is usually performed on a treadmill (Tl-TM), supine bicycle-ergometer-exercise thallium 201 testing (Tl-SB) has been reported. We performed a study to evaluate the accuracy of Tl-SB in evaluation of coronary artery disease and to correlate its results with those of Tl-TM. Fifty patients underwent both Tl-SB and Tl-TM testing in random sequence an average of 1 week apart. Tl-TM produced significantly higher maximal pulse rates and pulse-pressure products. Cardiac thallium kinetics differed significantly between Tl-SB and Tl-TM with Tl-TM producing greater initial myocardial uptake and greater thallium 201 washout between immediate and delayed images. Compared with results of catheterization, Tl-TM was significantly more accurate than Tl-SB for evaluation of coronary artery disease, with higher sensitivity and specificity.

Coronary Disease↗

Multiple-radionuclide autoradiography in evaluation of cerebral function.

We have developed the mathematical model and experimental technique for quantitative simultaneous multiple-radionuclide autoradiography. The technique is an extension of previously described dual-tracer methods and offers the advantage of a general approach in which any two or more radionuclides with different half-lives can be used to measure multiple parameters of cerebral function. The model allows the selection of nuclide doses and exposure times to balance cross-contamination of the multiple images with nuclide requirements. The technique was validated with homogeneous tissue sections containing combinations of 123I, 124I , 131I, 18F, 99mTc , 68Ga, and 14C, and then used in qualitative and quantitative investigations of interrelationships of local cerebral blood flow, glucose metabolism, and protein synthesis in normal and several pathological conditions in rats.

Animals↗

Percutaneous transhepatic electrohydraulic lithotripsy.

Calculi can be fragmented by hydraulic shock waves generated by an electrical discharge across the tip of a coaxial electrode. After testing a device by using this technique in the biliary trees of dogs, the authors fragmented a large common bile duct stone in a patient through a percutaneous transhepatic approach. The fragmentation allowed nonsurgical drainage of the obstructed duct.

Aged↗

Evaluation of [123I]isopropyliodoamphetamine as a tracer for local cerebral blood flow using direct autoradiographic comparison.

We investigated [123I]isopropyliodoamphetamine (IMP) for potential use in the autoradiographic determination of local cerebral blood flow (LCBF) in animals. The technique of direct autoradiographic comparison, derived from double radionuclide autoradiography, was used to compare the simultaneous uptakes of IMP and [14C]iodoantipyrine (IAP), a reference tracer, in awake and anesthetized rats. This new technique offers several advantages over the previously developed methods of comparing tracers, brain uptake index and first pass extraction ratio. These include the avoidance of disrupting normal cerebral blood-brain tracer exchange and the ability to compare uptakes at substructural levels, whereas the other methods are limited to larger areas. Mean values of LCBF obtained with IMP agreed closely with those using IAP, from 20 to 300 ml/100 g/min. Because IMP was found to have an extremely high effective brain:blood partition coefficient, approximately 25:1, a linear uptake tracer model could be used for IMP yielding more precise values than could IAP for LCBF values above 150. IMP was found to measure choroid plexus flows much more accurately than IAP, values being greater than 500 for IMP compared to approximately 200 for IAP. Because the mechanism of the extremely high partition coefficient of IMP is not yet defined, however, care must be used in measuring LCBF with IMP where the trapping mechanisms of normal vessels may be disrupted.

Amphetamines↗

Quantifying local cerebral blood flow by N-isopropyl-p-[123I]iodoamphetamine (IMP) tomography.

A model was validated wherein local cerebral blood flow (LCBF) in humans was quantified by single-photon emission computed tomography (SPECT) with intravenously injected N-isopropyl-p-[123I]iodoamphetamine (IMP) combined with a modification of the classic method of arterial input sampling. After intravenous injection of IMP in rat, autoradiograms of the brain showed activity distributions in the pattern of LCBF. IMP was nearly completely removed on first pass through monkey brain after intracarotid injection (CBF=33 ml/100 g/min) and washed out with a half-time of approximately 1 hr. When the modified method of arterial input and tissue-sample counting applied to dog brain, there was good correspondence between LCBF based on IMP and on that by microsphere injection over a wide flow range. In applying the method to human subjects using SPECT, whole-brain CBF measured 47.2 +/- 5.4 ml/100 g/min (mean +/- s.d., N=5), stable gray-white distinction persisted for over 1 hr, and the half-time for brain washout was approximately 1 hr. Perfusion deficits in patients were clearly demonstrated and quantified, comparing well with results now available from positron ECT.

Adolescent↗

Use of 123I and 14C in a double radionuclide autoradiographic technique for simultaneous measurement of LCBF and LCMRgl. Theory and method.

We have developed an autoradiographic technique for the simultaneous measurement of local cerebral blood flow (LCBF) and local cerebral metabolic rate for glucose (LCMRgl) using 123I-iodoantipyrine and 14C-2-deoxyglucose respectively. By exploiting the different half-lives of 123I and 14C, 13.0 hours versus 5730 years, we produce 2 autoradiographic images. The first is predominantly a result of the 123I and the second is predominantly from the 14C. Because of the impracticality of making 123I standards, it was necessary to determine the constant which relates the ability of 123I, with respect to 14C, to expose Kodak SB-54 film, so that the 123I exposure could be quantified using 14C standards. Subtraction equations can then be used to solve for the local 123I and 14C concentrations. The technique was validated in conditions simulating a 12-fold decoupling of flow and metabolism and the standard deviation of error in measuring tracer concentrations was less than 6%. It was then used to measure these parameters in the normal awake rats and values obtained agreed well with published values from single radionuclide studies. The technique is expected to be useful in the simultaneous measurement of LCBF and LCMRgl in various physiologic or pathologic states, including those with significant decoupling of flow and metabolism. In addition, by using other tracers labelled with 123I and 14C, other parameters can be measured concurrently.

Animals↗