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Biomedical subjects

P W Doherty

Publications and source records attributed to P W Doherty.

At least 19 recordsLinked to original sources
PubMed1988

Evaluation of technetium pertechnetate as a radionuclide marker of pulmonary aspiration of gastric contents in rabbits.

At present, there is no sensitive and specific test to confirm the clinical impression that a respiratory disorder is due to aspiration of gastric contents. Since intravenous technetium pertechnetate (99mTcO4-) has been shown to be safe, actively concentrated in the gastrointestinal tract, and secreted into gastric juice, we sought to determine whether 99mTcO4-, when given intravenously, is suitable to detect pulmonary aspiration of small amounts of gastric contents in rabbits. Biodistribution studies over 24 h revealed that 99mTcO4- persistently appeared in the stomach, thyroid, and salivary glands and did not appear in the lungs. Pharmacokinetic studies showed that 99mTcO4- was rapidly picked up by the stomach wall and secreted promptly into the stomach lumen and that the stomach wall persistently secreted 99mTcO4- into stomach contents for 24 h. By injecting 99mTcO4- through an intratracheal catheter in order to simulate aspiration, the radioactive threshold for imaging intrapulmonary 99mTcO4- was determined to range between less than 0.5 microCi and 2 microCi, depending on the amount of background activity in the blood pool. By measuring the radioactivity in stomach contents (microCi/g), over 24 h after intravenous injection of 2 mCi of 99mTcO4-, we were able to calculate the amount of aspirated stomach contents that our technique should reveal at various time points. We concluded from this preliminary feasibility study that 99mTcO4-, when given intravenously, is suitable to detect pulmonary aspiration of small amounts (less than or equal to 4 ml for 8 h after an intravenous dose of 2 mCi) of gastric contents in human patients. Since our biodistribution studies show that saliva as well as stomach contents are potential sources for any aspirated 99mTcO4-, how to distinguish aspiration of oropharyngeal from stomach contents remains to be determined. It also remains to be determined how long 99mTcO4- remains in the lungs after it has been instilled; clearance that is too rapid significantly decreases the ability of this agent to reveal aspiration.

Animals↗
PubMed1988

Stationary and nonstationary spatial domain Metz filtering.

Stationary and nonstationary finite-impulse-response (FIR) implementations of the count-dependent Metz filter were investigated in this study. Filter size was observed to be an important variable controlling image quality. For Metz filtering of 128 X 128 pixel images at least a 15 X 15 term FIR filter was deemed necessary. By using an algorithm which selected between a set of preformed FIR filters based on pixel count, a nonstationary FIR implementation of the Metz filter was developed which required very little increase in execution time to stationary filtering. In a limited comparison of 'tumor' detection with stationary and nonstationary FIR filtering all of the Metz filtering techniques showed a significant improvement in detection when compared to the unprocessed images. However, no significant difference was observed between the stationary and nonstationary Metz filtering techniques. Thus, for Metz filters optimized solely on the basis of count, nonstationary FIR filtering does not seem to offer an advantage when compared to stationary filtering.

Filtration↗
PubMed1988

Patient biodistribution of intraperitoneally administered yttrium-90-labeled antibody.

Although 90Y is one of the best radionuclides for radioimmunotherapeutic applications, the lack of gamma rays in its decay complicates the estimation of radiation dose since its biodistribution cannot be accurately determined by external imaging. A limited clinical trial has been conducted with tracer doses (1 mCi) of 90Y in five patients who then received second-look surgery such that tissue samples were obtained for accurate radioactivity quantitation by in vitro counting. The anti-ovarian antibody OC-125 as the F(ab')2 fragment was coupled with diethylenetriaminepentaacetic acid, radiolabeled with 90Y and administered intraperitoneally to patients with suspected or documented ovarian cancer. Size exclusion and ion exchange high performance liquid chromatography analysis of patient ascitic fluid and serum samples showed no evidence of radiolabel instability although a high molecular weight species (presumably immune complex) was observed in three patients. Total urinary excretion of radioactivity prior to surgery averaged 7% of the administered radioactivity while at surgery the mean organ accumulation was 8% of the administered radioactivity in serum, 10% in liver, 7% in bone marrow, and 19% in bone with large patient to patient variation. The mean tumor/normal tissue radioactivity ratio varied between 3 and 25. On the assumption that the above radioactivity levels were achieved immediately following administration, that the radioactivity remained in situ until decayed and that the dimensions of tumor were sufficient to completely attenuate the emissions of 90Y, the dose to tumor for a 1-mCi administration would be approximately 50 rad with normal tissues receiving approximately 8 rad.

Animals↗
PubMed1987

Characterization of indium-111 labeled recombinant tissue plasminogen activator for the imaging of thrombi.

The in vitro functional properties of recombinant tissue plasminogen activator (rt-PA), its biodistribution in mice, and its pharmacokinetics and clot localization properties in dogs have been investigated after labeling rt-PA with 111In. The rt-PA was coupled with the bicyclic anhydride of DTPA using standard methodology. Amidolytic and fibrinolytic assays showed retention of protein activity when rt-PA was conjugated with an average of one DTPA group or less per molecule. Size exclusion HPLC showed each preparation to be radiochemically pure with 111In bound exclusively to the attached DTPA groups. Biodistribution in mice showed major accumulation of activity in the liver and kidneys. After administration of 0.5-1.0 mg of the labeled protein to dogs, blood activity decreased with a half time of approximately 5 min in agreement with previous reports of rapid blood clearance. Largely because of decreased blood levels, clot: blood ratios of labeled protein increased rapidly, in one study reaching 6.3 after 31 min, and satisfactory images of fibrin thrombi were obtained. The rt-PA may be labeled with 111In without destroying the ability of the protein to localize in clot and images of forming clot can be obtained with this agent within 1 h after administration.

Animals↗
PubMed1987

Interactive visual optimization of SPECT prereconstruction filtering.

A number of factors must be considered when forming a digital filter to two-dimensionally filter single photon emission computed tomographic (SPECT) acquisition images. In an effort to provide subjectively optimal filtering, a program has been developed which provides "real-time" visual feedback. This allows a user to select from among a family of Metz filters tailored for the imaging conditions (i.e., formed to deconvolve scatter, septal penetration, and combined collimator and intrinsic spatial resolution losses). Also, a guideline for assisting the user in selecting from among the possible Metz filters has been formulated. This guideline is based upon knowledge of the probability distribution of the noise power spectrum, and consists of choosing the filter which has a value of 1.0 when the one-dimensional compression of the image power spectrum equals the 90% confidence limit for noise fluctuations. The program starts by filtering a planar reference image with the Metz filter computed for the radionuclide, collimator, magnification, and count-level of the image. This filter is displayed beside the image where it is overlayed on a plot of the logarithm of the one-dimensional compression of the image power spectrum. The user is then allowed to vary the filter parameters through movement of a joystick. By doing the filtering using an array processor, a new filtered image is formed and displayed less than a second after movement of the joystick. Visual feedback from the series of filtered images thus produced as well as the plots of the filter overlayed on the estimated blurred object power spectrum are used to obtain a visually "optimal" filter. The filter can be adapted to the visual preferences of the individual reader, and serves as a useful teaching tool on the effects of filtering.

Evaluation Studies as Topic↗
PubMed1987

The clinical implications of bilaterally abnormal impedance plethysmography.

Although impedance plethysmography (IPG) is a test of recognized value in the diagnosis of acute proximal deep venous thrombosis (DVT), its meaning in patients with bilaterally abnormal IPGs is unclear. Consequently, we sought to determine the clinical significance of the bilaterally abnormal IPG in hospitalized patients. In a five-month prospective study, 19% (81/425) of all IPGs done at our institution were bilaterally abnormal (55% of all abnormal IPGs). Acute proximal DVT was found in 26% (14/53) of patients with bilaterally abnormal IPGs who underwent further diagnostic testing. Thirty-five percent of the patients with DVT were found to have either bilateral lower extremity DVT or clots in the inferior vena cava. A numerical score, the venous function index (VFI), was computed for the 101 legs for which further definitive diagnostic evaluations for DVT had been completed. The mean VFI of seven for legs with acute proximal DVT was significantly less than the mean VFI of 13 for legs with no DVT. Fifty percent of legs with a VFI less than or equal to five had DVT, whereas only 7% of legs with a VFI greater than 15 had DVT. The bilaterally abnormal IPG is a common clinical occurrence, is frequently associated with acute DVT, and the VFI is helpful in discriminating legs with acute proximal DVT from normal legs in patients with a bilaterally abnormal IPG.

Adolescent↗
PubMed1986

Digital restoration of indium-111 and iodine-123 SPECT images with optimized Metz filters.

A number of radiopharmaceuticals of great current clinical interest for imaging are labeled with radionuclides that emit medium- to high-energy photons either as their primary radiation, or in low abundance in addition to their primary radiation. The imaging characteristics of these radionuclides result in gamma camera image quality that is inferior to that of 99mTc images. Thus, in this investigation 111In and 123I contaminated with approximately 4% 124I were chosen to test the hypothesis that a dramatic improvement in planar and SPECT images may be obtainable with digital image restoration. The count-dependent Metz filter is shown to be able to deconvolve the rapid drop at low spatial frequencies in the imaging system modulation transfer function (MTF) resulting from the acceptance of septal penetration and scatter in the camera window. Use of the Metz filter was found to result in improved spatial resolution as measured by both the full width at half maximum and full width at tenth maximum for both planar and SPECT studies. Two-dimensional, prereconstruction filtering with optimized Metz filters was also determined to improve image contrast, while decreasing the noise level for SPECT studies. A dramatic improvement in image quality was observed with the clinical application of this filter to SPECT imaging.

Brain↗
PubMed1985

A simple in vitro method of screening panels of monoclonal antibodies for tumor binding.

We have developed a simple in vitro method of evaluating the relative binding properties of anti-tumor antibodies to human tumor and normal tissues. Cryopreserved surgical explants of tissues as 1 mm cubes are incubated in microtiter plate wells containing media and radiolabeled antibody. We show that the accumulation of antibody in tumor tissue is a specific process which may be reduced by preincubation with saturating levels of unlabeled specific antibody. Evaluation of 7 anti-breast and 4 anti-colorectal tumor antibodies against their respective tumor tissues showed good reproducibility of repeat measurements and up to a 100-fold difference in accumulation among different antibodies to the same tissue. Equivalent results were obtained with the same tissues employed fresh and after cryopreservation. Because of the simplicity of the assay, panels of antibodies may be screened against the large numbers of tumor and normal tissues required to identify superior antibodies for human trials.

Acid Phosphatase↗
PubMed1985

Ejection fraction and heart rate correlate with diastolic peak filling rate at rest and during exercise.

We investigated the independent variables correlating with the multigated radionuclide peak filling rate (PFR) at rest and during supine bicycle exercise in 20 normal individuals. Independent variables were systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), ejection fraction (LVEF), time to PFR (TPFR), peak ejection rate (PER) and time to PER (TPER). Fifteen subjects completed at least five stages of exercise at 25 watts each. Correlating independent variables were selected by a forward-backward stepwise multiple linear regression (BMDP2R). A partial correlation statistical program was also used to allow control of critical independent variables. The final regression equations were: a) resting state, PFR = -2.5 + 0.03HR + 0.05LVEF + 0.02SBP-0.02DBP, and b) exercise state, PFR = -3.8 + 0.04HR + 0.08LVEF. All independent variables mentioned above correlated with PFR (simple correlations designated as zero partials). However, when LVEF and HR were held constant (second order partials), the correlation of PFR with any of the other independent variables disappeared. In summary, the radionuclide global LV PFR is predominantly correlated to LVEF and HR at rest and during exercise. These correlations should be considered when assessing exercise effects of disease states on PFR.

Adult↗
PubMed1985

Pharmacokinetics of an indium-111-labeled monoclonal antibody in cancer patients.

We have evaluated the pharmacokinetics in patients of a monoclonal antibody (19-9) F(ab')2 fragment coupled with DTPA and labeled with 111In. In addition to imaging and organ uptake determinations, serum and urine samples were analyzed to help determine the in vivo behavior of the label. Using a competitive binding assay, the immunoreactivity of the coupled fragment was found to be indistinguishable from that of the unmodified fragment. The absence of radiocolloids in the injectate was confirmed as was the in vivo stability of the attached DTPA groups. By a variety of techniques, we show that the only significant source of label instability was transcomplexation to circulating transferrin. About 9% per day of label exposed to transferrin (about 1-2% of the injected dose) dissociated with slight bone marrow accumulation. Following i.v. administration, serum activity levels fell rapidly (T 1/2 alpha 2 hr, T 1/2 beta 19 hr). Whole-body clearance of the label was slow (T 1/2 160 hr) and may be attributed entirely to urinary excretion (0.26% of the injected dose per hour). Organ accumulation was greatest in the liver and persisted after rapidly attaining high values (20% of the injected dose). A total of 14 cancer patients were studied, nine with identifiable sites of metastatic disease from colorectal [8], pancreatic [2], ovarian [3], or small cell lung [1] primaries. Eight of the 12 sites of documented tumor were visualized by external imaging (67%) most distinctly at 48-72 hr postadministration.

Adult↗
PubMed1985

DTPA-coupled antibodies labeled with yttrium-90.

Yttrium-90 has been described as one of the best radionuclides for tumor therapy when chelated to tumor-associated antibodies. This evaluation is based on the superior properties of this radionuclide (suitable half-life, pure beta-ray emitter of intermediate energy, stable daughter, and suitable chemical properties) and because it is available as a radionuclide generator product by decay of its 28-yr parent 90Sr. We have determined that 90Y obtained from one such generator is suitable for labeling antibodies coupled with DTPA. Furthermore, we have shown that the dissociation rate of [90Y]DTPA-IgG in serum at 37 degrees C is similar to that of [111In]DTPA-IgG at about 8-9%/day. Biodistribution studies of 111In- and 90Y-labeled to DTPA-coupled IgG show that the labels distribute nearly identically at 1 hr postadministration, although differences in distribution are apparent at 24 hr. It is possible that these differences reflect the redistribution of the labels following catabolism at the site of localization.

Animals↗
PubMed1984

Exercise testing and hemodynamic performance in healthy elderly persons.

To determine the effect of age on cardiovascular performance, 39 healthy elderly men and women, 70 to 83 years old, underwent treadmill thallium-201 exercise perfusion imaging and radionuclide equilibrium angiography at rest and during supine bicycle exercise. Five volunteers who had a positive exercise thallium test response were excluded from the study. Radionuclide left ventricular ejection fraction, regional wall abnormalities, relative cardiac output, stroke volume, end-diastolic volume and end-systolic volume were measured. Seventy-four percent of the subjects maintained or increased their ejection fraction with exercise. With peak exercise, mean end-diastolic volume did not change, end-systolic volume decreased and cardiac output and stroke volume increased. Moreover, in 35% of the subjects, minor regional wall motion abnormalities developed during exercise. There was no significant difference in the response of men and women with regard to these variables. However, more women than men had difficulty performing bicycle ergometry because they had never bicycled before. Subjects who walked daily performed the exercise tests with less anxiety and with a smaller increase in heart rate and systolic blood pressure.

Aged↗
PubMed1984

Non-invasive evaluation of ventricular function and volumes during atrioventricular sequential and ventricular pacing.

Thirteen patients who all had previously inserted temporary or permanent pacemakers (6, VVI; 7, A-V sequential) were studied by two-dimensional echocardiography and radionuclide gated blood pool ventriculography (RVG) for non-invasive evaluation of cardiac performance. Patients were paced in both the VVI mode and during sinus/atrial or A-V sequential pacing. Although there was no objective change of the ejection fraction during V-pacing and atrial/A-V sequential pacing or sinus rhythm, as has been previously reported, A-V sequential pacing did result in significant improvement in overall cardiac function and output as judged by radionuclide ventriculography and blood pressure response in most of our patients. An appropriately timed atrial contribution to ventricular systole resulted in improved ventricular function in those individuals with pre-existing systolic or diastolic myocardial dysfunction and/or sick sinus syndrome in whom pacemaker therapy was indicated. Radionuclide ventriculography appears to be a reliable, accurate, non-invasive method that can be used to evaluate patients before implantation of a permanent ventricular or atrioventricular pacemaker in order to decide which pacing mode is best for that particular individual.

Aged↗
PubMed1984

Two-dimensional filtering of SPECT images using the Metz and Wiener filters.

Two-dimensional filtering, both before and after reconstruction, has been applied to the processing of single photon emission computerized tomographic (SPECT) images. The filters investigated were the count-dependent Metz filter and Wiener filter, both of which automatically adapt to the image being processed. Using a SPECT phantom, with images reconstructed with these filters rather than the ramp, we observed a statistically significant increase (p less than 0.05) in the image contrast for solid Plexiglas spheres, and significant decrease (p less than 0.05) in the percent fractional standard deviation of counts in a region of uniform activity. The adaptability of these filters is demonstrated by a comparison of SPECT acquisitions of the phantom at two different count levels. An example of their application to clinical studies is presented. We conclude that two-dimensional digital image restoration with these techniques can produce a significant increase in SPECT image quality, with a small cost in processing time when these techniques are implemented on an array processor.

Filtration↗
PubMed1983

Radioactive labeling of antibody: a simple and efficient method.

A simple and efficient method of covalently coupling the strong chelator diethylenetriaminepentaacetic acid to proteins was developed for radiolabeling immunoglobulin G antibodies. After being coupled and labeled with indium-111, a monoclonal antibody to carcinoembryonic antigen retained its ability to bind to its antigen in vitro and in vivo. In nude mice with a human colorectal xenograft, 41 percent of the injected radioactivity became localized in each gram of xenograft at 24 hours compared with 9 percent for control antibody and 19 percent for radioiodinated antibody to carcinoembryonic antigen.

Animals↗
PubMed1983

Measurement of regional changes in myocardial perfusion using dynamic computed tomography and contrast medium.

Changes in regional myocardial perfusion were measured using rapid sequence dynamic transmission tomography to detect differences in the initial distribution of contrast medium injected as an intravenous bolus. The experiments were carried out on 8 mongrel dogs instrumented with flow probes and vascular occluders around the coronary arteries. Flow reductions of 50 per cent or more were detected as regions of myocardium with less contrast enhancement than those with normal perfusion. Reactive hyperemia induced by transient ischemia was detected as areas of relatively increased contrast enhancement. These changes could be demonstrated on the images and quantitated using data depicting changes in HU (Hounsfield units) with time to develop an index of perfusion. The images obtained were of satisfactory quality and differences between the underperfused and normal myocardium were made more prominent by using dipyridamole infusions.

Animals↗