Re: Concerning the labeling of DTPA-coupled proteins with Tc-99m.
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Biomedical subjects
Publications and source records attributed to P W Doherty.
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Array processors are "number crunchers" that dramatically enhance the processing power of nuclear medicine computer systems for applications dealing with the repetitive operations involved in digital image processing of large segments of data. The general architecture and the programming of array processors are introduced, along with some applications of array processors to the reconstruction of emission tomographic images, digital image enhancement, and functional image formation.
The formulation of an "optimal" filter for improving the quality of digitally recorded nuclear medicine images is reported in this paper. The method forms a Metz filter for each image based upon the total number of counts in the image, which in turn determines the average noise level. The parameters of the filter were optimized for a set of simulated images using the minimization of the mean-square error as the criterion. The speed of the image formation results from the use of an array processor. In a study of localization receiver operating characteristics (LROC) using the Alderson liver phantom, a significant improvement in tumor localization was found in images filtered with this technique, compared with the original digital images and those filtered by the nine-point binomial smoothing algorithm. The technique has been found useful for the filtering of static and dynamic studies as well as the two-dimensional pre-reconstruction filtering of images from single photon emission computerized tomography.
A program was written to convert the output of a scanning gamma camera into a whole body computer image which can then be used to study regional and whole body radiopharmaceutical localization. The electronically masked output of the camera is collected as a dynamic study on the computer with the time per frame set according to scan speed. The program overlays these frames onto a matrix in memory to form the image. The overlayed frame is incremented 1 pixel/frame in the direction of camera motion during camera scanning. The timing of camera motion is automatically determined by the program. Although written for a specific scanning gamma camera, the ideas inherent in the algorithm will allow the reconstruction of whole body images from other scanning cameras.
Acute osteomyelitis was induced in 18 rabbits after direct injection of a solution of Staphylococcus aureus culture into a proximal tibial metaphysis. Serial plain radiographs and radionuclide studies with indium-111 oxide labeled while blood cells and technetium-99m methylene diphosphonate were performed over the next 4 weeks. Visual and quantitative analysis by measuring the isotope activity of 111In and 99mTc over the infected tibias as compared with the opposite bones revealed that the white blood cell scans were positive in 15 (83%) of the 18 rabbits during the first week after injection of the microorganism. During the same period, the 99mTc bone scans were positive in only 22% of the animals (p less than 0.005). In the animals that survived, both white blood cell and bone scans were positive during the second week, and thereafter, the bone scans revealed consistently higher activity than was observed with white blood cell scans. Computed tomography performed in six rabbits revealed an increased attenuation coefficient of the medullary cavities in the infected bones of four animals during the first week and of one more during the second week. Plain radiographs became positive after the 12th day. Results indicate that in patients with suspected acute osteomyelitis, white blood cell scans and probably computed tomography can detect the disease earlier than 99mTc bone scans and plain radiographs.
In earlier work, DTPA has been covalently coupled to albumin via the cyclic anhydride of DTPA. Using fibrinogen, we have studied the effect of such coupling on protein viability by both an in vitro and an in vivo assay. Clotting time remained identical to that of the native protein whether the anhydride-to-protein molar ratio was 1:1 or 5:1. In vivo studies were done in dogs, with human fibrinogen labeled with 1-125 and In-111. Throughout 130 hr, blood clearances for the two tracers agreed whether with 1:1 or 5:1 coupling. In a dog model with a thrombogenic catheter, the clot-to-blood ratios for the two radiotracers agreed within experimental error. Finally, 1:1-coupled canine fibrinogen, labeled with In-111, was administered to dogs with a catheter in a jugular vein, and scintigrams at 24 hr clearly showed clotting along the length of the catheter. We conclude that fibrinogen, coupled to DTPA, retains its viability, behaving like radioiodinated fibrinogen in vivo, and In-111 labeled fibrinogen looks promising as a clinical diagnostic agent.
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In vivo studies were performed on 28 dogs to evaluate the usefulness of transmission computed tomography (CT) in the detection and quantitation of experimentally induced myocardial infarction. Intravenously administered contrast material was required to define the internal structure of the heart and to differentiate normal from infarcted tissue. Transmural infarcts with homogeneous central regions were visualized as areas of diminished contrast enhancement compared with the normal myocardium. All transmural infarcts of at least 24 hours' duration showed a surrounding border zone of patchy necrosis that was variable in size and had high CT numbers due to slow washout of the contrast material from this region. Infarct area determined from the images for individual slices correlated well (r = 0.976) with that calculated using pathology. The technique is very sensitive and can detect infarction within a papillary muscle. Nontransmural or patchy infarcts show up as areas of diffuse contrast enhancement without a central core of diminished enhancement. The distribution of the contrast material is similar to that of technetium-99m pyrophosphate in the border zone of the infarct in infusion studies, but in bolus studies it behaves more like thallium-201.
Platelets labeled with a lipid-soluble indium-111 8-hydroxyquinoline (oxine) complex were evaluated as an agent to measure the rate and degree of in vivo platelet accumulation on catheters. Polyethylene catheters and Teflon-coated guidewires were inserted into the femoral arteries or veins of dogs that had been injected with indium-labeled platelets. The catheters were passed to either the abdominal aorta or inferior vena cava and left in situ for 30 minutes to three hours. Images were obtained every five minutes with a gamma camera. This labeling technique is reproducible, allows multiple testing with a single preparation, and is relatively noninvasive. The results are easily quantitated to allow testing of different materials and coatings.
This study examined the pathophysiology of the myocaridal damage produced by direct current shock over a dose range of 10 to 90 watt-seconds, applied directly to the heart in 26 dosgs. The extent of injury produced was assessed with creatine kinase depletion and light and electron microscopy, and was correlated with in vivo imaging and tissue distributions of the isotopes technetium-99m pyrophosphate and thallium-201. Changes in intramyocardial temperature and regional myocardial blood flow were also measured. Uptake of technetium-99m pyrophosphate occurred exponentially with graded increases in shocks, and this agent was more sensitive than thallium-201 in detecting injury both on imaging and at tissue level. The threshold for significant injury was approximately 30 watt-seconds, and on electron microscopy a characteristic feature was marked dehiscence of the intercalated disks between the damaged myocytes. The use of different-size paddles did not appear to affect the total number of cells damaged. However, with large paddles the injury was more superficial and spread over a wider area. With short time intervals between successive shocks, a greater amount of injury occurred, in part because of a compounding of the thermal component of the damage. Hypothermia can reduce the degree of injury.
A case is reported in which a labeled white cell scan was helpful in the diagnosis of a periappendiceal abscess. The method of labeling is described and the usefulness of the technique discussed.
A 50-year-old man suffering from recurrent chest pain accompanied by transient ST-segment elevation developed spasm of the left anterior descending coronary artery after receiving ergonovine maleate. During spontaneous chest pain, thermodilution coronary sinus blood flow fell from 96 ml/min to 46 ml/min, while the coronary sinsu arteriovenous oxygen difference widened from 9.82 volumes percent to 11.3 volumes percent. During spontaneous relief of pain, coincident with resolution of the ST-segment changes, coronary sinus blood flow gradually rose to 135 ml/min, while coronary sinus arteriovenous oxygen difference narrowed to 6.82 volumes percent. Similar aterations in coronoary sinus blood flow accompanied chest pain provoked by ergonovine maleate. A thallium-201 scan confirmed a perfusion defect in the distribution the left anterior descending coronary artery. Thus, coronary artery spasm can produce a marked deficity in coronary blood flow that is associated with increased myocardial oxygen extraction; release of spasm creates a hyperemic response.
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Twenty-two patients suspected of having either venous or arterial thrombi were studied with In-111-labeled autologous platelets. Whole-body scans were performed 3, 24, and 48 hr following i.v. injection. Twelve patients studied with saline-washed platelets had unsatisfactory 15-min recovery and biologic half-time. When the labeling was carried out in plasma, these values compared favorably with normal values reported for Cr-51-labeled autologous platelets. Of ten patients studied using platelets labeled in plasma, three had normal scans, six had abnormal scans, and one had an equivocal scan. All six abnormal scans were confirmed with corresponding positive findings in either the venogram, arteriogram, or lung scan. J Nucl Med 19: 626-634, 1978.
A unique case is presented of variant angina pectoris with reproducible chest pain and S-T segment elevation in the immediate postexercise period and with normal coronary arteries. Coronary arterial spasm was deomnstrated with arteriography after intravenous administration of ergonivine maleate. Thallium-201 imaging during the pain reproducibility demonstrated malperfusion in the region supplied by the artery with documented spasm.
To improve the quality of digital nuclear medicine images, we have developed a new implementation of the Wiener restoration filter. The Wiener filter uses as its optimality criterion the minimization of the mean-square error between the undistorted image of the object and the filtered image. In order to form this filter, the object and noise power spectrums are needed. The noise power spectrum for the count-dependent Poisson noise of nuclear medicine images is shown to have a constant average magnitude equal to the total count in the image. The object power spectrum is taken to be the image power spectrum minus the total count, except in the noise dominated region of the image power spectrum where a least-squares-fitted exponential is used. Processing time is kept to a clinically acceptable time frame through use of an array processor. Pronounced noise suppression and detail enhancement are noted with use of this filter with clinical images.
Image restoration using the constrained least-squares (CLS) method theoretically adapts to the image being processed. In addition, it only requires knowing the modulation transfer function of the imaging system when applied to nuclear medicine images. Prompted by these observations, a systematic evaluation of the effects of the form of the "coarseness function" [C(f)] used by the CLS method has been conducted. Nine C(f)'s are evaluated using an observer preference and a normalized mean-squared error (NMSE) criterion. This evaluation is conducted for three modulation transfer functions and a wide range of count levels. The results of the subjective studies support using the form of C(f) which has been most widely employed in previous studies, i.e., the form designed to minimize the energy in the second derivative of the restored image. A different form of C(f) is generally found to be optimal by the mean-squared error criterion. The CLS method is then compared to: (1) no processing, (2) count-dependent smoothing, and (3) count-dependent Metz restoration. When evaluated using objective measurements of error and contrast, the CLS method is found to be slightly inferior to the best method, Metz restoration. However, CLS restoration is found to be equal to or better than the other methods when judged by the results of observer preference studies.
Image restoration methods have been shown to increase the contrast of nuclear medicine images by decreasing the effects of scatter and septal penetration. Image restoration can also reduce the high-frequency noise in the image. This study applies constrained least-squares (CLS) restoration to the projection images of single photon emission computed tomography (SPECT). In a previous study, it was noted that CLS restoration has the potential advantage of automatically adapting to the blurred object. This potential is confirmed using planar images. CLS restoration is then modified to improve its performance when applied to SPECT projection image sets. The modification was necessary because the Poisson noise in low count SPECT images causes considerable variation in the CLS filter. On phantom studies, count-dependent Metz restoration was slightly better than the modified CLS restoration method, according to measures of contrast and noise. However, CLS restoration was generally judged as yielding the best results when applied to clinical studies, apparently because of its ability to adapt to the image being restored.