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Biomedical subjects

L S Graham

Publications and source records attributed to L S Graham.

At least 19 recordsLinked to original sources

Gastric emptying of oil from solid and liquid meals. Effect of human pancreatic insufficiency.

Digestion of fat in pancreatic insufficiency (PI) is strongly affected by how rapidly fat enters the duodenum. We postulated that: (1) oil empties faster in PI than in normals and (2) in both, it empties in a load-dependent fashion. We used a gamma camera to test these ideas by comparing gastric emptying of iodine-123 iodinated oil in normal and pancreatic-insufficient subjects after 15 g of free oil were ingested in a small spaghetti meal and 60 g of oil were ingested in a large spaghetti meal and in a milk emulsion. Indium-113m marked gastric emptying of water in the milk. In both groups after all meals, oil emptied fastest initially, slowing later; and oil emptied three to four times faster when 60 g vs 15 g were ingested. There were no significant differences between the groups of subjects with respect to gastric emptying of the spaghetti meals, but the pancreatic-insufficient subjects emptied both oil and water faster from the milk emulsion than did the normal subjects. The slower emptying of oil in the normal subjects was associated with significantly more layering of oil to the top of the intragastric milk emulsion.

Adult

Relationships of the WISC-R and K-BIT for an adolescent clinical sample.

Correlations between the Wechsler Intelligence Scale for Children-Revised IQs and the Kaufman Brief Intelligence Test were determined for a clinical sample of 44 adolescents (35 with learning disabilities, 9 with mental retardation) who underwent routine three-year reevaluations. Even though three years had elapsed between the WISC-R and K-BIT scores, the correlations among the total and subscale scores of these measures were high and were all statistically significant. A significant mean difference was found between the WISC-R Verbal IQ and its K-Bit counterpart, the Vocabulary subscales. Implications of findings for assessment specialists are discussed.

Adolescent

Quantitation of SPECT performance: Report of Task Group 4, Nuclear Medicine Committee.

A comprehensive performance testing program is an essential ingredient of high-quality single-photon emission computed tomography (SPECT). Many of the procedures previously published are complicated, time consuming, or require a special testing environment. This Task Group developed a protocol for evaluating SPECT imaging systems that was simple, practical, required minimal test equipment, and could be performed in a few hours using processing software available on all nuclear medicine computers. It was designed to test rotational stability of uniformity and sensitivity, tomographic spatial resolution, uniformity and contrast, and the accuracy of attenuation correction. It can be performed in less than three hours and requires only a Co-57 flood source, a line source, and a tomographic cylindrical phantom. The protocol was used 51 times on 42 different cameras (seven vendors) by four different individuals. The results were used to establish acceptable ranges for the measured parameters. The variation between vendors was relatively small and appeared to reflect slight differences in basic camera performance, collimation, and reconstruction software. Individuals can use the tabulated values to evaluate the performance of individual systems.

Cobalt Radioisotopes

Quality control for SPECT systems.

A comprehensive set of acceptance tests is the basis for an effective quality control program. Acceptance tests indicate whether the scintillation camera meets published specifications but should also include evaluation of certain parameters not specified by the vendor but that can seriously affect image quality. Once a camera is "accepted," initial quality control tests serve as a benchmark for future measurements. Tomographic systems must be subjected to the same basic quality control program as planar cameras. Flood field images must be acquired and evaluated daily; spatial resolution must be tested once each week. Less frequently, parameters such as multiple-window spatial registration, collimator uniformity, system sensitivity, and camera "dead time" should be evaluated. Single photon emission computed tomographic systems require additional tests to ensure optimum performance. Center-of-rotation calibration and verification of detector registration are needed to avoid losses of spatial resolution. Flood corrections based on high-count images eliminate residual detector nonuniformiaties and correct for subtle collimator defects. Pixel size must be calibrated to avoid errors in attenuation correction and distortion when cardiac and brain reorientation software is used. Completed clinical studies must be checked for unacceptable patient movement and incomplete views. A quality control program may be time-consuming, but, from the standpoint of maximum benefit to patients and confidence in clinical interpretations, there is no alternative.

Artifacts

Control of canine gastric emptying of fat by lipolytic products.

Dietary fat is ingested in three forms: 1) in solid food, 2) as aqueous emulsions, and 3) as unemulsified, liquid oil. On the basis of a scant previous literature, we postulated that liquid fat (emulsions or oils) would empty from the stomach at speeds that varied with the amounts ingested but that this dynamic would be modulated by feedback inhibition from lipolytic products. To test these ideas, we used a gamma camera to track gastric emptying of 123I-labeled fat in dogs with chronic pancreatic fistulas by which lipase was excluded from or replenished in the duodenum in varied amounts after dogs were fed 15-, 30-, and 60-g loads of liquid fat given with solid foods or as emulsions. We also tracked concurrent gastric emptying of 113mIn, which marked the solid food phase or the water phase of emulsions. In some studies, we used a potent and specific inhibitor (orlistat) of pancreatic and gastric lipases to assess how lipolytic products modulated emptying of liquid fat. In the absence of pancreatic enzymes, both oils and emulsions emptied initially at high speeds that varied with fat loads, but emptying slowed 20 min after ingestion of emulsions and 60 min after ingestion of unemulsified oil. Studies with orlistat indicated that these changes in rates resulted from liberation of gastric lipolytic products. Emptying of oil emulsions was not altered by duodenal replenishment with pancreatic enzymes, but emptying of unemulsified oil was inhibited in a dose-related fashion, such that maximal inhibition was achieved when pancreatic enzymes were replenished at > or = 40% of normal amounts. Studies with orlistat confirmed that this dose-dependent slowing was due specifically to lipase. Emptying of solid food was much more sensitive to replenishment with enzymes, so that a 10% replenishment maximally inhibited solid emptying.

Animals

SPECT brain imaging in Alzheimer's disease during treatment with oral tetrahydroaminoacridine and lecithin.

Quantitative SPECT brain imaging was performed in five normal subjects and in six ambulatory patients with Alzheimer's disease before the initiation of treatment with tetrahydroaminoacridine (THA) and lecithin. Imaging data were acquired with a single-head SPECT camera and a high-resolution collimator after the intravenous injection of 5 mCi of (p,5n) I-123 IMP. Uptake per pixel in 28 regions of interest in the transverse projection of each study was normalized to uptake per pixel in the cerebellum. Perfusion in the patients with Alzheimer's disease was decreased compared with that of the subjects. Perfusion was decreased greater than 2 SD below the mean in the posterior parietal cortex of 5/6 patients, in the temporal cortex of 3/6 patients, and in the frontal cortex of 2/6 patients with Alzheimer's disease. SPECT imaging was repeated in the six patients after initial titration to peak therapy with oral THA (75 to 200mg per day). The same abnormalities were again seen in the same patients. No dramatic clinical or behavioral change in cerebral perfusion was observed from initial treatment of Alzheimer's disease with THA and lecithin.

Administration, Oral

Comparison of gas clearance and radioactive microspheres for pancreatic blood flow measurement.

Measurement of pancreatic blood flow (PBF) is technically demanding. Although radiolabeled microspheres are considered the "gold standard" for PBF assessment, they have practical limitations. In the current study, H2 and xenon-133 gas clearance techniques were adapted to PBF measurement and compared to radiolabeled microsphere techniques. Simultaneous measurements of PBF were made using either hydrogen or xenon gas washout and radiolabeled microspheres. Measurements were made under basal, vasoconstricted (vasopressin 2U i.v. or nicotine 4 micrograms/kg/h) and stimulated (secretin 125 ng/kg/h or 2 U/kg i.v.) conditions (random order). Mean PBF was 26.9 +/- 5.3, 50.5 +/- 2.3 and 27.6 +/- 5.2 ml/min/100 g basally, 36.9 +/- 8.0, 90.1 +/- 18.9, and 81.7 +/- 14.5 ml/min/100 g in the stimulated state, and 24.2 +/- 7.8, 25.0 +/- 3.5, and 14.9 +/- 7.5 ml/min/100 g in the vasoconstricted state for hydrogen gas clearance, xenon gas clearance, and radiolabeled microspheres, respectively. The H2 clearance technique resulted in tissue trauma, was complicated by frequent electrode displacement, and correlated poorly (r2 = 0.36, p greater than 0.05) with microsphere values. In contrast, xenon clearance measurement had no apparent effect on the pancreas and correlated well (r2 = 0.83, p less than 0.01) with microsphere data. We conclude that xenon clearance offers an attractive, validated alternative to radiolabeled microspheres for measuring pancreatic blood flow.

Animals

Nuclear medicine from Becquerel to the present.

During a period of a little over ninety years, the use of radioactive materials has moved from the discovery of natural radioactivity by Becquerel to the use of highly sophisticated equipment for in-house production of biologically important molecules labeled with radionuclides, for the measurement of body functions. Radiation detectors have progressed from photographic plates and the gold leaf electroscope to the routine use of improved scintillation detectors for imaging the three-dimensional distribution of radioactive materials in the body as a function of space and time. It is expected that future improvements will be along the line of instruments with better spatial resolution, contrast, and sensitivity. Advances in hardware and software will be more than matched by developments in radiopharmaceuticals, including the use of monoclonal antibodies and receptor mapping agents which promise the exquisite specificity and sensitivity of radioimmunoassay procedures.

Europe

Quantitative iodine-123 IMP imaging of brain perfusion in schizophrenia.

Decreased perfusion in the frontal lobes of patients with chronic schizophrenia has been reported by multiple observes using a variety of techniques. Other observers have been unable to confirm this finding using similar techniques. In this study quantitative single photon emission computed tomography brain imaging was performed using p,5n [123I]IMP in five normal subjects and ten chronically medicated patients with schizophrenia. The acquisition data were preprocessed with an image dependent Metz filter and reconstructed using a ramp filtered back projection technique. The uptake in each of 50 regions of interest in each subject was normalized to the uptake in the cerebellum. There were no significant confirmed differences in the comparable ratios of normal subjects and patients with schizophrenia even at the p = 0.15 level. "Hypofrontality" was not observed.

Adult

Detection of malignant melanoma with iodine-123 iodoamphetamine.

Iodoamphetamine (IMP) was shown by in vitro assay to have a high uptake by human melanotic melanoma cells, as compared to amelanotic melanoma cells. Eleven patients with proven malignant melanoma (MM) and 3 normal subjects were imaged at 2-4 hr and 16-24 hr after the i.v. injection 5 mCi (185 MBq) of [123I]IMP. One patient had a recurrent tumor that was subsequently shown to be squamous cell carcinoma. The index lesion was not visualized in the three patients with amelanotic melanomas. The index lesion/lesions were visualized in six of the seven other patients, except for 4/16 nodules in one patient. The seventh patient had a large, necrotic melanotic tumor that was not visualized, but an unsuspected lesion in the iliac nodes was detected. Multiple unsuspected lesions were detected in a second patient. While many lesions were seen at 2-4 hr, all lesions (other than a patient with small bowel disease) were seen best at 16-24 hr. No eye uptake was observed in any patient or control subject. Testicular uptake was seen in all males at 16-24 hr. Iodine-123 IMP appears to be a useful agent for the detection and follow-up of patients with melanotic MM.

Adult

Mastopathy in insulin-dependent diabetics.

A type of mastopathy is unique to insulin-dependent diabetic patients. The characteristic change is a connective tissue overgrowth with vasculitis and some proliferation of duct epithelium. It is not the type of change typically associated with an increased risk of breast cancer. Clinically this change is indistinguishable by physical or radiographic findings from breast malignancy. Eleven biopsies showing these characteristics were performed on insulin-dependent patients who had diabetes mellitus from childhood. Every patient had some major complication of diabetes mellitus, usually diabetic retinopathy. In every instance the mastopathy continued to manifest itself as a part of the healing process. The probability is that this is an evidence in the breast of collagen cross-linking changes seen in patients with diabetes mellitus. This observation should help in the supervision of patients with a clinical background compatible with this study.

Adult

[123I]iodoamphetamine SPECT imaging.

SPECT imaging of [123I]IMP is reviewed. Methods for radiopharmaceutical production are discussed with an emphasis on labeling small quantities of IMP. Limited angle tomography and full angle SPECT with standard cameras and special imaging systems are reviewed. Selection of collimator and methods of reconstruction are discussed. Clinical studies are described with emphasis on stroke, epilepsy and dementia. The efforts to perform quantitative imaging of rCBF with [123I]IMP are reviewed.

Alzheimer Disease

Cold lesions: enhanced contrast using asymmetric photopeak windows.

Cold-lesion contrast resolution was measured as a function of photopeak window position, photon energy, and scatter configuration using a clinical scintillation camera capable of asymmetric photopeak imaging. Two radionuclide solutions, technetium-99m and thallium-201, were studied at five photopeak window positions: the symmetric setting and window settings that were 5%, 10%, 20%, and 30% asymmetrically high (asymmetry was defined here by the intrinsic percentage of count loss relative to the symmetric window setting). Low contrast was examined with small cold-sphere phantoms and large cold-cube phantoms to produce high- and low-scatter conditions, respectively. High contrast was examined with a Hine cylindrical step phantom. Lesion contrast improved markedly with small degrees of window asymmetry but showed less dramatic improvement when positions at the higher degrees of asymmetry were studied. For the high-scatter and low-contrast situations, the maximum improvement in lesion contrast tended to be inversely proportional to lesion size. The maximum improvement in contrast resolution ranged from 10% to 45%, depending on lesion size, scatter configuration, and the radionuclide solution used.

Humans

Diagnosis of Alzheimer's disease and multiple infarct dementia by tomographic imaging of iodine-123 IMP.

Tomographic imaging of the brain was performed using a rotating slant hole collimator and [123I]N-isopropyl p-iodoamphetamine (IMP) in normal subjects (n = 6) and patients with either Alzheimer's disease (n = 5) or multiple infarct dementia (n = 3). Four blinded observers were asked to make a diagnosis from the images. Normal subjects and patients with multiple infarct dementia were correctly identified. Alzheimer's disease was diagnosed in three of the five patients with this disease. One patient with early Alzheimer's disease was classified as normal by two of the four observers. Another patient with Alzheimer's disease had an asymmetric distribution of IMP and was incorrectly diagnosed as multiple infarct dementia by all four observers. Limited angle tomography of the cerebral distribution of 123I appears to be a useful technique for the evaluation of demented patients.

Alzheimer Disease

Effects of asymmetric photopeak windows on flood field uniformity and spatial resolution of scintillation cameras.

Pulse height analyzer windows that are set on the high side of the photopeak are known to improve spatial resolution and contrast when used for scintillation camera imaging. Asymmetric windows can be used with some scintillation cameras that have energy correction circuitry. In this study the improvement in spatial resolution and loss of field uniformity for 99mTc, 201Tl, and 131I were measured as a function of window asymmetry (up to 30%, defined relative to the loss of counts as compared to a symmetric window under intrinsic conditions). Flood field uniformity was inversely related to the degree of window asymmetry. With 10 cm of scatter the 99mTc integral uniformity deteriorated from 7.9% with a symmetric window to 11.5% for a 30% asymmetric window. The corresponding values for 201Tl were 9.9 and 10.9%. Even without additional scatter, the values for 131I were 23.0 and 26.5%. Spatial resolution, as measured by the full width at half maximum in 10 cm of scatter improved by only 5% for 99mTc and 7% for 201Tl. However, the full width at tenth maximum increased by as much as 20% for 99mTc and 201Tl. A large percentage of this improvement was attained with small degrees of asymmetry. This study demonstrates that 10% or less asymmetry can provide most of the benefit in spatial resolution and contrast that is to be gained without significant losses in field uniformity and count rate.

Image Enhancement

Imaging of human tumor xenografts in nude mice with radiolabeled monoclonal antibodies. Limitations of specificity due to nonspecific uptake of antibody.

To determine if in vivo binding specificities of monoclonal antibodies to tumor nodules would reflect in vitro antibody specificities as determined by radioimmunoassay, two monoclonal antibodies were selected for imaging of human tumor xenografts in nude mice. By in vitro radioimmunoassay, antibody 436 binds to the M20 melanoma cell line, but not to the P3 carcinoma cell line; antibody 44 binds to P3 but not to M20. Both antibodies are IgG1 isotypes. Nude mice bearing an M20 melanoma in one flank and a P3 carcinoma in the other were injected intravenously with 5 to 25 micrograms of each antibody labeled with either I-125 or I-131; in separate animals the labels were reversed. Animals were imaged daily with a scintillation camera equipped with a pinhole collimator. On day 6 the animals were sacrificed, and binding of the antibodies to the tumors and normal tissue were compared. Antibody 436 had up to a two-fold binding advantage in vivo for the melanoma, whereas antibody 44 had up to a two-fold binding advantage for the carcinoma, thus confirming the in vitro specificities of each. However, imaging on day 4 and computer analysis of percent radioactivity in the tumors showed that tumor images were related directly to tumor size and relatively uninfluenced by antibody specificity. Thus, even though antibody specificity can be demonstrated by differential tissue counting, imaging of tumor deposits appears to involve a nonspecific phenomenon that is largely dependent upon tumor weight.

Animals

Measurement of metabolic extraction of tracers in the lung using a multiple indicator dilution technique.

Selective pulmonary uptake of many natural and synthetic substances has been demonstrated by physiologists and pharmacologists using isolated perfused lung preparations or invasive techniques. It is difficult, however, to relate these laboratory studies to disease processes and to the study of problems encountered in a clinical environment. Our goal was to develop a noninvasive method for studying the pulmonary uptake of tracer substances using available radiotracers, gamma cameras, and computers that would give information similar, if not identical, to that from the invasive laboratory methods, and that could be applied in a clinical setting. The multiple-indicator dilution technique, modified for external counting, is well suited for such studies of pulmonary uptake of tracer substances. In this study, Tc-99m micro sulfur colloid (Tc-99m micro SC) was used as an intravascular reference tracer, N-isopropyl-p-[123I]iodoamphetamine (I-123 IMP) as a cellular test tracer amine, and In-111 DTPA as an extracellular tracer. Calculated first-pass lung uptakes of I-123 IMP and In-111 DTPA were 0.92 +/- 0.04 and 0.17 +/- 0.04, respectively, relative to the reference tracer. Using this approach, the first-pass pulmonary extraction of a variety of radiolabeled test tracers can be measured in a clinical environment in a variety of physiologic settings.

Amphetamines