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Biomedical subjects

S C Moore

Publications and source records attributed to S C Moore.

At least 19 recordsLinked to original sources

Collimator optimization for lesion detection incorporating prior information about lesion size.

A Bayesian estimator has been developed as a paradigm for human observer performance in detecting lesions of unknown size in a uniform noisy background. The Bayesian observer used knowledge of the range of possible lesion sizes as a prior; its predictions agreed well with the results of a six-observer perceptual study. The average human response to changes in collimator resolution, as measured by the detectability index, dA, was tracked by the Bayesian detector's signal-to-noise ratio (SNR) somewhat better than by two other estimation models based, respectively, on lesser and greater degrees of lesion size uncertainty. As the range of possible lesion sizes increased, the Bayesian detector's SNR decreased and the optimal collimator resolution shifted towards better resolution. An analytic approximation for the variance of lesion activity estimates (which included the same prior) was shown to predict the variance of the Bayesian estimator over a wide range of collimator resolution values. Because the bias of the Bayesian estimator was small (< 1%), the analytic variance estimate permitted a rapid and convenient prediction of the Bayesian detection SNR. This calculation was then used to optimize the geometric parameters of a two-layer tungsten collimator being constructed from crossed grids for a new imaging detector. A Monte Carlo program was first run to estimate all contributions to the radial point-spread function for collimators of differing tungsten contents and spatial resolution values, imaging 140-keV photons emitted from the center of a 15-cm-diameter, water-filled attenuator. The optimal collimator design for detecting lesions with unknown diameters in the range 2.5-7.5 mm yielded a system resolution of approximately 8.5-mm FWHM, a geometric collimator efficiency of 1.21 x 10(-4), and a single-septum penetration probability of 1%.

Bayes Theorem

Quantitative SPECT imaging: a review and recommendations by the Focus Committee of the Society of Nuclear Medicine Computer and Instrumentation Council.

This article is a review of the physics principles, instrumentation and reconstruction methods behind SPECT imaging. Particular attention is paid to the mechanisms that can significantly affect the accuracy of a SPECT image. We describe instrumentation advances and reconstruction methods used to correct images to improve image quality and produce quantitative images. The clinical importance of improved image quality and quantitation are also reviewed.

Algorithms

Disability syndrome: the effects of early vs delayed rehabilitation intervention.

1. Disability syndrome occurs when an individual with a work related injury or other disability chooses not to work when it has been medically determined that they are capable of doing so. 2. A possible contributor to the development of disability syndrome includes systems reinforcers or rules that discourage return to work. For example, many attorneys discourage early return to work or modified duty. 3. Early intervention by rehabilitation counselors at the time of injury can facilitate a positive attitude and empower the worker to resist the negative effect of systems reinforcers that discourage early return to work.

Absenteeism

Mouse macrophages contain a truncated CD4 transcript.

Mouse macrophages do not express CD4 on their surfaces. We used the polymerase chain reaction to investigate CD4 gene transcription in individual clones of primary mouse splenic macrophages and cell lines of spleen and bone marrow macrophages. The results show only the presence of CD4 mRNA transcripts that are truncated in the 3' coding sequence, thus explaining the lack of expression of a mature CD4 gene product by these cells.

Animals

Transforming growth factor-beta is the major mediator of natural suppressor cells derived from normal bone marrow.

We previously reported that murine bone marrow cells activated by interleukin-3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF) had potent nonspecific natural suppressor (NS) cell activity. In the present study, we demonstrated that these activated NS cells released a soluble factor (or factors) capable of nonspecifically inhibiting T cell mitogenic responses. Consistent with the properties of transforming growth factor-beta (TGF-beta), treatment of the NS supernates with heat failed to denature the factor, and in fact significantly increased its suppressive activity. The NS suppressor factor strongly inhibited proliferation of the TGF-beta-sensitive tumor cell line, A549. Cytokine activation of suppressive activity correlated with the production of a 10- to 13-kDa protein, consistent with the size of TGF-beta and rIL-3 induced a sevenfold increase in TGF-beta transcription. Finally, neutralizing anti-TGF-beta antibody inhibited the suppressive activity of the supernates, indicating that TGF-beta was responsible for most, if not all, of the suppression expressed by these bone marrow NS cells.

Animals

Collimator design for single photon emission tomography.

We discuss recent trends in collimator design and technology, with emphasis on theoretical and practical issues of importance for single photon emission tomography (SPET). The well-known imaging performance parameters of parallel-hole collimators are compared with those of fan-beam collimators, which have enjoyed considerable success in recent years, particularly for brain SPET. We review a simplistic approach to the collimator optimization problem, as well as more sophisticated "task-dependent" treatments and important considerations for SPET collimator design. Practical guidance is offered for understanding trade-offs that must be considered for clinical imaging. Finally, selective comparisons among different SPET systems and collimators are presented for illustrative purposes.

Equipment Design

Cytokine regulation of bone marrow natural suppressor cell activity in the suppression of lymphocyte function.

Natural suppressor (NS) cells, which nonspecifically suppress immune responses, are present in the spleen following exposure to radiation, chronic graft-versus-host disease, or cancer and in normal bone marrow. A model system is described which allows the study of cytokines activating and inhibiting NS cells, cytokines mediating NS activity, and NS effects on cytokine synthesis. Recombinant interleukin-3 (rIL-3) and granulocyte-macrophage colony-stimulating factor (rGM-CSF) efficiently activated NS cells present in normal bone marrow and were effective at concentrations as low as 5 U/ml. At high concentrations, GM-CSF, but not IL-3, did not activate NS cells. Recombinant interferon-gamma (rIFN-gamma) blocked the activation of bone marrow NS cells by rIL-3, but did not down-regulate NS cells once activated. The NS cells secreted one or more soluble suppressor factors, which blocked IL-2 synthesis and also inhibited IL-2-dependent T cell proliferation in the presence of excess IL-2.

Animals

Mouse splenic macrophage cell lines with different antigen-presenting activities for CD4+ helper T cell subsets and allogeneic CD8+ T cells.

A panel of seven mouse splenic macrophage cell lines, derived from cloned progenitors, was compared for their ability to present antigen to Th1 or Th2 helper T cell lines and hybridomas, as well as to naive T cells, and to provide accessory cell function for the synthesis of antibody from primed B cells. One of the cell lines expressed MHC class II molecules and was the only line with constitutive antigen-presenting activity for Th1 cells. It may represent a subset of splenic macrophages responsible for the activation of naive Th1 helper cells in situ. The remaining six cell lines responded to INF-gamma by up-regulating their class II expression and acquiring Th1 antigen-presenting activity. They may represent cells which, in situ, lack constitutive antigen-presenting activity but are promoted to presenting status by Th1-derived INF-gamma. Five of the cell lines provided accessory cell function to Th2 cells, as indicated by antibody synthesis in suspensions of spleen cells from primed mice depleted of their antigen-presenting cells. One of the cell lines lacking accessory cell activity had constitutive antigen-presenting activity for Th1 cells. This reciprocal expression of antigen-presenting activity supports the idea that Th1 and Th2 helper cells are activated by different antigen-presenting cells. Finally, the cell lines differed in their ability to constitutively induce an allogeneic response; a response that was limited to CD8+ T cells occurred in a CD4+ helper cell-independent manner and was unaffected by the addition of INF-gamma. The alloantigen-presenting macrophage cell lines also possessed the most efficient accessory cell activity for antibody synthesis. These cell lines, which represent a spectrum of antigen-presenting activities in the spleen afford models for defining the roles of macrophages in the induction of immune responses and for resolving issues concerning their development.

Animals

Phenotypes and alloantigen-presenting activity of individual clones of microglia derived from the mouse brain.

To clarify the origin and function of the microglia residing in the central nervous system, we cloned brain cells from newborn and adult mice in soft agar containing the macrophage-specific growth factor, colony-stimulating factor-1 and expanded the cells from individual colonies in liquid culture medium. The results of molecular, immunophenotypic and functional analyses showed that the clones consisted of microglia derived from the macrophage family of cells. For instance, the microglia contain mRNA transcripts for the receptor for colony-stimulating factor-1 and truncated CD4 transcripts similar to those found in mouse macrophages but not T helper cells. About a third of the microglial progenitors gave rise to progeny that constitutively induced the selective proliferation of naive allogeneic CD8+ T cells in a CD4+ T cell-independent manner, a response that was inhibited by monoclonal antibodies to major histocompatibility complex (MHC) class I molecules on the microglia. Since all microglia expressed similar levels of MHC class I molecules, the basis for the alloantigen presentation likely resides in the ability of some clones of microglia to synthesize co-stimulator molecules that are required for CD8+ T cell proliferation. Thus, at least some microglia in mouse brain arise from endogenous progenitors and appear capable of specialized functions.

Animals

Bone marrow natural suppressor cells inhibit the growth of myeloid progenitor cells and the synthesis of colony-stimulating factors.

Natural suppressor (NS) cells, which nonspecifically suppress immune responses, are generally found at sites of hemopoietic generation or regeneration. Murine bone marrow NS cells were activated by recombinant interleukin 3 (rIL-3) or recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) and produced a soluble suppressor factor. In the present study, the soluble suppressor factor from bone marrow NS cells was found to be a potent inhibitor of myeloid colony formation at concentrations below those required for immunosuppression. NS cell supernatants inhibited the growth of granulocyte-macrophage colony-forming units (CFU-GM), granulocyte erythrocyte macrophage megakaryocyte colony-forming units (CFU-GEMM), and erythroid colony-forming units (CFU-E) to a similar extent. Neutralizing anti-transforming growth factor beta (TGF-beta) reversed the suppressive effects of the supernatants, suggesting that TGF-beta was involved in the suppression. The NS cell supernatants also inhibited the production of colony-stimulating activity by bone marrow stromal cells and the transcription of GM-CSF mRNA by activated T cells. These data suggest that NS cells are important regulators of hemopoiesis. NS cells, which are non-adherent, radioresistant non-T cells resident in the bone marrow, were shown to be sensitive to treatment with the lysosomotropic agent, L-leucine methyl ester, suggesting that the NS cells may be of large granular lymphocytic or monocytic lineage. Cytotoxicity studies revealed that cells in the NS population had natural cytotoxic (NC), but not natural killer (NK) activity.

Animals

Maximum-likelihood estimation: a mathematical model for quantitation in nuclear medicine.

In a stimulation study, we investigated the limitations of quantitation in nuclear medicine using a maximum-likelihood (ML) estimation model. We estimated activity, size, and position of a disk-shaped object on a circular, uniform background of unknown activity. The parameter estimates were unbiased, and their standard error was proportional to the square root of the total image counts. The estimates of object activity and size were strongly (negatively) correlated; the position estimates, however, were not correlated with estimates of any other parameters. This implies that a priori knowledge of object location does not improve precision. The minimal model of quantitation tasks should incorporate unknown object activity and size as well as unknown background activity. The ML estimation procedure was used to investigate the trade-off between resolution and sensitivity in gamma camera collimator design. The results implied that for complex tasks such as the multiparameter estimation task investigated here, optimum performance is achieved at a better resolution than that previously found optimal for detection of a well-specified object in a known background.

Humans

Delayed phalaris grass toxicosis in sheep and cattle.

A phalaris grass (Phalaris caroliniana) caused neurologic signs and lesions in cattle and sheep. The sheep were hyperexcitable and uncoordinated, with severe muscle twitching, stiff gait, and head nodding. The cattle were thin, nervous, and ataxic. One feature of chronic phalaris toxicosis in these cases was onset of signs weeks or months after removal of the animals from the forage.

Animals

SPECT image noise power: effects of nonstationary projection noise and attenuation compensation.

The effects of nonstationary projection noise and attenuation compensation are included in a theoretic calculation of the radial noise power spectrum (NPS) of single photon emission computed tomographic (SPECT) images. The nonstationary projection noise is shown to cause a relatively large d.c. component in the NPS, especially for small objects; whereas, attenuation compensation increases the total noise variance while only changing the d.c. component slightly. The theoretic calculation agrees well with a radial NPS estimated from 1,250 SPECT images simulated from projections of random Gaussian noise, even though the effects of discrete data collection and reconstruction were not included in the theoretical model.

Computer Simulation

Diagnostic laparoscopy in gastroenterology. A 14-year experience.

Between 1970 and 1983, we performed 1121 diagnostic laparoscopies in 1119 patients. More than 50% of the examinations were performed for malignant disease. An adequate examination was accomplished in 917 (82%) procedures. The most frequent reason for inadequate evaluation was the presence of dense intraabdominal adhesions from previous surgery. We observed 105 (9.4%) minor complications and 20 (1.8%) major complications including one death following hemorrhage from liver biopsy. Major complications included abdominal wall hematoma, perforated abdominal viscus, hemoperitoneum, bleeding from liver biopsy, and respiratory depression. We observed a trend to decreased use of laparoscopy. Ascites of unknown origin and certain specific situations in patients with chronic liver disease remain as major indications for this diagnostic technique.

Biopsy

Interrelationships among gastric mucosal morphology, secretion, and motility in peptic ulcer disease.

Pathophysiologic abnormalities associated with ulcer disease include gastritis (particularly of the antral mucosa), excessive duodenogastric reflux, and altered motor activity of the stomach. It is not known whether these abnormalities are interrelated and whether they occur during periods of ulcer inactivity. We have tested the hypothesis that the morphological abnormalities of the gastric mucosa in inactive ulcer disease are proportional to an alteration of the gastric luminal milieu itself due to abnormal secretory and motor function. Thus, multiple endoscopic biopsies and 24-hr physiologic measurements were performed in 12 patients with well-documented ulcers in the past (seven type I gastric ulcer patients, five duodenal ulcer patients), now clinically and endoscopically in remission. Seven healthy individuals underwent similar studies and served as controls. Histologic quantification of inflammation and metaplasia (expressed as a gastritis index) was found to be significantly different among groups (P less than 0.01). Gastric ulcer patients exhibited a higher gastritis index than controls, while duodenal ulcer patients were intermediate. A significant inverse relationship was found between gastritis index and postprandial motility index (R2 = 0.59, P less than 0.01) and a nonsignificant trend between gastritis index and fasting motility index. There was no difference among groups or detectable associations between gastritis index and intragastric pH or bile acid concentration. We conclude that gastric mucosal disease, expressed as gastritis index, persists during inactive ulcer disease. There is an association with antral hypomotility, which is more strongly manifested postprandially. It is not associated with gastric pH or bile acid concentration. Gastric mucosal inflammation and antral hypomotility predispose to ulceration rather than simply accompanying it.

Adult

Defects in prostaglandin synthesis and metabolism in ulcer disease.

Ulcers occur because of an imbalance between mucosal protective resistance and damaging luminal factors, allowing the latter to predominate. The primary injurious elements are acid and peptic activity. Bile reflux, drugs, and gastroduodenal stasis may alter the luminal milieu and act together with acid-peptic activity to produce injury, weaken mucosal resistance, or both. Since prostaglandins modulate several key mucosal protective mechanisms, and since some exogenous prostaglandins and their derivatives accelerate peptic ulcer healing, it seems plausible that prostaglandin deficiency may contribute to the development of peptic ulcers. At the present time, however, evidence for this postulate is mostly indirect and can be summarized as follows: (1) Defects of mucosal protective mechanisms modulated by prostaglandins have been found in different forms of ulcer disease. Such defects include impaired duodenal bicarbonate secretion, deficient secretion or accelerated degradation of mucus, and reduced mucosal cell proliferation. (2) Drugs that inhibit cyclooxygenase, the key enzyme in tissue prostaglandin synthesis, have ulcerogenic activity. Presumably, in this situation, reduced prostaglandin production renders the mucosa more vulnerable to the action of acid and pepsin, or reduces the capability of the mucosa to repair itself. (3) Decreased mucosal prostaglandin synthesis or prostaglandin content has been found in patients with ulcer disease. Several studies have provided quantitative evidence of disturbed prostaglandin metabolism in some forms of ulcer disease. These studies are of high interest, but they need to be interpreted with caution given the present scientific debate regarding the physiological role of different prostanoids, as well as uncertainty as to the specific cellular source of prostaglandins in gastroduodenal mucosa.

Animals

Inversion of the 3D Radon transform for a multidetector, point-focused SPECT brain scanner.

The Radon transform is presented for unattenuated projection data acquired with a multidetector, point-focused SPECT brain scanner. The three-dimensional (3D) integral transform is shown to be exactly invertible only for the case of an ideal machine whose detectors scan away from the source to infinity in all directions. The two-dimensional (2D) ramp filter reconstruction algorithm previously used for this scanner is a limiting case of the 3D method and is exact only for sources with cylindrical symmetry, (f(x,y,z) = f(x,y) for all z). Projection data from a long cylinder and a 1.5 cm thick disc of equal diameters and activity concentrations were simulated by computer for the same scan pattern used on the machine. The data were reconstructed with both the 2D and 3D analytic methods. The 2D method produced a 20% bowl-shaped dip in the centre of the disc, whereas the central slice of the 3D reconstruction was more than 97% accurate. The effective, noise-equivalent sensitivity when reconstructing the central slice of the disc with the necessary 3D method is 10.1 times lower than the sensitivity obtained for the long cylindrical source when reconstructing with the 2D method.

Brain

Improved performance from modifications to the multidetector SPECT brain scanner.

A multidetector single photon emission computerized tomographic brain scanner was modified to improve the angular sampling. The detector plate was rotated such that 12, 24, or 36 angular projections could be acquired. Phantom experiments demonstrated that the angular aliasing artifacts seen in images obtained with 12 detectors were eliminated with 36 effective detectors. In addition, the reconstructed image noise in a uniform source was decreased by a factor of 1.7 by the use of 36 instead of 12 angular projections, as predicted by computer simulation.

Brain