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Biomedical subjects

M B Williams

Publications and source records attributed to M B Williams.

At least 19 recordsLinked to original sources
PubMed2000

Application and maintenance habits do make a difference in adhesion of Alora transdermal systems.

OBJECTIVES: To explore and evaluate Alora placebo patch application and maintenance habits of women in order to identify the factors that influence adhesion success. METHODS: This single-center, open-label, placebo, randomized, multiple-application, parallel-group study involved 99 healthy naïve users of transdermal patches. Participants applied and wore an Alora placebo patch for ten consecutive applications of approximately 3.5 days each and evaluated adhesion of the patches twice-daily. Three subgroups comprising participants achieving low, moderate or high adhesion success took part in focus groups to discuss their wear habits, practices and attitudes regarding transdermal patches. RESULTS: There was a significant behavioral component involved in patch adhesion. The habits, practices and attitudes of high achievers were clearly different from the other two subgroups. The three most important issues identified to improve adhesion were: mastering the removal of the patch liner, identifying the best site of application, and developing and implementing techniques to maintain patch adhesion. The Alora placebo patch was well tolerated throughout the study. CONCLUSION: The data showed that there is a learning curve involved in achieving maximal adhesion with a transdermal patch. During the study, a novel patch application method ('press, fold and slide') was demonstrated for the participants. This method was very well received by all participants and was more easily executed than the previous method. An adaptation of this method was incorporated into the Alora patient information leaflet, together with several other changes to help improve adhesion success.

Adhesiveness↗
PubMed2000

Detection of regional pulmonary perfusion deficit of the occluded lung using arterial spin labeling in magnetic resonance imaging.

Detection of regional perfusion deficit in the lung has been demonstrated using an arterial spin labeling technique called flow-sensitive alternating inversion recovery with an extra radiofrequency pulse (FAIRER). A pulmonary artery was occluded using a nondetachable balloon catheter to simulate an acute pulmonary embolism in 3 of 10 rabbits. Inflating the balloon occludes the artery, and deflating the balloon allows for reperfusion. Perfusion imaging was performed pre-occlusion, during occlusion, and after reperfusion. Signal enhancement due to perfusion of the pulmonary parenchyma was observed in the perfusion images with negligible artifacts. The perfusion deficit of the pulmonary parenchyma was detected distal to the site of occlusion in all three rabbits. Return of the pulmonary parenchymal perfusion was observed after reperfusion. Magnetic resonance imaging using FAIRER can detect signal loss due to absence of perfusion caused by pulmonary embolism.

Animals↗
PubMed2000

Performance of a PSPMT based detector for scintimammography.

In breast scintigraphy, compact detectors with high intrinsic spatial resolution and small inactive peripheries can provide improvements in extrinsic spatial resolution, efficiency and contrast for small lesions relative to larger conventional cameras. We are developing a pixelated small field-of-view gamma camera for scintimammography. Extensive measurements of the imaging properties of a prototype system have been made, including spatial resolution, sensitivity, uniformity of response, geometric linearity and energy resolution. An anthropomorphic torso phantom providing a realistic breast exit gamma spectrum has been used in a qualitative study of lesion detectability. A new type of breast imaging system that combines scintimammography and digital mammography in a single upright unit has also been developed. The system provides automatic co-registration between the scintigram and the digital mammogram, obtained with the breast in a single configuration. Intrinsic spatial resolution was evaluated via calculation of the phase-dependent modulation transfer function (MTF). Measurements of extrinsic spatial resolution, sensitivity and uniformity of response were made for two types of parallel hole collimator using NEMA (National Electrical Manufacturers Association) protocols. Geometric linearity was quantified using a line input and least squares analysis of the measured line shape. Energy resolution was measured for seven different crystal types, and the effectiveness of optical grease coupling was assessed. Exit gamma spectra were obtained using a cadmium zinc telluride based spectrometer. These were used to identify appropriate radioisotope concentrations for the various regions of an anthropomorphic torso phantom, such that realistic scatter conditions could be obtained during phantom measurements. For prone scintimammography, a special imaging table was constructed that permits simultaneous imaging of both breasts, as well as craniocaudal views. A dedicated breast imaging system was also developed that permits simultaneous acquisition and superposition of planar gamma images and digital x-ray images. The intrinsic MTF is nonstationary, and is dependent on the phase relationship between the signal and the crystal array matrix. Averaged over all phases, the MTF is approximately 0.75, 0.57 and 0.40 at spatial frequencies of 1.0, 1.5 and 2.0 cycles per cm, respectively. The phase averaged line spread function (LSF) has a FWHM value of 2.6 mm. Following uniformity corrections, the RMS deviations in flood images are only slightly greater than is predicted from counting statistics. Across an 80 mm section of the active area, the differential linearity is 0.83 mm and the absolute linearity 2.0 mm. Using an anthropomorphic torso phantom with detachable breasts, scatter radiation similar to that observed exiting the breast of scintimammography patients was observed. It was observed that scattered gamma rays can constitute the majority of the radiation incident on the detector, but that the scatter-to-primary ratio varies significantly across the field of view, being greatest in the caudal portion of the breast, where scatter from the liver is high. Using a lesion-to-breast concentration ratio of 6:1, a 1.0 cm3 simulated breast lesion was detectable in lateral images obtained with both the developmental camera and with a clinical camera, while a 0.35 cm3 lesion was detectable in neither. Utilization of the dual x-ray transmission, gamma emission breast imaging system greatly increases the conspicuity of scintimammographic lesions relative to prone imaging, as well as greatly facilitating the localization and identification of structures in the gamma image. The prototype imaging gamma detector exhibits spatial resolution superior to that of conventional cameras, and comparable uniformity of response and geometric linearity. Because of light losses in the crystals, the energy resolution is inferior to that of single crystal NaI(Tl) came

Equipment Design↗
PubMed2000

Radiologists' preferences for digital mammographic display. The International Digital Mammography Development Group.

PURPOSE: To determine the preferences of radiologists among eight different image processing algorithms applied to digital mammograms obtained for screening and diagnostic imaging tasks. MATERIALS AND METHODS: Twenty-eight images representing histologically proved masses or calcifications were obtained by using three clinically available digital mammographic units. Images were processed and printed on film by using manual intensity windowing, histogram-based intensity windowing, mixture model intensity windowing, peripheral equalization, multiscale image contrast amplification (MUSICA), contrast-limited adaptive histogram equalization, Trex processing, and unsharp masking. Twelve radiologists compared the processed digital images with screen-film mammograms obtained in the same patient for breast cancer screening and breast lesion diagnosis. RESULTS: For the screening task, screen-film mammograms were preferred to all digital presentations, but the acceptability of images processed with Trex and MUSICA algorithms were not significantly different. All printed digital images were preferred to screen-film radiographs in the diagnosis of masses; mammograms processed with unsharp masking were significantly preferred. For the diagnosis of calcifications, no processed digital mammogram was preferred to screen-film mammograms. CONCLUSION: When digital mammograms were preferred to screen-film mammograms, radiologists selected different digital processing algorithms for each of three mammographic reading tasks and for different lesion types. Soft-copy display will eventually allow radiologists to select among these options more easily.

Algorithms↗
PubMed1999

Noise power spectra of images from digital mammography detectors.

Noise characterization through estimation of the noise power spectrum (NPS) is a central component of the evaluation of digital x-ray systems. We begin with a brief review of the fundamentals of NPS theory and measurement, derive explicit expressions for calculation of the one- and two-dimensional (1D and 2D) NPS, and discuss some of the considerations and tradeoffs when these concepts are applied to digital systems. Measurements of the NPS of two detectors for digital mammography are presented to illustrate some of the implications of the choices available. For both systems, two-dimensional noise power spectra obtained over a range of input fluence exhibit pronounced asymmetry between the orthogonal frequency dimensions. The 2D spectra of both systems also demonstrate dominant structures both on and off the primary frequency axes indicative of periodic noise components. Although the two systems share many common noise characteristics, there are significant differences, including markedly different dark-noise magnitudes, differences in NPS shape as a function of both spatial frequency and exposure, and differences in the natures of the residual fixed pattern noise following flat fielding corrections. For low x-ray exposures, quantum noise-limited operation may be possible only at low spatial frequency. Depending on the method of obtaining the 1D NPS (i.e., synthetic slit scanning or slice extraction from the 2D NPS), on-axis periodic structures can be misleadingly smoothed or missed entirely. Our measurements indicate that for these systems, 1D spectra useful for the purpose of detective quantum efficiency calculation may be obtained from thin cuts through the central portion of the calculated 2D NPS. On the other hand, low-frequency spectral values do not converge to an asymptotic value with increasing slit length when 1D spectra are generated using the scanned synthetic slit method. Aliasing can contribute significantly to the digital NPS, especially near the Nyquist frequency. Calculation of the theoretical presampling NPS and explicit inclusion of aliased noise power shows good agreement with measured values.

Biophysics↗
PubMed1999

Treatment planning considerations and quality assurance for CT-guided transischiorectal implantation of the prostate.

A CT-guided technique for prostate brachytherapy has been developed which can be performed on patients with large prostates and which allows real time evaluation and modification of implant geometry. The patient is positioned prone and radioactive Pd 103 or I 125 seeds are implanted through the transischiorectal space. Needles are inserted through a template whose plane is oriented at a nominal angle of 26 degrees away from the horizontal to facilitate needle penetration through the ischiorectal space. The CT gantry is tilted 26 degrees, so that its plane is orthogonal to that of the template. The oblique geometry between the CT gantry and direction of couch translation must be considered during source position planning, implantation, and post-treatment evaluation. This consideration is presented along with discussion of relevant quality assurance procedures and recommended tolerances. The mechanical and radiological tolerances of the CT scanner must be consistent with the high level of precision required in radiation therapy. Special emphasis was placed on gantry laser and image plane alignment, sensitivity and radiation profiles, and spatial accuracy of image reconstruction, table translation, and gantry tilt.

Biophysical Phenomena↗
PubMed1999

Analysis of the detective quantum efficiency of a developmental detector for digital mammography.

We are developing a modular detector for applications in full field digital mammography and for diagnostic breast imaging. The detector is based on a design that has been refined over the past decade for applications in x-ray crystallography [Kalata et al., Proc. SPIE 1345, 270-279 (1990); Phillips et al. ibid. 2009, 133-138 (1993), Phillips et al., Nucl. Instrum. Methods Phys. Rev. A 334, 621-630 (1993)]. The full field mammographic detector, currently undergoing clinical evaluation, is formed from a 19 cm x 28 cm phosphor screen, read out by a 2 x 3 array of butted charge-coupled device (CCD) modules. Each 2k x 2k CCD is optically coupled to the phosphor via a fiber optic taper with dimensions of 9.4 cm x 9.4cm at the phosphor. This paper describes the imaging performance of a two-module prototype, built using a similar design. In this paper we use cascaded linear systems analysis to develop a model for calculating the spatial frequency dependent noise power spectrum (NPS) and detective quantum efficiency (DQE) of the detector using the measured modulation transfer function (MTF). We compare results of the calculation with the measured NPS and DQE of the prototype. Calculated and measured DQEs are compared over a range of clinically relevant x-ray exposures and kVps. We find that for x-ray photon energies between 10 and 28 keV, the detector gain ranges between 2.5 and 3.7 CCD electrons per incident x-ray, or approximately 5-8 electrons per absorbed x ray. Using a Mo/Mo beam and acrylic phantom, over a detector entrance exposure range of approximately 10 to 80 mR, the volume under the measured 2-d NPS of the prototype detector is proportional to the x-ray exposure, indicating quantum limited performance. Substantial agreement between the calculated and measured values was obtained for the frequency and exposure dependent NPS and DQE over a range of tube voltage from 25 to 30 kVp.

Algorithms↗
PubMed1998

The memory B cell subset responsible for the secretory IgA response and protective humoral immunity to rotavirus expresses the intestinal homing receptor, alpha4beta7.

Infection of mice with murine rotaviruses induces life-long immunity, characterized by high levels of IgA in the intestine and large numbers of rotavirus (RV)-specific Ab-secreting cells in gut-associated lymphoid tissues. Lymphocyte trafficking into gut-associated lymphoid tissues is mediated by interaction of the alpha4beta7 integrin on lymphocytes with the vascular mucosal addressin cell adhesion molecule-1. To determine whether B cell memory for RV correlates with alpha4beta7 expression, we transferred sorted B220+ phenotypically defined memory (IgD- alpha4beta7(high) and IgD- alpha4beta7-) and naive (IgD+ alpha4beta7+) splenocytes into recombination-activating gene-2 knockout mice (B and T cell-deficient) that were chronically infected with RV. Only mice receiving alpha4beta7(high) memory (IgD-) B cells produced RV-specific IgA in the stool, cleared the virus, and were immune to reinfection. Alpha4beta7(high) (but not alpha4beta7-) memory B cells from donors boosted as much as 7 mo previously also cleared the virus, indicating that alpha4beta7(high) memory B cells maintain long term functional immunity to RV. Although only alpha4beta7(high) memory cells provided mucosal immunity, alpha4beta7- cells from recently boosted donor animals could generate RV-specific serum IgG, but, like naive (IgD+) B cells, were unable to induce viral clearance even 60 days after cell transfer. These data indicate that protective immunity for an intestinal pathogen, RV, resides in memory phenotype B cells expressing the intestinal homing receptor, alpha4beta7.

Animals↗
PubMed1998

Establishing minimum performance standards, calibration intervals, and optimal exposure values for a whole breast digital mammography unit.

Methods are developed to establish minimum performance standards, calibration intervals, and criteria for exposure control for a whole breast digital mammography system. A prototype phantom was designed, and an automatic method programmed, to analyze CNR, resolution, and dynamic range between CCD components in the image receptor and over time. The phantom was imaged over a 5 month period and the results are analyzed to predict future performance. White field recalibration was analyzed by subtracting white fields obtained at different intervals. Exposure effects were compared by imaging the prototype phantom at different kVp, filtration (Mo vs Rh) and mAs. Calcification detection tests showed that phantom images, obtained at 28 kVp with a Mo/Mo anode/filter and low mAs technique, often could not depict Al2O3 specks 0.24 mm in diameter, while a 28 kVp Mo/Rh, higher mAs technique usually could. Stability of the system tested suggests that monthly phantom imaging may suffice. Differences in CCD performance are greater (12%) than differences in a single CCD over time (6%). White field recalibration is needed weekly because of pixel variations in sensitivity which occur if longer intervals between recalibration occur. When mean glandular dose is matched, Rh filtration gives better phantom performance at 28 kVp than Mo filtration at 26 kVp and is recommended for clinical exposures. An aluminum step wedge shows markedly increased dynamic range when exit exposure is increased by using a higher energy spectrum beam. Phantoms for digital mammography units should cover the entire image receptor, should test intersections between components of the receptor, and should be automatically analyzed.

Female↗
PubMed1998

Expression of the mucosal homing receptor alpha4beta7 correlates with the ability of CD8+ memory T cells to clear rotavirus infection.

The integrin alpha4beta7 plays an important role in lymphocyte homing to mucosal lymphoid tissues and has been shown to define a subpopulation of memory T cells capable of homing to intestinal sites. Here we have used a well-characterized intestinal virus, murine rotavirus, to investigate whether memory/effector function for an intestinal pathogen is associated with alpha4beta7 expression. Alpha4beta7(hi) memory phenotype (CD44hi), alpha4beta7- memory phenotype, and presumptively naive (CD44(lo)) CD8+ T lymphocytes from rotavirus-infected mice were sorted and transferred into Rag-2 (T- and B-cell-deficient) recipients that were chronically infected with murine rotavirus. Alpha4beta7(hi) memory phenotype CD8+ cells were highly efficient at clearing rotavirus infection, alpha4beta7- memory cells were inefficient or ineffective, depending on the cell numbers transferred, and CD44(lo) cells were completely unable to clear chronic rotavirus infection. These data demonstrate that functional memory for rotavirus resides primarily in memory phenotype cells that display the mucosal homing receptor alpha4beta7.

Animals↗
PubMed1998

Future directions in imaging of breast diseases.

In the near future, investigation and refinement of emerging anatomic and functional breast imaging techniques will enable clinical trials that will evaluate their utility and potential for improving the survival and quality of life for patients with breast cancer. In the longer term, strategic research collaborations among investigators in the fields of functional imaging, molecular biology, and pathology are needed to merge existing science and advance the development of biomarker and genetic techniques focused on detecting and characterizing disease at the cellular and molecular levels. This research could create clinical tools for (a) detecting breast cancer earlier, (b) more accurately quantifying the extent of disease, (c) noninvasively evaluating lymph node involvement, (d) identifying micrometastases and residual microscopic disease, and (e) enhancing therapy by means of imaging-guided biomarker or tumor-specific delivery of pharmacologic, chemosensitizing, or radiosensitizing agents to tumors.

Breast↗
PubMed1997

Expression of mucosal homing receptor alpha4beta7 by circulating CD4+ cells with memory for intestinal rotavirus.

The integrin alpha4beta7 mediates lymphocyte binding to mucosal addressin cell adhesion molecule-1, and its expression defines lymphocytes capable of trafficking through the intestines and the intestinal lymphoid tissues. We examined the ability of discrete alpha4beta7(hi) and alpha4beta7- subsets of circulating memory phenotype (CD45RA-) CD4+ T cells to proliferate in response to rotavirus, a ubiquitous intestinal pathogen. alpha4beta7(hi) memory (CD45RA-) CD4+ T cells displayed much greater reactivity to rotavirus than alpha4beta7- memory or naive (CD45RA+) CD4+ T cells. In contrast, alpha4beta7- memory cells were the predominant population responsive to mumps antigen after intramuscular vaccination. Our results are consistent with the conclusion that natural rotavirus infection, an enteric pathogen, results in a specific circulating memory CD4+ response that is largely limited to the gut-homing alpha4beta7+ subpopulation. This phenotype is not shared with memory cells elicited by intramuscular immunization (shown here) or by skin contact allergens. The results support the hypothesis that gut trafficking memory CD4+ T cells comprise cellular memory for intestinal antigens and suggest that regulated expression of alpha4beta7 helps target and segregate intestinal versus systemic immune response.

Adult↗
PubMed1997

Homing of naive and memory T lymphocyte subsets to Peyer's patches, lymph nodes, and spleen.

The specificity and efficiency of extravasation of subsets of memory and naive lymphocytes into organized lymphoid tissues has been the subject of recent controversy, but has not been directly assessed in physiologic systems. Here, we compare the lymphoid organ homing of naive and phenotypically defined memory T cells, focusing on memory subsets differentially expressing the integrin receptor alpha4beta7, which is implicated in homing to mucosal sites. Naive T cells (CD44(low), Thy1+) home to all secondary lymphoid organs. Alpha4beta7(high) memory-phenotype (CD44(high)) T cells home to Peyer's patches as efficiently as naive lymphocytes, whereas alpha4beta7- memory-phenotype T cells are essentially excluded from entry into these mucosal lymphoid organs. In contrast, alpha4beta7- memory-phenotype cells home approximately twice as efficiently as alpha4beta7(high) T cells to peripheral lymph nodes, but only approximately 20% as well as naive T cells. Interestingly, the spleen recruits all three identified subsets with nearly equal efficiency. The relative subset localization is similar 2.5 h after injection and after overnight trafficking, suggesting that memory cells can directly extravasate from blood into Peyer's Patches and lymph nodes. We conclude that subsets of memory T cells defined by patterns of homing receptor expression display differential homing to organized lymphoid tissues, an ability that may facilitate homeostatic interactions and target contributions to specialized regional immune responses.

Animals↗
PubMed1997

Factor-derived subsyndromes of schizophrenia and familial morbid risks.

Factor analysis was performed on OPCRIT checklist ratings from 66 patients with RDC schizophrenia. Eight substantive factors were found, characterised respectively by: positive formal thought disorder; first rank delusions; first rank hallucinations; inappropriate affect/bizarre behaviour; negative symptoms; grandiose/bizarre delusions; delusions of influence/persecution; and other hallucinations. A history of schizophrenia and other non-affective psychoses was ascertained in the probands' first-degree relatives using a family history approach. Illness in relatives was best predicted by probands' scores on subsyndromes derived from the inappropriate affect/bizarre behaviour and positive formal thought disorder factors.

Adult↗
PubMed1995

Modulation by inositol of cholinergic- and serotonergic-induced seizures in lithium-treated rats.

Hippocampal and cortical EEG recordings in rats were used to monitor the in vivo modulation by lithium of responses to agonists for 5HT2/5HT1c serotonergic (DOI) and cholinergic (pilocarpine) receptors and the influence of inositol administration. Administration of DOI (8 mg/kg) or pilocarpine (30 mg/kg) to rats pretreated with lithium acutely (3 mmol/kg) or chronically (dietary, 4 weeks) resulted in seizures, whereas these doses did not cause seizures without lithium pretreatment. This indicated that lithium most likely affects a signal transduction process common to both systems, which is the phosphoinositide second messenger system. To examine the potential influence of altered inositol levels on these responses, we tested the effects of infusions (10 mg, i.c.v.) of myo-inositol, a precursor of phosphoinositide synthesis, and of epi-inositol, an isomer not used for phosphoinositide synthesis. Administration of myo-inositol (10 mg) slightly reduced the incidence of seizures induced by acute lithium plus DOI but almost completely blocked seizures induced by acute lithium plus pilocarpine. This was surprising since seizures induced by acute lithium plus DOI were less severe than those after acute lithium plus pilocarpine, but myo-inositol was more effective in blocking the latter. Epi-inositol also blocked seizures under both conditions but it was less effective than myo-inositol after treatment with acute lithium plus pilocarpine. The latencies to seizures and/or severity of seizures were potentiated more by chronic than acute lithium pretreatment with both DOI and pilocarpine, but attenuation by myo-inositol was less with each agonist after chronic lithium compared with acute lithium treatment. Peripheral administration of a high dose of myo-inositol blocked seizures induced by acute lithium plus pilocarpine, but the inositol treatment itself was toxic and caused seizures prior to pilocarpine administration, so the mechanism of action cannot simply be attributed to increased brain inositol levels. These results demonstrate that lithium modulates the in vivo responses to DOI and pilocarpine, most probably through an effect on the phosphoinositide signal transduction system. They also show that centrally administered myo-inositol modifies responses to these agents, but the effectiveness of epi-inositol and other results leave unclear the mechanistic basis of its actions.

Amphetamines↗