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Biomedical subjects

I Soutar

Publications and source records attributed to I Soutar.

12 recordsLinked to original sources

Luminescence techniques and characterization of the morphology of polymer latices 2. Fluorescence lifetime, phosphorescence and fluorescence anisotropy studies.

Five poly(n-butyl methacrylate), PBMA, latex dispersions have been prepared, each incorporating a different fluorescent label, via a two-stage seeded emulsion polymerization. The resultant latices contain ca. 35% by weight total solids and are of 80 (+/-10) nm diameter as determined by photon correlation spectrometry. Luminescence spectroscopic techniques, namely fluorescence (and phosphorescence) excited state lifetime measurements in addition to time-resolved anisotropy experiments have provided useful information regarding the morphology, microviscosity and water permeability of the resultant particles. A picture of the PBMA colloid emerges of an interior which is highly viscous and water impermeable in nature. Indeed, the environment is protective enough to sustain room temperature stabilized phosphorescence from both an acenaphthylene and 9-phenanthrylmethyl methacrylate labeled dispersion through simple nitrogen purging of the solutions. However, the current spectroscopic measurements should be viewed with the knowledge that each luminescent label may fashion its own distinctive microenvironment within the latex during polymerization.

Journal Article↗

Luminescence techniques and characterization of the morphology of polymer latices. 3. An investigation of the microenvironments within stabilized aqueous latex dispersions of poly(n-butyl methacrylate) and polyurethane.

Fluorescence techniques (including time-resolved anisotropy measurements, TRAMS) have been used to probe differences in morphology between two stabilized aqueous latex dispersions (poly(n-butyl methacrylate), PBMA, and polyurethane, PU). Use of the emission characteristics of probes such as pyrene and phenanthrene dispersed within particles reveals that the PU latices are more heterogeneous in nature: evidence exists, particularly from quenching measurements and TRAMS, that voids and channels of water permeate the PU structure, resulting in a relatively soft, open particle, swollen by ingress of the bulk aqueous phase. Fluorescence measurements indicate that PBMA colloids, however, are composed of relatively hard, hydrophobic particles. In addition, TRAMS are considered to be a valuable tool both for probing the morphological characteristics of such dispersions and in estimating the average particle size.

Journal Article↗

Fluorescence anisotropy: a method for early detection of Alzheimer beta-peptide (Abeta) aggregation.

Time-resolved anisotropy measurements (TRAMS) have been used to study the aggregation of the beta-amyloid (Abeta) peptide which is suspected of playing a central role in the pathogenesis of Alzheimer's Disease (AD). The experiments, which employ small quantities of fluorescently-labelled Abeta, in addition to the untagged peptide, have shown that the sensitive TRAMS technique detects the presence of preformed "seed" particles in freshly prepared solutions of Abeta. More importantly, as 100 microM solutions of Abeta containing tagged Abeta at a concentration level of either 0.5 or 1 microM are incubated, the TRAMS prove capable of detection of the peptide aggregation process through the appearance of a continuously increasing "residual anisotropy" within the time-resolved fluorescence data. The method detects Abeta aggregation in its earliest stages, well before complexation becomes apparent in more conventional methods such as the thioflavin T fluorescence assay. The TRAMS approach promises to provide a most attractive route for establishment of a high-throughput procedure for the early detection of the presence of amyloid aggregates in the screening of biological samples.

Alzheimer Disease↗

Designing fault-tolerant distributed archives for picture archiving and communication systems.

PURPOSE: Distributed archives in a picture archiving and communication system (PACS) environment can provide added fault tolerance and fail-over capability, as well as increased load capacity at a more economical price than traditional 'high-availability" systems. Systems can be configured with varying levels of fault tolerance, depending on the amount of redundancy desired. There is, however, a direct correlation between the level of hardware redundancy and cost to implement. This presentation details the system design for fault-tolerant distributed archives as well as several options for redundancy, referencing implementation of a fault-tolerant archive system at the University of Utah. METHODS: The distributed archive system described here is based on Image Devices' image archive software, which can be implemented on multiple individual archive servers in order to distribute archive functionality and operational load. The configuration and implementation of the individual servers together make up the distributed archive system and does not impact the ability of the system to be scaled to meet future requirements. Several implementation and configuration options exist, including the ability for servers to maintain replicated databases containing patient and image information. Thus, each archive can be aware of all information and the location of this information within the distributed archive system. RESULTS: The goal is to produce systems that will still be operational in the event of any single point of failure, ie, a network connection failure between facilities or the failure of a single archive server within the distributed system. During normal operation, workload for image acquisition, image routing and image query requests will be distributed between the archive servers. If the system is deployed in a multifacility environment, each archive server can be configured to be responsible for the acquisition and image distribution management within that server's local facility. If the system is deployed in a single facility environment, load can be distributed evenly between the archive servers based on an understanding of the workload requirements generated be each acquisition and display device in the system. In the event that an archive server fails, other archive servers within the system will have the ability to provide some or all of the failed server's functionality. The degree of fail-over capability is dependent on the archive server's configuration as well as hardware redundancy employed. Three levels of fault-tolerant design can be achieved with this system architecture: (1) duplicate work capability only; (2) duplicate work capability and short-term image cache; (3) duplicate work capability, short-term image cache, and longterm image archival. Using the basic fault-tolerant design above, we have implemented a multifacility distributed archive system at the University of Utah. This system was implemented at a fraction of the cost of true "high-availability" archive architectures yet provides constant up time for the PACS system. If the network connection between the two locations goes down, each site is still fully functional for soft-copy read, as well as image acquisition and distribution. If either of the archive servers goes down, the image sources are redirected to the other archive server. The operational server then handles image distribution for both locations. Access to images in the short-term image cache is available to both archive servers and is not affected by loss of the network connection or remote server. Because there is ony one long-term archive device, the ability to retrieve images from long-term storage is the only function compromised by a network or server failure. CONCLUSION: By implementing distributed archives in a PACS environment, it is possible to achieve a highly fault-tolerant system without the expense of high-availability hardware and software. The design concepts outlined here can be applied to any PACS system that supports distributed archive functionality.

Computer Systems↗

Modulation of beta-amyloid production and fibrillization.

Alzheimer's disease (AD) is the most common cause of dementia in old age and presently affects an estimated 4 million people in the U.S.A. and 0.75 million people in the U.K. It is a relentless, degenerative brain disease, characterized by progressive cognitive impairment. In the final stages of the disease, patients are often bedridden, doubly incontinent and unable to speak or to recognize close relatives. Pathological changes of Alzheimer's disease include extensive neuronal loss and the presence of numerous neurofibrillary tangles and senile plaques in the brain. The senile plaques contain amyloid fibrils derived from a 39-43-amino-acid peptide referred to as beta-amyloid or A beta. The basic theory of the so-called 'amyloid hypothesis' is that the deposition of aggregated forms of A beta in the brain parenchyma triggers a pathological cascade of events that leads to neurofibrillary tangle formation, neuronal loss and the associated dementia [1]. Here we discuss progress towards the identification of inhibitors of A beta production and fibrillization.

Alzheimer Disease↗

Photophysics of Carbazole-Containing Systems. 3 Fluorescence of Carbazole-Containing Oligoethers in Dilute Solution.

Fluorescence techniques, including quenching and anisotropy measurements, have been used to study the photophysical behavior of the carbazole-based oligoethers poly{9-(2,3-epoxypropyl)carbazole}, PEPCz, and poly{1,2-epoxy-6-(9-carbazolyl)-4-oxahexane}, PECzOH, and their model compounds, in dilute fluid solutions in THF. These compounds show no evidence of excimer formation under these conditions and their fluorescences exhibit first-order decay behavior regardless of the degree of polymerization of the oligomer. Both steady-state and time-resolved anisotropy measurements upon dilute, glassy solutions show that intramolecular energy migration occurs in the oligomers. Fluorescence quenching experiments, using both dimethylterephthalate and oxygen as quenchers, produced evidence which supports the supposition that in the absence of excimer trapping sites, intramolecular energy migration will be encouraged in dilute fluid solutions of the oligoethers. Unfortunately, the fluorescence quenching data did not permit evaluation of the extents of energy migration in the various polymers or the relative efficiencies with which migration occurs in the two different types of oligoether. This limitation would appear to be a general feature of fluorescence quenching measurements, despite their frequent adoption, in the past, in studies of energy migration in polymers.

Journal Article↗

Hearing screening in Jamaica: prevalence of otitis media with effusion.

Hearing screening is well established in most developed countries, and the data extensively published. However, little information has been presented by the developing, nonwhite populations. A screening study was carried out on 2202 Jamaican children aged 5 to 7 years. This involved tympanometry and pure-tone audiometry (frequencies of 0.5, 1, and 2 kHz.) Failure was considered to have occurred if a type B or C curve was obtained or if the threshold of hearing was greater than 20 dB. These children were further evaluated by a full ear, nose, and throat examination, inclusive of pneumatic otoscopy, and audiologic testing. The prevalence of hearing impairment was 4.9%. Otitis media with effusion (OME) was present in 1.9%. The prevalence of OME in Jamaica is low when compared with that of the same age-group in the developed countries.

Acoustic Impedance Tests↗

Role of equalisation mammography of dense breasts.

Parenchymal patterns characteristic of dense breasts are known to degrade the mammographic detection of small breast cancers and microcalcifications. This arises from large variations in exposure of the film, resulting in reduced image contrast over areas of suboptimal exposure. Based on sensitometric measurements of mammograms from a typical patient population, it is shown that over 60% of a typical mammogram in Wolfe's DY classification was found to be exposed suboptimally, suggesting a significant margin for improving mammography for these patients. In order to address this problem, a prototype mammographic version of scanning equalisation radiography (MSER) has been developed, which delivers a patient-specific spatially non-uniform distribution of breast exposure, adjusted to maintain optimal film exposure and contrast over the entire mammogram. Anthropomorphic phantom MSER images show a marked improvement in subjective image quality relative to conventional mammograms, while exhibiting a similar radiation risk. The detection of small microcalcifications and fibrils over clinically significant breast densities is found to be improved by factors eight and four, respectively. Such a system may be clinically practical through the use of multiple-beam equalisation methods with available X-ray tube technology.

Breast Neoplasms↗

An MR compatible flow simulator for intravascular pressure simulation.

An MR compatible flow simulator is described which generates physiologically realistic pressure and flow waveforms. The simulator is based on a servomotor-driven gear pump which produces pulsatile flow by modulation of the servomotor rotation rate. Operation of the simulator is under the control of a personal computer, which executes an iterative feedback loop to minimize errors between measured and desired pressure waveforms. The simulator is totally automatic, requiring only a few minutes of iteration to generate the desired pressure waveform. Accurate sinusoidal waveforms with frequencies up to 10 Hz have been generated using the simulator, with high-frequency contamination of the measured waveform at least 80 dB below the fundamental frequency. Aortic waveforms have been produced with realistic flow rates and pressure variations. The pump assembly is mechanically straightforward and can operate at an 8-m distance from the flow phantom to allow the device to be isolated from the MR magnet room.

Biophysical Phenomena↗

Errors in quantitative dynamic three-dimensional keyhole MR imaging of the breast.

Three-dimensional (3D) keyhole magnetic resonance (MR) imaging has been proposed as a means of providing dynamic monitoring of contrast agent uptake by breast lesions, with complete breast coverage and high spatial and temporal resolution. The 3D keyhole technique dynamically samples the central regions of k-space in both phase-encoding directions and provides high-frequency data from a precontrast acquisition. Errors due to data truncation with two-dimensional and 3D region-of-interest measurements are estimated from a numerical simulation of various implementations of the 3D keyhole technique. Errors were found to increase with increasing temporal resolution and reduced object size. Errors of 75% are possible for objects with a diameter approaching 1 pixel when a 3D keyhole implementation that samples 50% of phase-encoding data in each direction is used. Preliminary clinical images with this approach illustrate artifacts consistent with inadequate k-space sampling.

Artifacts↗

Visualizing tissue compliance with MR imaging.

We propose a method for visualizing the mechanical properties of tissue based on the use of periodic mechanical compression in conjunction with phase-contrast MR imaging. A specialized mechanical transducer was used to provide programmable compression pulses to the surface of compliant phantoms. These compression pulses were synchronized to a spin-echo sequence with motion-sensitizing gradients to generate phase information reflecting spin displacement throughout the phantom. This sequence was tested with two agarose gel phantoms. The first was a cylinder containing three parallel layers of varying compliance and the second was composed of a semirigid sphere suspended in a uniform layer of decreased elastic modulus. Images showed complex patterns of motion throughout the phantom, which correlated with expected motion behavior of the phantom structures. This indicates that the biomechanical properties of tissues may be elucidated through the use of motion-sensitized MR imaging and suggests that a form of image contrast relating to tissue elasticity may be feasible.

Compliance↗