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Biomedical subjects

J F Southern

Publications and source records attributed to J F Southern.

At least 19 recordsLinked to original sources

Vesiculopustular eruptions in Down syndrome neonates with myeloproliferative disorders.

BACKGROUND: Infants with Down syndrome are at increased risk for hematologic abnormalities, including leukemoid reaction, transient myeloproliferative disorder, and congenital leukemia. The differential diagnosis of a vesiculopustular eruption in an infant with Down syndrome and these hematologic abnormalities is broad and includes benign, self-limited disorders as well as life-threatening infections. OBSERVATION: We describe 3 newborns with Down syndrome and vesiculopustular eruptions associated with myeloproliferative disorders during the neonatal period. These lesions differ from other neonatal vesicular eruptions in that they have a unique distribution, display pathergy, and contain immature hematopoietic cells similar to circulating blast cells. Resolution occurs without treatment as the hematologic disorder subsides. CONCLUSIONS: Infants with Down syndrome and hematologic abnormalities may have a cutaneous eruption that has characteristic clinical and histopathologic findings. It is possible that this eruption has been unrecognized in the past because of its self-limited course. Whether this eruption is a prognostic factor for the subsequent development of leukemia is uncertain.

Diagnosis, Differential↗

Optical biopsy with optical coherence tomography.

A need exists in medicine for a technology capable of 'optical biopsy,' imaging at or near the resolution of histopathology without the need for excisional biopsy. Optical coherence tomography (OCT) is a recently developed imaging technology that uses infrared light to generate cross-sectional images on a micron scale. In this work, the feasibility of OCT for optical biopsy was confirmed with in vitro tissue from the skeletal and male reproductive systems. This work supports the hypothesis that OCT is an attractive technology for in vivo optical biopsy.

Biopsy↗

New technology for high-speed and high-resolution optical coherence tomography.

Optical coherence tomography (OCT) is an optical imaging technique that is capable of performing micron-scale, cross-sectional imaging of internal microstructure in biological systems. OCT is analogous to ultrasound B mode imaging except that it uses light rather than sound and performs imaging by measuring the back-scattered intensity of light from structures in tissue. We describe recent advances in OCT technology including the application of short pulse solid state lasers based on Ti: Al2O3 and Cr: Mg2SiO4 to enable high-resolution, high-speed imaging as well as the development of OCT catheter/endoscope delivery to permit imaging of internal organ systems. OCT enables the nonexcisional, in situ, real-time imaging of tissue microstructure and is thus a powerful and promising technique for optical biopsy.

Animals↗

Measurement of pS2 protein in pancreatic cyst fluids. Evidence for a potential role of pS2 protein in the pathogenesis of mucinous cystic tumors.

CONCLUSION: Elevated levels of the growth factor pS2 protein in the cyst fluids of mucinous cystic tumors correlate with earlier observations using immunohistochemical techniques showing that pS2 protein is expressed by these tumors. The markedly elevated levels of pS2 protein compared to normal plasma values suggest that this growth factor may be important in the pathogenesis of pancreatic mucinous cystic tumors. BACKGROUND: Cystic lesions of the pancreas include inflammatory pseudocysts, serous cystadenomas, and mucinous cystic tumors, some of which are malignant. Previous studies using immunohistochemical techniques have shown that virtually all pancreatic mucinous tumors express pS2 protein. pS2 protein is a growth factor that is believed to be important in the normal process of inflammation and repair. We measured pS2 protein and other growth factors in pancreatic cyst fluids to assess their potential pathophysiologic and diagnostic significance. METHODS: Levels of pS2 protein were measured in 54 pancreatic cyst fluids by radioimmunoassay. The growth factors, epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), and insulin-like growth factors I and II (IGF-I, IGF-II) were measured in 22 cyst fluids using commercial immunoassays. RESULTS: Mucinous cysts exhibited significantly higher levels of cyst fluid pS2 protein than nonmucinous lesions, including pseudocysts and serous cystadenomas (median: 78,303 pg/mL; range: 218-361,176 pg/mL vs median: 886 pg/mL; range: 0-14,206 pg/mL; p = 0.0001). The level of pS2 in mucinous tumors was markedly higher than plasma values (median: 392 pg/mL). Levels of pS2 protein in malignant mucinous lesions tended to be higher than those in benign mucinous cysts, but this difference was not statistically significant (median: 88,817 vs 64,350 pg/mL; p = 0.159). Levels of other growth factors, including EGF, TGF-alpha, IGF-I, and IGF-II, did not discriminate among the different cyst types, and the values were within normal plasma ranges.

Cyst Fluid↗

Two- and three-dimensional high-resolution imaging of the human oviduct with optical coherence tomography.

OBJECTIVE: To evaluate the feasibility of optical coherence tomography, a new method of micron-scale imaging, for high-resolution assessment of the oviduct. Optical coherence tomography is analogous to ultrasound except that it measures the backreflection of infrared light rather than acoustical waves. DESIGN: The ampulla of a human fallopian tube was imaged in vitro using optical coherence tomography. Images were generated in 2 and 3 dimensions. SETTING: University. PATIENT(S): Samples were obtained from women who had undergone hysterectomy for leiomyomatosis. INTERVENTION(S): None MAIN OUTCOME MEASURE(S): The ability to perform imaging on a micron scale, which is a level of resolution higher than that of any currently available clinical technology. RESULT(S): Two- and three-dimensional data sets of the reflectance of a human fallopian tube were acquired. A volume of 5 x 5 x 2.5 mm (length x width x depth) was scanned. The axial resolution was 11 microm, and the lateral resolution at the focus was 20 microm. The data sets showed detailed structures of the fallopian tube. CONCLUSION(S): Our ability to obtain micron-scale two- and three-dimensional images of an in vitro oviduct suggests that it may be possible to identify and surgically treat tubal causes of infertility.

Diagnostic Imaging↗

Behavior of atherosclerotic plaque components after in vitro angioplasty and atherectomy studied by high field MR imaging.

AIMS: Using magnetic resonance imaging (MRI), we developed in vitro models to image the response of fatty, fibrous, and calcified plaques to in vitro models of angioplasty and atherectomy, and tested the resistance of collagenous cap and lipid core to radial compression. METHODS AND RESULTS: We studied the effects of balloon compression on 10 fibrous plaques with a complete collagenous cap (group A), 6 fatty plaques without cap (group B), and 5 calcified plaques (group C). Atherectomy was performed on nine other fibrous lesions (group D). In group A, fibrous cap, lipid core, and plaque did not change after radial compression despite a decrease in luminal obstruction due to medial stretching. In group B, a reduction of plaque (-30%) and lipid core (-35%) were observed. Compression dissected calcified plaques at the shoulder level. In group D, atherectomy reduced collagenous cap by 54%, and plaque by 35%. CONCLUSIONS: In these models, MRI shows 1) the high resistance of collagenous caps to radial compression, 2) a stretching effect of compression on disease-free walls, enlarging lumen in case of fibrous plaque, but a reduction and redistribution of lipid cores in case of fatty plaques, 3) the rupture of calcified arteries at the plaque shoulder, and 4) the reduction of fibrous components by atherectomy but not by angioplasty. By characterizing plaque composition, MRI may allow a predictable response of atherosclerotic arteries to interventional procedures.

Angioplasty, Balloon↗

Optical biopsy in human pancreatobiliary tissue using optical coherence tomography.

Optical coherence tomography (OCT) is a new technique for performing high-resolution, cross-sectional tomographic imaging in human tissue. OCT is analogous to ultrasound B mode imaging except that it uses light rather than acoustical waves. As a result, OCT has over 10 times the resolution of currently available clinical high-resolution cross-sectional imaging technologies. In this work, we investigate the capability of OCT to differentiate the architectural morphology of pancreatobiliary tissues. Normal pancreatobiliary tissues, including the gallbladder, common bile duct, pancreatic duct, and pancreas were taken postmortem and imaged using OCT. Images were compared to corresponding histology to confirm tissue identity. Microstructure was delineated in different tissues, including tissue layers, glands, submucosal microvasculature, and pancreatic islets of Langerhans. The ability of OCT to provide high-resolution imaging of pancreatobiliary architectural morphology suggests the feasibility of using OCT as a powerful diagnostic endoscopic imaging technology to image early stages of pancreatobiliary disease.

Biliary Tract↗

Intraoperative assessment of microsurgery with three-dimensional optical coherence tomography.

PURPOSE: To evaluate three-dimensional optical coherence tomography (OCT) for use in the assessment of the microsurgical anastomoses of vessels and nerves. MATERIALS AND METHODS: OCT is an optical analogue of ultrasonography and is capable of imaging nontransparent biologic tissue by detecting backscattered infrared light. Cross-sectional in vitro images of rabbit and human vessels and nerves were obtained in as little as 125 msec at 10-micron resolution by using a solid-state laser as a light source. A surgical microscope was integrated with OCT to perform simultaneous imaging with en face visualization. Cross-sectional images were assembled to produce three-dimensional reconstructions of microsurgical specimens. RESULTS: Three-dimensional OCT reconstructions depicted the structure within an arterial anastomosis and helped identify sites of luminal obstruction. The longitudinal spatial orientation of individual nerve fascicles was tracked in three dimensions to identify changes in position. In vitro human arteries and nerves embedded in highly scattering tissue and not visible at microscopy were located and imaged with OCT at eight frames per second. CONCLUSION: The three-dimensional, micrometer-scale, diagnostic imaging capabilities of OCT permit rapid feedback for assessment of microsurgical procedures. OCT technology can be readily integrated with surgical microscopes and has potential for intraoperative monitoring to improve patient outcome.

Anastomosis, Surgical↗

High resolution imaging of the upper respiratory tract with optical coherence tomography: a feasibility study.

A need exists in respiratory medicine for a technology capable of identifying airway pathology on a micron scale. This study has demonstrated the feasibility of optical coherence tomography (OCT) for ultrahigh resolution imaging of the upper respiratory tract by in vitro studies of human tissue. OCT is a relatively new technique that can be used to noninvasively collect tomographic images of tissue microstructure with micron-scale resolution. OCT is analogous to ultrasound, measuring the intensity of infrared light rather than acoustical waves. Samples throughout the upper respiratory tract, from the epiglottis to the secondary bronchi, were imaged. The resulting images were compared with histopathology and verified the ability of OCT to delineate relevant structures such as the epithelium, mucosa, cartilage and its sublayers, and glands at a resolution higher than any clinical imaging technology. The ability of OCT to generate image resolution in the range close to that of histopathology in real time, as well as easy integration with small, relatively inexpensive endoscopes, low cost, and lack of a need for a transducing medium, supports the hypothesis that this optical technology could become a powerful modality in the diagnosis and management of a wide range of clinical respiratory pathology.

Feasibility Studies↗

Optical biopsy with optical coherence tomography: feasibility for surgical diagnostics.

BACKGROUND: Optical coherence tomography (OCT) is a recently developed compact technology which uses infrared light to perform cross-sectional imaging on a micrometer scale. Since OCT provides imaging at a resolution comparable to conventional histology and does not require direct contact with the tissue surface, a role in real-time surgical diagnostics represents a logical extension. In this work, we test the feasibility of OCT for surgical diagnostics by demonstrating imaging in tissue relevent to microsurgical intervention, a previously undescribed observation. MATERIALS AND METHODS: Over 50 sites on nervous, reproductive, and microvascular specimens from 10 patients were examined postmortem with OCT. After imaging, tissue was registered with microinjections of dye, under visible light laser guidance, followed by routine histologic processing to confirm the identity of microstructure. RESULTS: The 16 +/- 1 microm resolution allowed subsurface microstructure to be identified at unprecedented resolution. Structures identified included fascicles of peripheral nerves, the internal elastic membrane of microvessels, and the granular layer of the cerebellum. CONCLUSIONS: The ability of OCT to provide micrometer-scale definition of tissue microstructure suggests a role in surgical diagnostics. Future in vivo investigations are merited to establish its utility for morbidity reduction associated with surgical intervention.

Animals↗

In vivo endoscopic optical biopsy with optical coherence tomography.

Current medical imaging technologies allow visualization of tissue anatomy in the human body at resolutions ranging from 100 micrometers to 1 millimeter. These technologies are generally not sensitive enough to detect early-stage tissue abnormalities associated with diseases such as cancer and atherosclerosis, which require micrometer-scale resolution. Here, optical coherence tomography was adapted to allow high-speed visualization of tissue in a living animal with a catheter-endoscope 1 millimeter in diameter. This method, referred to as "optical biopsy," was used to obtain cross-sectional images of the rabbit gastrointestinal and respiratory tracts at 10-micrometer resolution.

Anatomy, Cross-Sectional↗

Noninvasive assessment of the developing Xenopus cardiovascular system using optical coherence tomography.

Studies investigating normal and abnormal cardiac development are frequently limited by an inability to assess cardiovascular function within the intact organism. In this work, optical coherence tomography (OCT), a new method of micron-scale, noninvasive imaging based on the measurement of backscattered infrared light, was introduced for the high resolution assessment of structure and function in the developing Xenopus laevis cardiovascular system. Microstructural details, such as ventricular size and wall positions, were delineated with OCT at 16-microm resolution and correlated with histology. Three-dimensional representation of the cardiovascular system also was achieved by repeated cross-sectional imaging at intervals of 25 microm. In addition to structural information, OCT provides high speed in vivo axial ranging and imaging, allowing quantitative dynamic activity, such as ventricular ejection fraction, to be assessed. The sensitivity of OCT for dynamic assessment was demonstrated with an inotropic agent that altered cardiac function and dimensions. Optical coherence tomography is an attractive new technology for assessing cardiovascular development because of its high resolution, its ability to image through nontransparent structures, and its inexpensive portable design. In vivo and in vitro imaging are performed at a resolution approaching that of histopathology without the need for animal killing.

Animals↗

Acute hydrocephalus following carbon monoxide poisoning.

Carbon monoxide remains a significant cause of poisoning in children. Cerebral edema is often the cause of significant morbidity and mortality in exposed children. While lesions of the basal ganglia have been well documented, the advent of neuroimaging has allowed antemortem demonstration of infarctions of the globus pallidus and putamen with carbon monoxide intoxication. Acute hydrocephalus following carbon monoxide poisoning has been a rare occurrence. We report a 2 year 6 month-old boy who, to our knowledge, represents the first reported case in which repeat computed tomography documented the evolution of hydrocephalus due to carbon monoxide exposure in a child.

Acute Disease↗

Assessing atherosclerotic plaque morphology: comparison of optical coherence tomography and high frequency intravascular ultrasound.

BACKGROUND: OCT can image plaque microstructure at a level of resolution not previously demonstrated with other imaging techniques because it uses infrared light rather than acoustic waves. OBJECTIVES: To compare optical coherence tomography (OCT) and intravascular ultrasound (IVUS) imaging of in vitro atherosclerotic plaques. METHODS: Segments of abdominal aorta were obtained immediately before postmortem examination. Images of 20 sites from five patients were acquired with OCT (operating at an optical wavelength of 1300 nm which was delivered to the sample through an optical fibre) and a 30 MHz ultrasonic transducer. After imaging, the microstructure of the tissue was assessed by routine histological processing. RESULTS: OCT yielded superior structural information in all plaques examined. The mean (SEM) axial resolution of OCT and IVUS imaging was 16 (1) and 110 (7), respectively, as determined by the point spread function from a mirror. Furthermore, the dynamic range of OCT was 109 dB compared with 43 dB for IVUS imaging. CONCLUSIONS: OCT represents a promising new technology for intracoronary imaging because of its high resolution, broad dynamic range, and ability to be delivered through intravascular catheters.

Aorta, Abdominal↗

Water diffusion properties of human atherosclerosis and thrombosis measured by pulse field gradient nuclear magnetic resonance.

Using pulsed field gradient methods combined with magnetic resonance imaging, we calculated the apparent water diffusion coefficient D in different atherosclerotic components to probe the microstructure of normal and diseased arteries by characterizing molecular motion. D was equal to 0.26 +/- 0.13 x 10(-5) cm2.s-1 in plaque lipid core, 1.45 +/- 0.41 x 10(-5) cm2.s-1 in collagenous cap, and 1.54 +/- 0.30 x 10(-5) cm2.s-1 in normal media. Water diffuses isotropically in the atheromatous core of the plaque, suggesting the absence or destruction of confining structures. The comparable diffusion coefficients in collagenous cap and normal media are consistent with similar biophysical barriers in both components. In thrombi, D varies with the aging processes (fresh thrombus, 0.72 +/- 0.11 x 10(-5) cm2.s-1; 1-week-old thrombus, 0.36 +/- 0.08 x 10(-5) cm2.s-1; old occluding thrombus, 1.33 +/- 0.33 x 10(-5) cm2.s-1), consistent with the cross-linking of the fibrin strands occurring in the early phase and the later thrombus organization. Defining an indirect index of arterial lipid infiltration, remodeling, and aging, diffusion imaging provides a new nuclear magnetic resonance characterization of atherothrombosis.

Arteries↗