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Biomedical subjects

Brian C Wilson

Publications and source records attributed to Brian C Wilson.

At least 37 records · Page 2Linked to original sources
PubMed2005

Relaxin inhibits central angiotensin II expression in killifish: a central osmoregulatory role for relaxin and angiotensin II in the killifish Fundulus heteroclitus.

We investigated whether relaxin and brain angiotensin II (AII) are osmoregulatory hormones in killifish. Four groups of killifish acclimatized to different saline environments (freshwater, 25% sea water, 50% sea water [brackish], and sea water) were euthanized and their brains were embedded in paraffin. A separate group of brackish water killifish were injected with relaxin 1 h before dissection and embedding. Serial sagittal sections were immunohistochemically stained for AII. Angiotensin II immunostaining did not differ between saline environments. Contrary to expectation, relaxin decreased the number of AII-immunoreactive cells in hypothalami of brackish water fish.

Angiotensin II↗
PubMed2005

Optical techniques for the endoscopic detection of dysplastic colonic lesions.

PURPOSE OF REVIEW: Within the past decade, advances in biomedical optics have been applied to overcome sensitivity and specificity limitations in conventional diagnostic endoscopy for detecting dysplasia and noninvasive cancer. This review presents the current status of emerging optical techniques that rely on the complex interaction of light with tissue, and their possible roles in detection, mapping, staging, and therapy of dysplasia. RECENT FINDINGS: Progress in endoscopic autofluorescence imaging has been dominated by efforts to enhance the detection of dysplasia with tumor-localizing prodrugs. Raman and light-scattering spectroscopy have had very limited reporting for the colon. Endoscopic optical coherence tomography has now acquired real-time Doppler capabilities, and rudimentary endoscopic criteria for hyperplastic and adenomatous polyps have been described. Narrow-band imaging endoscopy awaits large-scale testing in the colon. The greatest activity has been reported for chromoendoscopy. Although contradictory results of diagnostic accuracy must be clarified and optimal methodologies are yet to be outlined, magnifying endoscopy has resuscitated chromoendoscopy. Single-cell subsurface imaging has been achieved with confocal fluorescence microendoscopy on excised tissues and now the first clinical experience has been reported. New and exciting research using highly specific and bright tumor-targeted fluorescence contrast agents is thrusting diagnostic endoscopy into a new era of "molecular endoscopy." SUMMARY: Most studies reported to date have mainly focused on refining existing prototype instruments or continue on a basic research level, with the ultimate goal of improving sensitivity and specificity for colonic dysplasia, compared with the gold standard of histopathology. It is more than likely that the future diagnostic role of these evolving technologies will involve the combination of two or more complementary technologies, and "molecular targeting" approaches will be crucial for earliest detection. However, despite innovative applications and refinement of the existing ones, large, controlled, prospective multicenter trials are still anxiously awaited by the practicing endoscopist to evaluate the diagnostic role and cost-effectiveness of these emerging technologies in the gastroenterology clinic.

Chromogenic Compounds↗
PubMed2004

Protease-triggered photosensitizing beacon based on singlet oxygen quenching and activation.

We report a new concept for type-II photosensitization, based on incorporating the photosensitizer (PS) and a singlet-oxygen (1O2) quenching/scavenging molecule onto a disease-targeting linker, such that the PS becomes activatable by light only when targeting has occurred. In this first proof-of-concept report, a model photosensitizing beacon was synthesized containing a pyropheophorbide as the PS and a carotenoid as the 1O2 quencher. These were kept in close proximity by the self-folding of a caspase-3-specific peptide sequence. Upon caspase-3-induced cleavage, the 1O2 production increased markedly, as measured directly by 1O2 near-infrared luminescence and lifetime measurements.

Carotenoids↗
PubMed2004

Micromachined array tip for multifocus fiber-based optical coherence tomography.

High-resolution optical coherence tomography demands a large detector bandwidth and a high numerical aperture for real-time imaging, which is difficult to achieve over a large imaging depth. To resolve these conflicting requirements we propose a novel multifocus fiber-based optical coherence tomography system with a micromachined array tip. We demonstrate the fabrication of a prototype four-channel tip that maintains a 9-14-microm spot diameter with more than 500 microm of imaging depth. Images of a resolution target and a human tooth were obtained with this tip by use of a four-channel cascaded Michelson fiber-optic interferometer, scanned simultaneously at 8 kHz with geometric power distribution across the four channels.

Equipment Design↗
PubMed2004

Radiance-based monitoring of the extent of tissue coagulation during laser interstitial thermal therapy.

Optical monitoring relates the dynamic changes in measured light intensity to the extent of treatment-induced coagulation that occurs during laser interstitial thermal therapy. We utilized a two-region Monte Carlo simulation to elucidate the nature of the changes in interstitial radiance and fluence that result from the formation of a volume of thermal coagulation surrounding a cylindrical emitter. Using simulation results, we demonstrate that radiance sensors are more sensitive than traditional fluence sensors to coagulation-induced scattering changes. Radiance measurements take advantage of directional detection angles that are more receptive to the onset and passing of the coagulation boundary. We performed experiments with albumen phantoms to demonstrate the practicality of the radiance method for monitoring interstitial laser thermal therapy.

Albumins↗
PubMed2004

The potential of autofluorescence for the detection of single living cells for label-free cell sorting in microfluidic systems.

A novel method for studying unlabeled living mammalian cells based on their autofluorescence (AF) signal in a prototype microfluidic device is presented. When combined, cellular AF detection and microfluidic devices have the potential to facilitate high-throughput analysis of different cell populations. To demonstrate this, unlabeled cultured cells in microfluidic devices were excited with a 488 nm excitation light and the AF emission (> 505 nm) was detected using a confocal fluorescence microscope (CFM). For example, a simple microfluidic three-port glass microstructure was used together with conventional electroosmotic flow (EOF) to switch the direction of the fluid flow. As a means to test the potential of AF-based cell sorting in this microfluidic device, granulocytes were successfully differentiated from human red blood cells (RBCs) based on differences in AF. This study demonstrated the use of a simple microfabricated device to perform high-throughput live cell detection and differentiation without the need for cell-specific fluorescent labeling dyes and thereby reducing the sample preparation time. Hence, the combined use of microfluidic devices and cell AF may have many applications in single-cell analysis.

Equipment Design↗
PubMed2004

Increased brain tumor resection using fluorescence image guidance in a preclinical model.

BACKGROUND AND OBJECTIVES: Fluorescence image-guided brain tumor resection is thought to assist neurosurgeons by visualizing those tumor margins that merge imperceptibly into normal brain tissue and, hence, are difficult to identify. We compared resection completeness and residual tumor, determined by histopathology, after white light resection (WLR) using an operating microscope versus additional fluorescence guided resection (FGR). STUDY DESIGN/MATERIALS AND METHODS: We employed an intracranial VX2 tumor in a preclinical rabbit model and a fluorescence imaging/spectroscopy system, exciting and detecting the fluorescence of protoporphyrin IX (PpIX) induced endogenously by administering 5-aminolevulinic acid (ALA) at 4 hours before surgery. RESULTS: Using FGR in addition to WLR significantly increased resection completeness by a factor 1.4 from 68+/-38 to 98+/-3.5%, and decreased the amount of residual tumor post-resection by a factor 16 from 32+/-38 to 2.0+/-3.5% of the initial tumor volume. CONCLUSIONS: Additional FGR increased completeness of resection and enabled more consistent resections between cases.

Aminolevulinic Acid↗
PubMed2004

Effects of Pd-bacteriopheophorbide (TOOKAD)-mediated photodynamic therapy on canine prostate pretreated with ionizing radiation.

The aim of this study was to evaluate the effects of photodynamic therapy (PDT) using a novel palladium bacteriopherophorbide photosensitizer TOOKAD (WST09) on canine prostate that had been pretreated with ionizing radiation. To produce a physiological and anatomical environment in canine prostate similar to that in patients for whom radiotherapy has failed, canine prostates (n = 4) were exposed to ionizing radiation (54 Gy) 5 to 6 months prior to interstitial TOOKAD-mediated PDT. Light irradiation (763 nm, 50-200 J/cm at 150 mW/cm from a 1-cm cylindrical diffusing fiber) was delivered during intravenous infusion of TOOKAD at 2 mg/kg over 10 min. Interstitial measurements of tissue oxygen profile (pO(2)) and of local light fluence rate were also measured. The prostates were harvested for histological examination 1 week after PDT. The baseline pO(2) of preirradiated prostate was in the range 10-44 mmHg. The changes in relative light fluence rate during PDT ranged from 12 to 43%. The acute lesions were characterized by hemorrhagic necrosis, clearly distinguishable from the radiotherapy-induced pre-existing fibrosis. The lesion size was correlated with light fluence and comparable to that in unirradiated prostate treated with a similar TOOKAD-PDT protocol. There was no noticeable damage to the urethra, bladder or adjacent colon. The preliminary results obtained from a small number of animals indicate that TOOKAD-PDT can effectively ablate prostate pretreated with ionizing radiation, and so it may provide an alternative modality for those prostate cancer patients for whom radiotherapy has failed.

Animals↗
PubMed2004

Mapping ALA-induced PPIX fluorescence in normal brain and brain tumour using confocal fluorescence microscopy.

We have mapped the microscopic distribution of aminolevulinic acid (ALA) induced protoporphyrin IX (PPIX) in normal rabbit brain and in brain tumour at various time intervals after i.v. injection of ALA. In normal brain, regions without a blood-brain barrier (BBB) such as the choroid plexus and meninges and also structures associated with the CSF synthesized the highest amounts of PPIX. We also detected ALA in the CSF within 2 h after ALA administration when the serum concentration was high. Our fluorescence studies have shown that ALA is able to cross an intact BBB and be metabolized in regions with a BBB. This is evident in regions of the brain such as the hippocampus, thalamus, cerebellar folia and brain stem that are remote from the meninges or choroid plexus. However, the relative peak PPIX fluorescence in these regions are much lower than in regions without a BBB. Our imaging studies have shown that neurons in different regions of normal brain with an intact BBB exhibit varying capacities to metabolize ALA. The grey matter regions of the cerebrum and cerebellum also showed higher PPIX fluorescence compared to white matter regions in these same structures. Our study showed that tumour tissue had the highest PPIX fluorescence compared to normal contralateral cerebral cortex. Maximum selectivity was achieved between tumour and normal tissue at 24 h. PPIX fluorescence in normal blood vessels appear to be mainly due to metabolism of internalized ALA from serum and not due to high PPIX levels. In conclusion, ALA does cross the BBB and all regions of the brain with the exception of the hypothalamus, exhibit a dynamic synthesis of PPIX from ALA. Increased PPIX accumulation in tumour and inflamed brain tissue in comparison to normal brain tissue suggest the feasibility of selective photosensitization of such tissue.

Aminolevulinic Acid↗
PubMed2003

In vitro tests of the validity of singlet oxygen luminescence measurements as a dose metric in photodynamic therapy.

Singlet oxygen ((1)O(2)) is widely believed to be the major cytotoxic agent involved in photodynamic therapy (PDT). We showed recently that measurement of the weak near infrared luminescence of (1)O(2) is possible in cells in vitro and tissues in vivo. Here, we investigated the relationship between the integrated luminescence signal and the in vitro PDT response of AML5 leukemia cells sensitized with aminolevulinic acid-induced protoporphyrin IX (PpIX). Sensitized cell suspensions were irradiated with pulsed 523 nm laser light at average fluence rates of 10, 25, or 50 mWcm(-2) and, (1)O(2) luminescence measurements were made throughout the treatment. Cell survival was measured with either propidium iodide-labeled flow cytometry or colony-forming assay. The PpIX concentration in the cells, the photobleaching, and the pO(2) in the cell suspensions were also monitored. There were large variations in cell survival and (1)O(2) generation in different experiments due to different controlled treatment parameters (fluence and fluence rate) and other uncontrolled factors (PpIX synthesis and oxygenation). However, in all of the cases, cell kill correlated strongly with the cumulative (1)O(2) luminescence and allowed direct estimation of the (1)O(2) per cell required to achieve a specific level of cell kill. This study supports the validity and potential utility of (1)O(2) luminescence measurement as a dosimetric tool for PDT, as well as confirming the likely role of (1)O(2) in porphyrin-based PDT.

Aminolevulinic Acid↗
PubMed2003

A multispectral fluorescence imaging system: design and initial clinical tests in intra-operative Photofrin-photodynamic therapy of brain tumors.

BACKGROUND AND OBJECTIVES: Intra-operative identification of tumor by fluorescence may improve surgical resection or photodynamic therapy (PDT). A novel instrument was designed, constructed, and tested for this purpose. STUDY DESIGN/MATERIALS AND METHODS: The instrument was designed to provide high-resolution, multi-spectral (five band) fluorescence imaging, and non-contact point spectroscopy, with long working distance ( approximately 50 cm), large field-of-view ( approximately 3 cm diameter), large depth of view ( approximately 2 cm), and 'point-and-shoot' operation. Its performance was determined in tissue-simulating phantoms and in pilot studies in brain tumor resection patients, with or without intra-operative Photofrin-PDT. RESULTS: In phantoms the imaging resolution was approximately 150 microm, while Photofrin concentrations as low as 0.05 or 0.1 microg/g could be detected at the tissue surface or at 0.5 mm depth, respectively. Red Photofrin fluorescence could be clearly visualized post radical resection in all PDT patients, with biopsy confirmation of residual tumor tissue in regions that were not seen as tumor under white light. Photobleaching of Photofrin during PDT was also demonstrated. CONCLUSIONS: The system performed to specification under realistic operating conditions and could reveal unresected residual tumor tissue. It may be used for either PDT dosimetry/monitoring and/or for surgical guidance.

Adult↗
PubMed2003

Diagnostic potential of near-infrared Raman spectroscopy in the colon: differentiating adenomatous from hyperplastic polyps.

BACKGROUND: Near-infrared Raman spectroscopy is a promising optical technique for GI tissue diagnosis. This study assessed the diagnostic potential of near-infrared Raman spectroscopy in the colon by evaluating its ability to distinguish between adenomatous and hyperplastic polyps. METHODS: Ex vivo and in vivo Raman spectra of colon polyps were collected by using a custom-built, fiber-optic, near-infrared Raman spectroscopic system. Multivariate statistical techniques, including principal component analysis and linear discriminant analysis, were used to develop diagnostic algorithms for classifying colon polyps based on their spectral characteristics. With the number of samples available, spectral classification of polyps was tested by using a leave-one-out, cross-validation method. RESULTS: Fifty-four ex vivo Raman spectra were analyzed (20 hyperplastic, 34 adenomatous). The spectral-based diagnostic algorithms identified adenomatous polyps with 91% sensitivity, 95% specificity, and 93% accuracy. In vivo, adenomas (n = 10) were distinguished from hyperplastic polyps (n = 9) with 100% sensitivity, 89% specificity, and 95% accuracy. CONCLUSIONS: Near-infrared Raman spectroscopy differentiated adenomatous from hyperplastic polyps with high diagnostic accuracy. To our knowledge, this is the first demonstration of the potential of near-infrared Raman spectroscopy for differentiation of colonic polyps during GI endoscopy.

Adenomatous Polyps↗
PubMed2003

In vivo Doppler optical coherence tomography of mucocutaneous telangiectases in hereditary hemorrhagic telangiectasia.

BACKGROUND: Hereditary hemorrhagic telangiectasia is characterized by mucocutaneous telangiectases and visceral arteriovenous malformations. Knowledge is limited concerning the development hemodynamics of mucocutaneous telangiectases. Doppler optical coherence tomography can demonstrate microvascular blood flow at flow rates as low as 20 microm/second, which is up to approximately 100 times more sensitive than Doppler US. The aims of this study were to collect in vivo Doppler optical coherence tomography images of mucocutaneous telangiectases and normal surrounding mucosa and skin, and to gain experience for an in vivo GI endoscopic study. It was hypothesized that visibly normal areas may have occult telangiectases and that mucocutaneous telangiectases that have bled may have a higher rate of blood flow than mucocutaneous telangiectases with no history of bleeding. METHODS: Twelve patients with hereditary hemorrhagic telangiectasia and mucocutaneous telangiectases were studied. Two to 3 visible mucocutaneous telangiectases on the digits, lips, and tongue were imaged with Doppler optical coherence tomography, along with visually normal surrounding areas at each site. The Doppler optical coherence tomography images were obtained in 0.5 second by using 1310 nm light. RESULTS: A total of 67 mucocutaneous telangiectases from the 12 patients were imaged (38 digit, 16 lip, 13 tongue). Blood flow was demonstrated within every mucocutaneous telangiectasis imaged. Doppler optical coherence tomography did not identify any abnormal vasculature within visually normal areas. Mucocutaneous telangiectases with a history of bleeding (n = 18) were situated closer to the surface, compared with mucocutaneous telangiectases with no bleeding history (n = 49), but there was no difference in the Doppler flow appearance. CONCLUSIONS: Visually normal areas in patients with hereditary hemorrhagic telangiectasia did not appear to have abnormal vasculature. Mucocutaneous telangiectases with a history of bleeding were more superficial but were otherwise similar to mucocutaneous telangiectases with no bleeding history.

Adult↗
PubMed2003

Potential applications of photodynamic therapy in regenerative medicine.

Photodynamic therapy (PDT) is an emerging field that uses light-activated drugs to produce specific biological effects in cells and tissues. Its particular strengths arise from the ability to spatially localize the biological responses by the way the light is applied; the range of possible mechanisms of action at the cell, tissue, and organism levels; and the combination of novel molecular and optical technologies. This paper presents the basic principles of PDT and considers some of the possible applications in regenerative medicine.

Bone Regeneration↗
PubMed2003

Molecular fluorescence excitation-emission matrices relevant to tissue spectroscopy.

In vivo and ex vivo studies of fluorescence from endogenous and exogenous molecules in tissues and cells are common for applications such as detection or characterization of early disease. A systematic determination of the excitation-emission matrices (EEM) of known and putative endogenous fluorophores and a number of exogenous fluorescent photodynamic therapy drugs has been performed in solution. The excitation wavelength range was 250-520 nm, with fluorescence emission spectra collected in the range 260-750 nm. In addition, EEM of intact normal and adenomatous human colon tissues are presented as an example of the relationship to the EEM of constituent fluorophores and illustrating the effects of tissue chromophore absorption. As a means to make this large quantity of spectral data generally available, an interactive database has been developed. This currently includes EEM and also absorption spectra of 35 different endogenous and exogenous fluorophores and chromophores and six photosensitizing agents. It is intended to maintain and extend this database in the public domain, accessible through the Photochemistry and Photobiology website (http://www.aspjournal. com/).

Colon↗
PubMed2002

New optical technologies for earlier endoscopic diagnosis of premalignant gastrointestinal lesions.

Gastrointestinal malignancies continue to be the second leading cause of cancer-related deaths in the developed world. The early detection and treatment of gastrointestinal preneoplasms has been demonstrated to significantly improve patient survival. Conventional screening tools include standard white light endoscopy (WLE) and frequent surveillance with biopsy. Well-defined endoscopic surveillance biopsy protocols aimed at early detection of dysplasia and malignancy have been undertaken for groups at high risk. Unfortunately, the poor sensitivity associated with WLE is a significant limitation. In this regard, major efforts continue in the development and evaluation of alternative diagnostic techniques. This review will focus on notable developments made at the forefront of research in modern gastrointestinal endoscopy based on novel optical endoscopic modalities, which rely on the interactions of light with tissues. Here we present the 'state-of-the-art' in fluorescence endoscopic imaging and spectroscopy, Raman spectroscopy, optical coherence tomography, light scattering spectroscopy, chromoendoscopy, confocal fluorescence endoscopy, and immunofluorescence endoscopy. These new developments may offer significant improvements in the diagnosis of early lesions by allowing for targeted mucosal excisional biopsies, and perhaps may even provide 'optical biopsies' of equivalent histological accuracy. This enhancement of the endoscopist's ability to detect subtle preneoplastic changes in the gastrointestional mucosa in real time and improved staging of lesions could lead to curative endoscopic ablation of these lesions and, in the long term, improve patient survival and quality of life.

Endoscopy, Digestive System↗
PubMed2002

Photodynamic therapy for cancer: principles.

The principles of photodynamic therapy (PDT), using drugs (photosensitizers) that are activated by light to become cytotoxic, provide the basis for understanding the current and potential future clinical applications in gastroenterology, general oncology and other specialties. The properties of photosensitizers are key to their biological efficacy, while lasers and optical fibres allow convenient and flexible light delivery for endoscopic use. PDT has several distinct and unique advantages, both as a stand-alone treatment and in combination with other established modalities. The current limitations are also recognized, as is the need for rigorous randomized trials of this emerging technology. The fluorescence of many photosensitizers may be useful, either for (endoscopic) diagnosis or for PDT treatment guidance and monitoring.

Humans↗