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Biomedical subjects

Norman E Marcon

Publications and source records attributed to Norman E Marcon.

At least 19 recordsLinked to original sources

Feasibility of interstitial Doppler optical coherence tomography for in vivo detection of microvascular changes during photodynamic therapy.

INTRODUCTION: Doppler optical coherence tomography (DOCT) is an emerging imaging modality that provides subsurface microstructural and microvascular tissue images with near histological resolution and sub-mm/second velocity sensitivity. A key drawback of OCT for some applications is its shallow (1-3 mm) penetration depth. This fundamentally limits DOCT imaging to transparent, near-surface, intravascular, or intracavitary anatomical sites. Consequently, interstitial Doppler OCT (IS-DOCT) was developed for minimally-invasive in vivo imaging of microvasculature and microstructure at greater depths, providing access to deep-seated solid organs. Using Dunning prostate cancer in a rat xenograft model, this study evaluated the feasibility of IS-DOCT monitoring of microvascular changes deep within a tumor caused by photodynamic therapy (PDT). MATERIALS AND METHODS: The DOCT interstitial probe was constructed using a 22 G (diameter approximately 0.7 mm) needle, with an echogenic surface finish for enhanced ultrasound visualization. The lens of the probe consisted of a gradient-index fiber, fusion spliced to an angle-polished coreless tip to allow side-view scanning. The lens was then fusion spliced to a single-mode optical fiber that was attached to the linear scanner via catheters and driven along the longitudinal axis of the needle to produce a 2D subsurface DOCT image. The resultant IS-DOCT system was used to monitor microvascular changes deep within the tumor mass in response to PDT in the rat xenograft model of Dunning prostate cancer. Surface PDT was delivered at 635 nm with 40 mW of power, for a total light dose of 76 J/cm(2), using 12.5 mg/kg of Photofrin as the photosensitizer dose. RESULTS: IS-DOCT demonstrated its ability to detect microvasculature in vivo and record PDT-induced changes. A reduction of detected vascular cross sectional area during treatment and partial recovery post-treatment were observed. CONCLUSIONS: IS-DOCT is a potentially effective tool for real-time visualization and monitoring of the progress of PDT treatments. This capability may play an important role in elucidating the mechanisms of PDT in tumors, pre-treatment planning, feedback control for treatment optimization, determining treatment endpoints and post-treatment assessments.

Animals↗

Spectroscopy and fluorescence in esophageal diseases.

Malignant tumors of the esophagus continue to be a major health issue associated with high mortality primarily because most present with symptoms of dysphagia or anaemia. The disease at that stage is advanced and not likely curable. The big issue for squamous dysplasia and that associated with BE is that only a small proportion are discovered in surveillance programs when they are asymptomatic, either because the patient lives in a high-incidence geographical area, has a family history, previously diagnosed head and neck cancer or chronic reflux, as in Barrett's. Current endoscopic methods are hampered by the endoscopist's inability to recognize subtle topographic clues of dysplasia, sampling errors related to biopsy protocols, and confounding inflammation-induced artifacts both for the endoscopist and pathologist. What is desperately needed would be a biomarker (e.g. serological, fecal, urinary) that selects patients for endoscopy. However, such a test is not yet on the horizon. This article examines the current status in practice and research of novel optically based 'bioendoscopic' devices (i.e. fluorescence spectroscopy and imaging, confocal fluorescence microendoscopy (CFM), light scattering spectroscopy (LSS), Raman spectroscopy (RS), and immunophotodiagnostic endoscopy) which may enhance the diagnosis of dysplasia in all patients undergoing conventional white light endoscopy. Perhaps these new technologies will lead to more cost-effective diagnosis, mapping (e.g. surface), and staging (e.g. depth) of dysplasia, thereby allowing timely cure by endoscopic means (e.g. EMR and/or PDT), biological interventions (e.g. Cox-2 inhibitors) rather than esophajectomy.

Endoscopy, Gastrointestinal↗

Esophageal intramural pseudodiverticulosis with food impaction.

Esophageal intramural pseudodiverticulosis is a rare condition of unknown etiology originally described in 1960. It is characterized by multiple, flask-shaped outpouchings of pinhead size in the wall of the esophagus. Very small outpouchings on endoscopy and tiny collections of barium outside of the esophagus wall on esophagography are typical diagnostic findings. During the era of widespread endoscopic and radiological evaluation of esophageal disorders, approximately 200 cases were published in the literature. A 52-year-old man with esophageal intramural pseudodiverticulosis with food impaction is reported. The patient's symptoms of dysphagia resolved with endoscopic dilations and proton pump inhibitor therapy.

Catheterization↗

Gastric calcifying fibrous tumor.

Intramucosal gastric tumours are most commonly found to be gastrointestinal stromal tumours or leiomyomas (smooth muscle tumours); however, a variety of other uncommon mesenchymal tumours can occur in the stomach wall. A rare benign calcifying fibrous tumour is reported and the endoscopic appearance, ultrasound findings and morphology are documented. A review of the literature found only two similar cases.

Calcinosis↗

Interstitial Doppler optical coherence tomography.

Doppler optical coherence tomography (OCT) can image tissue structure and blood flow at micrometer-scale resolution but has limited imaging depth. We report a novel, linear-scanning, needle-based Doppler OCT system using angle-polished gradient-index or ball-lensed fibers. A prototype system with a 19-guage (diameter of approximately 0.9 mm) echogenic needle is constructed and demonstrates in vivo imaging of bidirectional blood flow in rat leg and abdominal cavity. To our knowledge, this is the first demonstration of Doppler OCT through a needle probe in interstitial applications to visualize deeply situated microcirculation.

Animals↗

Colonoscopic diagnosis of mucocele of the appendix.

BACKGROUND: Appendiceal mucoceles are uncommon cystic neoplasms characterized by distension of the appendiceal lumen with mucus. There have been no reported series of colonoscopically diagnosed mucoceles with clinicopathologic correlation. METHODS: A retrospective review of colonoscopies performed at our institution over the past 14 years was undertaken with patient demographics, clinical data, surgical outcomes, and histopathology obtained from hospital records. OBSERVATIONS: Seven patients (6 women) with mucocele of the appendix were identified at colonoscopy. Three had complained of right lower quadrant pain. All 7 patients underwent surgical resection. Histopathology demonstrated mucinous cystadenoma in all. No cases revealed carcinoma, and there have been no deaths related to the mucocele. CONCLUSIONS: Appendiceal mucoceles may be recognized at colonoscopy as a smooth bulbous submucosal lesion of the cecum with an impression formed by the appendiceal orifice. Recognition at colonoscopy is important because it enables accurate diagnosis and directs management. Surgery is recommended in all cases given the risk of malignancy or perforation with resultant pseudomyxoma peritonei.

Adult↗

Endoscopic Doppler optical coherence tomography in the human GI tract: initial experience.

BACKGROUND: Expanding the current endoscopic optical coherence tomography (OCT) system with Doppler capability may augment this novel high-resolution cross-sectional imaging technique with functional blood flow information. The aim of this feasibility study was to assess the clinical feasibility of an endoscopic Doppler OCT (EDOCT) system in the human GI tract. METHODS: During routine endoscopy, 22 patients were imaged by using a prototype EDOCT system, which provided color-Doppler and velocity-variance images of mucosal and submucosal blood flow at one frame per second, simultaneously with high-spatial-resolution (10-25 mum) images of tissue microstructure. The images were acquired from normal GI tract and pathologic tissues. OBSERVATIONS: Subsurface microstructure and microcirculation images of normal and pathologic GI tissues, including Barrett's esophagus, esophageal varices, portal hypertensive gastropathy, gastric antral vascular ectasia, gastric lymphoma, and duodenal adenocarcinoma, were obtained from 72 individual sites in vivo. Differences in vessel diameter, distribution, density, and blood-flow velocity were observed among the GI tissue pathologies imaged. CONCLUSIONS: To our knowledge, this is the first study to demonstrate the feasibility of EDOCT imaging in the human GI tract during routine endoscopy procedures. EDOCT may detect the different microcirculation patterns exhibited by normal and diseased tissues, which may be useful for diagnostic imaging and treatment monitoring.

Adult↗

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↗

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↗

Diagnosis of small-bowel varices by capsule endoscopy.

BACKGROUND: Capsule endoscopy is being used increasingly to investigate GI bleeding of obscure origin and disorders of the small bowel. METHODS: Four cases of small-bowel varices of various etiologies diagnosed by capsule endoscopy are described: a bleeding small-bowel varix because of hepatic portal hypertension, oozing small-bowel anastomotic or adhesion-related varices, small-bowel varices secondary to mesenteric vein thrombosis, and "idiopathic intestinal varices." OBSERVATIONS: Over a 12-month period, small-bowel varices were found in 4 of 46 patients (8.7%) who underwent capsule endoscopy for GI bleeding. Fresh blood adjacent to the varices was documented in 3 patients. The small-bowel varices had serpiginous or nodular shapes, with or without a bluish coloration. The variceal mucosa appeared mosaic-like, shining, or normal compared with surrounding mucosa. CONCLUSIONS: Capsule endoscopy is invaluable for the diagnosis of small-bowel varices. It is highly sensitive for detection of fresh blood in the small bowel. Clinical suspicion, capsule endoscopy image recognition, and alertness during capsule endoscopy interpretation are keys to diagnosis.

Adult↗

Wireless capsule endoscopy for obscure gastrointestinal bleeding: a single-centre, one-year experience.

BACKGROUND: Wireless capsule endoscopy (CE) is increasingly being used in the investigation of obscure gastrointestinal (GI) bleeding, but some studies have found that many of the bleeding lesions recognized by this technique are within the reach of conventional endoscopy. METHODS: The results of CE performed in the authors' centre in a 12 month period for obscure GI bleeding were retrospectively reviewed. RESULTS: Of the 46 patients with obscure GI bleeding, CE found a definite or probable cause in 19 (41%) and a possible cause in another 10 (22%), with an overall diagnostic yield of 63%. One of these lesions was found to be within reach of conventional gastroscopy, two were within reach of push enteroscopy, four were within reach of colonoscopy and one was within reach of retrograde enteroscopy through a stoma. The percentage of patients with a bleeding source within reach of routine endoscopy but missed during pre-CE endoscopy was significantly higher for those patients having endoscopy only in the community (30% [eight of 27]) versus in the authors' centre (0% [zero of 19]). CONCLUSIONS: CE was valuable for diagnosing bleeding lesions not only within the small bowel, but also in the stomach and colon. However, "second-look" endoscopy may be considered before ordering CE for obscure GI bleeding when local expertise is available.

Adult↗

Fluorescence and Raman spectroscopy.

Table 2 provides a summary of selected in vivo fluorescence and Raman studies performed in BE. Although the findings from these studies appear promising, these techniques are still under development, and it is anticipated that technological refinements will further enhance their diagnostic accuracy. Ultimately, however, large-scale prospective clinical trials are required to determine their true diagnostic potential in BE and other sites. Ideally, the instrumentation of choice would be a real-time endoscopic system that combines excellent diagnostic accuracy with wide-area sampling. In this regard, fluorescence imaging is most appealing, although a variety of issues remain to be resolved, including the choice between autofluorescence versus drug-induced fluorescence and the problematic distinction between dysplastic (true positive) and confounding background metaplastic fluorescence (false positive), among others. It is also not clear whether exogenous fluorophores are necessary to achieve clinically useful sensitivity and specificity for lesion detection in BE. Point spectroscopic techniques, either fluorescence or Raman scattering, are inherently limited by the small volume of tissue (biopsy specimen size) they sample, but more detailed information can be extracted from the spectra, which may increase diagnostic accuracy. Moreover, it may be that the optimal system will be a combination of multiple optical spectroscopic or imaging techniques (multimodality approach), as suggested by Georgakoudi et al. For instance, a lesion could be detected by fluorescence imaging and its dysplastic nature characterized (graded) by Raman spectroscopy. In this era of cost containment, however, the critical challenge is to demonstrate whether an increase in diagnostic accuracy merits investment in costly technology, regardless of the technique used.

Barrett Esophagus↗

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↗

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↗

Capsule endoscopy regional transit abnormality: a sign of underlying small bowel pathology.

BACKGROUND: Wireless capsule endoscopy is being used increasingly to investigate GI bleeding of obscure etiology and other small bowel abnormalities. Currently, there is no standard for capsule endoscopy image interpretation and classification METHODS: This report describes an abnormality, termed "regional transit abnormality," noted during a review of capsule endoscopic images. Capsule regional transit abnormality simply refers to delayed capsule transit within a segment of small bowel, with or without visualization of a mucosal abnormality. The slowed transit usually is accompanied by mucosal collapse, sometimes with the appearance of the capsule pressing or impacting upon the mucosa. Regional transit abnormality usually persists more than 15 minutes CONCLUSIONS: Capsule regional transit abnormality is considered to be a "red flag" sign that indicates a likelihood of some underlying small bowel pathology.

Adult↗