Two models better than one.
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Barrett Esophagus↗
Biomedical subjects
N S Nishioka
Publications and source records attributed to N S Nishioka.
Diagnosis of specialized intestinal metaplasia by optical coherence tomography.
BACKGROUND AND AIMS: Optical coherence tomography (OCT) is an imaging technique that produces high-resolution cross-sectional images in vivo. The aim of this study was to establish the sensitivity and specificity of OCT for diagnosing specialized intestinal metaplasia (SIM). METHODS: OCT was used to image the stomach and esophagus of 121 patients. A total of 288 biopsy-correlated OCT images were acquired. OCT criteria for SIM were formulated by analyzing 75 images of SIM. The SIM image criteria were retrospectively tested by applying them to images of gastric, squamous, SIM, and cardiac epithelium. The criteria were then tested prospectively to determine the sensitivity and specificity of OCT for diagnosing SIM. RESULTS: OCT images of SIM are characterized by (1) absence of the layered structure of normal squamous epithelium and the vertical "pit and crypt" morphology of gastric mucosa, (2) disorganized architecture with inhomogeneous tissue contrast and an irregular mucosal surface, and (3) presence of submucosal glands. These criteria were 100% sensitive and 93% specific for SIM when applied retrospectively and 97% sensitive and 92% specific when tested prospectively. CONCLUSIONS: OCT is highly sensitive and specific for SIM and may aid in the diagnosis and surveillance of this preneoplastic lesion.
Adult↗
Long-term effects of photodynamic therapy on fluorescence spectroscopy in the human esophagus.
Clinical interest in laser-induced fluorescence (LIF) spectroscopy and photodynamic therapy (PDT) is growing rapidly and may ultimately lead to close parallel use of these techniques. However, variations in LIF due to photosensitizer retention as well as tissue damage and healing processes may interfere with autofluorescence-based diagnostic methods. We have investigated the compatibility of these two techniques by quantifying PDT-induced changes in LIF in the human esophagus. Fluorescence spectra were collected endoscopically at excitation wavelengths (lambda ex) of 337, 400 and 410 nm in 32 patients. Measurements were performed immediately before and after PDT treatment with porfimer sodium and during follow-up procedures. In the months following PDT regions of reepithelialized squamous showed reduced autofluorescence in comparison with untreated squamous regions (P = 0.0007). Photosensitizer fluorescence was undetectable with lambda ex = 337 nm during follow-up procedures, whereas for lambda ex = 400 and 410 nm porfimer sodium fluorescence was noted for nearly a year after treatment. Therefore, residual photosensitizer fluorescence is likely to affect certain LIF-based diagnostic techniques during a period when patients are at high risk for tumor recurrence. Modification of LIF systems and/or the use of alternative photosensitizers may be required to optimize the detection of lesions in the post-PDT patient. Given the potential of LIF as a method for surveillance following cancer therapy, further investigation of the compatibility of specific LIF approaches with cancer pharmaceuticals may be warranted.
Esophageal Neoplasms↗
High-resolution imaging of the human esophagus and stomach in vivo using optical coherence tomography.
BACKGROUND: Optical coherence tomography is a new, high spatial-resolution, cross-sectional imaging technique. We investigated the ability of optical coherence tomography to provide detailed images of subsurface structures in the upper gastrointestinal (GI) tract. METHODS: Optical coherence tomography was performed during routine upper GI endoscopy on 32 patients including 20 patients with Barrett's esophagus. An endoscopic mucosal biopsy was obtained immediately after imaging and was used for histopathologic correlation. RESULTS: Optical coherence tomography provided clear delineation of layers of the normal human esophagus extending from the epithelium to the longitudinal muscularis propria. Gastric mucosa was differentiated from esophageal mucosa, Barrett's esophagus was differentiated from normal esophageal mucosa, and esophageal adenocarcinoma was distinguished from normal esophagus and Barrett's esophagus. CONCLUSIONS: Optical coherence tomography allows visualization of the subsurface architectural morphology of the upper GI tract. The diagnostic information provided by this new imaging modality suggests that it may be a useful adjunct to endoscopy.
Anatomy, Cross-Sectional↗
Optical coherence tomography in the gastrointestinal tract.
Optical coherence tomography (OCT) is a high-resolution, cross-sectional optical imaging technique that allows in situ imaging of tissue by measuring back-reflected light. OCT provides images in real time with a resolution approaching that of conventional histopathology, but without the need for tissue removal. OCT imaging can be performed endoscopically to visualize gastrointestinal tissue using a fiberoptic catheter passed through the instrument channel of a conventional endoscope. The resolution of OCT allows visualization of the different layers of gastrointestinal epithelium and the differentiation of Barrett's epithelium from normal gastric and squamous mucosa. OCT has also been used to image esophageal adenocarcinoma and colonic polyps. Recent developments include Doppler OCT, spectroscopic OCT, and ultrahigh-resolution OCT, which can visualize nuclei within single cells. Although still in its infancy as a clinical tool, OCT currently provides high-resolution images over the same imaging depth as conventional mucosal biopsy, and may prove to be a useful and minimally invasive technique for evaluating gastrointestinal tissue, particularly for early neoplastic changes.
Digestive System↗
Mucosal exposure to light during routine endoscopy.
BACKGROUND: The spectral irradiance delivered by a variety of gastrointestinal endoscopes was measured as a function of wavelength and used to estimate the amount of light delivered to the mucosal surface during routine endoscopic procedures. METHODS: Spectral irradiances from seven different endoscopes were measured using a commercial spectroradiometer calibrated against a National Institute of Standards and Technology traceable source. RESULTS: The largest maximum irradiance was 8.0 W/cm2 obtained from an endoscope used in transillumination mode. In the typical viewing mode, the largest maximum irradiance measured was 1.6 W/cm2. The majority of the light energy delivered by these gastrointestinal endoscopes was in the visible wavelength region (400 to 700 nm). DISCUSSION: The measurements revealed surprisingly high light exposures in the visible wavelength range. In fact, the estimated tissue exposures can exceed by 40-fold the standards established for skin exposure to light set forth by the American National Standards Institute. Because gastrointestinal endoscopy is widely viewed to be safe, it is probable that the gastrointestinal tract has significant tolerance to light exposure.
Calibration↗
Burn wound assessment in porcine skin using indocyanine green fluorescence.
BACKGROUND: An accurate assessment of deep dermal burns within the first week after burn is still an unresolved clinical problem. Infrared-excited fluorescence of indocyanine green was examined as a method of early determination of burn depth. METHODS: Burns of varying depths were placed on the paraspinal region, flank, and abdomen of swine using a heated brass block. Fluorescence images of the burns were recorded 1, 24, 48, and 72 hours later. RESULTS: The ratio of fluorescence in 64 burn wounds relative to adjacent normal tissue identified wounds that healed and did not heal within 21 days with an accuracy of 100%, after accounting for the age of the burn. Higher fluorescence ratios were observed in newly placed burns relative to older burns having comparable depths. CONCLUSION: Deep partial-thickness burns were differentiated from deep dermal full-thickness burns in a porcine skin burn model independent of body location. Diagnosis was possible between 1 and 72 hours after injury.
Animals↗
Influence of light delivery on photodynamic synovectomy in an antigen-induced arthritis model for rheumatoid arthritis.
BACKGROUND AND OBJECTIVE: Minimally invasive synovectomy techniques have been unsuccessful due to lack of selectivity. The purpose of this study was to evaluate the potential of photodynamic therapy to destroy diseased synovium in an antigen-induced arthritis model. STUDY DESIGN/MATERIALS AND METHODS: Three sets of experiments evaluated the biodistribution and treatment effects of Photofrin (PF) in rabbits with bilateral knee antigen-induced arthritis. The first set of experiments evaluated the biodistribution of PF in articular tissues of 30 rabbits from 6-72 hours after systemic injection of 2 mg/kg. In the second series of experiments, light was delivered to the knee joint via cleaved optical fibers, whereas for the third, light was delivered via a 600 microm diffusion tip fiber. Tissues were harvested at 2 and 4 weeks posttreatment. RESULTS: The biodistribution experiments demonstrated maximal uptake in inflamed synovium at 48 hours and a lack of uptake in normal tissues. With bare cleaved fibers, necrosis was observed in one specimen at 2 weeks and was absent in all specimens at 4 weeks. In the third experiment, synovial necrosis was observed in 3 of 7 specimens at 2 weeks and 3 of 8 at 4 weeks. No damage to articular cartilage or periarticular tissues was seen with either mode of light delivery. CONCLUSION: These studies indicate that selective destruction of synovium can be achieved with PF and suggest that optimization of light delivery techniques will play an important role in development of this new technique.
Analysis of Variance↗
Comparison of pulsed CO2 laser ablation at 10.6 microm and 9.5 microm.
BACKGROUND AND OBJECTIVE: The pulsed CO2 laser has received attention because of its successful application to dermatologic surgery and burn debridement surgery. Despite impressive results, tissue removal using pulsed CO2 laser irradiation has not been optimized. We examined the ablation processes by performing mass removal and thermal injury experiments at wavelengths where tissue water is the primary absorber (10.6 microm), and where water and collagen have comparable absorption (9.5 microm). STUDY DESIGN/MATERIALS AND METHODS: Samples of porcine reticular dermis were irradiated with 180-ns laser pulses at either wavelength. Tissue removal was measured using a digital balance. Thermal injury was assessed using a microscope with a calibrated reticle after hematoxylin and eosin staining. RESULTS: Tissue removal using 10.6-microm radiation resulted in a heat of ablation of 3,740 J/g, an ablation threshold of 1.15 J/cm2, and a zone of thermal injury of 53 microm. By contrast, tissue removal using 9.5-microm radiation resulted in a heat of ablation of 3,330 J/g, an ablation threshold of 1.47 J/cm2, and a zone of thermal injury of 34 microm. The differences in ablation threshold and thermal injury were statistically significant. CONCLUSION: Pulsed CO2 laser irradiation at 9.5 microm removes tissue more efficiently and with a smaller zone of thermal injury than at 10.6 microm.
Animals↗
Drug, light, and oxygen: a dynamic combination in the clinic.
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Aminolevulinic Acid↗
Colonic polyp differentiation using time-resolved autofluorescence spectroscopy.
BACKGROUND: Steady-state autofluorescence spectroscopy has been examined previously as a technique for distinguishing polyp types during colonoscopy. Although time-resolved methods have shown promise for tissue diagnosis in vitro, they have never been applied endoscopically. The aim of this study was to examine the feasibility of performing time-resolved autofluorescence spectroscopy in vivo and to determine the diagnostic accuracy of the technique as applied to colonic dysplasia. METHODS: A time-resolved spectrometer was used to measure the spectrally resolved transient decay of laser-induced autofluorescence emission from colonic tissue in vivo. RESULTS: Seventeen patients with 24 polyps (13 adenomatous, 11 non-adenomatous) were studied. The autofluorescence decay from adenomas was faster than that from non-adenomas. The measured decay time provided a means of distinguishing adenomas from non-adenomas with a sensitivity of 85%, a specificity of 91%, a positive predictive value of 92%, and a negative predictive value of 83%. CONCLUSIONS: Time-resolved autofluorescence spectroscopy is a promising optical diagnostic technique for determining polyp types in vivo.
Adenomatous Polyps↗
Initial experience with a real-time video processor for enhancing endoscopic image contrast.
BACKGROUND: An initial experience using a digital video processor to enhance contrast in endoscopic images in real-time is described. METHODS: Endoscopic images were examined with a system using locally adaptive processing to balance variations in illumination and sharpen fine features in real-time. For comparison, indigo carmine dye, a popular exogenous contrast agent, was applied to one patient. RESULTS: In general, contrast-enhanced images appeared to contain more mucosal detail, with reduced glare and features in shadowed areas revealed. When used in conjunction with indigo carmine, the enlarged crypt openings in an aberrant crypt focus were visible, the first such detection in vivo without the use of magnifying endoscopy. CONCLUSIONS: Real-time video contrast enhancement during endoscopic procedures appears to provide excellent mucosal detail and improve contrast in a clinically useful manner.
Endoscopes↗
Carbon dioxide laser ablation with immediate autografting in a full-thickness porcine burn model.
OBJECTIVE: To compare the long-term clinical and histologic outcome of immediate autografting of full-thickness burn wounds ablated with a high-power continuous-wave CO2 laser to sharply débrided wounds in a porcine model. SUMMARY BACKGROUND DATA: Continuous-wave CO2 lasers have performed poorly as tools for burn excision because the large amount of thermal damage to viable subeschar tissues precluded successful autografting. However, a new technique, in which a high-power laser is rapidly scanned over the eschar, results in eschar vaporization without significant damage to underlying viable tissues, allowing successful immediate autografting. METHODS: Full-thickness paravertebral burn wounds measuring 36 cm2 were created on 11 farm swine. Wounds were ablated to adipose tissue 48 hours later using either a surgical blade or a 150-Watt continuous-wave CO2 laser deflected by an x-y galvanometric scanner that translated the beam over the tissue surface, removing 200 microm of tissue per scan. Both sites were immediately autografted and serially evaluated clinically and histologically for 180 days. RESULTS: The laser-treated sites were nearly bloodless. The mean residual thermal damage was 0.18+/-0.05 mm. The mean graft take was 96+/-11% in manual sites and 93+/-8% in laser sites. On postoperative day 7, the thickness of granulation tissue at the graft-wound bed interface was greater in laser-debrided sites. By postoperative day 180, the manual and laser sites were histologically identical. Vancouver scar assessment revealed no differences in scarring at postoperative day 180. CONCLUSIONS: Long-term scarring, based on Vancouver scar assessments and histologic evaluation, was equivalent at 6 months in laser-ablated and sharply excised sites. Should this technology become practical, the potential clinical implications include a reduction in surgical blood loss without sacrifice of immediate engraftment rates or long-term outcome.
Animals↗
Biodistribution of indocyanine green in a porcine burn model: light and fluorescence microscopy.
BACKGROUND: Infrared-excited fluorescence of intravenously administered indocyanine green (ICG) is being used as a method of early determination of burn depth. METHODS: Fluorescence microscopy and tissue fluorescence were recorded in a porcine burn model and correlated to burn severity and age. RESULTS: Recently placed superficial burns show significant fluorescence compared with adjacent normal tissue as a result of a strong inflammatory reaction in the superficial dermis with minimal vascular occlusion. The magnitude of the inflammatory reaction decreases with time. For deeper burns, vascular occlusion prevents transport of ICG into the burn and the intensity of ICG fluorescence in burn eschar is negligible. CONCLUSION: The intensity of ICG fluorescence measured at the surface of the wound for burns of similar age was shown to decrease exponentially with the depth of the burn. The enhanced fluorescence of partial-thickness burns is attributable to increased permeability, and the decreased signal associated with deeper injuries is attributable to vascular occlusion. These results suggest that it is possible to differentiate burns that will heal spontaneously with minimal granulation from those that will not by measuring the intensity of ICG fluorescence.
Animals↗
Characterization of tissue ablation with a continuous wave holmium laser.
BACKGROUND AND OBJECTIVE: The pulsed holmium laser is a promising tool for tissue ablation but possesses some limitations. For example, it is capable of producing significant mechanical damage in certain tissues in the form of fissures and fractures. Because longer pulse durations should reduce mechanical damage, this study examined the tissue effects produced by a prototype continuous wave holmium laser. STUDY DESIGN/MATERIALS AND METHODS: A prototype liquid nitrogen cooled holmium operating at 2.12 microns was used. The heat of ablation and ablation threshold were determined using a mass loss technique. Fresh pig skin was irradiated in air or under saline, and prepared for histologic analysis. Hemostasis was qualitatively assessed in vivo during incisions made in the skin, liver, and small intestine. RESULTS: Threshold radiant exposure and heat of ablation were calculated from the mass loss measurements to be 191 J/cm2 with a 95% confidence interval of -80-440 J/cm2. Residual thermal damage in skin ranged from 390 to 690 microns in saline and from 390 to 490 microns in air. Excellent hemostasis was achieved in all incisions. CONCLUSION: Using appropriate irradiation parameters, the continuous wave holmium laser produces tissue effects suitable for a general use surgical instrument. In addition, the laser source could become compact and inexpensive when diode-pumped and direct diode devices become available.
Air↗
Thermodynamic response of soft biological tissues to pulsed infrared-laser irradiation.
The physical mechanisms that achieve tissue removal through the delivery of short pulses of high-intensity infrared laser radiation, in a process known as laser ablation, remain obscure. The thermodynamic response of biological tissue to pulsed infrared laser irradiation was investigated by measuring and analyzing the stress transients generated by Q-sw Er:YSGG (lambda = 2.79 microns) and TEA CO2 (lambda = 10.6 microns) laser irradiation of porcine dermis using thin-film piezoelectric transducers. For radiant exposures that do not produce material removal, the stress transients are consistent with thermal expansion of the tissue samples. The temporal structure of the stress transients generated at the threshold radiant exposure for ablation indicates that the onset of material removal is delayed with respect to irradiation. Once material removal is achieved, the magnitude of the peak compressive stress and its variation with radiant exposure are consistent with a model that considers this process as an explosive event occurring after the laser pulse. This mechanism is different from ArF- and KrF-excimer laser ablation where absorption of ultraviolet radiation by the collagenous tissue matrix leads to tissue decomposition during irradiation and results in material removal via rapid surface vaporization. It appears that under the conditions examined in this study, explosive boiling of tissue water is the process that mediates the ablation event. This study provides evidence that the dynamics and mechanism of tissue ablation processes can be altered by targeting tissue water rather than the tissue structural matrix.
Animals↗
Effects of laser versus scalpel tenolysis in the rabbit flexor tendon.
The use of surgical lasers has been shown to decrease adhesion formation as compared with scalpel control groups in various surgical procedures. The potential benefits of laser technology have not been assessed in the treatment of adherent tendons. The current study was designed to first develop a reliable and reproducible model for consistent adhesion formation following flexor tendon trauma. The second goal was to compare the effects of laser tenolysis procedures on tendon gliding with those of traditional scalpel tenolysis. In phase I, the adhesion-induction model utilized bilateral standardized crush- abrasion injuries to the hind limb digital flexor tendons of New Zealand White rabbits. Following 4 weeks of immobilization, the animals were sacrificed, and peritendoneal adhesions were assessed biomechanically. A significantly higher maximal force was required to extract the adherent tendons from the foot as compared with nontraumatized control tendons. In phase II, six groups of animals underwent the same standardized tendon trauma. Four weeks later the rabbits were randomly assigned to undergo either CO2 laser or holmium:YAG laser tenolysis on one foot. Scalpel lysis was used on the contralateral foot and served as an intraindividual control. Biomechanical assessment was performed at 1, 2, and 4 weeks following tenolysis. Significantly less force was required to extract the treated tendons at 1 and 2 weeks following holmium:YAG laser tenolysis when compared with scalpel or CO2 laser tenolysis. After 4 weeks, differences between holmium:YAG and CO2 laser and scalpel treatment were no longer significant. Extracted tendons were pulled apart to failure, and no difference in breaking strength was noted between groups. We conclude that holmium:YAG laser tenolysis results in easier tendon gliding as compared with scalpel or CO2 laser tenolysis at early time points. Laser tenolysis does not affect intrinsic tendon strength.
Anesthesia, General↗
Reflectance spectroscopy of pancreatic microcirculation.
A technique employing diffuse reflectance spectroscopy (DRS) is described to assess and mirror dynamic changes of pancreatic tissue perfusion. An especially designed reflectance spectrophotometer was initially used to derive the quantitative relation between hemoglobin concentration ([Hb]) and reflectance measurements in vitro. Over a wide range of scattering related to the medium in which the measurements were made (scattering coefficient: 6.5-13 cm-1), a close, direct correlation existed with a slope of 0.376 +/- 0.012. In Sprague-Dawley rats under general anesthesia, the pancreas was isolated in situ and perfused with graded infusions of hemoglobin solutions. A correlation, comparable to the in vitro setting, was found between a [Hb] of 0 and 14 g/dl in the perfusate with slopes of 0.0037 and 0.0035. Changes in perfusion induced by adrenergic drugs produced changes in hemoglobin oxygen saturation and [Hb] that correspond with measured alterations of systemic arterial pressure and aortic blood flow. We conclude that diffuse reflectance spectroscopy reliably provides data on intrapancreatic hemoglobin oxygen saturation and [Hb] that can be a valuable tool for minimally invasive on-line evaluation of these aspects of pancreatic perfusion in the rat. This newly designed device is superior to previously used ones in that it analyzes the entire spectrum and therefore can account for changes in scattering that are very likely to occur with pathophysiological alterations such as edema formation.
Animals↗