Norman S. Nishioka

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 Barretts 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, Barretts esophagus was differentiated from normal esophageal mucosa, and esophageal adenocarcinoma was distinguished from normal esophagus and Barretts 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.

Comprehensive volumetric optical microscopy in vivo.

Comprehensive volumetric microscopy of epithelial, mucosal and endothelial tissues in living human patients would have a profound impact in medicine by enabling diagnostic imaging at the cellular level over large surface areas. Considering the vast area of these tissues with respect to the desired sampling interval, achieving this goal requires rapid sampling. Although noninvasive diagnostic technologies are preferred, many applications could be served by minimally invasive instruments capable of accessing remote locations within the body. We have developed a fiber-optic imaging technique termed optical frequency-domain imaging (OFDI) that satisfies these requirements by rapidly acquiring high-resolution, cross-sectional images through flexible, narrow-diameter catheters. Using a prototype system, we show comprehensive microscopy of esophageal mucosa and of coronary arteries in vivo. Our pilot study results suggest that this technology may be a useful clinical tool for comprehensive diagnostic imaging for epithelial disease and for evaluating coronary pathology and iatrogenic effects.

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.

Safety and efficacy of endoscopic spray cryotherapy for Barrett's esophagus with high-grade dysplasia.

BACKGROUND Endoscopic ablation to treat Barretts esophagus (BE) with high-grade dysplasia (HGD) is associated with a decreased incidence of esophageal adenocarcinoma. Endoscopic spray cryotherapy (CRYO) demonstrates promising preliminary data. OBJECTIVE To assess the safety and efficacy of CRYO in BE with HGD. DESIGN Multicenter, retrospective cohort study. SETTING Nine academic and community centers; treatment period, 2007 to 2009. PATIENTS Subjects with HGD confirmed by 2 pathologists. Previous EMR was allowed if residual HGD remained. INTERVENTIONS CRYO with follow-up biopsies. MAIN OUTCOME MEASUREMENTS Complete eradication of HGD with persistent low-grade dysplasia, complete eradication of all dysplasia with persistent nondysplastic intestinal metaplasia, and complete eradication of all intestinal metaplasia. RESULTS Ninety-eight subjects (mean age 65.4 years, 83% male) with BE and HGD (mean length 5.3 cm) underwent 333 treatments (mean 3.4 treatments per subject). There were no esophageal perforations. Strictures developed in 3 subjects. Two subjects reported severe chest pain managed with oral narcotics. One subject was hospitalized for bright red blood per rectum. Sixty subjects had completed all planned CRYO treatments and were included in the efficacy analysis. Fifty-eight subjects (97%) had complete eradication of HGD, 52 (87%) had complete eradication of all dysplasia with persistent nondysplastic intestinal metaplasia, and 34 (57%) had complete eradication of all intestinal metaplasia. Subsquamous BE was found in 2 subjects (3%). LIMITATIONS Nonrandomized, retrospective study with no control group, short follow-up (10.5 months), lack of centralized pathology, and use of surrogate outcome for decreased cancer risk. CONCLUSIONS CRYO is a safe and well-tolerated therapy for BE and HGD. Short-term results suggest that CRYO is highly effective in eradicating HGD.

Diagnosis of Barrett's esophagus using optical coherence tomography.

OCT is a promising optical technology that permits real-time, high-resolution, cross-sectional imaging of tissue during endoscopy. It has been shown to be a highly sensitive and specific means of identifying the presence of SIM. Preliminary studies suggest that OCT is capable of grading dysplasia occurring within BE and has the potential to assist with the staging of superficial malignancies, particularly squamous cell cancers. In the near future, the capabilities of OCT systems are expected to improve with systems capable of much higher resolution and with Doppler capability becoming available.

Optical properties of rat liver between 350 and 2200 nm

Previous investigators have determined the optical properties of the liver at isolated wavelengths using various models of light propagation. In this study we derived coefficients for absorption, scattering, and anisotropy for rat liver between 350 and 2200 nm using measurements of integrated reflectance, transmittance, and on-axis attenuation and a diffusion approximation algorithm to solve the 1-D transport equation. These results were used to estimate the effective attenuation coefficient, penetration depth, and temperature rise induced by laser irradiation. The data should be of value to investigators in the field of tissue optics and developers of photomedical applications involving the liver.

Tethered capsule endomicroscopy enables less invasive imaging of gastrointestinal tract microstructure

Here we introduce tethered capsule endomicroscopy, which involves swallowing an optomechanically engineered pill that captures cross-sectional microscopic images of the gut wall at 30 μm (lateral) × 7 μm (axial) resolution as it travels through the digestive tract. Results in human subjects show that this technique rapidly provides three-dimensional, microstructural images of the upper gastrointestinal tract in a simple and painless procedure, opening up new opportunities for screening for internal diseases.

Comprehensive Microscopy of the Esophagus in Human Patients with Optical Frequency Domain Imaging

BACKGROUND Optical coherence tomography (OCT) is a cross-sectional, high-resolution imaging modality that has been shown to accurately differentiate esophageal specialized intestinal metaplasia (SIM) from gastric cardia at the squamocolumnar junction (SCJ) and diagnose high-grade dysplasia and intramucosal carcinoma in patients with SIM. The clinical utility of OCT has been limited, however, by its inability to acquire images over large areas. OBJECTIVE The aim of this study was to use recently developed high-speed OCT technology, termed optical frequency domain imaging (OFDI), and a new balloon-centering catheter (2.5 cm diameter) to demonstrate the feasibility of large area, comprehensive optical microscopy of the entire distal esophagus (approximately 6.0 cm) in patients. DESIGN A pilot feasibility study. SETTING Massachusetts General Hospital. PATIENTS Twelve patients undergoing routine EGD. RESULTS Comprehensive microscopy of the distal esophagus was successfully performed in 10 patients with the OFDI system and balloon catheter. There were no complications resulting from the imaging procedure. Volumetric data sets were acquired in less than 2 minutes. OFDI images at the SCJ showed a variety of microscopic features that were consistent with histopathologic findings, including squamous mucosa, cardia, SIM with and without dysplasia, and esophageal erosion. LIMITATIONS Inability to obtain direct correlation of OFDI data and histopathologic diagnoses. CONCLUSIONS Comprehensive volumetric microscopy of the human distal esophagus was successfully demonstrated with OFDI and a balloon-centering catheter, providing a wealth of detailed information about the structure of the esophageal wall. This technique will support future studies to compare OFDI image information with histopathologic diagnoses.

Effectiveness of current technology in the diagnosis and management of lower gastrointestinal hemorrhage

Lower gastrointestinal hemorrhage is a common clinical problem for which multiple diagnostic tests and therapeutic interventions have been developed but no optimal approach has been established. We reviewed 107 consecutive patients admitted to the Massachusetts General Hospital for management of acute lower gastrointestinal hemorrhage to determine the effectiveness of diagnostic and management technologies, with particular attention to urgent colonoscopy. Colonoscopy yielded a diagnosis in 90% of patients, provided the opportunity for successful therapy in 9 of 13 patients (69%), and shortened hospital stay. Angiography performed after a scan positive for bleeding was often diagnostic, and angiography provided the means for successful therapy in 5 of 10 patients (50%). Barium enema and sigmoidoscopy had lower clinical yields. Although roles exist for other technologies, colonoscopy is the most convenient and effective first test in the evaluation of patients with significant lower gastrointestinal hemorrhage. Diagnostic yield, therapeutic opportunity, and cost effectiveness are maximized in early studies.

Endoscopic mucosal resection: an improved diagnostic procedure for early gastroesophageal epithelial neoplasms.

Endoscopic mucosal resection (EMR), which is advocated for the treatment of early (superficial) gastroesophageal neoplasms, has also been alluded to represent a superior diagnostic and staging modality. We compared the diagnostic concordance of preceding biopsies with EMR specimens in 31 gastric and 10 esophageal EMRs consisting of 6 low-grade and 12 high-grade dysplasias, 21 intramucosal adenocarcinomas, and 2 submucosal invasive adenocarcinomas. Discrepancies were considered as either major or minor if the histologic grades differed by 2 or more, or by only 1, respectively. Discrepant and concordant cases were compared with regard to the size of lesion (maximum dimension and surface area), number of biopsy fragments, and extent of biopsy sampling (ratio between lesion size and number of biopsy fragments). These same variables were used to evaluate the differences seen between gastric and esophageal cases. Of the 41 cases, 16 (39%) had discrepant diagnoses, including 14 gastric and 2 esophageal neoplasms. A major discrepancy was seen in 2% of the cases (n = 1, gastric) and a minor discrepancy, in 15 cases. All but 2 of the discrepant cases were found to have a higher grade on EMR. The average number of biopsy fragments was 4.4 in both concordant and discrepant groups. The maximal dimension, surface area, and biopsy sampling ratios of the lesion were significantly greater in the discrepant cases than in the concordant cases. The esophageal cases trended toward having smaller size and a significantly extensive biopsy sampling. We conclude that EMR is superior to biopsy for diagnosing superficial gastroesophageal tumors. Discrepancies between the specimens occur in larger lesions (>10 mm) with less extensive biopsy sampling. EMR can substantially modify the diagnostic grade of a lesion and therefore facilitate optimal therapeutic decisions by avoiding undertreatment and overtreatment based on inaccurate grading and staging.