Joseph M. Schmitt

Micromotor endoscope catheter for in vivo, ultrahigh-resolution optical coherence tomography

A distally actuated, rotational-scanning micromotor endoscope catheter probe is demonstrated for ultrahigh-resolution in vivo endoscopic optical coherence tomography (OCT) imaging. The probe permits focus adjustment for visualization of tissue morphology at varying depths with improved transverse resolution compared with standard OCT imaging probes. The distal actuation avoids nonuniform scanning motion artifacts that are present with other probe designs and can permit a wider range of imaging speeds. Ultrahigh-resolution endoscopic imaging is demonstrated in a rabbit with <4-microm axial resolution by use of a femtosecond Cr:forsterite laser light source. The micromotor endoscope catheter probe promises to improve OCT imaging performance in future endoscopic imaging applications.

Characterization of buried glands before and after radiofrequency ablation by using 3-dimensional optical coherence tomography (with videos)

BACKGROUNDnRadiofrequency ablation (RFA) is an endoscopic technique used to eradicate Barretts esophagus (BE). However, such ablation can commonly lead to neosquamous epithelium overlying residual BE glands not visible by conventional endoscopy and may evade detection on random biopsy samples.nnnOBJECTIVEnTo demonstrate the capability of endoscopic 3-dimensional optical coherence tomography (3D-OCT) for the identification and characterization of buried glands before and after RFA therapy.nnnDESIGNnCross-sectional study.nnnSETTINGnSingle teaching hospital.nnnPATIENTSnTwenty-six male and 1 female white patients with BE undergoing RFA treatment.nnnINTERVENTIONSn3D-OCT was performed at the gastroesophageal junction in 18 patients before attaining complete eradication of intestinal metaplasia (pre-CE-IM group) and in 16 patients after CE-IM (post-CE-IM group).nnnMAIN OUTCOME MEASUREMENTSnPrevalence, size, and location of buried glands relative to the squamocolumnar junction.nnnRESULTSn3D-OCT provided an approximately 30 to 60 times larger field of view compared with jumbo and standard biopsy and sufficient imaging depth for detecting buried glands. Based on 3D-OCT results, buried glands were found in 72% of patients (13/18) in the pre-CE-IM group and 63% of patients (10/16) in the post-CE-IM group. The number (mean [standard deviation]) of buried glands per patient in the post-CE-IM group (7.1 [9.3]) was significantly lower compared with the pre-CE-IM group (34.4 [44.6]; P = .02). The buried gland size (P = .69) and distribution (P = .54) were not significantly different before and after CE-IM.nnnLIMITATIONSnA single-center, cross-sectional study comparing patients at different time points in treatment. Lack of 1-to-1 coregistered histology for all OCT data sets obtained in vivo.nnnCONCLUSIONnBuried glands were frequently detected with 3D-OCT near the gastroesophageal junction before and after radiofrequency ablation.

Three-dimensional optical coherence tomography of Barrett’s esophagus and buried glands beneath neosquamous epithelium following radiofrequency ablation

We report three-dimensional (3D) endoscopic microscopy findings in Barretts esophagus, using an endoscopic optical coherence tomography (OCT) system in one patient before and in one patient after radiofrequency ablation (RFA). Findings were compared with those in a normal patient without Barretts esophagus. In the normal patient,findings were of regular flat squamous mucosa with small subepithelial vessels and glands. In the Barretts esophagus patient, findings were of large, densely packed glands with distortion of mucosal architecture. In the post-RFA case, findings were of a small number of isolated glands buried beneath 300-500 microm of neosquamous epithelium and lamina propria. Neosquamous epithelium is a marker of successful ablative therapy, while buried glands may have potential for dysplastic progression and are difficult to detect using conventional methods. These results indicate a potential role of 3D-OCT endoscopic microscopy for follow-up, including subsurface assessment, of ablative treatments for Barretts esophagus.

Extended coherence length megahertz FDML and its application for anterior segment imaging

We present a 1300 nm Fourier domain mode locked (FDML) laser for optical coherence tomography (OCT) that combines both, a high 1.6 MHz wavelength sweep rate and an ultra-long instantaneous coherence length for rapid volumetric deep field imaging. By reducing the dispersion in the fiber delay line of the FDML laser, the instantaneous coherence length and hence the available imaging range is approximately quadrupled compared to previously published MHz-FDML setups, the imaging speed is increased by a factor of 16 compared to previous extended coherence length results. We present a detailed characterization of the FDML laser performance. We demonstrate for the first time MHz-OCT imaging of the anterior segment of the human eye. The OCT system provides enough imaging depth to cover the whole range from the top surface of the cornea down to the crystalline lens.

Structural markers observed with endoscopic 3-dimensional optical coherence tomography correlating with Barrett's esophagus radiofrequency ablation treatment response (with videos)

BACKGROUNDnRadiofrequency ablation (RFA) is effective for treating Barretts esophagus (BE) but often involves multiple endoscopy sessions over several months to achieve complete response.nnnOBJECTIVEnIdentify structural markers that correlate with treatment response by using 3-dimensional (3-D) optical coherence tomography (OCT; 3-D OCT).nnnDESIGNnCross-sectional.nnnSETTINGnSingle teaching hospital.nnnPATIENTSnThirty-three patients, 32 male and 1 female, with short-segment (<3 cm) BE undergoing RFA treatment.nnnINTERVENTIONnPatients were treated with focal RFA, and 3-D OCT was performed at the gastroesophageal junction before and immediately after the RFA treatment. Patients were re-examined with standard endoscopy 6 to 8 weeks later and had biopsies to rule out BE if not visibly evident.nnnMAIN OUTCOME MEASUREMENTSnThe thickness of BE epithelium before RFA and the presence of residual gland-like structures immediately after RFA were determined by using 3-D OCT. The presence of BE at follow-up was assessed endoscopically.nnnRESULTSnBE mucosa was significantly thinner in patients who achieved complete eradication of intestinal metaplasia than in patients who did not achieve complete eradication of intestinal metaplasia at follow-up (257 ± 60 μm vs 403 ± 86 μm; P < .0001). A threshold thickness of 333 μm derived from receiver operating characteristic curves corresponded to a 92.3% sensitivity, 85% specificity, and 87.9% accuracy in predicting the presence of BE at follow-up. The presence of OCT-visible glands immediately after RFA also correlated with the presence of residual BE at follow-up (83.3% sensitivity, 95% specificity, 90.6% accuracy).nnnLIMITATIONSnSingle center, cross-sectional study in which only patients with short-segment BE were examined.nnnCONCLUSIONnThree-dimensional OCT assessment of BE thickness and residual glands during RFA sessions correlated with treatment response. Three-dimensional OCT may predict responses to RFA or aid in making real-time RFA retreatment decisions in the future.

Extended coherence length Fourier domain mode locked lasers at 1310 nm

Fourier domain mode locked (FDML) lasers are excellent tunable laser sources for frequency domain optical coherence tomography (FD-OCT) systems due to their combination of high sweep rates, large tuning ranges, and high output powers. However, conventional FDML lasers provide coherence lengths of only 4-10 mm, limiting their use in demanding applications such as intravascular OCT where coherence lengths of >20 mm are required for optimal imaging of large blood vessels. Furthermore, like most swept lasers, conventional FDML lasers produce only one useable sweep direction per tunable filter drive cycle, halving the effective sweep rate of the laser compared to the filter drive frequency. Here, we demonstrate a new class of FDML laser incorporating broadband dispersion compensation near 1310 nm. Elimination of chromatic dispersion in the FDML cavity results in the generation of forward (short to long wavelength) and backward (long to short wavelength) sweeps with substantially identical properties and coherence lengths of >21 mm. This advance enables long-range, high-speed FD-OCT imaging without the need for optical buffering stages, significantly reducing laser cost and complexity.

Neointimal tissue characteristics following sirolimus-eluting stent implantation: OCT quantitative tissue property analysis

The neointimal tissue characteristics inside sirolimus-eluting stent (SES) were evaluated by optical coherence tomography (OCT) according to follow-up duration. One hundred and thirty-three Optical coherence tomography was performed in 96 patients with 143 SES which were retrospectively included and divided into 2 groups according to follow-up duration: Group 1, <24xa0months (98 stents in 71 patients); Group 2, >24xa0months (35 stents in 25 patients). The neointimal tissue coverage pattern and characteristics were studied using a new OCT analysis system which can quantitatively analyze tissue property by measuring attenuation, backscatter and signal intensity in the region of interest. Using these parameters, a multivariable logistic regression model was constructed to divide neointima into homogenous or heterogeneous type. We defined homogeneous nointima as neointimal tissue having uniform optical properties and does not showing focal variations in backscattering pattern and heterogeneous neointima as neointimal tissue with focally changing optical properties and showing various backscattering patterns. The average time between stent implantation and follow-up OCT imaging was 1.2xa0years in Group 1 and 3.2xa0years in Group 2. The number of neointima covered cross-sections, neointimal thickness, and neointimal area increased significantly with the length of follow-up duration after SES implantation (Pxa0<xa00.01). The incidence of heterogeneous neointima was higher in Group 2 than in Group 1 (Pxa0<xa00.01). Heterogeneous neointima was associated with higher incidence of microvessels (Pxa0=xa00.0023) and lipid rich plaque (Pxa0=xa00.0015) compared with homogeneous neointima. The neointimal tissue characteristics may change over time after SES implantation. The incidence of heterogeneous pattern was higher in the SES group with longer follow-up duration. Microvessels and lipid rich plaques were more frequently observed in neointima with heterogeneous pattern. Neointimal heterogeneity could be an important factor for the late stability of SES.

The Development of OCT

Optical coherence tomography (OCT) enables cross sectional and volumetric imaging of internal structure and pathology in biological tissues. OCT can perform an “optical biopsy”, imaging pathology in situ and in real time without the need for excisional biopsy. OCT imaging has become a standard of care in ophthalmology and is an emerging imaging modality in cardiology, where it provides information that often cannot be obtained by any other means. This chapter reviews the early history of OCT development with an emphasis on basic concepts and the process of technology translation. Early OCT technology and catheter imaging devices as well as advances in imaging speed using swept source/Fourier domain detection are reviewed. The process of clinical translation, beginning with ex vivo imaging and histology, preclinical animal studies and progressing to clinical studies in patients is discussed. The history of commercial intravascular OCT development is also summarized.

Ultrahigh-resolution endoscopic optical coherence tomography

Early detection of gastrointestinal cancer is essential for the patient treatment and medical care. Endoscopically guided biopsy is currently the gold standard for the diagnosis of early esophageal cancer, but can suffer from high false negative rates due to sampling errors. Optical coherence tomography (OCT) is an emerging medical imaging technology which can generate high resolution, cross-sectional images of tissue in situ and in real time, without the removal of tissue specimen. Although endoscopic OCT has been used successfully to identify certain pathologies in the gastrointestinal tract, the resolution of current endoscopic OCT systems has been limited to 10 - 15 m for clinical procedures. In this study, in vivo imaging of the gastrointestinal tract is demonstrated at a three-fold higher resolution (< 5 m), using a portable, broadband, Cr4+:Forsterite laser as the optical light source. Images acquired from the esophagus, gastro-esophageal junction and colon on animal model display tissue microstructures and architectural details at high resolution, and the features observed in the OCT images are well-matched with histology. The clinical feasibility study is conducted through delivering OCT imaging catheter using standard endoscope. OCT images of normal esophagus, Barretts esophagus, and esophageal cancers are demonstrated with distinct features. The ability of high resolution endoscopic OCT to image tissue morphology at an unprecedented resolution in vivo would facilitate the development of OCT as a potential imaging modality for early detection of neoplastic changes.