Double-Clad Fiber-Based Multifunctional Biosensors and Multimodal Bioimaging Systems: Technology and Applications.

Optical fibers have been used to probe various tissue properties such as temperature, pH, absorption, and scattering. Combining different sensing and imaging modalities within a single fiber allows for increased sensitivity without compromising the compactness of an optical fiber probe. A double-clad fiber (DCF) can sustain concurrent propagation modes (single-mode, through its core, and multimode, through an inner cladding), making DCFs ideally suited for multimodal approaches. This study provides a technological review of how DCFs are used to combine multiple sensing functionalities and imaging modalities. Specifically, we discuss the working principles of DCF-based sensors and relevant instrumentation as well as fiber probe designs and functionalization schemes. Secondly, we review different applications using a DCF-based probe to perform multifunctional sensing and multimodal bioimaging.

Balloon catheter-based radiofrequency ablation monitoring in porcine esophagus using optical coherence tomography.

We present a microscopic image guidance platform for radiofrequency ablation (RFA) using a clinical balloon-catheter-based optical coherence tomography (OCT) system, currently used in the surveillance of Barrett's esophagus patients. Our integrated thermal therapy delivery and monitoring platform consists of a flexible, customized bipolar RFA electrode array designed for use with a clinical balloon OCT catheter and a processing algorithm to accurately map the thermal coagulation process. Non-uniform rotation distortion was corrected using a feature tracking-based technique, which enables robust, frame-to-frame analysis of the temporal fluctuation of the complex OCT signal. With proper noise calibration, precise delineation of the thermal therapy zone was demonstrated using cumulative complex differential variance in porcine esophagus ex vivo with the integrated OCT-RFA system, as validated by nitroblue tetrazolium chloride (NBTC) histology. The ability to directly and accurately visualize the thermal coagulation process at high resolution is critical to the precise delivery of thermal energy to a wide range of epithelial lesions.

Radiometric model for coaxial single- and multimode optical emission from double-clad fiber.

Double-clad fibers (DCFs) are versatile waveguides supporting a single-mode core surrounded by a multimode inner cladding. DCFs are increasingly used for multimodal biomedical applications, such as imaging or therapy, for which the core is typically used for coherent illumination and the inner cladding, to support a concurrent modality. Proper optimization is, however, critical to ensure high optical performance and requires accurate modeling of coaxial single- and multimode output beams. In this paper, we present an approach based on geometrical optics and radiometry, which provides a simple and efficient modeling tool for designing and optimizing DCF-based systems. A radiometric definition of single- and multimode output beams in terms of irradiance and radiant intensity allows for the modeling of the energy distribution along the beams' propagation. We confirmed the validity of the model through comparison with experimental measurements and demonstrate the use of the model for optimizing a catheter for concurrent OCT and laser coagulation.

Tissue-like phantoms for quantitative birefringence imaging.

Birefringence imaging, including polarization sensitive optical coherence tomography (PS-OCT), can provide valuable insight into the microscopic structure and organization of many biological tissues. In this paper, we report on a method to fabricate tissue-like birefringence phantoms for such imaging modalities. We utilize the photo-elastic effect, wherein birefringence is induced by stretching a polymer sample after heating it above its glass-transition temperature. The cooled samples stably exhibit homogeneous birefringence, and were assembled into phantoms containing multiple well-defined regions of distinct birefringence. We present planar slab phantoms for microscopy applications and cylindrical phantoms for catheter-based imaging and demonstrate quantitative analysis of the birefringence within individual regions of interest. Birefringence phantoms enable testing, validating, calibrating, and improving PS-OCT acquisition systems and reconstruction strategies.

Collagen Content Limits Optical Coherence Tomography Image Depth in Porcine Vocal Fold Tissue.

OBJECTIVE: Vocal fold scarring, a condition defined by increased collagen content, is challenging to treat without a method of noninvasively assessing vocal fold structure in vivo. The goal of this study was to observe the effects of vocal fold collagen content on optical coherence tomography imaging to develop a quantifiable marker of disease. STUDY DESIGN: Excised specimen study. SETTING: Massachusetts Eye and Ear Infirmary. SUBJECTS AND METHODS: Porcine vocal folds were injected with collagenase to remove collagen from the lamina propria. Optical coherence tomography imaging was performed preinjection and at 0, 45, 90, and 180 minutes postinjection. Mean pixel intensity (or image brightness) was extracted from images of collagenase- and control-treated hemilarynges. Texture analysis of the lamina propria at each injection site was performed to extract image contrast. Two-factor repeated measure analysis of variance and t tests were used to determine statistical significance. Picrosirius red staining was performed to confirm collagenase activity. RESULTS: Mean pixel intensity was higher at injection sites of collagenase-treated vocal folds than control vocal folds (P < .0001). Fold change in image contrast was significantly increased in collagenase-treated vocal folds than control vocal folds (P = .002). Picrosirius red staining in control specimens revealed collagen fibrils most prominent in the subepithelium and above the thyroarytenoid muscle. Specimens treated with collagenase exhibited a loss of these structures. CONCLUSION: Collagen removal from vocal fold tissue increases image brightness of underlying structures. This inverse relationship may be useful in treating vocal fold scarring in patients.

Using attenuation coefficients from optical coherence tomography as markers of vocal fold maturation.

OBJECTIVES/HYPOTHESIS: Optical coherence tomography (OCT) is a promising technology to noninvasively assess vocal fold microanatomy. The goal of this study was to develop a methodology using OCT to identify quantifiable markers of vocal fold development. STUDY DESIGN: In vivo study. METHODS: A two-step process was developed to reproducibly image the midmembranous vocal fold edge of 10 patients younger than 2 years and 10 patients between 11 and 16 years of age using OCT. An image analysis algorithm was implemented to extract OCT-derived A-lines for each patient. These A-lines were divided into three zones according to apparent changes in slope. Relative attenuation coefficients, or tissue- and system-dependent parameters that describe the rate at which optical signal decays, were calculated for each zone. RESULTS: Young patients had distinct relative attenuation coefficients in zone 1 (P < .0001), whereas zones 2 and 3 were indistinct (P = .1129). Older patients had distinct relative attenuation coefficients in zones 1, 2, and 3 (P < .0370). Between age groups, relative attenuation coefficients were different in zones 2 and 3 (P < .0001, P = .0315, respectively) and indistinct in zone 1 (P = .1438). CONCLUSIONS: Relative attenuation coefficients can be used as markers of vocal fold development. Differences in relative attenuation coefficients likely represent changes in extracellular matrix structure within the lamina propria and may become useful for guiding treatment of voice disorders in the pediatric population. LEVEL OF EVIDENCE: NA Laryngoscope, 126:E218-E223, 2016.

Laser tissue coagulation and concurrent optical coherence tomography through a double-clad fiber coupler.

Double-clad fiber (DCF) is herein used in conjunction with a double-clad fiber coupler (DCFC) to enable simultaneous and co-registered optical coherence tomography (OCT) and laser tissue coagulation. The DCF allows a single channel fiber-optic probe to be shared: i.e. the core propagating the OCT signal while the inner cladding delivers the coagulation laser light. We herein present a novel DCFC designed and built to combine both signals within a DCF (>90% of single-mode transmission; >65% multimode coupling). Potential OCT imaging degradation mechanisms are also investigated and solutions to mitigate them are presented. The combined DCFC-based system was used to induce coagulation of an ex vivo swine esophagus allowing a real-time assessment of thermal dynamic processes. We therefore demonstrate a DCFC-based system combining OCT imaging with laser coagulation through a single fiber, thus enabling both modalities to be performed simultaneously and in a co-registered manner. Such a system enables endoscopic image-guided laser marking of superficial epithelial tissues or laser thermal therapy of epithelial lesions in pathologies such as Barrett's esophagus.

Optical coherence tomography for the identification of musculoskeletal structures of the spine: a pilot study.

Adolescent idiopathic scoliosis (AIS) is a complex three-dimensional deformity of the spine requiring in severe cases invasive surgery. Here, we explore the potential of optical coherence tomography (OCT) as a guiding tool for novel fusionless minimally invasive spinal surgeries on an ex vivo porcine model. We show that OCT, despite its limited penetration depth, may be used to precisely locate structures such as growth plate, bone and intervertebral disk using relative attenuation coefficients. We further demonstrate a segmentation algorithm that locates growth plates automatically on en-face OCT reconstructions.

Towards a handheld probe based on optical coherence tomography for minimally invasive spine surgeries.

Minimally invasive surgical (MIS) techniques for the correction of scoliosis are under development. The installation of fusionless implants targeting the vertebral growth plate requires precise identification of spinal micro-structures. During ex vivo studies, we demonstrate that optical coherence tomography (OCT) allows visualization of spinal tissues including the growth plate, the intervertebral disc and the vertebral body. This study aims at designing a handheld probe using OCT and assessing its potential for use in MIS. An OCT handheld probe was built which satisfies criteria for resolution, penetration and field of view required for spinal MIS techniques. Ex vivo images of rat tail and porcine vertebrae enabled differentiating musculoskeletal tissues of the spine (growth plate, intervertebral disc and vertebral body). Pending in vivo studies on porcine models, we evaluated the probe on a human finger and demonstrated its ability to image human tissues at video rate (25 fps) with proper imaging depth and resolution. These preliminary results showed the potential of the OCT probe for dynamic and precise imaging of spinal tissues.