A forward-imaging needle-type optical coherence tomography (OCT) probe with Doppler OCT (DOCT) capability has the potential to solve critical challenges in interventional procedures. A case in point is stereotactic neurosurgery where probes are advanced into the brain based on predetermined coordinates. Laceration of blood vessels in front of the advancing probe is an unavoidable complication with current methods. Moreover, cerebrospinal fluid (CSF) leakage during surgery can shift the brain rendering the predetermined coordinates unreliable. In order to address these challenges, we developed a forward-imaging OCT probe (740 μm O.D.) using a gradient-index (GRIN) rod lens that can provide real-time imaging feedback for avoiding at-risk vessels (8 frames/s with 1024 A-scans per frame for OCT/DOCT dual imaging) and guiding the instrument to specific targets with 12 μm axial resolution (100 frames/s with 160 A-scans per frame for OCT imaging only). The high signal-to-background characteristic of DOCT provides exceptional sensitivity in detecting and quantifying the blood flow within the sheep brain parenchyma in real time. The OCT/DOCT dual imaging also demonstrated its capability to differentiate the vessel type (artery/vein) on rat's femoral vessels. We also demonstrated in ex vivo human brain that the location of the tip of the OCT probe can be inferred from micro-anatomical landmarks in OCT images. These findings demonstrate the suitability of OCT guidance during stereotactic procedures in the brain and its potential for reducing the risk of cerebral hemorrhage.

Optical coherence tomography (OCT) provides high-resolution, cross-sectional imaging of tissue microstructure in situ and in real-time, while fluorescence molecular imaging (FMI) enables the visualization of basic molecular processes. There are great interests in combining these two modalities so that the tissue's structural and molecular information can be obtained simultaneously. This could greatly benefit biomedical applications such as detecting early diseases and monitoring therapeutic interventions. In this research, an optical system that combines OCT and FMI was developed. The system demonstrated that it could co-register en face OCT and FMI images with a 2.4 × 2.4 mm field of view. The transverse resolutions of OCT and FMI of the system are both ~10 μm. Capillary tubes filled with fluorescent dye Cy 5.5 in different concentrations under a scattering medium are used as the phantom. En face OCT images of the phantoms were obtained and successfully co-registered with FMI images that were acquired simultaneously. A linear relationship between FMI intensity and dye concentration was observed. The relationship between FMI intensity and target fluorescence tube depth measured by OCT images was also observed and compared with theoretical modeling. This relationship could help in correcting reconstructed dye concentration. Imaging of colon polyps of APC min mouse model is presented as an example of biological applications of this co-registered OCT/FMI system.

Doppler optical coherence tomography (DOCT) is a functional extension of optical coherence tomography (OCT) and is currently being employed in several clinical arenas to quantify blood flow in vivo. In this study, the objective was to investigate the feasibility of DOCT to image kidney microcirculation, specifically, glomerular blood flow. DOCT is able to capture 3D data sets consisting of a series of cross-sectional images in real time, which enables label-free and non-destructive quantification of glomerular blood flow. The kidneys of adult, male Munich-Wistar rats were exposed through laparotomy procedure after being anesthetized. Following exposure of the kidney beneath the DOCT microscope, glomerular blood flow was observed. The effects of acute mannitol and angiotensin II infusion were also observed. Glomerular blood flow was quantified for the induced physiological states and compared with baseline measurements. Glomerular volume, cumulative Doppler volume, and Doppler flow range parameters were computed from 3D OCT/DOCT data sets. Glomerular size was determined from OCT, and DOCT readily revealed glomerular blood flow. After infusion of mannitol, a significant increase in blood flow was observed and quantified, and following infusion of angiontensin II, a significant decrease in blood flow was observed and quantified. Also, blood flow histograms were produced to illustrate differences in blood flow rate and blood volume among the induced physiological states. We demonstrated 3D DOCT imaging of rat kidney microcirculation in the glomerulus in vivo. Dynamic changes in blood flow were detected under altered physiological conditions demonstrating the real-time imaging capability of DOCT. This method holds promise to allow non-invasive imaging of kidney blood flow for transplant graft evaluation or monitoring of altered renal hemodynamics related to disease progression.

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The defining characteristic of the annulus fibrosus (AF) of the intervertebral disc (IVD) has long been the lamellar structures that consist of highly ordered collagen fibers arranged in alternating oblique angles from one layer to the next. However, a series of recent histologic studies have demonstrated that AF lamellae contain elastin- and type VI collagen-rich secondary “cross-bridge” structures across lamellae. In this study, we use optical coherence tomography (OCT) to elucidate the three-dimensional (3D) morphologies of these translamellar cross-bridge in AF tissues. Mesoscale volumetric images by OCT reveal a highly heterogeneous spatial network and distribution of 3-D translamellar cross-bridges. The results of this study confirm the translamellar cross-bridge is identified as a distinguishable structure, which is laid in the interbundle space of adjacent lamellae and crisscrosses multiple lamellae in the radial direction. In contrast to previously proposed models extrapolated from 2-D sections, results from this current study show that translamellar cross-bridges exist as a complex, interconnected network. We also found much greater variation in lengths of cross-bridges within the interbundle space of lamellae (0.8-1.4 mm from the current study versus 0.3-0.6 mm from 2-D sections). OCT-based 3-D morphology of translamellar cross-bridge provides novel insight into the AF structure.