Lamellar keratoplasty using position-guided surgical needle and M-mode optical coherence tomography

Deep anterior lamellar keratoplasty (DALK) is an emerging surgical technique for the restoration of corneal clarity and vision acuity. The big-bubble technique in DALK surgery is the most essential procedure that includes the air injection through a thin syringe needle to separate the dysfunctional region of the cornea. Even though DALK is a well-known transplant method, it is still challenged to manipulate the needle inside the cornea under the surgical microscope, which varies its surgical yield. Here, we introduce the DALK protocol based on the position-guided needle and M-mode optical coherence tomography (OCT). Depth-resolved 26-gage needle was specially designed, fabricated by the stepwise transitional core fiber, and integrated with the swept source OCT system. Since our device is feasible to provide both the position information inside the cornea as well as air injection, it enables the accurate management of bubble formation during DALK. Our results show that real-time feedback of needle end position was intuitionally visualized and fast enough to adjust the location of the needle. Through our research, we realized that position-guided needle combined with M-mode OCT is a very efficient and promising surgical tool, which also to enhance the accuracy and stability of DALK

Deep learning for quantitative motion tracking based on optical coherence tomography

Optical coherence tomography (OCT) is a cross-sectional imaging modality based on low coherence light interferometry. OCT has been widely used in diagnostic ophthalmology and has found applications in other biomedical fields such as cancer detection and surgical guidance. In the Laboratory of Biophotonics Imaging and Sensing at New Jersey Institute of Technology, we developed a unique needle OCT imager based on a single fiber probe for breast cancer imaging. The needle OCT imager with sub-millimeter diameter can be inserted into tissue for minimally invasive in situ breast imaging. OCT imaging provides spatial resolution similar to histology and has the potential to become a device to perform virtual biopsy to fast and accurate breast cancer diagnosis, because abnormal breast tissue and normal breast tissue have different characteristics in OCT image. The morphological features of OCT image are related to the microscopic structure of the tissue and the speckle pattern in OCT image is related to cellular/subcellular optical properties of the tissue. In addition, depth attenuation of OCT signal depends on the scattering and absorption properties of the tissue. However, the above described OCT image features are at different spatial scales and it is challenging for human visualization to effectively recognize these features for tissue classification. Particularly, our needle OCT imager, given its simplicity and small form factor, does not have a mechanical scanner for beam steering and relies on manual scan to generate 2D images. The nonconstant translation speed of the probe in manual scanning inevitably introduces distortion artifacts in OCT imaging, which further complicates the tissue characterization task.] OCT images of tissue samples provide comprehensive information about the morphology of normal and unhealthy tissue. Image analysis of tissue morphology can help cancer researchers develop a better understanding of cancer biology. Classification of tissue images and recovering distorted OCT images are two common tasks in tissue image analysis. In this master thesis project, a novel deep learning approach is investigated to extract beam scanning speed from different samples. Furthermore, a novel technique is investigated and tested to recover distorted OCT images. The long-term goal of this study is to achieve robust tissue classification for breast cancer diagnosis, based on a simple single fiber OCT instrument. The deep learning network utilized in this study depends on Convolutional Neural Network (CNN) and Naïve Bayes Classifier. For image retrieval, we used algorithms that extract, represent and match common features between images. The CNN network achieved accuracy of 97% in tissue type and scanning speed classification, while the image retrieval algorithms achieved very high-quality recovered image compared to the reference image

Endoscopic Optical Coherence Tomography: Design and Application

This thesis presents an investigation on endoscopic optical coherence tomography (OCT). As a noninvasive imaging modality, OCT emerges as an increasingly important diagnostic tool for many clinical applications. Despite of many of its merits, such as high resolution and depth resolvability, a major limitation is the relatively shallow penetration depth in tissue (about 2∼3 mm). This is mainly due to tissue scattering and absorption. To overcome this limitation, people have been developing many different endoscopic OCT systems. By utilizing a minimally invasive endoscope, the OCT probing beam can be brought to the close vicinity of the tissue of interest and bypass the scattering of intervening tissues so that it can collect the reflected light signal from desired depth and provide a clear image representing the physiological structure of the region, which can not be disclosed by traditional OCT. In this thesis, three endoscope designs have been studied. While they rely on vastly different principles, they all converge to solve this long-standing problem. A hand-held endoscope with manual scanning is first explored. When a user is holding a hand- held endoscope to examine samples, the movement of the device provides a natural scanning. We proposed and implemented an optical tracking system to estimate and record the trajectory of the device. By registering the OCT axial scan with the spatial information obtained from the tracking system, one can use this system to simply ‘paint’ a desired volume and get any arbitrary scanning pattern by manually waving the endoscope over the region of interest. The accuracy of the tracking system was measured to be about 10 microns, which is comparable to the lateral resolution of most OCT system. Targeted phantom sample and biological samples were manually scanned and the reconstructed images verified the method. Next, we investigated a mechanical way to steer the beam in an OCT endoscope, which is termed as Paired-angle-rotation scanning (PARS). This concept was proposed by my colleague and we further developed this technology by enhancing the longevity of the device, reducing the diameter of the probe, and shrinking down the form factor of the hand-piece. Several families of probes have been designed and fabricated with various optical performances. They have been applied to different applications, including the collector channel examination for glaucoma stent implantation, and vitreous remnant detection during live animal vitrectomy. Lastly a novel non-moving scanning method has been devised. This approach is based on the EO effect of a KTN crystal. With Ohmic contact of the electrodes, the KTN crystal can exhibit a special mode of EO effect, termed as space-charge-controlled electro-optic effect, where the carrier electron will be injected into the material via the Ohmic contact. By applying a high voltage across the material, a linear phase profile can be built under this mode, which in turn deflects the light beam passing through. We constructed a relay telescope to adapt the KTN deflector into a bench top OCT scanning system. One of major technical challenges for this system is the strong chromatic dispersion of KTN crystal within the wavelength band of OCT system. We investigated its impact on the acquired OCT images and proposed a new approach to estimate and compensate the actual dispersion. Comparing with traditional methods, the new method is more computational efficient and accurate. Some biological samples were scanned by this KTN based system. The acquired images justified the feasibility of the usage of this system into a endoscopy setting. My research above all aims to provide solutions to implement an OCT endoscope. As technology evolves from manual, to mechanical, and to electrical approaches, different solutions are presented. Since all have their own advantages and disadvantages, one has to determine the actual requirements and select the best fit for a specific application.</p

Microscopy with ultraviolet surface excitation for rapid slide-free histology.

Histologic examination of tissues is central to the diagnosis and management of neoplasms and many other diseases, and is a foundational technique for preclinical and basic research. However, commonly used bright-field microscopy requires prior preparation of micrometre-thick tissue sections mounted on glass slides, a process that can require hours or days, that contributes to cost, and that delays access to critical information. Here, we introduce a simple, non-destructive slide-free technique that within minutes provides high-resolution diagnostic histological images resembling those obtained from conventional haematoxylin-and-eosin-histology. The approach, which we named microscopy with ultraviolet surface excitation (MUSE), can also generate shape and colour-contrast information. MUSE relies on ~280-nm ultraviolet light to restrict the excitation of conventional fluorescent stains to tissue surfaces, and it has no significant effects on downstream molecular assays (including fluorescence in situ hybridization and RNA-seq). MUSE promises to improve the speed and efficiency of patient care in both state-of-the-art and low-resource settings, and to provide opportunities for rapid histology in research

Dual beam swept source optical coherence tomography for microfluidic velocity measurements

Microfluidic flows are an increasing area of interest used for “lab-on-a-chip” bioanalytical techniques, drug discovery, and chemical processing. This requires optical, non-invasive flow-visualization techniques for characterising microfluidic flows. Optical Coherence Tomography (OCT) systems can provide three-dimensional imaging through reasonably-opaque materials with micrometre resolution, coupled to a single optical axis point using optical fibre cables. Developed for imaging the human eye, OCT has been used for the detection of skin cancers and endoscopically in the human body. Industrial applications are growing in popularity including for the monitoring of bond-curing in aerospace, for production-line non-destructive-testing, and for medical device manufacturing and drug encapsulation monitoring. A dual beam Optical Coherence Tomography system has been developed capable of simultaneously imaging microfluidic channel structures, and tracking particles seeded into the flow to measure high velocity flows, using only a single optical access point. This is achieved via a dual optical fibre bundle for light delivery to the sample and a custom high-speed dual channel OCT instrument using an akinetic sweep wavelength laser. The system has 10 μm resolution in air and a sweeping rate of 96 kHz. This OCT system was used to monitor microfluidic flows in 800 μm deep test chips and Poiseuille flows were observed

Optical coherence tomography (OCT) - guided ophthalmic therapy

In this work, we demonstrate OCT-based guidance of two ophthalmic therapies, subretinal injection and selective retina therapy (SRT). Firstly, the “SMART,” a hand-held robotic surgical device actively guided by a common-path OCT (CP-OCT) distal sensor, improves in two aspects for being applied to subretinal injection: (i) A high-performance fiber probe based on high index epoxy lensed-fiber to enhance the CP-OCT retinal image quality; (ii) Automated retinal layer identification and tracking : retinal layer boundaries are tracked using convolutional neural network (CNN)-based segmentation for accurate subretinal injection guidance. It is shown that high index epoxy lensed-fiber probe improves the SNR and retinal image quality of the CP-OCT system. We propose and implement real-time retinal boundary tracking of A-scan OCT images using CNNs for accurate localization of a surgical tool tip. Unwanted axial motions of the surgical tools are compensated by a piezo-electric linear motor based on the retinal boundary tracking. A CNN-based CP-OCT distal sensor successfully tracks retinal boundaries, especially the PR/CH boundary for subretinal injection, and automatically guides the needle’s axial position in real-time. The micro-scale depth targeting accuracy of our system shows its promising possibility for clinical application. We also propose and demonstrate SRT monitoring based on speckle variance OCT (svOCT) for dosimetry control. M-scans of a phantom, ex vivo bovine iris, and ex vivo bovine retina are obtained by a swept-source OCT system during laser pulses irradiation. SvOCT images are calculated as interframe intensity variance of the sequence, and they show abrupt speckle variance change induced by laser pulse irradiation. The axially averaged svOCT signals show a sharp peak corresponding to each laser pulse, and the peak values are proportional to irradiated laser pulse energy. For the ex vivo retinal study, microscopic images of treated spots are obtained before and after removing the upper neural retinal layer to assess the damage in both RPE and neural layers. Spatial and temporal temperature distributions in the retina are numerically calculated in a 2D retinal model using COMSOL Multiphysics. We find that the svOCT peak values have a reliable correlation with the degree of retinal lesion formation. The temperature at the neural retina and RPE is estimated from the svOCT peak values using numerically calculated temperature, which is consistent with the observed lesion creation

Experimental characterization of the twin-eye laser mouse sensor

This paper proposes the experimental characterization of a laser mouse sensor used in some optical mouse devices. The sensor characterized is called twin-eye laser mouse sensor and uses the Doppler effect to measure displacement as an alternative to optical flow-based mouse sensors. The experimental characterization showed similar measurement performances to optical flow sensors except in the sensitivity to height changes and when measuring nonlinear displacements, where the twin-eye sensor offered better performance. The measurement principle of this optical sensor can be applied to the development of alternative inexpensive applications that require planar displacement measurement and poor sensitivity to -axis changes such as mobile robotics.The authors acknowledge the support of the Government of Catalonia (Comissionat per a Universitats i Recerca, Departament d’Innovació, Universitats i Empresa) and the European Social Fund