2D MEMS-based high-speed beam-shifting technique for speckle noise reduction and flow rate measurement in optical coherence tomography.

In this manuscript, a two-dimensional (2D) micro-electro-mechanical system (MEMS)-based, high-speed beam-shifting spectral domain optical coherence tomography (MHB-SDOCT) is proposed for speckle noise reduction and absolute flow rate measurement. By combining a zigzag scanning protocol, the frame rates of 45.2 Hz for speckle reduction and 25.6 Hz for flow rate measurement are achieved for in-vivo tissue imaging. Phantom experimental results have shown that by setting the incident beam angle to ϕ = 4.76° (between optical axis of objective lens and beam axis) and rotating the beam about the optical axis in 17 discrete angular positions, 91% of speckle noise in the structural images can be reduced. Furthermore, a precision of 0.0032 µl/s is achieved for flow rate measurement with the same beam angle, using three discrete angular positions around the optical axis. In-vivo experiments on human skin and chicken embryo were also implemented to further verify the performance of speckle noise reduction and flow rate measurement of MHB-SDOCT.

Differential phase standard-deviation-based optical coherence tomographic angiography for human retinal imaging in vivo.

We present a differential phase standard-deviation (DPSD)-based optical coherence tomographic (OCT) angiography (OCTA) technique to calculate the angiography images of the human retina. The standard deviation was calculated along the depth direction on the differential phase image of two B-scans (from the same position, at different times) to contrast dynamic vascular signals. The performance of a DPSD was verified by both phantom and in vivo experiments. When compared to other OCTA algorithms such as phase variance OCT, speckle variance OCT, and optical microangiography, we showed that a DPSD achieved improved image contrast and higher sensitivity. Furthermore, we also found the improved signal-to-noise ratio and contrast-to-noise ratio of 1.6 dB and 0.5, respectively, in large scanning range images.

Beam-shifting technique for speckle reduction and flow rate measurement in optical coherence tomography.

In this Letter, we propose a beam-shifting optical coherence tomography scheme for speckle reduction and blood flow rate calculation, where variations of the speckle pattern and Doppler angle were generated by parallel shifting of the sample beam incident on the objective lens. The resultant optical coherent tomography images could then be averaged for speckle noise reduction and simultaneously analyzed for flow rate measurement. The performance of the proposed technique was verified by both phantom and in vivo experiments.

High speed, wide velocity dynamic range Doppler optical coherence tomography (Part V): Optimal utilization of multi-beam scanning for Doppler and speckle variance microvascular imaging.

In this paper, a multi-beam scanning technique is proposed to optimize the microvascular images of human skin obtained with Doppler effect based methods and speckle variance processing. Flow phantom experiments were performed to investigate the suitability for combining multi-beam data to achieve enhanced microvascular imaging. To our surprise, the highly variable spot sizes (ranging from 13 to 77 µm) encountered in high numerical aperture multi-beam OCT system imaging the same target provided reasonably uniform Doppler variance and speckle variance responses as functions of flow velocity, which formed the basis for combining them to obtain better microvascular imaging without scanning penalty. In vivo 2D and 3D imaging of human skin was then performed to further demonstrate the benefit of combining multi-beam scanning to obtain improved signal-to-noise ratio (SNR) in microvascular imaging. Such SNR improvement can be as high as 10 dB. To our knowledge, this is the first demonstration of combining different spot size, staggered multiple optical foci scanning, to achieve enhanced SNR for blood flow OCT imaging.

Post-infectious opsoclonus and reversible magnetic resonance imaging changes: a case report and review of the literatures.

PURPOSE: Opsoclonus is a rare neurological disorder in adult. The etiology of opsoclonus includes parainfectious, paraneoplastic, toxic, and metabolic disorders. We reported an old female with post-infectious opsoclonus who had a benign clinical course and reversible brain MRI lesions, and its review of the literature. CASE REPORT: A 67-year-old woman presented with opsoclonus and truncal ataxia for two weeks. The magnetic resonance imaging (MRI) showed the hyperintensity lesions in bilateral medial thalamus, hypothalamus, and tegmentum of pons on Fluid-attenuated inversion recovery (FLAIR) imaging. Investigations of neoplasm and autoimmune disorders showed negative findings. Clinical symptoms subsided in two-week duration and MRI abnormalities also disappeared one month later. CONCLUSION: A benign clinical course and reversible MRI lesions could be found in the patients with postinfectious opsoclonus such as our case. However, detailed investigations and long-term follow-up are needed to exclude paraneoplastic or other systemic and immunological disorders.

Quantification metrics for telangiectasia using optical coherence tomography.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder that causes vascular malformations throughout the body. The most prevalent and accessible of these lesions are found throughout the skin and mucosa, and often rupture causing bleeding and anemia. A recent increase in potential HHT treatments have created a demand for quantitative metrics that can objectively measure the efficacy of new and developing treatments. We employ optical coherence tomography (OCT)-a high resolution, non-invasive imaging modality in a novel pipeline to image and quantitatively characterize dermal HHT lesion behavior over time or throughout the course of treatment. This study is aimed at detecting detailed morphological changes of dermal HHT lesions to understand the underlying dynamic processes of the disease. We present refined metrics tailored for HHT, developed from a pilot study using 3 HHT patients and 6 lesions over the course of multiple imaging dates, totalling to 26 lesion images. Preliminary results from these lesions are presented in this paper alongside representative OCT images. This study provides a new objective method to analyse and understand HHT lesions using a minimally invasive, accessible, cost-effective, and efficient imaging modality with quantitative metrics describing morphology and blood flow.

Real-time en-face Gabor optical coherence tomographic angiography on human skin using CUDA GPU.

We recently proposed an optical coherence tomographic angiography (OCTA) algorithm, Gabor optical coherence tomographic angiography (GOCTA), which can extract microvascular signals from a spectral domain directly with lower computational complexity compared to other algorithms. In this manuscript, we combine a programmable swept source, an OCT complex signal detecting unit, and graphics process units (GPU) to achieve a real-time en-face GOCTA system for human skin microvascular imaging. The programmable swept source can balance the A-scan rate and the spectral tuning range; the polarization-modulation based complex signal detecting unit can double the imaging depth range, and the GPU can accelerate data processing. C++ and CUDA are used as the programming platform where five parallel threads are created for galvo-driving signal generation, data acquisition, data transfer, data processing, and image display, respectively. Two queues (for the raw data and en-face images, respectively) are used to improve the data exchange efficiency among different devices. In this study, the data acquisition time and data processing time for each 3D complex volume (256×304×608 pixels,) are 405.3 and 173.7 milliseconds respectively. To the best of our knowledge, this is the first time to show en-face microvascular images covering 3×3 mm2 at a refresh rate of 2.5 Hz.

Gabor optical coherence tomographic angiography (GOCTA) (Part II): theoretical basis of sensitivity improvement and optimization for processing speed.

We previously proposed a Gabor optical coherence tomography angiography (GOCTA) algorithm for spectral domain optical coherence tomography (SDOCT) to extract microvascular signals from spectral fringes directly, with speed improvement of 4 to 20 times over existing methods. In this manuscript, we explored the theoretical basis of GOCTA with comparison of experimental data using solid and liquid displacement sample targets, demonstrating that the majority of the GOCTA sensitivity advantage over speckle variance based techniques was in the small displacement range (< 10 ∼ 20 µm) of the moving target (such as red blood cells). We further normalized GOCTA signal by root-mean-square (RMS) of original fringes, achieving a more uniform image quality, especially at edges of blood vessels where slow flow could occur. Furthermore, by transecting the spectral fringes and using skipped convolution, the data processing speed could be further improved. We quantified the trade-off in signal-to-noise-ratio (SNR) and contrast-to-noise-ratio (CNR) under various sub-spectral bands and found an optimized condition using 1/4 spectral band for minimal angiography image quality degradation, yet achieving a further 26.7 and 34 times speed improvement on GPU and CPU, respectively. Our optimized GOCTA algorithm has a speed advantage of over 140 times compared to existing speckle variance OCT (SVOCT) method.

Doppler optical coherence tomography for energy seal evaluation and comparison to visual evaluation (Erratum).

The erratum corrects a misspelled author surname.

Doppler optical coherence tomography for energy seal evaluation and comparison to visual evaluation.

Laser energy sealing systems have attracted much attention over the past decade given the general shift in surgical paradigm toward less invasive surgical approaches. Given this, it is paramount to have an objective method with which the quality of energy seals can be evaluated. Current methodologies used for this purpose can be problematic in the evaluation of small vessel seals. A methodology employing Doppler optical coherence tomography (DOCT) for the evaluation of energy seals is introduced. Avian chorioallantoic membrane vessels were subjected to thulium laser irradiation and were then scanned via OCT. Outcomes were classified based on several markers, predominantly the presence or absence of flow postirradiation. Vessel diameter and general morphology were also taken into consideration. Vessels were classified into four groups: seal (29%), rupture (30%), partial seal (19%), and unaffected (22%). All vessels were also evaluated visually by a trained neurovascular surgeon, and these visually classified outcomes were compared with DOCT evaluated outcomes. It was found that whether the vessel was considered sealed or not sealed was dependent on the evaluation method (p = 0.01) where visual classification resulted in 18% more seals than DOCT classification. Further, the specificity of visual classification was found to be strongly dependent on the number of partial seals (p < 0.0001). DOCT has shown to be an indispensable method for the evaluation of energy seals not only solely due to its high velocity resolution but also due to valuable microscopic morphological insight regarding the biological mechanisms responsible for energy sealing.

Optimization of laser osteotomy at 1064 nm using a graphite topical absorber and a nitrogen assist gas jet.

Laser ablation of bone for the purposes of osteotomy is not as well understood as ablation of homogeneous, non-biological materials such as metals and plastics. Ignition times and etch rate can vary during ablation of cortical bone. In this study, we propose the use of two techniques to optimize bone ablation at 1064nm using a coaxial nitrogen jet as an assist gas and topical application of graphite as a highly absorbing chromophore. We show a two order of magnitude reduction in mean time to ignition and variance by using the graphite topical chromophore. We also show that an increase in volumetric flow rate of the assist gas jet does show an initial increase in etch rate, but increased pressure beyond a certain point shows decreased return. This study also demonstrates a 2 nd order relationship between exposure time, volumetric flow rate of nitrogen, and etch rate of cortical bone. The results of this study can be used to optimize the performance of laser ablation systems for osteotomy. This is a companion study to an earlier one carried out by Wong et al. [Biomedical Opt. Express6, 1 (2015)].

Robotic laser osteotomy through penscriptive structured light visual servoing.

PURPOSE: Planning osteotomies is a task that surgeons do as part of standard surgical workflow. This task, however, becomes more difficult and less intuitive when a robot is tasked with performing the osteotomy. In this study, we aim to provide a new method for surgeons to allow for highly intuitive trajectory planning, similar to the way an attending surgeon would instruct a junior. METHODS: Planning an osteotomy, especially during a craniotomy, is performed intraoperatively using a sterile surgical pen or pencil directly on the exposed bone surface. This paper presents a new method for generating osteotomy trajectories for a multi-DOF robotic manipulator using the same method and relaying the penscribed cut path to the manipulator as a three-dimensional trajectory. The penscribed cut path is acquired using structured light imaging, and detection, segmentation, optimization and orientation generation of the Cartesian trajectory are done autonomously after minimal user input. RESULTS: A 7-DOF manipulator (KUKA IIWA) is able to follow fully penscribed trajectories with sub-millimeter accuracy in the target plane and perpendicular to it (0.46 mm and 0.36 mm absolute mean error, respectively). CONCLUSIONS: The robot is able to precisely follow cut paths drawn by the surgeon directly onto the exposed boney surface of the skull. We demonstrate through this study that current surgical workflow does not have to be drastically modified to introduce robotic technology in the operating room. We show that it is possible to guide a robot to perform an osteotomy in much the same way a senior surgeon would show a trainee by using a simple surgical pen or pencil.

Buffer-averaging super-continuum source based spectral domain optical coherence tomography for high speed imaging.

In super-continuum (SC) source based spectral domain optical coherence tomography (SC-SDOCT), the stability of the power spectral density (PSD) has a significant impact on OCT system sensitivity and image signal to noise ratio (SNR). High speed imaging decreases the camera's exposure time, thus each A-scan contained fewer laser pulse excited SC wideband emissions, resulting in a decrease of SNR. In this manuscript, we present a buffer-averaging SC-SDOCT (BASC-SDOCT) to improve the system's performance without losing imaging speed, taking advantage of the excess output power from typical SC sources. In our proposed technique, the output light from SC was passed through a fiber based light buffering and averaging system to improve the PSD stability by averaging 8 SC emissions. The results showed that 6.96 µs of SC emission after buffering and averaging can achieve the same PSD stability equivalent to a longer exposure time of 55.68 µs, despite increasing the imaging speed from 16.8 kHz to 91.9 kHz. The system sensitivity was improved by 8.6 dB, reaching 100.6 dB, which in turn improved SNR of structural imaging, Doppler OCT velocity measurement, and speckle variance OCT (SVOCT) angiographic imaging as demonstrated by phantom and in vivo experiments.

Smart laser osteotomy: integrating a pulsed 1064nm fiber laser into the sample arm of a fiber optic 1310nm OCT system for ablation monitoring.

Real-time depth metrology during material removal via laser ablation is useful in many forms of laser machining. Until now, coaxial optical coherence tomography (OCT) metrology was achieved by the coupling of an OCT imaging beam and ablating beams using a dichroic filter. We present an alternative design with all fiber delivery that is more suitable for surgical laser ablation applications. The novel system design integrates a high peak-power pulsed Yb-doped fiber laser (1064nm) coupled directly into the sample arm of a swept-source OCT system (λc = 1310nm). We measured the OCT signal degradation due to dispersion and attenuation through the ablation fiber laser cavity. Ablation progression is measured in real-time using M-mode OCT. The mean depth targeting error was found to range from 10µm to 80µm in phantom ablation experiments and 21µm to 60µm in bone ablation. A number of issues have been solved, including point-spread function (PSF) peak broadening due to signal delay and dispersion, high bending loss due to dissimilar fiber used throughout the design, and problems due to the extremely high ablation power to swept-source power ratio (> 2×104 peak to average power). To our knowledge, this is the first demonstration of thermal-mediated laser ablation drilling integrated with coaxial OCT imaging through a single-mode, single-cladded output fiber, without using dichroic beam splitters or free-space optic filters anywhere in the optical path and with this high ablation laser power to OCT source power ratio. The removal of bulk optics compared to existing designs opens a new path for compact integration of the entire system. Also, since the ablation laser and OCT feedback system exist along the same fiber path, the need for maintenance and repair are greatly reduced since spatial beam alignment and the potential open-air contamination of optical surfaces are virtually eliminated. We believe that this integrated system is a great candidate for adoption in depth-controlled surgical ablation applications.

Gabor optical coherence tomographic angiography (GOCTA) (Part I): human retinal imaging in vivo.

Recently, parallel high A-line speed and wide field imaging for optical coherence tomography angiography (OCTA) has become more prevalent, resulting in a dramatic increase of data quantity which poses a challenge for real time imaging even for GPU in data processing. In this manuscript, we propose a new OCTA processing technique, Gabor optical coherence tomographic angiography (GOCTA), for label-free human retinal angiography imaging. In spectral domain optical coherence tomography (SDOCT), k-space resampling and Fourier transform (FFT) are required for the entire data set of interference fringes to calculate blood flow information in previous OCTA algorithms, which are computationally intensive. As adults' eye anterior-posterior radii are nearly constant, only 3 A-scan lines need to be processed to obtain the gross orientation of the retina by using a sphere model. Subsequently, the en face microvascular images can be obtained by using the GOCTA algorithm from interference fringes directly without the steps of k-space resampling, numerical dispersion compensation, FFT, and maximum (mean) projection, resulting in a significant improvement of the data processing speed by 4 to 20 times faster than the existing methods. GOCTA is potentially suitable for SDOCT systems in en face preview applications requiring real-time microvascular imaging.

Differential standard deviation of log-scale intensity based optical coherence tomography angiography.

In this paper, a differential standard deviation of log-scale intensity (DSDLI) based optical coherence tomography angiography (OCTA) is presented for calculating microvascular images of human skin. The DSDLI algorithm calculates the variance in difference images of two consecutive log-scale intensity based structural images from the same position along depth direction to contrast blood flow. The en face microvascular images were then generated by calculating the standard deviation of the differential log-scale intensities within the specific depth range, resulting in an improvement in spatial resolution and SNR in microvascular images compared to speckle variance OCT and power intensity differential method. The performance of DSDLI was testified by both phantom and in vivo experiments. In in vivo experiments, a self-adaptive sub-pixel image registration algorithm was performed to remove the bulk motion noise, where 2D Fourier transform was utilized to generate new images with spatial interval equal to half of the distance between two pixels in both fast-scanning and depth directions. The SNRs of signals of flowing particles are improved by 7.3 dB and 6.8 dB on average in phantom and in vivo experiments, respectively, while the average spatial resolution of images of in vivo blood vessels is increased by 21%.

Imaginary part-based correlation mapping optical coherence tomography for imaging of blood vessels in vivo.

We present an imaginary part-based correlation mapping optical coherence tomography (IMcmOCT) technique for in vivo blood vessels imaging. In the conventional correlation mapping optical coherence tomography (cmOCT) method, two adjacent frames of intensity-based structural images are correlated to extract blood flow information and the size of correlation window has to be increased to improve the signal-to-noise ratio of microcirculation maps, which may cause image blur and miss the small blood vessels. In the IMcmOCT method, the imaginary part of a depth-resolved complex analytic signal in two adjacent B-scans is correlated to reconstruct microcirculation maps. Both phantom and in vivo experiments were implemented to demonstrate that the proposed method can provide improved sensitivity for extracting blood flow information in small vessels.

[Culture conditions optimization and high cell density fermentation of recombinant bacteria producing heparinase II from Flavobacterium heparinum].

Heparinase II (Hep II) from Flavobacterium heparinum is an enzyme that could specifically cleave certain sequence of heparin and heparan sulfate. In this work, fermentation conditions of recombinant heparinase II (His-Hep II) producing bacteria were optimized, including initial induction time, inducer (IPTG) concentration, induction temperature and induction time. The optimum conditions were as follows: cultivating recombinant bacteria to exponential prophase under 37 degrees C, then adding IPTG to a final concentration of 0.3 g/L, finally cultivating recombinant bacteria under 20 degrees C for 10 h. The total crude enzyme activity reached 570 U/L. Based on these results, high cell density fermentation of recombinant bacteria was studied. The final OD600 could reach 98 and the total crude enzyme activity of His-Hep II increased to 9 436 U/L.

Renal vascular injury during percutaneous nephrolithotomy and migration of a double-J catheter fragment into pulmonary artery in the following nephrectomy--a case report.

A 60-year-old male underwent percutaneous nephrolithotomy (PCNL) for left renal stone at a community hospital. The surgery was, in general, unremarkable and a double-J ureteral catheter was placed before completion of surgery. Dyspnea, irritability, hypotension and flank pain developed in the recovery room. In addition, pleural effusion and elevation of the left hemidiaphragm were revealed on chest roentgenogram, and mild hypoxemia and respiratory acidosis were also detected by gas analysis. He was transferred to our hospital for further management. After arrival at our hospital, we decided to reintubate the patient and transfer him to the intensive care unit (ICU). There, the vital signs deteriorated, so an emergent laparotomy was performed and left nephrectomy was done because of severe and unmanageable renal hemorrhage. A catheter fragment was found to be missing after left kidney was dissected. During the search for the missing fragment, pulseless electrical activity (PEA) happened. The patient recovered shortly after the use of vasopressors. Postoperatively, a chest X-ray (CXR) taken to search for the missing section of the cather revealed that there was a catheter-like foreign body in the heart, which was also demonstrated by computed tomography (CT) scan. The catheter fragment was quickly removed soon via percutaneous angiography. The patient was discharged 2 weeks later. We present this case with two iatrogenic complications, each in two consecutive renal procedures, to emphasize the importance of vigilance in anesthesia.