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Introduction: An optimal placement of bone conduction implants can provide more efficient mechanical transmission to the cochlea if placed in regions with greater bone column density. The aim of this study was to test this hypothesis and to determine the clinical potential of preoperative bone column density assessment for optimal implant placement. Methods: Five complete cadaver heads were scanned with quantitative computed tomography imaging to create topographic maps of bone density based on the column density index (CODI). Laser Doppler vibrometry was used to measure cochlear promontory acceleration under bone conduction stimulation in different locations on the temporal bone, using a bone-anchored hearing aid transducer at frequencies ranging from 355 Hz to 10 kHz. Results: We found a statistically significant association between CODI levels and the accelerance of the cochlear promontory throughout the frequency spectrum, with an average increase of 0.6 dB per unit of CODI. The distance between the transducer and the cochlear promontory had no statistically significant effect on the overall spectrum. Discussion: We highlight the importance of bone column density in relation to the mechanical transmission efficiency of bone conduction implants. It may be worthwhile to consider column density in preoperative planning in clinical practice.

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This study investigates the water flow characteristics on a solid surface with nanoscale compared to a normal solid surface. The experiment uses a high-speed video system and Fiber-optic Laser Doppler Velocimetry to measure the flow condition of the droplet and velocity distribution profile in the inclined surface flow of the open channel, respectively. The results showed that the movement speed of water droplets on the nanoscale surface was about 2 times faster than on the normal surface. The mean error of each velocity profile was 0.6%. The results reveal that the velocity profile is not significantly influenced by whether the flume bottom is coated with nanoscale material or not in the inclined surface flow of the open channel.

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SIGNIFICANCE: The development of a technique allowing for non-invasive measurement of retinal blood flow (RBF) in humans is needed to understand many retinal vascular diseases (pathophysiology) and evaluate treatment with potential improvement of blood flow. AIM: We developed and validated an absolute laser Doppler velocimeter (LDV) based on an adaptive optical fundus camera that provides simultaneously high-definition images of the fundus vessels and absolute maximal red blood cells (RBCs) velocity to calculate the absolute RBF. APPROACH: This new absolute LDV is combined with the adaptive optics (AO) fundus camera (rtx1, Imagine Eyes©, Orsay, France) outside its optical wavefront correction path. A 4-s recording includes 40 images, each synchronized with two Doppler shift power spectra. Image analysis provides a vessel diameter close to the probing beam, and the velocity of the RBCs in the vessels are extracted from the Doppler spectral analysis. A combination of these values gives an average of the absolute RBF. RESULTS: An in vitro experiment consisting of latex microspheres flowing in water through a glass capillary to simulate a blood vessel and in vivo measurements on six healthy humans was done to assess the device. In the in vitro experiment, the calculated flow varied between 1.75 and 25.9 µL / min and was highly correlated (r2 = 0.995) with the flow imposed by a syringe pump. In the in vivo experiment, the error between the flow in the parent vessel and the sum of the flow in the daughter vessels was between -11 % and 36% (mean ± sd, 5.7 ± 18.5 % ). RBF in the main temporal retinal veins of healthy subjects varied between 0.9 and 13.2 µL / min. CONCLUSIONS: The AO LDV prototype allows for the real-time measurement of absolute RBF derived from the retinal vessel diameter and the maximum RBCs velocity in that vessel.

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Laser Doppler velocimetry estimates tissue perfusion providing a record of microvascular blood flow. Patients with heart disease or diabetes mellitus have impaired microvascular perfusion leading to impaired wound healing. Aged garlic extract (AGE) has a positive effect on vascular elasticity. This study aimed to assess the effect of long-term treatment with AGE on cutaneous tissue perfusion. A total of 122 patients with Framingham Risk Score ≥ 10 were randomised in a double-blinded manner to placebo or 2400 mg AGE daily for 1 year and monitored. Cutaneous microcirculation was measured at 0 and 12 months using laser Doppler velocimetry. A repeated measures analysis of variance (ANOVA) with a Greenhouse-Geisser correction determined that mean post-occlusive reactive hyperaemia differed significantly between time points. The mean percent change between the two time points 0 and 12 months was 102, 64 (174, 15)% change for AGE and 78, 62 (107, 92)% change for the placebo group (F[1, 120] = 5. 95, P < 0.016), 12 months of AGE increases the microcirculation in patients with an increased risk for cardiovascular events estimated using the Framingham risk score. Increased microcirculation could hypothetically facilitate wound healing.

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We present a novel calibration method for a multi-view laser Doppler speed sensing (MLDSS) system. In contrast with the traditional method where only the laser geometry is independently calibrated, the proposed method simultaneously optimizes all the laser parameters and directly associates the parameters with a motion sensing model. By jointly considering the consistency among laser Doppler velocimetry, the laser geometry and a visual marker tracking system, the proposed calibration method further boosts the accuracy of MLDSS. We analyzed the factors influencing the precision, and quantitatively evaluated the efficiency of the proposed method on several data sets.

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The purpose of this paper is to show the feasibility of grasping force control by feeding back signals of the developed micro-laser Doppler velocimeter (µ-LDV) and by discriminating whether a grasped object is slipping or not. LDV is well known as a high response surface velocity sensor which can measure various surfaces-such as metal, paper, film, and so on-thus suggesting the potential application of LDV as a slip sensor for grasping various objects. However, the use of LDV as a slip sensor has not yet been reported because the size of LDVs is too large to be installed on a robotic fingertip. We have solved the size problem and enabled the performance of a feasibility test with a few-millimeter-scale LDV referred to as micro-LDV (µ-LDV) by modifying the design which was adopted from MEMS (microelectromechanical systems) fabrication process. In this paper, by applying our developed µ-LDV as a slip sensor, we have successfully demonstrated grasping force control with three target objects-aluminum block, wood block, and white acrylic block-considering that various objects made of these materials can be found in homes and factories, without grasping force feedback. We provide proofs that LDV is a new promising candidate slip sensor for grasping force control to execute target grasping.

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We report the use of ultrasound modulated optical tomography (UOT) with heterodyne parallel detection to locally sense and image blood flow deep inside a highly scattering medium. We demonstrate that the UOT signal is sensitive to the speed of the blood flow in the ultrasound focus and present an analytical model that relates UOT signals to the optical properties (i. e. scattering coefficient, anisotropy, absorption, and flow speed) of the blood and the background medium. We found an excellent agreement between the experimental data and the analytical model. By varying the integration time of the camera in our setup, we were able to spatially resolve blood flow in a scattering medium with a lateral resolution of 1.5 mm.

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The eye offers a unique opportunity for the non-invasive exploration of cardiovascular diseases. Optical angiography in the retina requires sensitive measurements, which hinders conventional full-field laser Doppler imaging schemes. To overcome this limitation, we used digital holography to perform laser Doppler perfusion imaging of human retina with near-infrared light. Two imaging channels with a slow and a fast CMOS camera were used simultaneously for real-time narrowband measurements, and offline wideband measurements, respectively. The beat frequency spectrum of optical interferograms recorded with the fast (up to 75 kHz) CMOS camera was analyzed by short-time Fourier transformation. Power Doppler images drawn from the Doppler power spectrum density qualitatively revealed blood flow in retinal vessels over 512 × 512 pixels covering 2.4 × 2.4 mm2 on the retina with a temporal resolution down to 1.6 ms. The sensitivity to lateral motion as well as the requirements in terms of sampling frequency are discussed.

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We propose and experimentally prove an algorithm for demodulation of interferometric signals, modified for use in a totally implantable hearing aid device. A fiber optic configuration, which generates two quasi-quadrature signals by a passive 3x3 coupler, for a non-contact detection of the middle ear ossicle vibration is employed. We simulated the ossicle vibration and large movements and demonstrated the effectiveness of the algorithm to compensate changes of the signal DC values and the phase shift introduced by the coupler. Applying the proposed algorithm we obtained the output signal stability better than 0.5 dB, and the system equivalent input noise of about 31 dB (A) SPL @ 1 kHz.

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Thrombosis is a significant issue for cardiovascular device development and use. While thrombosis models are available, very few are device-related and none have been thoroughly validated experimentally. Here, we introduce a surface adherent platelet transport equation into a continuum model to account for the biomaterial interface/blood interaction. Using a rotating disc system and polyurethane-urea material, we characterize steady and pulsatile flow fields using laser Doppler velocimetry. In vitro measurements of platelet adhesion are used in combination with the LDV data to provide further experimental validation. The rotating disc system is computationally studied using the device-induced thrombosis model with the surface platelet adherent transport equation. The results indicate that the flow field is in excellent agreement to the experimental LDV data and that the platelet adhesion simulations are in good agreement with the in vitro platelet data. These results provide good evidence that this transport equation can be used to express the relationship between blood and a biomaterial if the correct platelet adhesion characteristics are known for the biomaterial. Further validation is necessary with other materials.

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OBJECTIVES: The present study aimed to examine hypoperfusion in response to epinephrine following the administration of a local anaesthetic. The concentration of epinephrine that causes maximal hypoperfusion, the spread of hypoperfusion in the tissue and the time to the stabilization of hypoperfusion were investigated. METHODS: Blood perfusion was monitored using laser Doppler velocimetry and laser speckle contrast imaging of random-pattern advancement flaps (1 × 4 cm) or intact skin on the pig flank. Epinephrine was either injected cumulatively (0.1, 1.0, 10 or 100 µg/ml) after injecting 20 mg/ml lidocaine, to determine the concentration response, or given as a single dose (12.5 µg/ml epinephrine+20 mg/ml lidocaine). Control experiments were performed with saline or lidocaine (without epinephrine). RESULTS: Increasing concentrations of epinephrine resulted in a gradual decrease in skin perfusion, approaching a minimum after injecting 10 µg/ml. The area of hypoperfusion was 12 mm in radius, and the time from the injection to the stabilization of hypoperfusion was approximately 120 s. After the administration of 10 µg/ml epinephrine in flaps with small pedicle, 25% blood perfusion still remained. CONCLUSIONS: Local anaesthetic with an epinephrine concentration of approximately 10 µg/ml appears to be adequate for vasoconstriction before surgery. Incisions were required to be delayed only for 2 min following local anaesthetic with epinephrine in pigs. The remaining 25% blood perfusion observed after the administration of epinephrine supports the use of epinephrine in flaps with a small pedicle. Obviously, these experimental findings must be clinically assessed before being considered for infiltration anaesthesia during plastic surgery procedures.

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We present a novel active-passive path-length encoded (APPLE) swept source Doppler optical coherence tomography (DOCT) approach, enabling three-dimensional velocity vector reconstruction of moving particles without prior knowledge of the orientation of motion. The developed APPLE DOCT setup allows for non-invasive blood flow measurements in vivo and was primarily designed for quantitative human ocular blood flow investigations. The system's performance was demonstrated by in vitro flow phantom as well as in vivo retinal vessel bifurcation measurements. Furthermore, total retinal blood flow - a biomarker aiding in diagnosis and monitoring of major ocular diseases such as glaucoma, diabetic retinopathy or central/branch retinal vein occlusion - was determined in the eyes of healthy human volunteers.

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A phase gradient angiography (PGA) method is proposed for optical coherence tomography (OCT). This method allows the use of phase information to map the microvasculature in tissue without the correction of bulk motion and laser trigger jitter induced phase artifacts. PGA can also be combined with the amplitude/intensity to improve the performance. Split-spectrum technique can further increase the signal to noise ratio by more than two times. In-vivo imaging of human retinal circulation is shown with a 70 kHz, 840 nm spectral domain OCT system and a 200 kHz, 1050 nm swept source OCT system. Four different OCT angiography methods are compared. The best performance was achieved with split-spectrum amplitude and phase-gradient angiography.

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Transitional and turbulent flow through a simplified medical device model is analyzed as part of the FDA's Critical Path Initiative, designed to improve the process of bringing medical products to market. Computational predictions are often used in the development of devices and reliable in vitro data is needed to validate computational results, particularly estimations of the Reynolds stresses that could play a role in damaging blood elements. The high spatial resolution of laser Doppler velocimetry (LDV) is used to collect two component velocity data within the FDA benchmark nozzle model. Two flow conditions are used to produce flow encompassing laminar, transitional, and turbulent regimes, and viscous stresses, principal Reynolds stresses, and turbulence intensities are calculated from the measured LDV velocities. Axial velocities and viscous stresses are compared to data from a prior inter-laboratory study conducted with particle image velocimetry. Large velocity gradients are observed near the wall in the nozzle throat and in the jet shear layer located in the expansion downstream of the throat, with axial velocity changing as much as 4.5 m/s over 200 µm. Additionally, maximum Reynolds shear stresses of 1000-2000 Pa are calculated in the high shear regions, which are an order of magnitude higher than the peak viscous shear stresses (<100 Pa). It is important to consider the effects of both viscous and turbulent stresses when simulating flow through medical devices. Reynolds stresses above commonly accepted hemolysis thresholds are measured in the nozzle model, indicating that hemolysis may occur under certain flow conditions. As such, the presented turbulence quantities from LDV, which are also available for download at https://fdacfd.nci.nih.gov/ , provide an ideal validation test for computational simulations that seek to characterize the flow field and to predict hemolysis within the FDA nozzle geometry.

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We present measurements of total retinal blood flow in healthy volunteers using a three beam Doppler optical coherence tomography (D-OCT) technique. This technology has the advantage of a precise determination of the flow vector without the use of any a-priori information on the vessel geometry. Circular D-OCT scans around the optic disc were recorded and venous as well as arterial total blood flow was determined and compared for each subject. The reproducibility of the method was assessed in 6 subjects by repeated measurements. Only small deviations of around 6% between the measurements were found which indicates the high precision of the proposed method.

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We developed a miniature quantitative optical coherence elastography (qOCE) instrument with an integrated Fabry-Perot force sensor, for in situ elasticity measurement of biological tissue. The technique has great potential for biomechanics modeling and clinical diagnosis. We designed the fiber-optic qOCE probe that was used to exert a compressive force to deform tissue at the tip of the probe. Using the space-division multiplexed optical coherence tomography (OCT) signal detected by a spectral domain OCT engine, we were able to quantify the probe deformation that was proportional to the force applied, and to quantify the tissue deformation corresponding to the external stimulus. Simultaneous measurement of force and displacement allowed us to extract Young's modulus of biological tissue. We experimentally calibrated our qOCE instrument, and validated its effectiveness on tissue mimicking phantoms and biological tissues.

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Numerous in vitro systems have previously been developed and employed for studying the effects of hemodynamics on endothelial cell (EC) dysfunction. In the majority of that work, accurate flow quantification (e.g., uniformity of the flow over the ECs) remains elusive and wall shear stress (WSS) quantifications are determined using theoretical relationships (without considering the flow channel aspect ratio effects). In addition, those relationships are not applicable to flows other than steady laminar cases. The present work discusses the development of a novel hemodynamic flow system for studying the effects of various well-quantified flow regimes over ECs. The current work presents a novel hemodynamic flow system applying the concept of a parallel plate flow chamber (PPFC) with live microscopy access for studying the effects of quantified WSS on ECs. A range of steady laminar, pulsatile (carotid wave form) and low-Reynolds number turbulent WSSs were quantified through velocity field measurements by a laser Doppler velocimetry (LDV) system, to validate the functionality of the current hemodynamic flow system. Uniformity of the flow across the channel width can be analyzed with the current system (e.g., the flow was uniform across about 65-75% of the channel width for the steady cases). The WSS obtained from the experiments had higher values in almost all of the cases when compared to the most commonly-used theoretical solution (9% < error < 16%), whereas another relationship, which considers the channel dimensions, had better agreement with the experimental results (1% < error < 8%). Additionally, the latter relationship predicted the uniform flow region in the PPFC with an average difference of <5% when compared to the experimental results. The experimental data also showed that the WSS at various locations (D, E and F) at the test section differed by less than 4% for the laminar cases representing a fully developed flow. WSS was also determined for a low-Re (Re = 2750) turbulent flow using (1) the Reynolds shears stress and (2) the time-averaged velocity profile gradient at the wall, with a good agreement (differences <16%) between the two where the first method returned a higher value than the second. Porcine aortic endothelial cell (PAEC) viability in the system and morphological cell response to laminar WSS of about 11 dyne/cm(2), were observed. These results provide performance validation of this novel in vitro system with many improved features compared to previous similar prototypes for investigation of flow effects on ECs. The integration of the LDV technique in the current study and the comparison of the results with those from theory revealed that great care must be taken when using PPFCs since the commonly used theoretical relation for laminar steady flows is unable to predict the flow uniformity (which may introduce significant statistical bias in biological studies) and the predicted WSS was subjected to greater error when compared to a more comprehensive equation presented in the current work. Moreover, application of the LDV technique in the current system is essential for studies of more complex cases, such as disturbed flows, where the WSS cannot be predicted using theoretical or numerical modelling methods.

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Microscale quantification of cilia-driven fluid flow is an emerging area in medical physiology, including pulmonary and central nervous system physiology. Cilia-driven fluid flow is most completely described by a three-dimensional, three-component (3D3C) vector field. Here, we generate 3D3C velocimetry measurements by synthesizing higher dimensional data from lower dimensional measurements obtained using two separate optical coherence tomography (OCT)-based approaches: digital particle image velocimetry (DPIV) and dynamic light scattering (DLS)-OCT. Building on previous work, we first demonstrate directional DLS-OCT for 1D2C velocimetry measurements in the sub-1 mm/s regime (sub-2.5 inch/minute regime) of cilia-driven fluid flow in Xenopus epithelium, an important animal model of the ciliated respiratory tract. We then extend our analysis toward 3D3C measurements in Xenopus using both DLS-OCT and DPIV. We demonstrate the use of DPIV-based approaches towards flow imaging of Xenopus cerebrospinal fluid and mouse trachea, two other important ciliary systems. Both of these flows typically fall in the sub-100 µm/s regime (sub-0.25 inch/minute regime). Lastly, we develop a framework for optimizing the signal-to-noise ratio of 3D3C flow velocity measurements synthesized from 2D2C measures in non-orthogonal planes. In all, 3D3C OCT-based velocimetry has the potential to comprehensively characterize the flow performance of biological ciliated surfaces.

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Ripasudil (K-115) is a novel Rho kinase inhibitor with a potent intraocular pressure-lowering effect. However, it is unclear whether ripasudil affects the retinal blood flow (RBF). We investigated the effect of ripasudil on feline retinal microcirculation. Ripasudil (5 µM, 50 µM or 5 mM; n = 5 each concentration) or vehicle (PBS; n = 5) was injected intravitreally. The vessel diameter (D) and blood velocity (V) were measured by laser Doppler velocimetry simultaneously in the first-order retinal arterioles and the RBF was calculated. The measurements started 5 min before the injection and were performed every 10 min for 120 min. After the intravitreal injection, the retinal circulatory parameters did not change significantly in PBS or 5 µM of ripasudil. The blood V and RBF increased significantly compared to baseline, whereas the vessel D did not change significantly in 50 µM and 5 mM of ripasudil. The V in 50 µM, and the V and RBF in 5 mM of ripasudil significantly increased compared to those in PBS. Intravitreal administration of ripasudil increased the blood V and RBF in cats, suggesting that ripasudil has the potential to improve the retinal blood flow.

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To improve the reproducibility of photocoagulation, the ability to quantitatively monitor the thermal change of laser-irradiated retinal tissue is required. Recently, optical coherence tomography has enabled non-invasive and non-contact monitoring of the tissue structural changes during laser irradiation. To further improve the capability of this technique, a method is proposed to measure tissue displacement by simultaneously using Doppler phase shifts and correlation coefficients. The theoretical approach for this method is described, and its performance is experimentally confirmed and evaluated. Finally, lateral and axial displacements in the laser-irradiated retinal tissues of an enucleated porcine eye are observed. The proposed method is found to be useful for further understanding the direct thermal response of laser-irradiated retinal tissue.