Biology subjects

Wang, R. K.

Publications and source records attributed to Wang, R. K..

8 recordsLinked to original sources

bioRxiv2026

DINOCT: robust skin surface localization for robotic noncontact dynamic optical coherence elastography

Noncontact dynamic optical coherence elastography (OCE) can measure the elastic properties of anterior soft tissues. However, applying OCE to skin requires tracking mechanical waves propagating in multiple directions to reconstruct mechanical anisotropy. Robotic scanning is well suited to this task but requires accurate probe positioning, alignment to the surface normal, and precise, repeatable rotation. To ensure phase and polarization stability, polarization-maintaining (PM) fibers can be used, although they introduce stripe and ghost artifacts that can destabilize surface detection. We present DINOCT, a DINO-based method to localize the skin surface from optical coherence tomography (OCT) images that combines self-supervised pretraining with DINO (self-DIstillation with NO labels) and iBOT (image BERT pre-training with Online Tokenizer) objectives, low-rank adaptation, and a lightweight curve decoder. Compared with classical and supervised learning baselines, DINOCT achieved competitive localization accuracy on clean test data with a near-zero spike rate. Among the learned methods, DINOCT achieved the lowest average and maximum values of mean absolute error (MAE) for severe synthetic stress conditions and the lowest catastrophic failure rates on a separate recording with strong PM-fiber artifacts.

bioengineering↗

bioRxiv2025

Multimodal optical imaging and modulation through Smart Dura in non-human primates

Multimodal neural interfaces that integrate electrical and optical functionalities are promising tools for neuroscientific and clinical applications that involve recording and manipulating neuronal activity. However, most technologies for multimodal implementation are largely restricted to small animal models and lack the ability to translate to the larger brains of non-human primates (NHPs). Smart Dura, a recently developed large-scale neural interface for NHPs, enables high-density electrophysiological recordings and broad optical accessibility, providing multiscale information with enhanced spatiotemporal resolution. In this paper, the multimodal capabilities of Smart Dura are demonstrated through integration with multiphoton imaging, optical coherence tomography angiography (OCTA), and intrinsic signal optical imaging (ISOI), as well as optical manipulations such as photothrombotic lesioning and optogenetics. Through the transparent Smart Dura, in vivo fluorescence vascular imaging is achieved down to depths of 200 and 550 m using two-photon and three-photon microscopy, respectively. When combined with simultaneous electrophysiology, Smart Dura also enables assessment of vascular and neural dynamics via OCTA and ISOI, the induction of ischemic stroke, and the application of optogenetic neuromodulation across a wide cortical area of 20 mm in diameter. These capabilities support comprehensive investigations of brain dynamics in NHPs, advancing translational neurotechnology for human applications.

neuroscience↗

bioRxiv2024

Type 2 diabetes remodels collateral circulation and promotes leukocyte adhesion following ischemic stroke

AbstractType 2 diabetes mellitus (T2DM) is associated with impaired leptomeningeal collateral compensation and poor stroke outcome. Neutrophils tethering and rolling on endothelium after stroke can also independently reduce flow velocity. However, the chronology and topological changes in collateral circulation in T2DM is not yet defined. Here, we describe the spatial and temporal blood flow dynamics and vessel remodeling in pial arteries and veins and leukocyte- endothelial adhesion following middle cerebral artery (MCA) stroke using two-photon microscopy in awake control and T2DM mice. Relative to control mice prior to stroke, T2DM mice already exhibited smaller pial vessels with reduced flow velocity. Following stroke, T2DM mice displayed persistently reduced blood flow in pial arteries and veins, resulting in a poor recovery of downstream penetrating arterial flow and a sustained deficit in microvascular flow. There was also persistent increase of leukocyte adhesion to the endothelium of veins, coincided with elevated neutrophils infiltration into brain parenchyma in T2DM mice compared to control mice after stroke. Our data suggest that T2DM-induced increase in chronic inflammation may contribute to the remodeling of leptomeningeal collateral circulation and the observed hemodynamics deficiency that potentiates poor stroke outcome. HighlightsO_LIBlood flow and leukocyte imaging in awake mice by two-photon microscopy before and after stroke under physiological conditions C_LIO_LIT2DM induces collateral remodeling prior to stroke C_LIO_LIT2DM reduces blood flow and impedes recovery in pial arteries and veins after ischemic stroke C_LIO_LIPoor recovery of penetrating arterial flow and sustained deficit in microvascular flow after ischemic stroke in T2DM mice C_LIO_LIT2DM increases persistent leukocyte adhesion to endothelium of veins and elevates neutrophils infiltration into the brain parenchyma after ischemic stroke. C_LI

neuroscience↗

bioRxiv2021

A toolbox for studying cortical physiology in primates

Lesioning and neurophysiological studies have facilitated the elucidation of cortical functions and mechanisms of functional recovery following injury. Clinical translation of such studies is contingent on their employment in non-human primates (NHPs), yet tools for monitoring and modulating cortical physiology are incompatible with conventional NHP lesioning techniques. To address these challenges, we developed a toolbox demonstrated in seven macaques. We introduce the photothrombotic method to induce focal cortical lesions alongside a quantitative model for the design of lesion profiles based on experimental needs. Large-scale ([~]5 cm2) vascular and neural dynamics can be monitored and lesion induction can be validated in vivo with optical coherence tomography angiography and our electrocorticographic array, the latter of which also enables testing stimulation-based interventions. By combining optical and electrophysiological techniques in NHPs, we can enhance our understanding of cortical functions, investigate functional recovery mechanisms, integrate physiological and behavioral findings, and develop treatments for neurological disorders.

neuroscience↗

bioRxiv2021

Multi-modal artificial dura for simultaneous large-scale optical access and large-scaleelectrophysiology in non-human primate cortex

ObjectiveNon-human primates (NHPs) are critical for development of translational neural technologies because of their neurological and neuroanatomical similarities to humans. Large-scale neural interfaces in NHPs with multiple modalities for stimulation and data collection poise us to unveil network-scale dynamics of both healthy and unhealthy neural systems. We aim to develop a large-scale multi-modal interface for NHPs for the purpose of studying large-scale neural phenomena including neural disease, damage, and recovery. ApproachWe present a multi-modal artificial dura (MMAD) composed of flexible conductive traces printed into transparent medical grade polymer. Our MMAD provides simultaneous neurophysiological recordings and optical access to large areas of the cortex (~3 cm2) and is designed to mitigate photo-induced electrical artifacts. The MMAD is the centerpiece of the interfaces we have designed to support electrocorticographic recording and stimulation, cortical imaging, and optogenetic experiments, all at the large-scales afforded by the brains of NHPs. We performed electrical and optical experiments bench-side and in vivo with macaques to validate the utility of our MMAD. Main resultsUsing our MMAD we present large-scale electrocorticography from sensorimotor cortex of three macaques. Furthermore, we validated surface electrical stimulation in one of our animals. Our bench-side testing showed up to 90% reduction of photo-induced artifacts with our MMAD. The transparency of our MMAD was confirmed both via bench-side testing (87% transmittance) and via in vivo imaging of blood flow from the underlying microvasculature using optical coherence tomography angiography. SignificanceOur results indicate that our MMAD supports large-scale electrocorticography, large-scale cortical imaging, and, by extension, large-scale optical stimulation. The MMAD prepares the way for both acute and long-term chronic experiments with complimentary data collection and stimulation modalities. When paired with the complex behaviors and cognitive abilities of NHPs, these assets prepare us to study large-scale neural phenomena including neural disease, damage, and recovery.

neuroscience↗

bioRxiv2020

Selective targeting of non-centrosomal AURKA functions through use of a novel targeted protein degradation tool

Targeted protein degradation tools are becoming a new therapeutic modality, allowing small molecule ligands to be reformulated as heterobifunctional molecules (PROteolysis Targeting Chimeras, PROTACs) that recruit ubiquitin ligases to targets of interest, leading to ubiquitination and destruction of the targets. Several PROTACs against targets of clinical interest have been described, but detailed descriptions of the cell biology modulated by PROTACs are missing from the literature. Here we describe the functional characterization of a PROTAC derived from AURKA inhibitor MLN8237 (alisertib). We demonstrate efficient and specific destruction of both endogenous and overexpressed AURKA by Cereblon-directed PROTACs. At the subcellular level, we find differential targeting of AURKA on the mitotic spindle compared to centrosomes. The phenotypic consequences of PROTAC treatment are therefore distinct from those mediated by alisertib, and in mitotic cells differentially regulate centrosome- and chromatin-based microtubule spindle assembly pathways. In interphase cells PROTAC-mediated clearance of non-centrosomal AURKA modulates the cytoplasmic role played by AURKA in mitochondrial dynamics, whilst the centrosomal pool is refractory to PROTAC-mediated clearance. Our results point to differential sensitivity of subcellular pools of substrate, governed by substrate conformation or localization-dependent accessibility to PROTAC action, a phenomenon not previously described for this new class of degrader compounds.

cell biology↗

bioRxiv2019

Quantifying subclinical and longitudinal microvascular changes following episcleral plaque brachytherapy (EPB) using spectral-domain OCT angiography.

BackgroundI-125 episcleral plaque brachytherapy (EPB) is standard-of-care for globe-conserving treatment of medium-sized choroidal melanomas. Radiation retinopathy is a potential consequence of treatment, characterized by deleterious effects on retinal microvasculature. We investigated the application of Optical Coherence Tomography Angiography (OCTA) for detecting and longitudinally monitoring I-125 episcleral plaque brachytherapy induced radiation retinopathy. MethodsHigh resolution OCTA of the central 3x3mm macula were obtained from I-25 episcleral plaque brachytherapy treated and untreated fellow eyes of 62 patients. Capillary density (vessel skeleton density, VSD) and caliber (vessel diameter index, VDI) were quantified using previously validated semi-automated algorithms. Nonperfusion was also quantified as flow impairment regions (FIR). Exams from treated and fellow eyes obtained pre-treatment and at 6-month, 1-year, and 2-year intervals were compared using generalized estimating equation linear models. Dosimetry maps were used to evaluate spatial correlation between radiation dose and microvascular metrics. ResultsMean time from treatment to last follow-up was 10.8 months. Mean{+/-}SD and median radiation dose at the fovea were 64.5 {+/-} 76 Gy and 32.0 Gy, respectively. Preoperative logMAR (Snellen) mean visual acuity was 0.26 {+/-} 0.05 ([~]20/35) and 0.08 {+/-} 0.02 ([~]20/25) in treated and fellow eyes, respectively. At 6 months, treated eyes had significantly lower VSD (0.147 {+/-} 0.003 vs 0.155 {+/-} 0.002; p = 0.023) and higher FIR (1.95 {+/-} 0.176 vs 1.45 {+/-} 0.099; p = 0.018) compared to fellow eyes. There was a significant decrease in VSD and a corresponding increase in FIR even for treated eyes without clinically identifiable retinopathy at 6 months. VDI was significantly higher in treated eyes than in fellow eyes at 2 years (2.93 {+/-} 0.022 vs 2.84 {+/-} 0.016; p = 0.002). Microvascular changes were spatially correlated with a radiation gradient of 85-250 Gy across the fovea. ConclusionsOCTA can be used to quantify and monitor EPB induced radiation, and can detect vascular abnormalities even in the absence of clinically observable retinopathy. OCTA may therefore be useful in investigating treatment interventions that aim to delay EPB-induced radiation retinopathy.

scientific communication and education↗

bioRxiv2018

Generating perfusion maps from structural optical coherence tomography with artificial intelligence

Despite advances in artificial intelligence (AI), its application in medical imaging has been burdened and limited by expert-generated labels. We used images from optical coherence tomography angiography (OCTA), a relatively new imaging modality that measures retinal blood flow, to train an AI algorithm to generate flow maps from standard optical coherence tomography (OCT) images, exceeding the ability and bypassing the need for expert labeling. Deep learning was able to infer flow from single structural OCT images with similar fidelity to OCTA and significantly better than expert clinicians (P < 0.00001). Our model allows generating flow maps from large volumes of previously collected OCT data in existing clinical trials and clinical practice. This finding demonstrates a novel application of AI to medical imaging, whereby subtle regularities between different modalities are used to image the same body part and AI is used to generate detailed inferences of tissue function from structure imaging.

neuroscience↗