Biology subjects

Bharadwaj, S.

Publications and source records attributed to Bharadwaj, S..

5 recordsLinked to original sources

bioRxiv2026

Supervised 3D Virtual Fluorescence and Pseudo-H&E Staining of Fresh Bulk Tissues via Multimodal qOBM and Fluorescence Microscopy

We introduce a multimodal microscope that combines quantitative oblique back-illumination microscopy (qOBM) with wide-field epi-fluorescence deconvolution microscopy to acquire intrinsically co-registered phase and fluorescence volumes of fresh, bulk tissue. Using paired qOBM phase and DAPI fluorescence images of fresh ex vivo mouse brain tissue, we train a supervised conditional generative adversarial network (cGAN) to predict DAPI-like nuclear contrast from the structural information encoded in the phase images. Results not only demonstrate high-fidelity image translation but also show improved imaging depth and more homogeneous staining. Additionally, we combine the qOBM phase contrast with captured or virtual fluorescence nuclear images to produce volumetric pseudo-H&E representations of fresh tissue, enabling a supervised approach for achieving robust virtual histological staining. This work paves the way for virtual fluorescence imaging of many more structural targets and supervised virtual histological staining of thick, unaltered, bulk tissues ex vivo and potentially in vivo. Such capabilities could have significant implications for biological research as well as for point-of-care, intraoperative, and other clinical applications.

bioengineering↗

bioRxiv2026

Distinct Roles of Working Memory and Inhibitory Control in Speech-in-Noise Perception

Difficulty perceiving speech in noise is the primary complaint of patients seeking hearing healthcare, even absent overt losses in audiometric thresholds. Yet current clinical practice largely focuses on sensory function while ignoring the potentially outsized effects of executive function on everyday suprathreshold listening. Speech perception in noise depends on the dynamic interplay between the fidelity of sensory coding along the auditory pathway and higher-order top-down cognitive processes that support goal-directed listening, both of which can independently change across the lifespan. Here we examined how two subcomponents of executive function, working memory and inhibitory control, vary across the adult lifespan and contribute to speech-in-noise performance. Two hundred participants aged 18 to 73 with normal hearing thresholds were tested on a validated online auditory psychophysics platform. Working memory was assessed with an n-back task and inhibitory control with an auditory Stroop task. Participants then performed two speech-in-noise tasks: a modified rhyme test emphasizing sensory coding through energetic masking at the cochlea, and a matrix sentence task emphasizing executive function through informational masking. Age significantly affected performance on both tasks. Aging was associated with reduced inhibitory control (increased Stroop cost) but no significant effect on working memory. Regression analyses revealed that both working memory and inhibitory control predicted performance on the informational masking task, whereas only inhibitory control predicted performance on the energetic masking task. These findings underscore the critical role of executive function in everyday suprathreshold listening and support including cognitive measures in clinical assessments of hearing difficulties.

neuroscience↗

bioRxiv2026

Tumors accumulate expanded GATA3-dependent tissue Tregs

Targeting Tregs is a potential strategy to improve cancer therapies. However, which Tregs accumulate in response to tumoral processes, and how tumors affect their phenotype, is poorly understood. Here we show that tumor Tregs are equivalent to effector tissue Tregs in steady state organs. We used a mouse model of intestinal neoplasia to demonstrate that one early event in carcinogenesis is sufficient to induce local accumulation of Tregs resembling human tumor Tregs. Treg accumulation was driven by TCR-dependent oligoclonal expansion of tissue Tregs with an effector Treg phenotype. Treg expansion was independent of CCR8, IL33R and CD137, which were previously linked to tumor Treg. In contrast, GATA3 was required for effector tissue Tregs and for their expansion in response to neoplasia. Our findings identify GATA3-dependent clonal expansion of effector tissue Tregs as a key event in promoting tumor growth. HighlightsO_LIAn early tumorigenic event alone drives accumulation of effector tissue Tregs C_LIO_LITregs in tumors are phenotypically akin to effector tissue Tregs C_LIO_LIThe accumulation of Tregs is driven by TCR-dependent oligoclonal expansion C_LIO_LIGATA3 controls tumor-promoting effector tissue Tregs C_LI

immunology↗

bioRxiv2025

Label-Free, Real-Time, In Vivo Optical Biopsy with a Handheld Quantitative Phase Microscope

In this work we develop and demonstrate the utility of a compact, handheld quantitative phase imaging microscope that enables label-free, in vivo optical imaging of bulk tissues with clear cellular and subcellular histological detail in real-time. The proposed device overcomes significant challenges in optical imaging for in vivo applications, particularly for clinical human use. The approach uses quantitative oblique back illumination microscopy (qOBM) to obtain quantitative phase information of opaque samples using epi-illumination. The compact handheld probe achieves 0.8 {micro}m lateral resolution, 5 {micro}m axial resolution, 300 {micro}m X 300 {micro}m field of view, and operates at 25Hz in a wide-field (non-scanning) configuration, enabling real-time imaging. The probe is also inexpensive and has no moving components, making it robust. The utility of the probe is demonstrated in (1) human skin in vivo, (2) brain tumor tissue ex vivo from a murine tumor model and from discarded human tissue from neurosurgery, and (3) in vivo using healthy brain tissue from a large animal model (swine), simulating neurosurgical conditions. Given the clear cellular and subcellular histological detail (i.e., "optical biopsy") obtained in real-time, combined with the ease-of-use and low-cost of the system, the proposed device has significant implications for a broad range of clinical applications.

bioengineering↗

bioRxiv2025

Single Capture Quantitative Oblique Back-Illumination Microscopy

Quantitative oblique back-illumination microscopy (qOBM) has emerged as a powerful technique for label-free, 3D quantitative phase imaging of arbitrarily thick biological specimens. However, in its initial embodiment, qOBM requires multiple captures for phase recovery, which reduces imaging speed and increases system complexity. In this work, we present a novel advancement in qOBM: single-capture qOBM (SCqOBM) which utilizes a deep learning model to accurately reconstruct phase information from a single oblique back-illumination capture. We demonstrate that SCqOBM achieves remarkable phase imaging accuracy, closely matching the results of traditional four-capture qOBM in diverse biological samples. We first highlight the unique potential of SCqOBM for non-invasive, in-vivo imaging applications by visualizing blood flow in mouse brain and human arm. Additionally, we demonstrate single-slice (en-face) quantitative phase imaging at 2 kHz and volumetric refractive index tomography at speeds up to 10 volumes per second. SCqOBM offers transformative advantages in speed, simplicity, and system accessibility, making it highly suitable for dynamic and real-time imaging applications. Its ability to produce high-resolution, quantitative phase and refractive index images with minimal hardware complexity opens new frontiers in biomedical research and clinical diagnostics, including non-invasive hematological assessments and in-vivo tissue imaging.

bioengineering↗