Biology subjects

Simkulet, M. G.

Publications and source records attributed to Simkulet, M. G..

3 recordsLinked to original sources

bioRxiv2026

Mapping Slow Speckle Dynamics to Probe Cellular Metabolic Activity In Vivo using Laser Speckle Contrast Imaging

SignificanceLaser speckle contrast imaging (LSCI) is widely used to measure blood flow, but speckle fluctuations may also encode biologically meaningful dynamics beyond perfusion. Foundational studies in dynamic light scattering (DLS) and micro-optical coherence tomography (OCT) have also demonstrated that slow coherent signal fluctuations can arise from energy-dependent intracellular motion in in vitro and ex vivo systems. Building upon these advances, recent work has shown that LSCI has the potential to detect slow speckle dynamics (SSD) correlated with cellular dynamics in vivo. However, the biophysical mechanisms underlying SSD in intact brain tissues remain insufficiently validated. Establishing a mechanistic bridge from controlled ex vivo and in vitro conditions to in vivo brain measurements is critical for translating speckle-based imaging beyond perfusion measurements to enable label-free assessment of cellular and metabolic activity in disease models. AimThe objective of this study is to investigate the biophysical origin of the SSD in vivo and evaluate its sensitivity to intracellular metabolic activity in brain tissue. ApproachWe utilize an epi-illumination LSCI system to measure speckle contrast as a function of camera exposure time and extract characteristic decorrelation time constants. SSD was investigated in acute mouse brain slices, where blood flow is absent, to eliminate vascular confounds. Cellular metabolism was systematically modulated using 2-deoxyglucose and glucose. Complementary in vivo measurements were performed to reveal SSDs response to hyperoxia and normoxia after ischemic stroke. ResultsSSD signals persisted in acute brain slices in the absence of blood flow. Inhibition of glycolysis significantly reduced SSD, while restoration of metabolic substrates partially recovered the signal. In in vivo measurements, SSD increased during hyperoxia compared to normoxia after ischemic stroke, suggesting increased oxygen-supported cellular metabolic activity. ConclusionsThese results indicate that SSD is sensitive to energy-dependent cellular processes closely tied to metabolic activity. SSD represents a previously uncharacterized, label-free in vivo optical contrast that enables assessment of cellular metabolic activity as well as vascular dynamics. This work establishes a mechanistic foundation for using SSD as a general optical marker of cellular viability in in vivo measurements.

neuroscience↗

bioRxiv2024

Optical coherence tomography enables longitudinal evaluation of cell graft-directed remodeling in stroke lesions

Stem cell grafting can promote glial repair of adult stroke injuries during the subacute wound healing phase, but graft survival and glial repair outcomes are perturbed by lesion severity and mode of injury. To better understand how stroke lesion environments alter the functions of cell grafts, we employed optical coherence tomography (OCT) to longitudinally image mouse cortical photothrombotic ischemic strokes treated with allogeneic neural progenitor cell (NPC) grafts. OCT angiography, signal intensity, and signal decay resulting from optical scattering were assessed at multiple timepoints across two weeks in mice receiving an NPC graft or an injection of saline at two days after stroke. OCT scattering information revealed pronounced axial lesion contraction that naturally occurred throughout the subacute wound healing phase that was not modified by either NPC or saline treatment. By analyzing OCT signal intensity along the coronal plane, we observed dramatic contraction of the cortex away from the imaging window in the first week after stroke which impaired conventional OCT angiography but which enabled the detection of NPC graft-induced glial repair. There was moderate, but variable, NPC graft survival at photothrombotic strokes at two weeks which was inversely correlated with acute stroke lesion sizes as measured by OCT prior to treatment, suggesting a prognostic role for OCT imaging and reinforcing the dominant effect of lesion size and severity on graft outcome. Overall, our findings demonstrate the utility of OCT imaging for both tracking and predicting natural and treatment-directed changes in ischemic stroke lesion cores.

neuroscience↗

bioRxiv2024

Thioether-functionalized cellulose for the fabrication of oxidation-responsive biomaterial coatings and films

Biomaterial coatings and films can prevent premature failure and enhance performance of chronically implanted medical devices. However, current hydrophilic polymer coatings and films have significant drawbacks, including swelling and delamination. To address these issues, we modified hydroxyethyl cellulose with thioether groups to generate an oxidation-responsive polymer, HECMTP. HECMTP readily dissolves in green solvents and can be fabricated as coatings or films with tunable thicknesses. HECMTP coatings effectively scavenge hydrogen peroxide, resulting in conversion of thioether groups to sulfoxide groups on the polymer chain. Oxidation-driven, hydrophobic-to-hydrophilic transitions that are isolated to the surface of HECMTP coating under physiologically relevant conditions increase wettability, decrease stiffness, and reduce protein adsorption to generate a non-fouling interface with minimal coating delamination or swelling. HECMTP can be used in diverse optical applications and permits oxidation-responsive, controlled drug release. HECMTP films are non-resorbable in vivo and evoke minimal foreign body responses. These results highlight the versatility of HECMTP and support its incorporation into chronically implanted medical devices.

bioengineering↗