Establishing a sensitive, scalable physiological test for neurovascular reflex integrity and investigating whether targeted peripheral neural stimulation can enhance perfusion and vasodilatory responsiveness.
The overarching goal of this project is to define how targeted afferent activation can be used to restore impaired neurovascular reflexes, improve skin perfusion, and ultimately prevent further decline in limb health in Veterans. By integrating functional and structural imaging with neural modulation, this work will establish foundational evidence for diagnostic and therapeutic strategies aimed at early detection of neurovascular decline and prevention of tissue breakdown in both Diabetic Peripheral Neuropathy (DPN) and residual-limb contexts. Furthermore, this work will establish the feasibility of preventing or delaying the mechanical trauma of the insensate distal limb which invariably leads to deep pressure injuries, infections, and amputation in Veterans with DPN. The findings have the potential to transform care by enabling earlier diagnosis, improving neurovascular responsiveness, and optimizing neuromodulation protocols to prevent skin complications, delay progression toward amputation, and improve quality of life in Veterans with DPN or limb loss.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
HEALTH_SERVICES_RESEARCH
Masking
SINGLE
Enrollment
42
The implanted neural and and muscular interface will be used to characterize neurovascular reflex testing (thermal axon reflex \& pressure-induced vasodilation) and microvascular imaging using Laser Doppler Flowmetry and PAI. Reflex responses will be evaluated under baseline and stimulation conditions (sham, tonic, biomimetic), with direct stimulation performed by the CFINE cohort for modality comparison. Structural-functional relationships will be modeled by integrating metrics from PAI with reflex outcomes.
The cutaneous peripheral nerve stimulation interface will be used to characterize neurovascular reflex testing (thermal axon reflex \& pressure-induced vasodilation) and microvascular imaging using Laser Doppler Flowmetry and PAI. Reflex responses will be evaluated under baseline and stimulation conditions (sham, tonic, biomimetic). Structural-functional relationships will be modeled by integrating metrics from PAI with reflex outcomes.
Louis Stokes VA Medical Center, Cleveland, OH
Cleveland, Ohio, United States
Cutaneous Vascular Conductance
Autonomic reflex testing including thermal axon reflex and pressure induced vasoconstriction will be applied. The cutaneous blood flow in the lower limb will be measured using laser doppler flowmetry. The flux is divided by mean arterial pressure to calculate cutaneous vascular conductance. This provides a physiologically relevant metric of microvascular control by accounting for systemic pressure fluctuations
Time frame: baseline and visits 1-15 until study completion, average 1 year
Vessel Density
Defined as the percentage of tissue volume occupied by vascular structures. The investigators use photoacoustic imaging of microvascular structure to quantify microvascular structural integrity at distal and proximal skin sites. From the reconstructed volumetric data, the investigators will extract the vessel density
Time frame: baseline and visits 1-15 until study completion, average 1 year
Tissue Oxygen Saturation
Tissue oxygen saturation or sO2 will be measured during different conditions of the study such as thermal axon reflex and pressure induced vasoconstriction using reflectance spectroscopy
Time frame: baseline and visits 1-15 until study completion, average 1 year
Mean Vessel Diameter
Calculated from the cross-sectional profiles of resolved vessels obtained from the photoacoustic imaging of microvascular structures
Time frame: baseline and visits 1-15 until study completion, average 1 year
Hemoglobin Oxygenation
From photoacoustic imaging, hemoglobin oxygenation is derived and compared across different study conditions
Time frame: baseline and visits 1-15 until study completion, average 1 year
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