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Neural Engineering

Neural Engineering - Poster Session C

Poster K7 - Local Heating-Induced Skin Blood Flow Response in Individuals with Diabetic Lower Limb Loss

Friday, October 25, 2024
10:00 AM - 11:00 AM EST
Location: Exhibit Hall E, F & G

Introduction:  Diabetic peripheral neuropathy (DPN) is a frequent complication of people with type 1 or type 2 diabetes, resulting in damage to both sensory and autonomic nerve fibers that are important in regulating blood flow to the skin. Impaired nerves result in changes to the neural control of skin blood vessels and often lead to ulcers and amputations in participants. Specifically, in diabetics, damage to sensory and autonomic nerve fibers limit the effective signaling required for vasomotor function resulting in poor skin perfusion. In this work, we studied how nerve health relates to cutaneous blood flux on the residual limb of individuals with diabetic limb loss. Using Laser Doppler Imaging (LDI), we quantified the cutaneous changes in blood flow following local heat application to the skin in the lower limb in individuals with diabetic and non-diabetic limb loss. Small, unmyelinated C-fibers are responsible for the vasodilation following local heating, manifesting as an area of increased blood flow, resulting in redness and warmth. This phenomenon, known as a flare extent, occurs due to the dilation of blood vessels within the skin. Quantifying the flare extent response in individuals with diabetes is therefore a test of small fiber function that could be useful in assessing effectiveness of interventions and improving clinical outcomes of those with diabetic lower limb amputations.

Materials and

Methods:  Cutaneous pressure thresholds were measured using Semmes-Weinstein monofilaments applied at five locations on the residual limb and eight locations on the contralateral intact foot to quantify the extent of large fiber neuropathy. The residual limb was elevated on a custom aluminum and wood cart providing easy placement of the residual limb on the imaging platform. LDI was used to measure the flare extent response to local heating. The multipoint laser allowed the full extent flare and the perfusion of surrounding tissue to be measured. In order to produce the flare, the skin was heated using two probes (Moor Instruments) placed on the residual limb at 44 °C for 20 minutes. The probes were then removed and the flare regions were imaged. Flare extent (total flare area - the probe area) was measured using LDI analysis software (Moor Instruments). A region of interest matching the size of the heated probe was drawn on the LDI perfusion image and the median flux within the heated region was extracted. A custom MATLAB script (Mathworks, Natik, MA) was used to apply active contour segmentation to differentiate the flare extent from the surrounding tissue and calculate the flare area. Flare extent and median skin blood flow of the heated region were calculated and compared between participants with and without DPN using Welch's two sample t-test.

Results, Conclusions, and Discussions: In this study, we assessed the cutaneous pressure thresholds and flare extents in individuals with and without DPN. The participant with DPN (L3) exhibited significantly larger cutaneous pressure threshold of 26 g, compared to 6 g and 8 g observed in participants without DPN (L1 & L2), respectively. Additionally, the median flare extent, indicative of small fiber nerve health, varied considerably among participants: L1 recorded 59.34 ± 18.7 mm² , L2 had 44.1 ± 10.71mm², and L3 showed 22.83 ± 1.75 mm². The pooled median flare extent for the participants without DPN was 53.51 ± 22 mm². Statistical analysis revealed a significant difference in flare extents between participants with and without DPN (Figure 1).
Furthermore, the median skin blood flow in the heated region was measured at 686 ± 156.75 perfusion units in participants without DPN and 539 ± 18.88 perfusion units in the participant with DPN. Although the difference in heated skin blood flow between groups was not statistically significant, there was a noticeable difference of 147 perfusion units (Figure 2). These findings suggest measuring the flare extent could serve as a reliable metric for evaluating peripheral neuropathy. These results support the hypothesis that nerve dysfunction, such as DPN, correlates with a reduced flare extent response to local heating. Our findings underscore the importance of developing a quantitative measurement methodology for detecting small fiber neuropathy, thereby improving the assessment of interventions in individuals with diabetic limb loss.

Acknowledgements (Optional):  This work was supported by the Wen H. Ko Summer Internship Program sponsored by the Advanced Platform Technology Center at Louis Stokes Cleveland VA Medical Center. In addition, this submission is the result of work supported with resources and the use of facilities at the Louis Stokes VA Medical Center.