Assessment of chronic wounds using in vivo diffuse near infrared spectroscopy

Chronic wounds are an increasing challenge as the population ages and the prevalence of obesity and diabetes increase in the U.S. and throughout the world. As the number and cost of treatments for chronic wounds increases, the importance of assessing the effectiveness of new therapies becomes critical. Current clinical methods for wound assessment rely on qualitative assessment of wound surface appearance and measurements of wound surface dimensions, but do not take the health of underlying tissue into account. The goal of this research is to develop a non-invasive method of assessing and predicting chronic wound healing using in vivo frequency-domain diffuse near infrared spectroscopy (DNIRS). The main hypothesis behind this research is that changes in blood vessel density and oxygen delivery beneath the surface of a wound can be measured using DNIRS. Furthermore, these changes could be used to quantitatively assess the healing status of a chronic wound and predict faster and more accurately than current clinical methods whether a wound treatment is working.The results of a study of twenty-eight human diabetic foot ulcers shows that changes in oxy- and total hemoglobin concentration measured with DNIRS can be used to differentiate healing from non-healing wounds, and the capability of DNIRS wound monitoring to predict healing in diabetic foot ulcers is examined. Additionally, data obtained from a study of impaired wound healing in obese rats demonstrate that DNIRS can be used to assess wound healing in an animal model, and a model for expected changes in DNIRS measurements of oxy- and deoxyhemoglobin concentration during wound healing is proposed. Wound size data obtained from this animal study show that obese rats may provide a better model of impaired healing than the chemically-induced diabetic rats which are often used by researchers when assessing novel wound therapies.Ph.D., Biomedical Engineering -- Drexel University, 201

Gene expression changes in therapeutic ultrasound-treated venous leg ulcers

IntroductionLow-frequency, low-intensity ultrasound has been previously shown to promote healing of chronic wounds in humans, but mechanisms behind these effects are poorly understood. The purpose of this study was to evaluate gene expression differences in debrided human venous ulcer tissue from patients treated with low-frequency (20 kHz), low-intensity (100 mW/cm2) ultrasound compared to a sham treatment in an effort to better understand the potential biological mechanisms.MethodsDebrided venous ulcer tissue was collected from 32 subjects one week after sham treatment or low-frequency, low-intensity ultrasound treatment. Of these samples, 7 samples (3 ultrasound treated and 4 sham treated) yielded sufficient quality total RNA for analysis by ultra-high multiplexed PCR (Ampliseq) and expression of more than 24,000 genes was analyzed. 477 genes were found to be significantly differentially expressed between the ultrasound and sham groups using cut-off values of p < 0.05 and fold change of 2.Results and DiscussionThe top differentially expressed genes included those involved in regulation of cell metabolism, proliferation, and immune cell signaling. Gene set enrichment analysis identified 20 significantly enriched gene sets from upregulated genes and 4 significantly enriched gene sets from downregulated genes. Most of the enriched gene sets from upregulated genes were related to cell-cell signaling pathways. The most significantly enriched gene set from downregulated genes was the inflammatory response gene set. These findings show that therapeutic ultrasound influences cellular behavior in chronic wounds as early as 1 week after application. Considering the well-known role of chronic inflammation in impairing wound healing in chronic wounds, these results suggest that a downregulation of inflammatory genes is a possible biological mechanism of ultrasound-mediated venous chronic wound healing. Such increased understanding may ultimately lead to the enhancement of ultrasound devices to accelerate chronic wound healing and increase patient quality of life