Photoacoustic monitoring of angiogenesis predicts response to therapy in healing wounds

Abstract

Chronic wounds are a major health problem that cause the medical infrastructure billions of dollars every year. Chronic wounds are often difficult to heal and cause significant discomfort. Although wound specialists have numerous therapeutic modalities at their disposal, tools that could 3D-map wound bed physiology and guide therapy do not exist. Visual cues are the current standard but are limited to surface assessment; clinicians rely on experience to predict response to therapy. Photoacoustic (PA) ultrasound (US) is a non-invasive, hybrid imaging modality that can solve these major limitations. PA relies on the contrast generated by hemoglobin in blood which allows it to map local angiogenesis, tissue perfusion and oxygen saturation - all critical parameters for wound healing. This work evaluates the use of PA-US to monitor angiogenesis and stratify patients responding vs. not-responding to therapy. We imaged 19 patients with 22 wounds once a week for at least three weeks. Our findings suggest that PA imaging directly visualizes angiogenesis. Patients responding to therapy showed clear signs of angiogenesis and an increased rate of PA increase (p = 0.002). These responders had a significant and negative correlation between PA intensity and wound size. Hypertension was correlated to impaired angiogenesis in non-responsive patients. The rate of PA increase and hence the rate of angiogenesis was able to predict healing times within 30 days from the start of monitoring (power = 88%, alpha = 0.05) This early response detection system could help inform management and treatment strategies while improving outcomes and reducing costs.

Photoacoustic imaging to monitor outcomes during hyperbaric oxygen therapy: Validation in a small cohort and case study in a bilateral chronic ischemic wound

“…Our previous work showed that PA monitoring of angiogenesis can predict wound healing. (37) Unfortunately, there is an increased risk of infection and secondary trauma after amputation and extensive debridement ( Fig. S3 and S4 ); hence, subsequent imaging was avoided.…”

“…Thus, visual inspection still remains the most common approach to monitoring wounds including response to therapy during HBO 2 . (37) Previously, we and others have reported the use of photoacoustic (PA) imaging to monitor changes in peripheral perfusion, oxygenation, and angiogenesis in chronic wounds. (37)(38)(39) Photoacoustic imaging is a hybrid imaging technique that combines optical spectroscopy with ultrasound.…”

“…Thus, visual inspection still remains the most common approach to monitoring wounds including response to therapy during HBO 2 . (37)…”

Monitoring peripheral hemodynamic response to changes in blood pressure via photoacoustic imaging

“…Hence, this work suggests that PA imaging can be used to monitor peripheral tissue perfusion, a risk factor for wound formation and impaired healing. [53,54] Others have also shown the use of PA imaging to visualize tissue perfusion but most studies use high-powered lasers which are expensive, bulky, and pose an exposure risk above the maximum permissible exposure limit. [28,55,56] Whether these changes in perfusion pose a significant risk to CKD/HD patients remains to be seen.…”

“…[30][31][32][33] Recently, we demonstrated the ability of PA imaging to monitor angiogenesis and predict wound healing. [34] The non-invasive, real-time, and enhanced penetration depth (>4 cm) of PA imaging make it an ideal tool to map peripheral tissue perfusion as a risk factor for the development of limb complications.…”