TY - JOUR T1 - Non-invasive monitoring of pharmacodynamics during the skin wound healing process using multimodal optical microscopy JF - BMJ Open Diabetes Research & Care JO - BMJ Open Diab Res Care DO - 10.1136/bmjdrc-2019-000974 VL - 8 IS - 1 SP - e000974 AU - Jose Rico-Jimenez AU - Jang Hyuk Lee AU - Aneesh Alex AU - Salma Musaad AU - Eric Chaney AU - Ronit Barkalifa AU - Darold R Spillman Jr AU - Eric Olson AU - David Adams AU - Marina Marjanovic AU - Zane Arp AU - Stephen A Boppart Y1 - 2020/04/01 UR - http://drc.bmj.com/content/8/1/e000974.abstract N2 - Objective Impaired diabetic wound healing is one of the serious complications associated with diabetes. In patients with diabetes, this impairment is characterized by several physiological abnormalities such as metabolic changes, reduced collagen production, and diminished angiogenesis. We designed and developed a multimodal optical imaging system that can longitudinally monitor formation of new blood vessels, metabolic changes, and collagen deposition in a non-invasive, label-free manner.Research design and methods The closure of a skin wound in (db/db) mice, which presents delayed wound healing pathologically similar to conditions in human type 2 diabetes mellitus, was non-invasively followed using the custom-built multimodal microscope. In this microscope, optical coherence tomography angiography was used for studying neovascularization, fluorescence lifetime imaging microscopy for nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) assessment, fluorescence intensity changes of NAD(P)H and flavin adenine dinucleotide (FAD) cofactors for evaluating metabolic changes, and second harmonic generation microscopy for analyzing collagen deposition and organization. The animals were separated into four groups: control, placebo, low concentration (LC), and high concentration (HC) treatment. Images of the wound and surrounding areas were acquired at different time points during a 28-day period.Results Various physiological changes measured using the optical imaging modalities at different phases of wound healing were compared. A statistically significant improvement in the functional relationship between angiogenesis, metabolism, and structural integrity was observed in the HC group.Conclusions This study demonstrated the capability of multimodal optical imaging to non-invasively monitor various physiological aspects of the wound healing process, and thus become a promising tool in the development of better diagnostic, treatment, and monitoring strategies for diabetic wound care.Data are available upon reasonable request and through a collaborative agreement. All data relevant to the study are included in the article or uploaded as supplementary information. Imaging data generated during this study may be available upon request. ER -