Non-invasive monitoring of pharmacodynamics during the skin wound healing process using multimodal optical microscopy

Jose Rico-Jimenez, Jang Hyuk Lee, Aneesh Alex, Salma Musaad, Eric Chaney, Ronit Barkalifa, Eric Olson, David Adams, Marina Marjanovic, Zane Arp, Stephen A. Boppart

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article numbere000974
JournalBMJ Open Diabetes Research and Care
Issue number1
StatePublished - Apr 22 2020


  • imaging systems
  • metabolic disturbances
  • microvascular changes
  • pharmacodynamics

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism


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