TY - JOUR
T1 - Non-invasive monitoring of pharmacodynamics during the skin wound healing process using multimodal optical microscopy
AU - Rico-Jimenez, Jose
AU - Lee, Jang Hyuk
AU - Alex, Aneesh
AU - Musaad, Salma
AU - Chaney, Eric
AU - Barkalifa, Ronit
AU - Olson, Eric
AU - Adams, David
AU - Marjanovic, Marina
AU - Arp, Zane
AU - Boppart, Stephen A.
N1 - Funding Information:
Contributors JRJ, JHL and AA built the optical system, acquired the images, processed the data, and wrote the manuscript. SM performed the data analysis. EC, RB and MM handled the animals and applied the treatment. EO, DA, ZA and SAB contributed to the study design and/or directed the study. SAB is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors reviewed and revised the manuscript prior to publication. Funding This work was supported by GlaxoSmithKline. Competing interests None declared.
PY - 2020/4/22
Y1 - 2020/4/22
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.
AB - 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.
KW - imaging systems
KW - metabolic disturbances
KW - microvascular changes
KW - pharmacodynamics
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U2 - 10.1136/bmjdrc-2019-000974
DO - 10.1136/bmjdrc-2019-000974
M3 - Article
C2 - 32327442
AN - SCOPUS:85084031002
VL - 8
JO - BMJ Open Diabetes Research and Care
JF - BMJ Open Diabetes Research and Care
SN - 2052-4897
IS - 1
M1 - e000974
ER -