Point-of-care autofluorescence imaging for real-time sampling and treatment guidance of bioburden in chronic wounds: first-in-human results
Ralph S DaCosta, Iris Kulbatski, Liis Lindvere-Teene, Danielle Starr, Kristina Blackmore, Jason I Silver, Julie Opoku, Yichao Charlie Wu, Philip J Medeiros, Wei Xu, Lizhen Xu, Brian C Wilson, Cheryl Rosen, Ron Linden, Ralph S DaCosta, Iris Kulbatski, Liis Lindvere-Teene, Danielle Starr, Kristina Blackmore, Jason I Silver, Julie Opoku, Yichao Charlie Wu, Philip J Medeiros, Wei Xu, Lizhen Xu, Brian C Wilson, Cheryl Rosen, Ron Linden
Abstract
Background: Traditionally, chronic wound infection is diagnosed by visual inspection under white light and microbiological sampling, which are subjective and suboptimal, respectively, thereby delaying diagnosis and treatment. To address this, we developed a novel handheld, fluorescence imaging device (PRODIGI) that enables non-contact, real-time, high-resolution visualization and differentiation of key pathogenic bacteria through their endogenous autofluorescence, as well as connective tissues in wounds.
Methods and findings: This was a two-part Phase I, single center, non-randomized trial of chronic wound patients (male and female, ≥18 years; UHN REB #09-0015-A for part 1; UHN REB #12-5003 for part 2; clinicaltrials.gov Identifier: NCT01378728 for part 1 and NCT01651845 for part 2). Part 1 (28 patients; 54% diabetic foot ulcers, 46% non-diabetic wounds) established the feasibility of autofluorescence imaging to accurately guide wound sampling, validated against blinded, gold standard swab-based microbiology. Part 2 (12 patients; 83.3% diabetic foot ulcers, 16.7% non-diabetic wounds) established the feasibility of autofluorescence imaging to guide wound treatment and quantitatively assess treatment response. We showed that PRODIGI can be used to guide and improve microbiological sampling and debridement of wounds in situ, enabling diagnosis, treatment guidance and response assessment in patients with chronic wounds. PRODIGI is safe, easy to use and integrates into the clinical workflow. Clinically significant bacterial burden can be detected in seconds, quantitatively tracked over days-to-months and their biodistribution mapped within the wound bed, periphery, and other remote areas.
Conclusions: PRODIGI represents a technological advancement in wound sampling and treatment guidance for clinical wound care at the point-of-care.
Trial registration: ClinicalTrials.gov NCT01651845; ClinicalTrials.gov NCT01378728.
Conflict of interest statement
Competing Interests: RSD, BCW and their institution have a pending patent related to this work (“Device and method for fluorescence-based imaging and monitoring” USPTO WO 2009140757 A1), which is being commercialized. RSD an independent investigator with a Scientist appointment at the Princess Margaret Cancer Centre, University Health Network, where he has been the principal investigator on this project. He is also is founder and a shareholder of a spin-off company commercializing the technology. He has Board membership and receives separate compensation as Chief Scientific Officer of the company. LT is a part time employee of the University Health Network (clinical associate); she also receives separate compensation as the clinical trials manager for the company. RSD and LT’s roles in this project were not on behalf of the company but rather in the context of their academic appointments/affiliations. No other authors are associated with or receive compensation or own shares of the company. The authors confirm that the above stated competing interests do not alter the authors’ adherence to all PLOS ONE policies on sharing data and materials. The authors confirm that there are no restrictions on sharing of data and/or materials presented in this work.
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