Wound Imaging and Noninvasive Wound Therapy
Number: 0372
Table Of Contents
PolicyApplicable CPT / HCPCS / ICD-10 Codes
Background
References
Policy
Scope of Policy
This Clinical Policy Bulletin addresses noncontact normothermic / nonthermal wound therapy and noncontact fluorescence imaging of wounds.
Experimental, Investigational, or Unproven
Aetna considers the following procedures experimental, investigational, or unproven because the effectiveness of these approaches has not been established:
- Clarifi Imaging System
- Concurrent optical and magnetic stimulation (COMS) therapy to promote wound healing in chronic leg and foot ulcers
- DeepView Wound Imaging System for burn assessment and wound healing prediction of acute and chronic burn wounds
- MolecuLight, a hand-held device, for point-of-care fluorescence imaging of wounds
- Noncontact, nonthermal, low-frequency ultrasound therapy for the treatment of wounds and all other indications (e.g., bacterial infections, deep tissue pressure injury, and femoral artery thrombosis)
- Warm-Up Active Wound Therapy, also known as noncontact normothermic wound therapy (NNWT) and warming therapy.
Background
Warm-Up Active Wound Therapy (Augustine Medical, Inc., Eden Prairie, MN), also known as noncontact normothermic wound therapy (NNWT) uses a non-contact radiant-heat bandage to treat chronic venous ulcers when conventional wound-healing therapy has failed. The device consists of a noncontact, domed wound cover into which a flexible infrared heating card is inserted. A battery pack powers the device and warms the wound to a pre-determined temperature. The inside of the wound cover contains a foam ring, which acts as a wick to drain away exudate.
In a Decision Memorandum, the Center for Medicare and Medicaid Services (CMS) reviewed the evidence of the effectiveness of noncontact normothermic wound therapy. The CMS concluded that “the medical literature does not support a finding that NNWT heals any wound type better than conventional treatment.” CMS concluded, therefore, that there is insufficient evidence in the peer-reviewed medical literature to consider this device as reasonable and necessary for the treatment of wounds.
An assessment of treatments for chronic pressure ulcers by the Ontario Ministry of Health and Long-Term Care (2009) concluded that "thermal dressings such as noncontact normothermic dressings or radiant heat dressings were associated with greater improvement in stage III and IV pressure ulcers; however, this did not translate into more wound closure. There is no evidence at present to conclude that thermal dressings will result in more complete healing in stage III or IV pressure ulcers."
Several recent studies have evaluated the effectiveness of NNWT for the treatment of chronic wounds. However, there are drawbacks from these studies -- small sample sizes and lack of long-term follow-up. McCulloch and Knight (2002) examined the effect of a noncontact, radiant warming device in the treatment of neuropathic foot wounds secondary to diabetes. Patients (n = 36) were assigned to management with off-loading and warming (treatment) or off-loading therapy only (control) for a period of 8 weeks or until healing. Wounds of subjects in the treatment group healed at a rate of 0.019 +/- 0.019 cm2/day compared with that of 0.008 +/- 0.009 cm2/day in the control group (p = 0.049). The difference between treatment and control groups barely reached statistical significance.
The authors of a small (13 patients) preliminary study on Warm-Up® Active Wound Therapy concluded that Warm-Up® Active Wound Therapy is a safe treatment modality for chronic venous stasis ulcers; however, further investigation using a larger prospective study is needed to demonstrate effectiveness
Kloth and associates (2002) studied the effect of NNWT versus standard wound care on patients (n = 40) with 43 stage III and IV pressure ulcers. A sterile noncontact wound dressing was applied to 21 wounds for 24 hours per day, 7 days per week. Each day after the wound was irrigated and the noncontact dressing was changed, a heating element in the dressing was activated for 3 1-hour periods for 12 weeks or until wound closure. Twenty-two control wounds were treated with standard, moisture-retentive dressings 24 hours per day, 7 days per week for 12 weeks or until wound closure. The healing rate for the treatment group was significantly greater than that for the control group (0.52 cm2 per week and 0.23 cm2 per week, respectively; p < 0.02). However, the difference in the incidence of closure among wounds that completed the entire 12-week protocol between treatment and control groups were not significant (11 of 14 or 78.5 % for the treatment group and 8 of 16 or 50 % for the control group).
- the control arm (11 patients with 11 ulcers) received standard wound care, and
- the treatment arm (5 patients with 6 ulcers) received NNWT.
Standard wound care resulted in complete ulcer healing at an average of 127 days, while NNWT resulted in complete ulcer healing at an average of 59 days, or 54 % faster than in the control arm. However, the mean wound healing times between the 2 groups were not significantly different (p < 0.33). Moreover, the median wound healing time for the 2 groups were quite similar (70 days for the control group and 68 days for the treatment group). The authors concluded that a larger prospective study that evaluates NNWT for ulcers associated with osteomyelitis is warranted.
In a prospective, randomized, controlled study, Alvarez and colleagues (2003) compared diabetic foot ulcer healing in patients being treated with either NNWT applied for 1 hour 3 times daily until healing or 12 weeks, or standard care (saline-moistened gauze applied once-daily). Surgical debridement and adequate foot off-loading was provided to both groups. Evaluations were performed weekly and consisted of acetate tracings, wound assessment, and serial photography. A total of 20 patients completed the study and both treatment groups were distributed evenly (n = 10). Ulcers treated with NNWT had a greater mean percent wound closure than control-treated ulcers at each evaluation point (weeks 1 to 12). After 12 weeks, 70 % of the wounds treated with NNWT were healed compared with 40 % for the control group. However, the differences were not significant (p < 0.069). The authors concluded that further study in a greater patient population is needed to assess the effectiveness of NNWT in treating neuropathic foot ulcers.
In a randomized controlled study, Thomas et al (2005) examined the effectiveness of radiant heat bandage on the healing of stage 3 or stage 4 pressure ulcers. A total of 41 subjects with a stage 3 or stage 4 truncal pressure ulcer greater than 1.0 cm2 were recruited from outpatient clinics, long-term care nursing homes, and a rehabilitation center. The experimental group was randomized to a radiant-heat dressing device and the control group was randomized to a hydrocolloid dressing, with or without a calcium alginate filler. Subjects were followed until healed or for 12 weeks. Eight subjects (57 %) in the experimental group had complete healing of their pressure ulcer compared with 7 subjects (44 %) with complete healing in the control group (p = 0.46). The authors noted that although a 13 % difference in healing rate between the 2 arms of the study was found, this difference was not statistically significant.
In a single center randomized study with 49 patients, Alvarez et al (2006) reported that NNWT improves the healing of diabetic neuropathic foot ulcers. Moreover, these researchers stated that further study in a greater patient population is needed to fully assess the effectiveness of this device and to provide additional information on whether local warmth can reduce the incidence of infection.
Serena et al (2009) examined if noncontact, nonthermal, low-frequency ultrasound (LFU) therapy is effective in controlling wound bacterial colony counts in a series of 4 related experiments. First, ultrasound penetration in both wounded and intact skin was assessed in-vitro. Compared to sham, noncontact ultrasound penetrated farther into both wounded (3.0 to 3.5 mm versus 0.35 to 0.50 mm) and intact (2.0 to 2.5 mm versus 0.05 to 0.07 mm, respectively) pig skin. Second, using an in-vitro model to stain and count live/dead bacteria, 0 % of sham-treated and 33 % of Pseudomonas aeruginosa, 40 % of Escherichia coli and 27 % of Enterococcus faecalis were dead after 1 ultrasound application. Minimal effects on methicillin-resistant Staphylococcus aureus (MRSA) and S. aureus were observed. Third, using an in-vivo model, after 1 week, while differences between different bacterial species were observed, overall bacterial quantity decreased with ultrasound treatment (from 7.2 +/- 0.79 to 6.7 +/- 0.91 colony forming units [CFU] per gram of tissue [CFU/g]) and silver anti-microbial dressings (from 7.2 +/- 0.79 to 5.7 +/- 0.6 CFU/g) but increased to 8.6 +/- 0.15 CFU/g for sham and 8.6 +/- 0.06 CFU/g for water-moistened gauze. Fourth, 11 patients (average age of 60 years) with pressure ulcers containing bacterial counts greater than 10(5) CFU/g of tissue received 2 weeks of noncontact ultrasound therapy. The quantities of 7 bacterial organisms were reduced substantially from baseline to 2 weeks post-treatment. None of the wounds exhibited signs of a clinical infection during the treatment period and no adverse events were observed. Taken together, these 4 studies indicated that noncontact ultrasound can be used to reduce bacterial quantity. The authors concluded that controlled clinical studies are needed to determine the effectiveness of this treatment and to further elucidate its effects on various Gram-negative and Gram-positive bacteria.
In an in-vitro study, Conner-Kerr and colleagues (2010) examined the effects of LFU delivered at 35 kHz on bacterial viability, cell wall structure, and colony characteristics, including antibiotic resistance on vegetative forms of MRSA. They concluded that studies to elucidate the observed effects of LFU on MRSA and evaluate its effect in-vivo are needed. Furthermore, in a Cochrane review on therapeutic ultrasound for venous leg ulcers, Cullum et al (2010) concluded that the studies evaluating ultrasound for venous leg ulcers are small, poor-quality and heterogeneous. There is no reliable evidence that ultrasound hastens healing of venous ulcers. There is a small amount of weak evidence of increased healing with ultrasound, but this requires confirmation in larger, high-quality randomized controlled trials. There is no evidence of a benefit associated with LFU.
Voigt and colleagues (2011) examined if LFU used as an adjunctive therapy improves the outcomes of complete healing and reduction of size of chronic lower limb wounds. PubMed, Cochrane/CENTRAL, technical assessment, relevant wound-related journals, and clinical guidelines were searched along with contacting manufacturers and authors of relevant randomized controlled trials (RCTs) were completed. Searches focused on the use of LFU in RCTs. Data were collected via a data collection form and was adjudicated independently via coauthors. Meta-analyses and heterogeneity checks were performed using Mantel-Haenszel and inverse variance (fixed and random effects) statistical methods on studies with similar outcomes (complete healing and percent wound area reduction) over similar time periods. Single study results were reported via the statistical methods used in the study; 8 RCTs were identified. Results demonstrated that early healing (at less than or equal to 5 months) in patients with venous stasis and diabetic foot ulcers was favorably influenced by both high- and low-intensity ultrasound delivered at a low frequency -- either via contact or noncontact techniques. However, the authors noted that the quality of the data may be suspect, especially for low-frequency, low-intensity noncontact ultrasound because of significant biases.
Madhok et al (2013) stated that debridement is a crucial component of wound management. Traditionally, several types of wound debridement techniques have been used in clinical practice such as autolytic, enzymatic, bio-debridement, mechanical, conservative sharp and surgical. Various factors determine the method of choice for debridement for a particular wound such as suitability to the patient, the type of wound, its anatomical location and the extent of debridement required. Recently developed products are beginning to challenge traditional techniques that are currently used in wound bed preparation. These investigators reviewed the current evidence behind the use of these newer techniques in clinical practice. They noted that there is some evidence to suggest that LFU therapy may improve healing rates in patients with venous ulcers and diabetic foot ulcers.
Low-Frequency Ultrasound Therapy Femoral Artery Thrombosis
- an ultrasound frequency of 2.2-MHz, and
- a 90,000 IU/kg dose of urokinase. Ultrasound exposure time (30 minutes versus 60 minutes) had no significant effect on the thrombolytic effects.
The combination of local LFU radiation, targeted microbubbles, and thrombolytic urokinase induced thrombolysis of femoral artery thrombosis in a rabbit model. The ultrasonic frequency of 2.2-MHz and urokinase dose of 90,000 IU/kg induced optimal thrombolytic effects, while the application of either 30 minutes or 60 minutes of ultrasound exposure had similar effects.
Low-Frequency Ultrasound Debridement in Chronic Wound Healing
Chang and colleagues (2017) stated that ultrasound debridement is a promising technology that functions to disperse bacterial biofilms and stimulate wound healing. These researchers focused on LFU (20 to 60 kHz) and summarized the findings of 25 recent studies examining ultrasound efficacy. Ultrasound debridement appears to be most effective when used 3 times a week and has the potential to decrease exudate and slough, decrease patient pain, disperse biofilms, and increase healing in wounds of various etiology. The authors concluded that although current studies are generally of smaller size, the results are promising and they recommended the testing of LFU therapy in clinical practice on a larger scale.
Low-Frequency Ultrasound for the Treatment of Bacterial Infections
Cai and colleagues (2017) noted that single anti-microbial therapy has been unable to resist the global spread of bacterial resistance. These researchers reviewed literatures of available in-vitro and in-vivo studies and the results showed that (LFU has a promising synergistic bactericidal effect with antibiotics against both planktonic and biofilm bacteria. It also can facilitate the release of antibiotics from medical implants. The authors stated that as a non-invasive and targeted therapy, LFU has great potential in treating bacterial infections. However, more in-depth and detailed studies are still needed before LFU is officially applied as a combination therapy in the field of anti-infective treatment. Moreover, these investigators noted that there is still a long way to go before clinical application of combination therapy of LFU with antibiotics. First of all, the current studies involved a narrow range of susceptible pathogens. There are very few studies on the most threatening MDR bacteria. Secondly, frequency, intensity, and pulse cycle varied a lot at present. The promising frequency and intensity from in-vitro studies are likely to cause local damage in in-vivo studies. Therefore, LFU parameters appropriate for clinical application need to be further explored. Thirdly, 1 study indicated that LFU treatment reduced the interface shear strength and initial stability of vancomycin-loaded acrylic bone cement-stem. So the impact of LFU on the physical properties of the implant materials requires a comprehensive examination. At last, because bacteria will partially be removed from the biofilm surface when LFU is applied, whether it will bring the risk of spreading the pathogens and forming systemic bloodstream infection also requires more careful evaluation.
Low-Frequency Ultrasound for the Treatment of Deep Tissue Pressure Injury
Honaker and associates (2016) stated that the optimal treatment for deep tissue pressure injuries (DTPI) has not been determined. Deep tissue pressure injuries represent a more ominous early stage pressure injury that may evolve into full thickness ulceration despite implementing the standard of care for pressure injury. In a longitudinal, prospective, historical case control study, these researchers examined the effectiveness of noncontact LFU (NLFU) plus standard of care (treatment group) in comparison to standard of care (control group) in reducing DTPI severity, total surface area, and final pressure injury stage. The Honaker Suspected Deep Tissue Injury Severity Scale (range of 3 to 18 [more severe]) was used to determine DTPI severity at enrollment (time 1) and discharge (time 2). A total of 60 subjects (treatment = 30; control= 30) were enrolled in the study. In comparison to the control group mean DTPI total surface area change at Time 2 (0.3 cm2 ), the treatment group had a greater decrease (8.8 cm2 ) that was significant (t = 2.41, p = 0.014, r2 = 0.10). In regards to the Honaker Suspected Deep Tissue Injury Severity Scale scores, the treatment group had a significantly lower score (7.6) in comparison to the control group (11.9) at time 2, with a mean difference of 4.6 (t = 6.146, p = 0.0001, r2 = 0.39). When considering the final pressure ulcer stage at time 2, the control group were mostly composed of unstageable pressure ulcer (57 %) and DTPI severity (27 %). In contrast, the treatment group final pressure ulcer stages were less severe and were mostly composed of stage 2 pressure injury (50 %) and DTPI severity (23 %) were the most common at time 2. The authors concluded that the results of this study showed that DTPI severity treated with NLFU within 5 days of onset and in conjunction with standard of care may improve outcomes as compared to standard of care only.
In a retrospective, descriptive study, Wagner-Cox and colleagues (2017) examined the effect of NLFU on DTPI, both hospital-acquired and those present on admission (POA). Medical records from 44 adult patients with a DTPI treated with NLFU were reviewed; 22 had a hospital-acquired DTPI (HADTPI) and 22 had DTPI POA. Age of subjects was 71.3 ± 16.3 years (mean ± SD); 52 % were men. Data were collected from the medical records including demographic as well as relevant clinical characteristics, DTPI measurements, and DTPI evolution/resolution. Data were summarized and examined using descriptive statistics (e.g., frequencies and percentages and means and standard deviations). Differences between groups were examined using paired t-tests or the Mann-Whitney U test and the Chi-square test as appropriate. In addition, the heel DTPI subgroup (n = 8) was examined separately due to the small sample size. All patients with HADTPI and DTPI POA treated with NLFU exhibited a statistically significant decrease in injury size from initiation to discontinuation of NLFU therapy (24.6 cm versus 14.4 cm, p = 0.02). No statistically significant difference in wound resolution was found between HADTPI versus DTPI POA (27 % versus 18 %, p = 0.47). Mean size of both HADTPI and DTPI POA decreased significantly from 15.9 to 13.4 cm (p = 0.045) by NLFU therapy. Wounds were classified as resolved at completion of treatment in 23 % (10 out of 44) of all treated patients. Of all patients with the potential to be resolved (not discharged early or expired), 63 % (10 out of 16) had wounds classified as resolved. The authors concluded that the findings of this study suggested that NLFU is a viable and promising therapeutic option for both HADTPI and DTPI POA. Moreover, they stated that future studies are needed to confirm these results and to examine efficacy and feasibility of DTPI across care settings.
The MolecuLight Device
The MolecuLight is a wound imaging device that can visualize fluorescent bacteria and measure wound surface area in real-time. However, there is currently insufficient evidence to support its use in identification and management of wounds with bacterial burden.
Blumenthal and Jeffery (2018) noted that the MolecuLight i:X Imaging Device is a portable, non-invasive, real-time camera used to visualize the bacterial load in a wound. It uses violet light illumination and a dual band-pass optical filter to capture the fluorescence of endogenous structures in the tissue matrix and harmful bacteria. The MolecuLight i:X captures images of wounds and highlights potentially detrimental levels of bacteria. This is an initial evaluation of using the MolecuLight i:X camera in the management of burns to demonstrate the following: the ability of the device to guide clinicians in their management of the burn (i.e., detect, identify, and specify swabbing locations). Burn wounds were photographed under standard light and violet light illumination to compare presentations of obvious infection signs and symptoms. Microbiology swab samples were obtained to correlate any bacterial presence to the images. The fluorescence images were used to guide swabs to where the bacteria were congregating. A total of 20 patients were imaged; 4 patients did not have bacterial contamination based on their images and swab results; 16 patients showed growth of Staphylococcus aureus, Pseudomonas aeruginosa, or other bacteria; 9 of the patients, by definition, had infections. These findings were correlated with the typical signs and symptoms of infection, the fluorescence images, and the microbiology results. The efficacy of the MolecuLight i:X was evident due to the microbiology results correlating to the images. The authors stated that further research is being done to test the device in terms of being an early intervention tool. These researchers stated that with these early results and guidance of swab samples, the MolecuLight i:X may be able to detect bacterial load before an infection and subsequent graft failure, thereby shortening lengths of hospital stay and improving overall healing. These preliminary findings from a small (n = 20) pilot study need to be validated by well-designed studies.
In a pilot study, Pijpe and colleagues (2019) compared the detection of bacteria in burn wounds between an bacterial fluorescence imaging device MolecuLight i:X, (Canada), and standard microbiological swabs. Wounds were swabbed 3 times on one occasion; once with a standard swab, once with a high-fluorescent area swab, indicating a bacterial load of greater than 104 colony-forming units (CFU)/g, and a finally with a non-fluorescent (nF) area swab. Proportion agreement of the microbiological results was calculated and the accuracy of the device to detect relevant bacteria was assessed. A total of 14 patients with 20 wounds participated in the study. Median post-burn day at sampling time was 21 days. Of the 20 wounds, 9 had a positive swab result in either of the 3 swabs, and 11 showed a high-fluorescent area. Overall, positive and negative proportion agreement between standard swab and high-fluorescent swab sample results were 100 %. Sensitivity, specificity, positive and negative predictive values (PPV and NPV) of presence of high-fluorescence were 78 %, 64 %, 64 %, and 78 %, respectively. For Pseudomonas aeruginosa detection, these results were 100 %, 70 %, 44 % and 100 %, respectively. The authors concluded that the diagnostic accuracy of the bacterial fluorescence imaging device to detect relevant bacteria in burn wounds was moderate and the reliability was equal to standard swabbing. Moreover ,these investigators stated that further research in larger sample sizes and on the relevance of minimal bacterial load and its potential to help with Pseudomonas aeruginosa management is needed.
Hurley and associates (2019) noted that sub-surface bacterial burden can be missed during standard wound examination protocols. The real-time bacterial fluorescence imaging device, MolecuLight i:X, visualizes the presence of potentially harmful levels of bacteria through endogenous auto-fluorescence, without the need for contrast agents or contact with the patient. The intended use of the imaging device is to assist with the management of patients with wounds by enabling real-time visualization of potentially harmful bacteria. In a prospective, single-center, observational study, these researchers examined the accuracy of the wound imaging device at detecting pathogenic bacteria in wounds. This trial was conducted in an out-patient plastic surgery wound care clinic. Patients had their wounds photographed under white and auto-fluorescent light with the imaging device. Auto-fluorescent images were compared with the microbiological swab results. A total of 33 patients and 43 swabs were included, of which 95.3 % (n = 41) were positive for bacteria growth. Staphylococcus aureus was the most common bacterial species identified. The imaging device had a sensitivity of 100 % and specificity of 78 % at identifying pathological bacteria presence in wounds on fluorescent light imaging. The PPV was 95.4 %; the NPV was 100 %. It demonstrated a sensitivity and specificity of 100 % at detecting the presence of Pseudomonas spp. The authors concluded that the imaging device used could be a safe, effective, accurate and easy-to-use auto-fluorescent device to improve the assessment of wounds in the out-patient clinic setting. In conjunction with best clinical practice, the device can be used to guide clinicians use of antibiotics and specialized dressings. Moreover, these investigators stated that further research should be directed to its application in other environments, including pre-operative and peri-operative applications as a surgical assessment tool.
The authors stated that this study had several drawbacks. Blood and highly vascularized tissue are demonstrated as black on the fluorescent light photographs. Often, these researchers encountered wounds with minimal active bleeding, which rendered the device incompatible. This was overcome with copious irrigation at the bedside with limited success. Thus, they considered active bleeding or visible vascularized tissue as a relative contraindication to use of the device. Dressings containing silver, a potent anti-microbial, also rendered the photograph black. This was a major drawback when applied in the authors’ out-patient burns clinic, as the majority of these patients had various silver-based dressings applied for their anti-microbial properties. Darkness was needed for the device to produce accurate and quality auto-fluorescent images. This was overcome by the use of the imaging device accessory product DarkDrape, which is made of high density polyethylene with an adjustable draw-string to ensure appropriate lighting conditions are met precisely. The accessory device is single-use only, which is not practical in everyday clinic use.
Rennie and colleagues (2019) stated that the persistent presence of pathogenic bacteria is one of the main obstacles to wound healing. Detection of wound bacteria relies on sampling methods, which delay confirmation by several days. However, a novel hand-held fluorescence imaging device has recently enabled real-time detection of bacteria in wounds based on their intrinsic fluorescence characteristics, which differ from those of background tissues. This device illuminates the wound with violet (405 nm) light, causing tissues and bacteria to produce endogenous, characteristic fluorescence signals that are filtered and displayed on the device screen in real-time. The resulting images allow for rapid assessment and documentation of the presence, location, and extent of fluorescent bacteria at moderate-to-heavy loads. This information has been shown to assist in wound assessment and guide patient-specific treatment plans. However, proper image interpretation is essential to assessing this information. To properly identify regions of bacterial fluorescence, users must understand: fluorescence signals from tissues (e.g., wound tissues, tendon, bone) and fluids (e.g., blood, pus); fluorescence signals from bacteria (red or cyan); the rationale for varying hues of both tissue and bacterial fluorescence; image artifacts that can occur; and some potentially confounding signals from non-biological materials (e.g., fluorescent cleansing solutions. The authors concluded that numerous publications on the device have discussed its high sensitivity for bacterial detection, benefits of use during wound assessment, and the various wound treatments that fluorescence images can guide. Moreover, these researchers stated that ongoing and future studies with the device will evaluate the clear potential for fluorescence-guided wound care to influence wound area reduction rates and wound healing.
Serena and colleagues (2019) noted that clinical evaluation of signs and symptoms (CSS) of infection is imperative to the diagnostic process. However, patients with heavily colonized and infected wounds are often asymptomatic, leading to poor diagnostic accuracy. Point-of-care (POC) fluorescence imaging rapidly provides information on the presence and location of bacteria. This clinical trial (#NCT03540004) aimed to evaluate diagnostic accuracy when bacterial fluorescence imaging was used in combination with CSS for identifying wounds with moderate-to-heavy bacterial loads. Wounds were assessed by study clinicians using NERDS and STONEES CSS criteria to determine the presence or absence of moderate-to-heavy bacterial loads, after which the clinician prescribed and reported a detailed treatment plan. Only then were fluorescence images of the wound acquired, bacterial fluorescence determined to be present or absent and treatment plan adjusted if necessary. These researchers examined 17 venous leg ulcers (VLUs) / 2 diabetic foot ulcers (DFUs). Compared with CSS alone, use of bacterial fluorescence imaging in combination with CSS significantly improved sensitivity (22 % versus 72 %) and accuracy (26 % versus 74 %) for identifying wounds with moderate-to-heavy bacterial loads (greater than or equal to 104 CFU/g, p = 0.002). Clinicians reported added value of fluorescence images in greater than 90 % of study wounds, including identification of wounds incorrectly diagnosed by CSS (47 % of study wounds) and treatment plan modifications guided by fluorescence (73 % of study wounds). Modifications included image-guided cleaning, treatment selection, debridement and anti-microbial stewardship. The authors concluded that findings from this pilot study suggested that when used in combination with CSS, bacterial fluorescence may improve the diagnostic accuracy of identifying patients with wounds containing moderate-to-heavy bacterial loads; and guide more timely and appropriate treatment decisions at the POC.
Farhan and Jeffery (2020) stated that pediatric burn injuries are vulnerable to severe complications, most often infection, making prompt and precise diagnosis of bacterial bioburden vital to preventing detrimental consequences and optimizing patients' outcomes. Currently, burn wounds are assessed for infection via examining the CSS of infection, which can be confirmed by swab culture analysis. While the former approach is subjective and experience-dependent, the latter technique is susceptible to missing sub-surface, biofilm-associated colonization, and any peripheral bacterial burden, and also delays confirmation by up to 5 days. The MolecuLight i:X is a hand-held, non-contact fluorescence imaging device, which can reveal real-time information regarding clinically significant levels of bacteria and their bio-distribution in surface and sub-surface burn wound tissues. These investigators conducted a single-center, observational study to examine the device’s efficacy in identifying critical bacterial levels in pediatric burn wounds and to test the children's compliance and the overall feasibility of the device integration into the current diagnostic practice. A total of 10 patients with 16 wounds were recruited and assessed for the presence or absence of CSS of infection and the presence or absence of bacterial fluorescence on images, with swabs taken to confirm findings. Results demonstrated the device's ability to visualize clinically significant bacterial burden and to localize distribution of pathogens. All clinicians agreed on the high compliance with the device and high feasibility of incorporating the device into routine wound assessments. The results of this study may pave the way toward including bacterial fluorescence imaging into the standard diagnostic algorithm for pediatric burn population.
Chew and associates (2020) stated that early diagnosis of wound infections are crucial as they have been shown to increase patient morbidity and mortality. These researchers examined the use of MolecuLight i:X to identify infections in acute open wounds in hand trauma. Data were collected from patients who attended the hand trauma unit over a 4-week period before having surgery. Wounds were inspected for clinical signs of infection and auto-fluorescence images were taken using the MolecuLight i:X device. Wound swabs were taken and results interpreted according to report by microbiologist. Auto-fluorescence images were interpreted by a clinician blinded to the microbiology results. A total of 31 patients were included and data collected from 35 wounds; 3 wounds (8.6 %) showed positive clinical signs of infection, 3 (8.6 %) were positive on auto-fluorescence imaging and 2 (5.7 %) of wound swab samples were positive for significant infection. Auto-fluorescence imaging correlated with clinical signs and wound swab results for 34 wounds (97.1 %). In 1 case, the clinical assessment and auto-fluorescence imaging showed positive signs of infection but the wound swabs were negative. The authors concluded that auto-fluorescence imaging in acute open wounds may be useful to provide real-time confirmation of bacterial infection and thus guide management.
A retrospective analysis by Price, et al. (2020) evaluated whether routine point of care fluorescence imaging of bacterial burden in foot ulcers could reduce antimicrobial use and improve healing outcomes. The study reviewed 229 chronic foot ulcers managed in a single outpatient setting and compared clinical decisions and outcomes before and after implementation of fluorescence imaging. The method involved assessing charts to determine changes in antibiotic prescribing, antimicrobial dressing selection, and wound healing trajectories once clinicians incorporated real time visualization of moderate to heavy bacterial loads. The results demonstrated reduced systemic antibiotic use, lower spending on antimicrobial dressings, and an increase in the proportion of wounds achieving closure within the study window. The authors concluded that earlier and more accurate detection of bacterial burden allowed clinicians to target debridement and cleaning more effectively, which in turn reduced reliance on antimicrobial products. Study limitations included its retrospective design, lack of randomization, potential for clinician behavior changes unrelated to imaging, and the single center context that may limit generalizability.
Hill and Woo (2020) noted that the UPPER/LOWER infection checklists look for signs and symptoms of local/superficial infection (UPPER) and deep infection (LOWER) to help clinicians in identifying and distinguishing between these infection levels, facilitating appropriate treatment. The presence of 3 or more UPPER or LOWER criteria is indicative of infection. In a prospective, multi-site, observational study, these researchers examined the use of incorporating real-time bacterial fluorescence imaging into the UPPER/LOWER checklists to enhance identification of infection in wounds. They evaluated 43 chronic wounds (1 wound per patient). Infection was identified in 27 wounds (62.8 %) according to the UPPER/LOWER checklist criteria; 3 wounds were positive for both UPPER and LOWER infection, 1 wound was positive for LOWER infection only, and 23 wounds were positive for UPPER infection only. Fluorescence images were taken to detect wounds with high bacterial loads (greater than 104 CFU/g), indicated by the presence of red or cyan fluorescence. Red or cyan fluorescence from bacteria was observed in 88 % of wounds (n = 38); all wounds positive for UPPER/LOWER were also positive for bacterial fluorescence. In 18 (41.9 %) of the 43 wounds, fluorescence information added a 3rd check to the UPPER/LOWER threshold, turning a negative diagnosis into a positive diagnosis of infection. Bacterial load was detected in 22/27 wounds swabbed, 17 of which exhibited heavy growth; in all wounds with detectable bacterial load, fluorescence signal was observed (PPV = 100 %, NPV = 83 %). Using microbiology as ground truth, inclusion of fluorescence information as an additional item in the checklists increased the sensitivity of the UPPER/LOWER checklist from 82 % to 95 %. The authors concluded that the findings of this study suggested that the UPPER/LOWER checklist and fluorescence imaging work in a complementary manner to identify wounds with high bacterial burden at the POC.
The authors stated that this study had several drawbacks. Both clinicians performing the evaluations were experts and familiar with the mnemonics and fluorescence imaging. Validation of the content of the mnemonics is needed to determine reliability of results among non-experts. Microbiology culture analysis was not available for all study wounds; therefore, the diagnostic accuracy measures reported in this study described 27 of 43 study wounds. The fluorescence imaging device could detect bacteria in wounds up to a maximum depth of 1.5 mm and did not provide real-time information on the bacterial species present or non-bacterial components (i.e., fungi) that may be present; wound sampling was needed to obtain this information. However, the high PPV of fluorescence reported in this trial, and in other studies, indicated that sampling may not always be needed. The single visit nature of this observational study prevented follow-up visits in most cases to examine if the treatment selections based on checklist classification and fluorescence information were appropriate. As outcomes data were not available for all patients to validate treatment plan changes, additional studies examining the impact of fluorescence-guided treatment selection are needed. However, in patients that were followed over multiple visits (e.g., case 6), reduction of UPPER/LOWER symptoms and bacterial fluorescence was observed at follow-up. Moreover, these researchers stated that due to the nature of the patient population, there was a low proportion of true negative study wounds (i.e., wounds with bacterial loads less than 104 CFU/g); therefore, specificity and NPV results should be interpreted with caution.
Le and co-workers (2021) stated that high bacterial load contributes to chronicity of wounds and is diagnosed based on assessment of clinical signs and symptoms (CSS) of infection, but these characteristics are poor predictors of bacterial burden; POC fluorescence imaging (FL) MolecuLight i:X could improve identification of wounds with high bacterial burden (greater than 104 CFU/g). FL detects bacteria, whether planktonic or in biofilm, but does not distinguish between the 2. In a prospective, controlled, multi-center study, these researchers compared diagnostic accuracy of FL to CSS during routine wound assessment. Post-assessment, clinicians were surveyed to examine the impact of FL on treatment plan. This trial was carried out by 20 clinicians from 14 outpatient advanced wound care centers in the U.S. Wounds underwent assessment for CSS followed by FL. Biopsies were collected to confirm total bacterial load. A total of 350 patients completed the study (138 diabetic foot ulcers, 106 venous leg ulcers, 60 surgical sites, 22 pressure ulcers, and 24 others); 287/350 wounds (82 %) had bacterial loads greater than 104 CFU/g, and CSS missed detection of 85 % of these wounds. FL significantly increased detection of bacteria (greater than 104 CFU/g) by 4-fold, and this was consistent across wound types (p < 0.001). Specificity of CSS+FL remained comparably high to CSS (p = 1.0). FL information modified treatment plans (69 % of wounds), influenced wound bed preparation (85 %), and improved overall patient care (90 %) as reported by study clinicians. The authors concluded that this novel non-contact, hand-held FL device provided immediate, objective information on presence, location, and load of bacteria at POC; and the use of FL facilitated adherence to clinical guidelines recommending prompt detection and removal of bacterial burden to reduce wound infection and facilitate healing.
The authors stated that this study had several drawbacks. First, due to the imprecision of soft tissue biopsy trimming, the biopsies were cut to a greater depth than the 1.5-mm excitation limit of the imaging device; therefore, it was possible that the biopsy may have detected slightly more anaerobic bacteria than the device was able to. Second, the conditions of culture analysis were unfavorable for fastidious bacteria and may have resulted in under-reporting the diversity of bacteria species present in the wound. This study focused primarily on high bacterial loads as a contributor to delayed wound healing; however, additional systemic factors that were not reported in this study, including vascular insufficiency and protease activity, must also be considered. Clinicians had limited experience using FL in a clinical context before the study, which may have contributed to lower sensitivity to detect bacteria at loads of greater than 104 CFU/g than previously observed. In prior FL studies, sensitivity estimates ranging from 72 % to 100 % were reported, likely due to more clinician experience using the device. As with other diagnostic imaging modalities, these investigators anticipated that the performance measures reported should be improved with increased experience. This single time-point study meant that effectiveness of changes in treatment plan based on FL could not be measured. Longitudinal RCTs examining wound healing may further elucidate the impact of POC diagnostic imaging of bacteria. Evidence from small longitudinal observational studies showed accelerated wound area reduction with use of FL. Due to the limited (1.5 mm) depth of excitation as well as inability to detect non-porphyrin-producing bacteria, including species from the Streptococcus, Enterococcus, and Finegoldia generas (which account for an estimated 12 % of the most prevalent wound pathogens and rarely occur mono-microbially), it is recommended that FL be used in combination with CSS.
Raizman and associates (2021) noted that pseudomonas aeruginosa (PA) is a common bacterial pathogen in chronic wounds known for its propensity to form biofilms and evade conventional treatment methods. Early detection of PA in wounds is critical to the mitigation of more severe wound outcomes. Point-of-care bacterial fluorescence imaging has been used to illuminate wounds with safe, violet light, triggering the production of cyan fluorescence from PA. A prospective, single-blind clinical study was carried out to determine the PPV of cyan fluorescence for the detection of PA in wounds. Bacterial fluorescence using the MolecuLight i:X imaging device revealed cyan fluorescence signal in 28 chronic wounds, including venous leg ulcers, surgical wounds, diabetic foot ulcers and other wound types. To correlate the cyan signal to the presence of PA, wound regions positive for cyan fluorescence were sampled via curettage. A semi-quantitative culture analysis of curettage samples confirmed the presence of PA in 26/28 wounds, resulting in a PPV of 92.9 %. The bacterial load of PA from cyan-positive regions ranged from light to heavy. Less than 20 % of wounds that were positive for PA exhibited the classic symptoms of PA infection. The authors concluded that the findings of this study suggested that cyan detected on fluorescence images can be used to reliably predict bacteria, specifically PA at the POC.
The authors stated that this study had several drawbacks. This trial was designed to test the PPV of cyan on fluorescence images; therefore, it did not provide information on NPV, sensitivity or specificity of the images. These have been evaluated by other studies, which demonstrated high sensitivity and specificity of the images for detecting high bacterial load. Future work that examines the presence of PA from wound regions positive or negative for cyan fluorescence may help to clarify the specificity of cyan for PA. Furthermore, the semi-quantitative culture based microbiological confirmation used has inherent limitations, as this method could under-estimate bacterial loads and each semi-quantitative category was associated with a wide range of CFU/g counts. For example, light growth has been shown to range from 103 to 106 CFU/g in wound samples. Under-estimating bacterial loads may have resulted in a slightly lower reported PPV in this study, as scant growth of PA was detected in 1 clearly cyan-positive wound and was considered a false positive in this analysis. Additional studies utilizing gold standard quantitative or molecular culture-based methods to analyze wound biopsies may help to clarify the bacterial loads detected from regions of cyan fluorescence. The fluorescence imaging procedure also has inherent limitations, namely the need for darkness during imaging and a limited depth of excitation (approximately 1.5 mm) for detection of subsurface bacteria; however, as PA tends to be a surface or immediately sub-surface pathogen, this posed less of a limitation for the detection of PA than it may be for other pathogens.
Lopez and colleagues (2021) stated that wound biofilms must be identified to target disruption and bacterial eradication but are challenging to detect with standard clinical assessment. These researchers examined if bacterial fluorescence imaging could detect porphyrin-producing bacteria within a biofilm using well-established in-vivo models. Mouse wounds were inoculated on Day 0 with planktonic bacteria (n = 39, porphyrin-producing and non-porphyrin-producing species, 107 colony forming units (CFU)/wound) or with polymicrobial biofilms (n = 16, 3 biofilms per mouse, each with 1:1:1 parts Staphylococcus aureus/Escherichia coli/Enterobacter cloacae, 107 CFU/biofilm) that were grown in-vitro. Mouse wounds inoculated with biofilm underwent fluorescence imaging up to Day 4 or 5. Wounds were then excised and sent for microbiological analysis. Bacteria-matrix interaction was examined with scanning electron microscopy (SEM) and histopathology. A total of 48 hours after inoculation with planktonic bacteria or biofilm, red fluorescence was readily detected in wounds; red fluorescence intensified up to Day 4. Red fluorescence from biofilms persisted in excised wound tissue post-wash. SEM and histopathology confirmed bacteria-matrix interaction. The authors concluded that this pre-clinical study was the first to demonstrate the fluorescence detection of bacterial biofilm in-vivo using a POC wound imaging device. These findings have implications for clinicians targeting biofilm and may facilitate improved visualization and removal of biofilms.
Oropallo, et al. (2021) created consensus guidelines for the clinical use of point of care fluorescence imaging to detect elevated bacterial burden in wounds. Their objective was to standardize how fluorescence imaging is used across wound care settings in order to address the limitations of relying on clinical signs and symptoms, which miss most wounds with high bacterial loads. To accomplish this, they used a two round Delphi process involving 32 experienced wound care clinicians who evaluated 80 statements about competencies, clinical indications, workflow steps, and imaging frequency. Participants reviewed literature based statements, contributed their own recommendations, and reached agreement on summary statements and an imaging workflow. The results demonstrated strong consensus on required competencies, indications for imaging based on clinical history and wound assessment, and appropriate integration of imaging into treatment planning. Participants overwhelmingly reported that fluorescence imaging changed treatment plans, improved wound healing, reduced microbiological sampling, and decreased amputation rates. The study is limited by its reliance on expert opinion, the absence of external validation of the proposed workflow, and the possibility that participants’ familiarity with the technology introduced bias in favor of its utility. Despite these limitations, the findings suggest that structured use of fluorescence imaging can enhance the detection of bacterial burden and guide more effective wound management.
The methodology used to produce this guideline has several important limitations, most of which arise from the structure and nature of the Delphi process itself. First, the Delphi method depends heavily on expert opinion rather than empirical data, which means the resulting statements reflect consensus but not necessarily validated clinical effectiveness. Because experts rely on their own experiences and interpretations, the process cannot fully eliminate subjectivity, and the absence of external verification limits the generalizability of the conclusions. Additionally, the panel was composed entirely of clinicians who already had firsthand experience with fluorescence imaging, which introduces selection bias. Their familiarity with and likely positive perceptions of the technology may have predisposed them to endorse its value, potentially inflating consensus levels and underrepresenting skeptical or inexperienced viewpoints. The Delphi survey also did not include patients or non clinical stakeholders, leaving out perspectives that influence real world adoption, resource use considerations, and feasibility. Another limitation lies in the structure of the survey: many statements that shaped the final guidelines originated from literature review and expert experience, but the authors did not formally measure interrater reliability or evaluate how individual experiences affected judgment. The methodology also did not incorporate clinical outcome data directly into the consensus process, meaning the guidelines are not evidence graded but instead rely on aggregated expert agreement. Finally, because the Delphi rounds were limited to two cycles, there is a possibility that additional rounds may have altered or further refined the consensus statements, especially for items that did not reach agreement in early phases. Overall, while the Delphi method is useful for generating expert driven guidance in areas such as bacterial fluorescence imaging that are lacking extensive evidence, these limitations should be considered when applying the guidelines to clinical practice.
A consensus document by an ISWCAP expert group (Sandy‑Hodgetts K, et al., 2022) concluded that "point-of-care fluorescence imaging is a diagnostic technology that could be of significant benefit in early identification of SSI and may be a useful tool for early detection of other SWCs." The consensus document identified several important limitations with this technology. First, the technology detects only bacteria that produce fluorescent metabolites, primarily porphyrins (red signal) and pyoverdines from Pseudomonas aeruginosa (cyan signal). Second, although emerging evidence shows improved SSI detection in surgical wounds, the strongest data come from chronic wound studies; research in surgical wounds is still developing. Third, interpretation of fluorescence images requires training, as multiple tissue components (e.g., blood, slough, dermis) also fluoresce, and differentiation between true bacterial signal and background fluorescence can be challenging for inexperienced clinicians. The document emphasizes that fluorescence imaging should complement, not replace, holistic clinical assessment. Finally, because the devices identify bacterial load above a threshold, they do not differentiate planktonic bacteria from biofilm nor specify bacterial species beyond the detection of Pseudomonas via cyan signal. This may limit its utility for precise microbiological decision‑making, and confirmatory testing may still be required in certain cases. The consensus document has a number of limitations. The methodology of the consensus document is limited primarily because it relies heavily on expert opinion rather than a formal systematic review process, offering no defined evidence‑grading framework, search strategy, or inclusion criteria; as a result, its recommendations reflect expert interpretation rather than rigorously appraised evidence. The document does not clearly describe how experts were selected, how consensus was measured, or how conflicts of interest (particularly relevant given industry sponsorship) were managed. In addition, much of the evidence incorporated is heterogeneous, preliminary, or derived from non‑surgical wound studies, which the authors themselves acknowledge requires further validation, limiting the generalizability of conclusions. Variability in global wound‑care practices and resource availability further constrains the applicability of the panel’s views, and the narrative approach increases the risk of confirmation bias in areas where panelists are active researchers or early adopters of new technologies.
Nair, et al (2024) aimed to provide an evidence based, holistic framework for assessing and managing leg ulceration associated with venous and arteriovenous insufficiency, with a focus on the role of compression therapy within comprehensive wound care. The study synthesized current pathophysiologic understanding, diagnostic approaches, and best practices for treatment, drawing on clinical guidelines, observational data, and expert consensus to highlight how accurate assessment of vascular status guides safe and effective compression. The authors emphasized a structured approach to evaluation that includes clinical examination, ankle brachial pressure index testing, duplex ultrasonography, and identification of complicating factors such as neuropathy, edema, infection, or mixed arterial disease. Although the primary focus was not infection diagnostics, the article referenced the importance of recognizing signs of bacterial burden and noted that emerging technologies such as bacterial fluorescence imaging may support earlier detection of increased bioburden, particularly when clinical signs are subtle, and could enhance decision making around debridement and antimicrobial interventions. In reviewing outcomes associated with compression therapy, the authors concluded that appropriately selected and consistently applied compression remains the cornerstone of venous ulcer management, improving healing rates, reducing recurrence, and addressing underlying venous hypertension. The article also identified limitations in the available evidence, including variability in study design across the literature, inconsistent definitions for mixed etiology ulcers, heterogeneity in compression systems and application techniques, and limited high quality comparative data for adjunctive therapies. These limitations underscore the need for further standardized clinical research to refine treatment pathways and evaluate supportive technologies such as fluorescence imaging within routine wound assessment.
In a pilot randomized controlled trial, Rahma and colleagues (2022) investigated whether adding point‑of‑care bacterial autofluorescence imaging to standard care could improve the clinical management of diabetic foot ulcers. The study aimed to determine whether real‑time visualization of bacterial burden would lead to more informed wound‑care decisions and ultimately faster healing. Adults with diabetic foot ulcers were randomized to receive either standard care alone or standard care supplemented with autofluorescence imaging at each clinic visit. Clinicians in the imaging arm could use the fluorescence findings to guide immediate interventions such as more targeted debridement, cleansing, or antimicrobial therapy. The investigators found that incorporating autofluorescence imaging significantly increased the detection of high bacterial loads compared with standard assessment alone and resulted in more frequent and more thorough debridement as well as more appropriately targeted antimicrobial measures. These imaging‑guided interventions were associated with a greater proportion of wounds achieving clinically meaningful reduction in area over the study period. As a pilot study, the trial was limited by its modest sample size, short follow‑up duration, and conduct at a limited number of centers, all of which may affect the generalizability of the findings. Additionally, clinicians were not blinded to group assignment, raising the possibility of performance bias. Despite these limitations, the results suggest that autofluorescence imaging may enhance decision‑making in diabetic foot ulcer care and warrants further evaluation in larger, multicenter trials.
Hsu and colleagues (2025) investigated whether real‑time fluorescence imaging could improve the quality of surgical debridement for chronic wounds by providing intraoperative visualization of bacterial burden. In this patient‑blinded randomized controlled trial, 200 adults with chronic wounds were assigned to either real‑time fluorescence imaging assisted debridement or conventional debridement. All patients first underwent an initial debridement, after which those in the fluorescence group received additional targeted debridement if more than 10 percent of the wound surface demonstrated red or cyan fluorescence, indicating elevated bacterial load. The primary outcomes included residual bacterial area before and after surgery, number of debridements performed, operation duration, high‑quality debridement rate defined as less than 10 percent residual bacterial area, and wound healing time. Secondary outcomes included antibiotic use, reinfection, complications, total operations, and hospitalization duration. The fluorescence group had significantly lower postoperative residual bacterial area, fewer wound healing days, fewer reinfections, shorter hospitalization, reduced antibiotic use, and fewer operations during hospitalization, although procedures took slightly longer and required an average of just over two debridements per case. Findings also indicated that experienced surgeons still left approximately 30 percent residual bacterial area after the initial debridement, highlighting the difficulty of visually identifying bioburden and the potential value of fluorescence guidance. Study limitations included the inability of fluorescence imaging to detect biofilm or differentiate bacterial species, restricted penetration depth, and limited performance in undermining wounds. The trial was conducted at a single center with a single operating surgeon, which may limit generalizability, and the operator could not remain blinded during later stages of the procedure. The study also did not assess patient‑reported outcomes such as pain or quality of life.
In a study by Kelso and Jaros (2024), the authors examined whether incorporating point‑of‑care bacterial fluorescence imaging could improve wound‑healing outcomes and infection control in long‑term care settings. Their objective was to determine whether real‑time visualization of bacterial burden, often asymptomatic in older, medically complex patients, would enable more targeted wound‑care decisions and reduce complications. Using a retrospective pre/post interventional cohort design, the investigators analyzed 167 pressure injuries from 100 Medicare beneficiaries before and after implementation of fluorescence imaging. The fluorescence cohort included 96 wounds compared with 71 wounds in the standard‑of‑care group, with similar baseline demographics and wound characteristics. Results showed markedly improved healing metrics after fluorescence imaging was introduced: 71% more wounds healed by 12 weeks, wounds healed 27.7% faster on average, and patients were 1.4 times more likely to achieve healing based on Kaplan‑Meier analysis. Infection‑related complications fell by 75.3%, and antibiotic prescribing shifted significantly from systemic to more appropriate topical therapy. These improvements suggest that earlier, objective bacterial detection enabled more proactive and targeted interventions. Study limitations include its retrospective design, the absence of randomization, potential confounding variables that could not be fully controlled, and limited generalizability beyond long‑term care and skilled nursing facility populations. Despite these constraints, the findings highlight the potential value of fluorescence imaging to improve wound care in highly complex patient groups.
A consensus document on antimicrobial resistance in wound care (Cole, et al., 2025) described bacterial fluorescence imaging as a useful point‑of‑care tool that detects clinically significant bacterial loads (≥10⁴ CFU/g) by illuminating bacterial fluorescence under 405‑nm violet light, allowing clinicians to verify the effectiveness of cleansing and debridement, localize residual bioburden, and improve diagnostic accuracy, particularly where visual assessment is limited, such as in patients with darker skin tones, while also supporting antimicrobial stewardship by helping reduce unnecessary antibiotic use. However, the document also notes key limitations: fluorescence imaging identifies fluorescence from bacteria but does not differentiate species with perfect specificity, does not replace cultures or PCR for identifying resistance genes or confirming infection, may detect fluorescence from dead or dormant bacteria, and therefore must be interpreted in clinical context rather than used as a standalone diagnostic method. The consensus document is built on the deliberations of a panel of 10 wound‑care experts who met during a single in‑person session at SAWC Fall 2024, meaning its recommendations stem primarily from expert opinion rather than a systematic, evidence‑graded methodology. The document explicitly notes that the content is "based on the discussion at the meeting," indicating that no formal consensus‑development framework (e.g., Delphi method, RAND/UCLA appropriateness methodology) was used, and thus the process lacked structured voting, predefined evidence‑grading criteria, or quantitative consensus thresholds. The supplement also acknowledges that panelists received honoraria and that the project was financially supported by multiple industry sponsors, introducing a potential conflict‑of‑interest bias, even though disclosures are provided. Additionally, many of the cited evidence bases discussed in the document include noted gaps, limited high‑quality comparative trials, and inconsistent clinical evidence, constraints that inherently limit the strength and generalizability of the guidance produced.
A consensus document (Serena, et al., 2025) outlined the multidisciplinary panel’s agreement that fluorescence imaging offers an objective and clinically valuable method for detecting clinically significant bacterial burden throughout the surgical care continuum. The objective of the consensus was to evaluate current evidence and expert experience to define how point-of-care fluorescence imaging should be integrated into pre operative, intra operative, and post operative surgical workflows in order to improve wound assessment, guide debridement, enhance graft and flap success, and reduce surgical site complications. The panel convened for a structured two hour roundtable discussion that involved review of pre meeting literature summaries and case studies, followed by thematic analysis to extract consensus points, which required at least 80 percent agreement among participants. Results showed that fluorescence imaging supports early identification of bacterial load greater than 10⁴ CFU per gram, improves accuracy of pre operative planning, and enhances patient education and interdisciplinary communication. Intra operatively, the technology aids precision debridement, helps confirm a cleaner surgical field before closure, and has been associated with improved graft outcomes and fewer revision surgeries. Post operative use allows earlier recognition of subclinical bacterial recurrence, informs antimicrobial decisions, and supports documentation that may be beneficial both clinically and medico legally. Study limitations include reliance on a brief expert panel discussion rather than systematic evidence grading, potential bias due to funding support from the device manufacturer, challenges in intra operative implementation due to lighting constraints, and the need for future prospective studies to validate the recommendations across broader patient populations and surgical specialties.
A systematic review and meta‑analysis by Berenguer‑Pérez and colleagues (2024) aimed to evaluate the diagnostic accuracy of non‑culture‑based methodologies for detecting microorganisms in chronic wounds, with the goal of identifying alternatives or complements to conventional microbiological culture. The authors specifically focused on tests that identify microbial presence rather than clinically diagnosing infection, which remains reliant on clinical signs and symptoms. The review included a wide range of chronic wound types and emphasized methods that could provide faster, more precise microbial detection to support targeted wound management.
The investigators conducted the review in accordance with PRISMA‑DTA guidelines, searching PubMed, CINAHL, Scopus, and Web of Science through February 2023. Nineteen studies met inclusion criteria, including cohort, cross‑sectional, and retrospective designs, and were assessed for risk of bias using the QUADAS‑2 tool. Diagnostic methods evaluated included autofluorescence imaging, polymerase chain reaction (PCR), colorimetric assays, voltammetry, biosensors (including electronic nose and metabolite sensors), enzymatic tests, and staining techniques. Meta‑analysis using random‑effects models was feasible for PCR‑based tests and colorimetric kits, while other technologies, including autofluorescence imaging, were synthesized narratively due to heterogeneity and incomplete reporting.
Overall results demonstrated that PCR‑based diagnostics showed the highest diagnostic accuracy, with pooled sensitivity of approximately 96%, specificity of 92%, and an excellent summary receiver‑operating characteristic curve (AUC ≈ 0.97), though with substantial heterogeneity across studies. Colorimetric tests exhibited high specificity but low sensitivity, limiting their utility as standalone diagnostic tools. Autofluorescence imaging was evaluated in several studies, primarily as a point‑of‑care technique detecting endogenous bacterial fluorescence. When used alone, autofluorescence imaging showed moderate diagnostic accuracy, but its performance improved substantially when combined with clinical signs and symptoms, clearly outperforming clinical assessment alone. Autofluorescence imaging was particularly valuable for identifying high bacterial burden, visualizing spatial distribution of microorganisms (including biofilm), and guiding sampling and treatment decisions. However, it did not reliably distinguish bacterial species and still required complementary microbiological or molecular testing for pathogen identification.
Key limitations of the review included marked heterogeneity in wound types, study designs, reference standards (culture vs clinical signs), and outcome definitions (bioburden vs pathogen detection), which complicated data synthesis and interpretation. Many studies had small sample sizes, variable use of antibiotics at the time of sampling, and potential conflicts of interest, particularly in technology‑specific trials. Additionally, no single non‑culture method demonstrated universal superiority over culture across all scenarios. The authors concluded that no single alternative diagnostic method can fully replace microbiological culture, but non‑culture‑based approaches—particularly PCR and autofluorescence imaging—offer meaningful advantages as adjunctive tools. Autofluorescence imaging was highlighted as a promising bedside technology that enhances bacterial detection and clinical decision‑making when integrated with clinical assessment, rather than used in isolation. Future research should prioritize standardized methodologies, clearer reference standards, and homogeneous study designs to better define how autofluorescence imaging and other rapid diagnostics can be optimally integrated into routine chronic wound care. A systematic evidence review by Edwards and colleagues (2024) evaluated the diagnostic accuracy of methods used to identify infection in chronic wounds that could be applicable to adult patients in community settings, where most wound care and antibiotic prescribing occurs. The primary objective was to determine whether emerging diagnostic technologies, beyond clinical signs and symptoms, can reliably distinguish infected from non‑infected chronic wounds and thereby support better clinical decision‑making and antimicrobial stewardship in non‑specialist settings. The authors conducted a systematic review of diagnostic test accuracy studies following PRISMA‑DTA guidance, with a protocol registered in PROSPERO. Comprehensive searches of MEDLINE, Embase, and CINAHL from 2011 to April 2022 identified studies that compared an index diagnostic test with an accepted reference standard (deep tissue biopsy culture or wound swab microscopy and culture) in adults with chronic wounds lasting more than four weeks. Study selection, data extraction, and risk‑of‑bias assessment were performed independently by two reviewers, with methodological quality evaluated using the QUADAS‑2 tool. Due to the small number of eligible studies and marked heterogeneity in study design and outcomes, results were synthesized narratively rather than by meta‑analysis. Only four studies met the stringent inclusion criteria. Two studies assessed autofluorescence imaging using the MolecuLight i:X device compared with deep tissue biopsy culture, while two evaluated biochemical biomarkers in wound fluid (enzymatic markers or bacterial protease activity) compared with wound swab culture. For autofluorescence imaging, sensitivities ranged from approximately 56% to 65% when used alone and increased modestly when combined with clinical judgement, while specificities ranged from 81% to 100%. Autofluorescence imaging improved sensitivity compared with clinical assessment alone, which consistently showed very poor sensitivity despite high specificity. However, negative predictive values for autofluorescence imaging were low, reflecting the high prevalence of infection in study populations. Biomarker‑based tests demonstrated mixed performance, with some showing high specificity but wide confidence intervals due to small sample sizes, and others showing low sensitivity and specificity. Overall, the review concluded that autofluorescence imaging shows promise as an adjunctive tool, particularly for improving detection of high bacterial burden and informing wound assessment beyond visual inspection. However, the evidence was insufficient to support its use as a standalone diagnostic test to rule in or rule out infection in community settings, particularly for guiding decisions about systemic antibiotic prescribing. Importantly, both autofluorescence imaging studies defined infection using a bacterial load threshold aligned with the device’s detection capabilities (>10⁴ CFU/g), rather than more traditional thresholds, and they used autofluorescence findings to guide biopsy sampling, introducing incorporation bias. Key limitations of the evidence base included the very small number of eligible studies, recruitment exclusively from secondary care wound clinics rather than true community settings, high or unclear risk of bias in all included studies, and heterogeneity in reference standards and infection definitions. As a result, the authors concluded that no currently available diagnostic method (including autofluorescence imaging) has sufficient high‑quality evidence to be recommended for diagnosing infection in chronic wounds in community practice. They emphasized the need for well‑designed, community‑based diagnostic accuracy studies that evaluate autofluorescence imaging and other emerging technologies under real‑world conditions and assess their impact on clinically meaningful outcomes such as antibiotic use, healing time, and patient quality of life.
A systematic evidence review by Badrie and colleagues (2025) aimed to evaluate the clinical utility and diagnostic accuracy of autofluorescence imaging (AFI) devices for detecting clinically significant bacterial burden in wounds, compared with conventional assessment methods such as white light inspection, clinical signs and symptoms, and microbiological sampling. The review specifically sought to determine whether AFI could reliably identify moderate to heavy bacterial loads (≥10⁴ CFU/g), improve wound swabbing accuracy, guide debridement, and support treatment decision-making in patients with chronic or non‑healing wounds.
The authors conducted a comprehensive systematic review following PRISMA 2020 guidelines and registered the protocol with PROSPERO. A structured literature search was performed in January 2025 across multiple databases, including MEDLINE, EMBASE, CINAHL, Cochrane CENTRAL, and Scopus. Quantitative clinical trials and observational studies published in English and evaluating AFI for bacterial detection in wounds were eligible. Two independent reviewers screened studies, extracted data, and appraised methodological quality using the Evidence‑Based Literature (EBL) checklist. Due to substantial heterogeneity in study design, populations, wound types, devices, and outcome measures, meta‑analysis was not performed; instead, a narrative synthesis was undertaken. Seventeen studies published between 2015 and 2023 met inclusion criteria, most evaluating the MolecuLight i:X device and one assessing the PRODIGI prototype. Across studies, AFI generally demonstrated higher diagnostic accuracy than conventional assessment methods, with reported sensitivities ranging from 45% to 100% and specificities from 55.6% to 92.3% for detecting bacterial loads ≥10⁴ CFU/g. AFI consistently outperformed white light and clinical signs‑based assessments, particularly in wounds without overt clinical signs of infection. Secondary outcomes showed that fluorescence‑guided swabbing identified higher bacterial yields by targeting peri‑wound and subsurface areas often missed by standard techniques. Multiple studies also reported that AFI‑guided debridement resulted in significant reductions in bacterial burden and prompted changes in treatment strategies, with some evidence of improved wound healing trajectories. The review’s limitations include marked heterogeneity among included studies, small sample sizes in several trials, and variability in microbiological reference standards and fluorescence interpretation thresholds, all of which limited comparability and precluded quantitative pooling of results. Many studies were non‑randomized or observational, and industry funding was common, raising the potential for bias. Additionally, the evidence base lacked large, independent multicenter randomized controlled trials, and long‑term clinical outcomes such as infection rates and sustained healing were inconsistently reported. Overall, while the review supports AFI as a promising adjunctive tool for wound assessment and bacterial detection, the certainty of evidence was judged as moderate to low, underscoring the need for further high‑quality research.
Clarifi Imaging System
The Clarifi Imaging System (Modulated Imaging Inc.) provides real-time micro-vascular assessment in the office setting. It is the 1st non-invasive, wide field of view, non-contact micro-vascular assessment tool that provides quantitative measurement of hemoglobin (Hb) oxygen and distribution with color images in seconds. This device can aid in identifying areas of potential compromised circulation in the tissue. Tissue hypoxia due to compromised circulation occurs in the feet of patients at risk for foot ulceration, with existing ulcer(s), and those with peripheral arterial disease (PAD). Clarifi employs a patented technology known as Spatial Frequency Domain Imaging (SFDI) to measure oxygen delivery and extraction. Using multiple wavelengths of light, Clarifi quantifies and maps oxygenation and distribution of Hb in tissue.
Jaspers et al (2019) stated that reliable and valid assessment of burn wound depth or healing potential is essential to treatment decision-making, to provide a prognosis, and to compare studies evaluating different treatment modalities. In a systematic review, these investigators examined the quality of relevant measurement properties of techniques that aim to evaluate burn wound depth or healing potential. They carried out a systematic literature search using PubMed, Embase and Cochrane Library. Two reviewers independently evaluated the methodological quality of included articles using an adapted version of the Consensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. A synthesis of evidence was performed to rate the measurement properties for each technique and to draw an overall conclusion on quality of the techniques. A total of 36 studies were included, evaluating various techniques, classified as laser Doppler techniques; thermography or thermal imaging; and other measurement techniques. Strong evidence was found for adequate construct validity of laser Doppler imaging (LDI). Moderate evidence was found for adequate construct validity of thermography, video-microscopy, and spatial frequency domain imaging (SFDI). Only 2 studies reported on the measurement property reliability. In addition, considerable variation was observed among comparator instruments. The authors concluded that considering the available evidence, it appeared that LDI is currently the most favorable technique for examining burn wound healing potential. Moreover, these researchers stated that further investigations are needed into thermography, video-microscopy, and SFDI to examine their full potential. Future studies should focus on reliability and measurement error, and provide a precise description of which construct is aimed to measure.
Zhang et al (2023) noted that post-operative surgical wound infection is a serious problem globally, including in countries with advanced healthcare systems, and a method for early detection of infection is needed. These researchers examined SFDI for distinguishing changes in surgical wound healing based on the tissue scattering properties and surgical wound width measurements. They developed a comprehensive numerical method by applying a three-dimensional (3D) Monte Carlo simulation to a vertical heterogeneous wound model. The Monte Carlo simulation results were validated using resin phantom imaging experiments. These investigators reported on the SFDI lateral resolution with varying reduced scattering value and wound width and discussed the partial volume effect at the sharp vertical boundaries present in a surgical incision. The detection sensitivity of this method was dependent on spatial frequency, wound reduced scattering coefficient, and wound width. The authors provided guidelines for future SFDI instrument design and explanation for the expected error in SFDI measurements.
Feng et al (2024) presented a motion-resistant 3-wavelength SFDI system with ambient light suppression using an 8-tap complementary metal-oxide semi-conductor (CMOS) image sensor (CIS) developed at Shizuoka University. The system addressed limitations in conventional SFDI systems, enabling reliable measurements in challenging imaging scenarios that are closer to real-world conditions. These researchers examined the system's capability of mitigating motion artifacts and ambient light bias via tissue phantom reflectance experiments and in-vivo volar fore-arm experiments. They incorporated the Hilbert transform to reduce the required number of projected patterns per wavelength from 3 to 2 per spatial frequency. The 8-tap image sensor had 8 charge storage diodes per pixel; thus, simultaneous image acquisition of 8 images based on multi-exposure was possible. Taking advantage of this feature, the sensor simultaneously acquired images for planar illumination, sinusoidal pattern projection at 3 wavelengths, and ambient light. The ambient light bias was eliminated by subtracting the ambient light image from the others. Motion artifacts were suppressed by reducing the exposure and projection time for each pattern while maintaining sufficient signal levels by repeating the exposure. The system was compared to a conventional SFDI system in tissue phantom experiments and then in-vivo measurements of human volar fore-arms. The 8-tap image sensor-based SFDI system achieved an acquisition rate of 9.4 frame sets/second, with 3 repeated exposures during each accumulation period. The diffuse reflectance maps of 3 different tissue phantoms using the conventional SFDI system and the 8-tap image sensor-based SFDI system showed good agreement except for high scattering phantoms. For the in-vivo volar fore-arm measurements, this system successfully measured total Hb concentration, tissue oxygen saturation, and reduced scattering coefficient maps of the subject during motion (16.5 cm/s) and under ambient light (28.9 lx), exhibiting fewer motion artifacts compared with the conventional SFDI. The authors concluded that this study showed the feasibility and potential of the motion-resistant and ambient light-resistant SFDI system, which can provide enhanced imaging capabilities for accurate measurements in real-world clinical settings.
Concurrent Optical and Magnetic Stimulation (COMS) Therapy
The COMS One therapy system (Piomic Medical AG, Zurich, Switzerland) is intended to promote wound healing in chronic leg and foot ulcers in addition to standard of care. The COMS One therapy system consists of the following: COMS One, a reusable therapy unit; COMStouch, a disposable sterile wound adapter for one time treatment; and COMsfix (single use)/COMSrefix (multi-use) fixation band, The device is locally applied to the wound area for 16 min, 2-3 times per week, over a recommended duration of 6-8 weeks. As of yet, the COMS One therapy system has not been granted FDA clearance. The technology of this therapy system incorporates optical and magnetic stimulation. The optical stimulation component emits light by two types of light-emitting diodes (LEDs) in the wavelength of 660 nm (red) and 830 nm (near infrared) range of the electromagnetic spectra. The magnetic stimulation component is produced by a coil emitting pulse modulated magnetic fields in the extremely low frequency ( ELF ) range of the electromagnetic spectra.
Reinboldt-Jockenhöfer et al. (2022) conducted a multicentre, prospective, comparative, clinical trial in patients with hard-to-heal wounds on lower extremities of different aetiologies who were treated with concurrent optical and magnetic stimulation (COMS) as an adjunct to standard of care (SOC). The primary endpoint was safety and secondary endpoints included wound healing, pain and wound-specific quality of life (Wound-QoL).
Of the 40 patients in the intention to treat population, 37 patients were included in the analysis of the primary endpoint (primary endpoint population, (PEP), n=37). A further subgroup of 30 patients was included in the analysis of the secondary endpoint (secondary endpoint population (SEP), n=30). The SEP was stratified based on patients' responsiveness to SOC in an SOC non-responder subgroup (NRSG), n=21, and in an SOC responder subgroup (RSG), n=9. Of the 102 adverse events (AEs) recorded, 96% were 'mild' or 'moderate', and 91% were either a singular or transient event. Only 11 AEs were serious and associated with inpatient treatments not related to the study intervention. In the NRSG, reductions in wound size were found to be statistically significant within the different study periods. Also, a quickening of healing rate was observed between the baseline and the first four weeks of COMS treatment (p=0.041). The near-complete and complete wound closure rate in the SEP following 12 weeks were 60% and 43%, respectively. A reduction in pain across the treatment group was statistically significant (p≤0.002 for both the SEP and NRSG). The Wound-QoL score improved by 24% during the study (p=0.001).
The investigators concluded that COMS is a novel treatment option that is safe and effective for patients with hard-to-heal wounds on lower extremities, especially in patients unresponsive to SOC.
Traber et al. (2023) conducted a multi-center, prospective, comparative clinical trial consisting of eleven patients with chronic leg and foot ulcers who were treated with concurrent optical and magnetic stimulation (COMS) additively to Standard of Care (SOC). The investigators aimed to evaluate the effects of COMS on oedema and perfusion through measuring tissue oxygenation and water index, using hyperspectral imaging.
Hyperspectral images were taken during patient visits prior to and following treatment to evaluate short- and long-term hemodynamic and immunomodulatory effects through changes in tissue oxygenation and water index.
The eleven patients had an average time of wound onset at 183 days with 64% of them not responsive to SOC. At week 12, the rate of near-complete and complete wound closure was 64% and 45%, respectively. COMS therapy with SOC resulted in an increased short-term tissue oxygenation over the 8-week treatment phase, with oxygen levels decreasing in-between patient visits. A decrease in tissue water content after the therapy, with a general accumulation of water levels was noted in-between patient visits. Long-term analysis was impeded by the lack of absolute values in hyperspectral imaging and the dynamic existence of patient parameters during visits, resulting in high interpatient and intervisit differences.
The study demonstrated that COMS therapy as an adjunct to SOC showed a positive short-term effect on inflammation and tissue oxygenation in chronic wounds of differing etiologies. These results reinforced the body of evidence for COMS therapy as a safe and effective treatment option, especially for stagnant and inflammatory wounds requiring efficient phase transition towards healing.
In a case series, Neyens et al. (2024) explored concurrent optical and magnetic stimulation (COMS) effects on hard-to-heal wounds in real world settings. Individuals received COMS 1 to 3 times per week for up to 12 weeks alongside standard wound care.
The series included 27 patient total (18 female and 9 male) and a mean patient age of 72 years. Wounds unresponsive to standard wound care included: venous leg ulcers (VLUs, n=13); mixed leg ulcers (MLUs, n=4); diabetic foot ulcers (DFUs, n=1); pressure ulcers (PUs, n=5); and traumatic wounds (TWs, n=4). COMS was applied twice a week on average with an overall mean wound area reduction of 69%. In 24 patients, COMS was used mainly to achieve wound closure by the 12-week period end, of which: 12 were classified as complete wound closure (50%; VLUs=8, PUs=3 and TW=1); four as likely-to-heal (17%; VLUs=2 and MLUs=2); four as 'improved' (17%; MLU=1, DFU=1 and TWs=2); and four as 'non-responding' (17%; VLUs=3 and MLU=1). The best outcomes were achieved in PUs and VLUs (100% and 62% categorised as completely healed, respectively). When used not for the purpose of wound closure, COMS was successfully used to debride two PUs, and for wound bed preparation in one TW.
COMS, in this case series, demonstrated positive effects and appeared to offer benefit in healing different types of hard-to-heal wounds in community health and homecare settings. Furthermore, Novel COMS therapy benefits that emerged included: positive outcomes for PU and VLU treatment; COMS as a potential debridement method when sharp debridement is impractical; and COMS as a promising approach to prepare wound beds for subsequent skin grafting or skin replacement procedures.
DeepView Wound Imaging System
The artificial intelligence (AI) driven DeepView System (Spectral AI Inc., Dallas, TX) received Breakthrough Device Designation from the U.S. Food and Drug Administration (FDA) in 2018. The device uses multispectral imaging and AI algorithms to predict burn healing potential. The DeepView System is intended for use in burn care settings, including both burn centers and emergency departments. Spectral AI is pursuing the De Novo regulatory pathway since this is a novel technology and does not have a predicate device in the current U.S. marketplace (Spectral AI, 2025).
The DeepView System is designed to function as a non-invasive, predictive medical device with an associated platform, which combines multispectral imaging with a proprietary AI algorithm to assess the healing potential of burn wounds. Furthermore, it provides healthcare providers with a non-healing prediction-on the same day of injury and up to a week (7 days) post injury, facilitating earlier and more informed treatment decisions (Spectral AI, 2025).
Thatcher et al. (2023) conducted a prospective feasibility study evaluating the performance of a rapid, non-invasive, multispectral imaging device using an artificial intelligence (AI)-powered algorithm in predicting burn wound healing potential, particularly for burns of indeterminate depth. The investigators collected 406 multispectral images from burn patients within 72 hours of injury and serially for up to 7 days. The patient population consisted of individuals with acute burns, including those with indeterminate depth wounds, as identified by the treating clinician. Burn depth was based on biopsy and 21-day healing outcomes as the reference standard. The study compared three convolutional neural network architectures and one ensemble model in their capability to automatically highlight areas of nonhealing burn regions within images.
The primary outcome measures were diagnostic accuracy (i.e., sensitivity, specificity, and positive predictive value [PPV]) using the reference standard. The top performing algorithm was the ensemble with 81% sensitivity, 100% specificity, and 97% PPV. The algorithm demonstrated 70% sensitivity, 100% specificity, 97% PPV and, 100% negative predictive value for for burns labeled as indeterminate. Secondary outcome measures included temporal evolution of algorithm performance, which showed improvement in accuracy (i.e., increase in sensitivity and PPV), peaking around day 2.5 post-injury.
Study limitations included the feasibility design (i.e., not powered for definitive diagnostic accuracy and generalizability limited by the single-device, single-algorithm approach), relatively small sample size, limited sample diversity (i.e., may not reflect all burn types or patient demographics), and short-follow up (i.e., focus was on early healing prediction, not long-term outcomes). A potential bias was that the reference standard included subjective clinical judgment and biopsy interpretation.
The study demonstrated that a non-invasive multispectral imaging device combined with an AI-powered algorithm can accurately identify nonhealing burns, including indeterminate burns, within the first week post-injury. The ensemble AI model showed high specificity and PPV suggesting that it could improve decision-making and outcomes in burn care.
Carter et al. (2025) conducted a prospective, multicenter, proof-of-concept study at three burn centers. The investigators aimed to refine and validate an artificial intelligence (AI)-based algorithm for burn wound depth assessment using multispectral imaging (MSI) data and convolutional neural networks (CNNs) analysis. Consenting subjects were prospectively enrolled and stratified into two groups based on anticipated course of wound healing: those with wounds likely to heal nonoperatively by 21 days and those expected to benefit from surgical intervention. All subjects underwent MSI sensor imaging at enrollment then once daily until discharge/excision. For the nonoperative subjects, wound healing was assessed at 21 days, while the operative subjects underwent tissue biopsies to provide histopathological confirmation of burn depth. A panel of burn experts, designated as the "Truthing Panel" established a "ground truth" for each wound, which was then converted to pixel-level data for algorithm training and validation. The algorithm training consisted of ten CNNs (eight unique deep learning algorithms and two ensemble models) on the collected MSI data.
The study collected 1,037 MSI images and 161 biopsies from 124 enrolled subjects (100 adult and 24 pediatric patients). The most effective CNN algorithm displayed an area under the curve (AUC) 0.95, with an overall accuracy of 89.29%, sensitivity of 90.51%, and specificity of 87.22% in classifying burn wound depth. These results show a high level of diagnostic performance, close to an accuracy of histopathological assessment and exceeding the typical accuracy of clinical examination alone.
A notable finding was the significant impact of "time-since-injury" on algorithm performance. The accuracy of CNN was lowest (88.5%) at 1 to 2 days post-injury and highest (93.5%) at 3 to 4 days post-injury, with covariate "time-since-injury" reaching statistical significance (p < 0.0001). These results are suggestive that the optical properties of burn wounds, as collected by MSI, develop over time and that the algorithm's performance is optimized when imaging is performed several days following injury.
The CNN's learning curve predicted that an accuracy of 94.04% could be achieved after enrolling 374 subjects in a future training study. This finding emphasizes the importance of large, high-quality datasets for the continued refinement of AI algorithms in burn care.
Several study limitations were noted by the investigators. First, the sample size in this proof-of-concept study was modest with respect to the heterogeneity of burn wounds found in clinical practice. Second, the use of an expert panel consensus and histopathology introduced potential interobserver variability and sampling error. Third, the findings about the impact of time-since-injury on algorithm performance suggest that the optimal timing for MSI imaging may vary between patients and wound types. Finally, the study did not provide a report of any unexpected adverse events or significant safety concerns related to MSI imaging or algorithm use.
The study demonstrated the accuracy of the AI algorithm, especially when imaging is performed several days after injury, suggests that MSI combined with deep learning can potentially augment or even surpass traditional methods of burn depth evaluation. The investigators showed that a deep learning algorithm can exhibit high accuracy in classifying burn wound depth, with performance optimized by considering the time elapsed since injury. Further validation in larger and more diverse populations is warranted.
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