Redefining Wound Healing Using Near-Infrared Spectroscopy

ABSTRACT OBJECTIVE No standard definition for a completely healed wound currently exists; it is recommended that providers use a reliable wound assessment tool to determine healing. The objective of this feasibility study was to determine if a point-of-care, noncontact, near-infrared (NIR) imaging device could provide an objective measure of wound resolution and guide clinical decision-making for the optimal time to transition from protective wound dressings and gradual return to full activity. METHODS In this single-center feasibility study, adult patients 18 years and older with a lower extremity wound of any size and etiology were seen weekly for wound assessment and standard-of-care treatment. The researchers performed serial imaging with a point-of-care, noncontact, NIR imaging device (SnapshotNIR; Kent Imaging Inc) to assess the wound and surrounding skin and evaluated the difference in time to 100% reepithelialization on visual inspection and homogeneous tissue oxygen saturation levels at the wound site and surrounding closed skin envelope. RESULTS An average time difference of 13.5 ± 10 days (median, 12 days; range, 0–35 days) was observed between 100% reepithelialization on visual wound inspection and imaging assessment. Further, NIR imaging could determine when a patient was at risk for recurrent wound breakdown. CONCLUSIONS The addition of point-of-care, noncontact, NIR imaging may help guide clinical decision-making for the optimal time to transition from protective wound dressings with gradual return to full activity and minimize wound recurrence.


INTRODUCTION
Industry guidance for the definition of complete wound closure is a wound that has achieved "reepithelialization without drainage or dressing requirements confirmed at two consecutive study visits 2 weeks apart." 1 Despite this guidance, standard use of this definition as a primary clinical and study end point in wound care is lacking. 1 In clinical studies, the definition of a healed wound ranges from achieving a wound area between 0 and 0.1 cm 2 to the proposed industry guidance definition. 3However, the most common definition used in clinical studies from 2010 to 2019 remains the date when a wound is determined to have achieved 100% reepithelialization on visual inspection. 2,4The primary concern with this latter definition is that the date of 100% reepithelialization may only signify transient wound coverage and not complete healing. 2 Discontinuation of protective wound coverings and activity restrictions at this point may result in recurrence if the wound is not truly healed.
8][9] Transitioning to normal activity when a wound is first reepithelialized but not fully healed may also contribute to wound recurrence.
Given that the common definition of complete wound healing primarily refers to visual inspection, there is an unmet clinical need for additional measurement tools to objectively assess wound healing progression.Therefore, the aim of this study was to determine if point-of-care use of a noncontact, near-infrared (NIR) imaging device that measures superficial tissue oxygenation could provide an objective measure of wound resolution and guide clinical decision-making regarding the optimal time to transition from protective wound dressings with gradual return to full activity to minimize the risk of wound recurrence.

METHODS
This was a single-center feasibility study conducted at a military treatment facility to evaluate the ability of pointof-care, noncontact, NIR imaging to provide objective assessment of wound resolution.Researchers selected eligible patients from those being seen by providers in the wound care department.Patients were included in the study if they were 18 years or older and had a wound on their lower extremity of any size and etiology.All wounds were negative for clinical signs and symptoms of infection.
Patients were seen weekly for wound assessment and standard-of-care treatment.Debridement, dressings used, frequency of dressing changes, offloading, and compression were performed at the discretion of the provider to manage exudate and promote a favorable (eg, moist) wound healing environment.Personnel trained on use of the point-of-care, noncontact, NIR imaging device (Snapshot NIR ; Kent Imaging Inc) performed site-specific wound tissue oxygenation and relative perfusion measures.The trained personnel would calibrate the device, per manufacturer directions, prior to positioning the device to capture an image of the wound bed and periwound area.Image capture takes seconds to obtain.
The first imaging assessment occurred when the patient was first evaluated for the wound.Imaging assessment then continued during the course of healing at intervals deemed necessary by the treating provider, on the date the wound was determined to be 100% reepithelialized on visual inspection, and thereafter until the tissue oxygenation saturation levels within the wound bed were similar to those of the surrounding, closed soft tissue envelope.Imaging assessment was performed after imaging capture with tissue oxygen saturation levels recorded at a standardized central point within the wound bed and several points away from the wound in an area free of soft tissue breakdown.Imaging analysis took no more than 5 minutes.
In addition to obtaining data from the NIR imaging device, researchers also obtained patient data from participants' electronic medical records.Collected data were deidentified and stored in an Excel spreadsheet (Microsoft Inc).Variables collected included patient age, sex, weight, height, body mass index, history of tobacco use, comorbidities (ie, diabetes; coronary arterial disease, including history of myocardial infarction; hypertension; cerebrovascular accident/transient ischemic attack; peripheral arterial disease; hyperlipidemia; and chronic kidney disease), wound etiology, the date the wound was healed on visual inspection, the date the wound was considered healed based on NIR imaging assessment, and wound recurrence.All patients were informed of the aim of the study and provided written informed consent to publish the case details and associated deidentified image assessments.

Statistical Analysis
Because this was a feasibility study, the authors did not perform a power calculation.The difference in time between the date 100% reepithelialization was noted on clinical examination and the date when wound area tissue oxygen saturation returned to patient baseline levels was calculated using descriptive statistics.
The average difference in time between wound resolution based on visual inspection versus return to patient baseline tissue oxygenation level at the wound site on NIR imaging was 13.5 (SD, 10) days (median, 12 days; range, 0-35 days; Table 2).One patient had ulcer recurrence following transition from total contact casting to custom shoe use after being determined as healed on both visual inspection and NIR imaging.The wound resolved with reinitiation of total contact casting.The time difference in healing on visual inspection and NIR imaging was 1 week for both the initial and recurrent wound.

DISCUSSION
Point-of-care, noncontact, NIR imaging provided an objective assessment of complete wound resolution at an average of 2 weeks following the date a wound was determined to be reepithelialized on visual inspection, coinciding with industry guidance on the definition of complete wound healing.However, even following industry guidance by continuing protective measures for 2 weeks beyond the index date of wound resolution on visual inspection may not be enough to prevent wound recurrence: Some patients took up to 5 weeks to demonstrate a healed wound with NIR imaging (Figure 1).These findings suggest that incorporating NIR imaging may help guide clinical decision-making on the optimal time for transition from protective wound dressings with gradual return to full activity to minimize the risk of wound recurrence.
An analysis of current research trends on DFUs from 2004 to 2020 found the top-cited article to be a review on DFUs and their recurrence, highlighting the importance of this topic. 7In an analysis of clinical studies involving the use of cellular and/or tissue-based products to aid in wound healing, when wound recurrence was reported, it most often occurred within the first 2 weeks after a wound was determined to be healed on clinical examination. 3hose findings combined with the results of the present study suggest that the date of 100% reepithelialization on visual inspection may not be the optimal time point for considering a wound to be completely healed.Discontinuation of protective measures at this time may result in a higher risk of wound recurrence in addition to further complications.Because of the complexity of determining if a wound is healed based on clinical examination alone, the US Food and Drug Administration recommends that a healed wound be defined using the industry guidance definition, a minimum of 3 months of follow-up, and use of a reliable wound assessment tool to determine resolution. 1 Noncontact NIR imaging may be such a tool.
As seen in this feasibility study, point-of-care, noncontact, NIR imaging provides rapid, objective assessment of ongoing activity related to wound healing not visible on clinical examination in wounds that have achieved 100% reepithelialization.The variance in time to healing noted on NIR imaging compared with time to 100% reepithelialization on visual inspection parallels study findings that skin tensile strength increases from 3% in the first week to 20% in the third week after wound healing has occurred, 10 corresponding with the time when deep dermal healing is happening. 11Deep dermal healing is associated with localized inflammation and hyperemia, resulting in elevated tissue oxygen saturation levels on NIR imaging. 12,13Wound healing corresponds with return of tissue oxygenation saturation levels and relative perfusion to the patient's baseline homeostatic flow (Figure 2). 14Visualization of deep dermal microvascular oxygenation and relative perfusion with NIR imaging can assist clinicians in determining when deep dermal healing has occurred and the optimal time for transition to protective shoe gear and normal activities.Return of maximal skin tensile strength, approximately 80% of baseline, occurs during the remodeling phase of wound healing, which can take from 3 months to several years. 11he use of point-of-care, noncontact, NIR imaging also helps providers determine when to reemploy protective dressings.For the one patient who experienced recurrent ulceration in this study, increased tissue oxygenation saturation levels were seen prior to breakdown, indicating inadequate offloading with the patient's protective shoe gear.Resumption of offloading in a total contact cast enabled wound resolution, and the patient's protective shoe gear was modified to prevent another recurrence.Use of NIR imaging in this capacity enables early identification of areas at risk for breakdown, allowing for early intervention and potential circumvention of detrimental sequelae of lower extremity ulcerations.

Limitations
Limitations of this study include that it was a single-center feasibility study with no control group or comparator, had a small sample size and short follow-up duration, and required correct interpretation of the images obtained.However, the present findings support current industry-recommended guidance on the definition of complete wound healing.However, the ability of point-ofcare, noncontact, NIR imaging to provide an objective assessment of wound healing is also in line with

Figure 1. CLINICAL AND NEAR-INFRARED IMAGING ASSESSMENT OF A TRAUMATIC ANTERIOR LEG WOUND
A, Clinical photograph of a wound on the date it was defined as 100% re-epithelialized (eg, healed) on visual inspection (June 13, 2022).B, In the corresponding near-infrared imaging assessment, note the increased oxyhemoglobin within the wound bed, most intense at the proximal aspect of the wound (red circle).C, Clinical photograph of wound approximately 2 weeks later (June 24, 2022).The wound remains closed, meeting industry guidance on the definition of a completely healed wound.D, The corresponding near-infrared imaging assessment shows continued increased tissue oxygenation saturation at the proximal aspect of the wound (red circle) signifying ongoing healing in this area.

ADVANCES IN SKIN & WOUND CARE • MAY 2024
recommendations for a standardized methodology for defining a healed wound. 2 Future research should use a control or comparator, include a larger sample size, consider how other risk factors may affect healing (eg, wound location, patient comorbidities, patient weight, and body mass index), and evaluate correlations with other measurements of healing (eg, transcutaneous oxygen pressure measurements, local temperature readings).Correct interpretation of NIR imaging assessments is also essential.Images can be affected by the phase of healing; local ischemia; infection; edema; tissue and material in the wound bed; and treatment measures, such as hyperbaric oxygen therapy, application of local vasoconstrictors to assist with debridement, and compression therapy. 15A standardized method of obtaining tissue oxygenation saturation levels percentages within the wound bed and in the periwound area may also be useful.

CONCLUSIONS
Currently, there is no standard definition of a healed wound in wound care.The widely used definition of 100% reepithelialization on clinical examination to discontinue protective measures and return the patient to activity may contribute to the incidence of wound recurrence.The additional clinical evidence obtained with point-of-care, noncontact, NIR imaging in this feasibility study provided an objective measure that wound resolution occurred an average of 2 weeks, and up to 5 weeks, after 100% reepithelialization on visual inspection.Point-of-care, noncontact, NIR imaging was also able to determine when a patient was at risk for breakdown.Addition of this objective modality for assessing wound healing may help guide clinical decision-making for the optimal time for transition from protective wound dressings with gradual return to full activity to minimize wound recurrence.•

Table 2 .
WOUND ETIOLOGY AND RESOLUTION AS DETERMINED BY VISUAL INSPECTION AND NIR IMAGING Abbreviations: DFU, diabetic foot ulcer; NIR, near-infrared; VLU, venous leg ulcer.a Patient with recurrent wound.