Near-Infrared Spectroscopy in Wound and Flap Management Form

Summary Of Evidence

Introduction

Limb threatening diabetic wounds are a significant and common health problem within the Medicare beneficiary population. Acute and chronic wound treatment is determined by many to still be subjectively rooted in clinical experience rather than having an actual evidence-based objective approach. It is understood that effective objective wound healing evaluation is needed in order to pursue an evidence-based medical approach that is logical and likely to have a positive outcome. For decades wound analysis with methods such as analysis of dermal microcirculation in wound punch biopsies, video-capillaroscopy, laser Doppler flow or pulse oximetry have been studied but all have been limited by the need to make contact with open wounds. Thus, optical spectroscopic methods are considered for wound monitoring based on radiation absorption in the visible and near-infrared spectral ranges.

The focus of this policy is on near-infrared spectroscopy (NIRS). NIRS relies on 2 principles: (a) that tissue is relatively transparent to near-infrared light, and (b) that compounds in tissue exist in which absorption of light is dependent on the oxygenation status of the tissue. NIRS is able to differentiate between oxygenated and deoxygenated blood.

Evidence

Literature from the early 2000s is available regarding early development of optical devices based on near infrared diffuse optical spectroscopy for the purpose of wound monitoring during healing. A paper involving the school of biomedical engineering at Drexel University noted that significant differences in optical properties like absorption and scattering coefficients could be followed during wound healing in study rats with and without chemically induced diabetes. The basic conclusion was that this type of technique could be used in monitoring and quantifying wound healing.¹

Schmidt, et al. published an article describing contact-free spectroscopy of leg ulcers in 2001. The need for some sort of objective wound monitoring was emphasized. It was noted that as far back as 1995 color measurement of wounds has been discussed with red suggesting healthy granulation tissue, pink denoting re-epithelialization, and black/yellow/green indicating necrosis or infection. In this study, 23 patients with chronic venous, arterial and mixed leg ulcers were enrolled. These patients were aged 40-80 years with a female to male ratio of 3:1. The overwhelming majority of the wounds (21 of 29) were classified as chronic venous. The majority of the wounds in the study were treated with hydroactive dressings. The 29 total wounds were followed for 6 weeks. A clinical wound score based on wound area, color and granulation tissue consistency was assigned to each wound. Spectroscopic readings were done in the visible and near-infrared range of the spectrum. Resolution was 5 nm. By using cross-validation, 69% of the predicted wound scores was felt to be correct. It was obvious that classification accuracy was better at low wound scores. Nearly 60% of higher wound scores was predicted correctly. At this point in time, the study authors noted bioengineering for spectroscopy was “developing from standard error to standard operative procedure.” Much work was still needed in terms of standardizing experimental test conditions. While different wound qualities led to changes in remittance spectra, the large standard deviations of the spectral data sets in this study did not allow for simple classification of wounds by some selected wavelengths. Individual variation of wound healing dynamics, ulcer etiology and treatment impacts created much variability in wound spectra. Cluster and discriminant analysis were used to evaluate an objective wound score successfully. The classification function allowed an overall prediction of wound scores of 95%. But cross-validation analysis provided a more realistic result by an accordance of 69% between predicted and observed wound scores. The final conclusion was simply that optical visible and NIRS could be a valuable tool for clinicians in the future.²

In 2008, Weingarten, et al.³ set out to correlate optical changes with healing wounds with actual histology. The optical changes were assessed with use of near infrared scattered light to assess blood vessel ingrowth and with diffuse reflectance spectroscopy (DRS) for assessment of collagen concentration. This group questioned whether such technologies could help assess the efficacy of wound treatments and also help guide the management of wounds. This study utilized an animal model of hairless rats in whom diabetes had been provoked with streptozotocin administration. Eighteen of 30 rats were rendered diabetic. Full thickness skin wounds were created on the left dorsal area of each rat in the study. Optical data was then collected from the peri-wound area, the center of the wound and the unwounded site on the symmetric right side twice weekly. Depth of tissue examined was 3-5 mm. An optical tomography instrument was used to noninvasively measure the amplitude and phase shift of light as it propagated through tissue. DRS was used to measure the intensity of backscattered light at a depth of 100-300 µm. Measurements of wound size, under anesthesia, were done by calculating wound surface area using digital photographs. A total of 28 wounds and 28 control areas were excised and examined histologically. A statistically significant (p < 0.05) difference between the percent healing of diabetic and control rats was found. Wound contraction in the diabetic group was slower than the control group. The average absorption coefficients by NIRS were significantly higher in the diabetic wounds when compared to the diabetic non wounded side and to the controls. Biopsy results showed that collagen concentration by trichrome staining correlated with the DRS measurements. The authors noted that decisions based on wound exam alone lacked accuracy. True wound surface area, precise wound edges, and wound width and depth all appeared to be variable and surface area did not reliably take into account changes in wound volume. Thus, the use of new, expensive technologies that stimulate wound healing must be carefully assessed in order to ensure cost-effectiveness. In conclusion, absorption coefficients obtained using NIRS spectroscopy did correlate with blood vessel ingrowth seen histologically and by vessel staining. Scattering function data using DRS did correlate with increasing collagen concentration during healing. They indicated that application of such technologies to human diabetic wounds was in progress.

In 2010, Weingarten, et al. studied humans with a total of 16 chronic diabetic foot wounds. The efficacy of in vivo diffuse NIRS was evaluated insofar as predicting wound healing. The wounds were followed and assessed for subsurface oxy-hemoglobin concentration. Weekly measurements were conducted until either closure, amputation or a total of 20 visits without healing. Photos were taken to follow wound size and the contraction of the wound was compared with NIRS results. For these 16 patients, 7 wounds healed, 6 amputations occurred, and 3 wounds did not heal after 20 visits. Initially all wounds had higher subsurface hemoglobin concentrations as compared to non-wound sites. Healed wounds showed a consistent reduction in hemoglobin concentration as wounds evolved toward closure. In wounds that did not heal or needed amputation, the hemoglobin concentration did not decline. It is noted in the article abstract that “some nonhealing wounds appeared to be improving clinically.” A negative slope for the rate of change of hemoglobin concentration was indicative of healing across all wounds. The authors concluded that NIRS wound evaluation may provide an effective measure of wound healing and that NIRS can determine wound healing earlier than that visibly assessed.⁴ They noted these preliminary findings needed to be validated by well-designed studies.

An article reviewing various optical noninvasive technologies for wound imaging, published out of the optical imaging laboratory at Florida International University in 2016 was read. Reviewed imaging approaches included hyperspectral imaging, multispectral imaging, NIRS, diffuse reflectance spectroscopy, optical coherence tomography, laser Doppler imaging, laser speckle imaging, spatial frequency domain imaging and fluorescence imaging. Use of a non-contact hand-held near-infrared optical scanner device for wound imaging was only briefly described. It was noted to have demonstrated potential to differentiate between healing and non-healing wounds. NIRS was also noted to have the potential to penetrate deeper with the optical imaging as compared to many other techniques. However, every technology reviewed, including NIRS were noted to be at various stages of translational efforts to the clinic.⁵ Within this article an Institutional Review Board (IRB)-approved study was noted at this University of Miami optical lab that was showing the ability to use NIRS to identify both increased and decreased reflectance in wounds thus corresponding to healing regions vs. nonhealing regions. Four diabetic subjects with diabetic foot wounds were assessed. This was a qualitative comparison only with no results related to how these findings could direct therapy or change health outcomes.

A retrospective study by Landsman in 2020⁶ was designed to determine if NIRS could be used to evaluate wounds and identify patterns centered on wound oxygenation and overall healing to help determine which wounds would ultimately heal and which ones would not. Twenty-five patients with either diabetic foot wounds or venous leg ulcers were included. All were being actively treated. The setting was a community hospital office setting. Regardless of treatment, all the wounds were tracked with NIRS at regular intervals. Wound management varied widely. De-identified images were then examined retrospectively looking for any helpful patterns. Wound bed and peri-wound oxygenation patterns were observed and classified. This work included correlation with clinical appearance and NIRS images. Images of wounds that closed and wounds that did not were compared. Results portrayed 4 distinct oxygenation patterns that appeared to predict healing opportunity. As compared to segmental pressures or ankle-brachial index (ABI) measures, spectroscopy was able to look at oxygenation at a capillary level within the wound bed. This was viewed as an advantage since methods like radio-isotope blood tracing would be more expensive and transcutaneous oxygen pressure would be limited by wound size. NIRS, to an advantage, could be used to examine large areas and deeper tissue through the use of reflected light to calculate perfusion by detecting color change related to oxygenated vs. deoxygenated hemoglobin. Landsman specifically noted the considerable past debate over how to interpret NIRS acquired images. He noted that earliest studies had indicated that 40% oxygenation was needed for wound healing, and it was that number that had been used to predict viability of skin flaps and grafts. However, he noted many wounds with greater than 40% oxygenation had ultimately failed to heal. Therefore, these authors noted it was important to realize wound healing was not wholly dependent on perfusion and that oxygenation depended on many factors such as mechanical forces on a wound, the disease state, general health of the patient, presence of infection, and presence of any bioactive materials.

In 2016, Chen and colleagues⁷ noted the potential for NIRS regarding post-operative flap monitoring. These investigators performed a systemic review to determine the clinical value of NIRS in the early detection of vascular crisis associated with a free flap. An extensive literature search through October of 2013 was conducted. Studies were selected strictly according to the inclusion/exclusion criteria by 2 independent reviews. A total of 8 studies were finally included. A total of 710 free flap procedures were performed in 629 patients using NIRS for monitoring. At the same time, 433 free flaps performed in 430 patients without the use of NIRS were included as the control group. There were no significant differences in the rates of vascular crisis (p = 0.917) and re-exploration (p = 0.187). However, there were significant differences in the salvage rates (p < 0.001) and flap failure rates (p = 0.003). For the free flaps monitored by NIRS that were not associated with vascular crisis, no alarms were raised by NIRS, giving 100% sensitivity and specificity. The authors concluded that NIRS appeared to be a highly suitable candidate for post-operative flap monitoring. They stated that larger scale, randomized, multi-centric clinical trials were needed in the future.

Kagaya, et al. also conducted a 2018 systematic review of NIRS in flap monitoring. They noted reported utility of NIRS as a reliable non-invasive method for free flap monitoring. However, they also noted the short history attached to this monitoring technique and the lack of any definite consensus regarding its use. They sought to clarify available pertinent evidence. A total of 15 clinical studies and 8 animal studies were identified and reviewed. The evidence and information on various aspects of NIRS flap monitoring were summarized. The overall flap success rate was 99.5%, and the flap salvage rate was 91.1%, when measuring tissue oxygenation saturation (StO₂) at intervals of every 2 hours or sooner. Single StO₂ monitoring was able to detect vascular compromise with 99.1% sensitivity and 99.9% specificity, and earlier than other monitoring methods, but additional hemoglobin concentration monitoring was useful for avoiding false negatives and differentiating arterial and venous occlusion. In the end they concluded NIRS can be used for flap monitoring and displayed high accuracy in various situations; however, further studies were needed to take full advantage of the potential of NIRS.⁸

In similar fashion Newton, et al.⁹ conducted a systematic review of free flap reconstruction outcomes utilizing NIRS monitoring. They denoted NIRS as a novel technique with a “propensity for early detection of vascular compromise” when compared to the current standard of clinical monitoring. They also conducted a comprehensive literature review and ended up including 10 articles out of a total of 590 for analysis. Overall, flaps with vascular compromise monitored with NIRS had a significantly higher salvage rate of 89% compared with a salvage rate of 50% in the flaps monitored by clinical monitoring alone (p < 0.01). Partial loss occurred in 15% of the successful salvages in the NIRS group versus 80% with clinical monitoring alone (p < 0.01). Detection of vascular compromise by NIRS preceded clinical signs on average by 82 ± 49 min. NIRS was accurate in detecting compromised flaps with a low false-positive and false-negative rate. They concluded however that there was a lack of robust data although the potential for postoperative NIRS monitoring of free flap monitoring was present.

A 2020 pilot study by Serena, et al.¹⁰ sought to compare NIRS and transcutaneous oxygen measurement (TCOM) for assessment of wounds that were healing poorly. It was noted that TCOM has numerous drawbacks and had fallen into disuse. This study compared measurement of tissue oxygenation of NIRS with TCOM in acute and hard-to-heal wounds. The level of agreement between NIRS and TCOM was determined using Bland-Altman analysis. The relationship between TCOM and NIRS was examined using Pearson correlation. A total of 24 observations were obtained from 10 patients using both TCOM and NIRS. Bland-Altman analysis suggested an overestimation of oxygen measurements using TCOM compared with NIRS. The oxygen levels measured by TCOM and NIRS showed a strong correlation (r=0.74). They concluded that further study in a larger population was recommended.

Analysis of Evidence

It does not appear that the promise of NIRS wound or surgical flap imaging technology has yet gained sufficient evidence to fully translate into clinical settings. Despite significant medical evidence review, it was not determined that NIRS could conclusively supplant the long-held gold standard of clinical assessment. Even as a complementary tool, it is not clear that results are robust or reliable enough to truly alter health outcomes in a beneficial way such that they should be covered as reasonable and necessary medical care.

The clinical relevance of the topic is not denied. Current clinical approaches based on visual inspection and physical measurements are less than perfect to be sure. It is understood that optical imaging for wound oxygenation or microstructure as correlating with healing is attractive. It could be a helpful clinical tool particularly with its noninvasive ability to assess an actual wound and as a means to provide consistent, meaningful data to support wound healing prediction and treatment effectiveness. But it is this latter potential that is not yet substantiated.

The literature, particularly regarding wounds, is dominated by a limited group of investigators. The studies reviewed, in general for wounds and flaps, did not appear to be well-designed and were not well powered due to very low subject numbers. There was a paucity of randomized controlled trials with a large subject population or one that was clearly analogous to a Medicare beneficiary demographic. Much of the literature was centered on retrospective studies or overall literature reviews.

As the literature was reviewed it only emphasized that previous strategies in wound care monitoring such as transcutaneous oxygen monitoring, once considered so promising, had not reaped any of the predicted benefits. It is also profoundly striking that despite decades of enthusiasm for NIRS and even other spectral monitoring, there has been little improvement in the quality of studies over time. New handheld instruments for purposes of NIRS represent interesting technology that make wound monitoring easier and yet still the underlying data and evidence-based medicine has lacked a robustness and randomized nature that would have been expected after all these years with a health problem that is ubiquitous and easily lends itself to study with an abundance of subjects.

Some of the reviewed literature also fully admitted to authors’ interpretation of healing patterns as completely hypothetical in nature. In noting that correlation with definitive microscopic vascular activity would be helpful, it only reinforced the sense that NIRS is still so poorly studied that there can be no assurance of exactly how it should be technically employed in order to ensure that there is reliability in the interpretation of findings nor is there a clear understanding by practitioners as to what NIRS imaging may be indicating. Without a clear understanding of the imaging patterns trending over time it appears that there can be no comfort in knowing that clinicians will use it in the right manner or interpret results in a consistent fashion leading to a next best step for a particular wound. It seems apparent that the subtleties of image interpretation are not fully fleshed out which would seem to be an absolute requirement in order to see reliably improved health outcomes. NIRS appears to involve much more than simple binary interpretation of signal and factors beyond perfusion and oxygen can alter imaging results.¹¹

If NIRS monitoring of wounds could help predict a lack of healing success or a need to change treatment, does it provide any clarity as to what a next advantageous treatment might be and thus advance toward a better clinical outcome for the patient? No evidence toward such potential could be readily identified.

It was also not readily determined that some of the early foundational examination of NIRS was not overly influenced by industry incentives versus real, live patient, improved clinical outcomes.

Randomized controlled trials that compare outcomes in patients whose treatment is standardized are needed to determine definitive patient selection criteria and clinical utility. The lack of level I evidence, clinical practice guideline endorsement, and consistent commercial coverage, argue strongly against current NIRS coverage for wounds or flaps as reasonable and necessary for treatment of Medicare beneficiaries.

At this juncture, this A/B MAC believes there is insufficient high-quality evidence to justify the use of contact or non-contact NIRS in wound or flap management unless perhaps within the confines of a well-designed clinical trial. Thus, this A/B MAC considers non-contact NIRS (e.g., SnapshotNIR^® or other similar devices) experimental and investigational for intra-operative, post-operative and non-operative wound or surgical flap assessment/management because of insufficient evidence of its effectiveness.

Despite an already lengthy history, NIRS remains an evolving area of research. This A/B MAC will continue to monitor scientific developments and may adjust this coverage policy accordingly.

This is a NON-coverage policy for non-contact near-infrared spectroscopy use in acute or chronic wound assessment and management and for use in flap or micro-flap assessment intra- or post-operatively.