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.

**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 m. 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.

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.