Evaluating NIRF Imaging in Hard-to-Heal Lower Leg Wounds

Clinical assessment of chronic wounds often relies on surface-level indicators such as granulation tissue formation, wound area reduction, and slough clearance. While informative, these visual signs do not always reflect what is happening inside the tissue right away. In fact, deeper physiological healing processes can begin well before they become noticeable on the wound’s surface.

To address this concern, a pilot cohort study published in the International Wound Journal in July 2025 investigates the feasibility of Near-Infrared Fluorescent (NIRF) imaging with Indocyanine Green (ICG) as a tool to visualize perfusion and inflammation in hard-to-heal lower leg wounds earlier than conventional methods allow.

Here’s a quick look at the study, its results, and its implications.

How Was the Study Designed?

Led by researchers from the University of Otago and Health New Zealand, the study enrolled 17 patients aged 16 years or older with lower limb wounds greater than 10 centimeters in diameter and present for more than four weeks. Exclusion criteria included:

• Exposed bone or tendon
• Active wound infection requiring antibiotics
• Dressing changes more frequent than every other day
• Slough covering more than 30 percent of the wound bed
• Severe kidney failure
• Pregnancy
• Prior reaction to ICG

47 percent of participants had diabetes, while 45 percent had peripheral arterial disease. All patients received standard multidisciplinary wound care over a 12-week period, during which NIRF imaging was performed at baseline, week six, and week 12. Using SPY Elite hardware and SPYQ software, the team analyzed fluorescence intensity to assess tissue perfusion.

What Did the Study Find?

Looking at the trial’s results, though 82 percent of participants experienced a reduction in wound size, changes in fluorescence intensity revealed non-significant trends suggestive of predictive value for healing outcomes. Dye intensity decreased over time in 10 patients, corresponding with reductions in wound area and increased granulation tissue. In contrast, seven patients exhibited increased intensity, three of whom later developed serious complications (two infections and one wound-associated malignancy) despite initially unremarkable clinical assessments.

Quantitative analysis of average, highest, and lowest fluorescence intensity values offered further insight. While statistical power was limited, a trend between perfusion (AUC) and wound volume reduction (ρ = 0.46, p = 0.06) suggested perfusion-driven changes may be more evident in wound depth than area. A significant inverse correlation between slough reduction and granulation improvement (ρ = −0.54, p = 0.02) aligned with expected tissue remodeling patterns. Notably, changes in the lowest intensity values tracked more closely with healing outcomes than average or peak values, potentially highlighting hypoperfused or necrotic zones invisible on routine inspection. Importantly, the imaging protocol proved feasible in routine care. The procedure, comprising intravenous ICG infusion and a brief, standardized imaging session, was well tolerated and integrated into clinical workflows.

What Could These Results Mean?

The findings are especially relevant for high-risk populations, such as patients with diabetes or peripheral vascular disease, where impaired perfusion and subclinical inflammation often precede overt wound deterioration. In these contexts, the ability to detect physiological changes before they become visible may allow for earlier intervention.

Although other modalities like near-infrared reflectance spectroscopy (NIRS) also assess tissue oxygenation, NIRF imaging captures dynamic perfusion in real time. This functional sensitivity may offer advantages in detecting early inflammatory activity or perfusion deficits that may be less apparent with reflectance-based techniques.

However, the study’s exploratory nature warrants caution. The small, region-specific, predominantly male cohort and lack of a control group limit generalizability. The absence of long-term outcome data and cost-effectiveness analysis also leaves unanswered questions about the broader clinical utility of NIRF imaging.

NIRF imaging offers a promising addition to the evolving toolkit for chronic wound surveillance, providing a non-invasive method to assess tissue perfusion and detect inflammatory changes that may not be apparent on visual examination. While not a substitute for clinical judgment, it may offer added value in cases where conventional indicators are ambiguous. Further validation through larger, controlled studies is necessary to establish its role in chronic wound management and to determine whether early detection of subclinical changes can translate into improved outcomes.

Reference:

Clifford KA, Schmidt E, Johnstone J, Krysa J. Assessment of Hard-To-Heal Lower Leg Wounds With Near-Infrared Fluorescent Imaging: A Pilot Cohort Study. Int Wound J. 2025;22(7):e70723.