Development of a Tissue Oxygenation Flow-Based Index Toward Discerning the Healing Status in Diabetic Foot Ulcers

Abstract

Objective: The objective of this study is to characterize breath-hold (BH)-induced oxygenation changes in diabetic foot ulcers (DFUs) and develop an oxygenation flow index (OFI) to discern nonhealing from healing DFUs. Approach: The imaging approach utilizes an innovative BH stimulus that induces vasoconstriction and measures for altering oxygenation flow in and around the tissues of DFUs and controls. The modified Beer-Lambert law was utilized to calculate hemoglobin-based spatiotemporal oxygenation maps in terms of oxygen saturation. Results: We found controls had synchronous BH-induced oxygenation changes across the dorsal (OFI: 29.0%) and plantar (OFI: 57.6%) aspects of the foot. Nonhealing DFUs, however, had less synchronous BH-induced oxygenation changes (OFI <28%). In addition, two complicated healing DFU cases, or cases with underlying issues or poor long-term healing outcomes, were observed to have OFIs <28%. Innovation: An OFI was developed to differentiate nonhealing DFUs from healing DFUs using a single, noncontact, near-infrared optical scanner for spatiotemporal oxygenation monitoring. The OFI has potential to provide immediate feedback on the microcirculation in DFUs, through hemoglobin-based oxygenation parameters. Conclusion: A preliminary threshold (OFI <28%) could differentiate nonhealing and complicated DFUs from healing DFUs. The overall oxygenation flow pattern was less synchronous (or the OFI value reduced) in the nonwound areas of the feet that were nonhealing. In other words, the reduced OFI value (<28%) in the entire foot, excluding the wound region is a possible indicator that the wound may not heal.

Keywords: breath-hold; diabetic foot ulcers; near infrared spectroscopy; oxygenation flow index; tissue oxygenation.

Anuradha Godavarty, PhD

Figure 1.

Schematic of NIROS utilized for noncontact imaging of control and DFU subjects. Arrows indicate the flow of information throughout the NIROS components. CMOS, complementary metal-oxide semiconductor; DFU, diabetic foot ulcer; LED, light-emitting diode; NIROS, near-infrared optical scanner.

Figure 2.

Schematic of the 120-s-long BH paradigm. The paradigm consisted of 40-s of initial rest, 20-s of end-exhalation breath holding, and 60-s of recovery. BH, breath-hold.

Figure 3.

Pearson-based correlation analysis approach. (A) A 50 × 50-pixel ROI was selected from the spatiotemporal maps, (B) ROI was binned to 5 × 5-pixel subregions, (C) ΔStO₂ trendlines of these subregions was plotted across the 120-s BH paradigm, and (D) the Pearson's correlation map was generated with respect to the chosen reference signal. The blue shaded region in (C) is the 20-s BH portion of the 120-s BH paradigm, and the two black vertical lines is the optimized 40-s period across which linear correlation analysis was performed. ΔStO₂, effective oxygen saturation concentration; ROI, region of interest.

Figure 4.

Correlation maps in terms of ΔStO₂ for control subjects (case 1–3) acquired from one repetition of dorsal and plantar imaging. Blue squares are segmented out fiducial markers. The selected reference region is demarcated by an encircled black square within an encircled boundary. The color bar for each map ranges from +1 (red) to −1 (blue). Red areas indicate regions of synchronous oxygenation changes with respect to the reference region (i.e., positive correlation), whereas blue areas indicate regions of asynchronous oxygenation changes (i.e., negative correlation). ΔStO₂, effective oxygen saturation concentration.

Figure 5.

Scatterplot of (A) the OFI of each correlation map in controls, nonhealing DFUs, and healing DFUs. (B) is a scatterplot of the OFI of the background region in DFUs. The red horizontal denotes the max median PCC for nonhealing DFUs. Nonhealing DFUs, healing DFUs, and controls are indicated as red squares, blue triangles, and black diamonds, respectively. In subfigure (A) the black vertical line indicates a separation of plantar and midfoot cases (left) and dorsal cases (right). OFI, oxygenation flow index; PCC, Pearson's correlation coefficient.