Quantifying dermal microcirculatory changes of neuropathic and neuroischemic diabetic foot ulcers using spatial frequency domain imaging: a shade of things to come?

Abstract

Introduction: The use of non-invasive vascular and perfusion diagnostics are an important part of assessing lower extremity ulceration and amputation risk in patients with diabetes mellitus. Methods for detecting impaired microvascular vasodilatory function in patients with diabetes may have the potential to identify sites at risk of ulceration prior to clinically identifiable signs. Spatial frequency domain imaging (SFDI) uses patterned near-infrared and visible light spectroscopy to determine tissue oxygen saturation and hemoglobin distribution within the superficial and deep dermis, showing distinct microcirculatory and oxygenation changes that occur prior to neuropathic and neuroischemic ulceration.

Research designs and methods: 35 patients with diabetes mellitus and a history of diabetic foot ulceration were recruited for monthly imaging with SFDI. Two patients who ulcerated during the year-long longitudinal study were selected for presentation of their clinical course alongside the dermal microcirculation biomarkers from SFDI.

Results: Patient 1 developed a neuropathic ulcer portended by a focal increase in tissue oxygen saturation and decrease in superficial papillary hemoglobin concentration 3 months prior. Patient 2 developed bilateral neuroischemic ulcers showing decreased tissue oxygen saturation and increased superficial papillary and deep dermal reticular hemoglobin concentrations.

Conclusions: Wounds of different etiology show unique dermal microcirculatory changes prior to gross ulceration. Before predictive models can be developed from SFDI, biomarker data must be correlated with the clinical course of patients who ulcerate while being followed longitudinally.

Trial registration number: NCT03341559.

Keywords: biosensing techniques; foot ulcer; hemoglobins; vascular surgical procedures.

Conflict of interest statement

Competing interests: RPS-M, AM and DJC are full-time employees of Modulim and have financial interests in the company. Modulim is commercializing SFDI technology.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Spatial frequency domain imaging (SFDI) technology for plantar foot imaging. (A) SFDI uses a combination of visible and near-infrared light to interrogate tissue and recover functional circulation characteristics. (B) Diagram illustrating SFDI characterization of tissue oxygen saturation (StO2) and stratified hemoglobin content (HbT1 and HbT2). HbT1 represents total hemoglobin levels originating from superficial microvasculature while HbT2 represents the subsurface macrovascular total hemoglobin levels.

Figure 2

Longitudinal microcirculatory monitoring for patient 1. Spatial frequency domain imaging (SFDI) biomarker profiles of the plantar forefoot are shown at weeks 0 (A), 13 (B) and 50 (C). Visual inspection of color images at week 0 show a seemingly innocuous appearance, however focal areas of elevated StO2 and decreased HbT1 at the second metatarsal phalangeal joint (MTPJ) bilaterally suggest a latent issue. At wound presentation (right second MTPJ) 13 weeks later, StO2 remains elevated within the peri-wound region coupled with rising HbT1. At week 50 on visible healing postosteotomy, StO2 and HbT1 signatures exhibited reduced focal activity near the right second MTPJ with a shift toward the third MTPJ. Numbers at the base of each foot represent forefoot median values. Numbers near dashed circles represent median values over the circumscribed region.

Figure 3

Longitudinal microcirculatory monitoring for patient 2 (left foot). Spatial frequency domain imaging (SFDI) biomarker profiles of the plantar forefoot are shown at weeks 9 (A), 18 (B), 37 (C), 46 (D) and 50 (E). At week 9, the hallux exhibited general signs of hyperemia and blood pooling as indicated by superficial (HbT1) and subsurface hemoglobin (HbT2), respectively. The pre-ulcer redness at the hallux tip coincided with focally elevated StO2 and reduced HbT1. Signatures of hyperemia and pooling persisted at week 18 throughout hallux ischemic wound presentation. Gangrene presentation at week 37 showed poor oxygenation surrounding the wound site and progressive hyperemia and pooling in the subhallux region. At week 46 following left popliteal artery to DVAA bypass, the eventually spreading of gangrene to the medial forefoot and lesser digits was forecasted by substantially low StO2 in these regions. At week 50, 2 weeks following TMA, signs of circulatory restoration were observed as indicated by a re-normalization of StO2 and HbT2 values. Numbers at the base of each foot represent forefoot median values. DVAA, dorsal venous arch arterialization; TMA, transmetatarsal amputation.

Figure 4

Longitudinal microcirculatory monitoring for patient 2 (right foot). Spatial frequency domain imaging (SFDI) biomarker profiles of the plantar forefoot are shown at weeks 9 (A), 18 (B) and 37 (C). At week 9, redness at the hallux tip coincided with hyperemia and pooling of blood as indicated by superficial (HbT1) and subsurface hemoglobin (HbT2), respectively. General hallux signatures of hyperemia and pooling persisted at week 18 throughout ischemic wound presentation coupled with substantially low oxygenation (StO2) localized at the tip. The peri-wound region demonstrated elevated StO2 and reduced HbT1. With gangrenous wound progression at week 37, an extension of the poorly oxygenated region was observed with further elevation of HbT1 and HbT2. Numbers at the base of each foot represent forefoot median values. Numbers near dashed circles represent median values over the circumscribed region.