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Quantifying dermal microcirculatory changes of neuropathic and neuroischemic diabetic foot ulcers using spatial frequency domain imaging: a shade of things to come?
  1. Grant A Murphy1,
  2. Rajinder P Singh-Moon2,
  3. Amaan Mazhar2,
  4. David J Cuccia2,
  5. Vincent L Rowe1,
  6. David G Armstrong1
  1. 1Department of Surgery, University of Southern California Keck School of Medicine, Los Angeles, California, USA
  2. 2Department of Research and Development, Modulim, Irvine, California, USA
  1. Correspondence to Grant A Murphy; gamurphy{at}


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.

  • foot ulcer
  • biosensing techniques
  • hemoglobins
  • vascular surgical procedures

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  • Contributors AM, DJC and DGA were involved in study conceptualization and design. GAM, RPS-M, AM and DGA were involved in data curation, analysis and interpretation. GAM and RPS-M wrote the original manuscript. GAM, RPS-M, AM, DJC, VLR and DGA critically reviewed and edited the manuscript. AM and DJC obtained funding and study resources. All authors have read and approved the final manuscript.

  • Funding This study was supported by National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NIDDK) grant 2R44DK094625.

  • 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.

  • Patient consent for publication Obtained.

  • Ethics approval This study was approved by the Institutional Review Board of Keck Medical Center of the University of Southern California (HS-17-00926).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article. Requests for deidentified biomarker data can be sent to and may be used with consent from Modulim.