Second-order spatial analysis of epidermal nerve fibers

Lance A. Waller, Aila Särkkä, Viktor Olsbo, Mari Myllymäki, Ioanna G. Panoutsopoulou, William R. Kennedy, Gwen Wendelschafer-Crabb

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


Breakthroughs in imaging of skin tissue reveal new details on the distribution of nerve fibers in the epidermis. Preliminary neurologic studies indicate qualitative differences in the spatial patterns of nerve fibers based on pathophysiologic conditions in the subjects. Of particular interest is the evolution of spatial patterns observed in the progression of diabetic neuropathy. It appears that the spatial distribution of nerve fibers becomes more 'clustered' as neuropathy advances, suggesting the possibility of diagnostic prediction based on patterns observed in skin biopsies. We consider two approaches to establish statistical inference relating to this observation. First, we view the set of locations where the nerves enter the epidermis from the dermis as a realization of a spatial point process. Secondly, we treat the set of fibers as a realization of a planar fiber process. In both cases, we use estimated second-order properties of the observed data patterns to describe the degree and scale of clustering observed in the microscope images of blister biopsies. We illustrate the methods using confocal microscopy blister images taken from the thigh of one normal (disease-free) individual and two images each taken from the thighs of subjects with mild, moderate, and severe diabetes and report measurable differences in the spatial patterns of nerve entry points/fibers associated with disease status.

Original languageEnglish (US)
Pages (from-to)2827-2841
Number of pages15
JournalStatistics in Medicine
Issue number23
StatePublished - Oct 15 2011


  • Diabetic neuropathy
  • K function
  • Neurology
  • Pair-correlation function
  • Spatial point/fiber processes


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