Optical and acoustic scattering in cutaneous neurofibromas: Implications for early detection

Abstract

Cutaneous neurofibromas (cNF) occur in individuals with germline neurofibromatosis type I (NF1) pathogenic variants. Current management involves monitoring and limited surgical removal. Nascent cNF are lesions detectable only through advanced imaging, and not observable with the unaided eye. Non-invasive early detection may enable intervention before cNF become visible. We introduce an imaging approach integrating spatial frequency domain imaging (SFDI) and high-frequency ultrasound (HFUS) to identify and characterize suspected nascent cNF. In 21 NF1 subjects, we identified 152 suspected nascent lesions using SFDI as skin regions with decreased optical scattering at near-infrared wavelengths. Of these, 120 were imaged with HFUS and 93% demonstrated subsurface hypoechoic dermal structures. Paired analyses of the reduced scattering coefficient (μ_s') at 851 nm showed μ_s' within suspected nascent cNF was significantly lower than that of adjacent uninvolved skin, supporting μ_s' as a candidate imaging feature for nascent cNF. Statistical variation in overlying dermal thickness and lesion dimensions is summarized. Integrating SFDI and HFUS represents a multimodal approach for imaging characterization of suspected nascent cNF and may advance understanding of cNF progression and the development of treatment strategies. This feasibility study does not establish nascent cNF diagnostic detection accuracy, as histologic confirmation was limited.

Keywords: Cutaneous neurofibromas; high-frequency ultrasound; spatial frequency domain imaging.