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

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