A pilot prospective cohort study using experimental quantification of early peripheral nerve regeneration with high-frequency three-dimensional tomographic ultrasound (HFtUS).

Quantification of peripheral nerve regeneration after injury relies upon subjective outcome measures or electrophysiology assessments requiring fully regenerated neurons. Nerve surgeons and researchers lack objective, quantifiable information on the site of surgical repair and regenerative front. To address this need, we developed a quantifiable, visual, clinically available measure of early peripheral nerve regeneration using high-frequency, three-dimensional, tomographic ultrasound (HFtUS). We conducted a prospective, longitudinal study of adult patients with ulnar and/or median nerve injury of the arm undergoing direct epineurial repair within 5 days of injury. Assessment of morphology, volumetric and 3D grey-scale quantification of cross-sectional views were made at baseline up to 15 months post-surgery. Sensory and motor clinical outcome measures and patient reported outcome measures (PROMs) were recorded. Five participants were recruited to the study. Our data demonstrated grey-scale values (an indication of axonal density) increased in distal stumps within 2-4 months after repair, returning to normal as regeneration completed (4-6 months) with concomitant reduction in intraneural volume as surgical oedema resolved. Two patients with abnormal regeneration were characterized by increased intraneural volume and minimal grey-scale change. HFtUS may quantify early peripheral nerve regeneration offering a window of opportunity for surgical intervention where early abnormal regeneration is detected.