A Quality Improvement Study of Diagnostic Sural Nerve Morphometry Using Gold Standard Light Microscopy Versus Whole Slide Imaging and Transmission Electron Microscopy

Nerve morphometry is a quantitative diagnostic laboratory technique used to analyze nerve structures, allowing clinicians to detect morphological differences in myelination and assess the progression of peripheral neuropathies. To quantify myelin and axon pathology, a nerve biopsy is prepared for observation using both light microscopy (LM) and transmission electron microscopy (TEM). Standardized morphometry enables the assessment of metrics, including myelinated fiber profile equivalent circle diameter and axon density. This process remains laborious and complex. This quality improvement study aimed to investigate a consolidated approach to conducting nerve morphometry using only TEM, or high-throughput whole-slide imaging (WSI) to replace standard LM imaging, reducing the complexity and time to conduct the procedure. Cases previously biopsied and analyzed for diagnosis by light microscopy were reimaged and assessed utilizing WSI and TEM. Data were then compared to those previously obtained for diagnosis by the standard LM procedure. While the WSI procedure resulted in good sensitivity and specificity (positive and negative predictive values, respectively) compared to the morphometric analyses originally obtained by the standard diagnostic LM, the results from the TEM analysis failed these statistical tests because of the inability to correctly characterize any of the normal cases. Therefore, we conclude that WSI may be an effective alternative to conducting standard LM myelinated fiber morphometry, reducing the time needed to complete the procedure, whereas the TEM morphometry protocol cannot be recommended at this time.