High-Frequency Ultrasound

High-frequency ultrasound was first used in the clinical diagnosis of DPN as a supplement to NCS. It measures the size, blood vessels, echo, and mobility of the diseased nerve to show the damage of the nerve tissue, which can effectively improve the diagnostic efficiency of DPN and reduce the missed diagnosis rate and the misdiagnosis rate (44). In patients with DPN, the cross-sectional area (CSA) and longitudinal section of the nerve are increased, and the echogenicity of the nerve, the boundary ambiguity, and the blood flow in the nerve are also significantly increased. The mean CSA in the examined nerves was higher in moderate to severe DPN than the mild DPN (45). High-resolution ultrasound has unique diagnostic advantages for early or subclinical neuropathy. High-frequency ultrasound can detect subclinical involvement of peripheral nerves and abnormalities in patients with normal electrical diagnosis (46).

Studies have shown that the maximum thickness of the median nerve and posterior tibial nerve tract, CSA, and hypoechoic area in people with diabetes are closely related to the degree of neuropathy (p < 0.0001) and are significantly greater than the control group (p < 0.05) (47), suggesting that high-frequency ultrasound can also be used to grade the severity of DPN. A study shows that the sensitivity and specificity of CSA and vascular proliferation in detecting DPN-induced carpal tunnel syndrome (CTS) are 90.9%, 94.0%, 93.4%, and 90.0%, respectively. The severity of CTS is significantly related to various stages of vascular proliferation, and high-frequency ultrasound can be used to diagnose CTS early and estimate its severity (48). However, some studies have found that NCS is more sensitive than ultrasound when determining the severity of ulnar neuropathy, especially in mild or moderate neuropathy (49).

The ultrasound image of DPN lacks a unified definition, and its results are easily affected by the subjective factors of the examiner. Therefore, it is necessary to establish a complete and unified ultrasound image quantitative scoring system. Some ultrasound scoring systems have been developed. For example, the Bochum ultrasound score (BUS) can effectively distinguish between subacute chronic inflammatory demyelinating polyneuropathy (CIDP) and acute inflammatory demyelinating polyneuropathy (AIDP) (sensitivity 90%, specificity 90.4%) (50). The DCEC scoring system uses the total scores of definition, CSA, echo, and nerve entrapment as quantitative evaluation indicators. The critical value of peripheral nerves in the arms and legs is 14.5, which is a good indicator of the presence or absence of DPN (the area under the curve is 0.85) (sensitivity is 0.81; specificity is 0.80) (51).

In addition, the newly developed ultrasound elastography can evaluate the neuroelasticity of DPN. As a new type of instrument, it can measure the hardness or elasticity of the tissue, reflecting the change of the elasticity of the compressed tissue with the degree of tissue deformation (52). Few studies have previously evaluated the changes in peripheral nerve elasticity in patients with DPN, but some studies have shown that this may be a new breakthrough point. The thickening of the peripheral nerve sheath fibers leads to changes in the elasticity of the tibial nerve in type 2 people with diabetes. The nerve stiffness of people with diabetes without clinical or electrophysiological signs of DPN was significantly higher than that of the control group, with a critical stiffness value of 51.05 kPa, a sensitivity of 90%, and a specificity of 85% (53, 54).

High-frequency ultrasound has the advantages of non-invasiveness and good repeatability, and has broad application prospects in the auxiliary diagnosis and prognosis judgment of DPN. The combination of ultrasound and nerve conduction examination can improve the diagnostic value of DPN and avoid missed diagnosis and misdiagnosis. It is helpful to evaluate the severity and prognosis of DPN with fuzzy boundary, enlarged CSA, and hypoechoic area, but it has certain limitations for the exploration of the deep neuromuscular plexus and lumbosacral plexus. With the popularity of high-resolution ultrasound, especially shear wave elastography, it is expected to replace neuroelectrophysiological examination in the diagnosis of DPN.

In summary, the above methods and technologies have their own advantages and disadvantages and need to be verified and further developed by large samples. They have not been widely used at present and are generally used as a supplement to traditional neuroelectrophysiological examinations. In clinical practice, it is still necessary to establish a unified, accurate, and convenient early screening method and diagnostic grading method for DPN, so as to quantitatively assess the degree of nerve damage, carry out early intervention and management, and improve the quality of life of DPN patients.