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* These authors contributed equally
The present protocol describes high-frequency neuromuscular ultrasonography of the digital and palmar branches of the median and ulnar nerve, which can aid in localizing peripheral nerve diseases and be adapted to evaluate digital nerve injuries.
Peripheral nerve ultrasound is a well-established imaging technique to evaluate certain peripheral nerve pathologies. However, there is a poor correlation between ultrasound abnormalities of peripheral nerves and electrodiagnostic or clinical evidence of axonal loss. This is a significant limitation of peripheral nerve ultrasound, as many peripheral nerve diseases encountered in clinical settings are related to axonal loss. Furthermore, clinical and electrodiagnostic evidence of axonal loss directly correlates with disability in all peripheral nerve diseases. However, due to the floor effects often encountered in electrodiagnostic studies, these correlations, as well as definitive diagnoses, are often challenging. Thus, imaging techniques that correlate with axonal loss are essential for expanding the utility of peripheral nerve ultrasound as a potential biomarker for peripheral nerve diseases. With new technological advancements and the ever-increasing imaging capabilities of high-frequency ultrasound, the palmar and digital nerve branches of the hand can be imaged with exceptionally high resolution even using point-of-care ultrasound devices. Their superficial and distal-most anatomic locations are ideal for evaluating polyneuropathies, as these branches degenerate earliest during axonal loss. However, no studies have systematically evaluated these nerve branches to determine if they can be reproducibly measured with ultrasound. The current protocol was adapted for the systematic assessment of cross-sectional areas of the median and ulnar nerves in the palmar surface and digits of the hand. This protocol provides reference data for a subset of nerves that demonstrate high intraclass correlation coefficients between three separate ultrasonographers. Finally, as a proof of concept and to demonstrate the clinical applications of this protocol, representative data from individuals with genetically confirmed inherited polyneuropathies are compared with established normative data to examine cross-sectional area differences.
The expansion of clinical ultrasound to evaluate peripheral nerves and muscles has substantially improved the ability to diagnose neuromuscular disorders1. Over the past 2 decades, ultrasound has emerged as a tool to directly image anatomical changes in the neuromuscular system, which correlate with pathological processes. Ultrasound is most commonly combined with clinical history and examination to provide further detail or support electrodiagnostic studies, which are considered a gold standard equivalent for diagnosing peripheral nerve disease2. In some cases of focal neuropathies such as carpal tunnel syndrome, ultrasound can be used in lieu of electrodiagnostic results with high sensitivity and specificity3. Due to its low cost, its ability to be performed at the bedside, and its non-invasive properties, ultrasound is the preferred imaging modality for the neuromuscular system for many clinicians4,5.
Peripheral nerve ultrasound has been explicitly proven invaluable for the localization of peripheral nerve diseases caused by abnormalities in myelin, such as chronic immune demyelinating polyneuropathies (CIDP)6,7 and Charcot-Marie-Tooth disease type 1A (CMT1A)7,8. In these diseases, the focal or diffuse cross-sectional area enlargements of nerves in the upper and lower extremities are well described. However, cross-sectional area enlargement is not specific to demyelinating diseases, as it has also been described in axonal polyneuropathies, albeit sparsely8. However, the cross-sectional enlargement in axonal diseases is significantly less robust and is non-uniform throughout the nerve. Due to these challenges, the utility of ultrasound in axonal neuropathies is limited.
Most peripheral nerve ultrasound studies have focused on imaging relatively proximal nerve locations primarily due to the larger nerve size, which makes identification more straightforward. However, the distal-most branches of peripheral nerves degenerate earliest in a Wallerian-like fashion during axonal loss in polyneuropathies9,10. Due to their smaller diameters, the imaging resolution has been a limiting factor for the reproducible imaging of these nerve branches. Recently, transducer resolution has improved sustainably due to more rapid and seamless image compounding techniques. Now, structures of approximately 500 µm can be routinely imaged with point-of-care ultrasound, and structures with sizes as low as 30 µm can be imaged using ultra-high frequency systems11. Thus, it is conceivable that the distal nerve branches in the feet and hands could be reliably evaluated with point-of-care ultrasound.
The palmar and digital nerve branches of the hand are the distal-most branches of the median, radial, and ulnar nerves. The palmar branches carry motor nerves (median and ulnar only) to the interossei muscles, in addition to the digital sensory nerves12. In cadaver studies, the palmar and digital branches measure between 0.8 mm and 2.1 mm in diameter13, which is well within the detection range for high-frequency ultrasound transducers. In addition, their superficial location allows for high- and ultra-high frequency imaging because of the minimal frequency loss through connective tissues or muscles. However, no studies have established normative cross-sectional areas of the digital or palmar nerve branches of the hand using ultrasound, which are necessary to allow for clinical and research studies. Therefore, the present protocol evaluates the palmar and digital nerve branches in hand.
Technical considerations
The principles of neuromuscular-focused ultrasound must be reviewed as a foundation before starting this protocol14. In addition, several specific considerations were made for the current protocol. A transducer with a small footprint and frequency above 15 MHz is recommended, given the hand's natural contours. A 10-22 MHz transducer, with a footprint of 8 mm x 13 mm (see Table of Materials), was used with a compatible digital ultrasound system.
The next considerations are imaging depth and focal zones. In all the present imaging studies, the palmar and digital nerves were less than 0.35 cm in depth. Thus, using a consistent depth of 1 cm is recommended for reproducibility. Furthermore, improved imaging can be achieved at this depth by placing two focal zones at the device's maximal heights.
Consistent image adjustments (frequency, gain, and grey maps) are strongly recommended. With the minimal superficial tissues overlying and surrounding the nerves, adjustments in these parameters during imaging will not improve the imaging resolution or quality. Given the small diameters of these nerves, utilizing secondary image analysis software such as ImageJ15,16 for cross-sectional area measurements is recommended.
All experiments in this study were performed in compliance with the Wayne State University and Detroit Medical Center Institutional Review Boards (IRB) under an approved protocol for the natural history of individuals with peripheral neuropathies. Informed consent was obtained from all human participants.
1. Instrumental setup
2. Patient preparation
NOTE: The patient inclusion criterion for inherited peripheral neuropathy was a confirmed mutation in a gene known to cause inherited peripheral neuropathy (please see the representative results section), with no exclusion criteria. For controls, the inclusion criterion was a normal result from electrodiagnostic testing of the upper extremities. Control exclusion criteria included a history or current diagnosis of diabetes mellitus, thyroid dysfunction, any known vitamin abnormalities, previous bariatric surgery, metabolic syndrome, a body mass index greater than 29, a history of traumatic nerve injury, or a history of large or small fiber peripheral neuropathy.
3. Ultrasound examination
NOTE: There are four common palmar branches of the median nerve and two common palmar branches of the ulnar nerve13. Each digit has a medial and lateral digital branch, with digits 1-3 being purely median innervated and digit 5 being purely ulnar innervated. Digit 4 is dually innervated by the median nerve on the lateral surface and the ulnar nerve on the medial surface. This protocol concentrates on imaging the median common palmar nerve to digit 2, the lateral digital branch to digit 2, the ulnar common palmar branch to digit 5, and the medial branch to digit 5.
4. Measuring cross-sectional area
NOTE: ImageJ, an open-source image processing software (see Table of Materials), was utilized for the present study, and the steps below are adapted for this software.
For the normative data, 20 individuals were selected with normal electrophysiology results, no neurological complaints, past medical history of or current diabetes mellitus, thyroid dysfunction, vitamin abnormalities, metabolic syndrome, carpal or cubital tunnel syndrome, exposure to chemotherapeutics, or severe hand trauma, and who had not been pregnant within the last 1 year (Table 1). Given the small subset, we did not stratify our data by age, gender, weight, or height, all of which are known to affe...
The present protocol describes high-frequency ultrasound of the hand's digital and palmar nerve branches. This study was designed to test the hypothesis that cross-sectional area enlargement in distal nerve branches correlates with axonal loss. Extensive multicenter natural history studies of individuals with different subsets of axonal diseases will be needed to resolve this hypothesis. In addition to its potential research benefits, this protocol can also be applied clinically to localize peripheral nerve complaint...
The authors have nothing to disclose.
This work was supported by the Wayne State University School of Medicine Departments of Neurology and Physical Medicine and Rehabilitation.
Name | Company | Catalog Number | Comments |
10-22mHz Transducer | General Electric Health Care | H48062AB | Small foot print transducer |
ImageJ | NIH | N/A | https://imagej.nih.gov/ij/ |
Logiq eR8 Ultrasound Beam Former | General Electric Health Care | H48522AS | This is the beamformer and image processor which includes Power Doppler Imaging |
Ultrasound Gel | Parker Labratories | 44873 | Standard ultrasonoic gel, non sterile |
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