Musculoskeletal Ultrasound and MRI in the Evaluation of Chemotherapy-Induced Peripheral Neuropathy: A Review

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is the primary dose-limiting toxicity in albumin-bound paclitaxel chemotherapy regimens. Current assessment methods based on clinical scales are limited by strong subjectivity and insufficient sensitivity, while most emerging technologies remain in the preclinical stage. Therefore, the development of objective and non-invasive imaging biomarkers is urgently needed. This review focuses on the transformative role of non-invasive imaging techniques in addressing unmet clinical needs such as the accurate imaging assessment of CIPN, and systematically analyzes the complementary value of musculoskeletal ultrasound (MSUS) and magnetic resonance imaging (MRI) in evaluating nervous system damage induced by albumin-bound paclitaxel-related CIPN. For key peripheral nerves including the radial nerve, ulnar nerve, median nerve, and common peroneal nerve, MSUS can visualize morphological abnormalities and hemodynamic changes in real time through high-frequency probes, enabling rapid, radiation-free anatomical assessment, and serial monitoring. MRI can detect early neurostructural damage, nerve edema, and abnormal nerve fascicle signals, while also evaluating soft-tissue lesions in the nerve trajectory area. Future research should conduct systematic validation of standardized imaging data to clarify the clinical value of these techniques as predictive biomarkers for risk stratification of CIPN. This article aims to construct a novel clinical diagnostic approach for CIPN, provide a more precise and efficient diagnostic pathway for patients with peripheral neuropathy symptoms, further support the timely formulation and implementation of targeted clinical treatment plans, and ultimately contribute to improving patient prognosis.

Introduction

In recent years, the incidence of breast cancer has shown a continuous upward trend [1,2]. Taxane-based chemotherapeutic agents, especially albumin-bound paclitaxel, have been increasingly widely used as one of the main treatment modalities [3]. Despite its superior antitumor efficacy compared to traditional taxanes, albumin-bound paclitaxel exhibits a more prominent neurotoxic profile, with particularly severe damage to the peripheral nervous system [4].

Peripheral neuropathy induced by albumin-bound paclitaxel exhibits a unique neuroanatomical distribution pattern, with the incidence of pain increasing with cumulative dosage [5]. It involves small fiber nerves (Aδ fibers and C fibers) and large fiber nerves (Aα/β fibers) in the “glove-and-stocking” distribution area, resulting in hand and foot numbness, tingling sensations, and abnormalities in temperature perception. Meanwhile, paclitaxel derivatives accumulate in the dorsal root ganglia (DRGs) [6], triggering neuronal apoptosis and exacerbating sensory dysfunction. In contrast, motor nerve damage has a lower incidence, usually associated with high-dose treatment regimens, primarily involving Aα fibers. Clinical motor symptoms such as muscle weakness and decreased tendon reflexes typically appear later than sensory symptoms.

Traditional assessment methods for CIPN have significant limitations. Although the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) scale is widely used, it has several shortcomings: its 1–4 grade classification system relies on patient-reported symptoms and clinicians’ experience, resulting in introducing subjectivity and a high risk of reporting bias. More importantly, this scale lacks sensitivity for detecting early or mild neuropathy, and its crude grading criteria fail to capture subtle changes in symptoms. In contrast, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-CIPN Module 20 (EORTC QLQ-CIPN20) scale, as a patient-reported outcome measure, can more comprehensively assess sensory, motor, and autonomic nerve symptoms, but confounding factors such as patients’ psychological status, cognitive level, and cultural differences may interfere with the assessment results [7]. Nerve conduction studies (NCS) have certain application value in evaluating nerve function; however, for patients with small-fiber neuropathy, electrophysiological examinations are ineffective, as the condition is still in the subclinical stage [8].

Recent advances have been made in CIPN assessment methods, including artificial intelligence-based analytical approaches [9,10] and biomarker detection technologies [11,12], and these methods show promising research potential. However, these innovative technologies currently face significant translational challenges – either remaining in the theoretical exploration stage or requiring invasive procedures, which limits their clinical feasibility and immediate applicability in routine patient diagnosis and treatment. This gap between research innovation and clinical application indicates an urgent need to further develop non-invasive and clinically practical CIPN assessment tools.

Therefore, this article systematically summarizes the utility of MSUS and MRI in the assessment of albumin-bound paclitaxel-induced peripheral neuropathy, clarifies the clinical adaptation scenarios of these 2 imaging techniques, provides practical references for overcoming the limitations of current CIPN assessment, and further assists in achieving precise diagnosis and individualized treatment decisions for this type of neurotoxicity in clinical practice.

Pathogenesis of Chemotherapy-Induced Neuropathy

The mechanism of paclitaxel-induced CIPN has not been fully elucidated, but it may involve microtubule dysfunction, oxidative stress, inflammatory responses, and ion channel abnormalities [13]. Chemotherapeutic agents are cytotoxic and can damage not only cancer cells but also peripheral nerves. For example, platinum-based drugs, after entering the human body, bind to DNA in nerve cells to form platinum-DNA adducts, interfering with the normal metabolism and function of nerve cells and leading to nerve cell damage. Taxane-based drugs mainly bind to tubulin, inhibiting the dynamic balance of microtubules, disrupting the normal transport function of nerve axons, and inducing neuropathy. In addition, chemotherapeutic agents can induce oxidative stress responses, resulting in the production of many reactive oxygen species (ROS) in the body. These ROS attack lipids, proteins, and nucleic acids on the nerve cell membrane, leading to membrane damage, abnormal ion channel function, and further exacerbation of nerve damage. Meanwhile, inflammatory responses play an important role in the occurrence and development of CIPN. Chemotherapeutic agents activate the immune system, triggering inflammatory cell infiltration and the release of inflammatory factors such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), which can directly or indirectly damage nerve cells and affect nerve conduction.

Traditional diagnostic methods such as clinical symptom assessment and neuroelectrophysiological examinations have certain value but also limitations. In contrast, imaging examinations can provide intuitive information on nerve structure and function, facilitating the early detection of CIPN and the accurate assessment of lesion severity and scope.

MSUS Technical Principles and Equipment Selection

This examination does not require special patient preparation, but to obtain optimal imaging results, the scanned area and limbs must be fully exposed according to the anatomical course of the target peripheral nerve. In terms of equipment selection, high-frequency linear array probes (10–18 MHz) have the best resolution for evaluating superficial nerves (such as the median nerve, ulnar nerve, and radial nerve) [14], while low-frequency probes (5–10 MHz) are required for deep or thick nerves (such as the sciatic nerve and brachial plexus) to ensure sufficient penetration depth [15]. Combined with dynamic imaging technology, MSUS can observe whether there is nerve compression, displacement, or morphological abnormality when the patient’s limbs are moving; paired with color Doppler mode, it can detect blood flow signals around the nerves, assisting in assessing pathological states such as nerve inflammation, edema, or neovascularization. For the fine structure of nerves, MSUS can clearly display the arrangement of nerve fascicles by adjusting imaging parameters, providing morphological evidence for assessing nerve injury [16].

Characteristic MSUS Manifestations of CIPN

MSUS is a highly sensitive imaging technique for evaluating peripheral nerve damage, mainly achieving diagnosis through the following 3 categories of key diagnostic features: (1) Abnormal structural continuity: Complete transection is manifested by interruption of the nerve fascicle structure, accompanied by retraction of the nerve stump or formation of a traumatic neuroma; partial laceration is manifested by local disorganization of nerve fascicles, often accompanied by perineural hematoma [17]. (2) Morphological changes: Including pathological nerve enlargement (such as median nerve cross-sectional area [CSA] >10–15 mm² in carpal tunnel syndrome) to chronic atrophic changes (nerve thinning accompanied by hyperechoic fibrotic transformation) [18,19]. (3) Microstructural evolution: The normal nerve structure (transverse section showing a “honeycomb” pattern with hypoechoic nerve fascicles within the hyperechoic epineurium; longitudinal section showing a “cord-like” nerve fascicle structure) undergoes acute-phase changes (blurred boundaries, heterogeneous echo) to chronic-phase degeneration (complete disappearance of nerve fascicle structure, replaced by fibrosis) [20]. This comprehensive ultrasound assessment can accurately evaluate nerve integrity, dynamically monitor lesion progression, and reliably predict prognosis, making MSUS an indispensable tool in the diagnosis and management of nerve damage (Table 1).

Table 1.

Analysis of direct and indirect sonographic features of chemotherapy-induced peripheral neuropathy (CIPN).

Direct ultrasonic signs	Indirect ultrasonic signs
Alterations in Nerve Continuity, Complete Rupture: Disruption of nerve fascicle echogenicity with retracted ends/traumatic neuroma formation. Partial Tear: Localized architectural disorganization accompanied by hematoma	Peripheral Tissue Abnormalities, Compressive Lesions: Ganglion cysts (anechoic cystic structures), osteophytic deformities. Subsequent Changes: Edema (hypoechoic areas), fibrosis (hyperechoic enhancement)
Neuromorphological Alterations, Pathological thickening (eg, cross-sectional area [CSA] of the median nerve >10–15 mm2 in carpal tunnel syndrome). Chronic atrophy (thinning with hyperechoic fibrotic changes)	Muscle Denervation Changes, Acute phase: Muscle fascicle edema (hypoechoic and loss of fascicular architecture). Chronic phase: Atrophy with fatty infiltration (hyperechoic appearance and thickening of perimysial septa)
Microstructural Changes in Nerve Fascicles, Acute phase: Loss of fascicular demarcation and heterogeneous echotexture. Chronic phase: Structural disintegration with fibrosis (disruption of the normal “honeycomb” or “cable-like” architecture)	Dynamic Functional Impairments Abnormal nerve gliding (eg, gliding distance <3 mm in carpal tunnel syndrome), Compression-induced deformation (morphological changes at the site of constriction during dynamic observation)

CIPN – chemotherapy-induced peripheral neuropathy; CSA – cross-sectional area.

High-resolution ultrasound can clearly evaluate the normal and pathological states of the radial nerve, ulnar nerve, median nerve, and common peroneal nerve. Under normal conditions, the radial nerve is superficially identifiable near the lateral epicondyle of the humerus, presenting a “honeycomb” pattern in transverse section with a diameter of 1.0–2.0 mm. The ulnar nerve is a flat ellipse in the ulnar groove of the elbow joint, with a cross-sectional area (CSA) <8 mm² and a “honeycomb” pattern. The median nerve is elliptical in the carpal tunnel with a CSA <10 mm²; the common peroneal nerve is a flat cord-like structure around the fibular head with a diameter <3 mm, and all nerves show a continuous, uninterrupted characteristic morphology in longitudinal section. When damaged, the radial nerve enlarges acutely due to edema or demyelination (diameter >2.0 mm) with reduced internal echo, and can further enlarge with disorganized structure in the chronic phase; the ulnar nerve has a CSA >10 mm², impaired mobility during elbow flexion, and echo changes from hypoechoic in the acute phase to hyperechoic in the chronic phase; the median nerve (in chemotherapy-related cases) enlarges in the proximal segment of the carpal tunnel with reduced flatness, echo changes from hypoechoic to hyperechoic, and enhanced color Doppler flow imaging (CDFI) signals during the inflammatory phase. The common peroneal nerve shows focal enlargement at the compression site, edema of nerve fascicles, limited mobility during ankle dorsiflexion, and epineural interruption in severe cases (each assessment corresponds to Table 2 and Figures 1–4).

Table 2.

Normal ultrasonographic features of four peripheral nerves in chemotherapy-induced peripheral neuropathy (CIPN) assessment.

Nerve type	Anatomical location features	Transverse section morphology/structure	Key quantitative indicators
Radial nerve	Long course in the upper arm and forearm; most superficial near the lateral epicondyle of the humerus, adjacent to the bone surface	Round or oval shape with clear boundaries, showing a characteristic “honeycomb-like” structure (hypoechoic nerve fascicles interspersed among hyperechoic epineurium)	Diameter: 1.0–2.0 mm (with normal anatomical variations)
Ulnar nerve	Located in the ulnar groove	Flattened oval shape, showing a “honeycomb-like” structure (hypoechoic nerve fascicles enclosed by hyperechoic epineurium with clear boundaries)	Cross-sectional Area (CSA): consistently <8 mm2
Median nerve	Within the carpal tunnel	Oval shape with clear boundaries of nerve fascicles, showing an alternating pattern of hypoechoic and hyperechoic signals	Cross-sectional Area (CSA): consistently <10 mm2
Common peroneal nerve	Around the fibular head	Flattened cord-like shape with intact nerve fascicle structure and continuous epineurium	Diameter: <3 mm

CIPN – chemotherapy-induced peripheral neuropathy; CSA – cross-sectional area.

Figure 1.

(A) Longitudinal and (B) transverse views of a normal peripheral nerve. (C, D) Nerve enlargement with hypoechoic fascicles and disrupted architecture, consistent with peripheral nerve injury.

Figure 2.

(A) Longitudinal and (B) transverse sections of a normal nerve. (C, D) Nerve swelling with hypoechoic fascicles and loss of tissue demarcation, indicating peripheral neuropathy.

Figure 3.

(A) Longitudinal and (B) transverse views of a normal median nerve. (C, D) Nerve swelling with epineurial thickening and loss of fascicular definition, consistent with median nerve pathology.

Figure 4.

(A) Longitudinal and (B) transverse views of a normal common peroneal nerve. (C, D) Nerve thickening with decreased echogenicity and fascicular texture loss, indicating peroneal neuropathy.

Quantitative Assessment Parameters of MSUS

MSUS can more accurately assess the degree of nerve damage and CIPN progression through several quantitative parameters. When the cut-off value of cross-sectional area (CSA) is ≥12 mm², the CSA change value (ΔCSA) is ≥4 mm², and the wrist–funnel ratio (WFR) is >1.4, the diagnostic accuracy is excellent. However, for any given ultrasound parameter, there is no statistically or clinically significant difference in accuracy between different measurement locations [21]. In CIPN, measuring changes in nerve CSA can intuitively reflect the degree of nerve swelling or atrophy, providing a quantitative basis for judging the condition. Vascular changes around the nerve are also a key indicator. Under normal conditions, there are no blood flow signals within the nerve, but during the acute inflammatory phase of CIPN, the number of intraneural blood flow signals increases as a stress response of the body attempting to provide more nutrients to the damaged nerve. In the chronic phase, with further impairment of nerve function and increased fibrosis, the blood flow signals decrease again. These vascular changes reflect the metabolic and functional status of the nerve, providing strong clues for evaluating CIPN progression.

Advantages and Limitations of MSUS

MSUS has many significant advantages in peripheral nerve assessment. It has excellent spatial resolution (up to ≤0.1 mm), enabling fine visualization at the nerve fascicle level. For superficial nerves such as the median nerve and ulnar nerve, its assessment effect is even better than that of MRI, as it can clearly show the subtle structure and lesions of the nerve. MSUS is also non-invasive and portable, eliminating the need for patients to endure the pain of invasive examinations. The equipment is easy to carry, allowing for serial monitoring and bedside examinations at any time, which improves the convenience and accessibility of the examination.

However, MSUS has obvious limitations in visualizing deep nerve structures such as the sacral plexus nerve, making it difficult to clearly show the entire picture. MSUS is significantly operator-dependent; differences in the experience and technical level of different operators may lead to deviations in examination results, which places high requirements on the professional training of ultrasound doctors. MSUS cannot evaluate nerve physiological functions and can only observe changes in the morphological structure of the nerve. For physiological function information such as nerve conduction velocity and nerve impulse firing, other examination methods are required.

Core Technical Principles of MRI (DTI/DKI)

Magnetic resonance neuroimaging (MRI) occupies an important position in the assessment of neuropathy due to its excellent soft-tissue resolution and multiplanar imaging advantages, especially having unique value in detecting deep nerve lesions. Among them, diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) are key technologies in MRI.

The core aim of DTI is to quantify the diffusion characteristics of water molecules in biological tissues. In human nerve tissue, the diffusion of water molecules is not completely free, but is affected by the structure of nerve fibers, showing anisotropy. DTI measures the diffusion degree of water molecules in different directions by applying diffusion-sensitive gradients in multiple different directions, thereby obtaining information on the directionality and connectivity of nerve fibers. The fractional anisotropy (FA) is an important quantitative parameter in DTI, with a value range of 0–1. When the FA value is close to 0, it indicates that the diffusion of water molecules is relatively uniform in all directions, and the tissue has a low degree of anisotropy; when the FA value is close to 1, it means that water molecules mainly diffuse in one direction, and the tissue has a high degree of anisotropy, which is common in areas where nerve fibers are closely and regularly arranged. For example, in normal nerve fiber bundles, water molecules diffuse more easily along the long axis of the nerve fibers, resulting in a high FA value. The apparent diffusion coefficient (ADC) reflects the overall diffusion capacity of water molecules, comprehensively considering the diffusion in all directions. In neuropathy, the ADC value will change; for example, nerve fiber damage leading to restricted diffusion of water molecules can result in a decreased ADC value.

DKI is a more advanced imaging technology developed on the basis of DTI, mainly used to capture the non-Gaussian diffusion characteristics of water molecules. In the complex microstructure of nerve tissue, the diffusion of water molecules does not completely conform to Gaussian distribution, especially in the presence of demyelination and crossing fibers. By introducing the concept of kurtosis, DKI can more accurately describe the diffusion behavior of water molecules. Mean kurtosis (MK) is a key derived parameter of DKI, which reflects the heterogeneity of the microstructure of nerve tissue. When nerve tissue is affected by lesions such as demyelination, the structure of nerve fibers becomes disorganized, the diffusion pattern of water molecules becomes more complex, and the MK value will increase accordingly. Compared with DTI, DKI is more sensitive in detection of these microstructural changes, enabling earlier detection of subclinical damage and providing more powerful support for the early diagnosis of diseases [22].

The Correlation Between MRI Features, CIPN Pathology, and Clinical Scales

There is a close correlation between MRI imaging features and the pathological changes of CIPN, providing important clues for the diagnosis and assessment of the disease. In CIPN, pathological changes mainly include axonal degeneration, demyelination, and edema of nerve fibers. From the perspective of MRI imaging, axonal degeneration and demyelination will destroy the integrity of nerve fibers, leading to restricted diffusion of water molecules and changes in anisotropy, which are further manifested as a decrease in the FA value. This is because in normal nerve fibers, the diffusion of water molecules along the orderly arranged nerve fibers has high anisotropy, while axonal degeneration and demyelination destroy this orderly structure, making the diffusion of water molecules more uniform in all directions, and the FA value decreases accordingly. At the same time, endoneurial edema will increase the water molecule content and expand the diffusion space, leading to an increase in the ADC value. In a study, pathological analysis of nerve tissue from CIPN patients was compared with MRI imaging, and it was found that the FA value was significantly negatively correlated with the degree of axonal injury, and the ADC value was positively correlated with the degree of nerve edema, which strongly proved this correlation [23].

MRI parameters also have a significant correlation with clinical scales in assessing the severity and prognosis of CIPN. Commonly used clinical assessment scales such as the Total Neuropathy Score (TNS) and Neuropathy Disability Score (NDS) comprehensively evaluate patients’ symptoms, signs, and nerve function. Studies have shown that the FA value and MK value in MRI are closely correlated with the scores of these clinical scales [24]. With the aggravation of CIPN, patients’ clinical symptoms become more obvious, the scale scores increase, and at the same time, the FA value on MRI images further decreases and the MK value increases [25]. Doctors can more accurately judge the disease progression trend of patients by analyzing MRI parameters combined with clinical scale scores, providing a scientific basis for formulating personalized treatment plans. Recent studies have shown that gadoxetic acid-enhanced MRI can predict early nab-paclitaxel-induced peripheral neuropathy during pancreatic cancer treatment [26].

Quantitative Assessment Parameters of MRI

The quantitative parameters of DKI/DTI are significantly correlated with the severity of CIPN [27]. The incidence of neurotoxicity induced by albumin-bound paclitaxel exceeds 50% [28], and the symptoms are often persistent. DTI can effectively and directly show nerve swelling and decreased signal intensity within the fiber bundles, while DKI is more sensitive to microstructural abnormalities such as blurred fiber bundles and unclear boundaries. Although MSUS has been widely used in the diagnosis of superficial nerve damage, its assessment of deep nerve damage is still significantly limited. MRI can be used to evaluate tibial nerve and common peroneal nerve damage, as shown in Figure 5.

Figure 5.

(A, C) Diffusion kurtosis imaging and diffusion tensor imaging show normal MRI findings of the tibial nerve and common peroneal nerve. (B) It presents with disruption of nerve fiber bundle structure, disappearance of perineural boundaries, and obvious fusiform thickening of the common peroneal nerve. (D) It presents with focal hypointensity along the nerve fiber bundles (indicated by arrows), consistent with the manifestations of axonal injury.

Limitations and Reproducibility Challenges of MRI

Despite the value of MRI in the diagnosis and assessment of CIPN, it also has some limitations. MRI is susceptible to motion artifacts and susceptibility artifacts. CIPN patients often experience symptoms such as pain and paresthesia, which may make it difficult for them to remain still during the examination. Even very slight movements can cause blurring or distortion of the acquired images, thereby affecting image quality and the accuracy of parameter measurement. Metal implants in the body, such as infusion ports and dentures, can interfere with the uniformity of the magnetic field, producing susceptibility artifacts that make local nerve structures unclear and can lead to misdiagnosis or missed diagnosis.

Insufficient anatomical resolution is also a key problem faced by MRI. For distal small nerves with a diameter of less than 2 mm, such as interdigital nerves, the imaging effect of MRI is not as good as that of high-frequency ultrasound. Since paclitaxel-induced neuropathy usually originates from the small nerves at the extremities, this limits the application of MRI in the early detection of these lesions. MRI examinations are relatively expensive, requiring high-field MRI equipment (usually ≥3.0T) and specialized post-processing software, which imposes a heavy economic burden on some primary hospitals and makes it difficult to use extensively. The single scan time of MRI is relatively long, generally 15–20 minutes, which is not suitable for emergency patients or patients who cannot maintain their position for a long time.

MRI also faces challenges in terms of reproducibility. Different MRI equipment, scanning parameters, and post-processing algorithms may lead to differences in the examination results of the same patient. Differences in the experience and technical level of different operators in image acquisition and analysis will also affect the accuracy and reproducibility of the results. To solve these problems, it is necessary to establish a unified scanning protocol and standardized post-processing, strengthen the training and quality control of operators, and improve the reproducibility and reliability of MRI examinations.

Standardized Protocol for Peripheral Nervous System Examination

Peripheral nerve examination follows a systematic 3-step process: (1) Anatomical localization: preliminary identification of nerves through guidance from surface landmarks, such as locating the median nerve in the carpal tunnel or the ulnar nerve in the ulnar groove area of the elbow joint; (2) Dynamic functional assessment: evaluating nerve mobility by observing the sliding pattern of the nerve during active limb movement (such as finger flexion-extension cycles), providing key information for potential nerve adhesion or compression syndrome [29]; and (3) Bilateral comparative analysis: comparing the affected nerve with the contralateral healthy nerve to identify significant morphological differences in nerve diameter, echo texture, and nerve fascicle structure.

Future Directions

Previous studies have confirmed that MSUS is a rapid, non-invasive assessment tool for CIPN with good patient tolerance. It can be performed at the bedside using a conventional 15 MHz linear probe [30]. However, there remains a gap in longitudinal studies on the cross-sectional area (CSA) of the sural nerve in CIPN patients, and its dynamic predictive value needs verification. Experiments in rabbit models have shown that both DKI and DTI can be used to evaluate peripheral nerve injury and are insensitive to confounding perineural edema. Nevertheless, given that DTI has a significantly shorter scanning time and sufficient signal-to-noise ratio, it is more practical and effective in assessing acute peripheral nerve injury, suggesting the need for further clinical validation of its longitudinal monitoring performance in CIPN.

MSUS and MRI each have distinct characteristics in diagnostic sensitivity, resolution, and clinical applicability (Table 3); however, their integrated clinical application still faces key challenges. The primary obstacle is the lack of internationally unified imaging-based severity grading standards for CIPN. In one study, significant differences were observed in the CSA proximal to the carpal tunnel and the CSA ratio change at the tunnel inlet among patients in different severity groups. When using a CSA >19 mm² proximal to the carpal tunnel as the cut-off value for predicting severe disease, the sensitivity and specificity were 75.0% and 65.9%, respectively. Using a CSA ratio change >1.5 at the carpal tunnel inlet as the cut-off value for predicting severe disease yielded a high specificity (82.9%) but low sensitivity (53.6%) [31]. This inconsistency hinders the accurate matching of imaging findings with clinical grading and impacts effective treatment decision-making. Future work should prioritize multicenter pathological control studies to develop biopsy-validated imaging diagnostic criteria and unify grading thresholds.

Table 3.

Comparison of diagnostic performance between MSUS and MRI in evaluating chemotherapy-induced peripheral neuropathy (CIPN).

Comparison dimension	Musculoskeletal ultrasound (MSUS)	Magnetic resonance imaging (MRI)
Diagnostic sensitivity	High detection rate for acute edema in superficial nerves (median nerve, ulnar nerve)	High detection rate for microstructural damage in deep nerves (sciatic nerve, sacral plexus)
Resolution and penetration depth	High-frequency probe (10–18 MHz): resolution of 0.1 mm, penetration depth <3 cm; Low-frequency probe: penetration depth up to 5 cm, resolution reduced to 0.3 mm	3.0T equipment: resolution of nerve fascicles is 0.2 mm, penetration depth >10 cm, but insufficient resolution for distal nerves with diameter <2 mm (eg, interphalangeal/interdigital nerves)
Clinical applicability	Suitable for bedside rapid screening (5-10 minutes per examination) and dynamic monitoring during chemotherapy cycles	Suitable for pre-treatment baseline assessment and localization of deep nerves; single examination takes 15–20 minutes, and patients need to remain still during the examination

MSUS – musculoskeletal ultrasound; MRI – magnetic resonance imaging; CIPN – chemotherapy-induced peripheral neuropathy.

The rational application pathway of MSUS and MRI in CIPN management has not yet been established. Based on existing evidence, a hierarchical strategy of “MSUS for superficial nerve screening + MRI for deep nerve assessment” is recommended for baseline pre-treatment evaluation: when mild symptoms occur during chemotherapy, MSUS should be the first choice for dynamic monitoring. If a CSA increase exceeding 20% is detected, MRI is recommended to further clarify the involvement of deep nerves. This pathway may reduce unnecessary examinations, but its cost-effectiveness, long-term efficacy in guiding treatment adjustments, and role in reducing the incidence of severe CIPN still need rigorous verification through large-sample, multicenter trials. Ultimately, clinical practice guidelines regulating the sequential or combined use of these 2 techniques are needed.

In addition, although these 2 techniques are complementary – MSUS for real-time dynamic monitoring of superficial nerves and MRI for quantifying microstructural damage of deep nerves – fundamental barriers remain in their translation from research tools to routine clinical practice. Future efforts should focus on formulating technical standards for MSUS and MRI in CIPN assessment to reduce operator dependence; developing and validating artificial intelligence (AI)-based automatic analysis systems through multicenter studies to improve result reproducibility and efficiency; and further exploring emerging imaging technologies. Examples include ultra-high-field MRI (7T MRI), which offers superior signal-to-noise ratio and spatial resolution and is expected to visualize the microstructure of small distal nerves [32], and PET-MRI fusion technology, which can simultaneously detect structural damage and active pathological processes such as neuroinflammation via specific molecular probes [33]. The diagnostic value, cost-effectiveness, and accessibility of these technologies require comprehensive verification through well-designed clinical studies.

Conclusions

This review systematically discussed the utility and challenges of MSUS and magnetic resonance neuroimaging in the diagnosis and assessment of CIPN. MSUS excels in superficial nerve assessment due to its high resolution, real-time dynamic capabilities, and portability, enabling clear identification of acute-phase edema, chronic-phase fibrosis, and blood flow changes. MRI, particularly quantitative imaging techniques based on DTI and DKI, can reveal microstructural changes in deep nerves and objectively quantify the degree of axonal injury and demyelination through parameters such as fractional anisotropy (FA) and mean kurtosis (MK). The combination of these 2 forms in multimodal imaging could effectively compensates for the deficiencies of traditional clinical assessment and electrophysiological examinations in objectivity and localization accuracy. However, the operator-dependence of MSUS, the high cost and long scanning time of MRI, and the differences in diagnostic thresholds and severity grading standards between the 2 techniques still pose challenges to their widespread application. Future efforts should promote the use of MSUS and MRI in the diagnosis and treatment of CIPN through standardization and multicenter studies, enabling them to become important tools for improving patient prognosis.

Abbreviations

CIPN

chemotherapy-induced peripheral neuropathy

MSUS

musculoskeletal ultrasound

MRI

magnetic resonance imaging

NCI-CTCAE

National Cancer Institute Common Terminology Criteria for Adverse Events

EORTC QLQ-CIPN20

European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-CIPN Module 20

NCS

nerve conduction studies

DRGs

dorsal root ganglia

CSA

cross-sectional area

CDFI

color Doppler flow imaging

DTI

diffusion tensor imaging

DKI

diffusion kurtosis imaging

FA

fractional anisotropy

ADC

apparent diffusion coefficient

MK

mean kurtosis

TNS

total neuropathy score

NDS

neuropathy disability score

WFR

wrist–funnel ratio