Background: Amyloidosis is a multisystem disease, often affecting the heart, nerves, and other organs. Transthyretin (ATTR) and Light-Chain (AL) amyloidosis are the most common causes of cardiac amyloidosis (CA), with ATTR being more prevalent. Although emerging treatments slow progression and reduce hospitalizations, the prognosis remains poor without early diagnosis. Carpal tunnel syndrome (CTS) frequently precedes cardiac symptoms by 5–10 years, providing a window for early detection. This study evaluates the ability of magnetic resonance imaging (MRI) to identify amyloid deposits in the carpal tunnel as a non-invasive alternative to biopsy, hypothesizing that MRI can differentiate amyloid-positive from amyloid-negative patients.
METHODS AND RESULTS: This cross-sectional pilot study enrolled 12 participants (50% female, mean age 70 ± 7.2 years; 6 amyloid-positive, 6 amyloid-negative) with moderate-to-severe CTS post-carpal tunnel release surgery, confirmed by biopsy and laser microdissection mass spectrometry. Wrist MRI was conducted on all participants, and imaging sequences included T1-weighted, proton density (PD), and magnetization transfer ratio (MTR). A musculoskeletal radiologist, blinded to the participants' amyloid status, reviewed the MRI results.
T1 and PD imaging revealed increased thickening and cross-sectional area (CSA) in the amyloid-positive group, particularly in the flexor tendons, tenosynovium, flexor retinaculum, and median nerve. The retinaculum thickness was 44% greater in amyloid-positive patients compared to the amyloid-negative group (0.23 ± 0.03 cm vs. 0.16 ± 0.04 cm, p = 0.007), suggesting fibrosis as a potential imaging biomarker for amyloid-induced tissue changes. Enlarged carpal tunnel and median nerve CSA were also noted, with the third space CSA increasing by 36% in amyloid-positive individuals (1.05 ± 0.16 cm² vs. 0.77 ± 0.16 cm², p = 0.004). Notably, selective tendon involvement was observed, including a 26% reduction in flexor pollicis CSA (0.17 ± 0.06 cm² vs. 0.23 ± 0.04 cm², p = 0.03), as well as enlargement of flexor digitorum tendons. MTR values were 118% higher in amyloid-positive tendons (0.81 ± 0.38 vs. 0.37 ± 0.06, p = 0.019), indicating a higher macromolecular composition consistent with amyloid deposition.
Conclusion: This pilot study shows that non-invasive wrist MRI can detect amyloid-related changes in the carpal tunnel, with larger structures and selective tissue involvement in amyloid-positive patients. Elevated MTR values further suggest amyloid deposition. These findings support MRI as a tool for early, non-invasive amyloidosis detection. Ongoing validation with larger samples is needed to refine this methodology.
