Utility of non-invasive MRI assessment of tenosynovial amyloidosis for early detection of cardiac amyloidosis: UNRAVEL, a pilot study

Abstract Background Amyloidosis is a multisystem disorder affecting the heart, peripheral nerves, and other organs. Transthyretin (ATTR) and Light-Chain (AL) amyloidosis account for most Cardiac amyloidosis (CA) cases, with ATTR being more prevalent. Recent treatments slow progression and reduce hospitalizations, but prognosis remains poor, underscoring the need for early detection and intervention. Carpal tunnel syndrome (CTS) often precedes cardiac symptoms by 5–10 years, offering a window for early detection, especially in the setting of carpal tunnel release surgery. This study explored the ability of magnetic resonance imaging (MRI) to detect amyloid deposits within the carpal tunnel as a non-invasive alternative to biopsy. We hypothesized that MRI can detect amyloid-related changes, distinguishing amyloid-positive from amyloid-negative patients. Methods This cross-sectional pilot study involving 12 subjects (50% female, mean age 70 ± 7.2 years; 6 amyloid-positive, 6 amyloid-negative) with moderate-to-severe CTS post-carpal tunnel release, biopsy, and laser microdissection mass spectrometry. Subjects with biopsy-confirmed amyloid-positive or amyloid-negative status were recruited for wrist MRI. MRI sequences included T1-weighted, proton density (PD), and magnetization transfer ratio (MTR), reviewed by a blinded musculoskeletal radiologist. 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 within the carpal tunnel. Retinaculum thickness was 44% higher in the amyloid-positive group than in 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 of amyloid-related tissue remodeling. Carpal tunnel and median nerve enlargement were observed, with third space CSA increasing by 36% in the amyloid-positive group (1.05 ± 0.16 cm² vs. 0.77 ± 0.16 cm², p = 0.004). Selective tendon involvement included a 26% reduction in flexor pollicis CSA (0.17 ± 0.06 cm² vs. 0.23 ± 0.04 cm², p = 0.03), and enlargement of both the flexor digitorum profundus and superficialis were observed. MTR was 118% higher in tendons of amyloid-positive patients (0.81 ± 0.38 vs. 0.37 ± 0.06, p = 0.019), suggesting increased macromolecular composition due to amyloid fibrils, and was also elevated in other structures. Conclusion This study evaluated the use of non-invasive wrist MRI for assessing amyloid deposition in the carpal tunnel of amyloid-positive patients. Our findings suggest a trend toward larger carpal tunnel structures in amyloid-positive patients and selective tissue involvement supported by the presence of macromolecular changes, suggesting the potential for MRI-based noninvasive identification of amyloidosis. Validation studies to refine the methodology in a larger sample size are ongoing.Proton-Density MRI of Amyloid CTS