Noninvasive Imaging in Pediatric Spinal Muscular Atrophy Patients Using Multispectral Optoacoustic Tomography: A Proof-of-Concept Study

Background/Purpose: Spinal muscular atrophy (SMA) is becoming a treatable condition but prognostic imaging biomarkers are missing. To enable the visualization and quantification of muscle tissue composition and degeneration in SMA, non-invasive laser-based multispectral optoacoustic tomography (MSOT) was used.

Methods: In this case–control proof-of-concept trial (clinicaltrails.gov ID NCT04115475), 10 SMA patients were imaged using MSOT and compared to 10 gender/age-matched healthy volunteers (HV). A total of 59 matched muscle sites were compared and analyzed for 13 single wavelengths (SWL) between 680 and 1,100 nm and five spectrally unmixed MSOT parameters (HbO₂/Hb_R/Hb_T/collagen/lipid). Results were correlated with standard motor outcome tests and standard B-mode ultrasound imaging.

Results: MSOT signal was homogeneous in muscles of HV, while SMA patients showed a moth-eaten optoacoustic imaging pattern. Performing signal quantification, the SWL 800 nm revealed the greatest difference between HV and SMA (58.6 [7.7] a.u. vs. 54.0 [10.7] a.u., p = 0.0082) with most robust correlation when compared to clinical standard assessments (HFMSE score, r = 0.63, p = 0.0037, and RULM score r = 0.72, p = 0.0004). For MSOT parameters, MSOT lipid was higher in SMA patients compared to HV (40.1 [18.1] a.u. vs. 53.0 [26.5] a.u., p = 0.0050). Mean MSOT Hb_T furthermore showed lower signal levels according to the severity of the SMA types (type III: 86.6 a.u. vs. type I: 54.6 a.u., p = 0.0136 and type II: 82.1 a.u. vs. type I: 54.6 a.u , p = 0.0274).

Conclusion: Handheld MSOT imaging is a promising technology for non-invasive, nonionizing evaluation of disease burden in pediatric SMA patients.

Publication History

Article published online:
28 October 2021