Biomarkers for monitoring disease progression and response to therapy are lacking for muscle diseases such as Duchenne muscular dystrophy. Non-invasive in vivo molecular imaging with multispectral optoacoustic tomography (MSOT) utilizes pulsed laser light to induce acoustic pressure waves, enabling the visualization of endogenous chromophores. Here, we describe a novel application of MSOT, in which illumination in the near-and extended near-infrared range (NIR and exNIR) from 680-1100 nm enables the visualization and quantification of collagen content. We first demonstrated the feasibility of this approach to non-invasively quantify tissue fibrosis in longitudinal studies in a large-animal DMD model in pigs, and then applied this approach to pediatric patients (NCT03490214). MSOT-derived collagen content measurements in skeletal muscle were highly correlated to the functional status of the patients and provided 86 additional information on molecular features as compared to magnetic resonance imaging. This 87 study highlights the potential of MSOT imaging as a non-invasive, age-independent biomarker for the implementation and monitoring of newly-developed therapies in muscular diseases.
Double quantum filtered 23Na MRI with magic angle excitation (DQF‐MA) can be used to selectively detect sodium ions located within anisotropic structures such as muscle fibers. It might therefore be a promising tool to analyze the microscopic environment of sodium ions, for example in the context of osmotically neutral sodium retention. However, DQF‐MA imaging is challenging due to various signal dependences, on both measurement parameters and external influences. The aim of this work was to examine how B0 in combination with B1 inhomogeneities alter the DQF‐MA signal intensity. We showed that, in the presence of B0 inhomogeneities, flip angle schemes with only one 54.7° pulse can be favorable compared with the classical 90°‐54.7°‐54.7° scheme. DQF‐MA images of the human lower leg were acquired at B0 = 3 T with a nominal spatial resolution of 12 × 12 × 36 mm3 within an acquisition time of TAcq < 10 min, and compared with spin density weighted (DW), as well as triple quantum filtration (TQF) 23Na images. We found mean normalized signal‐to‐noise ratios of TQF/DW = 13.7 ± 2.3% (tibialis anterior), 11.9 ± 2.3% (soleus) and 11.4 ± 2.2% (gastrocnemius medialis), as well as DQF‐MA/DW = 4.7 ± 1.1% (tibialis anterior), 3.3 ± 0.73% (soleus) and 3.4 ± 0.6% (gastrocnemius medialis). These ratios might serve as additional measures in future clinical studies of sodium retention within human skeletal muscle. However, the influence of B0 and B1 inhomogeneities should be considered when interpreting DQF‐MA images.
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