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.
The aim of this prospective cohort study was to evaluate the effect of compression garments under resting conditions and after the induction of delayed-onset muscle soreness (DOMS) by MR perfusion imaging using intravoxel incoherent motion (IVIM). Magnetic resonance imaging of both lower legs of 16 volunteers was performed before and after standardized eccentric exercises that induced DOMS. A compression garment (21-22 mmHg) was worn during and for 6 h after exercise on one randomly selected leg. IVIM MR imaging, represented as total muscle perfusion D*f, perfusion fraction f and tissue diffusivity D, were compared between baseline and directly, 30 min, 6 h and 48 h after exhausting exercise with and without compression. Creatine kinase levels and T2-weighted images were acquired at baseline and after 48 h. DOMS was induced in the medial head of the gastrocnemius muscle (MGM) in all volunteers. Compression garments did not show any significant effect on IVIM perfusion parameters at any time point in the MGM or the tibialis anterior muscle (p > 0.05). Microvascular perfusion in the MGM increased significantly in both the compressed and noncompressed leg between baseline measurements and those taken directly after and 30 min after the exercise: the relative median f increased by 31.5% and 24.7% in the compressed and noncompressed leg, respectively, directly after the exercise compared with the baseline value. No significant change in tissue perfusion occurred 48 h after the induction of DOMS compared with baseline. It was concluded that compression garments (21-22 mmHg) do not alter microvascular muscle perfusion at rest, nor do they have any significant Abbreviations used: C, compressed; CK, creatine kinase; DOMS, delayed-onset muscle soreness; EIMD, exercise-induced muscle damage; IFCC, International Federation of Clinical Chemistry and Laboratory Medicine; IVIM, intravoxel incoherent motion; MGM, medial head of the gastrocnemius muscle; NC, noncompressed; NEX, number of excitations; ROI, region of interest; SPAIR, spectral attenuated inversion recovery; TA, tibialis anterior muscle; TE, echo time; TIRM, turbo inversion recovery magnitude; TR, repetition time.
Background Long COVID occurs in lower frequency in children and adolescents than in adults. Morphologic and free-breathing phase-resolved functional low-field MRI may identify persistent pulmonary manifestations after SARS-CoV-2 infection. Purpose To characterize both morphologic and functional changes of lung parenchyma on low-field MRI in children and adolescents with post COVID-19 compared with healthy controls. Materials and Methods Between August and December 2021, a cross-sectional, prospective clinical trial using low-field MRI was performed in children and adolescents from a single academic medical center. The primary outcome was the frequency of morphologic changes on MRI. Secondary outcomes included MRI-derived functional proton ventilation and perfusion parameters. Clinical symptoms, the duration from positive RT-PCR test and serological parameters were compared with imaging results. Nonparametric tests for pairwise and corrected tests for groupwise comparisons were applied to assess differences in healthy controls, recovered participants and with long COVID. Results A total of 54 participants post COVID-19 infection (mean age, 11 years ±3 [SD], 56 males) and 9 healthy controls (mean age, 10 years ±3 [SD], 70 males) were included: 29 (54%) in the COVID-19 group had recovered from infection and 25 (46%) were classified as having long COVID on the day of enrollment. Morphologic abnormality was identified in one recovered participant. Both ventilated and perfused lung parenchyma (V/Q match) was reduced from 81±6.1% in healthy controls to 62±19% ( P =.006) in the recovered group and 60±20% ( P =.003) in the long COVID group. V/Q match was lower in post COVID patients with infection less than 180 days (63±20%, P =.03), 180 to 360 days (63±18%, P =0.03) and 360 days ago (41±12%, P <.001) as compared with the never-infected healthy controls (81±6.1%). Conclusion Low-field MRI showed persistent pulmonary dysfunction in both children and adolescents recovered from COVID-19 and with long COVID. ClinicalTrials.gov : NCT04990531
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Objective Our aim was to assess the role of quantitative 1H and 23Na MRI methods in providing imaging biomarkers of disease activity and severity in patients with Facioscapulohumeral muscular dystrophy (FSHD). Methods We imaged the lower leg muscles of 19 FSHD patients and 12 controls with a multimodal MRI protocol to obtain STIR-T2w images, fat fraction (FF), water T2 (wT2), water T1 (wT1), tissue sodium concentration (TSC), and intracellular-weighted sodium signal (inversion recovery (IR) and triple quantum filter (TQF) sequence). In addition, the FSHD patients underwent muscle strength testing. Results Imaging biomarkers related with water mobility (wT1 and wT2) and ion homeostasis (TSC, IR, TQF) were increased in muscles of FSHD patients. Muscle groups with FF > 10% had higher wT2, wT1, TSC, IR, and TQF values than muscles with FF < 10%. Muscles with FF < 10% resembled muscles of healthy controls for these MRI disease activity measures. However, wT1 was increased in few muscles without fat replacement. Furthermore, few STIR-negative muscles (n = 11/76) exhibited increased wT1, TSC, IR or TQF. Increased wT1 as well as 23Na signals were also present in muscles with normal wT2. Muscle strength was related to the mean FF and all imaging biomarkers of tibialis anterior except wT2 were correlated with dorsal flexion. Conclusion The newly evaluated imaging biomarkers related with water mobility (wT1) and ion homeostasis (TSC, IR, TQF) showed different patterns compared to the established markers like FF in muscles of FSHD patients. These quantitative biomarkers could thus contain valuable complementary information for the early characterization of disease progression.
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