Quantitative muscle MRI captures early muscle degeneration in calpainopathy

Abstract

To evaluate differences in qMRI parameters of muscle diffusion tensor imaging (mDTI), fat-fraction (FF) and water T2 time in leg muscles of calpainopathy patients (LGMD R1/D4) compared to healthy controls, to correlate those findings to clinical parameters and to evaluate if qMRI parameters show muscle degeneration in not-yet fatty infiltrated muscles. We evaluated eight thigh and seven calf muscles of 19 calpainopathy patients and 19 healthy matched controls. MRI scans were performed on a 3T MRI including a mDTI, T2 mapping and mDixonquant sequence. Clinical assessment was done with manual muscle testing, patient questionnaires (ACTIVLIM, NSS) as well as gait analysis. Average FF was significantly different in all muscles compared to controls (p < 0.001). In muscles with less than 8% FF a significant increase of FA (p < 0.005) and decrease of RD (p < 0.004) was found in high-risk muscles of calpainopathy patients. Water T2 times were increased within the low- and intermediate-risk muscles (p ≤ 0.045) but not in high-risk muscles (p = 0.062). Clinical assessments correlated significantly with qMRI values: QMFM vs. FF: r = − 0.881, p < 0.001; QMFM versus FA: r = − 0.747, p < 0.001; QMFM versus MD: r = 0.942, p < 0.001. A good correlation of FF and diffusion metrics to clinical assessments was found. Diffusion metrics and T2 values are promising candidates to serve as sensitive early and non-invasive methods to capture early muscle degeneration in non-fat-infiltrated muscles in calpainopathies.

Accelerated IVIM-corrected DTI in acute hamstring injury: towards a clinically feasible acquisition time

“…The high- b DTI approach can also be beneficial for other applications. For example, DTI has been used to monitor training effects in the hamstrings [ 30 , 31 ] and to detect disease progression in neuromuscular diseases [ 32 , 33 ], and using IVIM correction would be beneficial to avoid an IVIM bias in the DTI parameters. Moreover, our accelerated protocol could facilitate the use of DTI to study muscle microstructure and quality, which is an important topic for research, for example in cerebral palsy [ 34 ], neuromuscular disorders [ 35 ], and aging [ 36 ].…”

Evaluation of Neuromuscular Diseases and Complaints by Quantitative Muscle MRI

“…Differences in qMRI metrics between study groups were assessed in a multivariate general linear model with patient/control, body side, and muscle as fixed factors using BMI and gender as covariates. The same multivariate general linear model was used to analyse diffusion metrics, excluding muscles with an FF higher than 60% and an SNR lower than ten after denoising, suggesting low diffusion data quality [15,25]. Subsequently, post hoc tests were performed using Bonferroni correction.…”

“…This phenomenon could explain the notably reduced T2 relaxation times in LGMDR1, primarily driven by exceedingly low water T2 values in thigh muscles with high-fat replacement. To avoid the influence of fat replacement, water T2 values have been assessed as early detection in low-fat-replaced muscles [15,51]. However, the underlying pathophysiological mechanism leading to reduced water T2 values in PCC remains elusive and has not been observed in more significant cohorts of PCC patients [52].…”

“…Other promising candidates in the assessment of NMD are diffusion metrics, reflecting the movement of water molecules within muscle tissue [22]. These metrics can detect structural abnormalities in non-fat-replaced muscles and have shown sensitivity in fatreplaced muscles using adequate fat suppression methods [15,47,55]. However, highly effective fat suppression can lead to images dominated by noise.…”

“…Quantitative muscle MRI (qMRI) has emerged as a non-invasive and objective tool for assessing and monitoring NMD [13,14]. Through their ability to accurately derive individual muscle fat fractions (FF), Dixon-based sequences help identify typical patterns of muscular involvement [15][16][17]. They also can detect subtle disease progressions, even before clinical symptoms and assessments deteriorate [18,19].…”