Multi-parametric MRI characterization of inflammation in murine skeletal muscle

Abstract

Myopathies often display a common set of complex pathologies that include muscle weakness, inflammation, compromised membrane integrity, fat deposition, and fibrosis. Multi-parametric, quantitative, noninvasive imaging approaches may be able to resolve these individual pathological components. The goal of this study was to use multi-parametric MRI to investigate inflammation as an isolated pathological feature. Proton relaxation, diffusion tensor imaging (DTI), quantitative magnetization transfer (qMT-MRI), and dynamic contrast enhanced (DCE-MRI) parameters were calculated from data acquired in a single imaging session conducted 6 - 8 hours following the injection of λ-carrageenan, a local inflammatory agent. T2 increased in the inflamed muscle and transitioned to bi-exponential behavior. In diffusion measurements, all three eigenvalues and the apparent diffusion coefficient increased, but λ3 had the largest relative change. Analysis of the qMT data revealed that the T1 of the free pool and the observed T1 both increased in the inflamed tissue, while the ratio of exchanging spins in the solid pool to those in the free water pool (the pool size ratio) significantly decreased. DCE-MRI data also supported observations of an increase in extracellular volume. These findings enriched the understanding of the relation between multiple quantitative MRI parameters and an isolated inflammatory pathology, and may potentially be employed to other single or complex myopathy models.

Skeletal muscle quantitative nuclear magnetic resonance imaging and spectroscopy as an outcome measure for clinical trials (part II)

“…Активность болезни -достаточно расплывчатое понятие, предпо-лагающее, что изменение сигнала Т2 -результат неспе-цифических процессов, в основе которых лежат такие механизмы, как воспаление, некроз, дистрофия мышц, острая денервация, а также любые обстоятельства, при-водящие к внеклеточному или внутриклеточному отеку, или их комбинации. Этот факт неоднократно был про-демонстрирован у животных и у человека [17][18][19][20]. Физические упражнения умеренной или высокой ин-тенсивности приводят к увеличению сигнала Т2 от мышц в результате накопления воды в миоцитах.…”

Myeloid HIFs Are Dispensable for Resolution of Inflammation during Skeletal Muscle Regeneration

“…Although it has been suggested that T 2 variations represent a marker of muscle inflammation (33,34), it should be pointed out that a linear relationship of T 2 and intracellular volume has been previously reported (53). On that basis and considering the reduced second and third eigenvalues at day 7, the associated higher T 2 values might actually be related to the expansion of the extracellular component, including, for instance, a widened interstitial space (54,55), rather than to intracellular changes. Overall, the combination and/ or comparison of multimodal MRI with the recently introduced bioluminescence imaging technique (56) would be of interest for monitoring noninvasively and quantitatively the pathophysiological events, such as chronic inflammation, which are associated with skeletal muscle diseases.…”

Imagerie et spectroscopie par résonance magnétique nucléaire du muscle strié squelettique

“…Ce terme est intentionnellement vague étant donné qu'une variation de T2 est un processus non spécifique qui peut être engendré par différents mécanismes tels que l'inflammation, la nécrose, la dystrophie musculaire, la dénervation aiguë, ou toute autre situation pouvant être accompagnée par un oedème intracellulaire, extracellulaire, ou mixte. Cela a été montré de façon extensive sur des modèles animaux (Wishnia et al 2001 ;Heemskerk et al 2007 ;Bryant et al 2014 ;Ha et al 2015) ainsi que chez l'homme. L'exercice physique d'intensité modérée a beaucoup augmenté le T2 musculaire par un méca-nisme d'accumulation d'eau dans les myocytes impliqués.…”