Magnetization Transfer Ratio in Lower Limbs of Late Onset Pompe Patients Correlates With Intramuscular Fat Fraction and Muscle Function Tests

Abstract

Objectives: Magnetization transfer (MT) imaging exploits the interaction between bulk water protons and protons contained in macromolecules to induce signal changes through a special radiofrequency pulse. MT detects muscle damage in patients with neuromuscular conditions, such as limb-girdle muscular dystrophies or Charcot-Marie-Tooth disease, which are characterized by progressive fiber loss and replacement by fatty tissue. In Pompe disease, in which there is, in addition, an accumulation of glycogen inside the muscle fibers, MT has not been tested yet. Our aim is to estimate MT ratio (MTR) in the skeletal muscle of these patients and correlate it with intramuscular fat fraction (FF) and results of muscle function tests.Methods: We obtained two-point axial Dixon and Dixon-MT sequences of the right thigh on a 1.5 Teslas MRI scanner in 60 individuals, including 29 late onset Pompe disease patients, 2 patients with McArdle disease, and 29 age and sex matched healthy controls. FF and MTR were estimated. Muscle function using several muscle function tests, including quantification of muscle strength, timed test quality of life scales, conventional spirometry obtaining forced vital capacity while sitting and in the supine position, were assessed in all patients.Results: MTR was significantly lower in Pompe patients compared with controls (45.5 ± 8.5 vs. 51.7 ± 2.3, Student T-test, p < 0.05). There was a negative correlation between the MTR and FF muscles studied (correlation coefficient: −0.65, Spearman test: p < 0.05). MTR correlated with most of the muscle function test results. We analyzed if there was any difference in MTR values between Pompe patients and healthy controls in those muscles that did not have an increase in fat, a measure that could be related to the presence of glycogen in skeletal muscles, but we did not identify significant differences except in the adductor magnus muscle (48.4 ± 3.6 in Pompe vs. 51 ± 1.3 in healthy controls, Student T-test = 0.023).Conclusions: MTR is a sensitive tool to identify muscle loss in patients with Pompe disease and shows a good correlation with muscle function tests. Therefore, the MT technique can be useful in monitoring muscle degeneration in Pompe disease in clinical trials or natural history studies.

Magnetic field therapy enhances muscle mitochondrial bioenergetics and attenuates systemic ceramide levels following ACL reconstruction: Southeast Asian randomized-controlled pilot trial

“…MTR measures drop following injury [ 56 ] and are negatively correlated with muscular fat fraction [ 57 ]. Our results hence suggest that muscle recovery at 16 weeks was greater in the PEMF group, wherein MTR measures generally increased.…”

Magnetization transfer ratio of the sciatic nerve differs between patients in type 1 and type 2 diabetes

“…Meanwhile, in patients with T2D, we could not reproduce this finding, which agrees with the finding of previous studies that factors apart from hyperglycemia are the main contributors to nerve damage in patients with T2D [ 4 , 5 , 7 ]. However, the fact that fatty nerve lesions have been shown to predominate in T2D patients [ 7 ] may explain that MTR of the sciatic nerve is decreased in patients with T2D compared to patients with T1D and HC, as fatty tissues exhibit a low magnetization transfer [ 18 , 32 , 33 ]. It will be interesting to investigate which mechanisms are responsible for a similar sciatic MTR of HC and patients with T1D, especially because a previous study [ 26 ] was able to demonstrate that sciatic MTR was sensitive to discriminate between asymptomatic carriers of the mutant transthyretin gene causing hereditary transthyretin amyloidosis and HC.…”

“…Since the exact molecular mechanisms behind the development of DSN in T1D and T2D remain unknown to date, the application of magnetization transfer ratio (MTR) imaging may offer new insights into the pathophysiology of DSN by assessing the nerves macromolecular composition in vivo . Due to the short T2 time of protons bound to macromolecules, these protons do not contribute to the signal of conventional MRI sequences [ 18 ].…”

Rotator cuff muscle fibrosis can be assessed using ultrashort echo time magnetization transfer MRI with fat suppression

“…[8][9][10][11][12] Magnetization transfer (MT) measures, which provide information on the macromolecular and free water pools, have also been used on muscles. [13][14][15][16][17][18][19] However, the specificity of the MT measurements is unclear because some have shown significant correlations with intramuscular fat 19 and others have shown significant correlations with protein concentrations. 15 Fat suppression (FS) techniques have been suggested by some authors to disambiguate measurements of the macromolecular pool in the presence of fatty infiltration.…”

“…Quantitative MRI, in particular T1 (spin–lattice) relaxation time, has been investigated as a potential tool for the evaluation of muscle, but the measurements are believed to primarily reflect fat content 8–12 . Magnetization transfer (MT) measures, which provide information on the macromolecular and free water pools, have also been used on muscles 13–19 . However, the specificity of the MT measurements is unclear because some have shown significant correlations with intramuscular fat 19 and others have shown significant correlations with protein concentrations 15 .…”