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Observational Study
. 2022 Aug 30;99(9):e865-e876.
doi: 10.1212/WNL.0000000000200776. Epub 2022 Jun 3.

Longitudinal Changes in MRI Muscle Morphometry and Composition in People With Inclusion Body Myositis

Didier Laurent  1 , Jon Riek  2 , Christopher D J Sinclair  2 , Parul Houston  2 , Ronenn Roubenoff  2 , Dimitris A Papanicolaou  2 , Attila Nagy  2 , Steve Pieper  2 , Tarek A Yousry  2 , Michael G Hanna  2 , John S Thornton  2 , Pedro M Machado  2
Affiliations
Observational Study

Longitudinal Changes in MRI Muscle Morphometry and Composition in People With Inclusion Body Myositis

Didier Laurent et al. Neurology. .

Abstract

Background and objectives: Limited data suggest that quantitative MRI (qMRI) measures have potential to be used as trial outcome measures in sporadic inclusion body myositis (sIBM) and as a noninvasive assessment tool to study sIBM muscle pathologic processes. Our aim was to evaluate changes in muscle structure and composition using a comprehensive multiparameter set of qMRI measures and to assess construct validity and responsiveness of qMRI measures in people with sIBM.

Methods: This was a prospective observational cohort study with assessments at baseline (n = 30) and 1 year (n = 26). qMRI assessments include thigh muscle volume (TMV), inter/intramuscular adipose tissue (IMAT), muscle fat fraction (FF), muscle inflammation (T2 relaxation time), IMAT from T2* relaxation (T2*-IMAT), intermuscular connective tissue from T2* relaxation (T2*-IMCT), and muscle macromolecular structure from the magnetization transfer ratio (MTR). Physical performance assessments include sIBM Physical Functioning Assessment (sIFA), 6-minute walk distance, and quantitative muscle testing of the quadriceps. Correlations were assessed using the Spearman correlation coefficient. Responsiveness was assessed using the standardized response mean (SRM).

Results: After 1 year, we observed a reduction in TMV (6.8%, p < 0.001) and muscle T2 (6.7%, p = 0.035), an increase in IMAT (9.7%, p < 0.001), FF (11.2%, p = 0.030), connective tissue (22%, p = 0.995), and T2*-IMAT (24%, p < 0.001), and alteration in muscle macromolecular structure (ΔMTR = -26%, p = 0.002). A decrease in muscle T2 correlated with an increase in T2*-IMAT (r = -0.47, p = 0.008). Deposition of connective tissue and IMAT correlated with deterioration in sIFA (r = 0.38, p = 0.032; r = 0.34, p = 0.048; respectively), whereas a decrease in TMV correlated with a decrease in quantitative muscle testing (r = 0.36, p = 0.035). The most responsive qMRI measures were T2*-IMAT (SRM = 1.50), TMV (SRM = -1.23), IMAT (SRM = 1.20), MTR (SRM = -0.83), and T2 relaxation time (SRM = -0.65).

Discussion: Progressive deterioration in muscle quality measured by qMRI is associated with a decline in physical performance. Inflammation may play a role in triggering fat infiltration into muscle. qMRI provides valid and responsive measures that might prove valuable in sIBM experimental trials and assessment of muscle pathologic processes.

Classification of evidence: This study provides Class I evidence that qMRI outcome measures are associated with physical performance measures in patients with sIBM.

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Conflict of interest statement

D. Laurent, R. Roubenoff, and D.A. Papanicolaou are employees of Novartis and, as such, may be eligible for Novartis stock and stock options. J. Riek is an employee of BioTel Research, which is an imaging CRO that was contracted by Novartis Pharma AG to perform the image analysis in this study. P. Houston was also an employee of Novartis at the time of the study. A. Nagy and S. Pieper are employees of Isomics Inc., which is a technology development company that was contracted by Novartis Pharma AG to perform the semiautomatic image segmentation for individual muscle volume determination. A. Nagy is also an employee of the University of Szeged, Szeged, Hungary. M.G. Hanna receives research funding from the Medical Research Council UK and has previously acted as a consultant for Novartis and for Orphazyme. P.M. Machado has received grants and/or honoraria from AbbVie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche, and UCB Pharma. The other authors declare no relevant disclosures. Go to Neurology.org/N for full disclosures.

Figures

Figure 1
Figure 1. Comparison of Muscle and Fat Volumes Between Healthy Subjects and Patients With sIBM
IMAT = inter/intramuscular adipose tissue; SCAT = subcutaneous adipose tissue; sIBM = sporadic inclusion body myositis; TMV = thigh muscle volume. ***p < 0.0001, patients with sIBM vs healthy controls.
Figure 2
Figure 2. Thigh Muscle Structure and Composition in Patients With sIBM
Illustration of multiparametric MRI recordings at baseline in 2 different patients with sIBM. The first patient (A) is at an early stage of the disease (i.e., sIFA 16, 6MWD 462 m, and QMT 39.2 lbs), and the second patient (B) is at a more advanced stage of the disease (i.e., sIFA 75, 6MWD 90 m, and QMT 9.0 lbs). 6MWD = 6-minute walk distance; FF = fat fraction; IMAT = inter/intramuscular adipose tissue; IMCT = intramuscular connective tissue; MTR = magnetization transfer ratio; QMT = quantitative muscle testing; sIBM = sporadic inclusion body myositis; sIFA = sIBM Physical Functioning Assessment; TMV = thigh muscle volume.
Figure 3
Figure 3. sIBM Disease Progression Related to Muscle Structure
Changes observed in patients with sIBM after a 1-year follow-up in (A) thigh muscle volume (TMV) and associated inter/intramuscular adipose tissue (IMAT) and subcutaneous adipose (SCAT) volumes, as well as changes in (B) individual thigh muscle and associated IMAT volumes as measured by using the 3D-slicer segmentation approach. A segmentation example of anterior thigh muscles and the corresponding 3D reconstruction is shown in the center. BFB = biceps femoris short head; BFL = biceps femoris long head; GRA = gracilis; IMAT = inter/intramuscular adipose tissue; RF = rectus femoris; SAR = sartorius; SCAT = subcutaneous adipose tissue; SM = semimembranosus; ST = semitendinosus; TFL = tensor fascia latae; TMV = thigh muscle volume; VLI = vastus lateralis and intermedius; VM = vastus medialis. Values are mean ± SE, *adjusted p < 0.05, ***adjusted p < 0.0001, 1 year vs baseline (Bsl).
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