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Quantitative Muscle MRI Protocol as Possible Biomarker in Becker Muscular Dystrophy

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Abstract

Purpose

Aim of this study is to compare Quantitative Magnetic Resonance Imaging (qMRI) measures between Becker Muscular Dystrophy (BMD) and Healthy Subjects (HS) and to correlate these parameters with clinical scores.

Methods

Ten BMD patients (mean age ±standard deviation: 38.7 ± 15.0 years) and ten age-matched HS, were investigated through magnetic resonance imaging (MRI) at thigh and calf levels, including: 1) a standard axial T1-weighted sequence; 2) a volumetric T2-weighted sequence; 3) a multiecho spin-echo sequence; 4) a 2-point Dixon sequence; 5) a Diffusion Tensor Imaging (DTI) sequence.

Results

Mean Fat Fraction (FF), T2-relaxation time and Fractional Anisotropy (FA) DTI at thigh and calf levels were significantly higher in BMD patients than in HS (p-values < 0.01). FF at thigh and calf levels significantly correlated with North Star Ambulatory Assessment (NSAA) score (p-values < 0.01) and6 Minutes Walking Test (6MWT) (p-values < 0.01), whereas only calf muscle FF was significantly associated with time to get up from floor (p-value = 0.01). T2 significantly correlated with NSAA score (p-value < 0.01), 6MWT (p-value = 0.02) and time to get up from floor (p-value < 0.01) only at calf level. Among DTI values, only FA in thigh and calf muscles significantly correlated with NSAA score, 6MWT and 10-m walk (all p-values < 0.05); only FA in calf muscles significantly correlated with time to get up from floor (p = 0.01).

Conclusions

Muscle FF, T2-relaxometry and DTI, seem to be a promising biomarker to assess BMD disease severity, although further studies are needed to evaluate changes over the time.

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References

  1. Beggs AH, Hoffman EP, Snyder JR, Arahata K, Specht L, Shapiro F, Angelini C, Sugita H, Kunkel LM. Exploring the molecular basis for variability among patients with Becker muscular dystrophy: dystrophin gene and protein studies. Am J Hum Genet. 1991;49:54–67.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Bushby KM, Gardner-Medwin D. The clinical, genetic and dystrophin characteristics of Becker muscular dystrophy. J Neurol. 1993;240:98–104.

    Article  CAS  PubMed  Google Scholar 

  3. Comi GP, Prelle A, Bresolin N, Moggio M, Bardoni A, Gallanti A, Vita G, Toscano A, Ferro MT, Bordoni A, Fortunato F, Ciscato P, Felisari G, Tedeschi S, Castelli E, Garghentino R, Turconi A, Fraschini P, Marchi E, Negretto GG, Adobbati L, Meola G, Tonin P, Papadimitriou A, Scarlato G. Clinical variability in Becker muscular dystrophy genetic, biochemical and immunohistochemical correlates. Brain. 1994;117:1–14.

    Article  PubMed  Google Scholar 

  4. Bladen CL, Rafferty K, Straub V, Monges S, Moresco A, Dawkins H, Roy A, Chamova T, Guergueltcheva V, Korngut L, Campbell C, Dai Y, Barišić N, Kos T, Brabec P, Rahbek J, Lahdetie J, Tuffery-Giraud S, Claustres M, Leturcq F, Ben Yaou R, Walter MC, Schreiber O, Karcagi V, Herczegfalvi A, Viswanathan V, Bayat F, de la Caridad Guerrero Sarmiento I, Ambrosini A, Ceradini F, Kimura E, van den Bergen JC, Rodrigues M, Roxburgh R, Lusakowska A, Oliveira J, Santos R, Neagu E, Butoianu N, Artemieva S, Rasic VM, Posada M, Palau F, Lindvall B, Bloetzer C, Karaduman A, Topaloğlu H, Inal S, Oflazer P, Stringer A, Shatillo AV, Martin AS, Peay H, Flanigan KM, Salgado D, von Rekowski B, Lynn S, Heslop E, Gainotti S, Taruscio D, Kirschner J, Verschuuren J, Bushby K, Béroud C, Lochmüller H. The TREAT-NMD Duchenne muscular dystrophy registries: conception, design, and utilization by industry and academia. Hum Mutat. 2013;34:1449–57.

    Article  PubMed  Google Scholar 

  5. Fischmann A, Hafner P, Fasler S, Gloor M, Bieri O, Studler U, Fischer D. Quantitative MRI can detect subclinical disease progression in muscular dystrophy. J Neurol. 2012;259:1648–54.

    Article  CAS  PubMed  Google Scholar 

  6. Arpan I, Willcocks RJ, Forbes SC, Finkel RS, Lott DJ, Rooney WD, Triplett WT, Senesac CR, Daniels MJ, Byrne BJ, Finanger EL, Russman BS, Wang DJ, Tennekoon GI, Walter GA, Sweeney HL, Vandenborne K. Examination of effects of corticosteroids on skeletal muscles of boys with DMD using MRI and MRS. Neurology. 2014;83:974–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Bonati U, Hafner P, Schädelin S, Schmid M, Naduvilekoot Devasia A, Schroeder J, Zuesli S, Pohlman U, Neuhaus C, Klein A, Sinnreich M, Haas T, Gloor M, Bieri O, Fischmann A, Fischer D10.Quantitative muscle MRI: a powerful surrogate outcome measure in Duchenne muscular dystrophy. Neuromuscul Disord. 2015;25:679–85.

    Article  PubMed  Google Scholar 

  8. Morrow JM, Sinclair CD, Fischmann A, Machado PM, Reilly MM, Yousry TA, Thornton JS, Hanna MG. MRI biomarker assessment of neuromuscular disease progression: a prospective observational cohort study. Lancet Neurol. 2016;15:65–77.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Gaeta M, Scribano E, Mileto A, Mazziotti S, Rodolico C, Toscano A, Settineri N, Ascenti G, Blandino A. Muscle fat fraction in neuromuscular disorders: dual-echo dual-flip-angle spoiled gradient-recalled MR imaging technique for quantification—a feasibility study. Radiology. 2011;259:487–94.

    Article  PubMed  Google Scholar 

  10. Wren TAL, Bluml S, Tseng-Ong L, Gilsanz V. Three-point technique of fat quantification of muscle tissue as a marker of disease progression in Duchenne muscular dystrophy: preliminary study. AJR Am J Roentgenol. 2008;190:W8–12.

    Article  Google Scholar 

  11. Gaeta M, Messina S, Mileto A, Vita GL, Ascenti G, Vinci S, Bottari A, Vita G, Settineri N, Bruschetta D, Racchiusa S, Minutoli F. Muscle fat-fraction and mapping in Duchenne muscular dystrophy: evaluation of disease distribution and correlation with clinical assessments preliminary experience. Skeletal Radiol. 2012;41:955–61.

    Article  PubMed  Google Scholar 

  12. Forbes SC, Walter GA, Rooney WD, Wang DJ, DeVos S, Pollaro J, Triplett W, Lott DJ, Willcocks RJ, Senesac C, Daniels MJ, Byrne BJ, Russman B, Finkel RS, Meyer JS, Sweeney HL, Vandenborne K. Skeletal muscles of ambulant children with Duchenne muscular dystrophy: validation of multicenter study of evaluation with MR imaging and MR spectroscopy. Radiology. 2013;269:198–207.

    Article  Google Scholar 

  13. Triplett WT, Baligand C, Forbes SC, Willcocks RJ, Lott DJ, DeVos S, Pollaro J, Rooney WD, Sweeney HL, Bönnemann CG, Wang DJ, Vandenborne K, Walter GA. Chemical shift-based MRI to measure fat fractions in dystrophic skeletal muscle. Magn Reson Med. 2014;72:8–19.

    Article  CAS  PubMed  Google Scholar 

  14. Carlier PG. Global T2 versus water T2 in NMR imaging of fatty infiltrated muscles: different methodology, different information and different implications. Neuromuscul Disord. 2014;24:390–2.

    Article  PubMed  Google Scholar 

  15. Heemskerk AM, Strijkers GJ, Vilanova A, Drost MR, Nicolay K. Determination of mouse skeletal muscle architecture using three-dimensional diffusion tensor imaging. Magn Reson Med. 2005;53:1333–40.

    Article  PubMed  Google Scholar 

  16. Hooijmans MT, Damon BM, Froeling M, Versluis MJ, Burakiewicz J, Verschuuren JJ, Niks EH, Webb AG, Kan HE. Evaluation of skeletal muscle DTI in patients with duchenne muscular dystrophy. NMR Biomed. 2015;28:1589–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Oudeman J, Nederveen AJ, Strijkers GJ, Maas M, Luijten PR, Froeling M. Techniques and applications of skeletal muscle diffusion tensor imaging: a review. J Magn Reson Imaging. 2016;43:773–88.

    Article  PubMed  Google Scholar 

  18. Wokke BH, van den Bergen JC, Versluis MJ, Niks EH, Milles J, Webb AG, van Zwet EW, Aartsma-Rus A, Verschuuren JJ, Kan HE. Quantitative MRI and strength measurements in the assessment of muscle quality in Duchenne muscular dystrophy. Neuromuscul Disord. 2014;24:409–16.

    Article  CAS  PubMed  Google Scholar 

  19. Willcocks RJ, Rooney WD, Triplett WT, Forbes SC, Lott DJ, Senesac CR, Daniels MJ, Wang DJ, Harrington AT, Tennekoon GI, Russman BS, Finanger EL, Byrne BJ, Finkel RS, Walter GA, Sweeney HL, Vandenborne K. Multicenter prospective longitudinal study of magnetic resonance biomarkers in a large duchenne muscular dystrophy cohort. Ann Neurol. 2016;79:535–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Hogrel JY, Wary C, Moraux A, Azzabou N, Decostre V, Ollivier G, Canal A, Lilien C, Ledoux I, Annoussamy M, Reguiba N, Gidaro T, Le Moing AG, Cardas R, Voit T, Carlier PG, Servais L. Longitudinal functional and NMR assessment of upper limbs in Duchenne muscular dystrophy. Neurology. 2016;86:1022–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Fischer D, Hafner P, Rubino D, Schmid M, Neuhaus C, Jung H, Bieri O, Haas T, Gloor M, Fischmann A, Bonati U.The 6‑minute walk test, motor function measure and quantitative thigh muscle MRI in Becker muscular dystrophy: a cross-sectional study. Neuromuscul Disord. 2016;26:414–22.

    Article  PubMed  Google Scholar 

  22. Marty B, Coppa B, Carlier PG. Monitoring skeletal muscle chronic fatty degenerations with fast T1-mapping. Eur Radiol. 2018;28:4662–8.

    Article  PubMed  Google Scholar 

  23. Keller S, Wang ZJ, Aigner A, Kim AC, Golsari A, Kooijman H, Adam G, Yamamura J. Diffusion tensor imaging of dystrophic skeletal muscle. Clin Neuroradiol. 2019;29:231–42.

    Article  PubMed  Google Scholar 

  24. Løkken N, Hedermann G, Thomsen C, Vissing J. Contractile properties are disrupted in Becker muscular dystrophy, but not in limb girdle type 2I. Ann Neurol. 2016;80:466–71.

    Article  PubMed  Google Scholar 

  25. Ricotti V, Evans MR, Sinclair CD, Butler JW, Ridout DA, Hogrel JY, Emira A, Morrow JM, Reilly MM, Hanna MG, Janiczek RL, Matthews PM, Yousry TA, Muntoni F, Thornton JS. Upper limb evaluation in Duchenne muscular dystrophy: fat-water quantification by MRI, muscle force and function define endpoints for clinical trials. PLoS One. 2016;11:e162542.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Spitali P, Hettne K, Tsonaka R, Charrout M, van den Bergen J, Koeks Z, Kan HE, Hooijmans MT, Roos A, Straub V, Muntoni F, Al-Khalili-Szigyarto C, Koel-Simmelink MJA, Teunissen CE, Lochmüller H, Niks EH, Aartsma-Rus A. Tracking disease progression non-invasively in Duchenne and Becker muscular dystrophies. J Cachexia Sarcopenia Muscle. 2018;9:715–26.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Mazzone E, Martinelli D, Berardinelli A, Messina S, D’Amico A, Vasco G, Main M, Doglio L, Politano L, Cavallaro F, Frosini S, Bello L, Carlesi A, Bonetti AM, Zucchini E, De Sanctis R, Scutifero M, Bianco F, Rossi F, Motta MC, Sacco A, Donati MA, Mongini T, Pini A, Battini R, Pegoraro E, Pane M, Pasquini E, Bruno C, Vita G, de Waure C, Bertini E, Mercuri E. North star ambulatory assessment, 6‑minute walk test and timed items in ambulant boys with Duchenne muscular dystrophy. Neuromuscul Disord. 2010;20:712–6.

    Article  PubMed  Google Scholar 

  28. Enright PL. The six-minute walk test. Respir Care. 2003;48:783–5.

    Google Scholar 

  29. Schmidt S, Hafner P, Klein A, Rubino-Nacht D, Gocheva V, Schroeder J, Naduvilekoot Devasia A, Zuesli S, Bernert G, Laugel V, Bloetzer C, Steinlin M, Capone A, Gloor M, Tobler P, Haas T, Bieri O, Zumbrunn T, Fischer D, Bonati U. Timed function tests, motor function measure, and quantitative thigh muscle MRI in ambulant children with Duchenne muscular dystrophy. A cross-sectional analysis. Neuromuscul Disord. 2018;28:16–23.

    Article  PubMed  Google Scholar 

  30. Barp A, Bello L, Caumo L, Campadello P, Semplicini C, Lazzarotto A, Sorarù G, Calore C, Rampado A, Motta R, Stramare R, Pegoraro E. Muscle MRI and functional outcome measures in Becker muscular dystrophy. Sci Rep. 2017;7:16060.

    Article  CAS  Google Scholar 

  31. Bello L, Campadello P, Barp A, Fanin M, Semplicini C, Sorarù G, Caumo L, Calore C, Angelini C, Pegoraro E. Author information Functional changes in Becker muscular dystrophy: implications for clinical trials in dystrophinopathies. Sci Rep. 2016;6:32439.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Tasca G, Iannaccone E, Monforte M, Masciullo M, Bianco F, Laschena F, Ottaviani P, Pelliccioni M, Pane M, Mercuri E, Ricci E. Muscle MRI in Becker muscular dystrophy. Neuromuscul Disord. 2012;22:S100–6.

    Article  PubMed  Google Scholar 

  33. Arpan I, Forbes SC, Lott DJ, Senesac CR, Daniels MJ, Triplett WT, Deol JK, Sweeney HL, Walter GA, Vandenborne K. T2 mapping provides multiple approaches for the characterization of muscle involvement in neuromuscular diseases: a cross-sectional study of lower leg muscles in 5–15-year-old boys with Duchenne muscular dystrophy. NMR Biomed. 2013;26:320–8.

    Article  CAS  PubMed  Google Scholar 

  34. Arpan I, Willcocks RJ, Forbes SC, Finkel RS, Lott DJ, Rooney WD, Triplett WT, Senesac CR, Daniels MJ, Byrne BJ, Finanger EL, Russman BS, Wang DJ, Tennekoon GI, Walter GA, Sweeney HL, Vandenborne K. Examination of effects of corticosteroids on skeletal muscles of boys with DMD using MRI and MRS. Neurology. 2014;83:974–80.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Wokke BH, Van Den Bergen JC, Hooijmans MT, Verschuuren JJ, Niks EH, Kan HE. T2 relaxation times are increased in skeletal muscle of DMD but not BMD patients. Muscle Nerve. 2016;53:38–43.

    Article  CAS  PubMed  Google Scholar 

  36. Ponrartana S, Ramos-Platt L, Wren TA, Hu HH, Perkins TG, Chia JM, Gilsanz V. Effectiveness of diffusion tensor imaging in assessing disease severity in Duchenne muscular dystrophy: preliminary study. Pediatr Radiol. 2015;45:582–9.

    Article  PubMed  Google Scholar 

  37. Zaraiskaya T, Kumbhare D, Noseworthy MD. Diffusion tensor imaging in evaluation of human skeletal muscle injury. J Magn Reson Imaging. 2006;24:402–8.

    Article  PubMed  Google Scholar 

  38. Williams SE, Heemskerk AM, Welch EB, Li K, Damon BM, Park JH. Quantitative effects of inclusion of fat on muscle diffusion tensor MRI measurements. J Magn Reson Imaging. 2013;38:1292–7.

    Article  PubMed  Google Scholar 

  39. Qi J, Olsen NJ, Price RR, Winston JA, Park JH. Diffusion-weighted imaging of inflammatory myopathies: polymyositis and dermatomyositis. J Magn Reson Imaging. 2008;27:212–7.

    Article  PubMed  Google Scholar 

  40. Pierpaoli C, Basser PJ. Toward a quantitative assessment of diffusion anisotropy. Magn Reson Med. 1996;36:893–906.

    Article  CAS  Google Scholar 

  41. Li GD, Liang YY, Xu P, Ling J, Chen YM. Diffusion-tensor imaging of thigh muscles in Duchenne muscular dystrophy: correlation of apparent diffusion coefficient and fractional anisotropy values with fatty infiltration. AJR Am J Roentgenol. 2016;206:867–70.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Coombs BD, Szumowski J, Coshow W. Two-point Dixon technique for water-fat signal decomposition with B0 inhomogeneity correction. Magn Reson Med. 1997;38:884–9.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Neuroimmunology and Neuromuscular Diseases Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy

    Lorenzo Maggi, Rita Frangiamore, Maria Barbara Pasanisi & Renato Mantegazza

  2. Neuroradiology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy

    Marco Moscatelli, Federica Mazzi, Mattia Verri, Luisa Chiapparini, Maria Grazia Bruzzone & Domenico Aquino

  3. Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands

    Alberto De Luca

  4. Developmental Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy

    Giovanni Baranello

  5. Department of Research and Clinical Development, Scientific Directorate, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy

    Irene Tramacere

  6. Neurology IV—Neuroimmunology and Neuromuscular Diseases Unit, Fondazione IRCCS Istituto Neurologico “Carlo Besta”, Via Celoria 11, 20133, Milan, Italy

    Lorenzo Maggi

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  1. Lorenzo Maggi
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Correspondence to Lorenzo Maggi.

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Conflict of interest

L. Maggi, M. Moscatelli, R. Frangiamore, F. Mazzi, M. Verri, A. De Luca, M.B. Pasanisi, G. Baranello, I. Tramacere, L. Chiapparini, M.G. Bruzzone, R. Mantegazza and D. Aquino declare that they have no competing interests.

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All procedures performed in studies involving human participants or on human tissue were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

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Maggi, L., Moscatelli, M., Frangiamore, R. et al. Quantitative Muscle MRI Protocol as Possible Biomarker in Becker Muscular Dystrophy. Clin Neuroradiol 31, 257–266 (2021). https://doi.org/10.1007/s00062-019-00875-0

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