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Quantification of Skeletal Muscle Morphology and Mechanical Properties Using Medical Imaging
KTH, School of Engineering Sciences (SCI), Engineering Mechanics, Aerospace, moveability and naval architecture.ORCID iD: 0000-0003-2388-0365
2025 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Skeletal muscle is crucial for enabling movement, maintaining posture, and stabilising joints. These functions are largely related to the morphology and mechanical properties of skeletal muscle. To quantify these properties in vivo, medical imaging techniques have been widely used, with ultrasonography and magnetic resonance imaging (MRI) being the most commonly used imaging modalities. This thesis presents four studies using different imaging techniques to quantify the morphology and mechanical properties of skeletal muscle. 

In the first study, we used three-dimensional freehand ultrasound (3DFUS) and MRI to quantify 3D skeletal muscle morphological parameters, including muscle volume, fascicle length, and pennation angle. We demonstrated that 3DFUS provided reliable and repeatable measurements, with strong agreement with MRI-based measurements. Given its lower cost and better accessibility, we suggest that 3DFUS could serve as a viable alternative to MRI for quantifying skeletal muscle morphology. 

In the second and third studies, we used two elastography techniques, magnetic resonance elastography (MRE) and ultrasound shear wave elastography (SWE), to quantify the mechanical properties of skeletal muscle. We incorporated diffusion tensor imaging to determine the fascicle orientation and integrated this information into the direct inversion of the wave equation in MRE. This approach allowed for the quantification of anisotropic mechanical properties under the assumption that skeletal muscle behaves as an incompressible transversely isotropic material. This approach was first validated through comparison with ex vivo rheometry measurements, demonstrating a good agreement between the two techniques, and then applied in vivo to the medial gastrocnemius (MG), demonstrating muscle anisotropy as well. We also compared this technique with a commercial ultrasound SWE system, which assumes skeletal muscle to be isotropic, by measuring both ex vivo muscle samples and the MG in vivo. By quantifying shear wave velocity using both elastography techniques, we observed a moderate to strong correlation between SWE and MRE in ex vivo muscle samples and a strong correlation in the MG in vivo. These findings suggested that the isotropy assumption in commercial ultrasound SWE systems does not substantially affect the quantification of muscle mechanical properties. 

In the fourth study, we used MRI to evaluate changes in calf muscle morphology and intramuscular fat content 12 months after the first botulinum neurotoxin type A (BoNT-A) injection in children with cerebral palsy (CP), who were naive to muscle tone reduction therapy. Our findings showed that the calf muscle growth was not impaired 12 months after BoNT-A injection, as indicated by increased absolute muscle volume and unchanged normalized muscle volume. However, the calf muscle growth was compromised by concurrent intramuscular fat infiltration, evidenced by increased intramuscular fat content. 

The ultrasonography and MRI techniques presented in this thesis provide the biomechanics field with different options for quantifying skeletal muscle morphology and mechanical properties. These techniques not only contribute to the medical imaging methodological development but also offer practical implications for clinical assessments and rehabilitation strategies.

Abstract [sv]

Skelettmuskulaturens funktion är viktigför förmågan att producera kraft som i kombination med neurologiska komponenter gör det möjligt för människan att röra sig, bibehålla hållningen och stabilisera lederna. Förmågan att producera kraft (ofta mätt som styrka) kan relateras till muskulaturensstruktur och mekaniska egenskaper. För att kvanitfiera dessa egenskaper in vivo används ofta medicinska avbildningstekniker varav ultraljud och magnetisk resonanstomografi (MRI) är de två mest använda metoderna. I denna avhandling som omfattar fyra studier presenteras olika avbildningstekniker för kvantifiering av skelettmuskulatur. 

I den första studien använde vi två tekniker, tredimensionell frihands-ultraljudsteknink (3DFUS) och MRI för 3D-kvantifiering av muskulaturens morfologiska egenskaper som inkluderade muskelvolym, fascikellängd och pennationsvinkel. Vi kunde visa att 3DFUS gav valida och reliabla resultat som överensstämde väl med resultaten från MRI undersökningarna. Resultaten visar att 3DFUS kan användas som ett kostnadseffektivt alternativ till MRI för att mäta muskelmorfologi. 

I den andra och tredje studien använde vi två tekniker, magnetisk resonans-elastografi (MRE) och ultraljuds-elastografi (SWE), för att kvantifiera muskulaturens mekaniska egenskaper. Med diffusionstensoravbildning, identifierade vi fascikelns orientering och integrerade denna information i den direkta inversionen av vågekvationen i MRE. Detta tillvägagångssätt möjliggjorde kvantifiering av skelettmuskulaturens anisotropa mekaniska egenskaper antaget att skelettmuskulaturen beter sig som inkompressibelt tvärgående isotropiskt material. Metoden som först valideras med reometrimätningar ex vivo och visade god överensstämmelse mellan MRE och reometrimätningar. Därefter tillämpades mätningen i vivo på mediala gastrocnemius (MG) som också visade god anisotropi. Vi jämförde sedan denna teknik med ett kommersiellt ultraljuds SWE-system, där skelettmuskulaturen antogs vara isotrop. Genom att kvantifiera skjuvvågshastighet från dessa två tekniker visade vi en måttlig till stark korrelation mellan SWE och MRE i ex vivo muskelprover och en stark korrelation mellan dessa två tekniker i MG in vivo. Resultat tyder på att mätningar med det kommersiella ultraljuds SWE-systemet inte signifikant påverkade kvantifieringen av muskelmekaniska egenskaper även med det isotropiska antagandet. 

I den fjärde studien använde vi MRI för att utvärdera eventuella förändringar i vadmuskulaturen avseende morfologiska egenskaper och fettsammansättning 12 månader efter spasticitetsreducerande behandling med botulinumtoxin typ A (BoNT-A) injektioner hos barn med cerebral pares (CP), som inte fått muskeltonsreducerande behandling tidigare. Vi visade att vadmuskeltillväxten inte var försämrad 12 månader efter BoNT-A-injektion, vilket indikeras av ökad absolut muskelvolym och oförändrad normaliserad muskelvolym. Muskeltillväxten omfattades av samtidig fettinfiltration i form av ökning av intramuskulära fett. 

Ultraljuds- och MRI-teknikerna som presenteras i denna avhandling bidrar till ökad kunskap om metoder för kvantifiering av skelettmuskulaturens morfologi och dess mekaniska egenskaper att använda inom biomekaniken. Metoderna bidrar till ny kunskap och utveckling av medicinska avbildningstekniker som kan implementeras i kliniken och användas vid bedömning av muskelfunktion och för utvärdering av rehabiliteringsåtgärder. 

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2025. , p. xii, 64
Series
TRITA-SCI-FOU ; 2025:17
Keywords [en]
Magnetic resonance imaging, diffusion tensor imaging, magnetic resonance elastography, Dixon method, ultrasonography, three-dimensional freehand ultrasound, shear wave elastography, cerebral palsy
Keywords [sv]
Magnetisk resonanstomografi, diffusionstensoravbildning, magnetisk resonanselastografi, Dixonmetoden, ultraljud, tredimensionell frihandsultraljud, skjuvvågselastografi, cerebral pares
National Category
Medical Imaging Radiology and Medical Imaging
Research subject
Engineering Mechanics
Identifiers
URN: urn:nbn:se:kth:diva-361815ISBN: 978-91-8106-246-5 (print)OAI: oai:DiVA.org:kth-361815DiVA, id: diva2:1948336
Public defence
2025-04-25, Kollegiesalen, Brinellvägen 6, Stockholm, 09:00 (English)
Opponent
Supervisors
Note

QC 20250331

Available from: 2025-03-31 Created: 2025-03-28 Last updated: 2025-04-01Bibliographically approved
List of papers
1. In vivo 3D muscle architecture quantification based on 3D freehand ultrasound and magnetic resonance imaging
Open this publication in new window or tab >>In vivo 3D muscle architecture quantification based on 3D freehand ultrasound and magnetic resonance imaging
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2023 (English)In: Journal of Biomechanics, ISSN 0021-9290, E-ISSN 1873-2380, Vol. 152, article id 111567Article in journal (Refereed) Published
Abstract [en]

Muscle architecture parameters, such as the fascicle length, pennation angle, and volume, are important muscle morphology characteristics. Accurate in vivo quantification of these parameters allows to detect changes due to pathologies, interventions, and rehabilitation trainings, which ultimately impact on muscles' force-producing capacity. In this study, we compared three-dimensional (3D) muscle architecture parameters of the tibialis anterior and gastrocnemius medialis, which were quantified by 3D freehand ultrasound (3DfUS) and a magnetic resonance imaging (MRI) technique, diffusion tensor imaging (DTI), respectively. Sixteen able-bodied subjects were recruited where seven of them received both 3DfUS and MRI measurement, while the rest underwent 3DfUS measurements twice. Good to excellent intra-rater reliability and inter-session repeatability were found in 3DfUS measurements (intra-class correlation coefficient > 0.81). Overall, the two imaging modalities yielded consistent measurements of the fascicle length, pennation angle, and volume with mean differences smaller than 2.9 mm, 1.8 degrees, and 5.7 cm3, respectively. The only significant difference was found in the pennation angle of the tibialis anterior, although the discrepancy was small. Our study demonstrated, for the first time, that 3DfUS measurement had high reliability and repeatability for measurement of muscle architecture in vivo and could be regarded as an alternative to MRI for 3D evaluation of muscle morphology.

Place, publisher, year, edition, pages
Elsevier BV, 2023
Keywords
Tibialis anterior, Gastrocnemius medialis, Fascicle length, Pennation angle, Muscle volume
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:kth:diva-326883 (URN)10.1016/j.jbiomech.2023.111567 (DOI)000976289300001 ()37023558 (PubMedID)2-s2.0-85151538732 (Scopus ID)
Note

QC 20230515

Available from: 2023-05-15 Created: 2023-05-15 Last updated: 2025-03-28Bibliographically approved
2. Anisotropic mechanical properties quantification in skeletal muscle using magnetic resonance elastography and diffusion tensor imaging
Open this publication in new window or tab >>Anisotropic mechanical properties quantification in skeletal muscle using magnetic resonance elastography and diffusion tensor imaging
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Skeletal muscle contains a highly hierarchical structure, leading to anisotropic mechanical properties, with varying morphological responses to mechanical loadings from different directions. However, this feature is rarely studied in clinical studies, mainly due to the challenges in quantifying muscle anisotropic mechanical properties in vivo. The aim of the current study was to quantify the anisotropic mechanical properties of skeletal muscle using an integrated approach combining multi-frequency magnetic resonance elastography (MRE) and diffusion tensor imaging (DTI). Muscle fascicle orientation was determined through DTI tractography. Direct inversion of the curl-based wave equation was used to quantify three complex-valued moduli ( , , and ) assuming muscle as an incompressible transversely isotropic material. This approach was evaluated on one ex vivo muscle sample by comparing MRE-derived moduli to rheometry measurements, and further assessed in vivo in the ankle plantarflexors of nine able-bodied subjects. Consistency in the anisotropic ratio was observed between rheometry and MRE measurements in the ex vivo muscle sample, though discrepancies were noted in absolute shear moduli values. In vivo, the anisotropy of skeletal muscle was observed by the relationship of and at different MRE driving frequencies with higher parallel shear modulus () than the perpendicular shear modulus (). This study demonstrated a promising approach for quantifying the muscle anisotropic mechanical properties in vivo, which can be useful in various clinical applications. 

Keywords
Rheometry, direct inversion, incompressible transverse isotropy
National Category
Radiology and Medical Imaging Medical Imaging
Identifiers
urn:nbn:se:kth:diva-361810 (URN)
Note

QC 20250331

Available from: 2025-03-28 Created: 2025-03-28 Last updated: 2025-03-31Bibliographically approved
3. Skeletal muscle mechanical properties quantification: comparison between commercial ultrasound shear wave elastography and anisotropic magnetic resonance elastography
Open this publication in new window or tab >>Skeletal muscle mechanical properties quantification: comparison between commercial ultrasound shear wave elastography and anisotropic magnetic resonance elastography
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: Although elastography techniques, such as ultrasound shear wave elastography (SWE) and magnetic resonance elastography (MRE), are increasingly used to quantify mechanical properties of skeletal muscles, significant variation exists across the methods. These differences include measurement frequency ranges, post-processing approaches, and reported outcome parameters. This study aimed to compare the quantification of muscle mechanical properties between SWE and MRE.

Methods: SWE and MRE were performed on seven ex vivo muscle samples and medial gastrocnemius (MG) of nine able-bodied adults. Muscle anisotropic mechanical properties were quantified by estimating shear wave velocities (SWVs) parallel and perpendicular to the muscle fibers for ex vivo comparison. For in vivo comparison, only parallel SWV was assessed. Agreement between SWV estimation obtained from SWE and MRE was evaluated using Pearson correlation coefficient and the limit of agreement approach.

Results: SWV quantification using SWE and MRE demonstrated moderate to strong correlation in both ex vivo (perpendicular SWV: r = 0.777, p = 0.002, parallel SWV: r = 0.673, p = 0.012) and in vivo comparisons (parallel SWV: r = 0.707, p = 0.033). However, SWE consistently overestimated SWV compared to MRE across all conditions (average difference: perpendicular SWV ex vivo 0.42 m/s, parallel SWV ex vivo 0.67 m/s, parallel SWV in vivo: 0.53 m/s).

Conclusion: Muscle anisotropic mechanical property quantification using ultrasound SWE and MRE demonstrated good agreement in ex vivo muscle samples. In vivo, parallel SWV estimation from ultrasound SWE in pennate muscle showed good agreement with anisotropic MRE in able-bodied adult participants. 

Keywords
Skeletal muscle, shear wave elastography, magnetic resonance elastography, animal
National Category
Radiology and Medical Imaging Medical Imaging
Identifiers
urn:nbn:se:kth:diva-361813 (URN)
Note

QC 20250331

Available from: 2025-03-28 Created: 2025-03-28 Last updated: 2025-03-31Bibliographically approved
4. Muscle morphology and intramuscular fat after the first botulinum neurotoxin A injection in children with cerebral palsy: a 12-month longitudinal study
Open this publication in new window or tab >>Muscle morphology and intramuscular fat after the first botulinum neurotoxin A injection in children with cerebral palsy: a 12-month longitudinal study
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Aim: To explore changes in lower leg muscle morphology and intramuscular fat using magnetic resonance imaging (MRI) after 12 months of treatment as usual (TAU), starting with the first botulinum neurotoxin A (BoNT-A) injection in children with cerebral palsy (CP) naïve to muscle tone reduction treatment.

Method: A longitudinal study was performed including 10 children with spastic CP (5 girls, median age 8 years 11 months, unilateral/bilateral 6/4, Gross Motor Function Classification System (GMFCS) level I/II 8/2) and 10 typically developing (TD) peers (7 girls, median age 9 years 6 months). MRI scans were performed before and 12 months after the first BoNT-A injection. Muscle volume, fascicle length, and pennation angle of medial gastrocnemius (MG), lateral gastrocnemius (LG), soleus (SOL), and tibialis anterior (TA) were measured. Intramuscular fat fraction (IFF) was quantified using the Dixon method.

Results: Unchanged normalized muscle volume and elevated IFF (MG: p=0.002, SOL: p=0.026, TA: p=0.027) were observed in children with CP after the 12-month TAU. Compared to TD peers, children with CP showed smaller normalized muscle volume (MG: p=0.035, TA: p=0.007) and higher IFF (SOL: p=0.029).

Interpretation: Muscle growth was not hampered after the 12-month TAU starting with the first BoNT-A injection in children with CP but was compromised by concurrent fat infiltration in both injected and non-injected muscles. 

Keywords
Cerebral palsy, calf, magnetic resonance imaging, intramuscular fat infiltration
National Category
Pediatrics Neurology Rehabilitation Medicine Radiology and Medical Imaging
Identifiers
urn:nbn:se:kth:diva-361814 (URN)
Note

QC 20250331

Available from: 2025-03-28 Created: 2025-03-28 Last updated: 2025-03-31Bibliographically approved

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