Quantitative MR relaxometry study of muscle composition and function in duchenne muscular dystrophy

Huang, Yu‐Chen; Majumdar, Sharmila; Genant, Harry K.; Chan, Wing P.; Sharma, Khema R.; Yu, Pearl L.; Mynhier, Mark A.; Miller, Robert G.

doi:10.1002/jmri.1880040113

Cited by 94 publications

(102 citation statements)

References 15 publications

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“…[22][23][24][25][26][27][28] Previous MRI studies have demonstrated that dystrophic muscles have higher T2 relaxation times, 10,11,17 even in young boys with DMD. 15 Elevated T2 in dystrophic muscles has been linked to both the presence of muscle damage/inflammation and fatty tissue infiltration.…”

Section: Impact Of Initiation Of Corticosteroid Therapy In Boysmentioning

confidence: 99%

“…15 Elevated T2 in dystrophic muscles has been linked to both the presence of muscle damage/inflammation and fatty tissue infiltration. [11][12][13]25 Since the presumed mode of action of corticosteroids involves the suppression of inflammation, we examined their effects on skeletal muscle T2, using both T2 mapping and 1 H spectroscopic relaxometry. To our knowledge, there is only one previous study that used MRI techniques to study the effects of corticosteroids on skeletal muscles of boys with DMD.…”

Section: Impact Of Initiation Of Corticosteroid Therapy In Boysmentioning

confidence: 99%

“…8,9 MRI, in particular T2-weighted MRI, is sensitive to alterations in muscle chemistry and structure induced by processes like damage/inflammation and fat infiltration, [10][11][12][13][14][15][16][17] and therefore may have the potential to detect the effects of corticosteroid treatment on dystrophic muscles. Magnetic resonance spectroscopy (MRS) allows quantification of chemical compounds and can separate lipid and water components, allowing a more targeted investigation of skeletal muscles in DMD.…”

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Examination of effects of corticosteroids on skeletal muscles of boys with DMD using MRI and MRS

et al. 2014

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Objective: To evaluate the effects of corticosteroids on the lower extremity muscles in boys with Duchenne muscular dystrophy (DMD) using MRI and magnetic resonance spectroscopy (MRS).Methods: Transverse relaxation time (T2) and fat fraction were measured by MRI/MRS in lower extremity muscles of 15 boys with DMD (age 5.0-6.9 years) taking corticosteroids and 15 corticosteroid-naive boys. Subsequently, fat fraction was measured in a subset of these boys at 1 year. Finally, MRI/MRS data were collected from 16 corticosteroid-naive boys with DMD (age 5-8.9 years) at baseline, 3 months, and 6 months. Five boys were treated with corticosteroids after baseline and the remaining 11 served as corticosteroid-naive controls. Results:Cross-sectional comparisons demonstrated lower muscle T2 and less intramuscular (IM) fat deposition in boys with DMD on corticosteroids, suggesting reduced inflammation/damage and fat infiltration with treatment. Boys on corticosteroids demonstrated less increase in IM fat infiltration at 1 year. Finally, T2 by MRI/MRS detected effects of corticosteroids on leg muscles as early as 3 months after drug initiation.Conclusions: These results demonstrate the ability of MRI/MRS to detect therapeutic effects of corticosteroids in reducing inflammatory processes in skeletal muscles of boys with DMD. Our work highlights the potential of MRI/MRS as a biomarker in evaluating therapeutic interventions in DMD. Duchenne muscular dystrophy (DMD) is a devastating form of muscular dystrophy caused by the absence of dystrophin, making muscle cell membranes fragile and susceptible to mechanical damage.1,2 Currently, there is no cure for the disease. Corticosteroids have been reported to slow disease progression in DMD.3-7 However, the mechanism by which corticosteroids preserve muscle function in DMD is not fully understood.Among several proposed mechanisms, corticosteroids are thought to reduce inflammation in dystrophic muscles. 8,9 MRI, in particular T2-weighted MRI, is sensitive to alterations in muscle chemistry and structure induced by processes like damage/inflammation and fat infiltration, [10][11][12][13][14][15][16][17] and therefore may have the potential to detect the effects of corticosteroid treatment on dystrophic muscles. Magnetic resonance spectroscopy (MRS) allows quantification of chemical compounds and can separate lipid and water components, allowing a more targeted investigation of skeletal muscles in DMD. 18-21The overall goal of this study was to examine the ability of MRI/MRS to detect the effects of corticosteroids on skeletal muscles in boys with DMD. The specific aims of the study were to (1) perform a cross-sectional comparison between the lower extremity muscles of 5-to 6.9-year-old

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Section: Impact Of Initiation Of Corticosteroid Therapy In Boysmentioning

confidence: 99%

Section: Impact Of Initiation Of Corticosteroid Therapy In Boysmentioning

confidence: 99%

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confidence: 99%

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Examination of effects of corticosteroids on skeletal muscles of boys with DMD using MRI and MRS

et al. 2014

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“…In addition, we measured the magnetic resonance (MR) transverse relaxation (T 2 ) rates of multiple lower leg muscles because of their sensitivity to alterations in intramuscular fat 11 and the demonstrated enhancement in muscle T 2 in animal models of incomplete SCI. 12 …”

Section: Introductionmentioning

confidence: 99%

Non-invasive assessment of lower extremity muscle composition after incomplete spinal cord injury

et al. 2008

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Study Design: Cross-sectional study. Objective: (1) To quantify intramyocellular lipid (IMCL) content of the soleus muscle. (2) To assess the T 2 relaxation rates in the lower extremity skeletal muscles in persons with incomplete spinal cord injury (SCI). Setting: Academic Institution, Florida. Methods: Eight subjects (42 ± 10 years old; 70 ± 12 kg; 176 ± 10 cm) with chronic (17 ± 9 months post injury) motor SCI (C4-T12; ASIA C or D) and eight matched healthy controls were tested. Localized unsuppressed proton spectroscopy (H-MRS) was performed to estimate total lipid content and individual lipid components; IMCL and extramyocellular lipid (EMCL) from the soleus muscle. T 2 -weighted imaging of lower extremity muscles yielded muscle T 2 rates. Results: The IMCL content of the soleus muscle was 3.3 times higher in the patient group as compared to controls (P ¼ 0.002; 0.0401 (0.0234-0.0849) versus 0.0123 (0.0090-0.0175)). Similarly, EMCL measures were 4.5 times higher as compared to the controls (P ¼ 0.002). Significant differences were observed in the T 2 relaxation times of the soleus and gastrocnemius muscles (Po0.05). Conclusion:The increased levels of IMCL might interfere with the glucose uptake in skeletal muscle; potentially predisposing persons with incomplete SCI to the development of peripheral insulin resistance. Marked elevations in the T 2 relaxation times of the locomotor muscles are reflective of an altered muscle composition.

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“…MRI has been used to assess skeletal muscle injury (33,41,43) in studies of DMD patients (24,42) and mdx mice (46,48). Conventionally, skeletal muscle injury is revealed best by T 2 -weighted MRI, which optimizes contrast between edema and muscular tissue (16,50).…”

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Early metabolic changes measured by ¹H MRS in healthy and dystrophic muscle after injury

Pratt

Spangenburg

et al. 2012

Journal of Applied Physiology

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Xu S, Pratt SJ, Spangenburg EE, Lovering RM. Early metabolic changes measured by 1 H MRS in healthy and dystrophic muscle after injury. J Appl Physiol 113: 808 -816, 2012. First published June 28, 2012 doi:10.1152/japplphysiol.00530.2012.-Skeletal muscle injury is often assessed by clinical findings (history, pain, tenderness, strength loss), by imaging, or by invasive techniques. The purpose of this work was to determine if in vivo proton magnetic resonance spectroscopy ( 1 H MRS) could reveal metabolic changes in murine skeletal muscle after contraction-induced injury. We compared findings in the tibialis anterior muscle from both healthy wild-type (WT) muscles (C57BL/10 mice) and dystrophic (mdx mice) muscles (an animal model for human Duchenne muscular dystrophy) before and after contraction-induced injury. A mild in vivo eccentric injury protocol was used due to the high susceptibility of mdx muscles to injury. As expected, mdx mice sustained a greater loss of force (81%) after injury compared with WT (42%). In the uninjured muscles, choline (Cho) levels were 47% lower in the mdx muscles compared with WT muscles. In mdx mice, taurine levels decreased 17%, and Cho levels increased 25% in injured muscles compared with uninjured mdx muscles. Intramyocellular lipids and total muscle lipid levels increased significantly after injury but only in WT. The increase in lipid was confirmed using a permeable lipophilic fluorescence dye. In summary, loss of torque after injury was associated with alterations in muscle metabolite levels that may contribute to the overall injury response in mdx mice. These results show that it is possible to obtain meaningful in vivo 1 H MRS regarding skeletal muscle injury.in vivo magnetic resonance spectroscopy; eccentric injury; mdx; muscle damage INTENSE PHYSICAL EXERCISE can cause skeletal muscle damage and inflammation, resulting in pain and a loss of maximal force production. Skeletal muscle injury resulting from high-force lengthening contractions, such as intense physical exercise, is clinically termed a "muscle strain" and is one of the most common ailments seen by physicians. A diagnosis of acute muscle strains is still typically made based on physical exam and patient history. Several direct and indirect indicators of skeletal muscle damage have been observed, including disruption of contractile tissue, cellular accumulation of calcium, delayed onset muscle soreness, a prolonged reduction in muscular strength and range of motion, and an increase in the appearance of muscle proteins in the blood, such as creatine (Cr) kinase (CK), lactate dehydrogenase, and myoglobin (2, 6, 19). Duchenne muscular dystrophy (DMD) is characterized clinically by severe, progressive, and irreversible loss of muscular function. The disease is caused by the lack of dystrophin, a large membrane-associated protein expressed in skeletal muscle and localized to the inner face of the sarcolemma (63). There are significant parallels between the damage incurred after lengthening ("eccentric") contractions ...

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Quantitative MR relaxometry study of muscle composition and function in duchenne muscular dystrophy

Cited by 94 publications

References 15 publications

Examination of effects of corticosteroids on skeletal muscles of boys with DMD using MRI and MRS

Examination of effects of corticosteroids on skeletal muscles of boys with DMD using MRI and MRS

Non-invasive assessment of lower extremity muscle composition after incomplete spinal cord injury

Early metabolic changes measured by ¹H MRS in healthy and dystrophic muscle after injury

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Quantitative MR relaxometry study of muscle composition and function in duchenne muscular dystrophy

Cited by 94 publications

References 15 publications

Examination of effects of corticosteroids on skeletal muscles of boys with DMD using MRI and MRS

Examination of effects of corticosteroids on skeletal muscles of boys with DMD using MRI and MRS

Non-invasive assessment of lower extremity muscle composition after incomplete spinal cord injury

Early metabolic changes measured by 1H MRS in healthy and dystrophic muscle after injury

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Early metabolic changes measured by ¹H MRS in healthy and dystrophic muscle after injury