Noninvasive qMRI seen to detect muscle changes in LGMD type R1
Many quantitative MRI findings correlate with clinical assessments: Study
by |
A noninvasive quantitative MRI, or qMRI, was found to detect early muscle abnormalities among people with limb-girdle muscular dystrophy type R1 (LGMDR1), according to a small study from Europe.
Many of the qMRI findings correlated with clinical assessments of muscle function and patient-reported activities.
“Our findings revealed alterations in both clinical outcome indicators and qMRI measurements,” the scientists wrote, noting that the results “[emphasized] the value of employing a multimodal clinical assessment strategy.”
“Further research is needed to establish qMRI outcome measures for clinical trials,” the team added.
The study, “Quantitative muscle magnetic resonance imaging in limb-girdle muscular dystrophy type R1 (LGMDR1): A prospective longitudinal cohort study,” was published in the journal NMR in Biomedicine.
Scientists test the feasibility of qMRI over 1 year
LGMDR1, the predominant subtype of LGMD in Europe, is caused by mutations in the CAPN3 gene, which provides instructions to make the protein calpain-3. Like other forms of this disease type, LGMDR1 is characterized by progressive muscle weakness and wasting, particularly around the hips and shoulders.
qMRI is a noninvasive approach to assess muscular injuries, loss of muscle mass, and inflammation. The technique can potentially provide biomarkers to evaluate the natural course of LGMD and the impact of treatments.
Now, a team led by scientists at Ruhr-University Bochum in Germany decided to test the feasibility of qMRI in a group of LGMDR1 patients over one year.
The study enrolled 13 people, ages 26-57, with genetically confirmed LGMDR1, of whom seven were women. A group of 13 healthy age- and sex-matched individuals served as controls.
Muscle qMRI evaluated key measures, including fat fraction — muscle replaced by fat — and water T2 relaxation time (T2), a biomarker of active muscle damage reflecting processes such as inflammation.
Water diffusion parameters included fractional anisotropy, reflecting muscle fiber integrity, mean diffusivity, which can indicate muscle damage or degeneration, and axial and radial diffusivity, for the integrity and organization of muscle fibers.
Muscle function was assessed by the Medical Research Council (MRC) scale, the quick motor function measure (QMFM), the 6-minute walk test, the 10-meter walk test, and the timed up-and-go test. Patient questionnaires included activity limitation (ACTIVLIM) and the neuromuscular symptom score.
Test may give clinicians additional info on LGMDR1
Of all these clinical assessments, just two — QMFM and ACTIVLIM — showed significant worsening from the study’s start, or baseline, to the one-year follow-up. In terms of range of motion, plantarflexion, when the foot points away from the leg, and dorsiflexion, when the foot moves upward towards the shin, were also significantly worse after one year.
qMRI imaging analysis revealed significant differences in fat fraction and T2 values between LGMDR1 patients and healthy controls for all muscles, indicating muscle replaced by fat and active muscle damage. Therefore, according to the team, fat fraction “can be a valuable tool for monitoring LGMDR1, especially in mildly to moderately affected muscles.”
All water diffusion parameters were also significantly worse in all muscles when patients were compared with controls. Even the low-risk muscles of the lower leg showed significant differences between the patient and control groups in fractional anisotropy, mean diffusivity, and radial diffusivity.
Over one year, the fat fraction significantly worsened all patients’ muscles, particularly those of the thighs and calves. T2 measures also worsened in all muscles, particularly the hamstring, calves, and lower arm. No significant differences were observed over time for fractional anisotropy across all muscles.
The highest increase of fat replacement was found in muscles with a fat fraction between 10% and 50% at baseline.
qMRI measures can give additional information about underlying pathophysiology [disease processes], such as active muscle damage and [fiber] alterations, providing an enhanced sensitivity compared with conventional functional assessments alone.
Regarding relationships between clinical assessments and qMRI parameters, the researchers found that, at baseline, fat fraction, fractional anisotropy, and mean diffusivity in thigh muscles significantly correlated with QMFM scores. Meanwhile, fat fraction and mean diffusivity correlated with ACTIVLIM. In leg muscles, fat fraction and fractional anisotropy correlated with QMFM.
At one year, ACTIVLIM scores correlated with fat fraction and mean diffusivity in thigh muscles and fat fraction in leg muscles. QMFM correlated with fat fraction, fractional anisotropy, and mean diffusivity in thighs and fat fraction in legs.
Lastly, a change in water T2 relaxation time in thigh muscles significantly correlated with the change in ACTIVLIM scores.
“qMRI measures can give additional information about underlying pathophysiology [disease processes], such as active muscle damage and [fiber] alterations, providing an enhanced sensitivity compared with conventional functional assessments alone,” the scientists concluded.
About the Author
