Three‐year quantitative magnetic resonance imaging and phosphorus magnetic resonance spectroscopy study in lower limb muscle in dysferlinopathy

Abstract

Background Natural history studies in neuromuscular disorders are vital to understand the disease evolution and to find sensitive outcome measures. We performed a longitudinal assessment of quantitative magnetic resonance imaging (MRI) and phosphorus magnetic resonance spectroscopy ( 31 P MRS) outcome measures and evaluated their relationship with function in lower limb skeletal muscle of dysferlinopathy patients. Methods Quantitative MRI/ 31 P MRS data were obtained at 3 T in two different sites in 54 patients and 12 controls, at baseline, and three annual follow-up visits. Fat fraction (FF), contractile cross-sectional area (cCSA), and muscle water T 2 in both global leg and thigh segments and individual muscles and 31 P MRS indices in the anterior leg compartment were assessed. Analysis included comparisons between patients and controls, assessments of annual changes using a linear mixed model, standardized response means (SRM), and correlations between MRI and 31 P MRS markers and functional markers. Results Posterior muscles in thigh and leg showed the highest FF values. FF at baseline was highly heterogeneous across patients. In ambulant patients, median annual increases in global thigh and leg segment FF values were 4.1% and 3.0%, respectively (P < 0.001). After 3 years, global thigh and leg FF increases were 9.6% and 8.4%, respectively (P < 0.001). SRM values for global thigh FF were over 0.8 for all years. Vastus lateralis muscle showed the highest SRM values across all time points. cCSA decreased significantly after 3 years with median values of 11.0% and 12.8% in global thigh and global leg, respectively (P < 0.001). Water T 2 values in ambulant patients were significantly increased, as compared with control values (P < 0.001). The highest water T 2 values were found in the anterior part of thigh and leg. Almost all 31 P MRS indices were significantly different in patients as compared with controls (P < 0.006), except for pH w , and remained, similar as to water T 2 , abnormal for the whole study duration. Global thigh water T 2 at baseline was significantly correlated to the change in FF after 3 years (ρ = 0.52, P < 0.001). There was also a significant relationship between the change in functional score and change in FF after 3 years in ambulant patients (ρ = À0.55, P = 0.010).

Water T2 could predict functional decline in patients with dysferlinopathy

“…It has been observed that in dysferlinopathy, the T2 H2O does not correlate with baseline functional scores. 25 T2 H2O has been shown to be impacted by high levels of FF (i.e. >60%) as also described in dysferlinopathy.…”

“…>60%) as also described in dysferlinopathy. 25 The data described in the current study, however, were acquired in exclusively ambulant patients, where FF values were predominantly lower than 60%. This suggests that T2 H2O could be compared across patients at different stages of muscle loss to offer a snapshot of the current level of disease activity.…”

“…The baseline, 1‐year data, and 3‐year functional progression and quantitative muscle MRI analysis have previously been published. 7 , 8 , 25 …”

“… 19 , 21 Regions of interest (ROIs) were drawn manually using a free software tool ( https://www.itksnap.org ) in the same five central slices on the shortest echo time (TE) image of the MSE series images by a single investigator as has been already described. 25 ROIs were drawn on both the left and right sides for seven leg muscles (extensor digitorum, tibialis anterior, tibialis posterior, peroneus longus, soleus, gastrocnemius medialis, and gastrocnemius lateralis) and in nine thigh muscles (vastus lateralis, vastus intermedius, vastus medialis, gracilis, sartorius, adductor magnus, biceps femoris long head, semimembranosus, and semitendinosus). For the determination of FF and cross‐sectional area (CSA), the boundaries of the ROIs were drawn following individual muscle delineation, avoiding inclusion of other muscles, subcutaneous and intermuscular fat, tendons, and major blood vessels.…”

“… 21 , 22 , 23 , 24 Recent data from the Clinical Outcomes Study (COS) baseline visit suggest that T2 H2O correlates with fatty replacement over time in dysferlinopathy patients, confirming the capacity of T2 H2O to identify active damage leading to muscle fibre loss and expansion of fat tissue. 25 However, the capacity of T2 H2O to identify patients who will experience a quicker and more severe clinical progression over a short period of time remains to be demonstrated. If it could be shown to predict progression, T2 H2O could be used both in clinics to identify patients at risk of progression and also in clinical trials to select patients who may deteriorate over a short period of time and whose results could be more informative about the effectivity of experimental therapies.…”