Impaired skeletal muscle microcirculation in systemic sclerosis

Abstract

Introduction: Muscle symptoms in systemic sclerosis (SSc) may originate from altered skeletal muscle microcirculation, which can be investigated by means of blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI).

Methods: After ethics committee approval and written consent, 11 consecutive SSc patients (5 men, mean age 52.6 years, mean SSc disease duration 5.4 years) and 12 healthy volunteers (4 men, mean age 45.1 years) were included. Subjects with peripheral arterial occlusive disease were excluded. BOLD MRI was performed on calf muscles during cuff-induced ischemia and reactive hyperemia, using a 3-T whole-body scanner (Verio, Siemens, Erlangen, Germany) and fat-suppressed single-short multi-echo echo planar imaging (EPI) with four different effective echo times. Muscle BOLD signal time courses were obtained for gastrocnemius and soleus muscles: minimal hemoglobin oxygen saturation (T2*min) and maximal T2* values (T2*max), time to T2* peak (TTP), and slopes of oxygen normalization after T2* peaking.

Results: The vast majority of SSc patients lacked skeletal muscle atrophy, weakness or serum creatine kinase elevation. Nevertheless, more intense oxygen desaturation during ischemia was observed in calf muscles of SSc patients (mean T2*min -15.0%), compared with controls (-9.1%, P = 0.02). SSc patients also had impaired oxygenation during hyperemia (median T2*max 9.2% vs. 20.1%, respectively, P = 0.007). The slope of muscle oxygen normalization was significantly less steep and prolonged (TTP) in SSc patients (P<0.001 for both). Similar differences were found at a separate analysis of gastrocnemius and soleus muscles, with most pronounced impairment in the gastrocnemius.

Conclusions: BOLD MRI demonstrates a significant impairment of skeletal muscle microcirculation in SSc.

Figure 1

Imaging setup of the ischemia/reactive hyperemia paradigm conducted with a conventional leg sphygmomanometer wrapped around the middle of the thigh and flexible array coils. To prevent compression of the calf muscles the lower leg is supported at knee and foot level.

Figure 2

T1 images and T2* maps of the upper left calf region from a healthy volunteer and a patient with systemic sclerosis (SSc). T1 images are shown on the left and T2* maps on the right. (A) Healthy volunteer. (B) SSc patient. T1 images were correlated for anatomical reference with the respective T2* maps.

Figure 3

Key parameters of a typical blood oxygenation level-dependent (BOLD) T2* signal time course in a healthy volunteer. T2* is a magnetic resonance imaging signal.

Figure 4

Muscle blood oxygenation level-dependent (BOLD) time courses in patients with scleroderma and healthy controls. Time courses for patients with scleroderma are shown in red and for healthy controls in blue in (A) the soleus and (B) the gastrocnemius muscle. (C) Mean time courses over both muscle groups. T2* is a magnetic resonance imaging signal.