Accelerometric outcomes of motor function related to clinical evaluations and muscle involvement in dystrophic dogs

Abstract

Duchenne muscular dystrophy (DMD) is an X-linked muscle disorder characterized by primary muscle degeneration. Patients with DMD reveal progressive muscle weakness leading to ambulatory dysfunction. Novel outcome measures are needed for more sensitive evaluation of therapeutic effects in clinical trials. Multiple parameters of acceleration and angular velocity are used as efficient indicators to quantify the motion of subjects, and these parameters have been recently applied for evaluation of motor function in DMD. In the present study, we evaluated gait in a dystrophic dog model, CXMDJ, by measuring three-axial acceleration and angular velocity over the course of months. Hybrid sensors were placed on the dorsal thoracic and lumbar regions of dogs to detect a wide range of acceleration (±8 G) and angular velocity (±1000 degrees per second). Multiple parameters showed lower values in dystrophic dogs compared to wild-type (WT) dogs, and declined over the course of months. Acceleration magnitude (AM) at the thoracic region in dystrophic dogs was prominently lower compared with WT dogs, even at the age of 2 months, the onset of muscle weakness, whereas AM at the lumbar region drastically declined throughout the disease course. The angular velocity index in the vertical direction in the lumbar region increased in dystrophic dogs, suggesting waddling at the girdle. These parameters also accordingly decreased with exacerbation of clinical manifestations and a decrease in spontaneous locomotor activity. The AM of dystrophic dogs was analyzed with magnetic resonance imaging to look for a correlation with crus muscle involvement. Results showed that acceleration and angular velocity are multifaceted kinematic indices that can be applied to assess outcomes in clinical trials for hereditary neuromuscular disorders including DMD.

Enhanced Cell Survival and Therapeutic Benefits of IL-10-expressing Multipotent Mesenchymal Stromal Cells for Muscular Dystrophy

“…per kg body weight. In vivo images were acquired using the IVIS charge-coupled-device camera system (Xenogen Corp., Alameda, CA) at multiple time points (0, 3,7,18,27,31,34,42,49,54, and 67 days after transplantation). The region of interest (ROI) luminescence signals from individual MSCinjected sites were calculated using the Living Image hDPSCs or IL-10-transduced hDPSCs (4.0 × 10 cells/mL/kg body weight at a rate of 1 mL/min) were given via intravenous injection into CXMDJ that were pretreated with polaramine (chlorpheniramine maleate, 0.15 mg/kg, MSD) by nine injections at 2week intervals (Table I).…”

“…Siemens Medical Solutions, Erlanger, Germany) with an 18-cm diameter/18-cm length human extremity coil. The images were analyzed quantitatively using the Syngo MR2004A software (Siemens Medical Solutions), as previously reported [30,31]. Briefly, the ROIs were selected to avoid flow artifacts and large vessels and the signal intensities were measured for these ROIs.…”

“…The SNRs for each ROI were calculated using the following equation: SNR = signal intensity/SDair, where SDair is the standard deviation (SD) of the background noise. The average SNR (Ave SNR) was calculated using the equation described in our previous report [31]. The analysis was performed on the right and left side TA muscle, EDL, gastrocnemius medial head, GL, flexor digitorum superficialis, flexor digitorum longus, and flexor hallucis longus muscle.…”

Enhanced cell survival and therapeutic benefits of IL-10-expressing multipotent mesenchymal stromal cells for muscular dystrophy

“…We examined the crus muscles of the lower limbs using a superconducting 3.0-Tesla MRI device (MAGNETOM Trio; Siemens Medical Solutions, Erlanger, Germany) with an 18-cm diameter/18-cm length human extremity coil. The images were analyzed quantitatively using the Syngo MR2004A software (Siemens Medical Solutions), as previously reported [32,33]. Brie y, the ROIs were selected to avoid ow artifacts and large vessels and the signal intensities were measured for these ROIs.…”

“…The SNRs for each ROI were calculated using the following equation: SNR = signal intensity/SDair, where SDair is the standard deviation (SD) of the background noise. The average SNR (Ave SNR) was calculated using the equation described in our previous report [33]. The analysis was performed on the right and left side TA muscle, EDL, gastrocnemius medial head, GL, exor digitorum super cialis, exor digitorum longus, and exor hallucis longus muscle.…”