MRI blood oxygenation level dependence (BOLD) post-contractile response and relationship to function in Duchenne muscular dystrophy


Pre-Clinical Research

Poster Number: 17


christopher lopez PhD, Tanja Taivassalo PhD, Maria Berru , Andres Saavedra , Hannah Rasmussen , Abhinandan Batra PhD, Harneet Arora PhD, Alex Roetzheim , Glenn Walter PhD, Krista Vandenborne PT, PhD, Sean Forbes


1. University of Florida/Physical Therapy, 2. University of Florida/Physiology and Functional Genomics, 3. University of Florida/Physical Therapy, 4. University of Florida/Physical Therapy, 5. University of Florida/Physical Therapy, 6. University of Florida/Physical Therapy, 7. University of Florida/Physical Therapy, 8. University of Florida/Physical Therapy, 9. University of Florida/Physiology and Functional Genomics, 10. University of Florida, 11. University of Florida/Physical Therapy

Background: Duchenne muscular dystrophy (DMD) is an X-linked recessive condition that affects the dystrophin gene, and lack of dystrophin is accompanied by a deficiency in neuronal nitric oxide synthase (nNOS) localized to the sarcolemma. This lack of nNOS has the potential to alter microvascular function, that may be evaluated using magnetic resonance imaging blood oxygenation level dependent (MRI-BOLD) response after several single short muscle contractions with each followed by a recovery.
Objective: The objective of this study was to determine whether the post-contractile MRI-BOLD response in DMD was impaired versus unaffected controls and correlated with established markers of disease progression including fat-fraction (FF) and functional assessments.
Approach: This cross-sectional study implemented MRI-BOLD during and following muscle contractions in DMD (n=15, ages 5-14 years) and age matched unaffected controls (n=11, ages 5-14 years). All scans were performed using a 3-Tesla whole body scanner. The MRI-BOLD response was measured following five – two second maximal voluntary dorsiflexion muscle contractions, each separated by one minute.
Results: All participants successfully completed the MRI-BOLD protocol and was well tolerated with no adverse events reported. The post-contractile BOLD response was detected in each DMD and control subject; however, the magnitude of the peak post-contractile BOLD response was reduced (p<0.001) in DMD (101.8% SD 1.0) compared to controls (104.1% SD 1.8). The MRI-BOLD response also correlated with FF and functional assessments.
Conclusion: The reduced peak BOLD response following dorsiflexion contractions in DMD indicates impaired microvascular function, possibly due to lack of nNOS. The MRI-BOLD response may be a valuable marker of evaluating interventions targeting microvascular function in muscular dystrophies.

Supported by NIH R01AR070101-01