In vivo assessment of OXPHOS capacity using 3 T CrCEST MRI in Friedreich's ataxia.
In vivo assessment of OXPHOS capacity using 3 T CrCEST MRI in Friedreich's ataxia.
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DOI：
10.1007/s00415-021-10821-1
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发表时间：
2022-05
影响因子：
6
通讯作者：
中科院分区：
文献类型：
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弗里德赖希共济失调（FRDA）是由共济失调蛋白（frataxin）表达减少引起的神经退行性疾病，共济失调蛋白是参与许多细胞代谢过程（包括线粒体氧化磷酸化（OXPHOS））的蛋白质。我们的目的是使用化学交换饱和转移（CrCEST）MRI评估FRDA成人与无FRDA成人的体内骨骼肌氧化代谢，该MRI可测量磁内跖屈运动后随时间推移的游离肌酸（Cr）。参与者包括FRDA成人（n = 11）和健康成人（n = 25）。在扫描仪内跖屈运动前后，所有患者均接受了小腿3特斯拉CrCEST MRI。参与者还接受了全身双能X射线吸收测定法（DXA）扫描，以测量身体成分，并完成问卷调查，以评估身体活动。我们发现FRDA成人（与健康成人相比）外侧腓肠肌中CrCEST（τCr）的运动后指数下降时间延长（LG，274 s vs. 138 s，p = 0.01），可能反映了OXPHOS能力降低。患有FRDA的成年人（与健康成年人相比）在运动过程中也参与了不同的肌肉群，如运动时肌酸的肌肉群特异性变化所示（CCRCEST），可能反映了协调性下降。在所有参与者中，肥胖增加和日常体力活动减少与较小的CRCEST相关。在FRDA中，CrCEST MRI可能是肌肉组特异性OXPHOS能力下降的有用生物标志物，可用于跟踪参与者随时间的变化。适当的参与者选择和进一步优化的运动刺激将提高这项技术的实用性。在线版本包含补充材料，可通过10.1007/s 00415 -021-10821-1获得。
Friedreich’s ataxia (FRDA) is a neurodegenerative disease caused by decreased expression of frataxin, a protein involved in many cellular metabolic processes, including mitochondrial oxidative phosphorylation (OXPHOS). Our objective was to assess skeletal muscle oxidative metabolism in vivo in adults with FRDA as compared to adults without FRDA using chemical exchange saturation transfer (CrCEST) MRI, which measures free creatine (Cr) over time following an in-magnet plantar flexion exercise. Participants included adults with FRDA (n = 11) and healthy adults (n = 25). All underwent 3-Tesla CrCEST MRI of the calf before and after in-scanner plantar flexion exercise. Participants also underwent whole-body dual-energy X-ray absorptiometry (DXA) scans to measure body composition and completed questionnaires to assess physical activity. We found prolonged post-exercise exponential decline in CrCEST (τCr) in the lateral gastrocnemius (LG, 274 s vs. 138 s, p = 0.01) in adults with FRDA (vs. healthy adults), likely reflecting decreased OXPHOS capacity. Adults with FRDA (vs. healthy adults) also engaged different muscle groups during exercise, as indicated by muscle group-specific changes in creatine with exercise (∆CrCEST), possibly reflecting decreased coordination. Across all participants, increased adiposity and decreased usual physical activity were associated with smaller ∆CrCEST. In FRDA, CrCEST MRI may be a useful biomarker of muscle-group-specific decline in OXPHOS capacity that can be leveraged to track within-participant changes over time. Appropriate participant selection and further optimization of the exercise stimulus will enhance the utility of this technique. The online version contains supplementary material available at 10.1007/s00415-021-10821-1.
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影响因子：
4.4
作者：
Lanza, Ian R.;Bhagra, Sumit;Nair, K. Sreekumaran;Port, John D.
通讯作者：
Port, John D.
Frataxin缺乏症的功能基因组分析揭示了组织特异性的改变，并将PPARGAMMA途径鉴定为弗里德里希共济失调的治疗靶标。
影响因子：
3.5
作者：
Coppola G;Marmolino D;Lu D;Wang Q;Cnop M;Rai M;Acquaviva F;Cocozza S;Pandolfo M;Geschwind DH
通讯作者：
Geschwind DH
影响因子：
5.6
作者：
Martelli A;Puccio H
通讯作者：
Puccio H
影响因子：
2.5
作者：
Schöls, L;Vorgerd, I;Zange, J
通讯作者：
Zange, J
影响因子：
8
作者：
DeBrosse, Catherine;Nanga, Ravi Prakash Reddy;McCormack, Shana E.
通讯作者：
McCormack, Shana E.