Translational Molecular Imaging, Max-Planck Institute for Multidisciplinary Sciences, City Campus, 37075 Göttingen, Germany.
X-ray Based Preclinical Imaging Technologies, Institute for Diagnostic and Interventional Radiology, University Medical Center, 37075 Göttingen, Germany.
Cells. 2022 Mar 7;11(5):918. doi: 10.3390/cells11050918.
Duchenne muscular dystrophy (DMD) is the most common x-chromosomal inherited dystrophinopathy which leads to progressive muscle weakness and a premature death due to cardiorespiratory dysfunction. The mouse lacks functional dystrophin protein and has a comparatively human-like diaphragm phenotype. To date, diaphragm function can only be inadequately mapped in preclinical studies and a simple reliable translatable method of tracking the severity of the disease still lacks. We aimed to establish a sensitive, reliable, harmless and easy way to assess the effects of respiratory muscle weakness and subsequent irregularity in breathing pattern. Optical respiratory dynamics tracking (ORDT) was developed utilising a camera to track the movement of paper markers placed on the thoracic-abdominal region of the mouse. ORDT successfully distinguished diseased phenotype from healthy controls by measuring significantly higher expiration constants () in mdx mice compared to wildtype (wt), which were also observed in the established X-ray based lung function (XLF). In contrast to XLF, with ORDT we were able to distinguish distinct fast and slow expiratory phases. In mice, a larger part of the expiratory marker displacement was achieved in this initial fast phase as compared to wt mice. This phenomenon could not be observed in the XLF measurements. We further validated the simplicity and reliability of our approach by demonstrating that it can be performed using free-hand smartphone acquisition. We conclude that ORDT has a great preclinical potential to monitor DMD and other neuromuscular diseases based on changes in the breathing patterns with the future possibility to track therapy response.
杜氏肌营养不良症（DMD）是最常见的 X 连锁遗传性肌营养不良症，导致进行性肌肉无力，并因心肺功能障碍而导致过早死亡。 小鼠缺乏功能性肌营养不良蛋白，并且具有相对类似人类的膈肌表型。迄今为止，只能在临床前研究中对膈肌功能进行不充分的映射，并且仍然缺乏简单可靠的可翻译方法来跟踪疾病的严重程度。我们旨在建立一种敏感，可靠，无害且易于评估呼吸肌无力及其随后呼吸模式不规则的影响的方法。利用摄像机跟踪放置在小鼠胸腹部区域的纸质标记物的运动，开发了光学呼吸动力学跟踪（ORDT）。与野生型（wt）相比，ORDT 通过测量 mdx 小鼠明显更高的呼气常数（），成功地区分了患病表型和健康对照，这在基于 X 射线的肺功能（XLF）中也观察到。与 XLF 相比，我们能够在 ORDT 中区分出明显的快速和慢速呼气阶段。在 mdx 小鼠中，与 wt 小鼠相比，初始快速阶段中呼气标记物的位移量更大。在 XLF 测量中观察不到这种现象。我们进一步通过证明可以使用智能手机自由采集来执行该方法，验证了我们方法的简单性和可靠性。我们得出的结论是，基于呼吸模式的变化，ORDT 具有很大的临床前潜力，可以监测 DMD 和其他神经肌肉疾病，并且将来有可能跟踪治疗反应。
