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神经科学引导的双侧丘脑MRI深度学习用于阻塞性睡眠呼吸暂停诊断:一项双中心转化研究

Neuroscience-guided bilateral thalamic MRI deep learning for obstructive sleep apnea diagnosis: a dual-center translational study.

AI/ML鼻科IF 5.1Q1

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中文摘要

背景: 阻塞性睡眠呼吸暂停(OSA)仍存在大量诊断不足,而反复发作的间歇性缺氧(IH)是OSA的关键病理生理特征,并可能影响丘脑功能。我们旨在开发一种神经科学引导的基于MRI的深度学习模型,用于辅助OSA诊断。
方法: 将雄性C57BL/6J小鼠暴露于IH,并使用免疫荧光染色和体内钙成像评估丘脑激活。回顾性收集了两个中心760名成人的临床脑MRI和多导睡眠监测(PSG)数据。中心1被分为训练和验证队列,中心2作为独立的外部测试集。基于实验发现,分割双侧丘脑区域,并开发了一种具有基于Transformer的特征融合的双分支3D CNN。
结果: IH在小鼠中引起显著的丘脑激活,并且在所检查的丘脑亚区中,中央外侧丘脑核(CL)表现出最强的相对反应。与对照组相比,IH组CL中c-Fos阳性细胞显著增加(62.50±11.67 vs. 9.67±4.89,n=6,P<0.0001)。进一步的钙信号记录显示,刺激后1分钟时间窗内CL的钙活动显著增加。在人类MRI队列中,双侧丘脑深度学习模型在训练集、验证集和外部测试集中的AUC分别为0.944(95% CI,0.926-0.960)、0.928(95% CI,0.893-0.957)和0.911(95% CI,0.856-0.957),优于单侧模型(P<0.001)。
结论: IH诱导的丘脑激活,以CL作为代表性高反应性丘脑亚区,为丘脑ROI选择提供了实验支持。双侧丘脑MRI模型提供了一种有生物学依据且经过外部验证的基于影像的方法,可能有助于OSA识别。

英文摘要

BACKGROUND: Obstructive sleep apnea (OSA) remains substantially underdiagnosed, and recurrent intermittent hypoxia (IH) is a key pathophysiological feature of OSA and may affect thalamic function. We aimed to develop a neuroscience-guided MRI-based deep learning model for auxiliary OSA diagnosis.
METHODS: Male C57BL/6J mice were exposed to IH, and thalamic activation was assessed using immunofluorescence staining and in vivo calcium imaging. Clinical brain MRI and polysomnography (PSG) data were retrospectively collected from 760 adults across two centers. Center 1 was divided into training and validation cohorts, and center 2 served as an independent external test set. Based on the experimental findings, bilateral thalamic regions were segmented, and a dual-branch 3D CNN with Transformer-based feature fusion was developed.
RESULTS: IH induced prominent thalamic activation in mice, and central lateral thalamic nucleus (CL) showed the strongest relative response among the examined thalamic subregions. Compared with the control group, the IH group showed a marked increase in c-Fos-positive cells in the CL (62.50 ± 11.67 vs. 9.67 ± 4.89, n = 6, P < 0.0001). Further calcium signal recordings showed that calcium activity in the CL was significantly increased within the 1-minute time window after stimulation. In the human MRI cohort, the bilateral thalamic deep learning model achieved AUCs of 0.944 (95% CI, 0.926-0.960), 0.928 (95% CI, 0.893-0.957), and 0.911 (95% CI, 0.856-0.957) in the training, validation, and external test sets, respectively, outperforming the unilateral models (P < 0.001).
CONCLUSIONS: IH-induced thalamic activation, with CL serving as a representative highly responsive thalamic subregion, provided experimental support for thalamic ROI selection. The bilateral thalamic MRI model provides a biologically grounded and externally validated imaging-based approach that may assist OSA identification.