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正常衰老过程中大脑结构、氧合和灌注功能的轨迹和性别差异。

Trajectories and sex differences of brain structure, oxygenation and perfusion functions in normal aging.

机构信息

Department of Radiology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, China.

Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Neuroimage. 2024 Nov 15;302:120903. doi: 10.1016/j.neuroimage.2024.120903. Epub 2024 Oct 24.

DOI:10.1016/j.neuroimage.2024.120903
PMID:39461605
Abstract

BACKGROUND

Brain structure, oxygenation and perfusion are important factors in aging. Coupling between regional cerebral oxygen consumption and perfusion also reflects functions of neurovascular unit (NVU). Their trajectories and sex differences during normal aging important for clinical interpretation are still not well defined. In this study, we aim to investigate the relationship between brain structure, functions and age, and exam the sex disparities.

METHOD

A total of 137 healthy subjects between 20∼69 years old were enrolled with conventional MRI, structural three-dimensional T-weighted imaging (3D-TWI), 3D multi-echo gradient echo sequence (3D-mGRE), and 3D pseudo-continuous arterial spin labeling (3D-pCASL). Oxygen extraction fraction (OEF) and cerebral blood flow (CBF) were respectively reconstructed from 3D-mGRE and 3D-pCASL images. Cerebral metabolic rate of oxygen (CMRO) were calculated as follows: CMRO=CBF·OEF·[H], [H]=7.377 μmol/mL. Brains were segmented into global gray matter (GM), global white matter (WM), and 148 cortical subregions. OEF, CBF, CMRO, and volumes of GM/WM relative to intracranial volumes (rel_GM/rel_WM) were compared between males and females. Generalized additive models were used to evaluate the aging trajectories of brain structure and functions. The coupling between OEF and CBF was analyzed by correlation analysis. P or P < 0.05 was considered statistically significant.

RESULTS

Females had larger rel_GM, higher CMRO and CBF of GM/WM than males (P < 0.05). With control of sex, CBF of GM significantly declined between 20 and 32 years, CMRO of GM declined subsequently from 33 to 41 years and rel_GM decreased significantly at all ages (R = 0.27, P < 0.001; R = 0.17, P < 0.001; R = 0.52, P < 0.001). In subregion analysis, CBF declined dispersedly while CMRO declined widely across most subregions of the cortex during aging. Robust negative coupling between OEF and CBF was found in most of the subregions (r range = -0.12∼-0.48, P < 0.05).

CONCLUSION

The sex disparities, age trajectories of brain structure and functions as well as the coupling of NVU in healthy individuals provide insights into normal aging which are potential targets for study of pathological conditions.

摘要

背景

大脑结构、氧合和灌注是衰老的重要因素。区域性脑氧消耗与灌注的耦合也反映了神经血管单元 (NVU) 的功能。它们在正常衰老过程中的轨迹和性别差异对于临床解释非常重要,但目前仍未得到很好的定义。在这项研究中,我们旨在研究大脑结构、功能与年龄之间的关系,并检查性别差异。

方法

共纳入 137 名年龄在 20∼69 岁之间的健康受试者,进行常规 MRI、三维 T 加权成像 (3D-TWI)、三维多回波梯度回波序列 (3D-mGRE) 和三维伪连续动脉自旋标记 (3D-pCASL)。从 3D-mGRE 和 3D-pCASL 图像分别重建氧摄取分数 (OEF) 和脑血流量 (CBF)。脑氧代谢率 (CMRO) 按以下公式计算:CMRO=CBF·OEF·[H],[H]=7.377 μmol/mL。将大脑分为全脑灰质 (GM)、全脑白质 (WM) 和 148 个皮质亚区。比较男性和女性之间 OEF、CBF、CMRO 和 GM/WM 相对于颅内体积的相对值 (rel_GM/rel_WM)。采用广义加性模型评估脑结构和功能的老化轨迹。通过相关分析分析 OEF 与 CBF 的耦合关系。P 或 P < 0.05 被认为具有统计学意义。

结果

女性的 rel_GM 较大,GM/WM 的 CMRO 和 CBF 高于男性 (P < 0.05)。控制性别后,20∼32 岁 GM 的 CBF 显著下降,33∼41 岁 GM 的 CMRO 随后下降,所有年龄 rel_GM 均显著下降 (R = 0.27,P < 0.001;R = 0.17,P < 0.001;R = 0.52,P < 0.001)。在亚区分析中,随着年龄的增长,CBF 在皮质的大多数亚区呈弥散性下降,而 CMRO 在大多数亚区广泛下降。在大多数亚区发现 OEF 和 CBF 之间存在稳健的负相关 (r 范围 = -0.12∼-0.48,P < 0.05)。

结论

健康个体中 NVU 的性别差异、脑结构和功能的年龄轨迹以及耦合为研究病理状况提供了对正常衰老的深入了解,这可能是研究的潜在靶点。

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