Sanjida Islam, Alesa Netzley, Chenyang Li, Jiangyang Zhang, Bianca Dávila-Montero, Ana Vazquez, Shaun Subbaiah, Avner Meoded, Kirk Munoz, Aimee Colbath, Jie Huang, Ricardo Mejia-Alvarez, Jane Manfredi, Galit Pelled
Mechanical Engineering, Michigan State University, East Lansing, Michigan, USA.
Department of Emergency Medicine, University of Michigan, Ann Arbor, Michigan, USA.
NMR Biomed. 2025 Jul;38(7):e70074. doi: 10.1002/nbm.70074.
Mild traumatic brain injury (mTBI) caused by sports-related incidents in children and youth often leads to prolonged cognitive impairments but remains difficult to diagnose. In order to identify clinically relevant imaging and behavioral biomarkers associated concussion, a closed-head mTBI was induced in adolescent pigs. Twelve (n = 4 male and n = 8 female), 16-week old Yucatan pigs were tested; n = 6 received mTBI and n = 6 received a sham procedure. T1-weighted imaging was used to assess volumetric alterations in different regions of the brain and diffusion tensor imaging (DTI) to examine microstructural damage in white matter. The pigs were imaged at 1- and 3-month post-injury. Neuropsychological screening for executive function and anxiety were performed before and in the months after the injury. The volumetric analysis showed significant longitudinal changes in pigs with mTBI compared with sham, which may be attributed to swelling and neuroinflammation. Fractional anisotropy (FA) values derived from DTI images demonstrated a 21% increase in corpus callosum from 1 to 3 months in mTBI pigs, which is significantly higher than in sham pigs (4.8%). Additionally, comparisons of the left and right internal capsules revealed a decrease in FA in the right internal capsule for mTBI pigs, which may indicate demyelination. The neuroimaging results suggest that the injury had disrupted the maturation of white and gray matter in the developing brain. Behavioral testing showed that compare to sham pigs, mTBI pigs exhibited 23% increased activity in open field tests, 35% incraesed escape attempts, along with a 65% decrease in interaction with the novel object, suggesting possible memory impairments and cognitive deficits. The correlation analysis showed an associations between volumetric features and behavioral metrics. Furthermore, a machine learning model, which integrated FA, volumetric features and behavioral test metrics, achieved 67% accuracy, indicating its potential to differentiate the two groups. Thus, the imaging biomarkers were indicative of long-term behavioral impairments and could be crucial to the clinical management of concussion in youth.
儿童和青少年因体育相关事件导致的轻度创伤性脑损伤(mTBI)常导致长期认知障碍,但诊断仍很困难。为了识别与脑震荡相关的临床相关影像学和行为生物标志物,在青春期猪中诱导了闭合性头部mTBI。测试了12只(n = 4只雄性和n = 8只雌性)16周龄的尤卡坦猪;n = 6只接受mTBI,n = 6只接受假手术。使用T1加权成像评估大脑不同区域的体积变化,并使用扩散张量成像(DTI)检查白质的微观结构损伤。在受伤后1个月和3个月对猪进行成像。在受伤前和受伤后的几个月内进行执行功能和焦虑的神经心理学筛查。体积分析显示,与假手术组相比,mTBI猪有显著的纵向变化,这可能归因于肿胀和神经炎症。从DTI图像得出的分数各向异性(FA)值显示,mTBI猪胼胝体在1至3个月内增加了21%,明显高于假手术猪(4.8%)。此外,对左右内囊的比较显示,mTBI猪右内囊的FA降低,这可能表明脱髓鞘。神经影像学结果表明,损伤扰乱了发育中大脑白质和灰质的成熟。行为测试表明,与假手术猪相比,mTBI猪在旷场试验中的活动增加了23%,逃避尝试增加了35%,与新物体的互动减少了65%,表明可能存在记忆障碍和认知缺陷。相关性分析显示体积特征与行为指标之间存在关联。此外,一个整合了FA、体积特征和行为测试指标的机器学习模型的准确率达到了67%,表明其有区分两组的潜力。因此,影像学生物标志物可指示长期行为损伤,对青少年脑震荡的临床管理可能至关重要。
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