■创伤性脑损伤(TBI)的慢性神经元负荷未通过常规成像充分表征,限制对神经元底物在不良后果中的作用的理解。
为了确定在常规成像中看起来健康的组织是否可以使用[11C]氟马西尼(FMZ)正电子发射断层扫描(PET)进行选择性神经元丢失研究,并检查这种神经元丢失是否与长期结果相关。
■在这项横断面研究中,数据是在2004年9月1日至2021年5月31日期间从2个中心(英国剑桥大学和美国威尔康奈尔医学)收集的。将TBI患者(伤后>6个月)与健康对照参与者(均年龄>18岁)进行比较。患有神经系统疾病的人,使用苯二氮卓类药物,或排除了磁共振成像的禁忌症.数据与非连续招聘进行了回顾性整理,由于方便和扫描仪或PET配体的可用性。数据在2023年2月1日至9月30日之间进行了分析。
■氟马西尼相对于不可置换结合电位(BPND)的体素结合电位。
■用FMZPET鉴定的选择性神经元丢失在体素和区域尺度上进行比较,以及它与功能的联系,认知,并使用格拉斯哥结果量表(GOS)评分检查心理结果,持续的行政注意力措施(动物和持续的流畅性),和36项简表健康调查(SF-36)得分。扩散张量成像用于评估皮质损伤区域的结构连通性,及其与丘脑选择性神经元丢失的关系。
■在这项研究中,24例慢性TBI患者(平均[SD]年龄,39.2[12.3]岁;18名男性[75.0%])和33名健康对照参与者(平均[SD]年龄,47.6[20.5]年;23名男性[69.7%])接受FMZPET。TBI患者的中位时间为29(范围,从受伤到扫描的7-95)个月。他们在丘脑核中显示出选择性的神经元丢失,超过左丘脑的总体积损失,双边中央,中臭,腹侧-背侧,前,和腹侧丘脑前核,在广泛的伤害严重程度。使用GOS评分(左丘脑,左腹前,双边中央,中臭,和前核),持续执行注意力测量的认知结果更差(左丘脑,双边中央,和右中臭核),使用SF-36评分(右中央丘脑核)的情绪结果较差。慢性丘脑神经元丢失部分反映了原发性皮质挫伤的位置,这可能表明跨神经元变性的继发性损伤机制。
■这项研究的结果表明,选择性丘脑脆弱性可能具有与长期结果相关的慢性神经元后果,提示TBI的演变和潜在的终身丘脑神经元后果。FMZPET是比常规成像更敏感的神经元损伤负荷标志物;因此,它可以为预后提供信息,并可能导致个性化精准医学方法的发展。
UNASSIGNED: The chronic neuronal burden of traumatic brain injury (TBI) is not fully characterized by routine imaging, limiting understanding of the role of neuronal substrates in adverse outcomes.
UNASSIGNED: To determine whether tissues that appear healthy on routine imaging can be investigated for selective neuronal loss using [11C]flumazenil (FMZ) positron emission tomography (PET) and to examine whether this neuronal loss is associated with long-term outcomes.
UNASSIGNED: In this cross-sectional study, data were collected prospectively from 2 centers (University of Cambridge in the UK and Weill Cornell Medicine in the US) between September 1, 2004, and May 31, 2021. Patients with TBI (>6 months postinjury) were compared with healthy control participants (all aged >18 years). Individuals with neurological disease, benzodiazepine use, or contraindication to magnetic resonance imaging were excluded. Data were retrospectively collated with nonconsecutive recruitment, owing to convenience and scanner or PET ligand availability. Data were analyzed between February 1 and September 30, 2023.
UNASSIGNED: Flumazenil voxelwise binding potential relative to nondisplaceable binding potential (BPND).
UNASSIGNED: Selective neuronal loss identified with FMZ PET was compared between groups on voxelwise and regional scales, and its association with functional, cognitive, and psychological outcomes was examined using Glasgow Outcome Scale (GOS) scores, measures of sustained executive attention (animal and sustained fluency), and 36-Item Short Form Health Survey (SF-36) scores. Diffusion tensor imaging was used to assess structural connectivity of regions of cortical damage, and its association with thalamic selective neuronal loss.
UNASSIGNED: In this study, 24 patients with chronic TBI (mean [SD] age, 39.2 [12.3] years; 18 men [75.0%]) and 33 healthy control participants (mean [SD] age, 47.6 [20.5] years; 23 men [69.7%]) underwent FMZ PET. Patients with TBI had a median time of 29 (range, 7-95) months from injury to scan. They displayed selective neuronal loss in thalamic nuclei, over and above gross volume loss in the left
thalamus, and bilateral central, mediodorsal, ventral-lateral dorsal, anterior, and ventral anterior thalamic nuclei, across a wide range of injury severities. Neuronal loss was associated with worse functional outcome using GOS scores (left
thalamus, left ventral anterior, and bilateral central, mediodorsal, and anterior nuclei), worse cognitive outcome on measures of sustained executive attention (left
thalamus, bilateral central, and right mediodorsal nuclei), and worse emotional outcome using SF-36 scores (right central thalamic nucleus). Chronic thalamic neuronal loss partially mirrored the location of primary cortical contusions, which may indicate secondary injury mechanisms of transneuronal degeneration.
UNASSIGNED: The findings of this study suggest that selective thalamic vulnerability may have chronic neuronal consequences with relevance to long-term outcome, suggesting the evolving and potentially lifelong thalamic neuronal consequences of TBI. FMZ PET is a more sensitive marker of the burden of neuronal injury than routine imaging; therefore, it could inform outcome prognostication and may lead to the development of individualized precision medicine approaches.