Ultra High Resolution Brain PET Scanner for in-vivo Autoradiography Imaging

用于体内放射自显影成像的超高分辨率脑 PET 扫描仪

• 批准号: 10117728
• 负责人: Georges El Fakhri
• 金额: $ 31.18万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10117728
• 关键词: 3-Dimensional; Administrative Supplement; Adult; Aging; Alzheimer' s Disease; Alzheimer' s disease patient; Anatomy; Area; Autoradiography; Binding; Brain; Brain Stem; Brain region; Cell Nucleus; Cerebellum; Clinical; Clinical Trials; Communities; Data; Dementia; Deposition; Detection; Development; Dimensions; Disease; Disease Progression; Distributional Activity; Early Diagnosis; Elderly; Frequencies; Generations; Goals; Head; Hippocampus (Brain); Human; Image; Kinetics; Lesion; Link; Measures; Medial; Meninges; Methodology; Methods; Modeling; Monte Carlo Method; Motion; Neocortex; Neurodegenerative Disorders; Neurofibrillary Tangles; Noise; Optics; Participant; Pathology; Performance; Positioning Attribute; Positron-Emission Tomography; Resolution; Sampling; Scanning; Shapes; Signal Transduction; Site; Source; Staging; Structure; Substantia nigra structure; Symptoms; System; Tauopathies; Techniques; Temporal Lobe; Testing; Time; Tracer; Validation; Ventilator; Work; base; clinical trial participant; drug development; entorhinal cortex; falls; high resolution imaging; image reconstruction; improved; in vivo; interest; kinetic model; locus ceruleus structure; neocortical; noradrenergic; normal aging; novel; prodromal Alzheimer' s disease; reconstruction; response; sensor; spatiotemporal; targeted imaging; tau Proteins; transmission process; treatment optimization; ultra high resolution; uptake

Abstract Alzheimer’s disease (AD) is an irreversible neurodegenerative disease and the most common cause of dementia in elderly adults. Drug development for AD has been slow so far, in part due to the inability of detecting AD lesions in the brain regions that degenerate first in the early stages of the disease. The progression of AD has been strongly linked to the accumulation of neurofibrillary tangles (NFT), which first appear in the locus coeruleus and then spread to the transentorhinal cortex and finally to the neo-cortex. With the advent of selective tau tracers, NFT distributions can now be characterized in vivo by Positron Emission Tomography (PET). For the newly developed 18F-MK-6240 tau tracer, higher uptakes were observed in medial temporal and neocortical brain regions in AD patients as well as non-specific uptake in the meninges. Though the SAVANT will offer unparalleled spatial resolution performance for a human scanner, quantitative accuracy and detection precision of NFT distributions will still be impacted by partial volume effects. It is thus clear that improvements in resolution are needed to extract the pathophysiological information present in a 18F-MK-6240 scan and allow detection of early NFTs associated with very prodromal AD. The goal of this administrative supplement is to develop, validate and optimize Bayesian reconstruction methodology leveraging super- resolution principles to enable detection of early NFTs in the regions at the origin of tau pathology in AD. The resulting improvement in image quality has the potential to significantly improve very early AD staging, providing new opportunities to assess anti-tau therapies and to optimize selection of participants for clinical trials.

抽象的 阿尔茨海默氏病 (AD) 是一种不可逆的神经退行性疾病，也是导致痴呆的最常见原因 迄今为止，针对老年痴呆症的药物开发进展缓慢，部分原因是缺乏治疗能力。 检测在疾病早期阶段首先退化的大脑区域中的 AD 病变。 AD 的进展与神经原纤维缠结 (NFT) 的积累密切相关，这首先 出现在蓝斑，然后扩散到经内嗅皮质，最后到达新皮质。 随着选择性 tau 示踪剂的出现，现在可以通过正电子发射在体内表征 NFT 分布 对于新开发的 18F-MK-6240 tau 示踪剂，在内侧观察到更高的摄取。 AD 患者的颞叶和新皮质脑区以及脑膜中的非特异性摄取。 SAVANT 将为人体扫描仪提供无与伦比的空间分辨率性能、定量精度 可见，NFT分布的检测精度仍然会受到部分体积效应的影响。 需要提高分辨率来提取 18F-MK-6240 中存在的病理生理信息 扫描并允许检测与非常前驱期的 AD 相关的早期 NFT。 补充是开发、验证和优化贝叶斯重建方法，利用超级 分辨率原则能够检测 AD tau 病理起源区域的早期 NFT。 由此产生的图像质量的改善有可能显着改善早期 AD 分期， 提供新的机会来评估抗 tau 疗法并优化临床参与者的选择 试验。