Ultra-High Resolution PET of the Human Brain and Spinal Cord in Healthy Aging, Dementia, Movement Disorders, ALS and Psychotic Disorders
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- Volume distribution (mL/cm³) in small brain nuclei of tracers ¹⁸F-FDG, ¹⁸F-PE2I, ¹⁸F-SynVesT-1 and ¹⁸F-MK6240
研究概览
简要总结
The goal of this study is to use ultra-high-resolution (UHR) PET imaging to better understand how the brain and spinal cord change in healthy aging and in neurological and psychiatric disorders such as Alzheimer's disease (AD), Parkinson's disease and related movement disorders, amyotrophic lateral sclerosis (ALS), and psychotic disorders. Researchers will use the NeuroExplorer PET/CT system, a new scanner that can show very small structures in the brain and spinal cord in much more detail than regular PET.
The main questions this study aims to answer are:
- How do small but important brain regions (like the locus coeruleus, substantia nigra, and thalamic nuclei) change in healthy aging?
- What early brain changes occur in neurodegenerative and psychotic disorders, and can they help improve early diagnosis?
Participants will:
- Undergo PET and MRI brain scans using different tracers that measure brain metabolism (18F-FDG), synaptic density (¹⁸F-SynVesT-1), dopamine transporters (¹⁸F-PE2I), and tau protein buildup (¹⁸F-MK6240).
- Complete cognitive and clinical assessments related to memory, mood, and motor or psychiatric symptoms, depending on their group.
This study will include healthy volunteers and patients with mild cognitive impairment due to Alzheimer´s disease, ALS, Parkinson's disease and related disorders, or psychotic disorders.
The results will help create detailed brain imaging maps for healthy aging and identify early biomarkers for different diseases to support better diagnosis and treatment in the future.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •WP1: Healthy controls
- •Age between 18 and 90 years old (15 aged 18-50 years and 25 aged 50 90 years);
- •Subject is judged to be in good health by the investigator on the basis of medical history, physical examination including vital signs and clinical laboratory tests;
- •No history or evidence of current major neurological, internal or psychiatric disorder, based on the medical assessment as described hereabove and neuropsychological assessment;
- •No evidence of cognitive impairment as assessed by a Montreal Cognitive Assessment (MoCA) score of 26 or higher at baseline;
- •In subjects < 60 years of age, a normal structural MRI scan as assessed by expert radiologist.
- •In subjects >= 60 years of age white matter hyperintensities corresponding to a WML (white matter lesion) score <= 2 (of 3) on the Age-Related White Matter changes scale are acceptable;
- •When older than 50 years of age, the volunteer is willing to undergo a p- tau217 blood sample.
- •WP2: Dementia
- •Patient has a clinical diagnosis of biomarker-proven prodromal AD
- •WP3: ALS spectrum
- •Subject must meet El Escorial Criteria (30) and Awaji-Shima criteria (31) for at least possible ALS;
- •WP4: Movement disorders
- •(all): Patient (or legal representative, when applicable) is able to understand the patient information form and give written informed consent.
- •Parkinson´s disease (PD):
- •Patient has clinically established PD based on the Movement Disorder Society (MDS) diagnostic criteria (32);
- •Patient has an abnormal 18F-PE2I PET;
- •No evidence of cognitive impairment as assessed by a Montreal Cognitive Assessment (MoCA) score of 26 or higher at baseline.
- •Multiple system atrophy (MSA)
- •Patient has clinically established or clinically probable MSA-P based on the
- •Movement Disorder Society (MDS) diagnostic criteria (33);
- •Patient has an abnormal 18F-PE2I PET.
- •Progressive supranuclear palsy (PSP)
- •Patient has an abnormal 18F-PE2I PET;
- •Patient has clinically established probable PSP according to the latest MDS criteria
- •Dementia with Lewy bodies (DLB)
- •Patient has probable DLB by consensus criteria (cognitive impairment MoCA < 26 + visual hallucinations and/or fluctuating alertness);
- •Patient has an abnormal 18F-PE2I PET.
- •Idiopathic REM sleep behavior disorder (iRBD)
- •Patient has Polysomnography-confirmed iRBD;
- •No evidence of cognitive impairment as assessed by a Montreal Cognitive Assessment (MoCA) score of 26 or higher at baseline;
- •No clinical evidence of parkinsonism at baseline.
- •WP5: Psychosis
- •DSM 5 criteria for a non-affective schizophrenia spectrum psychotic disorder;
- •Age between 18 and 55 years old for adult-onset psychosis, onset of psychosis (and age) above 60 years old for very late onset psychosis.
排除标准
- •Subject has a history of any major (other) internal, psychiatric or neurological disease that may interfere with the investigations (especially liver and kidney disease, uncontrolled diabetes, cancer, severe depression, stroke, severe TBI);
- •Subject is currently a user (including recreational use) of any illicit drugs, including cannabis, or has a history of drug or alcohol abuse;
- •Subject chronically uses medication that has central nervous system effects (e.g. strong painkillers such as opioids, neuroleptics,..; ) (other than prescribed for the illness in case of patients);
- •Subject has had exposure to ionizing radiation (> 1 mSv) in other research studies within the last 12 months;
- •Subject has a contra-indication for MRI scanning;
- •Subject suffers from claustrophobia or cannot tolerate confinement during PET-MRI scanning procedures; subject cannot lie still for (at least) 60 minutes inside the scanner;
- •(For subjects with arterial sampling): The subject is hypersensitive to lidocaine (used for local anaesthesia during the placement of the arterial catheter), has an abnormal Allen test (a test to check blood flow in the arteries of the forearm) or is on anti-coagulant therapy;
- •Subject (or his/her legal representative) does not understand the study procedures;
- •Subject is unwilling or unable to perform all of the study procedures, or is considered unsuitable in any way by the principal investigator;
- •Subject is potentially pregnant (hCG test can be done if doubt exists).
研究组 & 干预措施
Healthy controls
Participants in this arm are healthy controls undergoing ultra-high-resolution (UHR) PET imaging on the NeuroEXPLORER system using multiple radiotracers (¹⁸F-FDG, ¹⁸F-PE2I, ¹⁸F-SynVesT-1 and ¹⁸F-MK6240), in combination with 3T MRI. No therapeutic intervention is administered.
干预措施: UHR PET/CT scan of the brain with ¹⁸F-FDG (Other)
Healthy controls
Participants in this arm are healthy controls undergoing ultra-high-resolution (UHR) PET imaging on the NeuroEXPLORER system using multiple radiotracers (¹⁸F-FDG, ¹⁸F-PE2I, ¹⁸F-SynVesT-1 and ¹⁸F-MK6240), in combination with 3T MRI. No therapeutic intervention is administered.
干预措施: UHR PET/CT scan of the brain with ¹⁸F-PE2I (Other)
Healthy controls
Participants in this arm are healthy controls undergoing ultra-high-resolution (UHR) PET imaging on the NeuroEXPLORER system using multiple radiotracers (¹⁸F-FDG, ¹⁸F-PE2I, ¹⁸F-SynVesT-1 and ¹⁸F-MK6240), in combination with 3T MRI. No therapeutic intervention is administered.
干预措施: UHR PET/CT scan of the brain with ¹⁸F-SynVesT-1 (Other)
Healthy controls
Participants in this arm are healthy controls undergoing ultra-high-resolution (UHR) PET imaging on the NeuroEXPLORER system using multiple radiotracers (¹⁸F-FDG, ¹⁸F-PE2I, ¹⁸F-SynVesT-1 and ¹⁸F-MK6240), in combination with 3T MRI. No therapeutic intervention is administered.
干预措施: UHR PET/CT scan of the brain with ¹⁸F-MK6240 (Other)
Healthy controls
Participants in this arm are healthy controls undergoing ultra-high-resolution (UHR) PET imaging on the NeuroEXPLORER system using multiple radiotracers (¹⁸F-FDG, ¹⁸F-PE2I, ¹⁸F-SynVesT-1 and ¹⁸F-MK6240), in combination with 3T MRI. No therapeutic intervention is administered.
干预措施: 3T MRI imaging of the brain (Other)
Patient with aMCI
Participants in this arm are patients with biomarker-confirmed amnestic mild cognitive impairment due to Alzheimer's disease undergoing UHR PET imaging using ¹⁸F-FDG and ¹⁸F-MK6240, in combination with 3T MRI. No therapeutic intervention is administered.
干预措施: UHR PET/CT scan of the brain with ¹⁸F-FDG (Other)
Patient with aMCI
Participants in this arm are patients with biomarker-confirmed amnestic mild cognitive impairment due to Alzheimer's disease undergoing UHR PET imaging using ¹⁸F-FDG and ¹⁸F-MK6240, in combination with 3T MRI. No therapeutic intervention is administered.
干预措施: UHR PET/CT scan of the brain with ¹⁸F-MK6240 (Other)
Patient with aMCI
Participants in this arm are patients with biomarker-confirmed amnestic mild cognitive impairment due to Alzheimer's disease undergoing UHR PET imaging using ¹⁸F-FDG and ¹⁸F-MK6240, in combination with 3T MRI. No therapeutic intervention is administered.
干预措施: 3T MRI imaging of the brain (Other)
Patients with ALS/ALS-FTD
Participants in this arm are patients within the ALS and ALS-FTD spectrum undergoing UHR PET imaging using ¹⁸F-FDG, with a subgroup additionally undergoing ¹⁸F-SynVesT-1 PET, in combination with 3T MRI. No therapeutic intervention is administered.
干预措施: UHR PET/CT scan of the brain with ¹⁸F-FDG (Other)
Patients with ALS/ALS-FTD
Participants in this arm are patients within the ALS and ALS-FTD spectrum undergoing UHR PET imaging using ¹⁸F-FDG, with a subgroup additionally undergoing ¹⁸F-SynVesT-1 PET, in combination with 3T MRI. No therapeutic intervention is administered.
干预措施: UHR PET/CT scan of the brain with ¹⁸F-SynVesT-1 (Other)
Patients with ALS/ALS-FTD
Participants in this arm are patients within the ALS and ALS-FTD spectrum undergoing UHR PET imaging using ¹⁸F-FDG, with a subgroup additionally undergoing ¹⁸F-SynVesT-1 PET, in combination with 3T MRI. No therapeutic intervention is administered.
干预措施: 3T MRI imaging of the brain (Other)
Patients with movement disorders
Participants in this arm include patients with Parkinson's disease, atypical parkinsonism, dementia with Lewy bodies or idiopathic REM sleep behavior disorder undergoing UHR PET imaging using ¹⁸F-FDG, ¹⁸F-PE2I and ¹⁸F-SynVesT-1, in combination with 3T MRI. No therapeutic intervention is administered.
干预措施: UHR PET/CT scan of the brain with ¹⁸F-FDG (Other)
Patients with movement disorders
Participants in this arm include patients with Parkinson's disease, atypical parkinsonism, dementia with Lewy bodies or idiopathic REM sleep behavior disorder undergoing UHR PET imaging using ¹⁸F-FDG, ¹⁸F-PE2I and ¹⁸F-SynVesT-1, in combination with 3T MRI. No therapeutic intervention is administered.
干预措施: UHR PET/CT scan of the brain with ¹⁸F-SynVesT-1 (Other)
Patients with movement disorders
Participants in this arm include patients with Parkinson's disease, atypical parkinsonism, dementia with Lewy bodies or idiopathic REM sleep behavior disorder undergoing UHR PET imaging using ¹⁸F-FDG, ¹⁸F-PE2I and ¹⁸F-SynVesT-1, in combination with 3T MRI. No therapeutic intervention is administered.
干预措施: 3T MRI imaging of the brain (Other)
Patients with psychotic disorders
Participants in this arm are patients with adult-onset or very late-onset psychotic disorders undergoing UHR PET imaging using ¹⁸F-FDG, in combination with 3T MRI. No therapeutic intervention is administered.
干预措施: UHR PET/CT scan of the brain with ¹⁸F-FDG (Other)
Patients with psychotic disorders
Participants in this arm are patients with adult-onset or very late-onset psychotic disorders undergoing UHR PET imaging using ¹⁸F-FDG, in combination with 3T MRI. No therapeutic intervention is administered.
干预措施: 3T MRI imaging of the brain (Other)
结局指标
主要结局
Volume distribution (mL/cm³) in small brain nuclei of tracers ¹⁸F-FDG, ¹⁸F-PE2I, ¹⁸F-SynVesT-1 and ¹⁸F-MK6240
时间窗: Through study completion, an average of 4 year
To evaluate the regional binding patterns in small brain nuclei using four PET tracers (18F-FDG, 18F-PE2I, 18F-SynVest-1, 18F-MK6240) in different subject groups (healthy controls and disease cohorts). Quantitative outcome metrics will include distribution volumes with and without partial volume correction (PVC).
Standardized uptake value ratios (SUVR) in small brain nuclei of tracers ¹⁸F-FDG, ¹⁸F-PE2I, ¹⁸F-SynVesT-1 and ¹⁸F-MK6240
时间窗: Through study completion, an average of 4 year
To evaluate the regional binding patterns in small brain nuclei using four PET tracers (18F-FDG, 18F-PE2I, 18F-SynVest-1, 18F-MK6240) in different subject groups (healthy controls and disease cohorts). Quantitative outcome metrics will include standardized uptake value ratios (SUVR) with and without partial volume correction (PVC).
次要结局
- Correlation between regional PET tracer uptake and cognitive performance(Through study completion, an average of 4 year)
- Correlation between regional PET tracer uptake and motor and functional impairment(Through study completion, an average of 4 year)