Non-Invasive Monitoring of Brain Metabolites Using Novel and Adapted Proton and Deuterium MR Techniques
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 140
- 试验地点
- 2
- 主要终点
- 3D spatial resolved Deuterium metabolite imaging (DMI)
研究概览
简要总结
MR pulse for whole brain optimal Deuterium (2H) Metabolic Imaging and EPSI (echo planar spectroscopic imaging) based SLOW-edited 1H-MRSI will be developed and optimized for use at an UHF scanner at 7 Tesla. The study has 4 phases.
Phase I: The 2H and 1H MRSI sequences are developed and optimized in vitro (phantoms)
Phase II: Sequences are applied in vivo in healthy volunteers and further optimized
Phase III: Optimal 2H 1H pulse sequences are applied in 4 cohorts of healthy volunteers, to study the effect of aging with whole brain 2H and 1H MRSI.
Phase IV: application of the sequences in 4 patient groups with different diseases: Alzheimer's diseases (AD) patients, diabetes mellitus type II (DM) patients, mild cognitive impaired (MCI) patients, and high grade carotid stenosis patients (HGCS).
The ultimate aim is to create for individual patient specific 3dimensional spatial resolved z-score maps (similar to FDG-PET) based on the healthy control data of phase III of the trial.
详细描述
Introduction - Aging of the world's population is being increasingly recognized as a crucial societal challenge. Yet, tools to perform high-quality metabolic research on aging of the brain are very limited.
The proposed study will focus on methods to assess metabolic brain changes that occur during aging as well as in 10 patients with Alzheimer's disease (AD). Apart from AD, also 10 patients with minimal cognitive impairment (MCI), 10 patient with diabetes mellitus type 2 (DM), and 10 patients with high grade carotid stenosis will be examined.
The currently most prominent clinical method to study brain metabolism in vivo, is Positron Emission Tomography (PET) using 18F-fluorodeoxyglucose (FDG). A major drawback of this method is the ionizing radiation. A magnetic resonance spectroscopic imaging (MRSI) based method, called deuterium metabolic imaging (DMI) expands the MRSI capabilities offered by proton-based techniques and enables in vivo glucose metabolism imaging without ionizing radiation. A unique feature of DMI is that, unlike PET, it not only maps glucose uptake but also downstream products such as lactate, glutamate and glutamine thereby offering the possibility to detect metabolic disturbances associated with aging and neurodegeneration.
Due to the relatively low sensitivity of DMI, strong magnetic fields are required to increase the signal to noise ratio (SNR) and enable DMI. Recently the first commercially available Ultra High Field (UHF) 7T MR-scanner was approved for clinical use and is now available in Bern, making DMI accessible. The investigators' motivation is to provide non-invasive, radiation free, deuterium and proton based MRSI methods enabling metabolic studies of the brain and lay the foundation for long-term longitudinal observational studies of aging; something that can hardly be done with PET due to the radiation burden for healthy controls.
Objectives - The primary goal of the proposed project is to establish 3D spatially resolved deuterium (2H) and proton (1H) based MRSI methodology for studies of brain metabolism and apply this methodology in an in vivo feasibility study. To complement DMI, the investigators will establish UHF 3D-resolved spectral-edited 1H-MRSI mapping for glucose, gamma-Aminobutyric acid (GABA) and glutamate using the investigators' recently developed technique called SLOW.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •General Inclusion Criteria (applicable to all groups):
- •Signed informed consent by the participant.
- •Ability to lie still in the MR scanner for at least one hour.
- •No current or lifetime history of drug or alcohol abuse.
- •No medications that interfere with cognition.
- •Normal or corrected-to-normal vision.
- •Disease-Specific Inclusion Criteria:
- •I. Type 2 Diabetes Patients group (PG-IV-2H-DM):
- •Diagnosis of Type 2 diabetes according to the ADA classification.
- •Treatment with lifestyle modification and/or non-insulin agents.
- •II. High-Grade Carotid Stenosis Patient Group (PG-IV-1H-HGCS):
- •≥50% stenosis of the carotid artery.
- •III. Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD) Patients (PG-IV-2H-AD/MCI):
- •Diagnosis of Mild Cognitive Impairment (MCI) or early Alzheimer's disease (AD).
- •Age range between 60-80 years.
- •Fluent in German.
- •Normal or corrected-to-normal vision and hearing.
- •Ability to understand the research and provide informed consent.
排除标准
- •Under 18 years of age.
- •Claustrophobia.
- •Pregnancy or current state of lactation.
- •Active implants (e.g., pacemakers, neuro-stimulators).
- •Passive ferromagnetic implants.
- •Passive non-ferromagnetic metallic implants > 4 cm in a region covered by the active radio frequency (RF) coils.
- •Large tattoos inside a region covered by the active RF coils.
- •Known or suspected non-compliance.
- •Underweight <30 kg body weight.
- •Body mass index (BMI) >
- •Overweight >135 kg
- •Persons with extreme big head circumference or extreme astigmatism, which cannot be corrected by MR-compatible eyeglasses.
- •Persons not able to understand the informed consent form.
- •Not agreeing with the institute's policy to inform the subject on incidental findings discovered during the examination.
- •Visual and auditory acuity impairing neuropsychological testing (if relevant).
- •Diabetes or glucose intolerance according to WHO recommendations (excluded in the diabetes patient group).
- •Evidence of overt heart or renal disease.
- •Evidence of gastrointestinal tract disease.
- •Cognitive impairment (Mini-mental state examination score <26/30, CDR score >0, memory complaints) (excluding AD, MCI groups).
- •Current or life-time drug or alcohol abuse
- •Untreated dyslipidemia, hypertension, or thyroid disease.
- •Antidepressant medications with anticholinergic properties.
- •Regular use of narcotic agents more than two doses per week within 4 weeks of screening.
- •Antiparkinsonian medications used within 4 weeks of screening.
- •Enrollment in any investigational drug studies within 4 weeks of screening.
- •Immunomodulating or oncological treatment.
- •Cardiac implantable electronic devices (CIED) such as pacemakers, implantable cardioverter defibrillators (ICDs), and cardiac resynchronization therapy (CRT) devices.
- •Metallic intraocular foreign bodies: patients who have ever welded without eye protection or had facial injuries involving metal must have an orbit x-ray reviewed by a radiologist before MRI.
- •Implantable neurostimulation systems.
- •Cochlear implants/ear implants.
- •Drug infusion pumps (insulin delivery, analgesic drugs, or chemotherapy pumps).
- •Catheters with metallic components (e.g., Swan-Ganz catheter).
- •Metallic fragments (e.g., bullets, shotgun pellets, shrapnel).
- •Cerebral artery aneurysm clips.
- •Magnetic dental implants.
- •Tissue expanders.
- •Artificial limbs.
- •Non-removable hearing aids.
- •Non-removable piercings.
- •Implantable cardiocerter defibrillators
- •Cardiac resynchronization therapy devices
- •Fever (temperature > 37.5°C measured prior to MRI).
- •Volunteers taking amphetamines or sedatives
结局指标
主要结局
3D spatial resolved Deuterium metabolite imaging (DMI)
时间窗: 36 months
Coregistered deuterium metabolite distributions (glucose, glutamate) is measured in a young healthy control group of 20 person (\<40 years) is obtained, as well as coregistered deuterium metabolic images of metabolite distribution in a elder healthy control group of 20 person (\>40 years) is obtained.
3D spatial resolved SLOW-EPSI MRSI metabolite mapping
时间窗: 36 months
Coregistered neuro-metabolite distributions (e.g. GABA, glutamate) distribution in a young healthy control group of 20 persons (age \< 40 years) are measured, as well as coregistered neuro-metabolite distributions (e.g. GABA, glutamate, ..) are measured in healthy control group of 20 persons (age \> 40 years).
3D spatial resolved 3D DMI and 3D SLOW-EPSI MRSI mapping in Alzheimer's disease (AD) patient group
时间窗: 48 months
Coregistered DMI (glucose, glutamate) maps and neuro-metabolite images (e.g. GABA, glutamate, ..) distribution in an Alzheimer's disease (AD) patient group of 10 persons are obtained.
3D spatial resolved 3D DMI and 3D SLOW-EPSI MRSI mapping in Mild Cognitive Impairment (MCI) patient group
时间窗: 48 months
Coregistered DMI (glucose, glutamate) maps and neuro-metabolite images (e.g. GABA, glutamate, ..) distribution in a Mild Cognitive Impairment (MCI) patient group of 10 persons are obtained.
3D DMI and 3D SLOW-EPSI MRSI mapping in a Diabetes Mellitus (DM) Type II patient group
时间窗: 48 months
Coregistered DMI (glucose, glutamate) maps and neuro-metabolite images (e.g. GABA, glutamate, ..) distribution in a Diabetes Mellitus (DM) Type II patient group of 10 persons is obtained
3D DMI and 3D SLOW-EPSI MRSI mapping in a High Grade Carotid Stenosis (HGCS) patient group
时间窗: 48 months
Coregistered DMI (glucose, glutamate) maps and neuro-metabolite images (e.g. GABA, glutamate, ..) distribution in a Diabetes Mellitus (DM) Type II patient group of 10 persons is obtained
次要结局
未报告次要终点