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Deuterium metabolic imaging (DMI) of neurological disease

神经系统疾病的氘代谢成像 (DMI)

基本信息

批准号：
10376176
负责人：
ROBIN A DE GRAAF
金额：
$ 65.78万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-15 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10376176
关键词：
3-Dimensional Acetates Alzheimer&apos s Disease Anesthesia procedures Animals Biological Markers Brain Brain Mapping Brain Neoplasms Brain imaging Cancer Detection Cerebrum Clinic Clinical Clinical Research Data Deoxyglucose Detection Deuterium Development Diagnosis Disease Progression Epilepsy Glucose Glutamates Glutamine Goals Gold Heating Human Human body Image Imaging Device Imaging Techniques Intake Intravenous Label Left Lesion Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Maps Mass Spectrum Analysis Measurement Metabolic Metabolic Pathway Metabolic dysfunction Metabolism Metastatic malignant neoplasm to brain Methodology Methods Monitor Multiple Sclerosis Neurodegenerative Disorders Noise Nutrient Oral Pathogenesis Pathway interactions Patients Physiologic pulse Plasma Play Positron-Emission Tomography Primary Brain Neoplasms Protocols documentation Publications Rattus Reaction Reporting Reproducibility Research Resolution Rodent Role Science Signal Transduction Techniques Three-Dimensional Imaging Tissue Sample Translations Traumatic Brain Injury Treatment Efficacy Warburg Effect Water base brain metabolism clinical application clinical practice clinically significant contrast imaging data acquisition drinking first-in-human glucose metabolism glucose uptake human data human disease imaging modality insight magnetic field metabolic imaging metabolic rate nervous system disorder new therapeutic target non-invasive imaging novel pre-clinical research quantitative imaging radio frequency reconstruction relating to nervous system spectroscopic imaging therapy development tool tumor tumor metabolism uptake

项目摘要

PROJECT SUMMARY Non-invasive imaging of metabolic pathways in neurological disease has been a long-standing goal to monitor disease progression or therapy efficacy. Clinicians have in reality only one metabolic imaging tool, which is detection of intravenously administered 2-18F-fluoro-2-deoxy-D-glucose (FDG) with positron emission tomography (PET). Its unrivaled sensitivity makes FDG-PET a mainstay application for cancer detection outside of the brain. However, the high uptake of FDG by normal brain drastically reduces the image contrast and the usefulness of FDG-PET in studying neurological disease. 1H and 13C MR spectroscopic imaging (MRSI), and hyperpolarized 13C MRSI are promising methods but have failed to reach clinical significance due to a variety of reasons including technical complexity and lack of robustness and/or sensitivity. Substrates labeled with deuterium (2H) have been used for decades to study whole body human metabolism by detecting the 2H label in downstream metabolic products in plasma or tissue samples using mass spectroscopy or magnetic resonance spectroscopy (MRS). Our first-in-man deuterium metabolic imaging (DMI) maps of glucose metabolism in healthy brain and DMI maps showing the distribution of the “Warburg-effect” in patients with high grade brain tumors illustrate that DMI has the potential to become a widely applicable brain imaging method with strong clinical utility. The proposal is organized around three specific aims that will establish the clinical applicability, scientific validity and reproducibility of DMI. As part of Aim 1, the 2H-based measurement of glucose metabolism will be validated with `gold-standard' 13C-based MRS on animal and human brain. The availability of affordable 2H-labeled substrates, such as glucose (and acetate), together with the relative ease of DMI data acquisition greatly expedites the translation to a clinical 3 Tesla MRI scanner. In Aim 2 we will optimize the protocol for use of DMI in the clinic, report on reproducibility of the DMI-based metabolic maps, and explore the metabolic differences detected with DMI in patients diagnosed with primary and secondary brain tumors. In the third aim we compare in patients diagnosed with brain tumors the metabolism-based image contrast observed using DMI with the image contrast detected using FDG-PET. By the completion of the proposed studies we expect to have a simple, but robust metabolic imaging modality that can provide 3D maps of the metabolic fate of multiple substrates in a wide range of neurological disorders.

项目摘要神经系统疾病代谢途径的非侵入性成像一直是监测的长期目标。疾病进展或治疗功效。临床医生实际上只有一种代谢成像工具，用正电子发射检测静脉内施用的2- 18 F-氟-2-脱氧-D-葡萄糖（FDG）断层扫描（PET）。其无与伦比的灵敏度使FDG-PET成为癌症检测的主要应用在大脑之外。然而，正常大脑对FDG的高摄取显著降低了图像对比度以及FDG-PET在研究神经系统疾病中的作用。~ 1H和~（13）C磁共振波谱成像（MRSI）和超极化13 C MRSI是有前途的方法，但由于缺乏临床意义，由于各种原因，包括技术复杂性和缺乏鲁棒性和/或灵敏度。几十年来，氘（2 H）标记的底物一直用于研究人体全身代谢通过使用质谱检测血浆或组织样品中下游代谢产物中的2 H标记，光谱学或磁共振光谱学（MRS）。我们的第一个人体氘代谢成像（氘）健康大脑的葡萄糖代谢图和显示“沃伯格效应”在大脑中的分布的神经网络图。患有高级别脑肿瘤的患者说明，具有很强的临床实用性的成像方法。该提案围绕三个具体目标组织，建立临床适用性、科学有效性和可重复性。作为目标1的一部分，葡萄糖代谢的测量将在动物上用基于“金标准”13 C的MRS进行验证，人脑可负担得起的2 H标记底物的可用性，如葡萄糖（和乙酸盐），以及 DMI数据采集相对容易，大大加快了向临床3特斯拉MRI扫描仪的转换。在目的2：优化临床使用的药物筛选方案，报告基于DMI的药物筛选方法的重现性，代谢图，并探讨在诊断为原发性肝癌的患者中，和继发性脑瘤在第三个目标中，我们比较了诊断为脑肿瘤的患者的基于代谢的图像对比度，使用FDG-PET检测图像对比度，使用SPECT观察。在完成拟议的我们希望有一个简单但强大的代谢成像模式，可以提供3D地图的研究，多种底物在广泛的神经系统疾病中的代谢命运。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

In vivo imaging of cerebral glucose metabolism informs on subacute to chronic post-stroke tissue status - A pilot study combining PET and deuterium metabolic imaging.

DOI：
10.1177/0271678x221148970
发表时间：
2023-05
期刊：
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
影响因子：
6.3
作者：
Meerwaldt, Anu E.;Straathof, Milou;Oosterveld, Wija;van Heijningen, Caroline L.;van Leent, Mandy M. T.;Toner, Yohana C.;Munitz, Jazz;Teunissen, Abraham J. P.;Daemen, Charlotte C.;van der Toorn, Annette;van Vliet, Gerard;van Tilborg, Geralda A. F.;De Feyter, Henk M.;de Graaf, Robin A.;Hol, Elly M.;Mulder, Willem J. M.;Dijkhuizen, Rick M.
通讯作者：
Dijkhuizen, Rick M.

NMR visibility of deuterium-labeled liver glycogen in vivo.

DOI：
10.1002/mrm.28717
发表时间：
2021-07
期刊：
Magnetic resonance in medicine
影响因子：
3.3
作者：
De Feyter HM;Thomas MA;Behar KL;de Graaf RA
通讯作者：
de Graaf RA

Deuterium metabolic imaging - Back to the future.

DOI：
10.1016/j.jmr.2021.106932
发表时间：
2021-05
期刊：
Journal of magnetic resonance (San Diego, Calif. : 1997)
影响因子：
0
作者：
De Feyter HM;de Graaf RA
通讯作者：
de Graaf RA

Interleaved fluid-attenuated inversion recovery (FLAIR) MRI and deuterium metabolic imaging (DMI) on human brain in vivo.

交错的流体侵入式反转恢复（FLAIR）MRI和氘代谢成像（DMI）在体内的人脑上。

DOI：
10.1002/mrm.29196
发表时间：
2022-07
期刊：
MAGNETIC RESONANCE IN MEDICINE
影响因子：
3.3
作者：
Liu, Yanning;De Feyter, Henk M.;Fulbright, Robert K.;McIntyre, Scott;Nixon, Terence W.;de Graaf, Robin A.
通讯作者：
de Graaf, Robin A.

Deuterium metabolic imaging in the human brain at 9.4 Tesla with high spatial and temporal resolution.