Mesoscopic Biomarkers of Neurodegeneration and Inflammation with Diffusion MRI
弥散 MRI 神经退行性变和炎症的细观生物标志物
基本信息
- 批准号:10673125
- 负责人:
- 金额:$ 62.77万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-09-30 至 2024-07-31
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAcuteAffectAlzheimer&aposs DiseaseAmericanAnatomyAstrocytosisAutoimmune DiseasesAxonBindingBiological MarkersCentral Nervous System DiseasesChronicClinicalComplexCuprizoneDemyelinationsDiffuseDiffusionDiffusion Magnetic Resonance ImagingDimensionsDiseaseDisease ProgressionDisease remissionEconomicsElectron MicroscopyFiberFundingGeometryGliosisHumanImageImaging TechniquesInfiltrationInflammationInflammatoryInjuryIntoxicationLesionLifeMRI ScansMacrophageMagnetic Resonance ImagingMapsMeasuresMethodsModelingMolecularMonitorMonte Carlo MethodMotionMultiple SclerosisNerve DegenerationNeurodegenerative DisordersNoiseParameter EstimationPathologicPathologic ProcessesPatientsPersonsPilot ProjectsProcessPrognostic MarkerProtocols documentationPublic HealthRelapseRelaxationReproducibilityRoentgen RaysRoleSeverity of illnessSignal TransductionSpecificityStructureTechniquesTestingTherapeuticTimeTranslatingUnited StatesWalkingWateraxonal degenerationcandidate markerchronic inflammatory diseasecomputer frameworkcostdisabilityimaging modalityin vivoinsightmagnetic resonance imaging biomarkermouse modelmultiple sclerosis patientnervous system disorderneuroinflammationnovelremyelinationsimulationsoft tissuetherapy developmentvolunteerwhite matter
项目摘要
PROJECT SUMMARY
Diseases of the central nervous system (CNS) are a significant public health and economic problem, affecting
one in three Americans at some point in life, and costing over $500 billion per year. Pathologically, the white
matter (WM) is compromised in CNS disorders by neuro-inflammatory processes (gliosis, astrocytosis,
macrophage infiltration), acute axonal beading, and neurodegenerative processes (demyelination, axonal
degeneration and loss). While axonal degeneration results in irreversible disability, the roles of different
inflammatory processes, and their interplay with neurodegeneration, are unknown, mainly due to the lack of
biomarkers that parse these concurrent processes in vivo in humans.
Our main objective is to distinguish and quantify neurodegenerative and inflammatory processes in WM with
MRI, and evaluate them as prognostic markers for Multiple Sclerosis (MS), a chronic inflammatory and
neurodegenerative disorder.
In Aim 1, we will develop a fast T2-weighted dMRI sequence unifying our TE-dependent Diffusion Imaging
(TEdDI) technique with free gradient wave forms reducing acquisition time to within 15 minutes, and employ
Cramer-Rao lower bound minimization to find an optimal protocol for estimating intra- and extra-axonal water
fractions, diffusion coefficients and relaxation times, which are the proposed markers of neurodegeneration
and inflammation. We will then test the protocol's accuracy and reproducibility on phantoms and volunteers.
In Aim 2, we will use our protocol to track neurodegeneration and inflammation both cross-sectionally and
longitudinally on MS patients at different stages in the disease, and identify specific changes of all parameters
with increasing disease severity. We expect that our neurodegeneration-related parameters will be more
sensitive than lesion load and volumetrics in tracking disability. Furthermore, we will for the first time assess
changes in compartmental diffusivities and relaxation times and relate them to MS disease progression.
In Aim 3, we will develop a framework of realistic Monte Carlo random walk simulations in WM geometries
reconstructed from 3d electron microscopy. Ab initio, we will quantitatively explore the effect of gliosis,
beading, demyelination and axonal loss in normal-appearing WM on diffusion and WM microstructure markers.
Overall, the project will yield novel non-invasive clinically feasible diffusion MRI markers sensitive and specific
to diffuse neurodegeneration and inflammatory processes, that could help better understand MS disease
progression and open new avenues for effective management of patients and therapy development. The
developed MRI pipeline for estimating WM microstructure markers will be straightforwardly extendable beyond
MS, to help understand and quantify neurodegeneration and inflammation in other neurological diseases.
项目总结
项目成果
期刊论文数量(42)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
The present and the future of microstructure MRI: From a paradigm shift to normal science.
- DOI:10.1016/j.jneumeth.2020.108947
- 发表时间:2021-03-01
- 期刊:
- 影响因子:3
- 作者:Novikov DS
- 通讯作者:Novikov DS
Training a neural network for Gibbs and noise removal in diffusion MRI.
- DOI:10.1002/mrm.28395
- 发表时间:2021-01
- 期刊:
- 影响因子:3.3
- 作者:Muckley MJ;Ades-Aron B;Papaioannou A;Lemberskiy G;Solomon E;Lui YW;Sodickson DK;Fieremans E;Novikov DS;Knoll F
- 通讯作者:Knoll F
Diffusion kurtosis imaging probes cortical alterations and white matter pathology following cuprizone induced demyelination and spontaneous remyelination.
- DOI:10.1016/j.neuroimage.2015.10.052
- 发表时间:2016-01-15
- 期刊:
- 影响因子:5.7
- 作者:Guglielmetti C;Veraart J;Roelant E;Mai Z;Daans J;Van Audekerke J;Naeyaert M;Vanhoutte G;Delgado Y Palacios R;Praet J;Fieremans E;Ponsaerts P;Sijbers J;Van der Linden A;Verhoye M
- 通讯作者:Verhoye M
The brain after COVID-19: Compensatory neurogenesis or persistent neuroinflammation?
- DOI:10.1016/j.eclinm.2020.100684
- 发表时间:2021-01
- 期刊:
- 影响因子:15.1
- 作者:Goldberg E;Podell K;Sodickson DK;Fieremans E
- 通讯作者:Fieremans E
On modeling.
- DOI:10.1002/mrm.27101
- 发表时间:2018-06
- 期刊:
- 影响因子:3.3
- 作者:Novikov DS;Kiselev VG;Jespersen SN
- 通讯作者:Jespersen SN
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Els Fieremans其他文献
Els Fieremans的其他文献
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{{ truncateString('Els Fieremans', 18)}}的其他基金
International Society for Magnetic Resonance in Medicine (ISMRM) workshop on WHATEVER: WHite Matter, Analysis, Translation, Experimental Validation, Evaluation, and Reproducibility
国际医学磁共振学会 (ISMRM) 研讨会主题为:白质、分析、翻译、实验验证、评估和再现性
- 批准号:
10757846 - 财政年份:2023
- 资助金额:
$ 62.77万 - 项目类别:
Random Matrix Theory-Based Noise Removal in MRI
MRI 中基于随机矩阵理论的噪声消除
- 批准号:
10456777 - 财政年份:2019
- 资助金额:
$ 62.77万 - 项目类别:
Random Matrix Theory-Based Noise Removal in MRI
MRI 中基于随机矩阵理论的噪声消除
- 批准号:
10229483 - 财政年份:2019
- 资助金额:
$ 62.77万 - 项目类别:
Random Matrix Theory-Based Noise Removal in MRI
MRI 中基于随机矩阵理论的噪声消除
- 批准号:
10018721 - 财政年份:2019
- 资助金额:
$ 62.77万 - 项目类别:
Mesoscopic Biomarkers of Neurodegeneration with Diffusion MRI
弥散 MRI 神经退行性变的细观生物标志物
- 批准号:
8744985 - 财政年份:2014
- 资助金额:
$ 62.77万 - 项目类别:
Mesoscopic Biomarkers of Neurodegeneration with Diffusion MRI
弥散 MRI 神经退行性变的细观生物标志物
- 批准号:
9134909 - 财政年份:2014
- 资助金额:
$ 62.77万 - 项目类别:
Mesoscopic Biomarkers of Neurodegeneration and Inflammation with Diffusion MRI
弥散 MRI 神经退行性变和炎症的细观生物标志物
- 批准号:
10022344 - 财政年份:2014
- 资助金额:
$ 62.77万 - 项目类别:
Mesoscopic Biomarkers of Neurodegeneration and Inflammation with Diffusion MRI
弥散 MRI 神经退行性变和炎症的细观生物标志物
- 批准号:
10457453 - 财政年份:2014
- 资助金额:
$ 62.77万 - 项目类别:
Mesoscopic Biomarkers of Neurodegeneration and Inflammation with Diffusion MRI
弥散 MRI 神经退行性变和炎症的细观生物标志物
- 批准号:
10251994 - 财政年份:2014
- 资助金额:
$ 62.77万 - 项目类别:
TR&D 4: Revealing Microstructure: Biophysical modeling and validation for discovery and clinical care
TR
- 批准号:
9804443 - 财政年份:2014
- 资助金额:
$ 62.77万 - 项目类别:
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