Microstructural Characterization of the Optic Nerve in Optic Neuritis

视神经炎视神经的微观结构特征

• 批准号: 9235287
• 负责人: Seth A Smith
• 金额: $ 26.42万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-03-01 至 2020-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9235287
• 关键词: Acute; Address; Anisotropy; Biochemistry; Biological Markers; Brain; Chemicals; Clinical; Congestive; Defect; Deposition; Development; Diagnosis; Diffuse; Diffusion Magnetic Resonance Imaging; Disease Management; Early Intervention; Environment; Evaluation; Event; Evolution; Functional disorder; Goals; Health; Human; Image; Image Analysis; Inflammation; Knowledge; Lesion; Location; MRI Scans; Magnetic Resonance Imaging; Malignant Neoplasms; Measures; Metabolic; Methods; Microscopic; Modality; Modeling; Morphologic artifacts; Motion; Multiple Sclerosis; Myelin; National Institute of Biomedical Imaging and Bioengineering; Nerve; Neuraxis; Neuroglia; Neurologic; Noise; Ophthalmology; Ophthalmoscopy; Optic Nerve; Optic Neuritis; Pathologic; Pathology; Patients; Peptides; Physiologic pulse; Prognostic Marker; Proteins; Radiology Specialty; Recovery; Resolution; Risk; Risk stratification; Signal Transduction; Spinal Cord; Statistical Models; Stratification; Stroke; Structure; Surrogate Markers; Symptoms; Techniques; Thick; Time; Tissues; United States National Institutes of Health; Vision; Visual; Visual evoked cortical potential; cohort; design; experience; healthy volunteer; human imaging; imaging approach; imaging modality; improved; in vivo; indexing; innovation; insight; magnetic resonance imaging biomarker; multiple sclerosis patient; myelination; myoinositol; neurochemistry; novel; optical imaging; outcome forecast; patient stratification; predictive modeling; prognostic; public health relevance; research clinical testing; retinal nerve fiber layer; targeted imaging; tool; treatment trial; visual performance

DESCRIPTION (provided by applicant): The overall goal of this proposal is to develop and implement novel, multi-modal magnetic resonance imaging (MRI) in the human optic nerve capable of understanding the relationship between optic neuritis (ON) and the evolution of visual (dys)function and clinical evaluation. We further propose that quantitative MRI methods sensitive to tissue microstructure (myelin and axonal integrity) and biochemistry can be utilized in prediction models to offer insight into the eventual development of multiple sclerosis (MS). Recent studies have shown that optic neuritis is the initial symptom in 17-25% of all MS cases though visual function and inflammation generally resolves in 4 to 12 weeks. Additionally, nearly two thirds of MS patients will experience episodes of optic neuritis in their lifetimes, and 40-60% of MS patients have visual defects localized to the optic nerve. Ophthalmological and conventional MRI evaluation demonstrates inflammation along the optic nerve, but long- term prognosis has been challenging. We hypothesize the reason for this paradox is that conventional MRI is insensitive to tissue composition (axonal, myelin, or neurochemical) throughout the recovery course. While advanced MRI methods have been developed to assess large structures of central nervous system, relatively few have been applied in the optic nerve due to its size, location, and motion. However, recent innovations of MRI hardware and sequence design have yielded an opportunity to study new imaging modalities in the optic nerve. Importantly, these techniques offer unprecedented non-invasive access to the entire optic nerve with indices sensitive to axonal and myelin integrity, macro-molecular arrangement, and neurochemical composition. We hypothesize that characterizing the neurological substrates of optic nerve damage resulting from ON is critical for improving our understanding of the earliest relationships between ON and MS. Significantly, these tools may provide an opportunity for earlier intervention, and enhancing disease management. We have demonstrated the feasibility of new, non-invasive MRI approaches to quantitatively assess the optic nerve and we will integrate for the first time a set of tools that are sensitive to the microstructural integrit, myelination, and neurochemical composition of the optic nerve in patients with ON. We will utilize advanced statistical modeling to parse out the association of these MRI indices to visual function and the relationship to clinical and quantitative ophthalmological measures. Lastly we will build predictive models to determine the relationship between novel MRI measures and the personal risk of developing MS from a single ON event. In appreciation of a K01 which provided the opportunity to develop advanced MRI of the human optic nerve, we now possess a unique toolbox to assess the multiple neuropathological substrates of ON in a single MRI scanning session even after resolution of inflammation, which we hypothesize will offer insight into the temporal evolution of ON.

描述（由申请人提供）：该提案的总体目标是在人类视神经中开发和实施新型多模态磁共振成像（MRI），能够理解视神经炎（ON）与视觉进化之间的关系功能（障碍）和临床评估。我们进一步提出，对组织微观结构（髓磷脂和轴突完整性）和生物化学敏感的定量 MRI 方法可用于预测模型，以深入了解多发性硬化症 (MS) 的最终发展。最近的研究表明，视神经炎是所有 MS 病例中 17-25% 的首发症状，尽管视觉功能和炎症通常会在 4 至 12 周内消退。此外，近三分之二的多发性硬化症患者一生中会经历视神经炎发作，40-60% 的多发性硬化症患者存在局限于视神经的视觉缺陷。眼科和常规 MRI 评估显示视神经有炎症，但长期预后一直具有挑战性。我们假设这种悖论的原因是传统的 MRI 对整个恢复过程中的组织成分（轴突、髓磷脂或神经化学物质）不敏感。虽然先进的 MRI 方法已被开发用于评估中枢神经系统的大型结构，但由于其大小、位置和运动，在视神经中的应用相对较少。然而，MRI 硬件和序列设计的最新创新为研究视神经的新成像方式提供了机会。重要的是，这些技术提供了前所未有的对整个视神经的非侵入性访问，其指标对轴突和髓磷脂完整性、大分子排列和神经化学成分敏感。我们假设，表征 ON 引起的视神经损伤的神经学基质对于提高我们对 ON 和 MS 之间最早关系的理解至关重要。值得注意的是，这些工具可能为早期干预和加强疾病管理提供机会。我们已经证明了新的非侵入性 MRI 方法定量评估视神经的可行性，并且我们将首次集成一套对患者视神经的微观结构完整性、髓鞘形成和神经化学成分敏感的工具与ON。我们将利用先进的统计模型来解析这些 MRI 指数与视觉功能的关联以及与临床和定量眼科测量的关系。最后，我们将建立预测模型来确定新的 MRI 测量与单次 ON 事件患 MS 的个人风险之间的关系。由于 K01 为开发人类视神经的先进 MRI 提供了机会，我们现在拥有一个独特的工具箱，即使在炎症消退后，也可以在单次 MRI 扫描过程中评估视神经炎的多种神经病理学底物，我们假设这将提供洞察 ON 的时间演变。

项目成果

Application and evaluation of NODDI in the cervical spinal cord of multiple sclerosis patients.

• DOI: 10.1016/j.nicl.2017.05.010
• 发表时间: 2017
• 期刊: NeuroImage. Clinical
• 作者: By S;Xu J;Box BA;Bagnato FR;Smith SA
• 通讯作者: Smith SA

Automatic segmentation of the spinal cord and intramedullary multiple sclerosis lesions with convolutional neural networks.

• DOI: 10.1016/j.neuroimage.2018.09.081
• 发表时间: 2019-01-01
• 期刊: NeuroImage
• 影响因子: 5.7
• 作者: Gros C;De Leener B;Badji A;Maranzano J;Eden D;Dupont SM;Talbott J;Zhuoquiong R;Liu Y;Granberg T;Ouellette R;Tachibana Y;Hori M;Kamiya K;Chougar L;Stawiarz L;Hillert J;Bannier E;Kerbrat A;Edan G;Labauge P;Callot V;Pelletier J;Audoin B;Rasoanandrianina H;Brisset JC;Valsasina P;Rocca MA;Filippi M;Bakshi R;Tauhid S;Prados F;Yiannakas M;Kearney H;Ciccarelli O;Smith S;Treaba CA;Mainero C;Lefeuvre J;Reich DS;Nair G;Auclair V;McLaren DG;Martin AR;Fehlings MG;Vahdat S;Khatibi A;Doyon J;Shepherd T;Charlson E;Narayanan S;Cohen-Adad J
• 通讯作者: Cohen-Adad J

Amide proton transfer CEST of the cervical spinal cord in multiple sclerosis patients at 3T.

• DOI: 10.1002/mrm.26736
• 发表时间: 2018-03
• 期刊: Magnetic resonance in medicine
• 影响因子: 3.3
• 作者: By S;Barry RL;Smith AK;Lyttle BD;Box BA;Bagnato FR;Pawate S;Smith SA
• 通讯作者: Smith SA

Quantifying the impact of underlying measurement error on cervical spinal cord diffusion tensor imaging at 3T.

• DOI: 10.1002/jmri.25308
• 发表时间: 2016-12
• 期刊: JOURNAL OF MAGNETIC RESONANCE IMAGING
• 影响因子: 4.4
• 作者: By, Samantha;Smith, Alex K.;Dethrage, Lindsey M.;Lyttle, Bailey D.;Landman, Bennett A.;Creasy, Jeffrey L.;Pawate, Siddharama;Smith, Seth A.
• 通讯作者: Smith, Seth A.

Dynamic Imaging of the Eye, Optic Nerve, and Extraocular Muscles With Golden Angle Radial MRI.

• DOI: 10.1167/iovs.17-21861
• 发表时间: 2017-08-01
• 期刊: Investigative ophthalmology & visual science
• 影响因子: 4.4
• 作者: Sengupta S;Smith DS;Smith AK;Welch EB;Smith SA
• 通讯作者: Smith SA