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.
Optic neuritis (ON) is often the presenting symptom in patients who develop multiple sclerosis (MS) with nearly 70% of patients with MS having at least one episode of ON in their lifetime. While ophthalmoscopy and conventional MRI can offer evidence to diagnose an event of ON, there is a paradox in that MRI struggles offer a prognosis of the permanence (or recovery) of visual dysfunction or ultimately the risk of developing MS. Recently developed, quantitative MRI approaches offer insight into the microscopic environment of the central nervous system by showing sensitivity to myelin, axonal integrity, inflammation, and neurochemical aberrations, and we hypothesize that a targeted, microstructural-specific set of MRI parameters can address the paradox between radiological presentation and prognosis of visual recovery.
|Dortch, Richard D; Bagnato, Francesca; Gochberg, Daniel F et al. (2018) Optimization of selective inversion recovery magnetization transfer imaging for macromolecular content mapping in the human brain. Magn Reson Med 80:1824-1835|
|By, Samantha; Barry, Robert L; Smith, Alex K et al. (2018) Amide proton transfer CEST of the cervical spinal cord in multiple sclerosis patients at 3T. Magn Reson Med 79:806-814|
|Gros, Charley; De Leener, Benjamin; Dupont, Sara M et al. (2018) Automatic spinal cord localization, robust to MRI contrasts using global curve optimization. Med Image Anal 44:215-227|
|By, Samantha; Xu, Junzhong; Box, Bailey A et al. (2018) Multi-compartmental diffusion characterization of the human cervical spinal cord in vivo using the spherical mean technique. NMR Biomed 31:e3894|
|Trujillo, Paula; Summers, Paul E; Smith, Alex K et al. (2017) Pool size ratio of the substantia nigra in Parkinson's disease derived from two different quantitative magnetization transfer approaches. Neuroradiology 59:1251-1263|
|Sengupta, Saikat; Smith, David S; Smith, Alex K et al. (2017) Dynamic Imaging of the Eye, Optic Nerve, and Extraocular Muscles With Golden Angle Radial MRI. Invest Ophthalmol Vis Sci 58:4390–4398|
|Harrigan, Robert L; Smith, Alex K; Mawn, Louise A et al. (2017) Improved Automatic Optic Nerve Radius Estimation from High Resolution MRI. Proc SPIE Int Soc Opt Eng 10133:|
|Smith, Alex K; By, Samantha; Lyttle, Bailey D et al. (2017) Evaluating single-point quantitative magnetization transfer in the cervical spinal cord: Application to multiple sclerosis. Neuroimage Clin 16:58-65|
|Smith, Alex K; Dortch, Richard D; Dethrage, Lindsey M et al. (2017) Incorporating dixon multi-echo fat water separation for novel quantitative magnetization transfer of the human optic nerve in vivo. Magn Reson Med 77:707-716|
|By, Samantha; Xu, Junzhong; Box, Bailey A et al. (2017) Application and evaluation of NODDI in the cervical spinal cord of multiple sclerosis patients. Neuroimage Clin 15:333-342|
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