Non-invasive Diagnostics and Treatment Monitoring of Ocular Disease Using Diffusion Weighted, Sodium and Chloride MRI of the Human Eye (ocularMRBIOPSY)

• Applicants: Dr. Ebba Beller; Professor Thoralf Niendorf, Ph.D.; Professor Oliver Stachs, Ph.D.
• Subject Area: Medical Physics, Biomedical Technology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 517901233

Sodium (23Na) and chloride (35Cl) content are considered key elements in numerous physiological processes in the eye, including the continuance of vitreous and aqueous humor, the constitution of the retina and the functionality of the optic nerve. In vivo assessment of 23Na and 35Cl content constitutes a particular challenge for the eye as the target region given the small organ size and the constraints of spatial resolution.To address this unmet clinical need, non-invasive imaging may provide markers that can inform on the different stages of pathophysiology, improve prediction and interception of ocular disease progression and to evaluate treatment. This proposal will conduct Magnetic Resonance Imaging (MRI)-based “virtual biopsies” to examine water diffusion and 23Na and 35Cl content of the eye. We will test the hypothesis that in vivo diffusion-weighted, 23Na and 35Cl MRI of the eye will increase the capabilities and the accuracy of non-invasive diagnostics and treatment monitoring of ocular melanoma and glaucoma. To advance the field of MR for imaging ocular disease, we will use a cross-domain approach, combining expertise in ophthalmology, radiology, imaging science, (bio)physics, (bio)engineering, physiology, forensics and data sciences. To test our hypothesis, we will implement novel magnetic resonance (MR) hardware and radiofrequency (RF) antennae enabling in vivo 35Cl and 23Na MRI of the eye at 7.0 T. We will develop innovative MR imaging technology allowing high resolution morphological, diffusion-weighted and 23Na and 35Cl MRI of the eye. To circumvent the challenges related to eye motion and degradation of image quality, we will focus on real time motion tracking and compensation in this work. To eliminate extra susceptibility-induced T2* shortening, an array of local B0-shim coils will be implemented to improve the magnetic field homogeneity in the region of the eye and orbit. This novel technology and methodology will be integrated and carefully validated in phantom studies, and subsequently applied for the first time in a feasibility study in healthy subjects, as a prelude to clinical studies. For swift translation we will conduct pilot clinical studies in two cohorts: patients with ocular melanoma who receive plaque brachytherapy-based radiotherapy for treatment and patients with glaucoma. These measures are essential for accomplishing the goal to provide guidance in diagnostic assessment and treatment of ophthalmological diseases based on in vivo diffusion weighted, 35Cl and 23Na MRI of the eye. The outcome of this project will provide a novel approach of using MR to conduct “virtual biopsies” that can reveal early, subclinical indications of ocular disease and monitor the effects of therapies. These results will provide a springboard for next generation ophthalmic MRI applications based on x-nuclei MR biomarkers that can quickly be moved into the clinic.

• DFG Programme: Research Grants