Non-invasive staining of tissue microstructure in temporal lobe epilepsy using in- vivo MRI

Introduction

Ex-vivo histology is the gold standard to investigate human brain microstructure. However, its invasive nature precludes its use in monitoring disease progression and the investigation of the pathophysiological origin of neurological disorders.

Project Overview

MRStain will address this shortcoming by exploiting the sensitivity of the Magnetic Resonance Imaging (MRI) signal to estimate aggregated histological metrics in the human brain non-invasively. Like established histology staining methods (e.g., myelin-basic protein), MRStain will be sensitive to changes in:

• Cellular populations
• Axons
• Myelin
• Iron

This will be achieved by augmenting the MRI measurements with computational biophysical models, which can disentangle tissue metrics at the micron-scale using the macroscopic spatial resolution (1–4 mm) of MRI. However, the clinical use of these models has not been employed because their validity and generalizability across disease trajectories has yet to be tested against the ex-vivo histological gold standard.

Dataset Generation

This project will address this shortcoming by generating a globally unique multi-modal dataset that combines:

1. Novel in-vivo MRI techniques
2. Ex-vivo MRI techniques
3. Biophysical models
4. Cutting-edge large-scale 3D histology

The project will benefit from a unique translational university hospital environment where large sections of freshly excised brain tissue from drug-resistant temporal lobe epilepsy patients (TLE, 80 sections of about 3 x 2 x cm^3) can be examined. This enables in-vivo MRI-based biophysical tissue parameters to be validated against their histological gold standard.

MRStain Model Development

I will develop an MRStain model to identify TLE relevant changes that will achieve a paradigm shift in how epilepsy is treated. This model will help identify target brain areas for surgery that will assist in predicting seizure-free outcomes after surgery.

Future Implications

The final validated MRStain models will also pave the way for similar non-invasive investigations of other neuropsychiatric diseases with unprecedented precision.