Understanding the mechanisms of atrophy associated with spinal cord injury: the application of MRI-based in vivo histology and ex vivo histology (call "ERA-Net NEURON" 2016)
Spinal cord injuries (SCI) are typically caused by traumatic events such as traffic and sports accidents. SCIs are devastating, life changing, often lead to paralysis, and have long-term health, economic, and social impact. After a traumatic SCI, extensive morphometric (i.e. volumetric) changes within the central nervous system occur above the level of the lesion, throughout the first year after injury. Paraplegia (leg paralysis) and tetraplegia (both leg and arm paralysis) permanently and severely reduce the quality of life of the affected person as well as their ability to remain a member of the workforce. These negative consequences arise because functional recovery, following SCI, remains limited and the majority of patients are left with severe impairments in the long term. While rehabilitative training can improve clinical outcome following SCI, which is of major benefit to the patients' quality of life, the degenerative processes as well as the mechanisms underpinning any neurological and functional recovery are not well understood.
Recent discoveries have improved our understanding of central nervous system regeneration and functional recovery in animal models of SCI. Some of these may translate into treatments which benefit patients, but their success depends on carefully designed clinical trials. Consequently, there is a present need to develop non-invasive (neuroimaging) biomarkers and relate them to underlying microscopic tissue properties and the ensuing disability. Such biomarkers can help us to understand disease processes because they can track tissue changes across course of the disease.
Non-invasive, advanced magnetic resonance imaging (MRI) technologies have been successful in revealing structural changes, such as atrophy, thereby improving our comprehension of brain disorders. Recent studies have demonstrated the feasibility of applying such techniques above the local injury site (i.e. in the brain) in patients with SCI. By means of in vivo histology using MRI (hMRI) - an emerging subfield - we aim to establish the missing link between measured MRI signals and structural changes in the brain. This will help us to explain and better understand the disease processes associated with spinal cord injury. In addition, advanced biophysical models will be developed to understand (micro‑)structural processes underlying the observed morphometric changes.
At present, we are developing multi-parameter mapping (MPM) and diffusion weighted imaging (DWI) acquisition protocols that maximize the signal to noise ratio (SNR) and the image quality in the somatomotor cortex and the corticospinal tract. Specifically, MPM is being optimized to minimize off-resonance artifacts and radio-frequency (RF) transmit field inhomogeneities, while maintaining high spatial resolution. The DWI optimization includes SNR, spatial resolution, diffusion weighting/b-factors, and artefact level. To provide sufficient SNR we are developing pulse sequences with non-cartesian readout and actual trajectory measurement, taking advantage of the Institute's 3T Siemens CONNECTOM MRI with 300 mT/m gradient amplitudes and Skope field camera system.
This project was funded from 2017 until 2020 by the Federal Ministry of Education and Research (BMBF) of the Federal Republic of Germany.