Microstructural brain changes often precede more obvious tissue damage in many progressive neurodegenerative diseases, but until now, conventional magnetic resonance imaging (MRI) could not ‘see’ them. Innovative MRI methodologies make this possible, paving the way to earlier diagnosis and treatment that could halt disease progression at much earlier stages.

MRI is a non-invasive imaging technique that creates detailed images of tissues and organs in awake patients. It is extensively used in brain imaging, enabling visualisation of the atrophy (decrease in size) of specific brain regions and the presence of ‘lesions’ in brain tissues that characterise many neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease (PD) and multiple sclerosis (MS).

Microstructural changes such as the loss of myelin sheaths often precede atrophy and lesions, but they are not visible using conventional MRI. With the support of the Marie Skłodowska-Curie programme, the MICROBRADAM project developed novel MRI techniques to overcome these barriers and improve patient outcomes.

Faulty wiring across distances

Information transmission between neurons relies largely on the propagation of action potentials in the axons of ‘sending’ neurons toward ‘receiving’ ones. The axons are surrounded by a fatty myelin sheath, much like electrical cable insulation that prevents signal loss over distances and enhances the transduction speed. The brain is characterised by large-scale network systems that involve many specialised areas. Without myelin, the brain cannot work, because long-distance interaction between brain areas is not possible. Many progressive brain diseases affect myelination, ultimately disrupting the integrity of neurotransmission.

Slower is better when it comes to small structures

Despite its critical role in neurodegenerative diseases, direct myelin imaging is currently only possible with invasive procedures. Project coordinator Federico Giove of the Enrico Fermi Centre for Study and Research (site in Italian) explains: “Conventional MRI exploits fast dynamics of water molecules subjected to a magnetic field. Our novel methodology capitalises on an enhanced sensitivity to slower motional regimes of water molecules that can better probe the intricate microstructure of the tissue and thus reveal myelin damage.”

Preclinical and clinical benefits for neurodegenerative diseases

MICROBRADAM’s MRI methodologies can detect subtle abnormalities in grey and white matter that characterise PD and MS, which are not accessible with conventional MRI; they potentially enable earlier detection and better monitoring of disease development and/or therapy effects. Serendipitously, they also demonstrated substantially reduced sensitivity to metal electrodes; this sensitivity affects the quality of functional MRI (fMRI) images when fMRI relies on implanted electrodes. As a result, scientists were able to develop innovative neurostimulation approaches to detect the functional effects of deep brain stimulation (DBS). They are now perfecting novel paradigms to deliver DBS and spinal cord stimulation, targeting pathways of interest in PD, depression, pain and spinal cord injury. Two patent applications have been submitted by partners.

“Perhaps most exciting, a new method was very effective in early-stage MS diagnosis and characterisation. Although patient outcomes depend on both early diagnosis and effective treatment, the effectiveness is often dramatically improved by early diagnosis. Drugs to stop degenerative disease progression are on the horizon, making early diagnosis even more valuable,” says Giove. The team has made great progress in establishing new MRI modalities to detect subtle changes in brain tissue, potentially even before disease symptoms appear. Aside from improving clinical outcomes, MICROBRADAM approaches should foster faster development of drugs and treatments targeting demyelination.