In a groundbreaking study, researchers from the UMH-CSIC Neurosciences Institute have conceived of an innovative non-invasive approach to imaging the microglial and astrocyte activation in the gray matter of the brain using diffusion-weighted magnetic resonance imaging (dw-MRI), according to a press release by the institution published on Friday. The development may have applications in Alzheimer's and other dementias, Parkinson's, and multiple sclerosis.
The first signal from this type of MRI
"This is the first time it has been shown that the signal from this type of MRI (dw-MRI) can detect microglial and astrocyte activation, with specific footprints for each cell population. This strategy we have used reflects the morphological changes validated post-mortem by quantitative immunohistochemistry," noted Dr. Silvia de Santis and Dr. Santiago Canals, both from the Institute of Neurosciences UMH-CSIC.
The previous gold standard for imaging brain inflammation in vivo was positron emission tomography (PET). However, this process was difficult to generalize and was associated with exposure to ionizing radiation.
It was therefore reserved for use in vulnerable populations and in longitudinal studies. On the other hand, diffusion-weighted MRI has the unique ability to image brain microstructure in vivo noninvasively and with high resolution by capturing the random movement of water molecules in the brain parenchyma to generate contrast in MRI images.
A cohort of healthy humans at high resolution
The new approach was tested in a cohort of healthy humans at high resolution, "in which we performed a reproducibility analysis. The significant association with known microglia density patterns in the human brain supports the usefulness of the method for generating reliable glia biomarkers. We believe that characterizing, using this technique, relevant aspects of tissue microstructure during inflammation, noninvasively and longitudinally, can have a tremendous impact on our understanding of the pathophysiology of many brain conditions, and can transform current diagnostic practice and treatment monitoring strategies for neurodegenerative diseases," added Silvia de Santis.
The technique has further been found to be sensitive and specific for detecting inflammation with and without neurodegeneration so that both conditions can be differentiated. It also makes it possible to discriminate between inflammation and demyelination characteristics of multiple sclerosis.
To validate the model, the researchers used an established paradigm of inflammation in rats based on intracerebral administration of lipopolysaccharide (LPS) as well as an established paradigm of demyelination, based on focal administration of lysolecithin, to demonstrate that the biomarkers developed do not reflect the tissue alterations frequently found in brain disorders.
The novel method may just revolutionize the treatment of neurodegenerative diseases. The study is published in the journal Science Advances.
While glia are increasingly implicated in the pathophysiology of psychiatric and neurodegenerative disorders, available methods for imaging these cells in vivo involve either invasive procedures or positron emission tomography radiotracers, which afford low resolution and specificity. Here, we present a noninvasive diffusion-weighted magnetic resonance imaging (MRI) method to image changes in glia morphology. Using rat models of neuroinflammation, degeneration, and demyelination, we demonstrate that diffusion-weighted MRI carries a fingerprint of microglia and astrocyte activation and that specific signatures from each population can be quantified noninvasively. The method is sensitive to changes in glia morphology and proliferation, providing a quantitative account of neuroinflammation, regardless of the existence of a concomitant neuronal loss or demyelinating injury. We prove the translational value of the approach showing significant associations between MRI and histological microglia markers in humans. This framework holds the potential to transform basic and clinical research by clarifying the role of inflammation in health and disease.