MMDTIAN

Multi-modal Diffusion Tensor Imaging of Active Neurons: Searching for Functional and Other Biophysical Components

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 Obiettivo del progetto (Objective)

'Diffusion Tensor Imaging (DTI) is a central tool in brain research and in the clinical neurological diagnosis. Despite its popularity in research and in clinical applications, the biophysical mechanisms underlying DTI are not fully understood. For example, with respect to essential parameters such as the amplitude of change of the apparent displacement post insults, the orientation of maximal change and its timing, theoretical models of displacement fail to describe the kinetics of water displacement following insults. Moreover, it was suggested that neuronal activity can directly modify the diffusion weighted MR signal to provide functional images with high temporal and spatial resolution. Our working hypothesis is that water displacement that occurs due to active cellular mechanisms, contributes significantly to the signal measured in DTI. We are interested in quantifying the contribution of various cellular events to the signal measured in DTI, where a pivotal mechanism that will explored is the suggested water displacement that is linked with neuronal activation. To address the limits of detectability of neuronal excitation via MR, we suggest employing a three-source, multi-modal system: MRI, electrical potential mapping and fluorescence microscopy of neuronal organotypic cell cultures. The use of organotypic cultures bypasses major sources of physiological artifacts such as blood flow and pulsation. MRI is performed with a low-field open MRI system. Electrical recordings will be performed simultaneously with a multi-electrode array system that will provide 2-D ‘imaging’ of neuronal electrical activity and optical microscopy will allow imaging of Calcium release. This multi-modal imaging system will allow testing previously proposed mechanisms of neural detection by MRI and will provide a test-bed to enable us to develop new ones.'

Introduzione (Teaser)

Microstructural tissue changes related to development, ageing and disease processes affect the diffusion of water. Scientists investigated and employed an important new imaging technique that exploits this phenomenon with pioneering outcomes.

Descrizione progetto (Article)

Diffusion tensor imaging (DTI) is a magnetic resonance imaging-based technique. It can be used to map the diffusion of water in three dimensions as a function of spatial location and to describe differences in diffusion rate along all three axes (anisotropy).

Despite its growing popularity for research and clinical applications, the actual mechanisms affecting the diffusion tensor are not clear. Theoretical models of displacement fail to predict the water movement and some reports have suggested that neuronal activity can modify it.

With EU funding, the project MMDTIAN employed three different types of imaging on neuronal cell culture to investigate that possibility. The use of organotypic cell cultures having more than one cell type in a 3D tissue network mimics the in situ situation without noise from blood flow.

The unique experimental paradigm employed excised vital newborn rat spinal cord. Researchers showed for the first time that enhanced neural activity affects water displacement in a way that is not merely a side-effect of blood oxygenation levels, supporting a potential mechanical role. This groundbreaking demonstration won several awards for innovation and led to an important publication in a peer-reviewed scientific journal.

In addition to biomedical applications, diffusion plays a role in many industrial devices. The team developed a novel method to estimate pore size distribution from multiple diffusion-weighted nuclear magnetic resonance (NMR) imaging measurements. It provides access to experiments and results previously not achievable and has also led to several publications, including one for applications to porous polymers.

Finally, the team developed faster and better imaging using an inexpensive, mobile unilateral NMR scanner. The mobile NMR led to several papers and is currently being used in a clinical application through another project.

The MMDTIAN project has significantly advanced our understanding of the mechanisms behind an important new imaging technique, DTI, and applied it with impressive results. Outcomes are touching a variety of fields and opening a new window on the world around us.