Singlet Assisted Diffusion Tensor Imaging (SAD-TI)

Lead Research Organisation: University of Southampton
Department Name: School of Chemistry

Abstract

Diffusion tensor imaging (DTI) is a magnetic resonance modality that provides unique biologically and clinically important information not available via other modalities, including microstructure and fibre orientation mapping. DTI, for example, is used in tractography to visualize anatomic connections between different parts of the brain.
DTI uses a combination of radiofrequency and magnetic field gradient pulses to determine the diffusion tensor of a substance in a medium (in clinical MRI is the diffusion tensor of water in tissues). The whole tensor, and not only the diffusion constant, is sought since diffusion is anisotropic in a medium where the microstructure can infer confinement. By plotting the value of the trace of the diffusion tensor voxel-by-voxel it is then possible to obtain anatomical images where the diffusion of water in different tissues is used as contrast. These images can report on anomalies associated with diseases.
DTI (as many other NMR technique) relies on the memory of spin states. These need to survive enough time for the molecule to diffuse in the medium and experience the confinement (no confinement would mean isotropic diffusion). Typically, spin memory is preserved for between a few millisecond and a few seconds. In such short time molecules can only travel up to ~100 and thus only structure of this size and below can infer enough confinement so that diffusion appears anisotropic in DTI experiments.
In my laboratory, we have recently developed [1-3] an NMR methodology to overcome such limitation and therefore be able to prolong spin memory for many minutes so to detect confinement in structures of up to 2 mm [2] or probe the tortuosity of the medium as experienced by molecules traveling for millimetres across many pores [3]. We dubbed the technique as singlet-assisted diffusion NMR (SAD-NMR) since singlet is the spin state with a long lifetime.
The PhD student will to extend this methodology into the field of DTI. The extended diffusion time available after incorporation of the SAD-NMR method into DTI (SAD-TI) will not only allow the characterisation of the diffusion tensor components with greater accuracy than what currently available, but also, and more interesting, will allow the possibility to visualise connections between large channels, fibres or pores in porous media, including biological tissues. In particular we will apply this technique to study the diffusion of nutrients inside 3D printed scaffoldings holding cells (sample provided by collaborators at QUT in Brisbane, AU). These scaffoldings are under development for tissue engineering purposes but as the cells grow along the support the channels close up and a necrotic core develops. The dimension of those channels (0.5-1 mm) are well above what currently measurable with DTI. The SAD-TI method will instead provide unprecedented data to be used to inform the design of next-generation scaffold architecture.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/R513325/1 30/09/2018 29/09/2023
2155181 Studentship EP/R513325/1 02/01/2019 30/03/2022 Giulia Melchiorre