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The fine-scale structure of brain tissue is crucial to neural function and health. We are developing MRI techniques that may enable non-invasive estimates of brain microstructure.

Axons in white matter measured by electron microscopy form the basis of detailed MRI signal simulations [by Michiel Kleinnijenhuis]

Member of the public? Check out the video at the bottom of this page.

The microscopic structure of brain tissue plays a key role in neural function and health: the shape, density and size of cellular and sub-cellular structures are all carefully regulated in health, and often implicated in disease. Since the late 1800s, these properties have been studied with microscopy, following an invasive tissue extraction. Our goal is to estimate microstructural properties non-invasively in living subjects using MRI, which could revolutionize our ability to study neuronal disease and health.

While MRI is unlikely to ever actually resolve cellular structures in living humans, it is exquisitely sensitive to the micro-environment of water molecules. This gives MRI the potential to detect and quantify the statistics of microstructure: how on average does a micrometer-level property of tissue vary from millimeter to millimeter in the brain?

We are developing methods that are sensitive to microstructure using a range of MRI contrast mechanisms, including diffusion, relaxometry and susceptibility-based contrast. We are developing biophysical models that relate measurements of these contrast properties to microstructural properties of interest. And we are relating MRI measurements using these contrasts to microscopy measurements, both for validation and to provide novel insight into MRI signals

A major thrust in our research is to acquire MRI measurements in post-mortem tissue that is later subjected to invasive microscopy. Examples of this approach include:

  • Many-to-many mappings between multi-modal MRI signals and a range of immunohistochemistry stains.
  • Estimation of the relative contributions of different changes to tissue microstructure, such as iron deposition and myelin loss, to MRI signal changes in pathology.
  • Validation of sophisticated biophysical models, such as fibre dispersion estimates from diffusoin MRI.
  • Joint modeling of MRI and microscopy to resolve measurement ambiguities and investigate model assumptions.

View our publications.

This research is conducted as part of the Physics Group at the Wellcome Centre for Integrative Neuroimaging.

Below: Watch Ben Tendler explains his research in microstructural imaging.



Selected publications