I have been working with diffusion over 2 years in developing new techniques for diffusion MRI, and the major challenge that I see is definitely relating the water diffusion with features of tissue microstructure. Diffusion MRI is a complex inverse problem. Different tissue configurations can origin the same diffusion parameters. Furthermore, some features of water diffusion cannot be directly related to microstructural features. Only to mentioned a small example, simulations have shown deviations between the ODF maximums and the actual fibre direction (Zhan and Yang, 2006). Image noise and artefact can also originate bias on diffusion estimates (as you had shown is several studies in the last years). Moreover, another factor that increases the complexity of relating diffusion metrics with microstructural features is the resolution limit of current MRI scanners. Another important challenge is to develop techniques for mining and relating the relevant diffusion MRI advances. Since work on diffusion MRI is increasing exponentially, finding relevant background for our studies is being harder and harder.

As futures directions I see advances in giving diffusion metrics an biological interpretation by exploring newly developed biological models (e.g. Nilsson et al. 2013). Diffusion studies using high resolution schemes (e.g. Dell'Aqua et al. 2013) can also reveal new insights of microstructures that could be useful to define prior knowledge to solve the inverse problem of diffusion MRI and to correct some bias on diffusion estimates.  These two mentioned advances can also be useful to derive new metrics that will be more robust biomarkers for tissue changes (on maturation and degeneration processes). These metrics could also be used to improve tractography techniques. Tractography might also be improved by debugging it using newly developed phantoms, histological data and other techniques as 3D polarized light imaging and CLARITY. Development of new MRI sequences will also be important to bring the more advanced diffusion techniques to protocols that could be used in clinical applications.  Finally, applying techniques of bioinformatic to relate the current knowledge about diffusion MRI and make predictions about diffusion changes on maturation, ageing and pathological conditions will be useful.

I hope that I was useful.

Best Regards,

Rafael Henriques

References

Nilsson, M., van Westen, D., Stahlberg, F., Sundgren, P.C., Latt, J., 2013, The role of tissue microstructure and water exchange in biophysical modelling of diffusion in white matter, Magn Reson Mater Phy 26(4): 345-70. doi: 10.1007/s10334-013-0371-x

Dell'Aqua, F., Bodi, I., Slater, D., Catani, M., Modo, M., 2013, MR Diffusion Histology and Micro-Tractography Reveal Mesoscale Features of the Human Cerebellum, The Cerebullum. doi:10.1007/s12311-013-0503-x 

Zhan, W., Yang, Y. 2006, How accurately can the diffusion profiles indicate multiple fiber orientations? A study on general fiber crossings in diffusion MRI, Journal of Magnetic Resonance 183: 193-202