Probing Microstructure Lengths Scales with Diffusion: Application

Joseph Ackerman¹
¹Washington University, United States

Synopsis

This didactic lecture will highlight illustrative measurements with physically-realizable model systems that provide simplifying parsimonious dMRI test platforms and deliver parameters useful for the modeling of microstructurally-complex real tissues. These dMRI test platforms will include: (i) perfused, cultured (in vitro), microbead-adherent HeLa cells; (ii) perfused, cultured (in vitro), microbead-adherent neurons and glia (aka, “brains-on-beads”); (iii) Xenopus laevis oocyte (aka, frog egg); and (iv) intracellular N-acetylaspartate (NAA) in rat brain in vivo.

Diffusion MRI (dMRI) has become the cornerstone of numerous protocols that are widely employed across many laboratories and clinics. The promise of dMRI is that, in principle, it provides subvoxel “resolution” of tissue microstructure at the micron scale via sensitivity to hindrances and restrictions to diffusion imposed by such microstructure. In practice, the tissue microstructure in even the smallest practically achievable MRI voxel is incredibly heterogeneous and complex. This complexity forces researchers to employ simplifying parsimonious dMRI signal models that seek to capture the most salient underlying microstructural properties.

An aphorism, generally attributed to the statistician George Box, is that “all models are wrong, but some are useful”. For example, dMRI signal models have provided powerful tools for white-matter track tracing and for assessing myelin and neuronal injury in human brain. More recently, dMRI signal models have been applied to provide an histology-like characterization of tissue microstructure vis-à-vis, for example, the presence of inflammation, macrophage infiltration, and necrosis.

In addition to employing simplifying parsimonious dMRI signal models, physically-realizable model systems can provide simplifying parsimonious dMRI test platforms. Such platforms can be leveraged to yield insight into specific questions and deliver parameters useful for the modeling of microstructurally-complex real tissues. (1, 2) For example, questions/parameters such as: (i) what is the free diffusivity – i.e., the diffusion constant in the absence of hindrances and restrictions to diffusion – of the intracellular milieu, or (ii) what is the average lifetime of intracellular water molecules – i.e., the intracellular pre-exchange lifetime – in the presence of ongoing transmembrane exchange with extracellular water, or (iii) does the water diffusivity in the intracellular or extracellular compartment, or both, decrease in cerebral injury?

This didactic lecture will highlight illustrative measurements with physically-realizable model systems that provide simplifying parsimonious dMRI test platforms and deliver parameters useful for the modeling of microstructurally-complex real tissues. These dMRI test platforms will include:

(i) Perfused, cultured (in vitro), microbead-adherent HeLa cells. (3, 4)

(ii) Perfused, cultured (in vitro), microbead-adherent neurons and glial cells (aka, “brains-on-beads”). (5)

(iii) Xenopus laevis oocyte (aka, frog egg). (6 - 9)

(iv) Intracellular N-acetylaspartate (NAA) in rat brain in vivo. (10)

Acknowledgements

No acknowledgement found.

References

1. "Biophysics of Diffusion in Cells”, J. J. H. Ackerman and J. J. Neil, “in Diffusion MRI: Theory, Methods and Applications (D Jones, ed.), Chapter 8, Pages 110-124, Oxford University Press, Oxford (2010).

2. “The Use of MR-detectable Reporter Molecules and Ions to Evaluate Diffusion in Normal and Ischemic Brain”, J. J. H. Ackerman, and J. J. Neil, NMR Biomed., 23: 725-733 (2010).

3. "Intracellular Water Specific MR of Microbead-adherent Cells: HeLa Cell Intracellular Water Diffusion", L. Zhao, A. L. Sukstanskii, C. D. Kroenke, J. Song, D. Piwnica-Worms, J. J. H. Ackerman, and J. J. Neil, Magn. Reson. Med., 59: 79-84 (2008).

4. "Intracellular Water Specific MR of Microbead-adherent Cells: The HeLa Cell Intracellular Water Exchange Lifetime", L. Zhao, C. D. Kroenke, J. Song, D. Piwnica-Worms, J. J. H. Ackerman, and J. J. Neil, NMR Biomed., 21: 159-164 (2008).

5. “Intracellular Water Preexchange Lifetime in Neurons and Astrocytes” D. M. Yang, J. E. Huettner, G. L. Bretthorst, J. J. Neil, J. R. Garbow, and J. J. H. Ackerman, Magn. Reson. Med., 79: 1616-1627 (2018).

6. “Water and Lipid MRI of the Xenopus Oocyte”, J. V. Sehy, J. J. H. Ackerman, and J. J. Neil, Magn. Reson. Med. 46: 900-906 (2001).

7. "The Apparent Diffusion Coefficient of Water, Ions, and Small Molecules in Xenopus Oocyte is Consistent with Brownian Displacement”, J. V. Sehy, J. J. H. Ackerman and J. J. Neil, Magn. Reson. Med., 48: 42-51 (2002).

8. "Evidence that both "Fast" and "Slow" Water ADC Components Arise from the Intracellular Space", J. V. Sehy, J. J. H. Ackerman and J. J. Neil, Magn. Reson. Med., 48: 765-770 (2002).

9. "Effects of Physiologic Challenge on the ADC of Intracellular Water of Xenopus Oocyte", J. V. Sehy, L. Zhao, J. Xu, H. J. Rayala, J. J. H. Ackerman, J. J. Neil, Magn. Reson. Med., 52: 239-247 (2004).

10. "On the Nature of the NAA Diffusion Attenuated MR Signal in the Central Nervous System", C. D. Kroenke, J. J. H. Ackerman, and D. A. Yablonskiy, Magn. Reson. Med., 52: 1052-1059 (2004).

Proc. Intl. Soc. Mag. Reson. Med. 28 (2020)