Quantifying the local tissue volume and composition in individual brains with magnetic resonance imaging


Here, we describe a quantitative neuroimaging method to estimate the macromolecular tissue volume (MTV), a fundamental measure of brain anatomy. By making measurements over a range of field strengths and scan parameters, we tested the key assumptions and the robustness of the method. The measurements confirm that a consistent quantitative estimate of MTV can be obtained across a range of scanners. MTV estimates are sufficiently precise to enable a comparison between data obtained from an individual subject with control population data. We describe two applications. First, we show that MTV estimates can be combined with T1 and diffusion measurements to augment our understanding of the tissue properties. Second, we show that MTV provides a sensitive measure of disease status in individual patients with multiple sclerosis. The MTV maps are obtained using short clinically appropriate scans that can reveal how tissue changes influence behavior and cognition.

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Figure 1: Assessment of MTV fraction accuracy and reliability.
Figure 2: The MTVF and dissimilarity index (DI) in different brain regions.
Figure 3: The mean MTVF values near the midline of three callosal tracts.
Figure 4: Corticospinal tract (CST) measurements in controls and two individuals with multiple sclerosis.
Figure 5: The relationship between T1 and WVF in white matter.


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We acknowledge J. Barral, M. Gutman, H. Horiguchi, I. Levesque, A. Sherbondy and A. Takahashi for helpful advice and feedback. We thank S. Phipps, I. Levesque and A. Kerr for help in data analysis and acquisition. This work was supported by the US National Institutes of Health research grants RO1-EY15000 and NSF grant BCS-1228397. A.M. is the recipient of support from the Human Frontier Science Program and a Jewish Community Federation Program Machiah Foundation Fellowship. N.-J.C. is the recipient of support from the Singapore National Research Foundation (NRF-NRFF2011-01).

Author information

A.M. and B.A.W. developed the method, wrote the manuscript and prepared the figures. J.D.Y., N.S., M.L.P., R.F.D., K.B.-P. and A.M. obtained the data. N.-J.C. provided the lipid phantoms. N.S., R.F.D., K.N.K. and A.M. developed analysis tools. J.P. and L.H.H. diagnosed the patient with multiple sclerosis and enabled those scans. A.M. and J.D.Y. developed the diffusion methods and applications. B.A.W. provided equipment and administered the experiment. All authors reviewed the manuscript.

Correspondence to Aviv Mezer.

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Competing interests

Stanford University has filed a US patent application describing the technology used to measure PD, T1, MTV, VIP and SIR in this study (A.M., R.F.D. and B.A.W.).

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Supplementary Table 1, Supplementary Figures 1–12, Supplementary Discussion and Supplementary Data. (PDF 3092 kb)

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Mezer, A., Yeatman, J., Stikov, N. et al. Quantifying the local tissue volume and composition in individual brains with magnetic resonance imaging. Nat Med 19, 1667–1672 (2013). https://doi.org/10.1038/nm.3390

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