Quantitative Estimates of Myelin Volume Fraction from T2 and Magnetization Transfer

Kathryn L West^{1,2}, Nathaniel D Kelm^{1,2}, Daniel F Gochberg^{2,3}, Robert P Carson^{4}, Kevin C Ess^{4}, and Mark D Does^{1,2}

Mouse brains from control (n=6)
and two models of tuberous sclerosis complex (Rictor CKO, n=3 and TSC, n=3)
were perfusion-fixed and loaded with 1mM of Gadolinium (Magnevist) for high
resolution 3D Extended Phase Graph (EPG)-compliant MET_{2} and
inversion-recovery prepared 3D fast spin echo qMT studies at 15.2 T with
150µm isotropic resolution for both. Myelin water fraction (MWF) was obtained
from voxel-wise T_{2}-spectra fitting of MET_{2} data and bound
pool fraction (BPF) was extracted voxel-wise from qMT data as previously
described (6). Histology was performed using transmission electron microscopy on 4
regions of white matter from each brain. Histologic images were carefully
segmented to obtain measures of myelin volume fraction (*f*_{HIST}), as shown in Fig 1.

We use a four-pool model (Fig 2)
to describe the fractions of water and macromolecular protons in non-myelin (*a* and *b, *respectively) and myelin (*c*
and *d*, respectively) tissues. We
assume approximately equal proton densities in each pool (7) and *a + b + c + d* = 1, therefore
the myelin volume fraction = *c *+ *d*. Assuming no exchange of magnetization
between the myelin and non-myelin proton pools, MWF = *d*/(*b*+*d*), and from the standard binary spin pool qMT model, assuming identical biexponential recovery rates of longitudinal magnetization, BPF = *a*+*c*.
We then define *f*_{MET2} and *f*_{MT} as measures of myelin
volume fraction (i.e., = *c* + *d*) which
are expressible in terms of MWF and BPF, respectively.

Using literature values of water
mass fractions in myelin (*ρ _{m}* =

Similarly for qMT analysis, we first
use the linear correlation between BPF and *f*_{HIST}
(Fig 3), to determine the contribution of the non-myelin macromolecular proton
fraction (*a*) to BPF. Then, using water
mass fraction in myelin, *ρ _{m}*, again, the myelin volume fraction (

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Figure 1. Examples of quantiative histology analysis of (left) original transmission electron microscopy images to (right) segmented myelin images to obtain myelin volume fraction in (top) control, (middle) Rictor CKO, and (bottom) TSC animals.

Figure 2. Four-pool model of white matter containing water and macromolecular protons in non-myelin tissue (a and b, respectively) and water and macromolecular protons in myelin (c and d, respectively). Equations I-V describe the steps taken to obtain measures MWF and BPF comparable to histology based on the model.

Figure; 3. (Top) MWF (black x) and
BPF (blue dot) versus *f*_{HIST} and (bottom) *f*_{MET2 }(black x) and *f*_{MT} (blue dot) versus *f*_{HIST} with line of unity (gray, dashed).

Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)

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