Synopsis
The
enhanced inhomogeneous magnetization transfer (ihMT) in certain tissues,
especially white matter, has recently been explained as a result of longer dipolar
relaxation times, T1Ds in
those tissues. Measurement of T1D
by modeling the frequency and power dependence of steady state ihMT has yielded
T1D estimates but with
great uncertainty. Here we introduce a dynamic ihMT experiment that switches
between positive and negative frequency irradiation at varying times. Fits to
the ihMT signal decay curve as a function of switching time at one (absolute) offset
frequency and power enabled highly precise mapping of T1D that was largely independent of other MT parameters.
A T1D of 6.4±0.5ms for
white matter was in good agreement with reported ex-vivo measurements using
Jeener-Broekaert echoes. Purpose
To develop
a fast and accurate method to measure the dipolar relaxation time,
T1D, in-vivo.
Introduction
The
contrast mechanism described as inhomogeneous magnetization transfer (ihMT) is
based on the signal difference following saturation at a single offset frequency and
that following dual frequency saturation [1-2]. This ihMT signal has been recently
modeled based on the interaction between the bound and free pool, with and
without inclusion of a dipolar component to the bound pool [3]. In the case of
a pulsed saturation preparation, the
ihMT signal is found to be dependent on the number of pulses between switching
frequencies for the dual offset
experiment [4]. In this work, the model that describes the ihMT signal was
adapted to describe the effect of a variation in the period between switches in
frequencies. In doing so, we provide a robust method by which a dipolar
relaxation time,
T1D can
be extracted from ihMT data from different substances.
Methods
A
modified ihMT pulse sequence was developed with MT saturation performed using 0.5ms
Hann shaped RF pulses every 1.2ms. Dual frequency irradiation is typically
achieved by alternating between positive and negative frequency pulses. By
increasing the number of pulses performed at the same frequency before
switching to the negative frequency, a frequency switching time,
w was introduced (Fig.1). An approximate
analytic solution to the dipolar ihMT model, described in [3], was derived to
enable rapid fitting of the signal decay curves as a function of switching time,
w. Data were acquired in 5 healthy
volunteers and hair conditioner (
hc)
on a GE 3T scanner with 500ms of saturation at B
1,RMS=3.5μT,
|Δ|=7kHz, and 8 values for
w ranging
from 1.2-43.2ms, followed by a single-shot spin-echo EPI acquisition. ihMT ratios (ihMTRs)
calculated from ROI analysis, e.g. of white matter (
WM) and gray matter (
GM)
(Fig.2a), were fit to the model for ihMT(
w).
Similarly, ihMT(
w) data acquired at 11.75T
from
WM,
GM and muscle (
mu) ROIs in
2 mice, 2/4% agarose (
aga), and
hc #2 with a short TE single-shot FSE sequence
and 1ms RF pulses every 1.3ms at |Δ|=8kHz and w=1.3-42.9ms, were also fit to the model. Mouse in-vivo data were
collected following saturation at B
1,RMS=4.7;5.8μT for 0.75s; whilst
for
aga and
hc 11.75T data, B
1,RMS=6;8.5;12μT for 1.2s. Initial values for exchange/relaxation parameters were based on previous literature [3,5-6].
Results
Initial
estimates for parameters other than dipolar relaxation time,
T1D, i.e.
R,
RM0B/RA,
1/RAT2A, and
T2B, showed large variation. Fixing
these parameters to the initial values, the ihMT(
w) model was modified to have two variable parameters:
T1D and a constant,
A by which the resultant ihMTR was
multiplied, such that ihMTR=
A*ihMT(
w,
T1D)
(Fig.2b).
T1D remained
relatively stable despite factor of 2 changes in the fixed parameters:
R,
RM0B/RA,
1/RAT2A, and
T2B. The
T1D values found in
GM
were similar to that in
WM for both
humans and mice (Fig.3);
A in human
GM was 0.54 times that of
WM in the posterior region (Fig.2c).
T1Ds extracted from fitting
were longer in samples associated with (previously reported) higher ihMTR
values. Indeed,
T1D was 100
times longer in
hc #2 than in
aga;
hc #1 sample chilled to 3°C showed a 35% increase in
T1D, compared to that at room
temperature.
Discussion
Although
there was variability in the amplitude and/or other parameters related to the
model, the shape of the ihMT signal as a function of
w (as defined for this type of experiment, Fig.1) was mostly
dictated by the
T1D
(Fig.2b). As in previous works, measurements of
T1D in
WM/
GM were longer than those in
mu [3]. Further work is warranted, in
particular detailed comparison with alternative measurements of
T1D, e.g. using Jeener-Broekaert
echoes [7-8].
Conclusions
The
experiments and model outlined provided a means by which the dipolar relaxation
time,
T1D may easily be measured
in-vivo (independent of other MT parameters). This approach may be used to
improve modeling of ihMT and to quantitatively characterize pathologic tissues.
Acknowledgements
We
would like to thank F. Kourtelidis for help with volunteer scans.References
[1] Varma et al. Magn Reson Med 73:614-22 (2015). [2] Girard et al. Magn Reson Med 73:2111-21 (2015). [3] Varma et al. J Magn Reson 260:67-76 (2015). [4] Varma et al. Proc Intl Soc Mag Reson Med 21:2536 (2013). [5] Morrison et al. J Magn Reson B 108:103-13 (1995). [6] Henkelman et al. Magn Reson Med 29:759-66 (1993). [7] Jeener et al. Phys Rev 157:232-40 (1967). [8] Swanson et al. Proc Intl Soc Mag Reson Med 23:0994 (2015).