Dominik Ludwig1,2, Frederik B. Laun3, Karel D. Klika4, Julian Rauch1,2, Mark E. Ladd1,2,5, Peter Bachert1,2, and Tristan A. Kuder1
1Deparment of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, 2Faculty of Physics and Astronomy, Heidelberg University, Heidelberg, Germany, 3Institute of Radiology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany, 4Molecular Structure Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany, 5Faculty of Medicine, Heidelberg University, Heidelberg, Germany
Synopsis
Diffusion
pore imaging might open a new window into pathologies by providing histology-like
information non-invasively by estimating pore size and shape distributions. For
current pore imaging approaches, closed pores filled with an NMR visible
diffusing medium are assumed, while extraporal components and exchange are
neglected, which limits applicability. We propose a method based on Gaussian phase approximation to suppress effects of extraporal fluids and transmembrane
water exchange and compare the approach to a filter-based method. Thus, one
main obstacle for in vivo applications is reduced, the required high gradient
amplitudes may be obtained using local gradient coils in the future.
Introduction
Diffusion
pore imaging1 (DPI) so far was mostly conducted in artificial
phantom systems that excluded extraporal signal contributions. In last year’s
ISMRM abstract2 we were able to show that by adding filter gradients
to the original long-narrow scheme, it is indeed possible to acquire diffusion
pore images in the presence of extraporal signals. However, this still implies negligible
exchange between the intra- and extraporal space, and the resulting gradient
scheme is quite sophisticated. Therefore, an easier solution based on the
Gaussian phase approximation is proposed in this study that is applicable for
the correction of both extraporal signal contributions and effects originating
from exchange between intra- and extraporal space.Methods
The
specialized diffusion encoded sequence used for DPI is depicted in Figure 1a.
This approach is called the long-narrow gradient scheme and the refocusing
condition for the gradients needs to be fulfilled:
$$\int^{T}_{0}\vec{G}_{\delta_\text{L},\delta_\text{S}}(t)dt=0$$
Considering multiple pores with no extraporal
detectable medium, in the limit of
$$$\delta_\text{L}\rightarrow\infty,\delta_\text{S}\rightarrow0$$$, the
average pore space function (PSF) of the pores illustrated in Figure 1b can be
reconstructed from the measured signal
$$$S_{\infty,0}(\vec{q})$$$ via a simple inverse Fourier transform:
$$\rho_\text{avg}(\vec{x})=iFT(S_{\infty,0}(\vec{q}))(\vec{x})=\sum^{M}_{n=1}f_n\rho_n(\vec{x}-\vec{x}_\text{CM})$$
where $$$\rho_n(\vec{x}-\vec{x}_{\text{CM}})$$$ is the pore space of the n-th pore shifted to the origin, $$$f_n=V_n/V$$$ is the respective volume fraction within the
total intraporal volume
$$$V$$$ and
$$$\vec{q}=\gamma\vec{G}_\text{L}\delta_\text{L}=\gamma\vec{G}_\text{S}\delta_\text{S}$$$. If also extraporal
signals of an NMR-visible medium are allowed and assuming that the
extraporal component follows the Gaussian phase approximation3, the
signal can be modeled using
$$$S_\text{extra}(\vec{q})=S_{0,\text{extra}}e^{-\vec{q}^2c_1}$$$ where
$$$c_1$$$ is a constant for radial acquisitions in
$$$q$$$-space. The projections in $$$x$$$-space obtained from radial acquisitions can
then be written as
$$S(x)=S_0[f_\text{e}e^{-\vec{x}^2c_2}+(1-f_\text{e})iFT(S_{\delta_\text{L},\delta_\text{S}}(\vec{x})]$$
where $$$f_\text{e}=V_\text{e}/V_\text{total}$$$ is the extraporal volume fraction and a constant $$$c_2$$$. If the signal drop of
the extraporal component is significantly faster than the intraporal one, in
the long-time limit $$$e^{-\vec{x}^2c_2}$$$ becomes broad in $$$x$$$-space and can be fitted by
a Gaussian for retrospective removal of the contamination by subtracting it
from the actual projection of the PSF.
Simulations were
carried out using our in-house developed Monte-Carlo simulation tool4
implemented in MATLAB. Simulation parameters used for the equilateral triangles
can be found in Table 1. Thirty-two gradient directions were simulated in order
to be able to reconstruct the two-dimensional pore space images using an inverse
Radon transformation.Results
Figure 2 shows
the simulated signals (a,c) and corresponding projections of the PSF (b,d) for
two representative gradient directions (x-,y-direction). It is obvious that the
extraporal signal leads to a deviation for small
values that results in a baseline in the
reconstructed projections of the PSF and in the pore image without any
correction (e). The filter approach (magenta) that we previously proposed is in
good agreement with the simulation of only intraporal contributions for both the
signal and the reconstructed projection. However, a small remaining baseline is
still present. The Gauss-corrected projection of the PSF shows no deviation
from the intraporal simulation and yields a slightly higher contrast in the
reconstructed image (f) when compared to the filter approach (g).
Simulations also considering
permeable membranes of the triangles are shown in Figure 3. When comparing the
signals in Fig. 3(a,c) to the ones in Figure 2(a,c), it is clearly visible that
the deviations from the expected signal are quite severe. Using the filter
approach (magenta) the deviation gets smaller; however, a quite significant
deviation remains. This deviation carries on to the projections of the PSF
(b,d) and the reconstructed images (e,g). When applying the proposed Gauss
correction to both the direct measurement and the filter approach, it is indeed
possible to obtain the projection of the PSF with almost no deviation from
intraporal simulations. This also translates to reconstructed pore images (f,h)
that are indistinguishable from the ones presented in Figure 2.Discussion and Conclusion
Using our
proposed correction method, the simulations indicate that it is indeed possible
to also apply DPI to pores that are not completely closed,
thereby simplifying the acquisition of pore imaging data in the presence of
extraporal signals and exchange. For very low packing
densities, the extraporal contribution to the signal is rather large. Since the
extraporal diffusion is very likely to be Gaussian in that case, it can easily
be removed by one of our proposed methods. When considering larger packing
densities, the extraporal contributions may become very small; nevertheless, these
contributions will be harder to remove since the signal in the extraporal space
will also decay much slower and the Gaussian phase approximation may not be valid
anymore. Regarding exchange, the applicability will be limited by the necessity
to reach the long-time limit within the pores.
While general
limitations such as the high necessary gradient amplitude are still a concern
for the application of DPI for in
vivo measurements, cell samples or small animals on preclinical systems
represent the natural next step to be investigated using the correction methods
presented here. Regarding human in vivo applications, especially local gradient
coils might open a perspective due to the high gradient amplitudes they may
provide, potentially opening a new window for further insight into pathologies5,6.Acknowledgements
No acknowledgement found.References
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the Defining Boundary in Nuclear Magnetic Resonance Diffusion Experiments”,
PRL, 107 (2011)
[2]: Ludwig, D.,
et al. “Filtered water diffusion pore imaging on a 14.1 T spectrometer
using strong gradients and capillary phantoms in the presence of extraporal
fluid.”, Proc. Intl. Soc. Mag. Reson. Med. 29: 3416, (2021)
[3]:
Grebenkov, D.S., et al., “NMR survey of reflected Brownian motion.”, Rev Mod
Phys, 79 (2007) 1077-1137.
[4]: Ludwig, D., et al., “Apparent exchange
rate imaging: On its applicability and the connection to the real exchange rate”,
MRM, 86.2 (2021): 677-692
[5]: Littin, S., et al., “Approaching order
of magnitude increase of gradient strength: Non-linear breast gradient coil for
diffusion encoding“, Proc. Intl. Soc. Mag. Reson. Med. 29: 3096, (2021)
[6]: Jia, F., et al., „Design of a high-performance non-linear gradient coil for diffusion
weighted MRI of the breast“, JMR, 331, (2021)