Synopsis
Physical
hardware diffusion phantoms with a well-defined structure, composition and
architectural organization can serve as a gold standard for the validation of
diffusion MRI. In this lecture, we aim to provide guidelines on how to choose
or manufacture a synthetic diffusion phantom that addresses the needs of your
project, going from setting up a quality assessment diffusion protocol on a
clinical scanner, developing and testing a novel diffusion sequence, validating
biophysical models to evaluating tractography models. Target audience
Scientists
and clinicians interested in learning what has been done in validation of
commonly used MRI diffusion methods (tractography and tissue microstructure)
and applying those methods in their own scientific inquiries and the use of
these in both basic research and clinical applications.
Outcome/Objectives
- Provide practical guidelines on how to choose or manufacture a synthetic phantom that addresses the needs of your project
- Understand
the critical factors that determine the SNR and diffusion properties (including
the mean diffusivity and fractional anisotropy) of a phantom
- Give a
state-of-the art overview on both simple and advanced diffusion phantoms and
how they can be used to validate diffusion experiments.
Liquids
As for most
things, the overall guideline when designing a (diffusion) phantom could be
“the simpler, the better”. Indeed, the human brain would be a terrible phantom,
as it is far from being well characterized! On the other hand, liquids are very
simple, and very useful phantoms. They typically exhibit isotropic Gaussian
diffusion and can hence be characterized with a well established (time-independent)
diffusion constant, making them useful as a standard for quality assurance (QA)
when calibrating diffusion protocols and evaluating new diffusion sequences and
postprocessing methods. Potential advantages of liquids are that they are often
stable, readily available and require only a minimum of on-site laboratory
work.
Following
factors to consider:
- The
diffusion coefficient depends on the liquid and the temperature
- T1 and T2
relaxation times will define the SNR of the measurement
- The NMR
spectrum: spurious peaks in the NMR spectrum may result in ghosting and
artifacts in echoplanar imaging, or, alternatively, may be a feature that can
be employed to create multicompartment systems (e.g, Figure 1: fat-water).
Examples: Water has been widely used as a test object. A potential
drawback of water is the relative high diffusion coefficient at room
temperature (2 μm2/ms) compared to the mean
diffusivity in brain (0.3 – 1 μm2/ms). Other test
liquids are cyclic and linear alkanes, (poly) ethylene glycol,
aqueous solutions of sucrose, polyvinylpyrolidone (PVP), albumin,
and agar gels. The diffusion coefficients of water and other molecular liquids
for the quantitative calibration of diffusion MRI are listed in [1, 2].
Structural phantoms
Surrounding
the diffusing molecules by (NMR invisible) materials such that the diffusion becomes
restricted and/or hindered opens additional ways for evaluating diffusion
anisotropy as well as validating biophysical models and mimicking biological
tissues. In this case, following properties of the phantom (NMR invisible) material should be
considered [3]:
- Magnetic
properties of the material: differences in magnetic susceptibility between the
liquid and confining structure will effect the SNR and may result in imaging
artifacts, as well as in a directional dependence of the SNR (and
diffusion) properties with respect to the static B0-field
- Surface
relaxation may affect the SNR and diffusion properties
Examples:
- Anisotropic
phantoms based on fibers [3-6] (Figure 2) or capillaries [7-9] have been used extensively for quality assurance and testing of
diffusion sequences, as well as for evaluating different fiber tracking
algorithms[10] and validating biophysical models. The
fractional anisotropy (FA) in such phantoms depends on the type of fiber,
diameter, diffusion protocol and fiber material [3]. Hollow fiber systems made from glass or
plastic capillaries with a known internal diameter serve as phantoms to study
the diffusion in the intra-axonal space, and have been used to evaluate axonal
diameter mapping using single and double pulsed field gradient methods[11-13]. Plain fiber bundles serve as a phantom to model the extra-axonal
space, and have been used to study the effect of axonal packing geometry on the
(time-dependent) diffusion coefficient [14], as well as to calibrate oscillating gradient
spin echo diffusion weighted images. Because of the technical challenge to
fabricate anisotropic fiber phantom, it is necessary to characterize the
density, directionality and inner/outer diameters of the created geometries
(bundles, crossings, etc.).
- Isotropic
phantoms featuring multi compartment or hindered and/or restricted diffusion: Packing
geometries of glass and polymer particles serve as models for restricted
diffusion (in porous media, to mimic tumors, etc. ). Avian egg latebra acts as
an isotropic phantom featuring restricted diffusion as in brain microstructure [15]. Cream (fat + water) can serve as a simple
phantom for bi-exponential diffusion (and relaxation) to test diffusion
kurtosis imaging protocols [16, 17].
- Phantoms
consisting of permeable membranes can be used to study time-dependent diffusion.
Acknowledgements
Presenter's work is sponsored by NIH R01NS088040, Fellowship from Raymond and Beverly Sackler Laboratories for Convergence of Physical, Engineering and Biomedical Sciences, and the Alzheimer's Drug Discovery Foundation.References
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