Thomas Gaass1,2, Moritz Schneider1, Michael Ingrisch1, Julia Herzen3, and Julien Dinkel1,2
1Institute for Clinical Radiology, Ludwig-Maximilians University, Munich, Germany, 2Comprehensive Pneumology Center, German Center for Lung Research, Munich, Germany, 3Department of Physics, Technische Universität München, Munich, Germany
Synopsis
The
presented work demonstrates the applicability of a dedicated 3-dimensional phantom as a
realistic MR- and CT-compatible phantom for microvascular perfusion simulation. The device constructed
using resin-embedded, melt-spun, sacrificial sugar structures was examined using dynamic contrast enhanced MRI. Parameters, such as flow and volume fraction gained from deconvolving the signal enhancement curve showed very good agreement with the pre-set perfusion parameters. The presented phantom showed great potential in realistically simulating the capillary bed and can
potentially serve as a quality insurance device for quantitative dynamic
contrast enhanced MRI in the future. Purpose
Currently,
only few three-dimensional phantoms are available for the accurate simulation
of perfusion on a capillary level. Approaches such as stacking of 2D structures
formed by lithographic methods
1 or 3D printing
2 either
lack accuracy in at least one dimension or are too coarse for the simulation on
micrometer level. Within this work we demonstrate the potential of a microvascular
phantom constructed using resin-embedded, melt-spun, sacrificial sugar
structures
3 as a simulation tool for dynamic contrast enhanced (DCE)
magnetic resonance imaging (MRI).
Methods
Phantom
construction: The employed phantom, as previously introduced by Bellan et al.
3,
was constructed by embedding a ball of sugar fibers into a synthetic resin and
subsequent dissolution of the fibers in a water ethanol bath. The sacrificial
sugar structures were melt-spun using a store-bought cotton candy machine
(Candyland, Klarstein, Berlin, Germany) modified in terms of rotational speed
and heating temperature to control the diameter and flexibility of the fibers.
A block of sugar fibers was impacted in between two plates formed from molten
sugar, equipped with an in- and outlet and placed into a PET mold (cf. Fig. 1).
A hydrophobic two-component resin (E45GB, Breddermann Kunstharze, Schapen,
Germany) at a hardener:resin ratio of 10:6 was used to fixate the sugar structures.
After approximately 24h of curing time the hardened resin block was placed in a
water-ethanol bath in order for the sugar structures to dissolve, leaving a
microstructure network within the resin block.
DCE imaging: Controlled water flow through the
phantom was induced via a Harvard Apparatus (PHD 2000, Harvard Bioscience Inc.,
Holliston, Massachusetts, United States). A bolus of 1ml water-gadopentetate-dimeglumine
solution (Magnevist, Bayer Vital, Leverkusen, Germany) of 1% concentration
followed by demineralized water was injected at a constant flow rate of
1ml/min. DCE MRI measurements were performed on a 3T whole body MRI (Siemens
Skyra, Siemens Healthcare, Erlangen, Germany) using a wrist coil and a
dynamically acquired TWIST sequence with the following parameters:
TR/TE=4.91/1.9ms, #slices=10, slice thickness=3.5mm, FA=12°, matrix=384x384,
FoV=260x260mm, temporal resolution=2.5s, TA=23min. The signal enhancement curve
in the phantom was averaged over all pixels in a central slice and deconvolved
with an ‘arterial input function’ measured in the supplying tube.
Postprocessing was performed using regularized deconvolution with generalized
cross validation
4, yielding estimates of flow (F), volume fraction (v)
and mean transit time (MTT). In addition to the MRI acquisition a high
resolution micro-CT was acquired using a GE VtomeX M (GE Measurement and
Control) with the following parameters: Voltage=70kVp, Current=120µA,
Resolution=18µm.
Results
Figure 1
depicts a 3-dimensional surface rendering (OsiriX Imaging Software) of the
microvascular system within a 5x5x5mm
3 cube generated from micro-CT
data. Connected vessels of different diameter (4-40µm) and water filled
spheres, stemming from imperfections in the fiber retrieval process are clearly
visible. An intensity histogram based volumetry performed on the CT dataset
yielded a mean volume fraction of the vessel network of 0.7 %.
The number
of enhancing voxels (voxel size: 1.604mm
3) over all slices of the
DCE acquisition yielded a total volume of 10.63cm
3 incorporated by
the ball of sugar fibers. Taking the pre-set flow rate of 1ml/min into account
an average plasma flow rate of 9.4ml/100ml/min can be expected from this
setting.
Figure 2 displays
the measured signal enhancement curve in the phantom. Deconvolution yielded F=9.9ml/100ml/min, v=0.6% and MTT=3.6s.
Discussion
The visual
inspection and size estimation based on the micro-CT reconstruction shows a
dimensionality and structure well comparable to in vivo capillary beds
5.
Both the diameter and the vessel density are adjustable via the construction
process and are subject of current optimizations for the specific simulation of
various manifestations of capillary networks.
Both the
estimated flow rate of 9.4ml/100ml/min, as well as the computed network volume
fraction of 0.7% are very closely reproduced by the DCE measurement results of F=9.9ml/100ml/min
and v=0.6%.
Conclusion
The
presented work demonstrates the applicability of the constructed device as a
realistic MR- and CT-compatible phantom for microvascular perfusion simulation.
Pre-set perfusion parameters in terms of total flow could be detected and
quantified via DCE MRI in very good agreement to the true values. Future work
will concentrate on a further standardization of the manufacturing process to
guarantee reproducible perfusion parameters. This phantom can potentially serve
as a quality insurance device for quantitative dynamic contrast enhanced MRI in
the future. It may even be used as a gold standard for tracer-kinetic
quantification techniques, with the limitation that the phantom currently can
only provide a single, vascular compartment.
Acknowledgements
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