Silvin P. Knight1, Jacinta E. Browne2, James F. Meaney1, David S. Smith3, and Andrew J. Fagan1
1National Centre for Advanced Medical Imaging (CAMI), St James Hospital / School of Medicine, Trinity College University of Dublin, Dublin, Ireland, 2School of Physics, Medical Ultrasound Group, Dublin Institute of Technology, Dublin, Ireland, 3Institute of Imaging Science / Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, United States
Synopsis
A method is lacking to comprehensively
validate and optimise the ability of prostate DCE-MRI techniques to accurately
measure pharmacokinetic (PK) parameters. We present a novel flow phantom
capable of simultaneously producing two measurable, reproducible, and known arbitrarily-shaped
contrast time-intensity curves, from which PK parameters can be derived. Ktrans values were derived
from MR data acquired at different temporal resolutions (2.3-20.3s) and were found
to differ by -8.1% to -44.6%, when compared to calibrated ‘truth estimate’
values, with the lowest variance measured at a temporal resolution of 6.8s. The
phantom can be used to help establish robust DCE-MRI prostate protocols.Introduction
Pharmacokinetic (PK) parameters derived from DCE-MRI
data are sensitive to both temporal resolution and signal to noise ratio (SNR)
1. There is a balance to be reached between
temporal resolution and SNR such that the data is optimised for a given PK
model; however, no method exists to quantitatively assess the PK
modelling accuracy of different acquisition approaches, a situation which is exacerbated by potential inaccuracies introduced by
fast acquisition techniques such as compressed sensing (CS). To address this
shortcoming, a flow phantom was designed and built which can produce contrast
time-intensity curves (CTCs) representative of those observed in DCE-MRI data
of the prostate. The ability of the device to quantitatively evaluate the
effects of different acquisition strategies on derived PK parameters is
demonstrated.
Methods
A prostate sized object was manufactured containing two measurement chambers, designed for optimum
homogeneous mixing of fluids at low flow rates (1-4ml/s)2, as well as a further arrangement of chambers (Figure 1(a)) that mimicked
the overall enhancement of the prostate observed in vivo. To realistically challenge DCE protocols, the ‘prostate’ was
set into a large custom-built anthropomorphic phantom that mimicked the male pelvis
(Figure 1(b)).
CTCs
were produced using a custom-built computer-controlled
multi-pump system (Reglo-Z, ISMATEC, Switzerland), capable of simultaneously
producing two different arbitrarily shaped CTCs within the measurement chambers
by varying the relative concentration of a gadolinium-based contrast agent (CA)
solution (Multihance, Bracco, USA), while keeping the overall flow rate
constant.
Calibrated ‘Truth Estimates’ for the CTCs
produced by the system after traveling the 11 m from the pumps to the
measurement chambers (pumps in the scanner control room) were measured using a
custom-built optical imaging system (Fujinon-Σ400 endoscopic
light source, and high resolution CMOS Cannon-20D camera), using black dye as a
CA surrogate.
To demonstrate the operation of the phantom,
DCE-MRI data was acquired using a 3T scanner (Achieva, Philips, Netherlands)
and 16-channel phased array detector coil (3D-SPGR, TR/TE = 3.6/1.75ms, flip angle = 10°, voxel size = 1.1 x 1.1 x 4 mm3, FOV = 224 x 224 x 72 mm3, slices = 18).
The parallel imaging factor and number of signal averages were varied to give
temporal resolutions from 2.3 s to 20.3 s. The DCEMRI.jl toolkit3 was used to derive Ktrans
values for the truth estimates and MR data from a hand selected region of
interest containing 35 voxels using the Extended Tofts model.
Results
Measurement chambers were manufactured with
wall thicknesses of 0.3 mm, minimising any susceptibility artefacts. Agar-based
tissue mimic materials were produced which closely match the T1 and T2 properties of bone, muscle, and fat tissue4 (+4%, -0.7%, and +20% respectively).
Good temporal stability was observed for measurements
made using the optical scanner (±0.37% over 30
minutes). Full CTC runs were measured using the optical system at flow rates
from 0.5 to 2.5 ml/s (Figure 2) and the minimum flow rate at which the CTCs are
accurately produced was found to be 1.5 ml/s (R2 = 0.98). Two different CTCs (healthy and tumorous)
were subsequently run four times at 1.5 ml/s to test for repeatability; good
correlation was observed between the repeated CTCs (Figure 3).
Ktrans values derived from the MR
data were compared with those derived from the truth estimates and were found
to differ by -8.1% to -44.6%, with the lowest variance from the truth estimate
values achieved at a temporal resolution of 6.8 s (see Figure 4).
Discussion
and Conclusion
The anthropomorphic nature of a phantom allows
for repeatable measurements of PK parameters in an environment closely emulating
that observed in vivo (see
representative MR image of the phantom in Figure 5). The optical scanner used
to calibrate the system provided a novel and inexpensive way to validate the
CTCs produced by the system using a modality other than MRI, and also allowed
for minimum flow rates to be established, which is important on two fronts: the
minimisation of flow artefacts and the reduction in the amount of CA used. For
the curve shapes used in this study, the lowest variation in
Ktrans values occurred at
6.8 s temporal resolution. At higher temporal resolutions, inaccuracies in the
resultant
Ktrans values
were most likely due to low SNR, and at the lower temporal resolutions due to
the reduced number of sampling points.
The device can be used for optimising DCE acquisition protocols and
investigating the effect of fast acquisition schemes (e.g. CS) on the PK
modelling accuracy. The ability of
faster acquisition schemes to faithfully measure rapidly-varying CTCs, such as
the arterial input function, can also be explored using this device.
Acknowledgements
Supported by Irish Cancer Society Research
Scholarship CRS13KNI and an Irish Association of Physicists in Medicine Young
Investigator Grant.References
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