A Novel Prostate DCE-MRI Flow Phantom for the Quantitative Evaluation of Pharmacokinetic Parameters
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

1. Li, X., W. Huang, and W.D. Rooney, Signal-to-noise ratio, contrast-to-noise ratio and pharmacokinetic modeling considerations in dynamic contrast-enhanced magnetic resonance imaging. Magn Reson Imaging, 2012. 30(9): p. 1313-22.

2. Hariharan, P., M. Freed, and M.R. Myers, Use of computational fluid dynamics in the design of dynamic contrast enhanced imaging phantoms. Phys Med Biol, 2013. 58(18): p. 6369-91.

3. Smith, D.S., et al., DCEMRI.jl: a fast, validated, open source toolkit for dynamic contrast enhanced MRI analysis. PeerJ, 2015. 3: p. e909.

4. de Bazelaire, C.M., et al., MR imaging relaxation times of abdominal and pelvic tissues measured in vivo at 3.0 T: preliminary results. Radiology, 2004. 230(3): p. 652-9.

Figures

Figure 1: (a) 3D model showing the internal structure of the ‘prostate’ (b) large anthropomorphic phantom.

Figure 2: Expected CTC derived from voltage input and CTCs measured using optical scanner at different flow rates.

Figure 3: Expected CTC derived from voltage input and four tumorous (left) and healthy (right) CTC runs measured using the optical set-up at 1.5 ml/s flow rate.

Figure 4: Difference between Ktrans values derived from DCE-MRI data and Ktrans values derived from truth estimates using the Extended Tofts model.

Figure 5: Axial T1-weighted image of the anthropomorphic phantom with the ‘prostate’ and measurement chambers highlighted.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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