Purpose: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is used to assess tissue perfusion/permeability by measuring the temporal variation of contrast-agent concentration in the tissue. However, the inter- and intra-scanner variability of quantitative DCE-MRI measurement remains a concern. We previously developed a point-of-care portable perfusion phantom (P4) that was small enough to be simultaneously imaged with a human subject, and thus can serve as a real-time calibration tool. The P4-based error correction was able to reduce the inter-scanner variation of quantitative DCE-MRI measurement approximately five-fold and the intra-scanner variation approximately four-fold.^1,2 The goal of this study was to upgrade the design of the P4 phantom to be disposable, easily operable, and conveniently deliverable for widespread, routine clinical use.
Methods: Our new disposable P4 phantom (see Fig. 1) is composed of top and bottom chambers with a semi-permeable membrane (pore size: 12~14 kDa) placed between them. The top chamber measures 1 × 15 × 150 mm (height × width × length), and the bottom chamber measures 15 × 15 × 150 mm. The top half has a ridge that protrudes along the perimeter of the top chamber, while the bottom half has a channel around it to accept the ridge. The membrane is placed such that the ridge and channel enclose it when the two halves are combined, clamping it into place and maintaining flatness. Both top and bottom chambers of the P4 phantom are filled with degassed/deionized water. To prevent water leakage that creates bubbles that cause variation in phantom performance, epoxy is used as a gasket between the two halves to prevent water leakage. The inlet and outlets of the phantom are closed with caps. Before use, the caps are removed, and a tube filled with an MR contrast agent is connected to the inlet. A computational fluid-dynamics (CFD) model was employed to optimize the top chamber geometry such that over 99% of the water would be displaced by the contrast agent infused into the top chamber. The CFD model was validated with samples collected from the top chamber using Liquid Chromatography–Mass Spectrometry (LC-MS). LC-MS also was utilized to measure the contrast enhancement curve (CEC) of the phantom. Two holes were drilled in the side of the bottom chamber and a 0.25 ml sample was extracted every minute for ten minutes after infusing 4 ml of gadoteridol (100 mM) at a constant rate (0.24 ml/s) into the top chamber. This process was repeated ten times for a total of 100 samples. The repeatability of the CEC was evaluated using DCE-MRI with five P4 phantoms located at the center of a single 3T MRI scanner (SIEMENS Prisma). A new phantom package (see Fig. 2) was designed to house up to three phantoms. The cassette was connected to a position-finder via a polymer and carbon-fiber cable system allowing an operator to adjust the cassette’s position by ±7.5 cm. A new patient bed (see Fig. 3) was made with wooden platforms (height × width × length = 6 × 48 × 206 cm, weight = 6 kg). The bed structure was configured using finite element analysis to support up to 136 kg of body weight when the subject sits on the bed. Using the cable controller indicated with an arrow at the end of the bed, the phantom’s location can be adjusted without interfering a human subject inside an MRI scanner.
Results: No bubble formation was observed in epoxy-sealed phantoms for at least four months. A CFD model of the top chamber geometry produced post-infusion gadoteridol purity of 99.2%, when 4 ml of gadoteridol is infused at a rate of 0.24 ml/s over 16.67 seconds. Figure 4 shows the CEC of the P4 phantom measured with LC-MS, confirming a linear increase (0.17 mM/min) of contrast-agent concentration in the phantom with 96% accuracy. Figure 5 shows the repeatability of the P4 phantom. Figure 5A shows the contrast agent concentration (CAC) maps of five phantoms (P1-P5) at 2, 3, and 5 minutes after the imaging initiation. Figure 5B shows the CECs of the phantoms. The intraclass correlation coefficient of the CECs was 0.997.
Discussion: We developed a new disposable P4 phantom and accompanying equipment for accurate quantitative DCE-MRI measurement in the routine clinical setting. The data consistency across different scanners and acquisition times will facilitate multi-institutional studies for drug development as well as improving diagnosis and prognosis accuracy of many diseases including cancer.

Acknowledgements

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