Multi-Center Validation of an Acetone-D2O Quantitative Diffusion Phantom
Xiaoke Wang1, Samir D Sharma2, Mustafa R Bashir3, Jean H Brittain2, Jean Shaffer3, Takeshi Yokoo4, Qing Yuan4, Scott B Reeder1,2,5,6,7, and Diego Hernando2

1Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, United States, 2Radiology, University of Wisconsin-Madison, Madison, WI, United States, 3Radiology, Duke University, Durham, NC, United States, 4Radiology, University of Texas Southwestern Medical Center, Dallas, TX, United States, 5Medical Physics, University of Wisconsin-Madison, Madison, WI, United States, 6Medicine, University of Wisconsin-Madison, Madison, WI, United States, 7Emergency Medicine, University of Wisconsin-Madison, Madison, WI, United States


A recently proposed acetone-D2O phantom, which has ADC tunable over the entire physiological range, has shown promise for the development and quality assurance of quantitative diffusion MRI. In this study, this phantom was shipped between three sites with different MRI vendors to demonstrate consistent diffusion quantification across imaging protocols, platforms, and field strengths. The results demonstrated consistent ADC measurements across sites/vendors, field strength, choice of b-values, intra-exam and inter-exam repetition. In conclusion, the acetone-D2O phantom is a promising tool for future multi-center validation and quality assurance of quantitative diffusion MRI techniques.


Quantitative diffusion MRI is widely utilized in oncologic research studies and is of increasing clinical interest as a tool to predict or assess treatment response. Quantitative diffusion phantoms are urgently needed to help clinicians and researchers to compare data acquired using different scanner platforms, imaging protocols, and field strengths. Such phantoms would ideally include samples with known apparent diffusion coefficients (ADC) spanning the entire physiological range (600-2600 μm2∙s-1) [1] at an easily reproducible temperature (e.g. using an ice water bath at 0°C) with a simple NMR spectrum (single peak) and Gaussian diffusion. Currently available diffusion phantoms that utilize an aqueous Polyvinylpyrrolidone solution [2,3] provide ADC values that cover only a portion of the physiological range when scanned at 0°C (<1120 μm2∙s-1)[2]. A recently proposed acetone-D2O phantom, where D2O modulates the ADC of acetone without producing MR signals, provides ADC values covering the entire physiological range at 0°C [4,5]. The purpose of this study was to test the reproducibility of quantitative diffusion measurements of the acetone-D2O phantom across three sites with different vendors at both 1.5T and 3T, and using two different acquisition protocols.


Phantom construction and shipment: An acetone-D2O phantom was constructed, which included 5 cylindrical vials (radius=2.75cm, height=9.5cm) filled with acetone-D2O mixtures with D2O concentrations of 0%, 5%, 10%, 20%, 40% (v/v). To test reproducibility across sites, vendors and platforms (Table 1), the phantom was scanned at Site 1, then sequentially shipped to and scanned at Site 2 and Site 3. At each site the phantom was stored under 0°C.To test the integrity of the phantom at the end of the study, the phantom was shipped back to Site 1 and rescanned using the same acquisition protocols.

Imaging protocol: All scans were performed with the phantom placed in an ice-water bath, where the water signal was eliminated with MnCl2 (5mM), after 30 minutes of equilibration. Cylinder vials were aligned in the S/I direction. A 2D single spin echo DW-EPI sequence was acquired in the axial plane without parallel imaging. Two different sets of b-values were applied to test the robustness of ADC measurements to protocol variations: (1) 0-2000s/mm2, and (2) 0-500s/mm2. Remaining acquisition parameters are listed in Table 2. Data obtained at sites 2 and 3 were transferred to Site 1 for centralized processing. At each site and field strength, each DW-EPI series was acquired twice to test the intra-exam repeatability of ADC measurements. Further, each imaging experiment was repeated in a different session to test the inter-exam reproducibility.

Diffusion quantification: For each DW-EPI scan, one slice with minimum image artifact such as EPI distortion was chosen for quantitative analysis. An ADC map was generated for this slice using a single-exponential model on a voxel-by-voxel basis. For each vial, a circular ROI (diameter=8mm) was chosen in the center of the vial while avoiding apparent artifacts. The ADC for the vial was calculated by averaging the ADC of each voxel inside the ROI. The measured ADC from all intra- and inter-exam repetitions, choice of b-values, sites, and field strengths were compared using intra-class correlation coefficient (ICC). In addition, Bland-Altman tests were performed to assess the individual effects of intra-exam repetitions, inter-exam repetitions, choice of b-values, sites/vendors, and field strengths, respectively.


ADCs were measured successfully from all datasets, with mean ADCs of 3411.4, 2686.4, 2093.7, 1337.7, 632.3μm2∙s-1 in ascending order of D2O concentrations. ICC was 0.9983 with 95% CI=[0.9950,0.9998] across all acquisitions. Bland-Altman analyses of ADC measurements between intra- and inter-exam repetition, field strengths and choices of b-values (Figure 1), as well as between sites (Figure 2) demonstrated good agreement. The close agreement between the ADC measured at Site 1 at the beginning and end of this project (Figure 3) validates the stability of the phantom during the entire study (37 days).


The acetone-D2O phantom was successfully built and shipped (three sites overall), scanned with similar protocols at each site, and returned to Site 1 where it was scanned again. Overall good agreement was observed across intra- and inter-exam repetition, sites/vendors, field strengths, and choices of b-values. This indicates good repeatability and reproducibility of ADC measured in the acetone-D2O phantom over a wide range of ADCs. Some of the variations across exams and sites may be due to temperature deviations (imperfect ice water bath) or residual imaging artifacts. These factors highlight the need for careful control of the temperature and imaging setup in diffusion MRI phantom studies. In conclusion, the acetone-D2O phantom is a promising phantom for future multi-center validation and quality assurance of quantitative diffusion MRI techniques.


The authors wish to acknowledge support from the NIH (R01 DK083380), the Discovery to Product (D2P) Igniter program, as well as GE Healthcare.


[1] Hara et al. Onco Lett 2014;8:819-824.

[2] Pierpaoli et al. ISMRM 2009 p.1414.

[3] Boss et al. AAPM 2015 TU-C-12A-8.

[4] Wang et al. ISMRM 2014 p. 0159.

[5] Toryanik et al. J Struct Chem 1988;28:714-719.


Table 1. Scanners used in this study.

Table 2. Imaging parameters

Figure 1. Bland-Altman plots demonstrating good agreement between series (intra-exam), exams (inter-exam), field strength, and choice of b-values. Results are shape and color coded by site. The limits of agreement are for all sites combined. The outliers circled are from one vial in a particularly artifact corrupted scan.

Figure 2. Bland-Altman analyses demonstrated good agreement in ADC values between each pair of sites. Each plot compares ADC (from all protocols, field strengths, and repetitions) between a pair of sites. The circled outliers are from the same corrupted scan as those shown in Figure 1.

Figure 3. Close agreement was observed in ADC measurements at Site 1 before and after the phantom was shipped between sites. The comparison includes ADC from all protocols, field strengths, and repetitions. This strongly supports the stability of the phantom during the entire study.

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