# Evaluation of Apparent Diffusion Coefficient Repeatability and Reproducibility for Preclinical MRIs Using Standardized Procedures and a Diffusion-Weighted Imaging Phantom

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## Abstract

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^{2}/ms, corresponded to 17% [12%, 31%] relative to the reference standard. Absolute bias at isocenter was low (within 4%) for 8 of 10 systems, whereas two high-bias (>10%) scanners were primary contributors to the relatively high RDC. Significant additional variance (>2%) due to site-specific analysis was observed for 2 of 10 systems. Base-level technical bias, repeatability, reproducibility, and spatial uniformity patterns were consistent with human MRIs (scaled for bore size). Well-calibrated preclinical MRI systems are capable of highly repeatable and reproducible ADC measurements.

## 1. Introduction

## 2. Materials and Methods

#### 2.1. DWI Phantom

#### 2.2. DWI Acquisition Protocol

^{2}; number of averages, NSA = 1; and repetition time/echo time, TR/TE = 2000/30 ms for nominal scan duration of 15 min.

#### 2.3. Participating Site Procedures

#### 2.4. Core Lab Processing

^{2}/ms is the known diffusion coefficient of water at 0 °C [39].

#### 2.5. Statistics

_{1}, ADC

_{2}) from the ith scanner, mean (M

_{i}) and variance (V

_{i}) were constructed as [10,40]

^{2}/ms [39], as 100% [(ADC–Dtrue)/Dtrue]. Likewise, wSD and SD were scaled by 100%/Dtrue on plots so that the degree of variability could be directly compared relative to the systematic bias. Unrealistic ADC values < 0.5 µm

^{2}/ms were automatically dropped from the plots and analysis. Each system’s absolute ADC bias was measured at the isocenter by averaging the ADC in the measurement tube over the three central slices.

## 3. Results

^{2}/ms). The small error-bar range relative to the offset from the truth indicates that the system absolute bias was measurable and repeatable on each system. Eight of ten MRI systems were within ±2.5% bias (mostly positive) and the remaining two exceeded +10% bias.

^{2}/ms) only occurred outside |z-offset| > 20 mm. Most systems display the pattern of maximum ADC at isocenter, with lower ADC as |z-offset| distance increases, which is consistent with gradient nonlinearity patterns for horizontal bore gradients on human scanners. Systems 9 and 10 showed >10% bias for ADC at isocenter, while others had low isocenter bias (comparable to measurement error). These two systems also showed the greatest gradient nonlinearity over the central region, within ±15 mm of isocenter.

## 4. Discussion

^{2}/ms or 6.2% of Dtrue). Spatial nonuniformity of ADC measurements along the z-axis on preclinical MRIs also resembles the gradient nonlinearity observed on human MRIs [26,42], though scaled for bore size. While reasonable ADC uniformity over the central region (within ≈10 mm of the isocenter) was observed for most systems, the importance of repeatable subject (mouse) positioning of the organ/lesion of interest at/near isocenter must not be overlooked.

## 5. Conclusions

## Supplementary Materials

## Author Contributions

## Funding

## Institutional Review Board Statement

## Informed Consent Statement

## Data Availability Statement

## Conflicts of Interest

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**Figure 1.**(

**a**) Schematic of DWI phantom constructed from a 50 mL centrifuge tube designed to hold water in an 8 mm measurement tube at known temperature, thus with known diffusion coefficient. (

**b**) Coronal and axial MRI with internal phantom components labeled. (

**c**) Plot of measurement tube temperature versus time after measurement tube, initially at room temperature, is inserted into frozen phantom. Note, thermal equilibrium at ≈0 °C is achieved.

**Figure 2.**Median ADC measured at the isocenter of each system. Each data point is the median of all scans (up to 4) from each system, and error bars indicate the maximum and minimum (range of) isocenter ADC values. The solid line marks Dtrue (1.1 µm

^{2}/ms), and dashed lines are ±5% relative to Dtrue.

**Figure 4.**Summary of bias and repeatability for all studied systems: (

**a**) mean bias (blue line) and short-term (intra-exam) repeatability relative to Dtrue, plotted as a function of z-axis location. Note, systems 8 and 9 did not provide short-term repeatability data (Table 1). (

**b**) Corresponding plots for long-term (inter-exam) repeatability. Shaded regions in (

**a**) and (

**b**) represent bias ± 100% wSD/Dtrue. (

**c**) Cross-system reproducibility, where shaded region represents bias ± 100% SD/Dtrue. Green line denotes ideal 0% bias. (

**d**) Difference between site-generated and core-lab-generated ADC relative to Dtrue. Difference for core-lab systems 1 and 10 is zero (not plotted). Plots are on the same scale to aid visual comparison of bias, short- and long-term repeatability, reproducibility, and difference between site- versus core-lab ADC generation routines.

System | Vendor | Field Strength (T) | Gradient Inner Diameter (mm) | SW Version | Day 1 Scan1 Scan2 | Day 2 Scan1 Scan2 | ITK Format | ||
---|---|---|---|---|---|---|---|---|---|

1 | Bruker | 7 | 114 | PV7.0.0 | ✓ | ✓ | ✓ | ✓ | MHD |

2 | Bruker | 9.4 | 120 | PV6.0.1 | ✓ | ✓ | ✓ | ✓ | MHD and Classic DICOM |

3 | Bruker | 7 | 120 | PV6.0.1 | ✓ | ✓ | ✓ | ✓ | Classic DICOM |

4 | Bruker | 9.4 | 114 | PV360 v2.0 | ✓ | ✓ | ✓ | ✓ | Enhanced DICOM |

5 | Agilent | 11.74 | 80 | VnmrJ4.2revA | ✓ | ✓ | ✓ | ✓ | Classic DICOM |

6 | Bruker | 3 | 105 | PV6.0.1 | ✓ | ✓ | ✓ | ✓ | Classic DICOM |

7 | Bruker | 9.4 | 60 | PV360 v3.0 | ✓ | ✓ | ✓ | ✓ | NIFTI |

8 | Bruker | 4.7 | 90 | PV6.0.1 | ✓ | ✓ | Classic DICOM | ||

9 | Bruker | 14 | 40 | PV5.1 | ✓ | ✓ | Classic DICOM | ||

10 | MR Solutions | 3 | 95 | V4.0.2.4 | ✓ | ✓ | ✓ | ✓ | MHD and Classic DICOM |

Short-Term Repeatability | Long-Term Repeatability | Cross-System Reproducibility | |||||
---|---|---|---|---|---|---|---|

wSD (µm^{2}/ms) | RC (µm^{2}/ms) | wCV (%) | wSD (µm^{2}/ms) | RC (µm^{2}/ms) | wCV (%) | SD (µm^{2}/ms) | RDC (µm^{2}/ms) |

0.009 [0.007, 0.014] | 0.025 [0.018, 0.038] | 0.73 [0.54, 1.12] | 0.015 [0.011, 0.023] | 0.042 [0.032, 0.064] | 1.26 [0.94, 1.89] | 0.068 [0.047, 0.124] | 0.188 [0.129, 0.343] |

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## Share and Cite

**MDPI and ACS Style**

Malyarenko, D.; Amouzandeh, G.; Pickup, S.; Zhou, R.; Manning, H.C.; Gammon, S.T.; Shoghi, K.I.; Quirk, J.D.; Sriram, R.; Larson, P.;
et al. Evaluation of Apparent Diffusion Coefficient Repeatability and Reproducibility for Preclinical MRIs Using Standardized Procedures and a Diffusion-Weighted Imaging Phantom. *Tomography* **2023**, *9*, 375-386.
https://doi.org/10.3390/tomography9010030

**AMA Style**

Malyarenko D, Amouzandeh G, Pickup S, Zhou R, Manning HC, Gammon ST, Shoghi KI, Quirk JD, Sriram R, Larson P,
et al. Evaluation of Apparent Diffusion Coefficient Repeatability and Reproducibility for Preclinical MRIs Using Standardized Procedures and a Diffusion-Weighted Imaging Phantom. *Tomography*. 2023; 9(1):375-386.
https://doi.org/10.3390/tomography9010030

**Chicago/Turabian Style**

Malyarenko, Dariya, Ghoncheh Amouzandeh, Stephen Pickup, Rong Zhou, Henry Charles Manning, Seth T. Gammon, Kooresh I. Shoghi, James D. Quirk, Renuka Sriram, Peder Larson,
and et al. 2023. "Evaluation of Apparent Diffusion Coefficient Repeatability and Reproducibility for Preclinical MRIs Using Standardized Procedures and a Diffusion-Weighted Imaging Phantom" *Tomography* 9, no. 1: 375-386.
https://doi.org/10.3390/tomography9010030