# Prediction of Lung Shunt Fraction for Yttrium-90 Treatment of Hepatic Tumors Using Dynamic Contrast Enhanced MRI with Quantitative Perfusion Processing

^{1}

^{2}

^{*}

## Abstract

**:**

## 1. Introduction

## 2. Materials and Methods

#### 2.1. Patients and MRI Protocols

#### 2.2. Quantitative Perfusion Processing of DCE MRI

#### 2.3. Data Analysis

^{3}. Statistical analysis was performed on 6 parameters: ROI averaged $\left|\mathit{u}\right|$, ${K}^{\mathit{trans}}$, ${V}_{e}$, $\tau $, as well as tumor volume and patient age. A Spearman correlation test was performed to test the relationship between these parameters and lung shunt fraction. The Mann–Whitney U test was performed comparing these values between the low-risk and the high-risk groups. p-values at or below 0.05 were considered to indicate statistical significance. A receiver operating characteristic curve (ROC) analysis was performed to investigate the risk prediction performance of all parameters, and the optimal threshold was calculated by maximizing sensitivity plus specificity. Statistical analysis was performed using the R Statistical Software (Foundation for Statistical Computing, Vienna, Austria).

## 3. Results

^{3}). The lesion demonstrated enhancement on post-contrast DCE MRI (red arrow in Figure 1a), and processed $\left|\mathit{u}\right|$, ${K}^{\mathit{trans}}$ and ${V}_{e}$ maps are shown in Figure 1b–d, respectively. For QTM, $\left|\mathit{u}\right|$ was 0.06 mm/s, while for Kety’s method ${K}^{\mathit{trans}\text{}}$= 0.0033, ${V}_{e}$ = 0.1073 and $\tau =15.86$s. As a comparison, Figure 2 shows similarly a representative high LSF case of a 78-year-old patient (LSF = 15.3%, tumor volume 14.43 cm

^{3}). For QTM, $\left|\mathit{u}\right|$ = 0.09 mm/s, while for Kety’s method ${K}^{\mathit{trans}}$= 0.0313, ${V}_{e}$ = 0.0560 and $\tau =15.82\mathrm{s}$.

## 4. Discussion

**u**| with parameters from traditional kinetic modeling (also known as extended Toft’s model) [26]. In the patient cohort, QTM velocity $\left|\mathit{u}\right|$ but not Kety’s parameters demonstrated significant correlation with LSF. Although Kety’s method has not been applied to lung shunting fraction estimation in previous studies, this result is consistent with the hypothesis that increased artery–vein connections bypassing capillaries (shunts) increases the mean liver blood velocity, and also consistent with previous reports showing QTM improves upon Kety’s method by replacing a global arterial input function in Kety’s model with the local mass flux gradient in QTM [14,18,19]. In addition to a significantly higher velocity $\left|\mathit{u}\right|$ observed in high LSF group, we also observed an increase in Kety’s parameters ${K}^{trans}$ and ${V}_{e}$ in high LSF group, which may reflect a higher tissue exchange rate and EES space in tumors with abnormal vasculature compared to normal tissue [34,35]. These observations should be evaluated in further studies, especially using histopathology for validation.

## Author Contributions

## Funding

## Institutional Review Board Statement

## Informed Consent Statement

## Data Availability Statement

## Conflicts of Interest

## References

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**Figure 1.**DCE MRI, QTM velocity, ${K}^{trans}$ and ${V}_{e}$ maps of HCC of a 74-year-old patient with lung shunting fraction 9.3%. (

**a**) post-Gd T1 weighted image showing the tumor (red arrow). (

**b**) QTM |

**u**| map, (

**c**) ${K}^{trans}$ map, and (

**d**) ${V}_{e}$ map.

**Figure 2.**DCE MRI, QTM velocity, ${K}^{trans}$ and ${V}_{e}$ maps of HCC of a 78-year-old patient with lung shunting fraction 15.3%. (

**a**) post-Gd T1 weighted image showing the tumor (red arrow). (

**b**) QTM |

**u**| and ${V}_{e}$ map, (

**c**) ${K}^{trans}$ map, and (

**d**) ${V}_{e}$ map.

**Figure 3.**Spearman correlation and Bland–Altman plot of (

**a**) QTM $\left|\mathit{u}\right|$, (

**b**) ${K}^{trans}$ (

**c**) ${V}_{e}$, (

**d**) $\tau $ with lung shunting fraction (LSF).

**Figure 4.**Mann–Whitney U test of QTM $\left|\mathit{u}\right|$ (

**a**), ${K}^{trans}$ (

**b**), ${V}_{e}$ (

**c**), $\tau $ (

**d**) between low-risk subjects (lung shunting fraction $\le 10\%$) and high-risk subjects (lung shunting fraction $>10\%$). (LSF: lung shunting fraction; *: p < 0.05; **: p < 0.01).

**Figure 5.**Receiver operating characteristic curve (ROC) for QTM $\left|\mathit{u}\right|$, ${K}^{trans},{V}_{e},\tau $ in differentiating low-risk (lung shunting fraction $\le 10\%$) and high-risk (lung shunting fraction $>10\%$) subjects.

R (95% CI) | p Value | F Value | |
---|---|---|---|

QTM |u| | 0.6156 (0.4148–0.8164) | 0.0011 | 14.0363 |

${K}^{\mathit{trans}}$ | 0.2778 (0.0244–0.5312) | 0.1786 | 1.9251 |

${V}_{e}$ | 0.3936 (0.1403–0.6469) | 0.0516 | 4.2168 |

$\tau $ | 0.0883 (−0.0921–0.2687) | 0.1815 | 0.6741 |

Tumor volume | 0.2735 (0.0206–0.5264) | 0.1858 | 1.8603 |

Age | 0.2272 (−0.0180–0.4724) | 0.2749 | 1.2508 |

AUC (95% CI) | Sensitivity (95% CI) | Specificity (95% CI) | |
---|---|---|---|

QTM |u| | 0.87 (0.63–0.97) | 0.92 (0.63–1) | 0.83 (0.5–1) |

${K}^{\mathit{trans}}$ | 0.74 (0.49–0.90) | 0.77 (0.42–0.93) | 0.67 (0.30–0.89) |

${V}_{e}$ | 0.80 (0.56–0.93) | 0.62 (0.30–0.85) | 0.92 (0.54–1) |

$\tau $ | 0.57 (0.32–0.82) | 0.54 (0.23–0.80) | 0.58 (0.29–0.88) |

Tumor volume | 0.54 (0.30–0.76) | 0.31 (0.08–0.66) | 0.92 (0.63–1) |

Age | 0.59 (0.32–0.80) | 0.62 (0.31–0.85) | 0.67 (0.32–0.9) |

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**MDPI and ACS Style**

Zhang, Q.; Lee, K.S.; Talenfeld, A.D.; Spincemaille, P.; Prince, M.R.; Wang, Y. Prediction of Lung Shunt Fraction for Yttrium-90 Treatment of Hepatic Tumors Using Dynamic Contrast Enhanced MRI with Quantitative Perfusion Processing. *Tomography* **2022**, *8*, 2687-2697.
https://doi.org/10.3390/tomography8060224

**AMA Style**

Zhang Q, Lee KS, Talenfeld AD, Spincemaille P, Prince MR, Wang Y. Prediction of Lung Shunt Fraction for Yttrium-90 Treatment of Hepatic Tumors Using Dynamic Contrast Enhanced MRI with Quantitative Perfusion Processing. *Tomography*. 2022; 8(6):2687-2697.
https://doi.org/10.3390/tomography8060224

**Chicago/Turabian Style**

Zhang, Qihao, Kyungmouk Steve Lee, Adam D. Talenfeld, Pascal Spincemaille, Martin R. Prince, and Yi Wang. 2022. "Prediction of Lung Shunt Fraction for Yttrium-90 Treatment of Hepatic Tumors Using Dynamic Contrast Enhanced MRI with Quantitative Perfusion Processing" *Tomography* 8, no. 6: 2687-2697.
https://doi.org/10.3390/tomography8060224