# MR Thermometry Accuracy and Prospective Imaging-Based Patient Selection in MR-Guided Hyperthermia Treatment for Locally Advanced Cervical Cancer

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## Abstract

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## Simple Summary

## Abstract

## 1. Introduction

^{2}= 0.67 and an accuracy of 1.5 °C between MR thermometry and thermistor probe readings. A follow-up study included patients with soft tissue sarcomas of the lower extremities and pelvis [44] and showed a correlation of R

^{2}= 0.96 between MR thermometry and thermistor probe readings. Craciunescu et al. [45] evaluated the bias between MR thermometry and invasive thermometry for high-grade extremity soft-tissue sarcomas. They found that the mean differences in a small volume of interest around interstitial probe positions were below 1 °C. However, Craciunescu et al. [45] showed that in regions at muscle/fat or tumor/fat, the bias was 1.89 °C. For large extremity soft tissue sarcoma, Stauffer et al. [46] showed that the bias between MR thermometry and interstitial measurements was 0.85 °C. In a more recent study, Unsoeld et al. [33] found a correlation between MR thermometry data and pathologic response for soft-tissue sarcomas of the lower extremities. Assessment of MR thermometry performance in deep pelvic tumors; i.e., nearby inner patient locations with motion such as moving air in the intestines has been evaluated in only a few studies [43,44,47]. These studies did show a qualitative correlation between invasive/intraluminal probe measurements and MR thermometry. However, these did not evaluate the accuracy in a volume of interest close to the temperature probes, the latter being crucial information for clinical acceptance. In addition, no studies have reported MR thermometry temporal precision for RF hyperthermia [48]. Finally, replicating these results is lacking and will be cumbersome in a retrospective setting due to the strong but not clearly defined patient selection. Hence, the accuracy of MR thermometry during deep pelvic hyperthermia treatments remains ambiguous.

## 2. Materials and Methods

#### 2.1. Patients and Clinical Protocol

#### 2.2. MR Thermometry Image Acquisition

#### 2.3. Contouring and Region Selection

^{2}. Body fat was delineated for MRT correction purposes and to evaluate its impact on MR thermometry accuracy. As presented in Figure 3, gastrointestinal air was delineated in the baseline scans to evaluate the impact of air volume and motion on MR thermometry accuracy during the treatment.

#### 2.4. MR Thermometry Processing

**Uncorrected MR thermometry maps**: MR thermometry maps were calculated by taking the difference between the phase maps (${\mathsf{\phi}}_{00}$ and ${\mathsf{\phi}}_{\mathrm{n}}$), which is formulated as:$$\u2206\mathrm{T}\left(\mathrm{n}\right)=\frac{{\mathsf{\phi}}_{\mathrm{n}}{-\mathsf{\phi}}_{00}}{{\mathsf{\gamma}\mathsf{\alpha}\mathrm{B}}_{0}\mathrm{TE}}$$^{6}rad/T∙s; $\mathsf{\alpha}$ is the PRF change coefficient, which is equal to −0.001 ppm/°C; ${\mathrm{B}}_{0}$ is the magnetic field strength equal to 1.5 T; TE is the echo time equal to 19.1 ms; and n is the scan time.**Low SNR masking**: For each MR thermometry map, voxels with low SNR corresponding to a temperature deviation > 3 °C with respect to three-by-three neighbors were masked to prevent the inclusion of noisy data in the voxels used for drift correction.**B0 drift correction**: In addition to the four fat-like tubes included in the hyperthermia device, body fat (Figure 2) was used to compensate for changes of the static magnetic field B0. A 2D polynomial spatial-temporal correction was applied across the MR temperature maps such that temperature changes are reversed to zero in the selected fat regions. Hence, ${\mathrm{T}}_{\mathrm{MR}}$ denotes the final corrected MR thermometry.**Inaccurate data exclusion**: Unrealistic data was removed to avoid pollution by data points affected by confounders such as moving air or other motion. The absolute difference between intraluminal measurements and average MR thermometry measurement within ROIs was minimized. The absolute difference between the two measurements is given by Equation (2), and the minimization is given by Equation (3). The threshold for removal was found to be 7 °C, which was iteratively found between 0 °C and 20 °C using an optimization cycle.$$\mathrm{G}\left(\mathrm{p}\right)=\left|\left(\frac{1}{\mathrm{card}\left(\mathrm{J}\right)}{\displaystyle \sum}_{\mathrm{j}=1}^{\mathrm{j}}{\mathrm{T}}_{\mathrm{MR}}{(\mathrm{n},\mathrm{p})}_{\mathrm{j}}\right)-{\overline{\mathrm{T}}}_{{\mathrm{probe}}_{\mathrm{ROI}}}\left(\mathrm{n}\right)\right|$$$$\mathrm{threshold}=\mathrm{arg}\underset{\mathrm{p}}{\mathrm{min}}\mathrm{G}\left(\mathrm{p}\right)\mathrm{subject}\mathrm{to}0\le \mathrm{p}\le 20$$**Average MR thermometry measurement within ROI**: For each probe location, at each scanning time, the average temperature was calculated within the delineated ROIs $({\overline{\mathrm{T}}}_{{\mathrm{MR}}_{\mathrm{ROI}}}$ ). The formulation of the average temperature is given by:$${\overline{\mathrm{T}}}_{{\mathrm{MR}}_{\mathrm{ROI}}}\left(\mathrm{n}\right)=\frac{1}{\mathrm{card}\left(\mathrm{J}\right)}{\displaystyle \sum}_{\mathrm{j}=1}^{\mathrm{j}}{\mathrm{T}}_{\mathrm{MR}}\left(\mathrm{n}\right){}_{\mathrm{j}}$$

#### 2.5. Imaging-Based MRT Accuracy Prediction Parameters

## 3. Results

#### 3.1. Predictive Value for MRT Accuracy of Imaging-Based Parameters

#### 3.2. MRT Accuracy for All Data versus MRT Accuracy from Selected Sessions

**All data**: The robustness of MR thermometry accuracy prediction was evaluated by quantifying the temperature accuracy for all probe locations (Figure 6). Figure 6a shows that the median accuracy within the ROIs for all probe locations was 1.7 °C. Light red circles in Figure 6a mark the mean accuracy expressed in Table 2. The mean MR thermometry accuracy in all intraluminal locations was outside the acceptable threshold of 1 °C [48,57]. In addition, the total mean accuracy was equal to 2 °C. The differences in accuracy and the number of voxels used between the different intraluminal locations were insignificant (p-value > 0.05).

**After selection**: The MR thermometry accuracy of the selected sessions (Jaccard coefficient ≥ 0.91) was lower than when considering all data. The median MR thermometry accuracy for the bladder, rectum, and vagina was 0.8 °C, 0.6 °C, and 0.7 °C, respectively (Figure 6b). The marked points in Figure 6b show that even though there was an improvement, the mean MR thermometry accuracy was within the acceptable values only in the vagina ROIs (0.9 °C). In contrast, the mean accuracy was equal to 1.1 °C in the bladder and rectum ROIs. Imaging-based selection excluded 36% of the total patients, but the percentage of voxels remaining after filtering increased from 76% to 88%. The differences in accuracy between the different intraluminal locations were not significant (p-value > 0.05). Note that significantly more voxels of the bladder ROIs remain after filtering than in the ROIs of the rectum and vagina (p-value = 0.04).

## 4. Discussion

#### 4.1. Image Parameters to Select Treatments with Robust MRT

#### 4.2. Clinical Relevance

#### 4.3. Study Limitations

## 5. Conclusions

## Author Contributions

## Funding

## Institutional Review Board Statement

## Informed Consent Statement

## Data Availability Statement

## Acknowledgments

## Conflicts of Interest

## References

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**Figure 1.**Description of the clinical MR protocol. Each sequence is represented with a color. High-resolution scan and two MR thermometry scans were taken before the treatment, and approximately nine MR thermometry scans were performed during treatment.

**Figure 2.**(

**a**) An axial and a sagittal T1-weighted MR image of the pelvic are shown along with an illustration of the location of the Bowman probes points and the corresponding delineated ROIs: vagina, rectum, and bladder. The left and right images correspond to the middle axial slice (z = −2 cm) and middle sagittal slice (x = 0 cm), respectively. Body fat and fat-like tube ROIs are indicated in the axial MR image. (

**b**) Schematic representation of the probe ROI contour in the axial and sagittal view.

**Figure 3.**The axial anatomic images and a zoomed region from MR thermometry reference scans are shown: (

**a**) presents the gastrointestinal air contours in the two first baseline scans and the overlap of these contours in the first baseline scan; (

**b**) shows the distances between the probe and gastrointestinal air contour. This representative treatment session presented: Jaccard coefficient = 0.67; minimum distance = 0.2 cm; fat volume = 8782.7 mL; and gastrointestinal air volume = 548.5 mL.

**Figure 4.**ROC curve analysis of each predicted condition. The cross marked in each curve indicates the optimal cut-off value, and the shade under each represents AUC. The identity line presented by a solid grey line represents the ROC curve with an AUC equal to 0.5.

**Figure 5.**Representative session with Jaccard coefficient equal to 1 and the gastrointestinal air volume was equal to 221 mL. The first image represents the MR thermometry map between the phase images of ${S}_{00}$ and ${S}_{01}$. The following three images represent the MR thermometry maps after 18, 29, and 50 min from when RF power was applied (treatment start).

**Figure 6.**Evaluation of MR thermometry accuracy in (

**a**) all treatment sessions and (

**b**) in the group of selected treatment sessions. The MR thermometry was calculated for the three intraluminal locations. The evaluation of MR thermometry was based on the voxels remaining after filtering and data used in the analysis. The dashed red line represents the acceptable mean accuracy threshold (1 °C) and, in light red circles, the mean MR thermometry accuracy in each location. The inter-quartile range denotes the middle 50% of the dataset. The top box shows 75% of the dataset that falls below the upper quartile, while the bottom line consists of 25% of the dataset that falls below the lower quartile. The middle line represents the median value, and the line extending from the box represents 2.5% and 97.5% limits of the dataset.

**Figure 7.**Evaluation of MR thermometry precision and bias in (

**a**) all treatment sessions and (

**b**) in the group of selected treatment sessions. The MR thermometry was calculated for the three intraluminal locations. The evaluation of MR thermometry was based on the voxels remaining after filtering and data used in the analysis. The dashed red line represents the acceptable mean accuracy threshold (1 °C) and, in light red circles, the mean MR thermometry accuracy in each location. The inter-quartile range denotes the middle 50% of the dataset. The top box shows 75% of the dataset that falls below the upper quartile, while the bottom line consists of 25% of the dataset that falls below the lower quartile. The middle line represents the median value, and the line extending from the box represents 2.5% and 97.5% limits of the dataset.

**Table 1.**Characterization of the data used in this study: patient and tumor characteristics, and hyperthermia treatment sessions characteristics. For continuous data, the age, total number of sessions, and values were expressed by the mean ± standard deviation.

Characteristic | Categories | Value |
---|---|---|

Patient/Tumor Characteristics | ||

Total number of patients | 14 | |

Age (years) | 56.5 ± 16.7 | |

Median age (years) | 60 | |

Histology | Adenocarcinoma | 3 |

Squamous cell carcinoma | 10 | |

Carcinosarcoma | 1 | |

FIGO stage | IA | 1 |

IB | 2 | |

IIB | 5 | |

IIIB | 4 | |

IVA | 2 | |

Hyperthermia Treatment Session Characteristics | ||

Total number of sessions | 39 | |

Number of treatment sessions per patient | 2.8 ± 1.5 | |

Duration of each treatment session (minutes) | 89.5 ± 1.6 | |

MR thermometry scans per treatment session | 8.8 ± 1.5 | |

The time between the start of the two baseline scans (seconds) | 97.0 ± 10.0 | |

Number of MR thermometry slices with identified probes | 7.3 ± 2.4 | |

Number of probe mapping measurements during treatment time | 15.2 ± 3.0 | |

Maximum probe measurements range (cm) | Bladder | 9.9 ± 2.2 |

Rectum | 6.9 ± 2.1 | |

Vagina | 8.4 ± 2.5 | |

Maximum net heating power (W) | 941.1 ± 118.7 |

**Table 2.**Accuracy, precision, and bias parameters of MR thermometry in all treatment sessions and the selected dataset based on the Jaccard coefficient threshold equal to 0.91. All evaluation parameters are expressed by the mean (µ) ± standard deviation (σ); these mean values are also indicated in light red circles in Figure 6 and Figure 7. The number of sessions and patients remaining after exclusion are indicated. In addition, the average deviation from the acceptable threshold is given for accuracy (1 °C), precision (1 °C), and bias (±0.5 °C). The equal values or below the acceptable threshold are in boldface and underline.

All Treatment Sessions | Selected for Air Motion (Jaccard Coefficient ≥ 0.91) | |||||||
---|---|---|---|---|---|---|---|---|

Bladder | Rectum | Vagina | Deviation from the Acceptable Threshold | Bladder | Rectum | Vagina | Deviation from the Acceptable Threshold | |

Accuracy | 2.2 ± 1.6 | 1.9 ± 1.4 | 2.0 ± 1.5 | +1.0 °C | 1.1 ± 0.7 | 1.1 ± 1.1 | 0.9 ± 0.6 | −0.0 °C |

Precision | 1.7 ± 0.9 | 1.6 ± 0.9 | 1.7 ± 0.8 | +0.7 °C | 1.2 ± 0.4 | 1.2 ± 0.6 | 1.3 ± 0.4 | +0.2 °C |

Bias | −1.5 ± 2.1 | −1.2 ± 1.7 | −1.2 ± 1.8 | +0.8 °C | −0.4 ± 1.1 | −0.4 ± 1.4 | 0.0 ± 1.0 | −0.3 °C |

Sessions | 39 sessions (100%) | 15 sessions (38%) | ||||||

Patients | 14 patients (100%) | 9 patients (64%) |

**Table 3.**Mean and standard deviation (µ ± σ) of temperature increase from MR thermometry measurements and intraluminal temperature measurements in delineated ROIs. The percentage of sessions and patients used in each study is compared with the total number. The mean temperature increase is reported for the dataset with low gastrointestinal air motion. MR thermometry measurements are expressed as MRT, and Intraluminal corresponds to the intraluminal measurements.

Measurements: Mean Temperature Increase (°C) | ||||||
---|---|---|---|---|---|---|

This Study | Other Studies | |||||

Location | LACC | Gellermann et al. [43] Recurrent Rectal cancer | Gellermann et al. [44] Soft Tissue Sarcoma | |||

MRT | Intraluminal | MRT | Intraluminal | MRT | Intraluminal | |

Bladder | 2.4 °C ± 1.7 °C | 2.5 °C ± 1.2 °C | >7 °C | No data | ≤4 to 5 °C | 2.6 °C ± 1.3 °C |

Vagina | 2.6 °C ± 1.6 °C | 2.4 °C ± 1.2 °C | No data | 2.2 °C ± 0.6 °C | ||

Rectum | 2.1 °C ± 1.4 °C | 2.5 °C ± 1.3 °C | ~3 °C | 3.5 °C ± 1.0 °C | ||

Sessions | 15 sessions (38%) | 15 sessions (20%) | 15 sessions (50%) | |||

Patients | 9 patients (64%) | 15 patients (100%) | 9 patients (100%) |

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**MDPI and ACS Style**

VilasBoas-Ribeiro, I.; Curto, S.; van Rhoon, G.C.; Franckena, M.; Paulides, M.M.
MR Thermometry Accuracy and Prospective Imaging-Based Patient Selection in MR-Guided Hyperthermia Treatment for Locally Advanced Cervical Cancer. *Cancers* **2021**, *13*, 3503.
https://doi.org/10.3390/cancers13143503

**AMA Style**

VilasBoas-Ribeiro I, Curto S, van Rhoon GC, Franckena M, Paulides MM.
MR Thermometry Accuracy and Prospective Imaging-Based Patient Selection in MR-Guided Hyperthermia Treatment for Locally Advanced Cervical Cancer. *Cancers*. 2021; 13(14):3503.
https://doi.org/10.3390/cancers13143503

**Chicago/Turabian Style**

VilasBoas-Ribeiro, Iva, Sergio Curto, Gerard C. van Rhoon, Martine Franckena, and Margarethus M. Paulides.
2021. "MR Thermometry Accuracy and Prospective Imaging-Based Patient Selection in MR-Guided Hyperthermia Treatment for Locally Advanced Cervical Cancer" *Cancers* 13, no. 14: 3503.
https://doi.org/10.3390/cancers13143503