Ventilation and perfusion MRI at a 0.35 T MR-Linac: feasibility and reproducibility study
Authors: Klaar Rabea , Rabe Moritz , Gaass Thomas , Schneider Moritz J. , Benlala Ilyes , Eze Chukwuka , Corradini Stefanie , Belka Claus , Landry Guillaume , Kurz Christopher , Dinkel Julien 
Published: April 2023

Abstract
Background
Hybrid devices that combine radiation therapy and MR-imaging have been introduced in the clinical routine for the treatment of lung cancer. This opened up not only possibilities in terms of accurate tumor tracking, dose delivery and adapted treatment planning, but also functional lung imaging. The aim of this study was to show the feasibility of Non-uniform Fourier Decomposition (NuFD) MRI at a 0.35 T MR-Linac as a potential treatment response assessment tool, and propose two signal normalization strategies for enhancing the reproducibility of the results.

Methods
Ten healthy volunteers (median age 28 ± 8 years, five female, five male) were repeatedly scanned at a 0.35 T MR-Linac using an optimized 2D+t balanced steady-state free precession (bSSFP) sequence for two coronal slice positions. Image series were acquired in normal free breathing with breaks inside and outside the scanner as well as deep and shallow breathing. Ventilation- and perfusion-weighted maps were generated for each image series using NuFD. For intra-volunteer ventilation map reproducibility, a normalization factor was defined based on the linear correlation of the ventilation signal and diaphragm position of each scan as well as the diaphragm motion amplitude of a reference scan. This allowed for the correction of signal dependency on the diaphragm motion amplitude, which varies with breathing patterns. The second strategy, which can be used for ventilation and perfusion, eliminates the dependency on the signal amplitude by normalizing the ventilation/perfusion maps with the average ventilation/perfusion signal within a selected region-of-interest (ROI). The position and size dependency of this ROI was analyzed. To evaluate the performance of both approaches, the normalized ventilation/perfusion-weighted maps were compared and the deviation of the mean ventilation/perfusion signal from the reference was calculated for each scan. Wilcoxon signed-rank tests were performed to test whether the normalization methods can significantly improve the reproducibility of the ventilation/perfusion maps.

Results
The ventilation- and perfusion-weighted maps generated with the NuFD algorithm demonstrated a mostly homogenous distribution of signal intensity as expected for healthy volunteers regardless of the breathing maneuver and slice position. Evaluation of the ROI’s size and position dependency showed small differences in the performance. Applying both normalization strategies improved the reproducibility of the ventilation by reducing the median deviation of all scans to 9.1%, 5.7% and 8.6% for the diaphragm-based, the best and worst performing ROI-based normalization, respectively, compared to 29.5% for the non-normalized scans. The significance of this improvement was confirmed by the Wilcoxon signed rank test with $$p\, <\, 0.01$$

p

<

0.01

at $$\alpha \, =\, 0.05$$

α

=

0.05

. A comparison of the techniques against each other revealed a significant difference in the performance between best ROI-based normalization and worst ROI ($$p\, =\, 0.01$$

p

=

0.01

) and between best ROI-based normalization and scaling factor ($$p\, =\, 0.02$$

p

=

0.02

), but not between scaling factor and worst ROI ($$p\, =\, 0.71$$

p

=

0.71

). Using the ROI-based approach for the perfusion-maps, the uncorrected deviation of 10.2% was reduced to 5.3%, which was shown to be significant ($$p\, <\, 0.01$$

p

<

0.01

).

Conclusions
Using NuFD for non-contrast enhanced functional lung MRI at a 0.35 T MR-Linac is feasible and produces plausible ventilation- and perfusion-weighted maps for volunteers without history of chronic pulmonary diseases utilizing different breathing patterns. The reproducibility of the results in repeated scans significantly benefits from the introduction of the two normalization strategies, making NuFD a potential candidate for fast and robust early treatment response assessment of lung cancer patients during MR-guided radiotherapy.