Nicholas Richards1, Michael Malmberg1, Samuel I. Adams-Tew1, Henrik Odéen1, Dennis Parker1, and Allison Payne1
1University of Utah, Salt Lake City, UT, United States
Synopsis
Keywords: Thermometry/Thermotherapy, Thermometry
Motivation: In current clinical magnetic resonance-guided focused ultrasound (MRgFUS) ablation applications, only aqueous tissues are monitored with MR thermometry. Accurate thermometry of heterogeneous aqueous and fat tissue volumes would increase treatment safety and efficacy.
Goal(s): Evaluate a single reference variable flip angle (SR-VFA) sequence for hybrid proton resonance frequency shift and ΔT1 MR thermometry in heterogeneous tissue volumes.
Approach: MRgFUS ablation in an in vivo rabbit model was monitored with SR-VFA thermometry. Cumulative thermal dose (CTD) maps calculated from SR-VFA images were compared with non-perfused volumes and histological samples.
Results: SR-VFA derived CTD maps accurately predicted volumes of thermal damage in muscle and fat.
Impact: Hybrid proton resonance frequency shift and T1 thermometry allows for accurate temperature monitoring of heterogeneous tissue volumes. This increases the safety and efficacy of MR-guided focused ultrasound treatments in mixed-tissue treatment areas by ensuring target temperatures reach appropriate thresholds.
Introduction
A significant advantage of MR-guided focused ultrasound (MRgFUS) is the ability to monitor temperature change during treatment using magnetic resonance thermometry (MRT). For aqueous tissues, the proton resonance frequency (PRF) shift method provides clinically relevant temporal and spatial resolution1,2 but is not sensitive to temperature changes in fat.3 While it is known that measuring T1 changes can measure temperature change in fat,4,5 this has not been used clinically.
A hybrid MRT sequence has been developed to simultaneously measure temperature using both the PRF and T1 thermometry methods.6-8 PRF shift is calculated at each time point while ΔT1 is calculated using a single reference image with the variable flip angle method in a stack-of-stars sampling method (SR-VFA-SoS). The SR-VFA-SoS sequence has been evaluated under phantom and non-heating conditions, demonstrating the ability to simultaneously measure 3D PRF and T1 changes.9 This work evaluates the SR-VFA-SoS approach for predicting thermal ablation in MRgFUS in an in vivo rabbit model through comparing thermal biomarkers to post-treatment images and histology data.Methods
In vivo
experiments (New Zealand white rabbits, N=4) were performed in a 3T MRI scanner
(Prisma, Siemens) using an MRgFUS system (Figure 1a).
Animals were positioned supine with the treatment area acoustically coupled
to the transducer (Figure 1b). Sequential volumetric
sonications (40s, 27-31W acoustic power, N=9) were performed in a grid pattern
centered at the perirenal fat-paraspinal muscle interface. Hybrid thermometry data
was acquired during sonications using the SR-VFA-SoS sequence with
pseudo-Golden Angle (pGA) view angle increment of 360x233/377 and 377 total
projections. Prior to each sonication, two baseline acquisitions at a lower
flip angle were acquired, and five total dynamic acquisitions at a higher flip
angle were acquired before, during, and after each sonication (Figure 2a).
The sonication was applied starting at the beginning of the third dynamic
acquisition. T1-weighted and T2-weighted MR images were
captured before and after MRgFUS ablation, with additional contrast-enhanced T1-weighted
imaging post-ablation. Animals were euthanized immediately following
post-ablation imaging.
Reconstruction
of the SR-VFA-SoS images were performed using a k-space weighted image contrast
(KWIC) method as described in Song, et al.,11 with 13 central
projections and 377 total projections using a sliding asymmetric window to
leverage oversampling at the center of radial projections (Figure 2b-d).
Temporal resolution for the T1 and PRF shift temperature data was
1.71 s. Temperature and ΔT1 data was acquired at 1.5 × 1.5 × 2 mm (zero-fill
interpolated to 0.75 × 0.75 × 2 mm). 2-point Dixon images were used to
calculate water- and fat-fraction images, which were in turn used to segment
images into muscle and fat voxels. Hybrid thermometry maps were formed by using
PRF thermometry data for muscle voxels and ΔT1 for fat voxels. The ΔT1 data was converted to
temperature using a previously experimentally derived conversion factor of 7.3
ms/°C.12
Cumulative
thermal dose (CTD) maps were calculated.13 The volume of
hyperintense regions of contrast-enhanced post-treatment images was calculated
and compared with the volume of the associated PRF shift only and hybrid SR-VFA-SoS
thermometry CTD maps.
Muscle and fat tissue
from the treated area were excised for histology. Tissue samples were fixed,
processed, embedded, sectioned, and stained with H&E. A compound light
microscope was used to assess tissue damage in sonicated regions.Results
PRF-only and hybrid PRF and ΔT1-based temperature changes were successfully calculated for all sonications (Figure 3). Peak temperature rises from 23.6 to 32.0 °C were observed for individual sonications. CTD maps based on PRF-only thermometry accurately monitored thermal damage in muscle but, as expected, did not measure any thermal damage in fat. CTD maps calculated from hybrid PRF and ΔT1-based temperature changes measured thermal damage in both muscle and fat, qualitatively aligning with hypointense regions in opposed-phase Dixon images (Figure 4). Histology confirmed thermal damage in sonicated regions of both muscle and fat (Figure 5).Discussion
This work demonstrates the capability of the SR-VFA-SoS method for predicting thermal ablation using simultaneous PRF shift and ΔT1 measurement in vivo. CTD maps calculated from the SR-VFA-SoS thermometry more accurately predicted thermal damage than CTD maps calculated from PRF shift-only thermometry. Predicted thermal damage was confirmed via histological samples taken from the treatment site. Future work will improve the SR-VFA-SoS sequence by reducing the reconstruction time to real time for clinical use.Conclusion
This work provides an in vivo evaluation of the SR-VFA-SoS method of 3D hybrid PRF shift and ΔT1 thermometry for predicting thermal ablation in heterogeneous tissue volumes. The SR-VFA sequence ultimately allows for accurate temperature monitoring across entire volumes of mixed tissue types with high temporal and spatial resolution.Acknowledgements
This work is supported by NIH R37CA224141, S10OD018482, and 5R01EB028316.References
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