Inter-scanner super-resolution of 3D cine MRI using a transfer-learning network for MRgRT.

OBJECTIVE: Deep-learning networks for super-resolution (SR) reconstruction enhance the spatial-resolution of 3D magnetic resonance imaging (MRI) for MR-guided radiotherapy (MRgRT). However, variations between MRI scanners and patients impact the quality of SR for real-time 3D low-resolution (LR) cine MRI. In this study, we present a personalized super-resolution (psSR) network that incorporates transfer-learning to overcome the challenges in inter-scanner SR of 3D cine MRI. Approach: Development of the proposed psSR network comprises two-stages: 1) a cohort-specific SR (csSR) network using clinical patient datasets, and 2) a psSR network using transfer-learning to target datasets. The csSR network was developed by training on breath-hold and respiratory-gated high-resolution (HR) 3D MRIs and their k-space down-sampled LR MRIs from 53 thoracoabdominal patients scanned at 1.5 T. The psSR network was developed through transfer-learning to retrain the csSR network using a single breath-hold HR MRI and a corresponding 3D cine MRI from 5 healthy volunteers scanned at 0.55 T. Image quality was evaluated using the peak-signal-noise-ratio (PSNR) and the structure-similarity-index-measure (SSIM). The clinical feasibility was assessed by liver contouring on the psSR MRI using an auto-segmentation network and quantified using the Dice-similarity-coefficient (DSC). Results. Mean PSNR and SSIM values of psSR MRIs were increased by 57.2% (13.8 to 21.7) and 94.7% (0.38 to 0.74) compared to cine MRIs, with the reference 0.55 T breath-hold HR MRI. In the contour evaluation, DSC was increased by 15% (0.79 to 0.91). Average time consumed for transfer-learning was 90 s, psSR was 4.51 ms per volume, and auto-segmentation was 210 ms, respectively. Significance. The proposed psSR reconstruction substantially increased image and segmentation quality of cine MRI in an average of 215 ms across the scanners and patients with less than 2 minutes of prerequisite transfer-learning. This approach would be effective in overcoming cohort- and scanner-dependency of deep-learning for MRgRT. .

Technical note: Minimizing CIED artifacts on a 0.35 T MRI-Linac using deep learning.

BACKGROUND: Artifacts from implantable cardioverter defibrillators (ICDs) are a challenge to magnetic resonance imaging (MRI)-guided radiotherapy (MRgRT). PURPOSE: This study tested an unsupervised generative adversarial network to mitigate ICD artifacts in balanced steady-state free precession (bSSFP) cine MRIs and improve image quality and tracking performance for MRgRT. METHODS: Fourteen healthy volunteers (Group A) were scanned on a 0.35 T MRI-Linac with and without an MR conditional ICD taped to their left pectoral to simulate an implanted ICD. bSSFP MRI data from 12 of the volunteers were used to train a CycleGAN model to reduce ICD artifacts. The data from the remaining two volunteers were used for testing. In addition, the dataset was reorganized three times using a Leave-One-Out scheme. Tracking metrics [Dice similarity coefficient (DSC), target registration error (TRE), and 95 percentile Hausdorff distance (95% HD)] were evaluated for whole-heart contours. Image quality metrics [normalized root mean square error (nRMSE), peak signal-to-noise ratio (PSNR), and multiscale structural similarity (MS-SSIM) scores] were evaluated. The technique was also tested qualitatively on three additional ICD datasets (Group B) including a patient with an implanted ICD. RESULTS: For the whole-heart contour with CycleGAN reconstruction: 1) Mean DSC rose from 0.910 to 0.935; 2) Mean TRE dropped from 4.488 to 2.877 mm; and 3) Mean 95% HD dropped from 10.236 to 7.700 mm. For the whole-body slice with CycleGAN reconstruction: 1) Mean nRMSE dropped from 0.644 to 0.420; 2) Mean MS-SSIM rose from 0.779 to 0.819; and 3) Mean PSNR rose from 18.744 to 22.368. The three Group B datasets evaluated qualitatively displayed a reduction in ICD artifacts in the heart. CONCLUSION: CycleGAN-generated reconstructions significantly improved both tracking and image quality metrics when used to mitigate artifacts from ICDs.

Feasibility of surface-guidance combined with CBCT for intra-fractional breath-hold motion management during Ethos RT.

PURPOSE: High-quality CBCT and AI-enhanced adaptive planning techniques allow CBCT-guided stereotactic adaptive radiotherapy (CT-STAR) to account for inter-fractional anatomic changes. Studies of intra-fractional respiratory motion management with a surface imaging solution for CT-STAR have not been fully conducted. We investigated intra-fractional motion management in breath-hold Ethos-based CT-STAR and CT-SBRT (stereotactic body non-adaptive radiotherapy) using optical surface imaging combined with onboard CBCTs. METHODS: Ten cancer patients with mobile lower lung or upper abdominal malignancies participated in an IRB-approved clinical trial (Phase I) of optical surface image-guided Ethos CT-STAR/SBRT. In the clinical trial, a pre-configured gating window (± 2 mm in AP direction) on optical surface imaging was used for manually triggering intra-fractional CBCT acquisition and treatment beam irradiation during breath-hold (seven patients for the end of exhalation and three patients for the end of inhalation). Two inter-fractional CBCTs at the ends of exhalation and inhalation in each fraction were acquired to verify the primary direction and range of the tumor/imaging-surrogate (donut-shaped fiducial) motion. Intra-fractional CBCTs were used to quantify the residual motion of the tumor/imaging-surrogate within the pre-configured breath-hold window in the AP direction. Fifty fractions of Ethos RT were delivered under surface image-guidance: Thirty-two fractions with CT-STAR (adaptive RT) and 18 fractions with CT-SBRT (non-adaptive RT). The residual motion of the tumor was quantified by determining variations in the tumor centroid position. The dosimetric impact on target coverage was calculated based on the residual motion. RESULTS: We used 46 fractions for the analysis of intra-fractional residual motion and 43 fractions for the inter-fractional motion analysis due to study constraints. Using the image registration method, 43 pairs of inter-fractional CBCTs and 100 intra-fractional CBCTs attached to dose maps were analyzed. In the motion range study (image registration) from the inter-fractional CBCTs, the primary motion (mean ± std) was 16.6 ± 9.2 mm in the SI direction (magnitude: 26.4 ± 11.3 mm) for the tumors and 15.5 ± 7.3 mm in the AP direction (magnitude: 20.4 ± 7.0 mm) for the imaging-surrogate, respectively. The residual motion of the tumor (image registration) from intra-fractional breath-hold CBCTs was 2.2 ± 2.0 mm for SI, 1.4 ± 1.4 mm for RL, and 1.3 ± 1.3 mm for AP directions (magnitude: 3.5 ± 2.1 mm). The ratio of the actual dose coverage to 99%, 90%, and 50% of the target volume decreased by 0.95 ± 0.11, 0.96 ± 0.10, 0.99 ± 0.05, respectively. The mean percentage of the target volume covered by the prescribed dose decreased by 2.8 ± 4.4%. CONCLUSION: We demonstrated the intra-fractional motion-managed treatment strategy in breath-hold Ethos CT-STAR/SBRT using optical surface imaging and CBCT. While the controlled residual tumor motion measured at 3.5 mm exceeded the predetermined setup value of 2 mm, it is important to note that this motion still fell within the clinically acceptable range defined by the PTV margin of 5 mm. Nonetheless, additional caution is needed with intra-fractional motion management in breath-hold Ethos CT-STAR/SBRT using optical surface imaging and CBCT.

Respiratory motion management using a single rapid MRI scan for a 0.35 T MRI-Linac system.

BACKGROUND: MRI has a rapidly growing role in radiation therapy (RT) for treatment planning, real-time image guidance, and beam gating (e.g., MRI-Linac). Free-breathing 4D-MRI is desirable in respiratory motion management for therapy. Moreover, high-quality 3D-MRIs without motion artifacts are needed to delineate lesions. Existing MRI methods require multiple scans with lengthy acquisition times or are limited by low spatial resolution, contrast, and signal-to-noise ratio. PURPOSE: We developed a novel method to obtain motion-resolved 4D-MRIs and motion-integrated 3D-MRI reconstruction using a single rapid (35-45 s scan on a 0.35 T MRI-Linac. METHODS: Golden-angle radial stack-of-stars MRI scans were acquired from a respiratory motion phantom and 12 healthy volunteers (n = 12) on a 0.35 T MRI-Linac. A self-navigated method was employed to detect respiratory motion using 2000 (acquisition time = 5-7 min) and the first 200 spokes (acquisition time = 35-45 s). Multi-coil non-uniform fast Fourier transform (MCNUFFT), compressed sensing (CS), and deep-learning Phase2Phase (P2P) methods were employed to reconstruct motion-resolved 4D-MRI using 2000 spokes (MCNUFFT2000) and 200 spokes (CS200 and P2P200). Deformable motion vector fields (MVFs) were computed from the 4D-MRIs and used to reconstruct motion-corrected 3D-MRIs with the MOtion Transformation Integrated forward-Fourier (MOTIF) method. Image quality was evaluated quantitatively using the structural similarity index measure (SSIM) and the root mean square error (RMSE), and qualitatively in a blinded radiological review. RESULTS: Evaluation using the respiratory motion phantom experiment showed that the proposed method reversed the effects of motion blurring and restored edge sharpness. In the human study, P2P200 had smaller inaccuracy in MVFs estimation than CS200. P2P200 had significantly greater SSIMs (p < 0.0001) and smaller RMSEs (p < 0.001) than CS200 in motion-resolved 4D-MRI and motion-corrected 3D-MRI. The radiological review found that MOTIF 3D-MRIs using MCNUFFT2000 exhibited the highest image quality (scoring > 8 out of 10), followed by P2P200 (scoring > 5 out of 10), and then motion-uncorrected (scoring < 3 out of 10) in sharpness, contrast, and artifact-freeness. CONCLUSIONS: We have successfully demonstrated a method for respiratory motion management for MRI-guided RT. The method integrated self-navigated respiratory motion detection, deep-learning P2P 4D-MRI reconstruction, and a motion integrated reconstruction (MOTIF) for 3D-MRI using a single rapid MRI scan (35-45 s) on a 0.35 T MRI-Linac system.

Characterization of the Targeting Accuracy of a Neuronavigation-Guided Transcranial FUS System In Vitro, In Vivo, and In Silico.

Focused ultrasound (FUS)-enabled liquid biopsy (sonobiopsy) is an emerging technique for the noninvasive and spatiotemporally controlled diagnosis of brain cancer by inducing blood-brain barrier (BBB) disruption to release brain tumor-specific biomarkers into the blood circulation. The feasibility, safety, and efficacy of sonobiopsy were demonstrated in both small and large animal models using magnetic resonance-guided FUS devices. However, the high cost and complex operation of magnetic resonance-guided FUS devices limit the future broad application of sonobiopsy in the clinic. In this study, a neuronavigation-guided sonobiopsy device is developed and its targeting accuracy is characterized in vitro, in vivo, and in silico. The sonobiopsy device integrated a commercially available neuronavigation system (BrainSight) with a nimble, lightweight FUS transducer. Its targeting accuracy was characterized in vitro in a water tank using a hydrophone. The performance of the device in BBB disruption was verified in vivo using a pig model, and the targeting accuracy was quantified by measuring the offset between the target and the actual locations of BBB opening. The feasibility of the FUS device in targeting glioblastoma (GBM) tumors was evaluated in silico using numerical simulation by the k-Wave toolbox in glioblastoma patients. It was found that the targeting accuracy of the neuronavigation-guided sonobiopsy device was 1.7 ± 0.8 mm as measured in the water tank. The neuronavigation-guided FUS device successfully induced BBB disruption in pigs with a targeting accuracy of 3.3 ± 1.4 mm. The targeting accuracy of the FUS transducer at the GBM tumor was 5.5 ± 4.9 mm. Age, sex, and incident locations were found to be not correlated with the targeting accuracy in GBM patients. This study demonstrated that the developed neuronavigation-guided FUS device could target the brain with a high spatial targeting accuracy, paving the foundation for its application in the clinic.

Real-time B0 compensation during gantry rotation in a 0.35-T MRI-Linac.

BACKGROUND: Rotation of the ferromagnetic gantry of a low magnetic field MRI-Linac was previously demonstrated to cause large center frequency offsets of ±400 Hz. The B0 off-resonances cause image artifacts and imaging isocenter shifts that would preclude MRI-guided arc therapy. PURPOSE: The purpose of this study was to measure and compensate for center frequency offsets in real time during gantry rotation on a 0.35-T MRI-Linac using a free induction decay (FID) navigator. METHODS: A nonselective FID navigator was added before each 2D balanced steady-state free precession cine image acquisition on a 0.35-T MRI-Linac. Images were acquired at 7.3 frames per second. Phase data from the initial FID navigator (while the gantry was stationary) was used as a reference. The phase data from each subsequent FID navigator was used to calculate the real-time B0 off-resonance. The transmitter/receiver phase and the phase accrual over the adjacent image acquisition were adjusted to correct for the center frequency offset. Measurements were performed using an MRI-Linac dynamic phantom prior to and while the gantry rotated clockwise and counterclockwise. Image quality and signal-to-noise ratio (SNR) were compared between uncorrected and B0 -corrected MRIs using a reference image acquired while the gantry was stationary. Four targets in the phantom were manually contoured on the first image frame, and an active contouring algorithm was used retrospectively on each subsequent frame to assess image variations and calculate Dice coefficients. Additionally, three healthy volunteers were imaged using the same pulse sequences with and without real-time B0 compensation during gantry rotation. Normalized root mean square errors (nRMSEs) were calculated for the phantom and in vivo to assess the efficacy of the B0 compensation on image quality. The measured center frequency offsets from the volunteer and MRI dynamic phantom navigator data were also compared. The sinusoidal behavior of the center frequency offsets was modeled based on the gantry layout and long-time constant eddy currents resulting from gantry rotation. RESULTS: The duration of the FID navigator and processing was 4.5 ms. The FID navigator resulted in a ≤11% drop in SNR in the phantom and in vivo (liver). Dice coefficients from the MRI-guided radiation therapy (MR-IGRT) phantom contour measurements remained above 0.8 with B0 compensation. Without B0 compensation, the Dice coefficients dropped below 0.8 for up to 21% of the time depending on the contour. Real-time B0 compensation resulted in mean reductions in nRMSE of 51% and 16% for the MR-IGRT phantom and in vivo, respectively. Peak-to-peak center frequency offsets ranged from 757 to 773 Hz in the phantom and 760 to 871 Hz in vivo. CONCLUSION: Dynamic real-time B0 compensation significantly improved image quality and reduced artifacts during gantry rotation in the phantom and in vivo. However, the FID navigator resulted in a small drop in the imaging duty cycle and SNR.

Technical note: Institutional solution of clinical cine MRI for tumor motion evaluation in radiotherapy.

PURPOSE: Since 4D-MRI is inadequate to capture dynamic respiratory variations, real-time cinematographic (cine) MRI is actively used in MR-guided radiotherapy (MRgRT) for tumor motion evaluation, delineation, and tracking. However, most radiotherapy imaging platforms do not support the format of cine MRI from clinical MRI systems. This study developed an institutional solution of clinical cine MRI for tumor motion evaluation in radiotherapy applications. METHODS: Cine MRI manipulation software (called Cine Viewer) was developed within a commercial Treatment Planning System (TPS). It consists of (1) single/orthogonal viewers, (2) display controllers, (3) measurement grids/markers, and (4) manual contouring tools. RESULTS: The institutional solution of clinical cine MRI incorporated with radiotherapy application was assessed through case presentations (liver cancer). Cine Viewer loaded cine MRIs from 1.5T Philips Ingenia MRI, handling MRI DICOM format. The measurement grids and markers were used to quantify the displacement of anatomical structures in addition to the tumor. The contouring tool was utilized to localize the tumor and surrogates on the designated frame. The stacks of the contours were exhibited to present the ranges of tumor and surrogate motions. For example, the stacks of the tumor contours from case-1 were used to determine the ranges of tumor motions (∼8.17 mm on the x-direction [AP-direction] and ∼14 mm on the y-direction [SI-direction]). In addition, the patterns of the displacement of the contours over frames were analyzed and reported using in-house software. In the case-1 review, the tumor was displaced from +146.0 mm on the x-direction and +125.0 mm on the y-direction from the ROI of the abdominal surface. CONCLUSION: We demonstrated the institutional solution of clinical cine MRI in radiotherapy. The proposed tools can streamline the utilization of cine MRI for tumor motion evaluation using Eclipse for treatment planning.

MR-assisted PET respiratory motion correction using deep-learning based short-scan motion fields.

PURPOSE: We evaluated the impact of PET respiratory motion correction (MoCo) in a phantom and patients. Moreover, we proposed and examined a PET MoCo approach using motion vector fields (MVFs) from a deep-learning reconstructed short MRI scan. METHODS: The evaluation of PET MoCo was performed in a respiratory motion phantom study with varying lesion sizes and tumor to background ratios (TBRs) using a static scan as the ground truth. MRI-based MVFs were derived from either 2000 spokes (MoCo2000 , 5-6 min acquisition time) using a Fourier transform reconstruction or 200 spokes (MoCoP2P200 , 30-40 s acquisition time) using a deep-learning Phase2Phase (P2P) reconstruction and then incorporated into PET MoCo reconstruction. For six patients with hepatic lesions, the performance of PET MoCo was evaluated using quantitative metrics (SUVmax , SUVpeak , SUVmean , lesion volume) and a blinded radiological review on lesion conspicuity. RESULTS: MRI-assisted PET MoCo methods provided similar results to static scans across most lesions with varying TBRs in the phantom. Both MoCo2000 and MoCoP2P200 PET images had significantly higher SUVmax , SUVpeak , SUVmean and significantly lower lesion volume than non-motion-corrected (non-MoCo) PET images. There was no statistical difference between MoCo2000 and MoCoP2P200 PET images for SUVmax , SUVpeak , SUVmean or lesion volume. Both radiological reviewers found that MoCo2000 and MoCoP2P200 PET significantly improved lesion conspicuity. CONCLUSION: An MRI-assisted PET MoCo method was evaluated using the ground truth in a phantom study. In patients with hepatic lesions, PET MoCo images improved quantitative and qualitative metrics based on only 30-40 s of MRI motion modeling data.

Sonobiopsy for minimally invasive, spatiotemporally-controlled, and sensitive detection of glioblastoma-derived circulating tumor DNA.

Though surgical biopsies provide direct access to tissue for genomic characterization of brain cancer, they are invasive and pose significant clinical risks. Brain cancer management via blood-based liquid biopsies is a minimally invasive alternative; however, the blood-brain barrier (BBB) restricts the release of brain tumor-derived molecular biomarkers necessary for sensitive diagnosis. Methods: A mouse glioblastoma multiforme (GBM) model was used to demonstrate the capability of focused ultrasound (FUS)-enabled liquid biopsy (sonobiopsy) to improve the diagnostic sensitivity of brain tumor-specific genetic mutations compared with conventional blood-based liquid biopsy. Furthermore, a pig GBM model was developed to characterize the translational implications of sonobiopsy in humans. Magnetic resonance imaging (MRI)-guided FUS sonication was performed in mice and pigs to locally enhance the BBB permeability of the GBM tumor. Contrast-enhanced T1-weighted MR images were acquired to evaluate the BBB permeability change. Blood was collected immediately after FUS sonication. Droplet digital PCR was used to quantify the levels of brain tumor-specific genetic mutations in the circulating tumor DNA (ctDNA). Histological staining was performed to evaluate the potential for off-target tissue damage by sonobiopsy. Results: Sonobiopsy improved the detection sensitivity of EGFRvIII from 7.14% to 64.71% and TERT C228T from 14.29% to 45.83% in the mouse GBM model. It also improved the diagnostic sensitivity of EGFRvIII from 28.57% to 100% and TERT C228T from 42.86% to 71.43% in the porcine GBM model. Conclusion: Sonobiopsy disrupts the BBB at the spatially-targeted brain location, releases tumor-derived DNA into the blood circulation, and enables timely collection of ctDNA. Converging evidence from both mouse and pig GBM models strongly supports the clinical translation of sonobiopsy for the minimally invasive, spatiotemporally-controlled, and sensitive molecular characterization of brain cancer.

Implementation of Magnetic Resonance Safety Program for Radiation Oncology.

During the last decade, radiation oncology departments have integrated magnetic resonance imaging (MRI) equipment, procedures, and expertise into their practices. MRI safety is an important consideration because a large percentage of patients receiving radiation therapy have histories of multiple surgeries and implanted devices. However, MRI safety guidelines and workflows were traditionally designed for radiology departments. This report presents an MR safety program designed for a radiation oncology department to address its specific needs.

Targetability of cervical cancer by magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU)-mediated hyperthermia (HT) for patients receiving radiation therapy.

PURPOSE: To evaluate the targetability of late-stage cervical cancer by magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU)-induced hyperthermia (HT) as an adjuvant to radiation therapy (RT). METHODS: Seventy-nine cervical cancer patients (stage IIIB-IVA) who received RT with lesions visible on positron emission tomography-computed tomography (PET-CT) were retrospectively analyzed for targetability using a commercially-available HT-capable MRgHIFU system. Targetability was assessed for both primary targets and/or any metastatic lymph nodes using both posterior (supine) and anterior (prone) patient setups relative to the transducer. Thirty-four different angles of rotation along subjects' longitudinal axis were analyzed. Targetability was categorized as: (1) Targetable with/without minimal intervention; (2) Not targetable. To determine if any factors could be used for prospective screening of patients, potential associations between demographic/anatomical factors and targetability were analyzed. RESULTS: 72.15% primary tumors and 33.96% metastatic lymph nodes were targetable from at least one angle. 49.37% and 39.24% of primary tumors could be targeted with patient laying in supine and prone positions, respectively. 25°-30° rotation and 0° rotation had the highest rate of the posterior and anterior targetability, respectively. The ventral depth of the tumor and its distance to the coccyx were statistically correlated with the anterior and posterior targetability, respectively. CONCLUSION: Most late-stage cervical cancer primaries were targetable by MRgHIFU HT requiring either no/minimal intervention. A rotation of 0° or 25°-30° relative to the transducer might benefit anterior and posterior targetability, respectively. Certain demographic/anatomic parameters might be useful in screening patients for treatability.

Evaluation of diffusion-weighted MRI and geometric distortion on a 0.35T MR-LINAC at multiple gantry angles.

Diffusion-weighted imaging (DWI) provides a valuable diagnostic tool for tumor evaluation. Yet, it is difficult to acquire daily MRI data sets in the traditional radiotherapy clinical setting due to patient burden and limited resources. However, integrated MRI radiotherapy treatment systems facilitate daily functional MRI acquisitions like DWI during treatment exams. Before ADC values from MR-RT systems can be used clinically their reproducibility and accuracy must be quantified. This study used a NIST traceable DWI phantom to verify ADC values acquired on a 0.35 T MR-LINAC system at multiple gantry angles. A diffusion-weighted echo planar imaging sequence was used for all image acquisitions, with b-values of 0, 500, 900, 2000 s/mm2 for the 1.5 T and 3.0 T systems and 0, 200, 500, 800 s/mm2 for the 0.35 T system. Images were acquired at multiple gantry angles on the MR-LINAC system from 0° to 330° in 30° increments to assess the impact of gantry angle on geometric distortion and ADC values. CT images, and three fiducial markers were used as ground truth for geometric distortion measurements. The distance between fiducial markers increased by as much as 7.2 mm on the MR-LINAC at gantry angle 60°. ADC values of deionized water vials from the 1.5 T and 3.0 T systems were 8.30 × 10-6  mm2 /s and -0.85 × 10-6  mm2 /s off, respectively, from the expected value of 1127 × 10-6  mm2 /s. The MR-LINAC system provided an ADC value of the pure water vials that was -116.63 × 10-6  mm2 /s off from the expected value of 1127 × 10-6  mm2 /s. The MR-LINAC also showed a variation in ADC across all gantry angles of 33.72 × 10-6  mm2 /s and 20.41 × 10-6  mm2 /s for the vials with expected values of 1127 × 10-6  mm2 /s and 248 × 10-6  mm2 /s, respectively. This study showed that variation of the ADC values and geometric information on the 0.35 T MR-LINAC system was dependent on the gantry angle at acquisition.

Estrogen, brain structure, and cognition in postmenopausal women.

Declining estrogen levels before, during, and after menopause can affect memory and risk for Alzheimer's disease. Undesirable side effects of hormone variations emphasize a role for hormone therapy (HT) where possible benefits include a delay in the onset of dementia-yet findings are inconsistent. Effects of HT may be mediated by estrogen receptors found throughout the brain. Effects may also depend on lifestyle factors, timing of use, and genetic risk. We studied the impact of self-reported HT use on brain volume in 562 elderly women (71-94 years) with mixed cognitive status while adjusting for aforementioned factors. Covariate-adjusted voxelwise linear regression analyses using a model with 16 predictors showed HT use as positively associated with regional brain volumes, regardless of cognitive status. Examinations of other factors related to menopause, oophorectomy and hysterectomy status independently yielded positive effects on brain volume when added to our model. One interaction term, HTxBMI, out of several examined, revealed significant negative association with overall brain volume, suggesting a greater reduction in brain volume than BMI alone. Our main findings relating HT to regional brain volume were as hypothesized, but some exploratory analyses were not in line with existing hypotheses. Studies suggest lower levels of estrogen resulting from oophorectomy and hysterectomy affect brain volume negatively, and the addition of HT modifies the relation between BMI and brain volume positively. Effects of HT may depend on the age range assessed, motivating studies with a wider age range as well as a randomized design.

Characterization of magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU)-induced large-volume hyperthermia in deep and superficial targets in a porcine model.

PURPOSE: To characterize temperature fields and tissue damage profiles of large-volume hyperthermia (HT) induced by magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) in deep and superficial targets in vivo in a porcine model. METHODS: Nineteen HT sessions were performed in vivo with a commercial MRgHIFU system (Sonalleve® V2, Profound Medical Inc., Mississauga, ON, Canada) in hind leg muscles of eight pigs with temperature fields of cross-sectional diameter of 58-mm. Temperature statistics evaluated in the target region-of-interest (tROI) included accuracy, temporal variation, and uniformity. The impact of the number and location of imaging planes for feedback-based temperature control were investigated. Temperature fields were characterized by time-in-range (TIR, the duration each voxel stays within 40-45 °C) maps. Tissue damage was characterized by contrast-enhanced MRI, and macroscopic and histopathological analysis. The performance of the Sonalleve® system was benchmarked against a commercial phantom. RESULTS: Across all HT sessions, the mean difference between the average temperature (Tavg) and the desired temperature was -0.4 ± 0.5 °C; the standard deviation of temperature 1.2 ± 0.2 °C; the temporal variation of Tavg for 30-min HT was 0.6 ± 0.2 °C, and the temperature uniformity was 1.5 ± 0.2 °C. A difference of 2.2-cm (in pig) and 1.5-cm (in phantom) in TIR dimensions was observed when applying feedback-based plane(s) at different locations. Histopathology showed 62.5% of examined HT sessions presenting myofiber degeneration/necrosis within the target volume. CONCLUSION: Large-volume MRgHIFU-mediated HT was successfully implemented and characterized in a porcine model in deep and superficial targets in vivo with heating distributions modifiable by user-definable parameters.

Direct tumor visual feedback during free breathing in 0.35T MRgRT.

To present a tumor motion control system during free breathing using direct tumor visual feedback to patients in 0.35 T magnetic resonance-guided radiotherapy (MRgRT). We present direct tumor visualization to patients by projecting real-time cine MR images on an MR-compatible display system inside a 0.35 T MRgRT bore. The direct tumor visualization included anatomical images with a target contour and an auto-segmented gating contour. In addition, a beam-status sign was added for patient guidance. The feasibility was investigated with a six-patient clinical evaluation of the system in terms of tumor motion range and beam-on time. Seven patients without visual guidance were used for comparison. Positions of the tumor and the auto-segmented gating contour from the cine MR images were used in probability analysis to evaluate tumor motion control. In addition, beam-on time was recorded to assess the efficacy of the visual feedback system. The direct tumor visualization system was developed and implemented in our clinic. The target contour extended 3 mm outside of the gating contour for 33.6 ± 24.9% of the time without visual guidance, and 37.2 ± 26.4% of the time with visual guidance. The average maximum motion outside of the gating contour was 14.4 ± 11.1 mm without and 13.0 ± 7.9 mm with visual guidance. Beam-on time as a percentage was 43.9 ± 15.3% without visual guidance, and 48.0 ± 21.2% with visual guidance, but was not significantly different (P = 0.34). We demonstrated the clinical feasibility and potential benefits of presenting direct tumor visual feedback to patients in MRgRT. The visual feedback allows patients to visualize and attempt to minimize tumor motion in free breathing. The proposed system and associated clinical workflow can be easily adapted for any type of MRgRT.

B0 field homogeneity recommendations, specifications, and measurement units for MRI in radiation therapy.

PURPOSE: The purpose is: (a) Relate magnetic resonance imaging (MRI) quality recommendations for radiation therapy (RT) to B0 field homogeneity; (b) Evaluate manufacturer specifications of B0 homogeneity for 34 commercial whole-body MRI systems based on the MRI quality recommendations and RT application; (c) Measure field homogeneity in five commercial MRI systems and one commercial MRI-Linac used in RT and compare the results with their B0 homogeneity specifications. METHODS: Magnetic resonance imaging quality recommendations for spatial integrity, image blurring, fat saturation, and null banding in RT were developed based on the literature. Guaranteed (maximum) and typical B0 field homogeneity specifications for various diameter spherical volumes (DSVs) were provided by GE, Philips, Siemens, and Canon. For each system, the DSV that conforms to each MRI quality recommendation and anatomical RT application was estimated based on the manufacturer specifications. B0 field homogeneity was measured on six MRI systems including Philips (1.5 T), Siemens (1.5 and 3 T), and ViewRay MRI (0.35 T) systems using 24 and 35 cm DSV spherical phantoms. Two measurement techniques were used: (a) MRI using phase contrast field mapping to measure peak-to-peak (pk-pk), volume root mean square (VRMS), and standard deviation (SD); and (b) Magnetic resonance (MR) spectroscopy by acquiring a volumetric free induction decay (FID) to measure full width at half maximum (FWHM). The measurements were used to assess: (a) conformance with the manufacturer specifications; and (b) the relationship between the various field homogeneity measurement units. Measurements were made with and without gradient shimming (gradshim) or second-order active shimming. Multiple comparisons, analysis of variance (ANOVA), and Pearson correlations were performed to assess the dependence of pk-pk, VRMS, SD, and FWHM measurements of field homogeneity on shim volume, level of shim, and MRI system. RESULTS: For a 40 cm DSV, the B0 homogeneity specifications ranged from 0.35 to 5 ppm (median = 0.75 ppm) VRMS for 1.5 T systems and 0.2 to 1.4 ppm (median = 0.5 ppm) VRMS for 3 T systems. The usable DSVs ranged from 16 to 49 cm (median = 35 cm) based on the image quality recommendations and the manufacturer specifications. There was general compliance between the six measured field homogeneities and manufacturer specifications although signal dephasing was observed in two systems at < 35 cm DSV. The relationships between pk-pk, VRMS, SD, and FWHM varied based on MRI system, shim volume, and quality of shim. However, VRMS and SD measurements were highly correlated. CONCLUSIONS: The delineation of the diseased lesion from organs at risk is the main priority for RT. Therefore, field homogeneity performance for RT must minimize image blurring and image artifacts (null bands and signal dephasing) while optimizing spatial integrity and fat saturation. Based on the specifications and recommendations for field homogeneity, some MRI systems are not well suited to meet the strict demands of RT particularly for the large imaging volumes used in body MRI. VRMS and SD measurements of B0 field homogeneity tend to be more stable and sensitive to field inhomogeneities in RT applications than pk-pk and FWHM.

Dose uncertainty and resolution of polymer gel dosimetry using an MRI guided radiation therapy system's onboard 0.35 T scanner.

Magnetic Resonance Imaging (MRI) scanners are widely used for 3D gel dosimeters readout. However, limited access to MRI scanners is a challenge in MRI-based gel dosimetry. Recent clinical implementation of MRI-guided radiation therapy machines provides potential opportunities for onboard gel dosimetry using its MRI subsystem. The objective of this study was to investigate the feasibility of gel dosimetry using ViewRay's onboard 0.35 T MRI scanner. A BANG® polymer gel dosimeter was irradiated by three beams of 3 × 3 cm2 field size. The T2 relaxation rate (R2) of the irradiated gel was measured using a Philips 1.5 T Ingenia MRI and a ViewRay 0.35 T onboard MRI and spin-echo pulse sequences. The number of signal averages (NSA) was set to 16 for the ViewRay acquisitions and one for the Philips 1.5 T MRI to achieve similar signal-to-noise ratios. The in-plane spatial resolution was 1.5 × 1.5 mm2 and the slice thickness was 5 mm. The relative dose uncertainty was obtained using R2 versus dose curves to compare the performance of dosimetry using the two different MRIs and field strengths. The dose uncertainty decreased from 12% at 2 Gy to 3.5% at 7.5 Gy at 1.5 T. The dose uncertainty decreased from 13% at 2 Gy to 4% at 7.5 Gy with NSA = 16 and 3 × 3 mm2 pixel size, and from 10.5% at 2 Gy to 3.2% at 7.5 Gy with NSA = 16 and denoised R2 maps (1.5 × 1.5 mm2 pixel size) at 0.35 T. The mean of dose resolution was 0.4 Gy at 1.5 T while the mean of dose resolution was 0.8 Gy and 0.64 Gy at 0.35 T by downsampling and denoising the R2 map, respectively. Therefore, comparable dose uncertainty was achievable using the ViewRay's onboard 0.35 T and Philips 1.5 T MRI scanners. 3D gel dosimetry using onboard low-field MRI scanner provides ViewRay users a 3D high resolution dosimetry option besides film and ionization chamber.

Characterizing MR Imaging isocenter variation in MRgRT.

We characterized MRI isocenter variation at various gantry positions in two 0.35 T MRgRT systems using two independent methods. First, image center-based quantification was employed on 3D volumetric and 2D cine images of a 24 cm diameter spherical phantom at various gantry positions in the MRI QA mode. The center of the phantom images was identified to quantify the variation of the imaging center at each gantry position. Second, image registration-based quantification was used in radiotherapy mode. 3D volumetric MRIs of a cylindrical phantom were acquired and corresponding image registration from MRI to planning CT was performed. The shifts of the couch were identified to quantify the variation of the imaging center. For verification of noticeable MRI isocenter variation, star-shot pattern measurements with five beams were delivered on the radio-chromic film inserted into the phantom after the couch was shifted. The center of the star-shot pattern was identified to quantify the variation of the imaging center. The proposed methods for measuring MRI isocenter variation were demonstrated with MR-LINAC and MR-60Co systems. Both of the MRgRT systems had field inhomogeneities <5 ppm over a 24 cm diameter spherical volume (DSV) and spatial integrity distortion: <1 mm within 100 mm radius and <2 mm within 175 mm radius. The MRI isocenter of the MR-LINAC system showed noticeable 3D variation (max magnitude: 1.8 mm) compared to that of MR-60Co system (max magnitude: 0.9 mm) relative to the reference gantry positions. In addition, 2D variations (max magnitude) of the MRI isocenter from sagittal cine images were 0.9 mm for the MR-LINAC system and 0.5 mm for the MR-60Co system. Two proposed methods quantified the MRI isocenter variation for various gantry positions in two 0.35 T MRgRT systems. The results of significant isocenter variation in the MR-LINAC system requires further investigation to determine the cause.

Lateral head flexion as a noncoplanar solution for ring gantry stereotactic radiosurgery.

PURPOSE: Ring gantry radiotherapy devices are often limited to deliver beams in the axial plane, severely limiting beam entrance angles and rendering noncoplanar beam delivery impossible. However, a ring gantry geometry greatly simplifies delivery machines and increases the efficiency of treatment with the potential to decrease the overall costs of radiotherapy. This study explores the use of lateral head flexion in order to increase beam entrance angles and extend the available solid angle space for a ring gantry stereotactic radiosurgery (SRS) application. MATERIALS AND METHODS: A 1.5 T magnetic resonance imaging scanner was used to scan seven healthy volunteers at three different head positions: a neutral position, a left lateral flexion position and a right lateral flexion position. The lateral flexion scans were co-registered to the neutral head position scan using rigid registration and extracting the rotational transformation. The head pitch, roll, and yaw were computed for each registration to evaluate the natural range of motion for all volunteers. A ring gantry plan geometry was used to generate two sets of single fraction SRS plans (21 Gy): one coplanar set for head neutral scans, and a three-arc plan set using the head neutral and lateral head flexion scans. The conformity index (CI), intermediate dose fall-off (R50), low dose spillage (R10), and gradient measure (GM) were used to evaluate both sets of plans. The treatment plans were generated for a ring-gantry linear accelerator (linac) (Varian Halcyon 2.0) as well as radiosurgery linac (Varian Edge) for comparison. RESULTS: The average pitch, yaw, and roll for the lateral head flexion scans were 4.1° ± 4.7°, 16.9° ± 3.7°, and 2.5° ± 4.9° for the right flexion and 4.9° ± 4.3°, 14.0° ± 3.7° and 2.8° ± 5.4° for left flexion. When comparing the head flexion technique with a fully coplanar geometry, the ring gantry plans showed an average improvement in CI of 7.3% (1.46 ± 0.25 vs 1.36 ± 0.28), a decrease of 13% in R50 (5.46 ± 1.14 vs 4.78 ± 1.12), a decrease of 32% in R10 (85.7 ± 20.3 vs 58.2 ± 15.1), and a decrease of 7.8% in GM (0.53 ± 0.05 vs 0.49 ± 0.04). The Edge plans showed an average improvement in CI of 3.0% (1.49 ± 0.26 vs 1.45 ± 0.25), a decrease of 6.8% in R50 (5.19 ± 1.03 vs 4.82 ± 0.83), a decrease of 29% in R10 (84.1 ± 16.3 vs 59.9 ± 12.5), and a decrease of 5.0% in GM (0.50 ± 0.04 vs 0.47 ± 0.03). CONCLUSION: Lateral head flexion was shown to increase beam entrance angles considerably improving plan conformity and normal tissue sparing in this pilot study of seven sets of plans. Rigid registrations demonstrated each lateral flexion to be analogous to a 15° couch kick. The head flexion technique outlined here was shown to be a feasible solution for SRS treatments being delivered on ring gantry devices.

Feasibility and safety assessment of magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU)-mediated mild hyperthermia in pelvic targets evaluated using an in vivo porcine model.

Purpose: To evaluate the feasibility and assess safety parameters of magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU)-mediated hyperthermia (HT; heating to 40-45 °C) in various pelvic targets in a porcine model in vivo.Methods: Thirteen HT treatments were performed in six pigs with a commercial MRgHIFU system (Sonalleve V2, Profound Medical Inc., Mississauga, Canada) to muscle adjacent to the ventral/dorsal bladder wall and uterus to administer 42 °C (±1°) for 30 min (±5%) using an 18-mm target diameter and 100 W power. Feasibility was assessed using accuracy, uniformity, and MR-thermometry performance-based metrics. Safety parameters were assessed for tissues in the targets and beam-path by contrast-enhanced MRI, gross-pathology and histopathology.Results: Across all HT sessions, the mean difference between average temperature (Tavg) and the target temperature within the target region-of-interest (tROI, the cross-section of the heated volume at focal depth) was 0.51 ± 0.33 °C. Within the tROI, the temperature standard deviation averaged 1.55 ± 0.31 °C, the average 30-min Tavg variation was 0.80 ± 0.17 °C, and the maximum difference between Tavg and the 10th- or 90th-percentile temperature averaged 2.01 ± 0.44 °C. The average time to reach ≥41 °C and cool to ≤40 °C within the tROI at the beginning and end of treatment was 47.25 ± 27.47 s and 66.37 ± 62.68 s, respectively. Compared to unheated controls, no abnormally-perfused tissue or permanent damage was evident in the MR images, gross pathology or histological analysis.Conclusions: MRgHIFU-mediated HT is feasible and safety assessment is satisfactory for treating an array of clinically-mimicking pelvic geometries in a porcine model in vivo, implying the technique may have utility in treating pelvic targets in human patients.