Clinical feasibility of a commercially available MRI-only method for radiotherapy treatment planning of the brain.

BACKGROUND: Advancements in deep-learning based synthetic computed tomography (sCT) image conversion methods have enabled the development of magnetic resonance imaging (MRI)-only based radiotherapy treatment planning (RTP) of the brain. PURPOSE: This study evaluates the clinical feasibility of a commercial, deep-learning based MRI-only RTP method with respect to dose calculation and patient positioning verification performance in RTP of the brain. METHODS: Clinical validation of dose calculation accuracy was performed by a retrospective evaluation for 25 glioma and 25 brain metastasis patients. Dosimetric and image quality of the studied MRI-only RTP method was evaluated by a direct comparison of the sCT-based and computed tomography (CT)-based external beam radiation therapy (EBRT) images and treatment plans. Patient positioning verification accuracy of sCT images was evaluated retrospectively for 10 glioma and 10 brain metastasis patients based on clinical cone-beam computed tomography (CBCT) imaging. RESULTS: An average mean dose difference of Dmean = 0.1% for planning target volume (PTV) and 0.6% for normal tissue (NT) structures were obtained for glioma patients. Respective results for brain metastasis patients were Dmean = 0.5% for PTVs and Dmean =1.0% for NTs. Global three-dimensional (3D) gamma pass rates using 2%/2 mm dose difference and distance-to-agreement (DTA) criterion were 98.0% for the glioma subgroup, and 95.2% for the brain metastasis subgroup using 1%/1 mm criterion. Mean distance differences of <1.0 mm were observed in all Cartesian directions between CT-based and sCT-based CBCT patient positioning in both subgroups. CONCLUSIONS: In terms of dose calculation and patient positioning accuracy, the studied MRI-only method demonstrated its clinical feasibility for RTP of the brain. The results encourage the use of the studied method as part of a routine clinical workflow.

Origin of Jupiter's cloud-level zonal winds remains a puzzle even after Juno.

How far Jupiter's cloud-level zonal winds penetrate into its interior, a question related to the origin of the winds, has long been a major puzzle about Jupiter. There exist two different views: the shallow scenario in which the cloud-level winds are confined within the thin weather layer at cloud top and the deep scenario in which the cloud-level winds manifest thermal convection in the deep interior. We interpret, using two different models corresponding to the two scenarios, the high-precision measurements of Jupiter's equatorially antisymmetric gravitational field by the Juno spacecraft. We demonstrate, based on the thermal-gravitational wind equation, that both the shallow and deep cloud-level winds models are capable of explaining the measured odd gravitational coefficients within the measured uncertainties, reflecting the nonunique nature of the gravity inverse problem. We conclude that the high-precision Juno gravity measurements cannot provide an answer to the long-standing question about the origin of Jupiter's cloud-level zonal winds.

Quantification of confounding factors in MRI-based dose calculations as applied to prostate IMRT.

Magnetic resonance (MR)-only radiotherapy treatment planning requires pseudo-CT (pCT) images to enable MR-based dose calculations. To verify the accuracy of MR-based dose calculations, institutions interested in introducing MR-only planning will have to compare pCT-based and computer tomography (CT)-based dose calculations. However, interpreting such comparison studies may be challenging, since potential differences arise from a range of confounding factors which are not necessarily specific to MR-only planning. Therefore, the aim of this study is to identify and quantify the contribution of factors confounding dosimetric accuracy estimation in comparison studies between CT and pCT. The following factors were distinguished: set-up and positioning differences between imaging sessions, MR-related geometric inaccuracy, pCT generation, use of specific calibration curves to convert pCT into electron density information, and registration errors. The study comprised fourteen prostate cancer patients who underwent CT/MRI-based treatment planning. To enable pCT generation, a commercial solution (MRCAT, Philips Healthcare, Vantaa, Finland) was adopted. IMRT plans were calculated on CT (gold standard) and pCTs. Dose difference maps in a high dose region (CTV) and in the body volume were evaluated, and the contribution to dose errors of possible confounding factors was individually quantified. We found that the largest confounding factor leading to dose difference was the use of different calibration curves to convert pCT and CT into electron density (0.7%). The second largest factor was the pCT generation which resulted in pCT stratified into a fixed number of tissue classes (0.16%). Inter-scan differences due to patient repositioning, MR-related geometric inaccuracy, and registration errors did not significantly contribute to dose differences (0.01%). The proposed approach successfully identified and quantified the factors confounding accurate MRI-based dose calculation in the prostate. This study will be valuable for institutions interested in introducing MR-only dose planning in their clinical practice.

An MRI-based mid-ventilation approach for radiotherapy of the liver.

MRI is increasingly being used in radiotherapy of the liver. The purpose of this study was to develop and validate a strategy to acquire MR images for treatment planning and image guidance in the presence of respiratory motion. By interleaving two navigator triggered MRI sequences, a fast but low-resolution image in mid-ventilation (midV) and a high-resolution image in exhale were acquired efficiently. Deformable registration was applied to map the exhale image to the midV anatomy. Cine-MRI scans were acquired for motion quantification. The method was validated with a motion phantom, 10 volunteers and 1 patient with a liver tumor. The time-weighted mean position of a local structure in a cine-scan was defined as the midV-position ground truth and used to determine the accuracy of the midV-triggering method. Deformable registration accuracy was validated using the SIFT algorithm. Acquisition time of the midV/exhale-scan was 3-5min. The accuracy of the midV-position was ⩽0.5±0.5mm for phantom motion and ⩽0.9±1.2mm for the volunteers. Mean residuals after deformable registration were ⩽0.2±1.8mm. The accuracy and reproducibility of the method are within inter- and intra-fraction liver position variability (Case et al., 2009) and could in the future be incorporated in a conventional liver radiotherapy or MR-linac workflow.

Using Jupiter's gravitational field to probe the Jovian convective dynamo.

Convective motion in the deep metallic hydrogen region of Jupiter is believed to generate its magnetic field, the strongest in the solar system. The amplitude, structure and depth of the convective motion are unknown. A promising way of probing the Jovian convective dynamo is to measure its effect on the external gravitational field, a task to be soon undertaken by the Juno spacecraft. We calculate the gravitational signature of non-axisymmetric convective motion in the Jovian metallic hydrogen region and show that with sufficiently accurate measurements it can reveal the nature of the deep convection.

First clinical experience with a dedicated MRI-guided high-intensity focused ultrasound system for breast cancer ablation.

OBJECTIVES: To assess the safety and feasibility of MRI-guided high-intensity focused ultrasound (MR-HIFU) ablation in breast cancer patients using a dedicated breast platform. METHODS: Patients with early-stage invasive breast cancer underwent partial tumour ablation prior to surgical resection. MR-HIFU ablation was performed using proton resonance frequency shift MR thermometry and an MR-HIFU system specifically designed for breast tumour ablation. The presence and extent of tumour necrosis was assessed by histopathological analysis of the surgical specimen. Pearson correlation coefficients were calculated to assess the relationship between sonication parameters, temperature increase and size of tumour necrosis at histopathology. RESULTS: Ten female patients underwent MR-HIFU treatment. No skin redness or burns were observed in any of the patients. No correlation was found between the applied energy and the temperature increase. In six patients, tumour necrosis was observed with a maximum diameter of 3-11 mm. In these patients, the number of targeted locations was equal to the number of areas with tumour necrosis. A good correlation was found between the applied energy and the size of tumour necrosis at histopathology (Pearson = 0.76, p = 0.002). CONCLUSIONS: Our results show that MR-HIFU ablation with the dedicated breast system is safe and results in histopathologically proven tumour necrosis. KEY POINTS: • MR-HIFU ablation with the dedicated breast system is safe and feasible • In none of the patients was skin redness or burns observed • No correlation was found between the applied energy and the temperature increase • The correlation between applied energy and size of tumour necrosis was good.

Degassing during quiescence as a trigger of magma ascent and volcanic eruptions.

Understanding the mechanisms that control the start-up of volcanic unrest is crucial to improve the forecasting of eruptions at active volcanoes. Among the most active volcanoes in the world are the so-called persistently degassing ones (e.g., Etna, Italy; Merapi, Indonesia), which emit massive amounts of gas during quiescence (several kilotonnes per day) and erupt every few months or years. The hyperactivity of these volcanoes results from frequent pressurizations of the shallow magma plumbing system, which in most cases are thought to occur by the ascent of magma from deep to shallow reservoirs. However, the driving force that causes magma ascent from depth remains unknown. Here we demonstrate that magma ascent can be triggered by the passive release of gas during quiescence, which induces the opening of pathways connecting deep and shallow magma reservoirs. This top-down mechanism for volcanic eruptions contrasts with the more common bottom-up mechanisms in which magma ascent is only driven by processes occurring at depth. A cause-effect relationship between passive degassing and magma ascent can explain the fact that repose times are typically much longer than unrest times preceding eruptions, and may account for the so frequent unrest episodes of persistently degassing volcanoes.

Volumetric MR-Guided High-Intensity Focused Ultrasound with Direct Skin Cooling for the Treatment of Symptomatic Uterine Fibroids: Proof-of-Concept Study.

OBJECTIVE: To prospectively assess the safety and technical feasibility of volumetric magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) ablation with direct skin cooling (DISC) during treatment of uterine fibroids. METHODS: In this proof-of-concept study, eight patients were consecutively selected for clinical MR-HIFU ablation of uterine fibroids with the use of an additional DISC device to maintain a constant temperature (T ≈ 20 °C) at the interface between the HIFU table top and the skin. Technical feasibility was verified by successful completion of MR-HIFU ablation. Contrast-enhanced T1-weighted MRI was used to measure the treatment effect (nonperfused volume (NPV) ratio). Safety was evaluated by recording of adverse events (AEs) within 30 days' follow-up. RESULTS: All MR-HIFU treatments were successfully completed in an outpatient setting. The median NPV ratio was 0.56 (IQR [0.27-0.72]). Immediately after treatment, two patients experienced coldness related discomfort which resolved at the same day. No serious (device-related) AEs were reported. Specifically, no skin burns, cold injuries, or subcutaneous edema were observed. CONCLUSION: This study showed that it is safe and technically feasible to complete a volumetric MR-HIFU ablation with DISC. This technique may reduce the risk of thermal injury to the abdominal wall during MR-HIFU ablation of uterine fibroids. This trial is registered with NTR4189.

Abrupt tectonics and rapid slab detachment with grain damage.

A simple model for necking and detachment of subducting slabs is developed to include the coupling between grain-sensitive rheology and grain-size evolution with damage. Necking is triggered by thickened buoyant crust entrained into a subduction zone, in which case grain damage accelerates necking and allows for relatively rapid slab detachment, i.e., within 1 My, depending on the size of the crustal plug. Thick continental crustal plugs can cause rapid necking while smaller plugs characteristic of ocean plateaux cause slower necking; oceanic lithosphere with normal or slightly thickened crust subducts without necking. The model potentially explains how large plateaux or continental crust drawn into subduction zones can cause slab loss and rapid changes in plate motion and/or induce abrupt continental rebound.

A clinically feasible treatment protocol for magnetic resonance-guided high-intensity focused ultrasound ablation in the liver.

OBJECTIVES: Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) allows for noninvasive thermal ablation under real-time temperature imaging guidance. The purpose of this study was to assess the feasibility and safety of MR-HIFU ablation of liver tissue in a clinically acceptable setting. The experimental protocol was designed with a clinical ablation procedure of a small malignant tumor in mind; the procedures were performed within a clinically feasible time frame and care was taken to avoid adverse events. The main outcome was the size and quality of the ablated liver tissue volume on imaging and histology. Secondary outcomes were safety and treatment time. MATERIALS AND METHODS: Healthy pigs (n = 10) under general anesthesia were positioned on a clinical MR-HIFU system, which consisted of an HIFU tabletop with a skin cooling system integrated into a 1.5-T MR scanner. A liver tissue volume was ablated with multiple sonication cells (4 × 4 × 10 mm, 450 W). Both MR thermometry and sonication were respiratory-gated using a pencil beam navigator on the diaphragm. Contrast-enhanced T1-weighted (CE-T1w) imaging was performed for treatment evaluation. Targeted total treatment time was 3 hours. The abdominal wall, liver, and adjacent organs were inspected postmortem for thermal damage. Ablated tissue volumes were processed for cell viability staining. The ablated volumes were analyzed using MR imaging, MR thermometry, and cell viability histology. RESULTS: Eleven volume ablations were performed in 10 animals, resulting in a median nonperfused volume (NPV) on CE-T1w imaging of 1.6 mL (interquartile range [IQR], 0.8-2.3; range, 0.7-3.0). Cell viability histology showed a damaged volume of 1.5 mL (IQR, 1.1-1.8; range, 0.7-2.3). The NPV was confluent in 10 of the 11 cases. The ablated tissue volume on cell viability histology was confluent in all 9 available cases. In all cases, there was a good correspondence between the aspects of the NPV on CE-T1w and the ablated volume on cell viability histology. Two treatment-related adverse events occurred: 1 animal had a 7-mm skin burn and 1 animal showed evidence of thermal damage on the surface of the spleen. Median ablation time was 108 minutes (IQR, 101-120; range, 96-181 minutes) and median total treatment time was 180 minutes (IQR, 165-224; 130-250 minutes). CONCLUSIONS: Our results demonstrate the feasibility and safety of MR-HIFU ablation of liver tissue volumes. The imaging data and cell viability histology show, for the first time, that confluent ablation volumes can be achieved with motion-gated ablation and MR guidance. These results were obtained using a readily available MR-HIFU system with only minor modifications, within a clinically acceptable time frame, and with only minor adverse events. This shows that this technique is sufficiently reliable and safe to initiate a clinical trial.

Intrapleural fluid infusion for MR-guided high-intensity focused ultrasound ablation in the liver dome.

RATIONALE AND OBJECTIVES: Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) ablation of tumors in the liver dome is challenging because of the presence of air in the costophrenic angle. In this study, we used a porcine liver model and a clinical MR-HIFU system to assess the feasibility and safety of using intrapleural fluid infusion (IPI) to create an acoustic window for MR-HIFU ablation in the liver dome. MATERIALS AND METHODS: Healthy adult Dalland land pigs (n = 6) under general anesthesia were used with animal committee approval. Degassed saline (200-800 mL) was infused into the intrapleural space under ultrasound guidance. A clinical 1.5-T MR-HIFU system was used to perform sonications (4-mm treatment cells, 300-450 W, 20-30 seconds) in the liver dome under real-time MR thermometry. An intercostal firing technique was used to prevent rib heating in one experiment. Technical success was defined as a temperature increase (>10°C) in the target area. After termination, the animal was examined for thermal damage to liver, diaphragm, pleura, lung, or intercostal muscle. RESULTS: An acoustic window was established in all animals. A temperature increase in the target area was achieved in all animals (max. 47°C-67°C). MR thermometry showed no heating outside the target area. Intercostal firing effectively reduced rib heating (55°C vs. 42°C). Postmortem examination revealed no unwanted thermal damage. One complication occurred, in the first experiment, because of an ill-suited needle (displacement of the needle). CONCLUSIONS: The results indicate that IPI may be used safely to assist MR-HIFU ablation of tumors in the liver dome. For reliable tissue coagulation, IPI must be combined with an intercostal sonication technique. Considering the proportion of patients with tumors in the liver dome, IPI widens the applicability of MR-HIFU ablation for liver tumors considerably.

Metal-to-insulator transition and electron-hole puddle formation in disordered graphene nanoribbons.

The experimentally observed metal-to-insulator transition in hydrogenated graphene is numerically confirmed for actual sized graphene samples and realistic impurity concentrations. The eigenstates of our tight-binding model with substitutional disorder corroborate the formation of electron-hole puddles with characteristic length scales comparable to the ones found in experiments. The puddles cause charge inhomogeneities and tend to suppress Anderson localization. Even though, monitoring the charge carrier quantum dynamics and performing a finite-size scaling of the local density of states distribution, we find strong evidence for the existence of localized states in graphene nanoribbons with short-range but also correlated long-range disorder.

Evidence of a global magma ocean in Io's interior.

Extensive volcanism and high-temperature lavas hint at a global magma reservoir in Io, but no direct evidence has been available. We exploited Jupiter's rotating magnetic field as a sounding signal and show that the magnetometer data collected by the Galileo spacecraft near Io provide evidence of electromagnetic induction from a global conducting layer. We demonstrate that a completely solid mantle provides insufficient response to explain the magnetometer observations, but a global subsurface magma layer with a thickness of over 50 kilometers and a rock melt fraction of 20% or more is fully consistent with the observations. We also place a stronger upper limit of about 110 nanoteslas (surface equatorial field) on the dynamo dipolar field generated inside Io.

Hydrothermal convection in moderately thin spherical shells.

Hydrothermal convection of pore water with a temperature-dependent viscosity within a permeable, internally heated, moderately thin spherical shell is investigated by both a perturbation analysis and a direct numerical simulation. The analysis and simulation are mainly focused on a thin spherical shell in that convective instabilities are characterized by the spherical harmonic degree l=6 with a 13-fold mathematical degeneracy. Four different three-dimensional analytical solutions of convection are derived by removing the degeneracy through the nonlinear effect. A direct numerical simulation of the nonlinear problem is also carried out, showing satisfactory agreement between the analytical solutions and the numerical simulations.

Saturn's gravitational field, internal rotation, and interior structure.

Saturn's internal rotation period is unknown, though it must be less than 10 hours, 39 minutes, and 22 seconds, as derived from magnetic field plus kilometric radiation data. By using the Cassini spacecraft's gravitational data, along with Pioneer and Voyager radio occultation and wind data, we obtain a rotation period of 10 hours, 32 minutes, and 35 +/- 13 seconds. This more rapid spin implies slower equatorial wind speeds on Saturn than previously assumed, and the winds at higher latitudes flow both east and west, as on Jupiter. Our related Saturn interior model has a molecular-to-metallic hydrogen transition about halfway to the planet's center.

Amalthea's density is less than that of water.

Radio Doppler data from the Galileo spacecraft's encounter with Amalthea, one of Jupiter's small inner moons, on 5 November 2002 yield a mass of (2.08 +/- 0.15) x 10(18) kilograms. Images of Amalthea from two Voyager spacecraft in 1979 and Galileo imaging between November 1996 and June 1997 yield a volume of (2.43 +/- 0.22) x 10(6) cubic kilometers. The satellite thus has a density of 857 +/- 99 kilograms per cubic meter. We suggest that Amalthea is porous and composed of water ice, as well as rocky material, and thus formed in a cold region of the solar system, possibly not at its present location near Jupiter.

Discovery of mass anomalies on Ganymede.

We present the discovery of mass anomalies on Ganymede, Jupiter's third and largest Galilean satellite. This discovery is surprising for such a large icy satellite. We used the radio Doppler data generated with the Galileo spacecraft during its second encounter with Ganymede on 6 September 1996 to model the mass anomalies. Two surface mass anomalies, one a positive mass at high latitude and the other a negative mass at low latitude, can explain the data. There are no obvious geological features that can be identified with the anomalies.