Martijn de Greef

In vivo T2‐based MR thermometry in adipose tissue layers for high‐intensity focused ultrasound near‐field monitoring

During MR‐guided high‐intensity focused ultrasound (HIFU) therapy, ultrasound absorption in the near field represents a safety risk and limits efficient energy deposition at the target. In this study, we investigated the feasibility of using T2 mapping to monitor the temperature change in subcutaneous adipose tissue layers.

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

ObjectivesMagnetic 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 MethodsHealthy 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. ResultsEleven 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). ConclusionsOur 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.

Influence of water and fat heterogeneity on fat-referenced MR thermometry

To investigate the effect of the aqueous and fatty tissue magnetic susceptibility distribution on absolute and relative temperature measurements as obtained directly from the water/fat (w/f) frequency difference.

Correction of proton resonance frequency shift MR-thermometry errors caused by heat-induced magnetic susceptibility changes during high intensity focused ultrasound ablations in tissues containing fat

In this study, we aim to demonstrate the sensitivity of proton resonance frequency shift (PRFS) ‐based thermometry to heat‐induced magnetic susceptibility changes and to present and evaluate a model‐based correction procedure.

Stochastic ray tracing for simulation of high intensity focal ultrasound therapya)

An algorithm is presented for rapid simulation of high-intensity focused ultrasound (HIFU) fields. Essentially, the method combines ray tracing with Monte Carlo integration to evaluate the Rayleigh-Sommerfeld integral. A large number of computational particles, phonons, are distributed among the elements of a phase-array transducer. The phonons are emitted into random directions and are propagated along trajectories computed with the ray tracing method. As the simulation progresses, an improving stochastic estimate of the acoustic field is obtained. The method can adapt to complicated geometries, and it is well suited to parallelization. The method is verified against reference simulations and pressure measurements from an ex vivo porcine thoracic tissue sample. Results are presented for acceleration with graphics processing units (GPUs). The method is expected to serve in applications, where flexibility and rapid computation time are crucial, in particular clinical HIFU treatment planning.

Multi-gradient echo MR thermometry for monitoring of the near-field area during MR-guided high intensity focused ultrasound heating.

The multi-gradient echo MR thermometry (MGE MRT) method is proposed to use at the interface of the muscle and fat layers found in the abdominal wall, to monitor MR-HIFU heating. As MGE MRT uses fat as a reference, it is field-drift corrected. Relative temperature maps were reconstructed by subtracting absolute temperature maps. Because the absolute temperature maps are reconstructed of individual scans, MGE MRT provides the flexibility of interleaved mapping of temperature changes between two arbitrary time points. The methods performance was assessed in an ex vivo water bath experiment. An ex vivo HIFU experiment was performed to show the methods ability to monitor heating of consecutive HIFU sonications and to estimate cooling time constants, in the presence of field drift. The interleaved use between scans of a clinical protocol was demonstrated in vivo in a patient during a clinical uterine fibroid treatment. The relative temperature measurements were accurate (mean absolute error 0.3 °C) and provided excellent visualization of the heating of consecutive HIFU sonications. Maps were reconstructed of estimated cooling time constants and mean ROI values could be well explained by the applied heating pattern. Heating upon HIFU sonication and subsequent cooling could be observed in the in vivo demonstration.

Procedural sedation and analgesia for respiratory-gated MR-HIFU in the liver: a feasibility study

BackgroundPrevious studies demonstrated both pre-clinically and clinically the feasibility of magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) ablations in the liver. To overcome the associated problem of respiratory motion of the ablation area, general anesthesia (GA) and mechanical ventilation was used in conjunction with either respiratory-gated energy delivery or energy delivery during induced apnea. However, clinical procedures requiring GA are generally associated with increased mortality, morbidity, and complication rate compared to procedural sedation and analgesia (PSA). Furthermore, PSA is associated with faster recovery and an increased eligibility for non- and mini-invasive interventions.MethodsIn this study, we investigate both in an animal model and on a small patient group the kinetics of the diaphragm during free-breathing, when a tailored remifentanil/propofol-based PSA protocol inducing partial respiratory depression is used. Subsequently, we demonstrate in an animal study the compatibility of the resulting respiratory pattern of the PSA protocol with a gated HIFU ablation in the liver by direct comparison with gated ablations conducted under GA. Wilcoxon signed-rank tests were performed for statistical analysis of non-perfused and necrosed tissue volumes. Duty cycles (ratio or percentage of the breathing cycle with the diaphragm in its resting position, such that acoustic energy delivery with MR-HIFU was allowed) were statistically compared for both GA and PSA using student’s t tests.ResultsIn both animal and human experiments, the breathing frequency was decreased below 9/min, while maintaining stable vital functions. Furthermore an end-exhalation resting phase was induced by this PSA protocol during which the diaphragm is virtually immobile. Median non-perfused volumes, non-viable volumes based on NADH staining, and duty cycles were larger under PSA than under GA or equal.ConclusionsWe conclude that MR-HIFU ablations of the liver under PSA are feasible and potentially increase the non-invasive nature of this type of intervention.

Cavitation-Enhanced Back Projection for Acoustic Rib Detection and Attenuation Mapping

High-intensity focused ultrasound allows for minimally invasive, highly localized cancer therapies that can complement surgical procedures or chemotherapy. For high-intensity focused ultrasound interventions in the upper abdomen, the thoracic cage obstructs and aberrates the ultrasonic beam, causing undesired heating of healthy tissue. When a phased array therapeutic transducer is used, such complications can be minimized by applying an apodization law based on analysis of beam path obstructions. In this work, a rib detection method based on cavitation-enhanced ultrasonic reflections is introduced and validated on a porcine tissue sample containing ribs. Apodization laws obtained for different transducer positions were approximately 90% similar to those obtained using image analysis. Additionally, the proposed method provides information on attenuation between transducer elements and the focus. This principle was confirmed experimentally on a polymer phantom. The proposed methods could, in principle, be implemented in real time for determination of the optimal shot position in intercostal high-intensity focused ultrasound therapy.

Improved intercostal HIFU ablation using a phased array transducer based on Fermat's spiral and Voronoi tessellation: A numerical evaluation

Purpose: A major complication for abdominal High Intensity Focused Ultrasound (HIFU) applications is the obstruction of the acoustic beam path by the thoracic cage, which absorbs and reflects the ultrasonic energy leading to undesired overheating of healthy tissues in the pre‐focal area. Prior work has investigated the determination of optimized transducer apodization laws, which allow for a reduced rib exposure whilst (partially) restoring focal point intensity through power compensation. Although such methods provide an excellent means of reducing rib exposure, they generally increase the local energy density in the pre‐focal area, which similarly can lead to undesired overheating. Therefore, this numerical study aimed at evaluating whether a novel transducer design could provide improvement for intercostal HIFU applications, in particular with respect to the pre‐focal area. Methods: A combination of acoustic and thermal simulations was used to evaluate 2 mono‐element transducers, 2 clinical phased array transducers, and 4 novel transducers based on Fermats Spiral (FS), two of which were Voronoi‐tessellated (VTFS). Binary apodizations were determined for the phased array transducers using a collision detection algorithm. A tissue geometry was modeled to represent an intercostal HIFU sonication in the liver at 30 and 50 mm behind the ribs, including subsequent layers of gel pad, skin, subcutaneous fat, muscle, and liver tissue. Acoustic simulations were then conducted using propagation of the angular spectrum of plane waves (ASPW). The results of these simulations were used to evaluate pre‐focal intensity levels. Subsequently, a finite difference scheme based on the Pennes bioheat equation was used for thermal simulations. The results of these simulations were used to calculate both the energy density in the pre‐focal skin, fat, and muscle layers, as well as the energy exposure of the ribs. Results: The acoustic simulations showed that for a sonication in a single point without beamsteering, comparing the best performing clinical phased array in this study to an equivalent VTFS transducer, the maximum intensity in the focal point was increased from 19.0 to 27.0 W/mm2 for the sonication 30 mm behind the ribs, while the rib area exposed to ≥20 J/cm2 was reduced from 0.88 to 0.14 cm2. For the sonication 50 mm behind the ribs, the maximum focal point intensity was increased from 13.4 to 21.5 W/mm2, while the rib area exposed to ≥40 J/cm2 was lowered from 2.71 to 0.01 cm2. The thermal simulations showed that for a circular sonication cell of 4 mm diameter in the transversal plane, sonication times for sonications 30/50 mm behind the ribs were reduced from 13.9 to 8.38 s/38.2 to 17.4 s, respectively. Energy density levels in the skin for these sonications were decreased from 5.28 to 2.22/9.45 to 3.78 J/mm2. Conclusions: VTFS transducers are expected to provide improvement for intercostal HIFU applications compared to currently available clinical transducers, as they reduce both the energy density in the pre‐focal zone and the energy exposure of the ribs. These characteristics allow for increasing either the re‐sonication rate or the treatment volume per sonication.

Spontaneous breathing vs . mechanical ventilation for respiratory-gated MR-HIFU ablation in the liver

Magnetic resonance-guided High Intensity Focused Ultrasound (MR-HIFU) ablation in the liver is complicated by the continuous motion of the target due to the respiratory cycle. Several motion compensation strategies have been proposed in the past, such as breath-holding, respiratory gating and dynamic beam steering. Respiratory gating for sonication and MR thermometry uses a pencil beam navigator on the diaphragm to limit power output and image acquisition to the resting phase of the diaphragm. Previously, we have used General Anesthesia with mechanical ventilation (GA) to obtain a long and reproducible resting phase of the diaphragm. From a patient’s perspective however, Procedural Sedation and Analgesia (PSA) has several advantages over GA such as a lower risk of complications and shorter recovery. In addition, it has lower associated costs and can be performed by non-anesthesiologists. The purpose of this animal study was to investigate the feasibility of respiratory-gated MR-HIFU ablation in the liver under PSA with spontaneous breathing.