A framework for continuous target tracking during MR-guided high intensity focused ultrasound thermal ablations in the abdomen

Scatterplot showing percentage changes in stroke volume index (ΔSVI, %) and functional hemodynamic markers, Stroke Volume Variation (SVV, %) Pulse Pressure Variation (PPV, %), with the three tested tidal volumes (V T ), 6, 12 and 18 ml/kg during intra-abdominal hypertension. Solid line shows regression line between variables. (PDF 56 kb

A framework for continuous target tracking during MR-guided high intensity focused ultrasound thermal ablations in the abdomen

International audienceBackground: During lengthy magnetic resonance-guided high intensity focused ultrasound (MRg-HIFU) thermal ablations in abdominal organs, the therapeutic work-flow is frequently hampered by various types of physiological motion occurring at different time-scales. If left un-addressed this can lead to an incomplete therapy and/or to tissue damage of organs-at-risk. While previous studies focus on correction schemes for displacements occurring at a particular time-scale within the work-flow of an MRg-HIFU therapy, in the current work we propose a motion correction strategy encompassing the entire work-flow.Methods: The proposed motion compensation framework consists of several linked components, each being adapted to motion occurring at a particular time-scale. While respiration was addressed through a fast correction scheme, long term organ drifts were compensated using a strategy operating on time-scales of several minutes. The framework relies on a periodic examination of the treated area via MR scans which are then registered to a reference scan acquired at the beginning of the therapy. The resulting displacements were used for both on-the-fly re-optimization of the interventional plan and to ensure the spatial fidelity between the different steps of the therapeutic work-flow. The approach was validated in three complementary studies: an experiment conducted on a phantom undergoing a known motion pattern, a study performed on the abdomen of 10 healthy volunteers and during 3 in-vivo MRg-HIFU ablations on porcine liver.Results: Results have shown that, during lengthy MRg-HIFU thermal therapies, the human liver and kidney can manifest displacements that exceed acceptable therapeutic margins. Also, it was demonstrated that the proposed framework is capable of providing motion estimates with sub-voxel precision and accuracy. Finally, the 3 successful animal studies demonstrate the compatibility of the proposed approach with the work-flow of an MRg-HIFU intervention under clinical conditions.Conclusions: In the current study we proposed an image-based motion compensation framework dedicated to MRg-HIFU thermal ablations in the abdomen, providing the possibility to re-optimize the therapy plan on-the-fly with the patient on the interventional table. Moreover, we have demonstrated that even under clinical conditions, the proposed approach is fully capable of continuously ensuring the spatial fidelity between the different phases of the therapeutic work-flow

Dynamic fluorescence microscopy of cellular uptake of intercalating model drugs by ultrasound-activated microbubbles

The combination of ultrasound and microbubbles can facilitate cellular uptake of (model) drugs via transient permeabilization of the cell membrane. By using fluorescent molecules, this process can be studied conveniently with confocal fluorescence microscopy. This study aimed to investigate the relation between cellular uptake and fluorescence intensity increase of intercalating model drugs. SYTOX Green, an intercalating fluorescent dye that displays > 500-fold fluorescence enhancement upon binding to nucleic acids, was used as a model drug for ultrasound-induced cellular uptake. SYTOX Green uptake was monitored in high spatiotemporal resolution to qualitatively assess the relation between uptake and fluorescence intensity in individual cells. In addition, the kinetics of fluorescence enhancement were studied as a function of experimental parameters, in particular, laser duty cycle (DC), SYTOX Green concentration and cell line. Ultrasound-induced intracellular SYTOX Green uptake resulted in local fluorescence enhancement, spreading throughout the cell and ultimately accumulating in the nucleus during the 9-min acquisition. The temporal evolution of SYTOX Green fluorescence was substantially influenced by laser duty cycle: continuous laser (100 % DC) induced a 6.4-fold higher photobleaching compared to pulsed laser (3.3 % DC), thus overestimating the fluorescence kinetics. A positive correlation of fluorescence kinetics and SYTOX Green concentration was found, increasing from 0.6 x 10(-3) to 2.2 x 10(-3) s(-1) for 1 and 20 mu M, respectively. Finally, C6 cells displayed a 2.4-fold higher fluorescence rate constant than FaDu cells. These data show that the temporal behavior of intracellular SYTOX Green fluorescence enhancement depends substantially on nuclear accumulation and not just on cellular uptake. In addition, it is strongly influenced by the experimental conditions, such as the laser duty cycle, SYTOX Green concentration, and cell line

Ultrasound and Microbubbles Mediated Bleomycin Delivery in Feline Oral Squamous Cell Carcinoma-: An In Vivo Veterinary Study

To investigate the feasibility and tolerability of ultrasound and microbubbles (USMB)-enhanced chemotherapy delivery for head and neck cancer, we performed a veterinary trial in feline companion animals with oral squamous cell carcinomas. Six cats were treated with a combination of bleomycin and USMB therapy three times, using the Pulse Wave Doppler mode on a clinical ultrasound system and EMA/FDA approved microbubbles. They were evaluated for adverse events, quality of life, tumour response and survival. Furthermore, tumour perfusion was monitored before and after USMB therapy using contrast-enhanced ultrasound (CEUS). USMB treatments were feasible and well tolerated. Among 5 cats treated with optimized US settings, 3 had stable disease at first, but showed disease progression 5 or 11 weeks after first treatment. One cat had progressive disease one week after the first treatment session, maintaining a stable disease thereafter. Eventually, all cats except one showed progressive disease, but each survived longer than the median overall survival time of 44 days reported in literature. CEUS performed immediately before and after USMB therapy suggested an increase in tumour perfusion based on an increase in median area under the curve (AUC) in 6 out of 12 evaluated treatment sessions. In this small hypothesis-generating study, USMB plus chemotherapy was feasible and well-tolerated in a feline companion animal model and showed potential for enhancing tumour perfusion in order to increase drug delivery. This could be a forward step toward clinical translation of USMB therapy to human patients with a clinical need for locally enhanced treatment

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 Fermat's 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/mm(2) for the sonication 30 mm behind the ribs, while the rib area exposed to >20 J/cm(2) was reduced from 0.88 to 0.14 cm(2) . For the sonication 50 mm behind the ribs, the maximum focal point intensity was increased from 13.4 to 21.5 W/mm(2) , while the rib area exposed to >40 J/cm(2) was lowered from 2.71 to 0.01 cm(2) . 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/mm(2) . 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. This article is protected by copyright. All rights reserved

On the accuracy and precision of PLANET for multiparametric MRI using phase-cycled bSSFP imaging

PURPOSE: In this work we demonstrate how sequence parameter settings influence the accuracy and precision in T1 , T2 , and off-resonance maps obtained with the PLANET method for a single-component signal model. In addition, the performance of the method for the particular case of a two-component relaxation model for white matter tissue was assessed. METHODS: Numerical simulations were performed to investigate the influence of sequence parameter settings on the accuracy and precision in the estimated parameters for a single-component model, as well as for a two-component white matter model. Phantom and in vivo experiments were performed for validation. In addition, the effects of Gibbs ringing were investigated. RESULTS: By making a proper choice for sequence parameter settings, accurate and precise parameter estimation can be achieved for a single-component signal model over a wide range of relaxation times at realistic SNR levels. Due to the presence of a second myelin-related signal component in white matter, an underestimation of approximately 30% in T1 and T2 was observed, predicted by simulations and confirmed by measurements. Gibbs ringing artifacts correction improved the precision and accuracy of the parameter estimates. CONCLUSION: For a single-component signal model there is a broad "sweet spot" of sequence parameter combinations for which a high accuracy and precision in the parameter estimates is achieved over a wide range of relaxation times. For a multicomponent signal model, the single-component PLANET reconstruction results in systematic errors in the parameter estimates as expected

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

Investigation of the influence of B0 drift on the performance of the PLANET method and an algorithm for drift correction

PURPOSE: The PLANET method was designed to simultaneously reconstruct maps of T1 and T2 , the off-resonance, the RF phase, and the banding free signal magnitude. The method requires a stationary B0 field over the course of a phase-cycled balanced SSFP acquisition. In this work we investigated the influence of B0 drift on the performance of the PLANET method for single-component and two-component signal models, and we propose a strategy for drift correction. METHODS: The complex phase-cycled balanced SSFP signal was modeled with and without frequency drift. The behavior of the signal influenced by drift was mathematically interpreted as a sum of drift-dependent displacement of the data points along an ellipse and drift-dependent rotation around the origin. The influence of drift on parameter estimates was investigated experimentally on a phantom and on the brain of healthy volunteers and was verified by numerical simulations. A drift correction algorithm was proposed and tested on a phantom and in vivo. RESULTS: Drift can be assumed to be linear over the typical duration of a PLANET acquisition. In a phantom (a single-component signal model), drift induced errors of 4% and 8% in the estimated T1 and T2 values. In the brain, where multiple components are present, drift only had a minor effect. For both single-component and two-component signal models, drift-induced errors were successfully corrected by applying the proposed drift correction algorithm. CONCLUSION: We have demonstrated theoretically and experimentally the sensitivity of the PLANET method to B0 drift and have proposed a drift correction method

Anatomically plausible models and quality assurance criteria for online mono- and multi-modal medical image registration

Medical imaging is currently employed in the diagnosis, planning, delivery and response monitoring of cancer treatments. Due to physiological motion and/or treatment response, the shape and location of the pathology and organs-at-risk may change over time. Establishing their location within the acquired images is therefore paramount for an accurate treatment delivery and monitoring.
 A feasible solution for tracking anatomical changes during an image-guided cancer treatment is provided by image registration algorithms. Such methods are, however, often built upon elements originating from the computer vision/graphics domain. Since the original design of such elements did not take into consideration the material properties of particular biological tissues, the anatomical plausibility of the estimated deformations may not be guaranteed. In the current work we adapt two existing variational registration algorithms, namely Horn-Schunck and EVolution, to online soft tissue tracking. This is achieved by enforcing an incompressibility constraint on the estimated deformations during the registration process. The existing and the modified registration methods were comparatively tested against several quality assurance criteria on abdominal in-vivo MR and CT data. These criteria included: the Dice Similarity Coefficient (DSC), the Jaccard index, the target registration error (TRE) and three additional criteria evaluating the anatomical plausibility of the estimated deformations.
 Results demonstrated that both the original and the modified registration methods have similar registration capabilities in high-contrast areas, with DSC and Jaccard index values predominantly in the 0.8 - 0.9 range and an average TRE of 1.6 - 2.0 mm. In contrast-devoid regions of the liver and kidneys, however, the three additional quality assurance criteria have indicated a considerable improvement of the anatomical plausibility of the deformations estimated by the incompressibility-constrained methods. Moreover, the proposed registration models maintain the potential of the original methods for online image-based guidance of cancer treatments