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Purpose : To investigate the ability of simultaneous multislice triple-echo steady-state (SMS- TESS) imaging to provide quantitative maps of multiple tissue parameters, i.e., longitudinal and transverse relaxation times (T 1 and T 2 ), proton density (PD), and off-resonance ( ∆ B 0 ), in the human brain at 3 T from a single scan. Methods : TESS acquisitions were performed in 2D mode to reduce motion sensitivity and accelerated by a simultaneous multislice excitation scheme (CAIPIRINHA) with SENSE reconstruction. SMS-acceleration factors (R) of 2 and 4 were evaluated. The in vitro and in vivo validation process included standard reference scans to analyze the accuracy of T 1 , T 2 , and  B 0 estimates, as well as single-slice TESS measurements. Results : For R=2, the quantification of T 1 , T 2 , PD, and ∆ B 0 was overall reliable with marginal noise enhancement. T 1 and T 2 values were in good agreement with the reference measurements and single-slice TESS. For R=4, the agreement of  B 0 with the standard reference was excellent and the determination of T 1 , T 2 , and PD was reproducible, however, increased variations in T 1 and T 2 values with respect to single-slice TESS were observed. Conclusion : SMS-TESS has shown potential to offer rapid simultaneous T 1 , T 2 , PD, and ∆ B 0 mapping of human brain tissues.

Purpose Motion management is crucial in scanned proton therapy for mobile tumours. Current motion mitigation approaches rely on single 4DCTs before treatment, ignoring respiratory variability. We investigate the consequences of respiratory variations on internal target volumes (ITV) definition and motion mitigation efficacy, and propose a probabilistic ITV based on 4DMRI. Materials and methods Four 4DCT(MRI) datasets, each containing 40 variable cycles of synthetic 4DCTs, were generated by warping single-phase CTs of two lung patients with motion fields extracted from two 4DMRI datasets. Two-field proton treatment plans were optimised on ITVs based on different parts of the 4DCT(MRI)s. 4D dose distributions were calculated by considering variable respiratory patterns. Different probabilistic ITVs were created by incorporating the voxels covered by the CTV in at least 25%, 50%, or 75% (ITV25, ITV50, ITV75) of the cycles, and compared with the conservative ITV encompassing all possible CTV positions. Results Depending on the selected planning 4DCT, ITV volumes vary up to 20%, resulting in significant variation in CTV coverage for 4D treatments. Target coverage and homogeneity improved with the conservative ITV, but was associated with significantly increased lung dose (~1%). ITV25 and ITV50 led to acceptable plan quality in most cases without lung dose increments. ITV75 best minimised lung dose, but was insufficient to ensure coverage under all motion scenarios. Conclusion Irregular respiration significantly affects CTV coverage when ITVs are only defined by single 4DCTs. A probabilistic ITV50 provides an adequate compromise between target coverage and lung dose for most motion and patient scenarios investigated.

International audience; The purpose of this study was to develop micron-sized droplet emulsions able to increase the heat deposition of high intensity focused ultrasound (HIFU), aiming to accelerate the tumour ablation in highly perfused organs with reduced side effects. The investigated droplets consisted of a perfluorooctyl bromide (PFOB) core coated with a biocompatible fluorinated surfactant called F-TAC. The novelty of this work relies on the use, for this application, of a high boiling point perfluorocarbon core (142 °C), combined with an in-house fluorinated surfactant to formulate the emulsion, yielding quasi-reversible strong interactions between the HIFU beam and the droplets. In order to fine-tune the emulsion size, surfactants with different hydrophobic/hydrophilic ratios were screened. Different concentrations of PFOB droplets were homogeneously embedded in two different MRI compatible materials, exhibiting either ultrasound (US) absorbing or non-absorbing properties. For the US absorbing TMM, the speed of sound at each droplet concentration was also assessed. These TMM were sonicated by 1 MHz HIFU with acoustical power of 94 W at two different duty cycles. The temperature elevation was monitored accurately by MRI proton shift resonance frequency in near real-time. The presence of sono-sensitive droplets induced a significant increase of the HIFU thermal effect that persisted under repeated sonication of the same locus. Optimal enhancement was observed at the lowest concentration tested (0.1%) with an additional temperature rise at the focal point of approximately 4 °C per applied kJ of acoustic energy corresponding to one order of magnitude augmentation of the thermal dose. Furthermore, no deformation of the heating pattern pre- or post-focal was observed.

Perfluorocarbon nano- and micron-sized emulsions are a new field of investigation in cancer treatment due to their ability to be used as imaging contrast agents, or as delivery vectors for pharmaceuticals. They also demonstrated capability to enhance the efficiency of high intensity focused ultrasound thermo-therapy. In the context of new biomedical applications we investigated perfluorooctyl bromide (PFOB) theranostic droplets usingLiquid PFOB and five samples of PFOB droplets of average diameter 0.177, 0.259, 1.43, 3.12 and 4.53 µm were tested with different oxygen levels. A dedicated gas exchange system was validated to maintain steady state oxygen concentrations, including a spatial gradient of oxygen concentration. A prototyped transmit-receive switchableExperimental data indicated that the longitudinal relaxation rate ofThe size-tunable PFOB theranostic droplets stabilized with F-TAC surfactants could be characterized by

Purpose Treatments using high-intensity focused ultrasound (HIFU) in the abdominal region remain challenging as a result of respiratory organ motion. A novel method is described here to achieve 3D motion-compensated ultrasound (US) MR-guided HIFU therapy using simultaneous ultrasound and MRI. Methods A truly hybrid US-MR-guided HIFU method was used to plan and control the treatment. Two-dimensional ultrasound was used in real time to enable tracking of the motion in the coronal plane, whereas an MR pencil-beam navigator was used to detect anterior–posterior motion. Prospective motion compensation of proton resonance frequency shift (PRFS) thermometry and HIFU electronic beam steering were achieved. Results The 3D prospective motion-corrected PRFS temperature maps showed reduced intrascan ghosting artifacts, a high signal-to-noise ratio, and low geometric distortion. The k-space data yielded a consistent temperature-dependent PRFS effect, matching the gold standard thermometry within approximately 1°C. The maximum in-plane temperature elevation ex vivo was improved by a factor of 2. Baseline thermometry acquired in volunteers indicated reduction of residual motion, together with an accuracy/precision of near-harmonic referenceless PRFS thermometry on the order of 0.5/1.0°C. Conclusions Hybrid US-MR-guided HIFU ablation with 3D motion compensation was demonstrated ex vivo together with a stable referenceless PRFS thermometry baseline in healthy volunteer liver acquisitions. Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

We present an ultrasound-driven 4D magnetic resonance imaging (US-4DMRI) method for respiratory motion imaging in the thorax and abdomen. The proposed US-4DMRI comes along with a high temporal resolution, and allows for organ motion imaging beyond a single respiratory cycle. With the availability of the US surrogate both inside and outside the MR bore, 4D MR images can be reconstructed for 4D treatment planning and online respiratory motion prediction during radiotherapy. US-4DMRI relies on simultaneously acquired 2D liver US images and abdominal 2D MR multi-slice scans under free respiration. MR volumes are retrospectively composed by grouping the MR slices corresponding to the most similar US images. We present two different US similarity metrics: an intensity-based approach, and a similarity measure relying on predefined fiducials which are being tracked over time. The proposed method is demonstrated on MR liver scans of eight volunteers acquired over a duration of 5.5 min each at a temporal resolution of 2.6 Hz with synchronous US imaging at 14 Hz-17 Hz. Visual inspection of the reconstructed MR volumes revealed satisfactory results in terms of continuity in organ boundaries and blood vessels. In quantitative leave-one-out experiments, both US similarity metrics reach the performance level of state-of-the-art navigator-based approaches.

Objective Perfluorocarbon nano- and micron-sized emulsions are a new field of investigation in cancer treatment due to their ability to be used as imaging contrast agents, or as delivery vectors for pharmaceuticals. They also demonstrated capability to enhance the efficiency of high intensity focused ultrasound thermo-therapy. In the context of new biomedical applications we investigated perfluorooctyl bromide (PFOB) theranostic droplets using 19F NMR. Each droplet contains biocompatible fluorinated surfactants composed of a polar Tris(hydroxymethyl)aminomethane head unit and hydrophobic perfluorinated tail (abbreviated as F-TAC). The influence of the droplet size on the oxygen loading capacity was determined from longitudinal relaxation (T1) data of 19F NMR signal. Material and methods Liquid PFOB and five samples of PFOB droplets of average diameter 0.177, 0.259, 1.43, 3.12 and 4.53 µm were tested with different oxygen levels. A dedicated gas exchange system was validated to maintain steady state oxygen concentrations, including a spatial gradient of oxygen concentration. A prototyped transmit-receive switchable 19F/1H quadrature coil was integrated on a 3 T clinical scanner. The coil is compatible with focused ultrasound sonication for future application. A spectroscopy FID inversion-recovery (IR) sequence was used to measure the T1 value per sample and per value of equilibrium oxygen pressure. Pixel wise, spatial T1 mapping was performed with magnetization prepared 2D gradient echo sequences in tissue mimicking gels doped with theranostic droplets. Results Experimental data indicated that the longitudinal relaxation rate of 19F signal of the investigated theranostic droplets depended approximately linearly on the oxygen level and its slope decreased with the particle size according to a second order polynomial over the investigated range. This semi-empirical model was derived from general thermodynamics and weak electrostatic forces theory and fitted the experimental data within 0.75% precision. The capacity of oxygen transportation for the described theranostic droplets tended to that of pure PFOB, while micron-sized droplets lost up to 50% of this capacity. In a specific setup producing a steady state gradient of oxygen concentration, we demonstrated spatial mapping of oxygen pressure gradient of 6 kPa/mm with 1 mm in-plane resolution. Conclusion The size-tunable PFOB theranostic droplets stabilized with F-TAC surfactants could be characterized by 19F MRI in a clinical setup readily compatible with interventional in vivo studies under MR guidance. Current precision and spatial resolution of T1 mapping are promising. A potential challenge for further in vivo studies is the reduction of the imaging time.

Respiratory organ motion is still the major challenge of various image-guided treatments in the abdomen. Dynamic organ motion tracking, necessary for the treatment control, can be performed with volumetric time-resolved MRI that sequentially acquires one image and one navigator slice. Here, a novel imaging method is proposed for truly simultaneous high temporal resolution acquisition.; A standard balanced steady state free precession sequence was modified to simultaneously acquire two superimposed slices with different phase cycles, namely an image and a navigator slice. Instead of multiband RF pulses, two separate RF pulses were used for the excitation. Images were reconstructed using offline CAIPIRINHA reconstruction. Phantom and in vivo measurements of healthy volunteers were performed and evaluated.; Phantom and in vivo measurements showed good image quality with high signal-to-noise ratio (SNR) and no reconstruction issues.; We present a novel imaging method for truly simultaneous acquisition of image and navigator slices for four-dimensional (4D) MRI of organ motion. In this method, the time lag between the sequential acquisitions is eliminated, leading to an improved accuracy of organ motion models, while CAIPIRINHA reconstruction results in an improved SNR compared with an existing 4D MRI approach.

Introduction Stereotactic body radiation therapy (SBRT) has been validated for liver lesions [1] . Because high dose per fraction is delivered on small volume, very accurate lesion segmentation is necessary. MRI is the most relevant imaging for liver lesion contouring but it is prone to motion artifacts if breathing is not managed. Evaluation of liver lesion motion induced by breathing is necessary in radiotherapy to guide patient treatment planning (respiratory gating). A 4D-MRI sequence was previously validated for liver [2] . In this study, an automated method was developed to sort images according to the breathing cycle. Methods The 4D-MRI acquisition is performed with an experimental sequence (bSSFP TrueFISP [3] ) on 1.5T Magnetom AeraTM (Siemens). This sequence allows very fast axial and sagittal 2D acquisition during free breathing. Axial slice positions (0.88 s/slice) are incremented to cover the liver volume. Sagittal slices (navigators) are acquired at a fixed position. The navigators are used to assign a phase for each axial slice which depend on an amplitude sequencing of the respiratory cycle (0% = inspiration, 16%, 33%, 50% = expiration, 66%, 83%). Lung volume is estimated on each navigator by automatic segmentation and allows to assign a phase for the coupled axial image in the breathing cycle. As the image number per respiratory cycle is low, the sequence is repeated 20 times in order to achieve satisfactory sampling. The sequence was evaluated on 4 volunteers with an audio coaching (5 and 6 s period) and 2 patients without audio coaching. Results Patient image sorting according to their position in the breathing cycle was realized by automated phase detection (Fig. 1) and images were imported into the treatment planning system Eclipse 13.7TM (Varian) in 6 phases. Audio coaching is not used here. It is required for patients with irregular breathing cycle. Download : Download high-res image (278KB) Download : Download full-size image From axial images, Eclipse reconstructs slices in sagittal and coronal plans, and allows to display a cine view with the 6 breathing phases in order to analyze the dynamic behavior of the liver. Conclusions 4D-MRI images from volunteers and patients were acquired with bSSFP TrueFISP sequence. After automated sorting with the method developed in this study, 6 breathing cycle phases were imported into Eclipse. Patient 4D-MRI can be registered with 4D-CT to increase the physician’s segmentation accuracy.

With the availability of new and more accurate tumour treatment modalities such as high-intensity focused ultrasound or proton therapy, accurate target location prediction has become a key issue. Various approaches for diverse application scenarios have been proposed over the last decade. Whereas external surrogate markers such as a breathing belt work to some extent, knowledge about the internal motion of the organs inherently provides more accurate results. In this paper, we combine a population-based statistical motion model and information from 2d ultrasound sequences in order to predict the respiratory motion of the right liver lobe. For this, the motion model is fitted to a 3d exhalation breath-hold scan of the liver acquired before prediction. Anatomical landmarks tracked in the ultrasound images together with the model are then used to reconstruct the complete organ position over time. The prediction is both spatial and temporal, can be computed in real-time and is evaluated on ground truth over long time scales (5.5 min). The method is quantitatively validated on eight volunteers where the ultrasound images are synchronously acquired with 4D-MRI, which provides ground-truth motion. With an average spatial prediction accuracy of 2.4 mm, we can predict tumour locations within clinically acceptable margins.

Purpose Magnetic resonance-guided high-intensity focused ultrasound is considered to be a promising treatment for localized cancer in abdominal organs such as liver, pancreas, or kidney. Abdominal motion, anatomical arrangement, and required sustained sonication are the main challenges. Methods MR acquisition consisted of thermometry performed with segmented gradient-recalled echo echo-planar imaging, and a segment-based one-dimensional MR navigator parallel to the main axis of motion to track the organ motion. This tracking information was used in real-time for: (i) prospective motion correction of MR thermometry and (ii) HIFU focal point position lock-on target. Ex vivo experiments were performed on a sheep liver and a turkey pectoral muscle using a motion demonstrator, while in vivo experiments were conducted on two sheep liver. Results Prospective motion correction of MR thermometry yielded good signal-to-noise ratio (range, 25 to 35) and low geometric distortion due to the use of segmented EPI. HIFU focal point lock-on target yielded isotropic in-plane thermal build-up. The feasibility of in vivo intercostal liver treatment was demonstrated in sheep. Conclusion The presented method demonstrated in moving phantoms and breathing sheep accurate motion-compensated MR thermometry and precise HIFU focal point lock-on target using only real-time pencil-beam navigator tracking information, making it applicable without any pretreatment data acquisition or organ motion modeling. Magn Reson Med 72:1087–1095, 2014. © 2013 Wiley Periodicals, Inc.

Objectives: The combination of ultrasound (US) and magnetic resonance imaging (MRI) may provide a complementary description of the investigated anatomy, together with improved guidance and assessment of image-guided therapies. The aim of the present study was to integrate a clinical setup for simultaneous US and magnetic resonance (MR) acquisition to obtain synchronized monitoring of liver motion. The feasibility of this hybrid imaging and the precision of image fusion were evaluated. Materials and Methods: Ultrasound imaging was achieved using a clinical US scanner modified to be MR compatible, whereas MRI was achieved on 1.5- and 3-T clinical scanners. Multimodal registration was performed between a high-resolution T1 3-dimensional (3D) gradient echo (volume interpolated gradient echo) during breath-hold and a simultaneously acquired 2D US image, or equivalent, retrospective registration of US imaging probe in the coordinate frame of MRI. A preliminary phantom study was followed by 4 healthy volunteer acquisitions, performing simultaneous 4D MRI and 2D US harmonic imaging (Fo = 2.2 MHz) under free breathing. Results: No characterized radiofrequency mutual interferences were detected under the tested conditions with commonly used MR sequences in clinical routine, during simultaneous US/MRI acquisition. Accurate spatial matching between the 2D US and the corresponding MRI plane was obtained during breath-hold. In situ fused images were delivered. Our 4D MRI sequence permitted the dynamic reconstruction of the intra-abdominal motion and the calculation of high temporal resolution motion field vectors. Conclusions: This study demonstrates that, truly, simultaneous US/MR dynamic acquisition in the abdomen is achievable using clinical instruments. A potential application is the US/MR hybrid guidance of high-intensity focused US therapy in the liver.

Introduction Liver imaging is challenging due to its constant movement with breathing. In Magnetic Resonance Imaging (MRI), different strategies have been developed for organ movement consideration [1] , [2] , [3] . These methods are limited by the temporal resolution, as well as image quality. A novel retrospective gating method for dynamic 3D MR imaging during free breathing was developed [1] and further improved by Celicanin et al. [4] . This work aims of assessing the method and the reconstruction technique for liver cases. The final clinical application is to improve liver lesion delineation for Stereotactic Body Radiation Therapy (SBRT). Methods The innovative 4D MRI approach has been evaluated for liver motion estimation during entire respiratory cycle on a healthy volunteer. It is based on simultaneous acquisition of 2D images and a navigator set using acceleration CAIPIRINHA technique [4] providing no temporal divergence between them. During the entire acquisition time, the navigator is fixed in the same position, while the image position is changing, in order to cover the entire organ during free breathing [1] . The entire respiratory cycle is acquired, using a modified balanced Steady State Free Precession sequence (bSSFP) and is reconstructed in a retrospective manner ( Fig. 1 ). Images are acquired with a 1.5T MRI (MAGNETOM Aera; Siemens Medical Solutions, Erlangen, Germany), using an 18-channel design body flex coil. The 3.5 mm 2D axial slices are obtained, using the following sequence parameters: TE = 2.27 ms, TR = 591.97 ms, FA = 70 °, FOV = 37 × 37 cm2, matrix = 256 × 246. Total acquisition time is 33.175 s (0.83 s per slice). Results The preliminary results obtained on a healthy volunteer are shown in Fig. 1 . Images are characterized by high resolution and great contrast, making this method promising for liver lesion examination. The reconstruction of 4D MRI and the sequence optimization to cover the entire respiration cycle with the appropriate time sampling is ongoing work. Conclusions The benefit of MRI acquisition in treatment position to improve lesion contouring for liver SBRT has already been demonstrated [5] . The presented 4D MRI method represents a highly time efficient technique for the free breathing liver motion registration, giving the possibility to sort and reconstruct the images according to the respiratory phases. It will allow registration with 4D CT planning, likely to improve delineation accuracy. The same approach can be applied to study moving organs others than liver.

Respiratory organ motion is still the major challenge of various image-guided treatments in the abdomen. Dynamic organ motion tracking, necessary for the treatment control, can be performed with volumetric time-resolved MRI that sequentially acquires one image and one navigator slice. Here, a novel imaging method is proposed for truly simultaneous high temporal resolution acquisition.A standard balanced steady state free precession sequence was modified to simultaneously acquire two superimposed slices with different phase cycles, namely an image and a navigator slice. Instead of multiband RF pulses, two separate RF pulses were used for the excitation. Images were reconstructed using offline CAIPIRINHA reconstruction. Phantom and in vivo measurements of healthy volunteers were performed and evaluated.Phantom and in vivo measurements showed good image quality with high signal-to-noise ratio (SNR) and no reconstruction issues.We present a novel imaging method for truly simultaneous acquisition of image and navigator slices for four-dimensional (4D) MRI of organ motion. In this method, the time lag between the sequential acquisitions is eliminated, leading to an improved accuracy of organ motion models, while CAIPIRINHA reconstruction results in an improved SNR compared with an existing 4D MRI approach.

Magnetic resonance (MR) imaging and ultrasound (US) imaging are complementary and synergetic noninvasive imaging modalities. US imaging is practically free of geometric distortion and provides high temporal resolution and direct visualization of acoustic obstacles. MR imaging offers excellent tissue contrast and a confirmed method for near-real-time thermometry. Their combination may help increase the intraoperative control and assessment in image-guided therapies. The added value of this dual-modality imaging would consist of a more complete description of the anatomy investigated, more accurate targeting, efficient motion tracking, and reliable immediate assessment of the therapeutic results. This chapter focuses on truly simultaneous US/MR technology integration and early applications. A prototype setup designed to clinical standards is described together with the preliminary evaluation of the hybrid imaging performance in the abdomen. In particular, the precision of image coregistration was assessed in healthy volunteers. Furthermore, a complex study investigated the thermal cavitation effects produced by radio-frequency ablations. Simultaneous US imaging/MR imaging acquisition permitted us to demonstrate that the latter effects induce subsequent magnetic-susceptibility-mediated errors in proton resonance frequency shift thermometry, both in ex vivo models and in patients treated for hepatic malignancies. The foreseen perspectives of the hybrid US imaging/MR imaging technique are included in the final section.