Hybrid Ultrasound/Magnetic Resonance Simultaneous

ORIGINAL ARTICLE

Hybrid Ultrasound/Magnetic Resonance Simultaneous Acquisition and Image Fusion for Motion Monitoring in the Upper Abdomen Lorena Petrusca, PhD,* Philippe Cattin, PhD,Þ Valeria De Luca, MS,þ Frank Preiswerk, MS,Þ Zarko Celicanin, MS,§ Vincent Auboiroux, PhD,* Magalie Viallon, PhD,* Patrik Arnold, MS,Þ Francesco Santini, PhD,§ Sylvain Terraz, MD,* Klaus Scheffler, PhD,||¶ Christoph D. Becker, MD,* and Rares Salomir, PhD*

may therefore emerge for improved diagnosis and more accurate Objectives: The combination of ultrasound (US) and magnetic resonance therapy monitoring. Several reports have already shown the poten- imaging (MRI) may provide a complementary description of the investigated tial interest and some initial advantages of hybrid imaging systems, anatomy, together with improved guidance and assessment of image-guided including positron emission tomography (PET)Ymagnetic resonance therapies. The aim of the present study was to integrate a clinical setup for (MR),1Y3 PETYCT,4Y8 and ultrasound (US)-MR.9Y13 simultaneous US and magnetic resonance (MR) acquisition to obtain syn- In particular, the combination between US and MR imaging chronized monitoring of liver motion. The feasibility of this hybrid imaging (MRI) is very attractive because of the clinical applicability of each and the precision of image fusion were evaluated. method and because both are fully noninvasive (ie, nonionizing). Materials and Methods: Ultrasound imaging was achieved using a clinical These 2 imaging modalities feature different spatial and temporal US scanner modified to be MR compatible, whereas MRI was achieved on resolutions and different sensitivities for measuring tissue properties 1.5- and 3-T clinical scanners. Multimodal registration was performed be- related to morphology. They are mutually complementary, and the tween a high-resolution T1 3-dimensional (3D) gradient echo (volume inter- expected added value of combining them would be better knowledge polated gradient echo) during breath-hold and a simultaneously acquired 2D of the investigated anatomy9,10 or improved assessment of the ther- US image, or equivalent, retrospective registration of US imaging probe in the apeutic results. coordinate frame of MRI. A preliminary phantom study was followed by 4 Ultrasound imaging is widely used in clinics for anatomic and healthy volunteer acquisitions, performing simultaneous 4D MRI and 2D US functional investigations because it is portable, readily available, and harmonic imaging (Fo = 2.2 MHz) under free breathing. inexpensive and permits the visualization and measurement of blood Results: No characterized radiofrequency mutual interferences were detected flow.14Y18 Ultrasound imaging is free of geometrical distortions, ex- under the tested conditions with commonly used MR sequences in clinical cept for the ‘‘thermal lens’’ effect caused by the small change in the routine, during simultaneous US/MRI acquisition. Accurate spatial matching speed of sound with respect to temperature.14,15 It is further consid- between the 2D US and the corresponding MRI plane was obtained during ered a valuable tool for intraoperative motion tracking in soft tissue,19 breath-hold. In situ fused images were delivered. Our 4D MRI sequence per- providing high temporal resolution. Especially for high-intensity fo- mitted the dynamic reconstruction of the intra-abdominal motion and the cused US (HIFU) applications, US imaging adds value by direct vi- calculation of high temporal resolution motion field vectors. sualization of acoustic obstacles and sonosensitive microbubbles20 or Conclusions: This study demonstrates that, truly, simultaneous US/MR dy- by its ability to characterize the HIFU thrombolysis.21 Nevertheless, namic acquisition in the abdomen is achievable using clinical instruments. A US imaging cannot currently provide a clinically validated method potential application is the US/MR hybrid guidance of high-intensity focused for thermometry.17 US therapy in the liver. Conversely, MRI offers a multiplanar view, excellent soft tissue 22,23 Key Words: MR, US, hybrid technology, image fusion, motion monitoring contrast, and a proven method for near real-time thermometry ; these are essential advantages for MR-guided thermal therapies.24Y26 Motion Y (Invest Radiol 2013;48: 00 00) robust near real-time MR thermometry (ie, reference-free MRT) integrated with high temporal resolution US-based motion tracking would be a near-ideal image guidance environment for HIFU ablation.27 ultimodal or hybrid imaging systems are successful combina- The technical challenges arising from the mutual interaction of Mtions used in research or clinical routine. They integrate the the 2 devices US and MRI (potentially generating static or dynamic strengths of 2 imaging modalities and, at the same time, eliminate 1 artifacts) are not trivial.9,10 Ultrasound and MR image coregistration or more weaknesses of the individual modalities. New opportunities was first reported using separate acquisitions at different times.9,28,29 Sequential imaging increases the total duration of acquisition and does not enable in situ image fusion, making this approach less de- Received for publication May 28, 2012; and accepted for publication, after revision sirable in clinical practice. Registering offline US and MR images30Y32 December 8, 2012. From the *Radiology Department, University Hospitals of Geneva, University of is, in general, difficult because each image contains features that are Geneva, Geneva; †Medical Image Analysis Center, University of Basel; not necessarily observable in the other modality. For this purpose, ‡Computer Vision Laboratory, ETH Zurich, Zurich; §Radiological Physics, different postprocessing techniques were developed. Mercier et al29 UniversityofBasel Hospital, Basel, Switzerland; ||Deptartment for Biomedical showed a technique (in the context of neurosurgery) that generates a Magnetic Resonance, University of Tu¨bingen; and ¶MRC Department, MPI for 33 Biological Cybernetics, Tu¨bingen, Germany. pseudo-US (MR image converted into a pseudo-US image ) from a Conflicts of interest and sources of funding: This work was partly funded by the preoperative MR image that improves the MRI-US rigid registration. Swiss National Science Foundation (project no. CRSII2 127549). A hardware coregistration platform for multimodal US and MRI was Reprints: Lorena Petrusca, PhD, Hoˆpitaux Univesitaires de Gene`ve, Service de developed recently by Chandrana et al.34 radiologie (P)YCIBM, Rue Gabrielle-Perret-Gentil 4, CH-1211 Gene`ve 14, Switzerland. E-mail: [email protected]. Ideally, US and MR data sets should be obtained simultaneously, Copyright * 2013 by Lippincott Williams & Wilkins for example, no postural change of the patient. The advantage of the ISSN: 0020-9996/13/4805Y0000 truly hybrid acquisition with multiple modalities is that the images can

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be inherently spatially and temporally registered.9 The use of an elec- A customized holder for the US probe (Fig. 1A) was produced trically shielded commercial US probe in a clinical 1.5-T MR scanner using the stereo-lithography (electrically insulator resin) to allow an has been published,10,35 showing a reduction in electrical interference optimal window for the US beam. The US head was rigidly attached between the 2 modalities, but this was not completely successful be- centrally inside this holder, allowing an internal free space of 3 to cause the transducers were not specifically MR compatible. In addi- 4 cm from the holder’s edge. To prevent noise at the RF detection tion, an evaluation of the effects of a modified US probe (with backing range of the MR scanner, electromagnetic shielding was required. materials changed for MR compatibility) on MR monitoring, including Therefore, the holder and the transmission line (7-m-long cable) were their use in tissue temperature measurement, was also published.36 entirely shielded using cooper and aluminum coating. The trans- Truly simultaneous US/MRI free of mutual interferences has mission line was further coated by a flexible plastic tube (electrically only recently been reported. Tang et al10 described a prototype im- insulator). The US imaging probe is manufactured with an external plementation using a PC-based portable US system radiofrequency layer of polymer, making contact between any metal part and the (RF) and detected minimal periodic RF noise in both modalities. coupling gel not possible. A nonmetalized perimeter of 2-mm thick- Later, cardiac CINE triggering using an MR-compatible US scanner ness was allowed on the frontal holder’s edge to avoid electrical prototype12 and an ex vivo study of RF ablation using a clinical contact to the skin (Fig. 1D), thus ensuring full galvanic isolation to standards compliant US scanner11 were reported in 2010. the patient. The transducer cable was passed through the Faraday cage The aim of the present study was to integrate an MR-compatible via a waveguide and the electromagnetic (EM) shielding structures clinical US scanner with the 4-dimensional (4D) MRI reconstruction were electrically grounded to the cage. The impedance matching at of the intra-abdominal motion37 to obtain a dual-modality charac- the entry gate of the beam-former was adjusted to compensate for the terization of free-breathing motion patterns in the liver, with the long- increased capacitance of the longer transmission line. During experi- term goal of hybrid US/MR guidance of HIFU treatments in the ments, the US imaging probe operated inside the magnet bore, whereas upper abdomen. The accuracy of in situ image fusion was evaluated the beam-former, reconstructor, and user interface computer operated on phantoms and healthy volunteers. outside the magnet room. The MR-compatible US imaging setup was integrated with 1.5-T Espree and 3-T Trio clinical MR scanners (Magnetom; Siemens, Erlangen, Germany). MATERIALS AND METHODS The US imaging probe was accommodated in a thin plastic bag, specially shaped to match the internal shape of the holder and US Imaging Inside the Magnet Bore filled with standard ultrasonic gel, free of air bubbles (Aquasonic, Ultrasound imaging was achieved using an Acuson clinical Parker Laboratories, Fairfield, NJ). Careful acoustic coupling was US scanner (Antares; Siemens Medical Solutions, Mountain View, achieved between the plastic bag and the volunteer’s skin to avoid CA) equipped with packages for abdominal imaging (real-time im- acoustic reflections as much as possible. Note that the bag compart- age reconstruction and display), B mode, pulse train, low energy, ment situated in front of the active part of the US probe fulfills color Doppler mode, and tissue harmonic imaging. Moreover, the multiple roles: (1) ensures acoustic coupling, (2) ensures respiratory system is equipped with contrast pulse sequence imaging.38,39 The motion decoupling, (3) enables a gap between the skin and US im- CH4-1 imaging probe (256 phase array transducer; bandwidth [BW], aging probe such that the US probe can lie inside the shield and 1.8Y4.0 MHz; multifocal option) was modified by the manufacturer avoids any risk of residual susceptibility artifact from the probe, and to avoid magnetic materials, thus ensuring the passive MR compati- (4) suppresses the risk of electrical contact between the shield of the bility of the probe. US probe to the patient skin (a safety issue in the context of MR

FIGURE 1. A, The US imaging probe accommodated in a gel-filled bag and its dedicated holder (EM shielded). B, C, The US probe’s holder attached using an articulated handler (B) on an MR-compatible orbital ring (C). D, Electromagnetic shield of the US probe: note that the acoustic gel bag (2) is exceeding by 5 to 10 mm the edge (3) of the polymer-based holder and only this bag is in contact with the skin (1) and the shielding sheet of cooper (4) is discontinued approximately 2 mm before the edge. E, Dedicated multielement interventional coil.

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Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Investigative Radiology & Volume 48, Number 5, May 2013 Simultaneous US/MR Monitoring in the Abdomen

excitation pulses). Because the operating frequency of the US device angular sector, set at approximately 8 cm radial distance from the is low (e 2.2 MHz), the beam attenuation inside the coupling gel can US probe. be considered negligible. Phantom studies of image coregistration were conducted on a The US probe located inside the shielded holder was attached 2-L volume of gelatin gel, with 3 different spheres (40 mm diameter) to an MR-compatible orbital ring using an MR-compatible articu- embedded inside that gel. The spheres were filled with gelatin gel lated handler (Fig. 1B). The orbital ring was positioned directly on doped with 0.1 mmol/L Gadovist (Bayer, Zurich, Switzerland). Care the MR bed (Fig. 1C) approximately at the isocenter of the scanner. was taken to avoid air bubbles trapped inside gels to avoid magnetic To facilitate the adjustment of the US probe position in an MR en- susceptibility and acoustic artifacts. The US image fusion through the vironment, 5 degrees of freedom of the holder was available with this 3D MR data set was investigated. Moreover, the importance of MR setup: head/feet translation of the orbital ring on the MR bed, circular image distortions, if any, was analyzed. revolution of the handler following the orbital ring’s perimeter, 2 The volunteer study was performed on 1.5- and 3-T MR rotations in the articulated handler (Fig. 1C), and 1 final translation scanners (see below), to demonstrate the feasibility of this hybrid of the shielded holder parallel to the base of the articulated handler, to technology and its applicability for clinical studies. Four healthy control the distance from the US imaging probe to the patient’s skin. volunteers were included in this study, and a written consent agree- A fixed position of the US imaging probe was achieved (ie, rigid ment was signed before the experiments. Magnetic resonance ac- reference frame) despite acoustic coupling with the body of the quisition was performed using a combination between a standard breathing volunteer. matrix coil (6 elements) placed under the patient and a dedicated interventional coil (Clinical MR Solutions, Brookfield, WI), with 3 Study Design elements (for the 3-T setup; Fig. 1E) or a standard loop coil placed on Device cross-compatibility investigation was limited to the scope top of the patient (for the 1.5-T setup). The central hole of the upper of this study, without aiming to provide any product approval docu- coils permitted the US holder’s positioning in contact with the skin. mentation. Therefore, regulatory compliance of the testing methods (Food and Drug Administration, European Conformity, American So- Simultaneous US/MR Motion Monitoring in Liver ciety for Testing and Materials, or other) was not addressed here. Under Free Breathing and Image Postprocessing Initial in vitro tests on static gel phantoms were performed on After placing the US probe, the first step in the healthy vol- 1.5- and 3-T MR scanners to evaluate the mutual influence of the 2 unteer study consisted of acquiring simultaneously a 2D second imaging devices (ie, US and MR) used simultaneously. During MR harmonic US image (typical depths range, 18Y21 cm; temporal res- acquisitions performed with several routine clinical sequences and olution, 15 to 25 fps; single focus mode; axial resolution, 0.52 mm; with a temperature-sensitive (proton resonance frequency shift) gra- lateral resolution, 1.66 mm; output gain/frequency/dynamic window/ dient echo (GRE)Yecho planar imaging (EPI) sequence (Table 1), the temporal average intensity/mechanical index parameters, 20 dB/ US device was successively set to the status (a) power off and (b) 2.2 MHz/45Y60 dB/30 mW cmj2/1, respectively) and a high-resolution active (ie, ongoing imaging) and the signal-to-noise ratio (SNR) in T1 3D GRE (volume interpolated GRE [VIBE]) data set40,41 during the MR images was analyzed. The MR manufacturer’s standard breath-hold. The MR sequence (voxel size, 1.2 Â 1.2 Â 2mm3; quality test for evaluation of active RF interferences due to the op- 96Y144 axial slices; echo time [TE]/repetition time [TR]/acquisition erating US probe inside the magnet bore was also performed on the time/flip angle [FA]/BW, 2.99 milliseconds/6.88 milliseconds/1.36 3-T scanner. minutes/10-/300 Hz/pixel) permitted visualization of the coupling The influence of MR acquisition on simultaneous US imaging gel in front of the US head (Fig. 2). The US imaging probe itself was was evaluated on gel phantoms with echogenic inclusions by suc- not directly visualized in MR images, being screened out by the cessively recording US images while the MR system was, respec- shield. The resin-made wall of the US applicator’s holder was visible tively, paused, performing the automatic shimming within a volume as the total signal void region in the 3D MR data set and the external of interest, or running 4D MRI balanced steady state free precession surface of the coupling gel coincided with the internal surface of the (bSSFP) sequence (see below). Two successive US images acquired additional homemade holder. Therefore, the US holder was manually for a given status of the MR system were subtracted. Should the localized in the 3D MRI volume as a starting point, a rapid online standard deviation of their difference depend on the MR system op- registration of the holder being performed. The localization was eration, an estimator of the additional electronic noise root mean helped by a standard segmentation algorithm applied to its front square was provided. This value was calculated within a region of edge, which is sufficient because precise a priori information on the interest (ROI) including more than 4000 pixels and defined as an full holder shape is known from its design. This localization allowed

TABLE 1. SNR for MR Images With (Simultaneous) and Without US, When Performing Different MR Sequences That Are Commonly Used in Routine Clinical Practice Magnetic Field MR SNR Loss Due to Sequence Strength, T Voxel Size, mm TR, ms TE, ms FA, - BW, Hz/pixel SNR US Off SNR US On US Operation, % T1 VIBE 3 1.2 Â 1.2 Â 2.0 3.32 1.19 10 650 64.08 58.60 8.55 T2 TSE 3 1.0 Â 0.8 Â 4.0 4000 100 120 171 129.56 128.42 0.88 T1 SE 3 1.2 Â 0.9 Â 4.0 464 9.6 70/160 172 118.28 114.22 3.43 T1-fl 3 1.0 Â 0.9 Â 4.0 300 2.46 80 340 84.59 83.73 1.02 T2-haste 3 1.7 Â 1.4 Â 5.0 2000 96 120 781 123.23 123.79 0.45 4D MRI 3 1.9 Â 1.9 Â 4.0 2.91 1.46 32 1502 44.08 44.85 1.75 GRE-EPI 3 1 Â 1 Â 5 200 9 20 294 71.20 67.27 5.52 GRE-EPI 1.5 1 Â 1 Â 6 200 18 20 460 76.78 71.17 7.31 TSE indicates turbo spin echo; SE, spin echo; fl, FLASH spoiled GRE; haste, single-shot TSE.

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FIGURE 2. Breath-hold VIBE T1w 3D MRI images with the installed US imaging setup at (A) 1.5 T and (B) 3 T (volunteer acquisition). The gel bag in front of the US imaging probe is indicated by arrows, and its signal permitted the rigid reconstruction of the known shape of the holder (ie, used as a passive MR marker). The US image corresponding to one of the interpolated MR planes is shown for each case. Numbers and drawings show the landmarks jointly visible in US/MR images. us to find a first rough estimate of the US imaging plane, the US location) acquired immediately before and after the respective data probe being rigidly and centrally located inside the holder. An ac- frames in the interleaved sequence. The frame similarity of the navigator curate registration between the 2D US and the corresponding plane in slices is determined by template matching, tracking, and comparing the the 3D coordinate system of the MRI volume was performed retro- position of 4 ROIs in the navigator frame. Morphological image slices spectively. An affine transformation of the US image allowed us to were acquired at 40 different spatial locations with the slice thickness of fuse the 2 images, the rigid registration being performed manually, 4 mm using a bSSFP sequence, which yields high contrast be- based on anatomical features. tween blood vessels and the surrounding tissue (TE/TR/FA/BW, Note that, in this study, we did not provide an accurate pro- 1.24 milliseconds/2.98 milliseconds/70-/977 Hz/pixel; at least 80 respective registration of the US probe in the MRI space but have ret- petitions). Image matrix was 148 Â 256, with an in-plane resolu- rospectively provided the best-matching interpolated plane from the tion of (1.37 Â 1.37) mm. The resultant acquisition time was 3D MR data set relative to the US image. The distance scale of the 184 milliseconds per frame, yielding a temporal resolution of about images was guaranteed using US image distance scale displayed 3 Hz for image and navigator. The field of view (FOV) was chosen automatically by the device and, respectively, MR Digital Imaging depending on the liver volume, whereas the total imaging time under and Communications in Medicine (DICOM) header embedded in- free breathing ranged from 13 to 20 minutes. The dynamic recon- formation. The magnitude of the US image spatial gradient was struction of the intra-abdominal motion was obtained by postprocessing computed to enhance meaningful features (for visual purposes). Ul- of the MR images according to von Siebenthal et al.37 Liver defor- trasound images were considered as distortion-free ground truth. The mation during the respiratory cycle can be determined using inten- geometric distortion in MR images was determined relative to the sity-based nonrigid registration on these images. Finally, maximum corresponding US image, taking into account the residual mismatch intensity projection (MIP) pseudo-3D transparent images were gen- between fused US/MR images after the best-matching 2D affine erated for visualization purpose. transformation was applied. Local mismatch (or, deformation) be- Four-dimensional MRI and 2D US acquisitions started at the tween US and MR images was calculated by placing point landmarks same time point (typical 0.1-second time offset), synchronized by separately in the 2 modalities and then calculating the local distance means of optical pulses generated by the MR scanner that unfroze between the corresponding points. the US acquisition. Ultrasound images were exported on-the-fly In the second step, 4D MRI37 images were acquired under free from the US reconstructor to an external PC using a Video Graphics breathing simultaneous to second harmonic US imaging (Fo =2.2 Array-Universal Serial Bus grabber (native resolution, 1280 Â 1024 MHz). The respiratory 4D organ motion of the liver during several re- exported 1:1 uncompressed, 30 fps). spiratory cycles was captured as previously described.37 The volume of interest in this acquisition protocol was covered by sagittal 2D slices, RESULTS henceforth called ‘‘data slices.’’ The key concept of this 4D MRI method is to additionally acquire a dedicated so-called navigator slice at a fixed Systems Compatibility anatomical position between each acquired data slice pair, resulting in an The passive MR compatibility of the US probe and its handler interleaved sequence of data and navigator slices. To generate 3D vol- was found to be very good, both at 1.5 and 3 T. The US probe could umes out of these 2D data slices, retrospective stacking of data slices be used inside the magnet bore without a susceptibility-artifact pen- showing the liver at a similar breathing state is performed. The temporal alty if a minimum distance of 3 cm was allowed from the skin. correspondence of data frames is determined by comparing the em- Neither MR image distortion nor B1 artifacts related to the EM shield bracing navigator frames (that always depict the same anatomical on the probe’s holder and/or the transmission line could be visually

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detected in the ROI with used MR sequences (Table 1). Local B1- indicate the position of the US device. The US imaging plane, which field disturbances due to the presence of the US imaging device was determined semiautomatically, corresponds to 1 of the MR were not measured explicitly in this study. planes interpolated into the 3D data stack. Different landmarks (eg, The MR manufacturer’s standard test performed on the 3-T vascularization, liver margins or the diaphragm) with the same shape scanner for the evaluation of active RF interferences originating from and dimensions could be easily detectable in both types of images. the US device indicated a minor reduction in the SNR delivered by a 6-element body matrix coil as compared with the standard MR ac- Image Fusion and Image Distortion quisition: j5.3% with a standing-by US device (frozen) and j5.6% Alignment phantom results are shown in Figure 3. After spa- with a US imaging device active (US parameters provided in ‘‘Ma- tial registration of the US imaging probe (Fig. 3A), a fused image is terial and Methods’’). delivered (Fig. 3D) between a 2D section (Fig. 3B) of the 3D MR The SNR measured in the MR images on phantoms simulta- data set and the US image (Fig. 3C). Note the accurate correspon- neously to US imaging, with MR sequences commonly used in dence between all the visible landmarks and features in these multi- clinical routine (Table 1), showed a very limited loss in the SNR modal images. (typically 3%Y6%), and no characterized RF mutual interferences Similar results are shown in Figure 4 on a healthy volun- were detected (eg, no spikes in the k-space). A minor decrease in the teer. The fused image during breath-hold (Fig. 4D) between the US SNR was detected with the temperature-sensitive GRE-EPI sequence (Fig. 4C) and its corresponding plane extracted from the MRI volume typically used for proton resonance frequency shift MRT: 7.3% at (Fig. 4B) was obtained after in-plane affine transformation as de- 1.5 T and 5.2% at 3 T. No temperature change could be detected in scribed previously. The multimodal registration was evaluated by the proximity of the electromagnetic shield of the US imaging probe visual inspection. As visible in Figure 4D, anatomical landmarks after 10 minutes of continuous acquisition with that temperature- such as vessels, skin, and other anatomical layers and the liver edges sensitive sequence (temperature measurement SD per pixel, 0.4-C). in correspondence to the diaphragm correspond well, showing an A synthesis of other results is shown in Table 1. Subtracting se- accurate correspondence between the 2 image modalities. Overall, quential MR images with US on and off indicated no spatial corre- the US/MR in situ image fusion on volunteers indicated no signifi- lation of the added noise. cant distortion in the central region of the MR images. An in-plane Ultrasound imaging was not significantly affected by the on- spatial mismatch of 1.5 mm between US and MR fused images going MR acquisition. The US image quality in B-mode, second was found for anatomic structures orientated nearly perpendicular harmonic imaging, or contrast-agent pulse mode was found to be to the imaging plane. Similar results (data not shown) were obtained visually invariable whatever the status of the MR acquisition or the for US and MR simultaneous acquisition on the 1.5-T MR scanner. position of the US imaging probe inside/outside the magnet bore. The range of variation of the angular orientation for the MR The electronic noise root mean square in the selected ROI in second best matching plane to the US imaging plane between the holder harmonic US images was increased by 1.5% during the MR shim- segmentation-based calculation and the anatomical landmark re- ming stage and by 4.8% during the high specific absorption rate 4D finement was between 0- and 5-. MRI acquisition. Note that the effective spatial resolution was slightly decreased Simultaneous US/4D MRI Imaging in the final US images because the imaging probe was not in direct Figures 5A and B illustrate a native 2D slice from the 4D MRI contact with the skin because a 3-cm thick layer of gel was interposed data at 2 different respiration phases acquired at 3 T simultaneously (see ‘‘Material and Methods’’). with the US imaging (Figs. 5C, D). Note the varying positions of the Overall, we are reporting a stable performance of the hybrid sys- diaphragm and the high contrast between blood vessels and the sur- tem without any sudden occurrences of accidental US or MR artifacts. rounding tissue. The reconstruction of the 4D MRI data to MIP pseudo-3D Spatial Registration of the US Probe transparent images is illustrated in Figures 6A and B at 2 different In the VIBE T1-weighted (T1w) 3D MRI images, acquired respiration phases. This sequence also permitted the retrospective during breath-hold of the volunteer, the unshielded distal tip of the calculation of temporally (3 Hz) and spatially well-resolved motion US imaging probe’s holder was easily detectable (arrows in Fig. 2) field vectors of tissue between different breathing phases using 3D via the embedded coupling gel visible as the homogeneous signal nonrigid image registration between the volumes and extracted for region. A section of the 3D MR data set (Fig. 2, second row) is the US imaging plane. Over the 4 volunteer series, the range of the presented along the US imaging plane. Because of the EM shield, the projected vector lengths under free breathing was between 5 and active head of the US probe is not directly visible in the MR images, 20 mm. Figure 6C illustrates the motion vectors for 1 respiratory cycle but the position of the holder’s edges could be used as surrogate to plotted on top of the corresponding US plane. Conversely, a 2D section

FIGURE 3. A, Registered US probe holder in the reference frame of the VIBE T1w 3D MR images at 3 T on phantom (3 orthogonal planes are shown). BYD, In vitro fusion between a 2D interpolated section in the 3D MR data set (B) and the corresponding 2D US image (C). A Fused MR/US image is shown in frame D.

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FIGURE 4. A, Registered US probe holder in the reference frame of the VIBE T1w 3D MR images at 3 T on breath-hold volunteer (3 orthogonal planes are shown). BYD, Example of fusion between a 2D section (B) in the 3D MR data set and the corresponding 2D US image (C). Fused image between MR and edge-detection US image (D). into the motion vector field can be plotted on the top of a reconstructed positioned across the organ of interest, and different values of the RF section into breath-hold 3D MR corresponding to the US imaging plane pulse phase were iteratively tested. Although a significant improve- (Fig. 6D). In this particular case, the vector lengths measurements were ment could be obtained from these user-dependent adjustments, in 4.9 mm (minimum), 20.6 mm (maximum), 10.1 mm (mean), and 9.4 mm general, it was not possible to completely remove banding from the (median). full volume of the liver. Analyzing the MR and US data sets acquired simultaneously during 10 to 180 free-breathing cycles (approximately 1Y20 minutes DISCUSSION time base), a stable correlation was observed between the in-plane Multimodal imaging is an important trend for present and fu- organ motion patterns detected with the 2 modalities. ture clinical applications, supported by the benefit of synergetic in- The expected increase in the sensitivity of the bSSFP image formation provided by coupled or integrated hybrid systems. to banding artifacts at 3 T versus 1.5 T, due to steep magnetic field Simultaneous US/MR modality imaging was performed in our changes caused by the presence of the lungs, was confirmed in the study using a technical setup integrating clinical devices. Practically, hepatic dome. To reduce the banding, the shimming volume was interference-free acquisition of US and MR (1.5 and 3 T) images was

FIGURE 5. Native bSSFP sagittal MR slices acquired at a 3-T scanner (A, B) serving for 4D MRI reconstruction and respective US images (C, D) synchronized in 2 different respiration phases. Note that US/MR image coregistration was not performed because the respective imaging planes are not matched. Vertical FOV in the MR images is 35 cm. See the embedded distance scale in US images.

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FIGURE 6. A, B, Pseudo-3D MIP from the 4D MRI reconstruction of the abdominal motion in 2 different respiration phases at 3 T (vertical FOV is 35 cm). C, US imaging plane acquired simultaneous to 4D MRI on the same volunteer, overlaid with the corresponding motion vectors extracted from 4D MRI data. D, On a different volunteer, a section of the motion vector field is overlaid on the fused US/MR breath-hold image. achievable, yielding the same image quality as delivered by each poorly identified markers from affecting the final matching. The rigid modality independently. Preliminary validation studies performed on transformation used to obtain the fused image confirms the low level static phantoms permitted assessment of the geometric distortion of distortion in the MR images because the US imaging is nearly of MR images, the spatial accuracy for the image fusion, the US distortion-free. Further investigations could use US information to imaging-induced changes of the SNR in MR images, and, recipro- correct the geometric distortion of the MR images. Dynamic trans- cally, the additional electronic noise added in US images during MR ferring of information between multimodal US/MR images has been scanner operation. addressed elsewhere.43 The external holder offered a material support for the elec- The truly simultaneous US/MR acquisition was investiga- tromagnetic shielding of the US imaging probe and was used as a ted here in static phantoms and in volunteers’ abdomen under free passive MR marker to determine in first order the orientation of the breathing, but this approach may be advantageous in other clinical probe. A better detection of the US probe could have been done with procedures as long as the US device is equipped with corresponding stereoscopic optical markers or with MR active markers. software packages, as summarized below. The in situ US/MR image fusion accuracy in volunteer abdo- Proof of principle was reported for hybrid US/MR for im- men was found to be equal to or better than 1.5 mm in-plane, for proved cardiac imaging under free breathing.12 Unlike MR navigator anatomic structures orientated nearly perpendicular to the US imag- techniques, the sequence was not interrupted by competing acquisi- ing plane (parallax angle close to 90-). This accuracy was decreased tions of navigator echoes or other k-space signals. for anatomic structures oblique or nearly parallel to the US imaging A particular field of application of this hybrid technology is plane because the US/MR image mismatch caused by a minor devi- foreseen to be MR/US hybrid-guided HIFU in moving organs. An ation in angulation of the US probe was rapidly amplified (inversely important challenge when targeting moving organs is to ensure a proportional to the sinus of the parallax angle). complete and safe noninvasive treatment by obtaining effective A comfortable position of the volunteers could be ensured thermal lesions of oncologic quality while preserving the healthy during simultaneous US/MR acquisitions. Because of the free-breathing tissue. Therefore, an appropriate imaging guiding tool is required conditions, long acquisition sessions (up to 20 minutes) were possible. during HIFU sonication. In general, high frame rate (eg, 25 images The 4D reconstruction37 of the MR data set was performed as per second) information of abdominal motion can be obtained using described previously, without any adaption owing to the simulta- US harmonic imaging or Doppler mode. The temperature-sensitive neous US acquisition. Motion patterns were accurately determined. MR images22,23 are not optimal to track abdominal organ motion The liver diaphragm and blood vessels were easily identified, and because the temporal resolution is traded off over the SNR and the their trajectory during breathing could be followed with both mo- T2* inherent contrast of GRE sequences is low. The ex vivo feasi- dalities; nevertheless, special care was required to align the US im- bility of 2D near-real-time (8 Hz) motion-compensated HIFU aging plane so that out-of-plane motion could be minimized. treatment, integrated with near-harmonic reference-free MRT,44 was Ultrasound and MR image fusion results (Fig. 4) confirmed the recently reported ex vivo,27 the motion compensation being ac- different sensitivity of the 2 methods in the abdominal region. Ultra- hieved based on 2D US data jointly with high-resolution multiplanar sound provided high contrast of tissue interfaces (skin, subcutaneous proton resonance frequency shift MRT. Advantageously, this approach tissue, liver capsule, diaphragm), whereas MR enabled more accurate does not require any underlying predictive model and is compatible visualization of liver vessels. Anatomical landmarks were sufficiently with nonperiodic motion. visible in both imaging modalities to enable accurate image fusion. The simultaneous US/MR hybrid method may be beneficial A challenging issue is the requirement for imaging exactly the for guiding local drug delivery using sonosensitive carriers and same plane with both techniques, for coregistration purposes.34 The pulsed HIFU: US imaging may visualize the microbubbles45 and marker-based technique, which usually involves identifying corre- sonosensitive particles distribution and breakage, whereas MRI vi- sponding landmarks in the FOV of both acquisitions, was described sualizes the target tumor and the eventual thermal effects.22 by Hong and Hashizume.42 In our study, a 2-step registration was Among other clinical applications of hybrid US/MRI, it is performed, first using the segmentation of the US probe holder and mentioned that echo Doppler US imaging may be a valuable tool for second refined by using anatomical landmark information. By using MR flow imaging calibration in the context of hemodynamic studies, simultaneous acquisition, some landmarks are dynamically visible and simultaneous temperature and cavitation monitoring during MR- during the acquisition period in US and MR images. This can prevent guided RF ablation were reported to be feasible.46

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CONCLUSION 19. Pernot M, Tanter M, Fink M. 3-D real-time motion correction in high-intensity focused ultrasound therapy. Ultrasound Med Biol. 2004;30:1239Y1249. We have demonstrated that truly simultaneous acquisition of 20. Dindyal S, Kyriakides C. Ultrasound microbubble contrast and current clinical US and MR images in the abdomen is achievable using clinical in- applications [review]. Recent Pat Cardiovasc Drug Discov. 2011;6:27Y41. struments (1.5- or 3-T MR scanners and clinical US scanner), de- 21. Wright C, Hynynen K, Goertz D. In vitro and in vivo high-intensity focused livering hybrid images of standard quality, practically free of mutual ultrasound thrombolysis. Invest Radiol. 2012;47:217Y225. 22. Ishihara Y, Calderon A, Watanabe H, et al. A precise and fast temperature interferences, and accurate image fusion. Four-dimensional MRI re- mapping using water proton chemical shift. Magn Reson Med. 1995;34: construction of the liver motion was obtained using the standard 814Y823. approach. The potential field of application of this hybrid technology 23. Okuda S, Kuroda K, Kainuma O, et al. Accuracy of MR temperature mea- is foreseen to be broad, especially in interventional MRI, owing to the surement based on chemical shift change for radiofrequency ablation using hook-shaped electrodes. Magn Reson Med Sci. 2004;3:95Y100. complementary information that can be obtained. 24. Jolesz FA. MRI-guided focused ultrasound surgery [review]. Annu Rev Med. 2009;60:417Y430. 25. Hynynen K. MRI-guided focused ultrasound treatments [review]. Ultrasonics. ACKNOWLEDGMENT 2010;50:221Y229. The authors acknowledge Dr Shelby Brunke (Siemens Health- 26. Kim YS, Lim HK, Kim JH, et al. Dynamic contrast-enhanced magnetic resonance care, Business Unit Ultrasound Mountain View, CA) for helpful support imaging predicts immediate therapeutic response of magnetic resonance-guided in US imaging integration with MR image acquisition and to the MR high-intensity focused ultrasound ablation of symptomatic uterine fibroids. Invest Radiol. 2011;46:639Y647. Division of Siemens Healthcare (Siemens Healthcare, Business Unit 27. Auboiroux V, Petrusca L, Viallon M, et al. Ultrasonography-based 2D motion- Magnetic Resonance, Erlangen, Germany) for real-time data transfer compensated HIFU sonication integrated with reference-free MR temperature software from the MR host computer. They are also acknowledging monitoring: a feasibility study ex vivo. Phys Med Biol. 2012;57:N159YN171. the Center for Biomedical Imaging, Switzerland, for access to the 28. Huang X, Hill NA, Ren J, et al. Dynamic 3D ultrasound and MR image registration of the beating heart. 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