Virtual Navigator Real-time Ultrasound-MRI Fusion Imaging of leg muscles in supine and weight bearing

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Virtual Navigator Real-time Ultrasound-MRI Fusion Imaging of leg muscles in supine and weight bearing Poster No.: C-1009 Congress: ECR 2015 Type: Scientific Exhibit Authors: M. Marinoni, V. Saia, T. Atzori, S. de Beni, S. D'Onofrio, M. 1 2 1 1 1 1 2 1 2 Olmi, L. Forzoni ; Firenze/IT, Genoa/IT Keywords: Extremities, Musculoskeletal system, Ultrasound, MR, Diagnostic procedure, Image registration DOI: 10.1594/ecr2015/C-1009 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. www.myesr.org Page 1 of 19

Aims and objectives Preliminary study to determine the feasibility to perform real-time MRI and Ultrasound fusion imaging of leg muscles. Tests were carried out by first acquiring leg muscle images while subject was lying supine and then standing using an Esaote MRI GScan Brio system. GScan Brio (Fig. 1) is a tilting MRI system equipped with a permanent magnetic unit (0.25T) that is able to rotate magnet and patient's bed from 0 to 90 degrees while scanning muscles in conventional (supine) and weight-bearing (standing) positions [1, 2]. This feature is especially useful as the MRI image sequence allows us to assess leg muscles' biomechanical and physiological changes as they shift from a standing (weightbearing) to a supine (conventional) position. Being able to attain MRI images of muscles in both positions, lets us study muscle structures at different stress and fatigue levels, possibly opening new valuable prospects in the assessment of rehabilitation treatments (for instance in order to study leg muscles' deep magnetic stimulation) and in the follow-up of patients with degenerative muscular structure diseases. Virtual Navigator fusion imaging technology was used to enhance real-time Ultrasound scans with double position MRI acquisitions, thereby supplementing MRI data [7, 8] with morphological (B-Mode), hemodynamic (Colour, Power and Pulsed Wave Doppler) [3-6] and stiffness (Elastosonography) data. Fusing together these real-time diagnostics supplied by Ultrasound with the highly detailed anatomical images offered by MRI, allows the operator to display in real-time a virtual space where the different imaging modes are merged and where Ultrasound scanning plane spatial data is correlated with threedimensional MRI volumes. This allows for an easier navigation that is based on the geometrical and spatial relationships between the real-time data and pre-acquired data. Virtual Navigator is based on electromagnetic tracking technology used in conjunction with Ultrasound probes (and biopsy instruments for instance) and accurate Motion Compensation Sensor. This sensor is placed on the body being examined to counteract voluntary and/or involuntary movements and to enable continuous motion compensation which preserves the previously set co-registration between two, or more than two, imaging modes. This preliminary study aims to show the potential of real-time fusion imaging for MSK clinical applications that are not limited to relaxed muscles supine assessments, but include the examination of weight bearing muscles structure in standing position. Virtual Navigator technology could also visually aid muscle biopsies in the assessment of Page 2 of 19

pathologies, rehabilitation and follow-up after therapies as well as to display biopsy needle thanks to the Virtual Biopsy technology [8]. In vivo tests for Virtual Navigator realtime fusion imaging between MRI and Ultrasound, both in standing and supine positions are being presented. Images for this section: Fig. 1: The Esaote G-Scan Brio MRI system that was used for image acquisitions. GScan Brio is a tilting MRI system equipped with a permanent magnetic unit that is able to rotate magnet and patient's bed from 0 to 90 degrees, performing patient's acquisitions in conventional (A - supine) and weight-bearing (B - standing) positions Page 3 of 19

Methods and materials Three (3) normal subjects were studied (ages 36, 39, 41; 1 female, 2 males). All of the subjects could stand firmly for an average of 15 minutes during the acquisition of the weight bearing MRI images (the same time frame was required for the acquisition of supine MRI images). A total of around 35 minutes, including patient positioning, was required for the full supine plus standing image acquisitions. Twenty minutes were needed also for the fusion imaging session (with an extra 3 minutes required to upload the MRI study on the Ultrasound system second mode database for each subject). MRI scans were performed using an Esaote GScan Brio system (0.25T, permanent magnet technology), see Fig. 2. An appropriate 4-channel coil was used to assure a good and homogeneous magnetic field signal over the entire area of interest. MRI femoral quadriceps images were acquired using a Spin Echo T1 sequence with a 5 mm slice thickness and a 0.5mm inter-slice distance. Scout lines and proper Localizer image were previously acquired for correct slice positioning. MRI scans were acquired in Axial and Sagittal plane to attain an optimal spatial image resolution of the two conventional Ultrasound scans. Fusion imaging was performed using an Esaote MyLabTwice Ultrasound system equipped with a Linear array 10 MHz probe (LA533, Esaote, Italy) in conjunction with the Virtual Navigator fusion imaging tool (LA533 electromagnetic receiver support 639-042; CIVCO Medical Solutions, Kalona, Iowa, USA). The Virtual Navigator Ultrasound fusion system is equipped with an accurate algorithm which automatically selects the highest spatial resolution for the second mode image acquisition from the available group of data and according to the Ultrasound probe's orientation. The registration procedure was performed with 5 pinpoints that were placed on femoral quadriceps. Registration was always successfully accomplished on first attempt (5 mm range). A second fine tuning was required for half of the procedures mostly because of tissues' bending/deformation due to MRI and Ultrasound different position acquisitions (due to MRI coil and leg possibly not being identically repositioned for MRI and Ultrasound scans). Five (5) pinpoints (Fig. 3) were applied over the leg to ensure that all pinpoints were on different planes (one in the centre and four on the sides forming a square pattern). Pinpoints were required as there are no anatomical landmarks available on the leg's surface or within the leg's structure (lack of vessel bifurcation or of specific muscular, joint or bone signs). Page 4 of 19

Registration could theoretically be performed also taking into account leg's internal planes/reference points. A higher possibility of co-registration error, at least on first attempt, must be taken into account in this case. Images for this section: Fig. 2: The MRI image were acquired using a tilting MRI system which is able to rotate the magnet and the patient's bed from 0 to 90 degrees while scanning the subject in (A) conventional (supine) and (B) weight-bearing (standing) positions Page 5 of 19

Fig. 3: Five (5) pinpoints were applied on the leg since there are no anatomical landmarks available on the leg surface or within the leg structure Page 6 of 19

Results MRI image acquisitions: Dedicated pads were placed over and under the leg (Fig. 4) of the subject being examined to ensure a stable positioning and that the anatomical structures were within FoV magnet's range during weight bearing image acquisitions. The use of pads did not affect leg muscular shape or produce any major leg shape deformation which would have entailed an MRI-US fusion imaging registration error. Pads were required also for supine image acquisitions in order to assure, as much as possible, that the same leg positioning was achieved for both MRI and Ultrasound images. There were no issues concerning FoV leg image reconstruction during MRI acquisitions other than with one subject due to an initial pad misplacement which created artefacts over the leg's skin and prevented the display of images for some pin points (specifically 2 out of 5 in this single case). MRI supine images were first acquired, then followed by weight bearing image acquisitions. Examined subjects were blocked by an appropriate lumbar support when standing (Fig. 5) that would avoid possible falls in the event of impaired postural control (i.e. autonomic failure, pyramidal and/or extrapyramidal syndromes). Thanks to extremely quiet acquisition operations and to an open bore MRI system, subjects had part of their chest, arms and head outside of the bore and were able to talk with the operator while images were acquired in both positions. Stressful/claustrophobic conditions were therefore greatly diminished which allowed patients to relax and to limit their movements also during weight bearing scans which, in turn, avoided major motion or significant image artefacts. Ultrasound-MRI Fusion Imaging: Ultrasound fusion images were acquired using a non-metallic table to avoid any interference with the electromagnetic transmitter. The transmitter was placed on a stable stand with arrow being directed towards the examined leg at the greatest electromagnetic field strength. An appropriate Motion Control Sensor was positioned over the examined leg's skin to counteract voluntary or involuntary movements thereby avoiding to re-perform coregistration between MRI and US. Page 7 of 19

Procedures were followed in order to properly co-register the two imaging modes and to preserve co-registration. During registration procedure the operator avoided to initially press skin with registration pen (not to shift pinpoints positioned on highly movable skin area) and did not press it with US probe during US fusion. These precautions we undertaken to prevent excessive compression of muscles and tissues underneath the skin layer that would allow to match MRI acquisition anatomical conditions as much as possible. By the same token, the operator also used large gel amounts that would avoid applying excessive pressure over the tissues while ensuring proper coupling during Ultrasound examination. Replicating MRI acquisition conditions (leg positions, muscle masses "space distribution", leg rotation, pillow position over leg during resting position acquisition and over the leg during standing acquisitions) as much as possible was important. For the examined subject's comfort, pinpoints can also be removed after MRI acquisition once their position is properly marked with a skin marking pen using the pins' centre hole to mark their position directly over the skin. This procedure would also avoid having pins shift position during co-registration phase (Fig. 6 and Fig. 7). Once the two image acquisition modes were co-registered together (Fig. 8), image acquisition was performed taking into account both B-Mode, Doppler (Color, Power and Pulsed Wave acquisitions) and Elastosonography modes (Fig. 9). Elastosonography showed the most interesting results as far as highlighting stiffness changes between supine and standing image acquisitions. The algorithm that automatically selects the highest spatial resolution for the pre-acquired second mode image acquisition, was tested on all examined subjects by changing probe's scanning orientation to check which resolution was automatically selected by the system for the fused second imaging mode sequence (Fig. 10). Images for this section: Page 8 of 19

Fig. 4: Dedicated pads were placed over and under the leg of the subject being examined to ensure a stable positioning and that the anatomical structures were within FoV magnet's range during weight bearing image acquisitions Page 9 of 19

Fig. 5: MRI images were acquired with examined subjects blocked by an appropriate lumbar support during weight-bearing acquisition in order to avoid possible falls in the event of impaired postural control Page 10 of 19

Fig. 6: Five (5) pinpoints were applied over the leg (A - pinpoints were later marked and removed for improved comfort of the examined subject). Pinpoints were required for fusion imaging registration (B) between US and MRI due to lack of anatomical landmarks both on skin and within the examined body area (C) Page 11 of 19

Fig. 7: Registration between Ultrasound and MRI volume using Virtual Navigator Registration Pen in order to match the pin points placed over leg's skin, with the ones visible on the skin rendering of the MRI volume DICOM data Page 12 of 19

Page 13 of 19

Fig. 8: The two imaging modes (Ultrasound and MRI) are fused together in real-time after registration. MRI volume changes view according to US probe's movement: transverse scan (A); longitudinal scan (B) Page 14 of 19

Fig. 9: Real-time Sonoelastography performed after fusion imaging between MRI and Ultrasound with patient in standing position. The system allows you to select different Page 15 of 19

Ultrasound and second imaging mode (in this case MRI) overlapping levels: no overlap (A); mid-level overlap (B) Fig. 10: A proper Algorithm automatically selects the highest spatial resolution among two MRI acquisitions: should spatial resolution of two uploaded MRI images acquisitions be different based on orientation, MRI volume would also change accordingly and the one Page 16 of 19

with the highest spatial resolution with respect to scanning orientation would automatically be selected (C) when Ultrasound scanning orientation changes from transverse (A) to longitudinal (B) Page 17 of 19

Conclusion Fusing MRI with real-time Ultrasound was always successful achieved with the three subjects and always led to a 5 to 2 mm registration error also on first attempt. The highest spatial resolution algorithm worked properly by automatically switching between the two acquired MRI scans. The highest spatial resolution was always selected based on the Ultrasound acquisition plane spatial position. Real-time fusion imaging between MRI and Ultrasound can be successfully achieved when examined subject is both is supine/relaxed and in weight bearing/standing positions. This method may be especially useful to achieve a higher confidence during US guided muscle biopsies and to follow-up on neurodegenerative diseases as well as to assess deep magnetic muscle stimulation treatments. As already demonstrated by the use of fusion imaging with other body areas and clinical applications [9] and as recently suggested by a paper concerning FDG PET and signs of muscle denervation [10], other second imaging modes could also be employed in conjunction with real-time Ultrasound to achieve fusion imaging. Personal information Marinella Marinoni, Neurology Dept., Careggi University Hospital, Firenze, Italy, marinella.marinoni@unifi.it References [1] "Weight-Bearing MR Imaging as an Option in the Study of Gravitational Effects on the Vocal Tract of Untrained Subjects in Singing Phonation", Traser L, Burdumy M, Richter B, Vicari M, Echternach M; PLoS ONE 2014-9(11): e112405. doi:10.1371/ journal.pone.0112405. Page 18 of 19

[2] "Assessment of the level of muscular strength and volume in physically active English adults", Román M., Del Campo V., Martín J., Romero A.; JOURNAL OF HUMAN SPORT AND EXERCISE - University of Alicante, North America, 7, mar. 2012. Available at: http://www.jhse.ua.es/jhse/article/view/204/503. [3] "Assessment of the cerebral venous system from the transcondylar ultrasound window using virtual navigator technology and MRI"; Laganà MM, Forzoni L, Viotti S, De Beni S, Baselli G, Cecconi P., Conf Proc IEEE Eng Med Biol Soc. 2011;2011:579-82. [4] "Virtual Navigator Registration Procedure for Transcranial Application", Leonardo Forzoni, Sara D'Onofrio, Stefano De Beni, Maria M. Laganà, David Skoloudik, Giuseppe Baselli, and Pietro Cecconi; DOI: 10.2316/P.2012.764-158; Proceedings (216) IASTED Biomedical Engineering 2012. [5] "Transcranial Ultrasound and Magnetic Resonance Image fusion with Virtual Navigator", Lagana, M.; Preti, M.; Forzoni, L.; D'onofrio, S.; De Beni, S.; Barberio, A.; Cecconi, P.; Baselli, G. - Multimedia, IEEE Transactions on Volume: PP, Issue: 99 (July 2013) - DOI: 10.1109/TMM.2013.2244871. [6] "Biopsy guided by real-time sonography fused with MRI: a phantom study", Ewertsen C1, Grossjohann HS, Nielsen KR, Torp-Pedersen S, Nielsen MB; AJR Am J Roentgenol. 2008 Jun;190(6):1671-4. DOI: 10.2214/AJR.07.2587. [7] "Virtual Navigator 3D Panoramic for Breast Examination", Leonardo Forzoni, Stefano De Beni, Sara D'Onofrio, Maria Marcella Laganà, Jacopo Nori, 35th Annual International Conference of the IEEE EMBS Osaka, Japan, 3-7 July, 2013, 1394-1397. [8] "Virtual Biopsy and 3DPan Fusion Imaging for Breast Core Biopsy", E. Giannotti, J. Nori, D. Abdulcadir, G. Bicchierai, L. Forzoni, S. de Beni, S. D'onofrio, G. Scaperrotta, epos ECR 2014: www.myecr.org/epos - DOI: 10.1594/ecr2014/C-0219. [9] "Virtual Navigator Real-Time Ultrasound Fusion Imaging with Positron Emission Tomography for Liver Interventions", Enzo Di Mauro, Marco Solbiati, Stefano De Beni, Leonardo Forzoni, Sara D'Onofrio, Luigi Solbiati, 35th Annual International Conference of the IEEE EMBS Osaka, Japan, 3-7 July, 2013, 1406-1409. [10] "Feasibility of 18F-FDG PET as a Noninvasive Diagnostic Tool of Muscle Denervation: A Preliminary Study", Seung Hak Lee, Byung-Mo Oh, Gangpyo Lee, Hongyoon Choi, Gi Jeong Cheon, and Shi-Uk Lee, J Nucl Med 2014; August 7, 2014 as DOI: 10.2967/jnumed.114.14073. Page 19 of 19