VEVO 2100 Sole Source Specifications Table of Contents 1

VEVO 2100 Sole Source Specifications

Table of Contents 1.SYSTEM ...... 2 1-1 Licensing for the User...... 2 1-2 Safety ...... 2 1-3 Portability ...... 2 2.TRANSDUCERS...... 2 2-1 MicroScan™ transducers ...... 2 3. IMAGING STATION ...... 3 3-1 Integrated Vevo imaging station ...... 3 3-2 Image-guided injection using high-frequency ultrasound ...... 3 3-3 ECG and respiration gating ...... 3 3-4 Integrated blood pressure capability ...... 4 4. Image analysis and software tools ...... 4 4-1 Small animal-based measurements and annotations ...... 4 4-2 Imaging data export and storage in multiple formats ...... 4 4-3 Digital RF ...... 5 4-4 Study management capabilities including user management mode and Time Logger .. 5 4-5 Vevo LAB workstation...... 5 4-6 M-Mode ...... 6 4-7Anatomical M-Mode...... 6 4-8 Pulse Wave (PW) Doppler Mode ...... 6 4-9 Power Doppler Mode ...... 6 4-10 Color Doppler Mode ...... 6 4-11 Tissue Doppler Imaging Mode ...... 6 4-12 3D Imaging ...... 7 4-13 3D-Mode Thresholding ...... 7 4-14 Contrast Imaging Software ...... 7 4-15 Vevo CQ™...... 7 4-16 Vevo Color ...... 7 4-17 VevoStrainTM Analysis ...... 8 4-18 EKV™ (ECG-Gated Kilohertz Visualization) ...... 8 4-19 ECG-Triggered - Respiration Gated Analysis ...... 8 4-20 Vevo®Vasc ...... 8 4-21 Vevo®Vasc Ultra ...... 8 5. TRAINING ...... 9

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VEVO 2100 Sole Source Specifications

1.SYSTEM

The Vevo® High-Frequency Ultrasound System is the only commercially available imaging platform that enables the researcher to obtain in vivo anatomical, functional, physiological and molecular data simultaneously, in real-time and with a resolution down to 30 µm. The system is easy to use, non-invasive and fast, providing extremely high throughput when needed. It is designed with the researcher in mind, with system presets and animal handling tools for fast image acquisition and numerous protocols, software and data management tools optimized for today’s scientists.

The system can also be upgraded to the Vevo LAZR photoacoustic imaging system by a hardware upgrade with Vevo LAZR imaging solution

 Patents o U.S. 7,255,678 High frequency, high frame-rate ultrasound imaging system

1-1 Licensing for the User  No special licensing requirements

1-2 Safety  No room with shielding required  With the VisualSonics ultrasound-based system, there are no radioactive substances used and unlike other imaging modalities, no dedicated room or special room shielding is required.

1-3 Portability  The VSI system is portable and can be moved with ease from one room or lab to another.

2.TRANSDUCERS

2-1 MicroScan™ transducers  Each MicroScan transducer consists of a 256-element array at frames up to 740 frames per second depending on the transducer type.  Seven transducers are offered with frequencies ranging from 15 MHz to 50 MHz to serve multiple applications in imaging animal models ranging from zebrafish to rabbits.  Vevo transducers are both hand held and mountable on an integrated Vevo imaging station. Each transducer can have up to three focus depths that can be adjusted to acquire the optimal image. All VisualSonics transducers can be used to acquire two modes to be viewed simultaneously.

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 Patents o U.S. 7,230,368 Arrayed ultrasonic transducer o U.S. 6,984,284 Piezoelectric composites and methods for manufacturing same o U.S. 7,808,156 Ultrasonic matching layer and transducer o U.S. 7,750,536 High frequency ultrasonic transducer and matching layer comprising cyanoacrylate

3. IMAGING STATION

3-1 Integrated Vevo imaging station  A heated handling table allows for secure positioning of the animal while maintaining physiological body temperature and overall physiological function.  Two types of handling tables facilitate dedicated imaging for mice and another for rats.  The transducer is mounted on the work station, and allows for hands-free scanning (image acquisition). In addition, physiological function can be observed and monitored from the animal platform (temperature, respiration, ECG and blood pressure). This information is displayed alongside the images and can be saved and exported for future reference.  An integrated isoflurane-based anesthesia system accommodates dual connection set up to include oxygen or air.  An injection mount allows for placement and positioning of syringes of different sizes  Patents o U.S. 7,133,713 Integrated multi-rail imaging system o U.S. 6,851,392 Small animal mount assembly

3-2 Image-guided injection using high-frequency ultrasound  A component of the integrated Vevo imaging station  Allows image-guided needle injections and extractions in real-time for targeted injection of cells, genetic material, drugs and retroviruses that can be visualized in small animal embryos through to adulthood.  Improves injection target placement and reduces unnecessary costs of surgical procedures and animal recovery.

3-3 ECG and respiration gating  ECG and respiration gating are used to suppress imaging artifacts due to respiration and cardiac movements. Both are important in cardiac and abdominal imaging for both 2D and 3D data sets.  ECG gating is controlled, using the acquired ECG signal that is input to the system. The software allows for gating to be turned on or off.  Respiration gating is controlled, using the respiration signal acquired also, by the system from the mouse/rat platform. The software allows for gating to be turned on or off.

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 Patents o U.S. 7,133,713 Integrated multi-rail imaging system o U.S. 6,851,392; U.S. 7,426,904; U.S.7,434,542 Small animal mount assembly o U.S. 7,798,963 Method for Synchronization of Breathing Signal with Capture of Ultrasound Doppler Data

3-4 Integrated blood pressure capability  The Vevo imaging system blood pressure input can be adjusted to accept a wide range of voltages from multiple types of blood pressure systems. The input gain of the blood pressure input can be adjusted within the software.  Exact positioning of the catheter can also be visualized.  Left ventricular pressure signals can be transferred into the Vevo imaging system simultaneously with left ventricle view to record real-time left ventricular inner diameter (LVID).  Two-dimensional targeted M-Mode tracings can be recorded through the walls of the left ventricle  Left ventricular pressure waveform input and pressure derivative (dP/dt) are superimposed on the electrocardiogram (ECG) trace, heart rate (HR), left ventricular systolic pressure (LVSP), body temperature and respiratory rate, all simultaneously monitored on the Vevo imaging system.  Pressure/volume loops can be generated within the software.

4. Image analysis and software tools

4-1 Small animal-based measurements and annotations  Over 200 small animal-based predetermined measurements and calculations embedded within the software.  Facilitates an easier learning curve for new users in the animal laboratory which, in turn, improves efficiency and effectiveness.  Measurements/calculations and annotations are customized to small animal anatomy and function (both units and terminology).  Vevo imaging system image files can be opened and shared with multiple investigators (with permission) and re-measured and annotated for purposes of validation and verification.  Multiple data sets can be aggregated to build larger study files. The researcher has complete control over how data is managed and reported.

4-2 Imaging data export and storage in multiple formats  The Vevo imaging platforms allow for image capture, review and export as static images or as video files.  Images can be copied as a group within a series/study, composite between series/studies or as individual images.  The Vevo LAZR platform allows for image acquisition, review and export in multiple image formats (BMP, TIFF, GIFF) or cine loop files (AVI, GIFF, DICOM). Audio signal

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from PW Doppler Mode files are also available for export as WAV audio files for flow analysis.  Studies can easily be stored on the system, external device, disc or network.  The flexibility offered with the Vevo LAZR platform data export enables researchers to compare animal to animal data sets with greater accuracy and integrity. VisualSonics remains at the leading edge of research by providing this facility. This is not currently available from any other ultrasound manufacturer.  Hard drive capacity of 300 GB

4-3 Digital RF  The Vevo 2100 imaging system allows for the export of IQ data (*.iq), envelope raw data (*.raw) or reconstructed RF data (*.rf).  RF formats (Raw, IQ, RF) are available in all of the different software modes.  The RF data can be reconstructed from IQ data by a process which includes interpolation of the I and Q signals and multiplication by a complex exponential e-jωt where ω=2πf; f= the quadrature sampling frequency and e-jωt= cos (2πf) + jsin (2πf).

4-4 Study management capabilities including user management mode and Time Logger  Study based data management – ability to add images/data to an existing study, this is ideal for long term studies  Ability to perform multiple measurements/calculations on all images  Ability to view images simultaneously in a side-by-side manner; aids in consistent imaging plane throughout the course of a study  Ability to perform data analysis on an off-line computer; reserves time on the system for acquisition not analysis  Analyze, label, annotate and archive images and studies through a flexible, open- architecture system. Software supports industry standard Dicom 3.0, providing flexibility in the analysis and production of research data; the software also provides a wide variety of video, image, and data export formats compatible with PC based software.  User magagement mode allows researchers to view their own data,  Time logger records the amount of time a user account spends on the system, to be used for billing purposes in a core-lab environments with multiple users.

4-5 Vevo LAB workstation  Workstation package includes all the post-processing software tools and features available on the Vevo imaging system.  The software package allows for offline post-processing, detailed analyses and data management of previously acquired images .  Installation in researchers’ offices accommodates access to the Vevo imaging system by other researchers for image acquisition.  Compatible with Windows 7, XP and Vista

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4-6 M-Mode  M-Mode imaging produces quantifiable images to characterize moving anatomy, such as a cardiac wall motion, by selecting a line in the B-Mode image and observing it over time.  Sample volume size down to 50 microns; adjustments can be made with sample sizes of 2 mm M-Mode cine loop has a maximum length of 30 seconds.

4-7Anatomical M-Mode  A modification to standard M-Mode typically used in echocardiography.  Allows the user to steer the sample volume to any angle they choose, rather than having the sample volume in a strict vertical position.

4-8 Pulse Wave (PW) Doppler Mode  In PW Mode, the Vevo transducer emits a series of pulses to detect motion. The Doppler shift that is measured is processed and then shown on screen in a spectral display.  Sampling rate for PW range from 1-2 kHz to 125 kHz; velocities that can be detected range from a few mm/s to approximately 6 m/s.  Sweep speed parameter can be set in within a range from 0.25 seconds at 4000 Hz to 5.1 seconds at 200 Hz.

4-9 Power Doppler Mode  Power Doppler assigns a color range to the energy generated by moving blood flow, according to intensity.  Specifically designed for slow flow detection.  Compatible with 3D Imaging

4-10 Color Doppler Mode  Color Doppler uses PW Doppler Mode ultrasound to produce an image of directional flow in blood vessels. The system overlays colors on the image of the blood vessels to represent the speed and direction of blood flow through the vessels.  Vascular flow moving toward the transducer is displayed in red hues. Vascular flow moving away from the transducer is displayed in blue hues. This mode allows quick detection of flow.  Patents o U.S. 7,674,228 System and method of ECG triggered receptive color flow imaging

4-11 Tissue Doppler Imaging Mode  A software tool to assess tissue movement typically preformed on the myocardium.  This tool is typically used to assess levels of diastolic function of the left ventricle by placing a sample volume at the mitral valve annulus, where changes in tissue motion are often detected prior to changes in blood flow spectrums through the same valve. Tissue Doppler Mode may also be used to assess regional myocardial strain, for example between the endocardium and epicardium in a model of myocardial infarction

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4-12 3D Imaging  3D-Mode imaging provides tools to create and manipulate three-dimensional renderings and make volumetric measurements of objects viewed with high- resolution ultrasound.  Acquires a series of 2-dimensional “slices” (as small as 10 µm) and assembles them into a 3D data set that can then be visualized and manipulated. Targets (for example, tumor growth) can be segmented and volumetric measurements made.  3D imaging can be used in B-Mode, Power Doppler Mode or Contrast mode imaging procedures.  3D acquisition functionality allows for precise control of step size, range and slice thickness. This functionality can be integrated with ECG and respiration gating to suppress heart and respiratory artefacts.  Range: min value = 0.5 mm; max value = 38 mm  Step Size: min value = 0.03175 mm; max value = 0.5 mm;  Patents o U.S. 7,798,963 Method for synchronization of breathing signal with capture of ultrasound Doppler data

4-13 3D-Mode Thresholding • A post-processing tool that optimizes and manages signal intensity for improved data analysis in nonlinear contrast mode

4-14 Contrast Imaging Software  Linear and nonlinear contrast mode software tools are available  Optimized to work with MicroMarker contrast agents  Detection and quantification of soft and hard shell microbubbles  Software optimized for molecular imaging experiments by allowing a destruction pulse to quantify microbubbles bound to their endothelial targets  Patent o U.S. 8,275,449 Overlay Image Contrast Enhancement

4-15 Vevo CQ™  Vevo CQ software is state of the art post-processing software for quantification of capillary and microvascular hemodynamics and molecular expression.  Perfusion parameters are derived from a curve fitting algorithm for both bolus kinetics and replenishment kinetics following destruction reperfusion  Perfusion parameters include a series of calculations for amplitude, time and combination of amplitude and time  Spatial rendering is available in the form of parametric maps  Data can be exported in TIFF, BMP, video files and CSV formats

4-16 Vevo Color  Highlight various anatomical targets in different colors for easy interpretation. Works in all software modes on the Vevo 2100 Imaging System.

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4-17 VevoStrainTM Analysis  Post-processing software based on a speckle tracking algorithm and provides information about the cardiac tissue at one point, at one segment or globally.  Five analysis screens: The first four allow for analysis and vector displays, graph tracings, parametric displays for Velocity, Displacement, Strain and Strain Rate. The Secondary Analysis Screen displays overall cardiac tissue performance, segmental Time-to-Peak and segmental phase quantification.

4-18 EKV™ (ECG-Gated Kilohertz Visualization)  A software tool for cardiovascular research to capture the high frame rates required for mouse and rat imaging (up to 650bpm)  EKV offers the highest temporal resolution available in small animal imaging today, with EKV imaging and image reconstruction up to 10 000 fps. With high temporal resolution, cardiac wall motions abnormalities can be assessed with exquisite image quality and resolution in diseased animal models.  Patents o U.S. 7,052,460 System for producing an ultrasound image line-based image reconstruction

4-19 ECG-Triggered - Respiration Gated Analysis  Supressess imaging artifacts due to respiration and cardiac movements  Option for both 2D and 3D imaging

4-20 Vevo®Vasc  Vascular software analysis package with automated vessel wall tracking for quantification of vascular strain, stiffness and thickness (including IMT measurements).  Quantification of pulse propagation velocity is also available when used in combination with EKV software.  Images can be exported in TIFF, AVI or CSVformats.

4-21 Vevo®Vasc Ultra  Combines Vevo®Vasc and EKV software tools  Allows quantification of pulse wave velocity

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5. TRAINING  VisualSonics is the only vendor to provide specialized applications/training support for high frequency ultrasound imaging of small animal models.  Training is offered once the equipment is acquired, on-site, to provide customized training with researchers’ animal models.  Workshops and specialized small animal imaging courses are also available in the North American and European headquarters.

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FUJIFILM VisualSonics, Inc. INFORMATION NOTE: PRELIMINARY SPECIFICATION

Information relating to this product and the application or design described herein is believed to be reliable, however such information is provided as a guide only and VisualSonics assumes no liability for any errors in this document, or for the application or design described herein. VisualSonics reserves the right to make changes to the product or this document at any time without notice.

FUJIFILM VisualSonics, Inc. T.1.416.484.5000 Toll Free (North America) 1.866.416.4636 Toll Free (Europe) +800.0751.2020 E. [email protected] www.visualsonics.com

VisualSonics, VisualSonics logo, VisualSonics dot design, Vevo, Vevo MicroMarker, VevoStrain, VevoCQ, SoniGene, RMV, EKV, MicroScan, LAZRTight, Insight through In Vivo Imaging, are registered trademarks (in some jurisdictions) or unregistered trademarks of VisualSonics Inc. © 2011 VisualSonics Inc. All rights reserved.

© 2010 VisualSonics Inc. All rights reserved. EDU00508 – Vevo 2100 Sole Source Specifications ver 3.4© 2010 VisualSonics, Inc. All rights reserved. Page 10 VisualSonics®, Vevo®, MicroMarkerTM, VevoStrainTM, VevoCQTM, Vevo LAZR, SoniGeneTM, RMVTM, EKVTM, MicroScanTM and Insight through In Vivo Imaging® are trademarks or registered trademarks of VisualSonics Inc.