Longitudinal analysis plug-in : mono- and multi-modalities (MR, CT/MR) Mono-modality: OLM7, Multi-modality: OLM8

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2 Olea Sphere TM SUMMARY ABOUT Olea Medical Our mission They trust us Unparalleled assets with Olea Sphere TM Core Applications MRI plug-ins Diffusion Weighted Imaging (DWI) plug-in OLM 3 Diffusion Tensor Imaging (DTI) plug-in OLM 4 Perfusion (DSC) plug-in OLM 1 Permeability (DCE) plug-in OLM 2 Lesion counting plug-in OLM 6 Lesion tracking plug-in OLM 9 Analysis plug-in OLM 5 Longitudinal analysis plug-in : mono- and multi-modalities (MR, CT/MR) Mono-modality: OLM7, Multi-modality: OLM8 RESEARCH MRI plug-ins Intravoxel incoherent motion (IVIM) plug-in OLM 10 Arterial spin labeling (ASL) plug-in OLM 11 CT plug-ins Perfusion plug-in OLM 15 Permeability plug-in OLM 16 Analysis plug-in OLM 17 Longitudinal analysis plug-in : mono- and multi-modalities (CT, CT/MR) Mono-modality: OLM7, Multi-modality: OLM8 OLEA SPHERE TM OPTIONS Deployment Maintenance

3 ABOUT OLEA MEDICAL OUR MISSION Olea Medical, a provider of advanced MR and CT perfusion imaging postprocessing, designs and markets innovative medical imaging applications significantly improving diagnostic processes and treatment evaluation. Olea europaea, antique olea, est species in genere Olearum, plantarum florentium in familia Oleacearum. Planta est arbor perutilis, endemica in regionibus quae Mare Mediterraneum circumiacent, cuius fructus est oliva. (Vikipaedia) The Olive (pronounced /ˈɒlɨv/), Olea europaea, is a species of a small tree in the family Oleaceae, native to the coastal areas of the eastern Mediterranean Basin (the adjoining coastal areas of southeastern Europe, western Asia and northern Africa) as well as northern Iran at the south end of the Caspian Sea. Its fruit, also called the olive, is of major agricultural importance in the Mediterranean region as the source of olive oil. After a ten-year career in military informatics, the idea of Olea Medical emerged with three other engineers, motivated and idealistic, and, with it, the mission of Olea Medical Improve Diagnosis for Life TM. Olea Medical, initially a 4-people adventure, is now an established company gathering engineers, mathematicians, astrophysicists, researchers accompanied by renowned clinicians and prestigious scientific advisors that share one common goal: improving the diagnosis and treatment of most devastating diseases. The credibility of Olea Medical has been established through the domestication of cutting-edge technology, partnerships with leading institutions, and a powerful vision: saving the highest number of lives. Olea Medical is the result of the meeting of men and women with strong values and one high ideal: create for life. «Athena scratched her spear and got the sun burned earth to give birth to an immortal tree, capable of healing and nourishing men: the olive tree» Olea Medical was incorporated in 2008, but its history began in 1998, when its founder, then a young medical school student, decided to transition to computer engineering. A trick of life plunged him into the world of medical research to design software dedicated to the processing of medical images for hyper acute stroke the ancestor of PerfScape TM and NeuroScape TM.

4 Olea Sphere TM They trust us ABOUT OLEA MEDICAL Some reputed partners deeply trust Olea Medical solutions: Famous university hospitals and clinical centers use our solutions on a daily basis in routine clinical practice and research: Famous manufacturers from OEM industry also trust Olea Medical s expertise: Compliant with * *To be able to integrate Olea Sphere perfusion data, using the DICOM interface for navigation purposes, Brainlab customers will have to be equipped with the following software package on either a VectorVision² or CURVE IGS System: - Patient Browser 2.1 (Data transfer module) or Patient Data Manager 1.0 ff (Data management module) - and Cranial 2.1 (Navigation module)

5 Olea Sphere TM Olea Sphere is an image processing software package intended for picture archive, post-processing and communication. It standardizes across vendors both viewing and analysis capabilities of conventional and dynamic MRI and CT imaging datasets. The solution features innovative multiparametric and multimodalities whole body image viewing and post-processing. Olea Sphere TM also offers optimal features for follow-up between different time points, modalities and series to efficiently track and assess lesion progression. Olea Medical s applications are compliant with the DICOM standard and Windows, Macintosh or Linux operating systems. Olea Sphere runs on any standard off-the-shelf workstation or it can be used through thin deployment.

6 Olea Sphere TM Unparalleled assets with Olea Sphere Olea Medical s pioneer 3D post-processing and visualization solution, Olea Sphere, delivers unique features: 1. User-friendly and customizable interface 2. Accurate quantitative & qualitative maps thanks to robust algorithms thoroughly tested & documented 3. Multimodal fusion, comparison and temporal substraction 4. Automated and customizable applications for easy step-by-step guidance with fewer clicks during the exam 5. Trusted and tested vendor neutral solution allowing seamless integration within on-site IT systems 6. Thin deployment Olea Sphere TM was thought and designed following radiologists expectations User-friendly 3 Innovative 3 Flexible 3 Fast3 4 Standard and customizable 4Accurate 4Massively scalable

7 CORE Data manager KEYWORDS - Multimodalities - Vendor and platform neutral Multiple DICOM nodes management Import/Export (DICOM nodes, file systems) Merging capabilities Search capabilities Save/load each plug-in individually User management HIPAA Compliance Auto log-out Connectivity and compatibility LDAP and Microsoft Active Directory Audit trails

8 Olea Sphere TM Applications Organ & Pathology Specific Applications Applications within Olea Sphere are far more advanced than the pre-formatted templates commonly available on the market. Olea Medical redefines the notion of workflows through unique and automated step-by-step guidance, offering large possibilities of computations in no time. These convenient applications have been designed for the post-processing of specific conditions imaging (oncology, stroke) and organs (brain, head & neck, breast, prostate, rectum, bones and joints), specifically adapted to physicians specialty. Brain tumor Stroke Head & Neck Spine Breast Female pelvis Prostate Rectum

9 Applications Olea Sphere TM also offers MR and CT cardiac applications with CVi 42 by Circle Cardiovascular Imaging Through partnership with Circle Cardiovascular Imaging, Olea Sphere TM now offers advanced cardiac applications. Circle Cardiovascular Imaging Inc. develops and markets cardiac post-processing software, among which cvi 42 application allowing for the evaluation and analysis of MR and CT images as well as reporting. Available for clinical and research use, the stand-alone software provides full DICOM and PACS connectivity. Olea Sphere TM cardiac application featuring CVi 42

10 Olea Sphere TM Applications Why use our applications? With only a few clicks, the physician will instantly have access to accurate metrics: - Automatic diffusion computation - DSC and / or DCE computation with possibility to select the deconvolution method and the permeability model among a complete range of options - Advanced multiparametric analysis including: - Specific display per organ and/or pathology - Kinetics and curves analysis - ROI, statistics, ratios & histograms - Multiple series fusion - Semi-automatic volume segmentation - MPR and 3D visualization: 3D MIP - Accurate volume rendering - Default and customizable layouts - Advanced follow-up options - Various export options including prostate and breast dedicated reports Apart from these predesigned applications per organ or pathology, Olea Medical also offers customized applications, addressing each physicians needs. Our product specialists will work with each medical team to select tools and functionalities among Olea Sphere plug-ins, to design customized applications, fully operational in their daily practice.

11 Applications Why use our applications? When opening one or several cases, images can: - Already be prepared and pre-processed (offline option) - Processed live (online option) Every automated sequence is processed and every step can be easily followed in the pre-planned order or re-processed to check and adjust. Therefore, this easy step-by-step guidance will allow the user to: - Reduce report turnaround time - Eliminate the need for redundant data entry - Remove broken interface issues - Simplify data analysis Some dedicated features - Automatic log of exam parameters and patient follow-up - Integration with most PACS systems - Seamless collaboration: users have access to clinical and image data from multiple locations - Automated applications for optimal reproducibility

12 Olea Sphere TM MRI plug-ins ADC computation ADC / T2 fusion Diffusion Weighted Imaging (DWI) plug-in KEY WORDS ref: OLM 3 - Automatic parametric mapping - Motion correction The DWI plug-in processes isotropic images from each diffusion gradient factor. The DWI plug-in also computes parametric maps such as ADC maps and exponential ADC maps.

13 MRI plug-ins Diffusion Tensor Imaging (DTI) plug-in ref: OLM 4 Spinal tract Exhaustive search Search from seeds KEYWORDS - Automatic parametric mapping - Fiber tracking - 3D visualization - Interactive statistics visualization The DTI plug-in computes parametric maps (Mean Diffusivity map, Trace- Weighted map, Fractional Anisotropy (FA) map, Relative Anisotropy (RA) map, Volume Ratio (VR) map, colorcoded fiber tracts direction map, Radial DIffusivity map and Axial Diffusivity) from raw diffusion tensor series. The DTI plug-in also allows to reconstruct axonal tracts. The Fiber Tracking is based on a seed approach or on exhaustive search. Mean Diffusivity map Fractional Anisotropy (FA) map Color-coded fiber tracts direction map

14 Olea Sphere TM MRI plug-ins Optimized parametric maps Perfusion (DSC) plug-in ref: OLM 1 KEYWORDS - Delay insensitive algorithms - Motion correction - Leakage correction The DSC plug-in computes optimized parametric maps (rbv, rbf, TTP, MTT, TMAX, tmip) from raw perfusion series. It also provides an algorithm to correct any effect of the contrast agent leakage, hence computing a permeability map. This plugin supports irregular time sampling. It is embedded with automatic or manual arterial input function and venous output function, automatic background segmentation, 4 deconvolution methods (ssvd, csvd, osvd and Bayesian) and instantaneous motion correction algorithm.

15 MRI plug-ins Quantitative and qualitative maps KEYWORDS Permeability (DCE) plug-in ref: OLM 2 - Supports various models - Motion correction - Computation on every time point The DCE plug-in computes the main permeability maps from raw perfusion series. This plug-in supports irregular time sampling and different mathematical models with computation on every time point. The Permeability plug-in provides optimized qualitative maps (TME, AUC, WASHIN, WASHOUT, PEAK) and semi-quantitative maps (VE, VP, Kep, Ktrans). It is embedded with automatic or manual arterial input function and venous output function, automatic or manual background segmentation and instantaneous motion correction algorithm.

16 Olea Sphere TM MRI plug-ins Lesion detection & tagging KEYWORDS Lesion counting plug-in ref: OLM 6 - Interactive statistics visualization - Customized display template - Automatic ROI duplication The Lesion Counting plug-in offers an efficient way to monitor patients response to treatment since it allows the physician to assess the size, number and metabolic activity of measurable lesions and automates the recording and reporting process.

17 MRI plug-ins Temporal lesion tracking KEYWORDS Lesion tracking plug-in ref: OLM 9 - Longitudinal analysis - Automatic 3D registration - Interactive statistics and volumetric visualization The Lesion Tracking plug-in allows the temporal comparison, helping the physician to estimate the overall increase or decrease in size and number of lesions observed.

18 Olea Sphere TM MRI plug-ins Multiparametric analysis KEY WORDS Analysis plug-in ref: OLM 5 - Instant volumetrics - Interactive statistics visualization - Automatic ROI duplication - Personalized display templates The Analysis plug-in allows to simultaneously visualize, segment, measure and evaluate a broad range of datasets from conventional series to perfusion and permeability series along with DTI and DWI series. Data are automatically processed and displayed in predefined layouts that can be interactively changed or in customized layouts. This plug-in allows one-click volumetric segmentation of different lesions or areas of interest. The Analysis plug-in also provides tools to process statistics, ratios and histograms of ROI and various other measurement tools. It offers several layouts and the ability to build customized templates. The MPR and 3D visualization allow the overlay of several series to create secondary capture DICOM series and visualize 3D series, volumes and fiber tracts.

19 MRI plug-ins Monomodality comparison Longitudinal Analysis: Mono or Multimodalities (MR, CT/MR) ref: Mono-modality: OLM7 Multi-modality: OLM8 KEY WORDS - Multimodalities - Longitudinal analysis - Automatic 3D registration - Interactive statistics and volumetric visualization - Temporal substraction - Substraction DICOM series generation Multimodality comparison Embedded with an unparalleled 3D registration between different dates, different modalities or different series within the same study, the Longitudinal Analysis plug-in provides an optimum interface to efficiently track lesions and assess their progression over time.

20 Olea Sphere TM RESEARCH MRI plug-ins IVIM maps INTRAVOXEL INCOHERENT MOTION (IVIM) plug-in KEY WORDS ref: OLM 10 - Biexponential analysis of multiple b-value DWI - Robust Bayesian post-processing method - Computation of pseudodiffusion coefficient (D*) and true diffusion coefficient (D) - Stretched exponential distribution - Motion correction Intravoxel Incoherent Motion (IVIM) imaging is a concept and a method to quantitatively assess all the microscopic translational motions that could contribute to the signal acquired with diffusion MRI. These motions are both molecular water diffusion (due to thermal Brownian motion) and microcirculation of blood (also called pseudo-diffusion). The IVIM plug-in computes the main IVIM maps (D, D*, F). Olea Medical s IVIM plug-in is the only one featuring the Bayesian post-processing method, a rigorous probabilistic estimation of diffusion parameters. This plug-in, offering optimized computational time, is embedded with motion correction algorithms and takes into account the number of excitations (NEX) or the number of acquisitions (NSA).

21 RESEARCH MRI plug-ins ASL maps ARTERIAL SPIN LABELING (ASL) plug-in ref: OLM 11 KEY WORDS - Quantitative blood flow - Pulsed ASL (PASL) and continuous ASL (CASL) - Non-contrast enhanced perfusion - Pediatric imaging Arterial Spin Labeling (ASL) is a noninvasive imaging technique capable of measuring perfusion. This is a great advantage over contrast agent based methods for patients with contraindications for contrast agent injection. The ASL plug-in allows loading repeated label/control images and performs 2D motion correction for realignment of repeated label/ control pairs as well as spatial smoothing and denoising of images to increase signal-to-noise ratio. This plug-in computes the perfusion weighted map and provides adaptive quantitative blood flow computation.

22 Olea Sphere TM CT plug-ins Optimized parametric maps KEYWORDS Perfusion plug-in ref: OLM 15 - Delay insensitive algorithms - Motion correction The Perfusion plug-in computes optimized parametric maps (rbv, rbf, TTP, MTT, TMAX, tmip) from raw perfusion series. This plug-in supports irregular time sampling. It is embedded with automatic or manual arterial input function and venous output function, automatic background segmentation, 4 deconvolution methods (ssvd, csvd, osvd and Bayesian) and instantaneous motion correction algorithm.

23 CT plug-ins Quantitative and qualitative maps KEYWORDS Permeability plug-in ref: OLM 16 - Supports various models - Motion correction - Computation on every time point The Permeability plug-in computes the main permeability maps from raw perfusion series. This plug-in supports irregular time sampling and different mathematical models with computation on every time point. It provides optimized qualitative maps (TME, AUC, WASHIN, WASHOUT, PEAK) and semi-quantitative maps (VE, VP, Kep, Ktrans). It is embedded with automatic or manual arterial input function and venous output function, automatic or manual background segmentation and instantaneous motion correction algorithm.

24 Olea Sphere TM CT plug-ins Multiparametric display KEY WORDS Analysis plug-in ref: OLM 17 - Instant volumetrics - Interactive statistics visualization - Automatic ROI duplication - Personalized display templates Mismatch ratio: 5,79 Relative mismatch: 82,72 % The Analysis plug-in allows to simultaneously visualize, segment, measure and evaluate a broad range of datasets from conventional series to perfusion and permeability series. Data are automatically processed and displayed in predefined layouts that can be interactively changed or in customized layouts. This plug-in allows one-click volumetric segmentation of different lesions or areas of interest. The Analysis plug-in also provides tools to process statistics, ratios and histograms of ROI and various other measurement tools. It offers several layouts and the ability to build customized templates. The MPR and 3D visualization allow the overlay of several series to create secondary capture DICOM series and visualize 3D series, volume.

25 CT plug-ins Monomodality comparison Longitudinal Analysis: Mono or Multimodalities (CT, CT/MR) ref: Mono-modality: OLM7 Multi-modality: OLM8 KEY WORDS - Multimodalities - Longitudinal analysis - Automatic 3D registration - Interactive statistics and volumetric visualization - Temporal substraction - Substraction DICOM series generation Multimodality comparison Embedded with an unparalleled 3D registration between different dates, different modalities or different series within the same study, the Longitudinal Analysis plug-in provides an optimum interface to efficiently track lesions and assess their progression over time.

26 Olea Sphere TM DEPLOYMENT OLEA SPHERE TM OPTIONS Olea Sphere tm DeploymentT» The different components in Olea Sphere can be integrated in customers information system, whatever the degree of complexity and security. Indeed, Olea Sphere can be implemented either in physical or virtualized environments through: USER INTERFACE - Stand-Alone installation (PC / MAC / LINUX) - deployment of the application in a Microsoft environment DICOM imaging devices OPTIONAL - VDI workstations with VmWare Horizon View DATA MANAGER LICENSE MANAGER SCANNERS OFFLINE PROCESSING PACS

27 MAINTENANCE OLEA SPHERE TM OPTIONS Olea Medical understands that providing physicians with state-of-the-art software is not alone a guarantee of success. Indeed, the proper use and dedication of users depend on a timely educational and technical support. Therefore, Olea Medical offers a variety of comprehensive services to support clinical productivity. Olea Medical s Customer Services and Support Solutions Teams actively gather customer s feedback to ensure that Olea Medical s Solutions meet the users needs for continuous clinical efficiency. Olea Medical Customer Services and Support Solutions are provided to those clients who have subscribed to Olea Medical Software Maintenance and Support options. Gold Platinum Updates - Purchased modules updates Support - Regular business hours in France (Mon. Fri. 9:00 to 12:00 am - 1:30 to 5:30 pm GMT+1) - Regular business hours in the US (Mon. Fri. 9:00 am to 5:00 pm GMT-5) - Online support within 72 hours Installation - Online installation Training - 1-day onsite training sessions * following installation - Unlimited access to technical and educational tutorials Extra fees Support - Onsite support* Installation - Onsite installation* Training - Additional onsite training* - 1 monthly webinar session Updates - Purchased modules updates Support - 24/7 - Online & phone support within 24 hours Installation - Online and/or onsite installation * Training - 2-day onsite training sessions * following installation - Unlimited access to technical and educational tutorials - 1 monthly webinar session Extra fees Support - Onsite support* Training - Additional onsite training* * Additional costs: Olea Medical TM personel s travelling & accomodation expenses are not included

28 Olea Medical 93, avenue des Sorbiers La Ciotat - FRANCE TEL + 33 (0) FAX +33 (0) contact@olea-medical.com USA Olea Medical USA 1955 Massachusetts Avenue Suite 12 & 14 Cambridge, MA TEL. +1 (617) FAX contact@olea-medical.com