Health Technology Assessment & Clinical Epidemiology Medical Informatics & Documentation Evaluative Clinical Research

Computational Bioengineering Orthopaedic Biomechanics Tissue Mechanobiology

Navigation around the Head Smart Surgical Instruments Medical Image Analysis Surgical Navigation

www.m

Fax: +41 31 631 5931 Fax: +41 31 631 5960

h

Phone: +41 31 631 5930 Phone: +41 31 631 5959

r.unibe.c

IEFO ISTB

emcente

University of Bern, MEM Research Center Stauffacherstrasse 78, CH-3014, Bern, Switzerland

MEM Research Center for Orthopaedic Surgery

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MEM Research Center http://www.memcenter.unibe.ch

Contents Introduction

2

Organization

3

Health Technology Assessment & Clinical Epidemiology

4

Medical Informatics & Documentation

6

Evaluative Clinical Research

8

Computational Bioengineering

10

Orthopaedic Biomechanics

12

Tissue Mechanobiology

14

Navigation Around the Head

16

Smart Surgical Instruments

18

Medical Image Analysis

20

Surgical Navigation

22

Mechanical Design & Production

24

Acknowledgments

26

Editorial & Review Contributions

26

Awards

26

MSc & PhD Degrees at the MEM Center

27

Dissertations & Theses

27

Guest Presentations

28

Invited Lectures

28

Publications

32

MEM Center 2006

1

This annual report intends to give an overview of our activities and projects over the last year. For further information see our web site (www.memcenter.unibe.ch) or contact us directly.

Introduction

Lutz P. Nolte

Max Aebi

Director ISTB

Director IEFO

For the research groups of the MEM Center, 2006 was another year of consolidation. Both institutes, the Institute for Surgical Technology and Biomechanics (ISTB) and the Institute for Evaluative Research in Orthopaedic Surgery (IEFO), remained within their scientific foci but strengthened and broadened their activities. As part of this process we began building up our competency in surgical disciplines other than orthopaedics and also in the general medical technology field. Increased research networking activities between the institutes were initiated and maintained throughout the year. External funding was maintained at a high level through both governmental funding and with major contributions by non-governmental organizations and our industrial partners. The MEM Center continues to co-direct the Swiss National Center of Competence in Research CO-ME (www.co-me.ch) and hosts various projects and subprojects that have a primary focus on computer aided interventions of the musculoskeletal system. This network of excellence has now moved into its sixth year. In addition, we participated in the National Research Program 53 on “Musculoskeletal Heath – Chronic Pain” of the Swiss National Science Foundation through three project grants. Close cooperation and support has been established with the Swiss Federal Office of Health. There have been significant achievements in the area of technology transfer and various patents were filed and granted during the year. Key collaborative projects with the Swiss MedTech industry continue to be developed through funding from KTI/CTI, which is the Innovation Promotion Agency of the Swiss Federal Office for Professional Education and Technology. In the past year, the MEM Center contributed to the organization of several international scientific meetings, most notably, the Advanced Training High-Tech Course for Paranasal Sinus and Skull Base Surgery (PSSB) 2006 in cooperation with the ISTB and the 7th Bernese Live Spine Surgery Symposium in cooperation with the IEFO. In addition, the IEFO organized several training courses such as the musculoskeletal infiltration course for practitioners. In 2006 we continued our activities in training undergraduates, graduate students, and postdoctoral fellows for future leadership roles in teaching, research, and industry. In the summer of 2006 a new Master of Science in Biomedical Engineering program (www.BIOENG.Master.unibe.ch) began with 25 students. With financial help from the Medical Faculty, a new space for teaching was created that directly adjoined the existing MEM Center facilities. The course of studies is administered by the Faculty of Medicine of the University of Bern, and is offered in cooperation with the Bern University of Applied Sciences. The focal areas of the program are the musculoskeletal system and micro sensor and actuator technology. Currently, more than 65 students are enrolled in the program to become specialists in biomedical engineering. In addition, more than 20 students from the ISTB are currently enrolled in the interdisciplinary biomedical science doctoral graduate program (www.gcb.unibe.ch).

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MEM Center 2006

Organization

2006 in Retrospect

Institute for Surgical Technology & Biomechanics L. P. Nolte

Institute for Evaluative Research in Orthopaedics M. Aebi

Director

Division of Biomechanics Orthopaedic Biomechanics & Tissue Mechanobiology S. Ferguson Division Head Computational Bioengineering P. Büchler Central Services Administration K. Fahnmann-Nolte

E. Gnahoré

A. Neuenschwander

Director

Division of Surgical Technology Medical Image Analysis M. González Division Head Surgical Navigation G. Zheng

Smart Surgical Instruments J. Kowal Navigation Around the Head M. González Central Services Mechanical Design & Production U. Rohrer

The Institute for Surgical Technology and Biomechanics conducts basic and applied research for the prevention and treatment of diseases of the locomotor apparatus. Currently, the institute focuses on two areas defined by its two primary divisions. The efforts of the Division of Surgical Technology are directed towards development of devices and technologies that provide improved surgical functionality, feedback, and integration, navigation and planning focused on less invasive procedures in various anatomical locations, and methods to process and optimally utilize data from a variety of medical imaging modalities. The Division of Biomechanics conducts basic and applied research focused on achieving a better understanding of the mechanisms of injury and degeneration of the human musculoskeletal system, with an aim of developing, evaluating and improving methods for effectively treating such disorders using in vivo and in vitro experimentation, linear and non-linear finite element methods, image analysis techniques, kinematic simulation, tissue culturing, histomorphometry and molecular biology methods.

Evaluative Clinical Research U. Müller

Medical Informatics & Documentation T. Ambrose

Health Technology Assessment & Clinical Epidemiology

Administration I. Zintel

A. Busato

The Institute for Evaluative Research in Orthopaedic Surgery has defined its mission as a dedicated academic research institute in the field of health technology assessment, at the interface of economy and delivery of care, and for outcome research in Orthopaedic Surgery. It has become an interdisciplinary think tank between surgeons, physicians, epidemiologists, computer scientists and experts from other disciplines involved in health care. Their input is crucial to IEFO‘s overall mission of contributing to the advancement and adaptation of musculoskeletal health in a continually and rapidly changing health care environment. IEFO is active in various areas of evaluative medicine and health technology assessment. Traditional clinical trials research is expanded on by including national and international registers, and designing and developing IT systems for the collection, archiving and distribution of evidence based data. Associated with the institute’s mission is a modern center for interactive postgraduate teaching and learning that uses the most sophisticated technology and methodology in this field.

MEM Center 2006

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Health Technology Assessment & Clinical Epidemiology Group Members:

André Busato

Cornelia Balmer

Contact:

+41 31 631 59 62 [email protected]

Klazien

Franziska

Matter-Walstra Schöni

Marcel Widmer

Research Profile Rising costs in health care are not only associated with the introduction of new technologies but also with the demographic transformations of society including increasing age and changes in the gender distribution of the workforce. Knowledge about the patterns of demand and performance of the health system and the impact of new and emerging technologies is therefore crucial for optimizing health service quality and minimizing costs. During 2006, the work of the group was focused on the completion of "Program Evaluation Complementary medicine" (PEK) project, on the continuing analysis of Swiss hospitalization data, and on a new project to study the availability and utilization of ambulatory care in Switzerland.

Current Research Areas Health Systems Research The Swiss Atlas of Musculoskeletal Healthcare was a project that aimed to comprehensively overview the geographical variation in the utilization of common orthopaedic procedures in Switzerland. Similar methodology has been used to study seasonal affects on the use of orthopaedic health care resources, to analyze patient flows for orthopedic procedures, to study the geographic variation in Cesarean delivery rates, to evaluate the sociodemographic factors associated with hospitalizations of children, and to analyze hospital admissions in the fields of gynecology, pediatrics and psychiatry. An interactive website will be activated in 2007 to document this entire body of work. This year, an additional grant from National Research Programme 53 (NFP 53) of the Swiss National Science Foundation has allowed us to expand the research of regional variations of musculoskeletal health care utilization to include a socio-economic perspective. This work will be done in collaboration with the Johann Wolfgang GoetheUniversität, Frankfurt (Prof. K. Allerbeck) and the Institute of Empirical Economics and Economic Policy of the University of Bern (Prof. R. Leu).

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MEM Center 2006

HTA - PEK Health Technology Assessment (HTA) is an increasingly important methodology in the evaluation of existing and new medical procedures. The PEK-HTA project was initiated as part of a nationwide evaluation of complementary and alternative medicine (CAM) with the goal of providing a scientific basis for inclusion of CAM procedures in Swiss basic health coverage. In the summer of 2005 a report was delivered to the Swiss health authorities to provide a decision basis for the status of CAM procedures. During 2006, several articles and multiple dissertations comparing the outcomes and cost of conventional and complementary medicine were completed. Part of the work has already been published and the remainder is currently under review and although the study has been completed, this subject will likely remain a current research topic of the group due to a pending initiative to re-include complementary therapies in basic health insurance coverage. Availability / Utilization of Ambulatory Care This project was mandated by the Swiss health observatory (OBSAN) and is aimed at the determination of socio-demographic and health system related factors of per capita consultation rates with ambulatory care physicians in the multicultural population of Switzerland. The data from this study was derived from claims to the Swiss health insurers (santesuisse) during 2004 and includes 43 million consultations provided by 17’366 Swiss ambulatory care physicians. Socio-demographic data was obtained from the Swiss Federal Statistical Office. Utilization-based health service areas were created and used as observational units for statistical procedures that included multivariate and hierarchical models. The first step focused on primary care in 1018 primary care service areas defined by spatial models. The association between the availability and utilisation of ambulatory care accounting for various geographical, socio-demographic and cultural factors was statistically estimated. Considerable differences with regard to the supply of ambulatory health resources provided either by primary care physicians, specialists, or hospitalbased ambulatory care were observed across the different Swiss language regions.

Hospital service areas with a constant hospitalization rate Hospital service areas with a seasonal hospitalization rate

Hospital service areas with a summer pattern

Winter sports area

Hospital service areas with a winter pattern

Areas with guest beds at >1000m altitude The Impact of Winter Sport Tourism A climate or holiday related seasonality in hospital admission rates is well known for many diseases. However, little research has addressed the impact of tourism on seasonality in admission rates. In Switzerland, hospital service areas defined as winter sport areas show a clear seasonal fluctuation in admission rates of only non-local residents, whereas hospital service areas defined as regular, non-winter sport areas do not show such seasonality. Of 83 hospital service areas in Switzerland, 24 lay within the winter sport area 18 of these show a seasonal pattern in hospital emergency admission rates.

MEM Center 2006

5

Medical Informatics & Documentation Group Members:

Tony Ambrose

Patrik Abt

Contact:

Emmanuel Adriano Benoist Brigante

Olivier Donatsch

Ives Gerber

Simon Gerber

Fabian Lietz

Edith Röösli

Christoph Seiler

Reto Sterchi

Urs Stettler

+41 31 631 59 40 [email protected]

Research Profile To meet the challenges of the 21st century, healthcare is turning to standardized and shared medical informatics systems to control costs, improve overall efficiency, and enhance patient care. New interest for centralized clinical documentation has recently increased with significant attention coming from national governments, medical societies, and industry. The Medical Informatics and Documentation group specializes in researching, designing, and developing novel approaches to centralized medical data management by employing the latest advances in online, offline, and mobile information technologies. The information technology systems that have been developed (www.MEMdoc.org) maintain a high degree of flexibility in order to relieve clinicians from an added documentation burden and to fit within the current clinical workflow. Integrated technologies offer a complete data management solution with clinical, surgical, patient, implant, and radiological data sets. Furthermore, dedicated application interfaces are designed to segregate personalized data from core anonymous data sets for quality assurance purposes, to satisfy data security requirements, and fulfill national regulations.

Current Research Areas MEMdoc Portal Development In 2006, the Medical Informatics group began a major redevelopment of the MEMdoc portal. This 2-year project is funded in part by a KTI grant from the Swiss Federal Office for Professional Education and Technology (www.kti-cti.ch). For this project, the IEFO has teamed up with Qualidoc AG and the Berne University of Applied Sciences to create a dynamic link between an in-hospital data collection system, a hospital’s existing Clinic Information System, and the central MEMdoc database. Such a link provides major advantages over using one or the other system alone. All data is stored locally and anonymously contributed to a central documentation pool. In addition to the link with Qualidoc, the MEMdoc portal itself will be redeveloped to provide increased speed, security, and flexibility.

6

MEM Center 2006

In parallel to the redevelopment of the MEMdoc portal, improvement of the current site continues. This year, the entire portal has been released in multiple languages and the speed and security improved. The SEDICO® interface, in partnership with Global Health Exchange AG, Switzerland, for the e-procurement and tracking of prosthetic devices also continues to grow in usage. Modular Documentation Technology In order to comply with increasing privacy demands, the MEMdoc “Module” has been developed to segregate personalized and anonymous data sets. The module is a fully self-sufficient interface to the MEMdoc central platform. Users and clinics participating in centralized documentation studies can only gain access via the locally hosted module. While purely anonymous user and patient data sets are submitted to the MEMdoc database, the module houses all personalized user and patient information. This year the module itself has been released with a new user interface as well as speed and security enhancements. Patient demographic information can be customized by the administrator to suit the specific needs of the registry while a one-way encrypted hash code of the patient demographic information is created to allow patients to be anonymously followed between clinics. Several new modules have been deployed for the Spine Society of Europe (www.eurospine.org) in Switzerland, Germany, and Austria and more modules are planned for deployment in 2007. Hosted Registries and Studies MEMdoc’s core competence is the design of collaborative models enabling the launch of national registers as well as pre/post market surveillance and regulatory clinical trails. In response to the emergence of novel technologies and regulatory standards, the centralized technology platform services four national registers and close to 20 studies with activities across 300 hospitals in North and South America, Europe, and Asia. Some of the major studies hosted by MEMdoc are: • A MEMdoc Module installation in Paris houses the SO.F.C.O.T. (Société Française de Chirurgie Orthopédique et Traumatologique) French Regis-

ter of the PTH which began as a pilot project in January of 2006. The official launch and announcement to the SO.F.C.O.T. members was done at their annual meeting in November 2006. From the beginning of the pilot through December 2006 the SO.F.C.O.T. Registry has grown to 1068 primary forms, and 191 revision forms. • The Swiss Spine Institute (www.swiss-spine. ch) provides state of the art continuing medical education in the latest non-invasive techniques, surgical procedures, interventional pain therapy and equipment innovations for the care of patients with spinal disorders. The MEMdoc portal hosts the official HTA register for disc arthroplasty and balloon kyphoplasty for the Swiss Spine Institute. Now in its 2nd year, the documentation discipline of the surgeons has been greatly improved and there is an estimated participation of between 65-80 % of Swiss spine surgeons. The first preliminary statistical analyses have been conducted.

MEMdoc Documentation System This figure shows the interdependent relationship between data collection devices (blue), the central repository (green), and data distribution schemes (red).

• The Swiss Society for Orthopedics and Traumatology (Schweiz. Gesellschaft für Orthopädie und Traumatologie - www.sgosso.ch) has formally accepted the IDES Register as the documentation standard for the implantation of their SOR Register. Documentation of real cases will begin in early 2007. • The Swiss Society of Nephrology (www.sgn-ssn. ch/SRRQAP) has adopted the MEMdoc platform to support its Swiss Renal Registry and Quality Assessment documentation system which was officially launched in March 2006. The data collection instruments are currently available in German and French and in the first nine months nearly 2000 forms have been documented. • The IDES (International Documentation and Evaluation System) Register continues to grow in terms of number of users and cases (IDES Hip Primary, 3345; IDES Hip Revision, 424; IDES Hip Follow-up, 3239; IDES Knee Primary, 2149; IDES Knee Revision, 167; IDES Knee Follow-up, 237). In 2006 all of the forms were translated from German/ English into French, Italian and Spanish. IDES has recently been extended with the IDES OSG (ankle joint) in German and additional translations are being performed.

MEMdoc Module Interface The redesigned interface of the MEMdoc Module provides faster access to patient data with increased security.

MEM Center 2006

7

Side

Evaluative Clinical Research

right

left

General -

Group Members:

Day

Number of

Clinical

hip arthropl

asties

Examinatio

Urs Müller

Markus Melloh

Contact:

+41 31 631 59 42 [email protected]

Christoph Röder

Lukas Staub

n Interval 6 wks 4 yrs 11 yrs

Özgür Tamcan

Follow-up Height (cm

3 mo 5 yrs 12 yrs Status

6 mo 6 yrs 13 yrs follow-up pe rformed patient un able to pr es-

)

Research Profile

The Evaluative Clinical Research Group conducts studies to define the basis for future multidimensional assessment methodologies and is involved in the training, setup, and implementation of various clinical HTA studies on musculoskeletal measures. An on-site computer assisted call center with up to 40 part time employees can realize both small and large scale surveys. The group has established close collaborations with various institutes and is a member of the Swiss Network for Health Technology Assessment. Day-to-day practices for improved study administration and planning include close cooperation with hospitals, orthopaedic surgeons, the Swiss Orthopaedic Society, the federal office, health care insurance providers, and leading implant manufacturers.

Current Research Areas Clinical Outcome Studies The analysis of the IDES database for hip arthroplasties helped discover deficiencies in a widely used and traditional hip classification system. A possible misclassification bias was demonstrated for the grouping of patients in classes A, B, and C, as proposed by Sir John Charnley in the 1960s. Using ten year followup data from the IDES database, it was revealed that the Charnley class B consists of two very different patient groups with respect to their walking capacities. Whilst patients with unilat8

MEM Center 2006

In a further analysis, the influence of patient characteristics such as age, sex, BMI, and activity levels on the risk for mechanical stem loosening in total hip arthroplasty was evaluated. Using a case-control study design, it was shown how young males with a high BMI and high activity levels have increased risk for early stem loosening. Healthcare in Motion Hypothesis: Patients consult their physicians in search of cures from disease and suffering. Restitutio ad integrum or health (with a comprehensive perspective) is therefore the final goal for any therapy. The better the therapy; the higher the likelihood of complete recovery. Health is therefore the perfect measure to assess outcome. But what is health? Health describes the state of both body and mind, and depends on gender, age, social and environmental circumstances, and many other factors. To determine the norm values of health perception in the Swiss-German & French population a cross-sectional study with 25’000 respondents was performed. The analysis of this data is ongoing. National Low Back Pain Study To assess the success of treatments for low back pain (LBP) we have to know its natural history and financial impact. Data collection for a longitudinal follow-up study of 2000 randomly selected individuals within the Healthcare in Motion study was finished in the summer of 2006. This data will deliver insights on the natural history of low back pain in relation to its direct and indirect costs. The study, which is supported from the Swiss National Science Foundation's National Research Program 53 is expected to be completed in 2008. This study involves a partnership with the Winterthur Institute of Healthcare Economics, the Schulthess Klinik in Zurich and the Department for Work and Organizational Psychology at the University of Bern.

Multicenter Studies The support, hosting, coaching, and administration of national and international multicenter studies remains a core competence of our group. Some of the main projects are listed below. • Several DGU (Deutsche Gesellschaft für Unfallchirurgie) groups are collaborating with us on studies related to thoracic injuries, and pelvic and brain trauma in children. • The “Virtopsy” study of the Institute of Legal Medicine at the University of Bern requires a high level of data privacy. It is therefore the only multicenter study using the MEMdoc module technology (see Medical Informatics & Documentation), a sophisticated technical set-up that restricts certain sensitive data items to the host institute, and forwards only anonymized data sets to the central server. • The first study sponsored by the Swiss National Science Foundation to use MEMdoc involves the injury patterns and chronification of symptoms after whiplash trauma. Registries The support of national and international registries remains a strength of the IEFO. SWISSspine, the first national Health Technology Assessment (HTA) registry was implemented and hosted on MEMdoc. This registry is setup to document all the disc arthroplasty and balloon kyphoplasty interventions performed in Switzerland for an minimum of three years. The evidence generated with the data shall support the decision for the inclusion or exclusion of the evaluated interventions into the Swiss basic health insurance coverage. The Spine Society of Europe’s Spine Tango registry continues its growth and success, highlighted recently by the creation of a two-year Spine Tango fellowship. The three modules in Bern, Austria and Cologne are used by a multitude of hospitals in the German speaking part of Europe and also by hospitals outside. Spine Tango is the best example demonstrating the feasibility of a European orthopaedic registry organized by the medical profession itself. Of final note are the French hip, German shoulder, and Swiss nephrology registries, which continue to collect data and have become an essential part of the institute’s day to day research and servicing activities.

Charnley Misclassification Bias The newly introduced Charnley class “BB” with patients demonstrating over average walking capacity was traditionally included in the Charnley class B with below average mobility potentially biasing follow-up results. 100%

A

Charnley Class

BB

Average

B C

90% Patients with ambulation > 60 min.

Clinical research on musculoskeletal injuries and diseases has undergone a major change in the last few decades. With the beginning of the new millennium, clinical research, hindered by increasing healthcare costs, has placed increasing importance on the economic aspects of outcome. Costly therapies are therefore critically examined since they may only be available to wealthy individuals or by out of pocket expenses thereby introducing social inequality into the healthcare system. Assessing the real value of therapeutic or preventive measures by including factors such as quality of life, social values, and direct versus indirect costs in both the short and long term is therefore an important goal.

eral hip arthroplasty and a contralaterally diseased hip have below-average walking capacities, those with bilateral total hip replacement have as good mobility as patients with only one hip replacement and a healthy contralateral hip. Consequently, we have suggested a revised classification that introduces a new fourth Charnley class BB for patients with bilateral total hip arthroplasty.

80% 70% 60% 50% 40% 30% 20% 10% 0% Pre-op.

1

2

3

4 5 6 Follow-up Years

7

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9

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Direct and Indirect Costs of LBP This graph shows the itemized mean costs per individual per year for the treatment of low back pain (LBP) in the Swiss population. The data comes from a sub-group of the Healthcare in Motion study. CHF 6000 Disability Pension (SUVA) Disability Pension (IV)

5000

Income Lost 4000 Lost Work Days Care provided by professionals, family and friends Prevention Devices and Appliances Medications

3000

2000

Diagnostic Procedures Reduction of Work Efficiency

Paramedical Care Physician Services

1000

Institutional Inpatient Care 0 Direct Costs

Indirect Costs

MEM Center 2006

9

Computational Bioengineering Group Members:

Philippe Büchler

Björn Olsen

Thibaut Bardyn

Xabier Larrea

Anne Lindberg

Arzu Tasci

Contact: +41 31 631 59 47 [email protected]

Research Profile In the Computational Bioengineering group, challenges in basic and applied medical research are approached by applying modern computational simulation tools. Rather than focusing on the computational methods themselves, we are concerned with their appropriate application to the resolution of practical and fundamental clinical problems. Numerical methods are validated with experimental and clinical results in order to ensure the fidelity of our models. Together with our collaborators, we form a strong research team that covers a wide spectrum of topics involving activities ranging from basic biological research at the cellular level to the direct support of surgical treatments. In addition to our core expertise in the application of finite element methods to the study of skeletal biomechanics, we are improving our presence in the area of computer aided interventions by developing and applying refined numerical techniques to the planning stage of computer aided surgery. Another important research focus of the group involves the modeling of metabolic activities at the organ and tissue level and the alteration of these activities that are caused by external stimuli.

Current Research Areas Integrating Finite Element Analysis into CAS Computer assisted planning has proven to be a useful tool for the placement of osseointegrating dental implants. However, existing systems can not provide quantitative information on the implant's mechanical stability to aid the selection of an optimal implant position. The integration of finite element analyses into the planning software can provide this missing information by giving both short- and long-term stability predictions for a location before the implant is placed. The aim of this project is to develop a computer assisted planning tool that uses finite element analysis and patient specific medical image data to predict the stability of an implant at any desired location.

10

MEM Center 2006

For this project, an in-house finite element solver was developed and integrated into in-house dental planning software. This combination allows for a fully automated and patient-specific analysis of the implant stability. Once the implant position has been decided upon, bone mechanical properties are obtained from CT data and physiological loads are applied to the numerical model of the implant to determine its stability. Once a satisfying primary stability is obtained, bone adaptation laws are used to predict the evolution of the bone mineral content around the implants and evaluate the long term stability.

under a flap cut into the cornea has been suggested as possible treatment. However, unresolved issues related to corneal metabolism need to be resolved. To perform its vital functions, the cornea needs a constant supply of nutrients as well as a pathway to dispose of waste products. Due to its avascularity, the supply must diffuse through the tissue. If the lens is not sufficiently permeable to nutrients, a gradual degeneration of the tissue around the implant could result. Computational methods are especially attractive to study corneal metabolism due to the difficulties associated with the in vivo or in vitro measurement of nutrient transport inside the cornea.

Improving Treatment for Scoliosis Adolescent idiopathic scoliosis is the most frequent deformity of the growing spine. Scoliosis predominantly affects girls during their adolescent growth spurt. Untreated deformities become social stigmas, are crippling and can compromise organ function. Therefore, uncontrollable progression of curvature and related complex deformities require surgical treatment. Surgery is currently the only way to effectively decrease the angle of curvature. Unfortunately, the surgical methods are still based on principles introduced by Hibbs in 1911 — long, stiff bony fusion of a major portion of the spine. These adolescent girls are therefore first subjected to the trauma of a major surgical procedure and then face a lifetime compromised physical activity due to their fused spine.

In this project, experimental techniques are used in conjunction with computational methods to determine the effect of altered corneal metabolism caused by the insertion of an intracorneal lens. Nutrient consumption and waste production are coupled and depend on cell metabolism. A custom FEM code is used to simulate cell metabolism and nutrient transport.

Although the evolution of the curvature is thought to have a primarily mechanical etiology, after the onset of the initial deformation, many questions remain unsolved concerning scoliosis progression. The project targets a better understanding of the biomechanics of the scoliotic spine which will provide improvements in the 3D diagnosis of the disease as well as non-fusion strategies for its correction. Nutrient Transport in Avascular Tissues Presbyopia is a condition of the eye resulting in a diminished ability to focus. This condition affects almost everybody over the age of 40. It is still unclear what exactly causes presbyopia, and no approved treatment exists. The insertion of a lens

Simulating Tissue Mechanobiology Nearly everyone in the world at some point in their lives has back pain that disrupts their work, routine daily activities or recreation. Even if most occurrences of low back pain go away within a few days, others take much longer to resolve or lead to more serious conditions. Intervertebral disc degeneration is a frequently suspected cause of back pain. Current treatment options are invasive and fail to restore the natural biomechanics of the spine. The tissue engineering of a functional intervertebral disc is seen as a future solution to this problem. The idea is to transplant intervertebral discs produced by a lab culture of the patient's own disc cells. Cells react to load. The project aims to study how cell mechanosensitivity may be used to control tissue formation. Experimental cell culture and finite element calculations are combined to gain a deeper understanding of the mechanobiology of disc cells. The objective is to define laws relating the mechanical stress environment of disc cells to their metabolic activity and production. This knowledge will be useful to optimize future tissue engineering experiments to produce a targeted tissue composition and set of mechanical properties.

Bone Adaptation in Response to Mechanical Stimuli Computer simulations of mathematical-based theories for bone adaptation have been implemented and qualitatively validated by comparison with experimental data. Identical laws will be used to evaluate the long term stability of implants.

Nutrient Transport and Cell Metabolism in the Cornea Custom FE analysis of the cornea incorporates Fick’s law of diffusion, which dictates the transport rate and concentration of each species through the tissue. The nutrient consumption and waste production are also incorporated. These are coupled and depend on cell metabolism.

Testing Cellular Responses to Loading Agar gels are used to provide a 3D scaffold for cells during mechanical stimulation. These constructs are used to provide empirical data for simulations. MEM Center 2006

11

Orthopaedic Biomechanics Group Members:

Stephen Salman Ferguson Chegeni

Contact:

Philippe Gédet

Paul Hulme

Jörg Krebs

Paul Anke Thistlethwaite Türger

Juan Diego Gomez Valencia

+41 31 631 59 25 [email protected]

Research Profile The Orthopaedic Biomechanics Group conducts basic and applied research focused on expanding the knowledge of the mechanisms of musculoskeletal disorders and developing improved strategies for their treatment. One main thematic area of study continues to be the complex relationship between spinal loading, spinal motion and the intrinsic structural properties of the spine. Work continues on the effective treatment of osteoporotic compression fractures of the spine, with our efforts divided between addressing the mechanical consequences of bone augmentation and reducing any potential risks of the process. With our collaborators in the CO-ME Research Network of the Swiss National Science Foundation, we continue to combine expertise in the area of functional simulation of the musculoskeletal system with our own extensive knowledge on the potential mechanisms of hip joint degeneration in the specific context of femeroacetabular impingement. High-fidelity finite-element joint models are used to validate the predictions of our partners’ near-realtime functional simulations. Our goal is to provide surgeons with an accurate and relevant software tool for planning surgical interventions.

Current Research Areas Applied Research Last year we continued our collaboration with partners in the dental, biomaterials and orthopaedic industries on research activities ranging from simple material tests to complex multidisciplinary in vivo implant studies. In one study we compared a new saw blade design with a current clinical standard. The bone temperature during and after the cutting process, the axial and radial cutting force and the bone removal rate were measured . Following mechanical tests, histological analysis of the cut surfaces was performed to investigate the influence of saw blade design on local bone damage. 12

MEM Center 2006

In another study we investigated the rheological properties and flow distribution patterns of a newly developed biocement for use in osteoporotic bone augmentation. After injecting the cement under controlled and repeatable conditions in to vertebral bodies, computer-tomography (CT) scans were made of each specimen and the cement cloud segmented. This cement cloud was then exported to CAD software to determine a variety of morphological properties (dimensions, volume, sphericity. Comparison of the known injected volume with the derived morphological parameters provided valuable insight into cement cohesiveness. The improvement of cement delivery will allow the further optimization of augmentation procedures. Femoroacetabular Impingement Femoroacetabular impingement, the direct contact of the femoral neck with the acetabular rim during extreme motions, has been proposed as a potential factor in the development of hip osteoarthritis. Our 3D finite element models combine representative geometry for both the dysplastic and impinging hip with poroelastic material properties for the cartilage and surrounding soft tissue. Our recent efforts have concentrated on simulating the full dynamic process of several relevant daily activities (e.g. walking, stair climbing, sit-to-stand motion), based on real kinematic and telemetric force data. Our results have shown areas of high shear stress consistent with regions of clinically observed degenerative changes. Further research is planned to investigate potential therapeutic interventions, such as femoral neck reshaping or acetabular rim resection. Kinematic Analysis In vivo kinematic analysis of the spine has significant potential for improving the diagnosis and understanding of spinal pathologies and the evaluation of treatments. Over the past few years we have been developing a system for dynamic 3D kinematic measurement of the spine using CT and fluoroscopic imaging. Currently viable solutions to this image registration problem can require more than a minute to solve a single vertebral pose. For a dynamic test (e.g. 100 images x 4 vertebra x 1min. = 6.6hrs) this methodology can quickly become impractical. Our solution uses kinematic

feedback and 3D bone models to aid the otherwise challenging automatic 2D segmentation of individual vertebrae. Recent work has improved the segmentation under real imaging conditions including proximity and overprojection. The reduced segmented data quantity contributes to solution times on the order of 1s (100x4x1s=6.6min) while yielding accuracy similar to existing registration methods. Cement & Fat Embolism in Vertebroplasty Vertebroplasty, the percutaneous injection of acrylic bone cement into fractured, osteoporotic vertebrae, is reported to be a safe and effective technique for pain relief. The most common complication is cement leakage into adjacent structures. If cement leaks into blood vessels it can be carried into the lungs resulting in blockage, i.e. pulmonary embolism. We have investigated the cardiovascular consequences of pulmonary embolism with different cement materials. Acrylic cement caused mild changes in blood pressures. More severe changes with calcium phosphate are thought to result from increased cement disintegration.

Modeling the Labrum Femoroacetabular impingement has been shown to be a mechanical initiator for hip joint degeneration. Poroelastic finite element models of the apposing tissue structures of the hip have been developed to evaluate novel surgical interventions for joint preservation.

5.0mm

Cement injected into vertebral bodies displaces fatty bone marrow into the circulation where it can block blood vessels in the lungs leading to cardiovascular complications. We have investigated different methods to prevent these complications. The administration of a phosphodiesterase inhibitor that causes dilation of lung vessels prevented the cardiovascular changes normally seen after bone marrow fat embolism. Effects of Vertebral Cement Augmentation New vertebral fractures have been observed to preferentially occur adjacent to vertebrae with cement augmentation. Whether these new fractures result from altered mechanical loading, or from a natural progression of osteoporosis, has not been ascertained. The cement material is stiffer than the surrounding cancellous bone, thus possibly altering the mechanical behavior of the augmented and adjacent vertebrae. To identify vertebral regions in which new fractures may preferentially occur, we found relevant variations in vertebral morphology, using microCT, and determined their relationship with mechanical strength. In addition, we developed a technique using microCT to noninvasively quantify the change in endplate deformation under loading before and after augmentation.

Micro-CT to Evaluate Vertebroplasty As a result of cement augmentation, there is a change in the overall stiffness of the vertebra. The consequences of this local stiffening in the surrounding structures and adjacent levels are evaluated using MicroCT imaging during in vitro loading.

Cement Embolism in the Lungs This image shows the 3D cement distributions in two sets of lungs after experimental embolism with two different types of cement. The acrylic cement distribution (Yellow) forms a relatively continuous casting of the blood vessels whereas the calcium phosphate cement (Orange) has fragmented into multiple pieces.

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Tissue Mechanobiology Group Members:

Stephen Jamison Ferguson Edmondson

Contact:

Ladina Ettinger

Daniel Haschtmann

Jivko Stoyanov

Bernice Jim (visitor)

+41 31 631 59 25 [email protected]

Research Profile The Tissue Mechanobiology Group conducts research leading towards improving the current treatment methods for degenerative disorders and traumatic injuries of the spine. The group focuses its efforts on developing a better understanding of the interaction between living tissues and biomaterials, studying the influence of mechanical and physiological stimuli on tissue repair and development, and evaluating the potential for achieving a successful biological repair to an injury or to degeneration. We employ a variety of cell, tissue and organ level models in the study of normal and compromised intervertebral disc metabolism. A major initiative in our group is the development of appropriate three-dimensional scaffolds for the repair of annular and nucleus defects. Our active collaboration with the Orthopaedic Research Laboratory of McGill University continued in 2006 with a visiting researcher performing experiments in our lab. Together we continued to develop and refine various methods for the longterm culture of ex vivo intervertebral disc with the goal of achieving an application-specific model for the evaluation of degenerative mechanisms and regenerative treatments.

Current Research Areas Osmotic Effects within the Intervertebral Disc It is generally agreed that the mechanical environment of intervertebral disc cells plays an important role in maintaining disc health with a balanced matrix metabolism. The precise mechanism by which the involved signals are transduced is poorly understood. Fluid flow and concurrent osmotic changes within the extracellular matrix (ECM) are thought to be involved. In our recently established whole-organ disc / endplate culture system, a degenerative ECM gene expression profile was demonstrated. The aim of this study was to investigate the effects of cyclic osmotic loading on metabolism and gene expression in the disc culture system. Intervertebral disc / endplate units were isolated from New Zealand White Rabbits and 14

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cultured either in iso-osmotic media (osmotic pressure: 335 mosmol/kg) or were diurnally exposed to hyper-osmotic conditions (485 mosmol/kg) for 8 hours to simulate a human loading / unloading scenario. Cell viability, metabolic activity, matrix composition and matrix gene expression profiles (aggrecan, collagen I/II) were monitored. We could demonstrate that diurnal osmotic stimulation had no significant effects on proteoglycan content, cellularity and disc cell viability after 28 days in culture and an initially decreased metabolic activity recovered with continued osmotic stimulation. However, hyper-osmolarity did cause increased cell death in the early culture phase and counteracted the up-regulation of type I collagen gene expression in nucleus and annulus cells. In contrast, collagen type II did not respond to the osmotic changes and was down-regulated in both groups. Therefore, we can conclude from this study that diurnal hyperosmotic loading partially inhibits a degenerative matrix gene expression profile and counteracts cellular metabolic hypo-activity in vitro in an organ culture model. Post-Traumatic Disc Degeneration There is a major controversy over whether or not spine trauma with vertebral endplate fractures can result in post-traumatic disc degeneration with concurrent functional impairment and possible chronic pain. However, the biological effects within the discs following endplate factures are poorly understood to date. The aim of our investigations was to establish a novel disc / endplate trauma culture model to reproducibly induce endplate fractures and investigate concurrent disc changes in vitro. The current model is based on the above mentioned full-organ disc / endplate culture system. Intervertebral disc / endplate specimens were isolated from New Zealand White Rabbits and cultured in media. Burst endplate fractures were induced in half of the specimens with a custommade fracture device and subsequently cultured for two weeks. Biological effects such as necrotic or apoptotic cell death and the expression of pro-apoptotic genes and other genes involved in organ degeneration e.g. matrix metalloproteinases (MMPs) were analyzed. Cell damage was assessed

by quantification of the lactate dehydrogenase (LDH) activity in the supernatant. The expression of genes involved in the cellular apoptotic pathway (Caspase 3) and the pro-apoptotic proteins FasL and TNF-α were monitored. The results demonstrate that LDH levels increased significantly within 24 hours post trauma compared to the control and remained elevated for three days. Furthermore, a constant up-regulation of the Caspase 3 gene in both disc compartments was noticed up until day 14. The pro-apoptotic proteins FasL and TNF-α were up-regulated predominantly in the nucleus. The MMP-1 and -13 genes (collagenases) were also increasingly expressed within the entire disc post trauma. From this study we can conclude that endplate burst fractures result in apoptotic disc cell death in nucleus and annulus tissues. Moreover, FasL and TNF-α expression by nucleus cells may lead to continued apoptosis induced by Fas- and TNF-α receptor bearing cells. In addition, TNF-α over-expression has numerous potentially deleterious effects on disc metabolism such as over-expression of matrix proteinases. Taken together, the short term biological response of the disc following endplate fracture exhibits major characteristics commonly seen in "idiopathic" disc degeneration. Adipose Tissue-Derived Stem Cells The use of adipose tissue-derived stem cells represents a novel and potentially powerful therapeutic approach for the treatment of intervertebral disc degeneration. Our laboratory is currently characterizing the growth and differentiation potential of rabbit adipose tissuederived stem cells (ATSC). These cells are tagged with green fluorescent protein (GFP) for positive identification, seeded in a fibrin carrier and introduced into our recently developed ex vivo whole organ rabbit intervertebral disc model and cultured in the presence of various growth and differentiation factors. The influence of mechanical stimulation on the differentiation of ATSCs will be evaluated using the loading apparatus developed for 3D scaffolds (see Computational Bioengineering section).

Adiapose Tissue Derived Stem Cells Rabbit adipose derived stem cells, stably transduced with a lentiviral vector, express a green fluorescent protein (GFP), which allows these cells to be distinguished from native cells both in vitro and in vivo.

Disc / Endplate Trauma Model An example of trauma induced in a rabbit specimen with a custom fracture device. The resulting fractures exhibited a burst configuration where the nucleus pulposus (NP) herniating through the fractured bony and cartilaginous endplates (EP).

Scaffolds for Tissue Engineering Polymeric scaffolds, which allow the oriented growth of annulus fibrosus and nucleus pulposus cells, have been evaluated for potential application in tissue engineering.

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Navigation Around the Head Group Members:

Miguel Frank González Langlotz

Contact:

Michael Bläuer

Jonas Chapuis

Roxana Djafarzedeh

Giséle Douta

Jordi Garcia Santacreu

+41 31 631 59 50 [email protected]

Research Profile The Navigation around the Head group focuses on the development of systems and methods to support the treatment of pathologies in the craniomaxillofacial (CMF) region. Consequently, our research is directed towards the planning, simulation, and intraoperative realization of complex surgical interventions. In addition, we work on more generalized research questions such as how to most effectively visualize complex 3D relocation tasks or how to utilize laser surface scanning as an alternative method for geometric data acquisition. Following the recent departure of Dr. Frank Langlotz, these research activities have been overseen by Dr. Miguel González.

Current Research Areas Cranio-Maxillofacial (CMF) Surgery A new system for computer-aided CMF surgery has been developed and introduced clinically. It offers a 3D surgical planning environment featuring realtime morphometrics, automatic mirroring, interactive osteotomy planning, and segment relocation simulation. The system can also integrate conventional assessment and simulation methods such as cephalometry standards and dental plaster models. The system allows for the simulation of a surgical correction on virtual 3D models of the facial skeleton generated from CT scans. For surgical execution, precise positioning guides and an accurate intraoperative navigation module that tracks bone segment positions provide valuable assistance. Using this software tool, operations have been performed on six patients at three hospitals. Evaluation of Surgical Outcome Providing accurate quantitative measures to evaluate surgical performance is also a topic of interest in our group. In particular, our CMF surgery system has been improved by providing surgical outcome measures based on the comparison of preoperative and postoperative surface models. These measures provide a means of assessing the performance of navigated procedures, which were judged satisfactory by our clinical partners. 16

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3D Relocation Guides The strength of a computer-assisted navigation system for bone surgeries lies in its ability to present the surgeon with a precise image of the surgical site on the monitor even if the site is not directly visible. With certain interventions (e.g. with the surgical treatment of fractures) it is necessary to move an irregularly shaped object to a position and an orientation that was previously planned on the computer. Currently, there is no generally accepted method to help visualize this six degree of freedom instruction in an intuitive way on a normal monitor. The goal of this project is to find new methods to present the complex geometric instructions consisting of 3D translations and rotations in such a way as to best help the surgeon in moving an object from its initial configuration to the planned one. With the help of a three-dimensional optical tracking system it is possible to constantly compare actual and specified conditions with one another and to adapt the instructions, which are represented on the monitor, continuously. Special software was developed to allow for a quantitative performance analysis of alternative graphical relocation guides in a laboratory setting. Laser Based Surface Scanning The registration of preoperative images with the intraoperative environment is an important element of image guided interventions. Data aquired during laser scanning of the surface of a surgical site can potentially be used to replace conventional marker-based registration, providing a convenient and non-contact alternative. An intelligent handheld scanner (T-SCAN, Steinbichler, Neubeuern, Germany) that is tracked by an optoelectronic camera system allows for the precise and easy digitization of free-form surfaces and character lines. The acquired surface data can then be used as the input to any of a number of established registration methods such as the Iterative Closest Point (ICP) algorithm. In addition, the device may serve as an alternative to segmented CT models by providing patient specific surface models for planning and simulation in cases where the bone surface is freely available for scanning.

Computer Aided Cranio-Maxillofacial Surgery Our system for computer-aided CMF surgery offers a 3D surgical planning environment featuring real-time morphometrics, automatic mirroring, interactive osteotomy planning, and segment relocation simulation. The system also incorporates new tools to help visualize the six degree of freedom instruction (3D translations and rotations) involved in moving an object from its initial configuration to a planned location.

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X: Y:

Smart Surgical Instruments Group Members:

Not Pictured: Reto Lauper

Jens Kowal

Christoph Anderegg

Contact:

+41 31 631 59 45 [email protected]

Anna Martina Lars Ebert Bröhan

Iwan Eicher

Mario Löffel

Marc Puls

Tobias Rudolph

Research Profile The Smart Surgical Instrumentation (SSI) group focuses its research efforts on developing innovative surgical instruments and implants. The aim of these devices is to enhance dexterity, increase surgical precision, facilitate minimally invasive approaches, reduce risks, and lower costs. An important step in this process is the introduction of these new solutions into the clinical environment and the evaluation of the treatment and clinical workflow benefits. Therefore, the main challenge of our group is the successful transformation of applied research and development into clinical implementation. Our group consists of a multi-disciplinary team of engineers with strong clinical ties. Our group has developed core competencies in mechatronic systems design, signal processing and computer graphics. Most of the group’s projects tackle problems in the orthopaedic area but in the last year we have extended our research focus to include problems in the field of ophthalmological surgery.

Current Research Areas Surgical Tooling for Vertebroplasty In vertebroplasty, bone cement is injected into a collapsed vertebral body to help stabilize fractures and relieve pain. Although rare, serious complications can result from cement leakage into the venous system and spinal canal. A cements propensity to leak is related to its viscosity: Fewer incidents are observed with higher viscosity cements. However, the required injection pressure for delivering these materials through a biopsy needle necessitates the use of high-pressure injection devices. We have developed a computer-assisted, motorized injection device that overcomes the limitations of currently available manual injectors, which can typically only achieve a low pressure with poor flow control. Our device couples high-pressure cement delivery with flow control and can be directly attached to a cannula. The sterilizable device uses standard syringes to hold the cement and provides a haptic user interface for remote operation. 18

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Retinal Laser Photocoagulation Laser photocoagulation is the treatment of choice for a large variety of retinal diseases such as diabetic retinopathy and age-related maculopathy. Current setups for laser photocoagulation typically consist of a viewing device equipped with a manually aimed laser. Computer assistance can provide the capability to improve the treatment's efficacy. The aim of this project is to develop a computer based laser photocoagulation system that assists in accurately, safely and rapidly placing therapeutic lesions at pre-planned locations and providing guidance during treatment execution. An essential part of the planning is a multi-modal retinal image registration to fuse complementary information from, for example, fundus photographs and fluorescein and indocyanine-green angiograms. We have developed and implemented a multi-step feature-based retinal registration algorithm to geometrically align retinal images of different modalities. Pelvic Fracture Reduction Fractures of the pelvis are serious and potentially life-threatening injuries that affect both young and old. It has been shown that an excellent anatomical reconstruction is essential to achieving a satisfactory functional outcome. However, this is technically challenging due to the restricted visual access and potentially high fracture complexity. We have developed new multimodal image registration algorithms as well as sophisticated visualization techniques in order to assist and improve the intraoperative implementation of preoperatively planned reconstructions. Several cadaveric experiments have been conducted to evaluate these algorithms. Ligament Balancing of the Knee To improve the ligament balancing procedure during total knee arthroplasty we have developed a load sensing device to intraoperatively measure knee joint forces and moments. This device, which is equipped with deformable sections that are instrumented with thick film piezoresistive sensors, allows for the accurate measurement of tibiofemoral contact force amplitudes and locations. The ligament imbalance can then be characterized by the calculation of the net varus-valgus moment. Experiments have demonstrated that the device functions as intended in an in situ environment. The results

obtained indicate that our novel force sensing device has a strong potential to offer useful quantitative information and effective assistance during the ligament balancing procedure in total knee arthroplasty. We have also successfully begun an in vivo evaluation of the system that compares both conventional and device assisted surgical approaches. Development Framework for CAS Software is a key part of assistive surgical technology, and is also important in the development of research tools. In order to streamline the software development process in our institute, we are developing an object oriented application framework that is flexible enough to be used in a research environment, and reliable enough to serve as a basis for clinical test applications. Cross-platform compatibility and independence from commercial libraries are central features. Currently, the framework allows for the seamless connection of navigation and planning steps and has been used as the basis of CAS systems installed in ten clinical sites across Europe. Moreover, it provides, for the first time, a consistent institute-wide data handling standard that allows for convenient exchange of data between individual research groups. In 2006, more than 50 registered developers from different research institutes within the SNF CO-ME research network participated in developing medical software projects using this framework.

Impingement Detection A model of the hip joint demonstrating the detection of an impingement between the femoral head and the acetabular rim of the pelvis. The impingement area represents a potential site for cartilage damage due to increased stress.

CAS Support for Pelvic Fracture Reduction An application screenshot demonstrating a successful coregistration between an Iso-C3D data set and a CT derived surface model.

Cement Injection Device for Vertebroplasty A demonstration setup for vertebroplasty cement injection consisting of an injection device with a loaded syringe, a control box, and a plastic bone with a cancelous bone analog insert.

Multi-modal Retinal Image Registration The registered fundus image and retinal angiogram serve as planning basis for computer assisted retinal laser photocoagulation. MEM Center 2006

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Medical Image Analysis Group Members:

Miguel Laura Xiaodong González Belenguer Ding

Contact:

Jaime Garcia

Nina Kozic

Matthias Peterhans

Kumar Rajamani

Mauricio Reyes

Rudolf Sidler

Haydar Talib

Thierry Zimmerman

+41 31 631 59 50 [email protected]

Research Profile The Medical Image Analysis Group performs theoretical and applied research on image processing, computer vision, virtual reality and artificial intelligence methods for the analysis of medical image data sets, with a focus on their use in computerguided surgical procedures. We work in conjunction with all the other groups in the institute and with a large network of internationally outstanding academic, clinical and industrial partners to provide advanced image analysis capabilities for computer assisted surgery systems. The three main research directions pursued in our group are: 1) incorporating anatomical and physiological knowledge into image analysis and navigation technology; 2) reducing the invasiveness of current CAS procedures by enabling image-based tracking of anatomical structures; and 3) transforming CAS technology into novel clinical applications.

Current Research Areas Statistical Shape Models We have developed a method to construct compact models representing the typical shape of a bone and its predominant patterns of variability across a given population. These statistical models can be used to generate new geometric bone models. This has been applied to the problem of estimating a patient’s bone shape from the limited information available intraoperatively, such as points obtained with a tracked pointer or contours segmented from ultrasound or X-ray images. With an estimated 3D model it is possible to navigate a surgery without any preoperative 3D data acquisition. These methods have been extended to include not only shape, but also bone density information. This allows us to investigate the distribution of biomechanical responses in a virtual population, by performing finite element analysis. This concept is applied to optimize implant designs to ensure optimal fit and function across the an entire target population.

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Augmented Reality Microscope / Endoscope A system for image-guided ENT surgery and neurosurgery has been developed that allows the superimposition of information on the view of an operating microscope. The surgeon can see 3D representations of the target anatomical structures, outlines of risk regions, slices of CT or MRI data, or access pathways previously planned in our preoperative surgical simulation module. The integration of a precise mini-tracker directly on the microscope eliminates the need to track the microscope externally allowing for a more flexible and ergonomic operating room environment. Extensive validation has been performed using synthetic phantoms and human cadaveric specimens allowing us to confirm that the system provides sub-millimeter accuracy. To date, three clinical cases have also been successfully performed with the augmented microscope. In collaboration with the Surgical Navigation Group, we have also applied this augmented reality concept to endoscopy, thus allowing the overlay of information onto the view provided by the endoscope, leading to better localization and control. Further, we have integrated ultrasound imaging so that surgeons can view the current ultrasound imaging plane directly on the view of the microscope or endoscope, complementing and enhancing intraoperative guidance. Ultrasound-based Referencing One of the main drawbacks of current surgeries that utilize CAS technology is their invasiveness. It is common practice to screw large rigid sets of markers to the bones being operated on. To replace this procedure, we are working on image-based tracking of anatomical structures (referencing). The basic idea is to track the imaging device, in this case an ultrasound probe, and use image analysis to identify the anatomical structures in the image, thus being able to find the position and orientation of these anatomical structures with respect to the surgical tools in a fully non-invasive manner. We have developed novel algorithms for the efficient tracking of structures from bone contour data, and have implemented a validation test bench both for 2D and 3D ultrasound.

Surgery with Engineered Tissue Replacements The latest advances in tissue engineering allow for the construction of biological implants that are grown from the patient’s own cells (autografts). In cooperation with the University of Freiburg (Germany), we have developed a system for computer assisted planning, manufacturing and implantation of bioengineered autografts to treat osteoarthritis in the ankle and knee joints. Clinical application has been evaluated by performing navigated arthroplasties on cadaver specimens. Additionally, in order to provide a means for outcome evaluation from postoperative images, a novel measure of joint congruency based on digital filters has been developed. Image Guided Clinical Applications Minimally invasive spine surgery is another area of interest. In collaboration with the University Hospital of Geneva and our Orthopaedic Biomechanics group, we are developing a system to plan and guide vertebral cement augmentation (vertebroplasty) procedures. As part of this work, an efficient segmentation method based on level sets has been developed to delineate the cement cloud in intraoperatively acquired fluoroscopic images.

Non-Invasive Referencing An ultrasound image is used to determine the position and orientation of a vertebra, thus eliminating the need to use surgically implanted referencing aids, which can be rather invasive.

Vertebroplasty Cement Cloud Tracking A time sequence showing the automatic segmentation of injected bone cement during vertebroplasty. This visual aid helps the detection of poorly defined cement boundaries and small cement particles.

Morphing Shape and Bone Density Statistical models combining both shape and bone density information may be used together with finite element analysis to perform biomechanical investigations over large virtual populations.

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Surgical Navigation Group Members:

Guoyan Zheng

Hidayet Akarçay

Xiao Dong

Serge Sagbo

Ramesh Gongli Steffen Schumann Thoranaghatte Wang

Xuan Zhang

Contact: +41 31 631 59 56 [email protected]

Research Profile In 2006, the Orthopaedic Navigation group evolved into the Surgical Navigation group reflecting our expanded aim of developing and validating medical image computing technology to enhance the autonomy and improve the usability of computer assisted interventional systems both within and beyond the orthopaedic field. In the past year we have continued to introduce and develop medical imaging computing methods for various clinical applications. These include automatic morphological measurement, femoral head segmentation, and pose determination of femoral nail distal locking holes as well as hardware accelerated 2D to 3D registration, registration of the small bones of the inner ear, and methodology to create a simple augmented endoscope.

Current Research Areas 3D Morphology from X-rays A computational framework based on particle filters has been developed for the fully automatic determination of morphological parameters of the femur from a set of calibrated 2D X-ray images. Accurate knowledge of the morphological parameters of the femur, such as the center and radius of the femoral head, the radii and axes of the femoral neck, shaft and medial and lateral condyles plays an important role in the evaluation of hip function, in the planning and computer assistance of various surgical procedures including osteotomies of the proximal femur and in the alignment of fractured femoral fragments. In this framework, the anatomical shape of the femur is decomposed into several simplified geometrical components. Constraints among these simplified components are defined according to the anatomical structure of the femur. Each component is represented by a set of parameters describing its 3D spatial position as well as its 3D geometrical shape. Particle filter based inference is then used to optimally estimate those parameters from the calibrated fluoroscopic images.

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Automatic Femoral Contour Extraction A 3D statistical shape model based framework for automatic extraction of the proximal femur contours from calibrated X-ray images was developed. Automatic identification and extraction of bone contours from X-ray images is an essential first step task for further medical image analysis. In our framework, we solve the automatic initialization by an estimation of Bayesian network algorithm to fit a multiple component geometrical model to the calibrated X-ray images. We then extract the contour through a graphical model based Bayesian inference using a statistical shape model. Preliminary experiments performed on image data from three patients show promising results. 3D Models from Sparse Data We have developed an integrated approach to reconstructing patient-specific surface models from sparse input data. At the heart of our approach lies the combination of sophisticated surface reconstruction techniques and a statistical shape model of the target anatomical structure. Outliers are effectively handled by consistently employing a least trimmed squares approach throughout the entire reconstruction process. Experiments performed on sparse input data and on a limited number of calibrated X-ray images have confirmed a robust performance in regards to handling outliers, pathology, and noise. Reconstructing Implant Features It has long been recognized that one of the most difficult steps of the intramedullary nailing of a femoral shaft fracture is distal locking – the insertion of distal transverse interlocking screws, for which it is necessary to know the position and orientation of the distal locking holes of the intramedullary nail. We developed a constrained optimization approach to solve this problem using a single calibrated fluoroscopic image. The two-stage optimization begins with automatic estimation of the distal nail axis. In the second stage, the translation and rotation of the distal locking holes around the estimated axis are resolved by iteratively fitting geometrical models to the image data. In vitro experiments have shown a high accuracy.

Hardware Accelerated Registration We have developed a method for generating digitally reconstructed radiographs (DRRs) and volume gradient projections using hardware accelerated 2D texture mapping and accumulation buffering. The application of this method is in the 2D-3D registration of X-ray fluoroscopy to CT images. A coarse-to-fine solution approach based on cubic B-splines improves robustness. Using data derived from a cadaveric spine specimen, this method was compared against a purely software-based scheme for generating DRRs in terms of accuracy, speed, and capture range. Our experiments revealed an equivalent accuracy and capture range with much shorter running time. Precision Registration in the Ear Research in collaboration with the Inselspital and the department of Technik und Informatik at the Berner Fachhochschule has begun for the development of an image-guided and mechatronically assisted surgical procedure to perform the drilling of the mastoid, which is a portion of the temporal bone behind the ear that is often used as an anchor point for implanted hearing aids and an access point for inner ear surgery. One of the fundamental issues raised by image-guided surgery is the registration between physical space and image space. A method using laser scanner technology and high-resolution surface data was developed to achieve a high-precision surface registration. In a feasibility study, an accuracy of better than half a millimeter was reached. Reality-augmented Endoscopic System We have developed a simplified system for endoscopic sinus/skull-based surgeries where an endoscopic view is augmented with segmented CT/MRI data to help surgeons with anatomical orientation in altered/ occluded operating areas. The endoscope is calibrated using a freely available software toolkit and registration is performed with a method developed within our institute. The whole application is implemented in our institute's own open source programming platform, which is used for the development of image guided surgical applications. This platform can be downloaded and used for free.

2D-3D Intensity-based Registration DRRs (top right) constructed from CT volume data are registered to an X-ray image (bottom left). The registration fidelity is shown visually with 3D segmented model and checkerboard overlaps.

Femoral Head Contour Extraction A 3D statistical model is used in conjunction with Bayesian inferences to determine the external contours of the femoral head in a pair of calibrated fluoroscopic images.

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Mechanical Design & Production Group Members:

Urs Rohrer

Thomas Gerber

Contact:

+41 31 631 59 35 [email protected]

Sebastian Marti

Erland Ronald Mühlheim Ramseier

MEM Research Center Machine Shop

Profile The primary function of the Mechanical Design and Production (MDP) group is the co-development and manufacturing of mechanical and electro-mechanical components related to the research pursuits of the ISTB. The MDP group supports all levels of the design and manufacturing process from concept to production. This includes computer assisted design (CAD) modelling with SolidWorks®, prototyping and production with technical drawings, standard tooling, and computer assisted manufacturing (CAM) with MasterCam® software and CNC tools. We also support external industrial and academic research collaborators with their mechanical design and production needs. Beginning in 2007, our mandate will also include the oversight of occupational health and safety in our institute. The MDP group has a secondary role in training. This training encompasses the skills required to safely and proficiently operate machine shop tooling and equipment, the knowledge required to achieve the best results with a variety of materials and the skills needed to efficiently manage the design and production workflow. Sebastian Marti, our third year polymechaniker (machinist) apprentice, completed his intermediate qualification exams with good results and also placed 12th out of 34 participants in a machining skills competition sponsored by Swiss milling tools manufaturer FRAISA AG. Ronald Ramseier became our new first year apprentice and Dominique von Ah completed our introductory course for entrance into a polymechanicer apprenticeship. Of special note this year, Urs Roher celebrated his 15th year with the MEM center (formerly the MEM Institute for Biomechanics) supporting biomedical research with equipment and tooling design and manufacture. Research Equipment Design & Manufacturing The requirements of a machine shop supporting research in the biomedical engineering field are as diverse as the field itself. The variety of subjects researched in the ISTB yield a number of diverse design and production requests from prototype clinical and surgical tooling to fixtures for mechanical, biological and kinematic testing, as well as imaging system accessories and calibration equipment. The following illustrations highlight a couple of this years projects.

Modified Tooling for CAS This surgical distractor is in its second phase of evolution. Previously, the ability to measure the distraction force was added. In this stage, the ability to measure the distraction distance allows the stiffness of the distracted region to be calculated. Optoelectronic tracking functionality completes the modification.

Elbow Joint Simulator This apparatus was designed in the Orthopaedic Biomechanics group to test the kinematic effects of different surgical interventions in the elbow. 24

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Acknowledgments

MSc & PhD Degrees at the MEM Center A research institution such as ours depends significantly on support from a number of bodies including government, industry and other private sponsors. We are indebted to the M.E. Müller- and AO-Foundations for their generous contributions to our budget. We graciously thank the Swiss National Science Foundation for its support within the Swiss National Center for Competence in Research CO-ME and the Federal KTI/CTI Innovation Promotion Agency for providing R&D matching funds. In addition, support in the form of equipment, donations, or finances for a large number of specific research projects by various foundations and companies is gratefully acknowledged.

MSc in Biomedical Engineering In a continuing effort to support Swiss innovation and ensure a critical mass of skilled labor in the field of Bioengineering, the University of Bern’s Medical Faculty in collaboration with the University of Applied Sciences Bern are launching a masters degree by coursework. The program offers advanced classes in fields ranging from orthopaedic mechanics and tissue engineering, to computer aided surgery, smart surgical instrumentation and outcome based research and is open for engineering and computer science graduates from the Universities of Applied Science (Fachhochschulen). For further information visit the program's web site at www.bioeng.master.unibe.ch

PhD in Biomedical Engineering

Editorial & Review Contributions Annals of Biomedical Engineering AO Foundation, Switzerland ASME Journal of Biomechanical Engineering Clinical Biomechanics Computer Aided Surgery Computer Methods and Programs in Biomedicine European Cells & Materials European Journal of Oral Sciences European Spine Journal IEEE Transactions on Medical Imaging IEEE Transactions on Biomedical Engineering IEEE Transactions on Information Technology in Biomedicine Journal of Biomechanics Journal of Biomedical Materials Research Journal of Digital Imaging Journal of Neuroscience Methods Medical Engineering & Physics Medical Image Analysis Natural Sciences and Engineering Research Council of Canada NeuroImage Proceedings of Mathematical, Physical and Engineering Sciences Spine Swiss National Science Foundation The Visual Computer Workers’ Compensation Board of BC, Canada

The doctorate degree in biomedical engineering at the MEM center is undertaken within the Graduate School for Cellular and Biomedical Sciences at the University of Bern, which is jointly administered by the Faculties of Medicine, Science and Veterinary Medicine (Vetsuisse). The programme usually lasts three years and offers structured post-graduate training in experimental research. For further information please visit the graduate schools web site at www.gcb.unibe.ch

Dissertations & Theses Belinda Bach, Dissertation thesis (medicine), University of Bern, Switzerland The role of preoperative patient characteristics in cemented and uncemented socket loosening in total hip arthroplasty. A matched case-control study on 4420 patients

Jonas Chapuis, PhD, University of Bern, Switzerland Computer Aided Cranio-Maxillofacial Surgery

Gisèle Douta, PhD, University of Bern, Switzerland Commonality and Variability Analysis to Support Component Based Architectural Modeling for Computer Assisted Orthopaedic Surgery

Fabian Hauser, Master of Science, ETH Zürich, Switzerland Real Time Direct Volume Rendering of Medical Image Data Sets for Computer Assisted Surgery

Kerstin Joost, Dissertation thesis (medicine), University of Bern, Switzerland Patient satisfaction with primary care: a comparison between homeopathy and conventional primary care

Jörg Krebs, PhD, University of Bern, Switzerland Pathophysiology of Cardiovascular Changes after Cement and Fat Embolism during Vertebroplasty in an Animal Model

Serge Sagbo, PhD, University of Bern, Switzerland

Awards

Virtual Implant Database for Computer Assisted Orthopaedic Surgery: Design, Implementation, and Validation

Best Technical Paper: Sixth Annual Meeting of the International Society for Computer Assisted Orthopaedic Surgery, Montréal, Canada, June 2006

Steffen Schumann, Diploma, University of Applied Sciences, Koblenz, Germany

Fellowship of the Japanese Society for the Promotion of Science (JSPS): Miguel González

Computer Assisted Ankle Joint Arthroplasty Using Bioengineered Autografts

X-ray Machine Calibration Toolkit (XMCT): Design, Implementation, and Accuracy Validation

Rudolf Sidler, PhD, University of Bern, Switzerland

Julien de Siebenthal, PhD, University of Bern, Switzerland Scientific Poster Award: 16th Interdisciplinary Research Conference on Biomaterials (GRIBOI), Bern, Switzerland

Design And Development of a Virtual Supervisor For Computer Assisted Surgery Training Procedures

Kumar Rajamani, PhD, University of Bern, Switzerland Shape Prediction for 3D Intra-operative Visualization

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Guest Presentations Dr. Peter Cripton Dept. of Mechanical Engineering. The University of British Columbia, Canada Biomechanics of Spinal Cord Injury

Aebi, M. ISSLS Instructional Course, Curitiba, Brazil, August 23-24 High grade spondylolisthesis: To reduce or not?

Dr. Fritz Grossenbacher Mediscope AG. Switzerland Deep insight in PubMed for searching orthopedic literature

Aebi, M. AOSpine Cervical Spine Symposium, Majorca, Spain, September 21-24 Indications and limits of anterior surgery

Florian Mitscherlich ICHI GmbH, Switzerland HTA (health technology assessment) in orthopedics and practical problems

Aebi, M. AOSpine Cervical Spine Symposium, Majorca, Spain, September 21-24 My worst case

Dr. Mauricio Reyes INRIA-Epidaure Group, Sophia Antipolis, France Respiratory motion compensation in PET imaging

Aebi, M. AO Symposium DGU: Osteoporose – Die Herausforderung der Zukunft, Berlin, Germany, October 5 Wirbelsäule

Dr.-Ing. Erik Schkommodau Institut für Medizinal- und Analysetechnologie, Fachhochschule Nordwestschweiz Potential of CAS for correction osteotomies of lower extremity Dr. Martin Styner Depts. of Computer Science and Psychiatry, Univ. of North Carolina, USA Neuro-developmental diffusion tensor imaging

Invited Lectures Aebi, M. Videosymposium “Trauma Problems Spine and Pelvis” Hannover, Germany, March 20-21 Minimally Invasive Approach for Anterior Fusion Aebi, M. AOSpine Wirbelsäulenseminar, Berlin, Germany, April 6-8 Bewährtes und Innovatives in der Wirbelsäulenchirurgie. Interaktive Lernveranstaltung Klassifikation der Verletzungen Aebi, M. Spine 2006: State of the Art in Spinal Disorders: An International Comprehensive Course, Sorrento, Italy May 18-20 Surgical option indications and reconstruction of metastatic tumors Aebi, M. Spine 2006: State of the Art in Spinal Disorders: An International Comprehensive Course, Sorrento, Italy May 18-20 Treatment of rheumatoid disease of the cervical spine

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Aebi, M. 1st International Course: New Trends in Spinal Surgery, Bologna, Italy, October 19-21 New trends in surgical treatment of adult scoliosis Aebi, M. 91st SIOT Annual Congress, Rome, Italy, November 12-16 The challenges of spine surgery – today and in the future Aebi, M. 13th Brussels International Spine Symposium, Brussels, Belgium, November 17-18 Surgical R/ upper, lower and middle cervical injuries and non-union: anterior procedures Aebi, M. 13th Brussels International Spine Symposium, Brussels, Belgium, November 17-18 Classification of spine fractures: thoraco-lumbar spine Aebi, M. AOSpine Davos 2006 courses, Davos, Switzerland, December 10-15 Degenerative and Deformity Course: Rheumatoid cervical spine, Rheumatoid arthritis Management of degenerative scoliosis in elderly patients Trauma and Tumor Course: Classification and management concepts for thoracolumbar fractures Thoracolumbar Spine Course: Rheumatoid arthritis Büchler, P., Olsen, S. 5th World Congress of Biomechanics, Munich, Germany, July 29 – Aug. 4 FE-enhanced computer assisted surgery: Application to femoral nailing

Aebi, M. AO ASIF Spine Deformity Symposium, Montreal, Canada, July 22-23 Ex novo and degenerative adult scoliosis – Global approach to surgical management

Ferguson, S.J. AO ASIF Symposium on Surgical Preservation of the Hip Mammoth Lakes, California, USA, January The Biomechanical Function of the Acetabular Labrum

Aebi, M. ISSLS Instructional Course, Curitiba, Brazil, August 23-24 Adult degenerative scoliosis

Gonzalez-Ballester, M.A. Invited seminar, Imperial College, London, June 2 Computer assisted orthopaedic surgery

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Gonzalez-Ballester, M.A. 20th International Conference on Computer Assisted Radiology and Surgery (CARS), Osaka, Japan, June 29 Statistical shape modelling for computer assisted surgery

Nolte L.-P. Jahresversammlung des Vereins nebenamtlicher Dozenten Bern, Switzerland, June 12, 2007 Collaboration of Academia and Industry in Research and Development

Gonzalez-Ballester, M.A. Invited seminar, Jikei University, Tokyo, Japan, July 5 Computer assisted orthopaedic surgery

Nolte L.-P. Research Networking Workshop, NCCR CO-ME Luzern, Switzerland, August 22-24, 2006 Knowledge & Technology Transfer

Gonzalez-Ballester, M.A. 2nd International Advanced Research Workshop on In Silico Oncology: Advances and Challenges, Crete, Greek, September 26 Statistical modelling of shape and biomechanical properties – application to computer-assisted orthopaedic surgery and population-based orthopaedic implant shape optimisation Gonzalez-Ballester, M.A. 15th Annual Meeting of the Japanese Society for Computer Assisted Surgery (JSCAS), Tokyo, Japan, October 29 Computer assisted orthopaedic surgery at University of Bern Gonzalez-Ballester, M.A. Invited seminar, Osaka University, Osaka, Japan, November 7 Computer assisted orthopaedic surgery Kowal, J.H. Schweizer Medizinaltechniktagung Inselspital Bern, Bern, Switzerland, June Navigation und Medizintechnik Krebs, J. 16th Interdisciplinary Research Conference on Biomaterials (GRIBOI), Bern, Switzerland, March 16-18 Cardiovascular changes after bone augmentation: experimental studies using an ovine vertebroplasty model Nolte L.-P. 3rd International Practical Knee Navigation and Training Course, Samedan, Switzerland, January 19-21, 2006 Smart Instruments for Orthopaedics Surgery Nolte L.-P. CAOS-UK Annual Conference, London, UK, February 10-11, 2006 The Basic Assumptions and Technical Points in Computer Assisted Osteotomy Nolte L.-P. CAOS-UK Annual Conference, London, UK, February 10-11, 2006 Basic Principles of CAOS Nolte L.-P. University of Bern Musculoskeletal Research Seminars, Bern, Switzerland, May 10, 2006 Smart Surgical Devices for Orthopaedic Surgery

Nolte L.-P. Wissenschaftliches Symposium zum Abschied von Peter und Eva Niederer Zürich, Switzerland, September 6, 2006 Eine neue Generation intelligenter chirurgischer Instrumente Nolte L.-P. 6th Dammam Annual Orthopaedic Meeting, Dammam Saudi Arabia, November 30-December 2, 2006 Basics of Orthopaedic Surgical Navigation Nolte L.-P. 6th Dammam Annual Orthopaedic Meeting, Dammam Saudi Arabia, November 30-December 2, 2006 Pitfalls of Orthopaedic Surgical Navigation Nolte L.-P. 58th Annual Congress of the Egyptian Orthopaedic Association Cairo, Egypt, December 4, 2006 CAOS for Arthroplasty: The Basics and the Pitfalls Nolte L.-P. 58th Annual Congress of the Egyptian Orthopaedic Association Cairo, Egypt, December 4, 2006 CAOS for Arthroplasty: Navigation for Osteotomies Around the Hip Röder, C. Capio Medical Seminar, Barcelona, Spain, April 28-29 International Quality Registers – SSE Spine Tango Röder, C. Spine Tango Workshop, SSE Jahreskongress, Istanbul, Turkey, October SSE Spine Tango: Genesis and Objectives Röder, C. Spine Tango Workshop, SSE Jahreskongress, Istanbul, Turkey, October Spine Tango training Röder, C. Hintegra Anwendertreffen, Hotel Nassauer Hof, Wiesbaden, Germany, Nov. 3 IDES OSG: Ein Dokumentationssystem für Sprunggelenksprothesen

Nolte L.-P. EMPA St. Gallen, Switzerland, June 6, 2006 Smart Devices for Orthopaedic Surgery

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Publications Journal Papers

Aebi, M., Gunzburg, R., Szpalski, M. Controversies in new technologies: how should a scientific journal stand? European Spine Journal, 15(7):1033-4 Aebli, N., Goss, B.G., Thorpe, P., Krebs, J. In vivo temperature profile of intervertebral discs and vertebral endplates during vertebroplasty: an experimental study in sheep Spine, 31(15): 1674-8 Antoniou, J., Mwale, F., Demers, C.N., Beaudoin, G., Goswami, T., Aebi, M., Alini, M. Quantitative magnetic resonance imaging of enzymatically induced degradation of the nucleus pulposus of intervertebral discs Spine, 31(14):1547-54 Arlet, V., Jiang, L., Steffen, T., Ouellet, J., Reindl, R., Aebi, M. Harvesting local cylinder autograft from adjacent vertebral body for anterior lumbar interbody fusion: surgical technique, operative feasibility and preliminary clinical results European Spine Journal, 15(9):1352-9 Benninger, M.I., Seiler, G.S., Robinson, L.E., Ferguson, S.J., Bonél, H.M., Busato, A.R., Lang, J. Effects of anatomical conformation of the canine caudal lumbar and lumbosacral spine on the 3D motion American Journal of Veterinary Research; 67(1):43-50 Burger, N.C., Nesvadba, J., Nesvadba, Z., Busato, A., Gottstein, B. Investigations on Dicrocoelium dendriticum in farm animals of the Emmental Berliner und Münchener Tierärztliche Wochenzeitschrift, 119(7-8):324-9 Busato, A., Dönges, A., Herren, S., Widmer, M., Marian, F. Health status and health care utilisation of patients in complementary and conventional primary care in Switzerland: An observational study Family Practice, 23(1):116-24 Busato, A., Eichenberger, R., Künzi, B. Extent and structure of health insurance expenditures for complementary and alternative medicine in Swiss primary care BMC Health Services Research 2006, 6:132 Charriere, E.A., Beutler, T., Caride, M., Mordasini, P., Orr, T.E., Zysset, P.K. Compliance of the L5-S1 spinal unit: a comparative study between an unconstrained and a partially constrained system European Spine Journal, 15:74-81 Ferguson, S.J., Broggini, N., Wieland, M., de Wild, N., Rupp, F., Geis-Gerstorfer, J., Cochran, D.L., Buser, D. Biomechanical evaluation of the interfacial strength of a chemically modified SLA titanium surface Journal of Biomedical Materials Research: Part A, 78(2):291-7 Ferguson, S.J., Weber, U., von Rechenberg, B., Mayer, J. Enhancing the mechanical integrity of the implant-bone interface with the BoneWelding® technology: Determination of quasi-static interfacial strength and fatigue resistance Journal of Biomedical Materials Research: Applied Biomaterials, 77:13-20

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Ferguson, S.J., Visser, J.M.A., Polikeit, A. The long-term mechanical integrity of non-reinforced PEEK-OPTIMA polymer for demanding spinal applications: experimental and finite-element analysis European Spine Journal, 15:149-156 Fluri, A, Nenci, C., Zahno, M.L., Vogt, H.R., Charan, S., Busato, A., Pancino, G., Peterhans, E., Obexer-Ruff, G., Bertoni, G. The MHC-haplotype influences primary, but not memory, immune responses to an immunodominant peptide containing T- and B- cell epitopes of the caprine arthritis encephalitis virus Gag protein Vaccine, 24(5):597-606 Goldhahn, J., Neuhoff, D., Schaeren, S., Steiner, B., Linke, B., Aebi, M., Schneider, E. Osseointegration of hollow cylinder based spinal implants in normal and osteoporotic vertebrae: a sheep study Archives of Orthopaedic and Trauma Surgery, 26(8):554-61 (Epub) Hallermann, W., Olsen, S., Bardyn, T., Taghizadeh, F., Banic, A., Iizuka, T. A new method for computer-aided operation planning for extensive mandibular reconstruction Plastic and Reconstructive Surgery,117(7):2431-7 Hankemeier S, Hufner T, Wang G, Kendoff D, Zeichen J, Zheng G, and Krettek C. Navigated open-wedge high tibial osteotomy: advantages and disadvantages compared to the conventional technique in a cadaver study Knee Surgery, Sports Traumatology, Arthroscopy, 4(10):917-21 Haschtmann, D., Stoyanov, J.V., Ettinger, L.E., Nolte, L.-P. and Ferguson, S.J. Establishment of a Novel Intervertebral Disc / Endplate Culture Model-Analysis of an ex-Vivo in-Vitro Whole-Organ Rabbit Culture System Spine, 31(25):2918-25 Haschtmann, D., Stoyanov, J.V. and Ferguson, S.J. Influence of diurnal hyper-osmotic loading on the metabolism and matrix gene expression of a whole-organ intervertebral disc model Journal of Orthopaedic Research, 24(10):1957-66 Hulme, P., Krebs, J., Ferguson, S.J., Berlemann, U. Vertebroplasty and Kyphoplasty: a systematic review of 69 clinical studies Spine, 31(17):1983-2001 Knop, C., Reinhold, M., Röder, C., Staub L., Schmid, R., Beisse, R., Bühren, V., Blauth, M. Internet based multicenter study for thoracolumbar injuries – a new concept and preliminary results C Knop European Spine Journal, 15(11):1687-94 Linguraru M.G., Ayache N., Bardinet E., González Ballester M.A., Galanaud D., Haïk S., Faucheux B., Haw J.J., Cozzone P., Dormont D., Brandel J.P. Differentiation of sCJD and vCJD forms by automated analysis of basal ganglia intensity distribution in multisequence MRI of the brain – definition and evaluation of new MRI-based ratios IEEE Transactions in Medical Imaging, 25(8):1052-67

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Marian, F., Widmer, M., Herren, S., Dönges, A., Busato, A. Physicians’ philosophy of care: A comparison between complementary and conventional medicine Forschende Komplementaermedizin und Klassiche Naturheilkunde,13(2)

Zheng G, Dong X, Langlotz F, and Nolte L-P. Zero-dose fluoroscopy-based close reduction and osteosynthesis of diaphyseal fracture of femurs Studies in Health Technology and Informatics, 119:592-594

Matter-Walstra, K., Widmer, M., Busato, A. Seasonal variation in orthopedic health services utilization in Switzerland: The impact of winter sport tourism BMC Health Services Research, 6:25

Zheng G, Maier B, Ploss C, Marzi I, and Nolte L-P. Computer-assisted, fluoroscopy-based ventral spondylodesis of thoracolumbar fractures Technology and Health Care, 14(2):109-122

Matter-Walstra, K., Widmer, M., Busato, A. Analysis of patient flows for orthopedic procedures using small area analysis in Switzerland BMC Health Services Research, 6:119 Münger P., Röder C., Ackermann-Liebrich U., Busato A. Patient-related risk factors leading to aseptic stem loosening in total hip arthroplasty. A case control study of 5035 patients Acta Orthoaedica Scandinavia, 77(4):567-74 Röder, C., Müller U., Aebi M. The rationale for a spine registry European Spine Journal, 15 Suppl 1:52-6 Röder C., Staub, L.P., Eichler, P., Widmer, M., Dietrich D., Eggli, S., Müller, U. Avoiding misclassification bias with the traditional Charnley classification: rationale for a fourth Charnley class BB Journal of Orthopaedic Research, 24(9):1803-8 Sidler, R., González Ballester, M.A., Styner, M., Bardyn, T., Nolte, L.-P., Südkamp, N.P., Köstler ,W. Computer-assisted ankle joint arthroplasty using bio-engineered autografts IEEE Engineering in Medicine and Biology Magazine, 25(4):63-69 Siegfried, R., Busato, A., Schawalder, P., Rytz, U. Evaluation of different techniques for percutaneous needle biopsy of synovial membrane in the dog Veterinary and Comparative Orthopaedics and Traumatology, 18(3):127-34 Sundararajan, S., Prasad, P., Rouhana, S.W., Demetropoulos, C.K., Yang,K.H., King, A.I., Nolte, L.P. Characteristics of PMHS Lumbar Motion Segments in Lateral Shear Stapp Car Crash Journal, 49:367-79 Widmer, M., Herren, S., Dönges, A., Marian, F., Busato, A. Complementary and conventional medicine in Switzerland: comparing characteristics of general practitioners Forschende Komplementaermedizin und Klassiche Naturheilkunde, 13(4):234-40 Widmer, M., Donges, A., Wapf, V., Busato, A., Herren, S. The supply of complementary and alternative medicine in swiss hospitals Forschende Komplementaermedizin und Klassiche Naturheilkunde,13(6):356-61 Zhang, X., Zheng, G., Langlotz, F., and Nolte, L.-P. Assessment of spline-based 2D-3D registration for image-guided spine surgery Minimally Invasive Therapy & Allied Technologies, 15(3):193-199

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Conference Papers Belenguer Querol, L., Buechler, P., Rueckert, D., Nolte, L.P., González Ballester, M.A. Statistical finite element model for bone shape and biomechanical properties Lecture Notes in Computer Science, Ed. Springer, vol. 4190 MICCAI 2006, 405-411 Chegini, S., Beck, M., Ferguson, S.J. Femoro-acetabular impingement as a possible initiator of cartilage degeneration CMBBE 2006 Dong, X., Zheng, G. Fully automatic determination of morphological parameters of proximal femur from calibrated fluoroscopic images through particle filtering Lecture Notes in Computer Science, Ed. Springer, vol. 4142 ICIAR 2006, 535-546 Dong, X., Zheng, G. Finding deformable shapes by point set matching through nonparameteric belief propagation MIAR 2006, 60-67 García Giráldez, J., Talib, H., Caversaccio, M., González Ballester, M.A. Multimodal augmented reality system for surgical microscopy SPIE Medical Imaging 2006, vol. 6141, 537-544 Rudolph, T., Ebert, L., Kowal, J.H. Noninvasive CT to Iso-C3D registration for improved intraoperative visualization in computer assisted orthopedic surgery SPIE Medical Imaging 2006, vol. 6141, 582-589 Talib, H., Rajamani, K.T., Kowal, J., Styner, M., González Ballester, M.A. A comparison study assessing the feasibility of ultrasound-initialized deformable bone models SPIE Medical Imaging 2006, vol. 6141 Tarte, S., Talib, H., González Ballester, M.A., Langlotz, F. Evaluating partial surface matching for fracture reduction assessment IEEE International Symposium on Biomedical Imaging 2006, 514-517 Zheng, G., González Ballester, M.A., Styner, M., Nolte, L.P. Reconstruction of patient-specific 3D bone surface from 2D calibrated fluoroscopic images and point distribution model Lecture Notes in Computer Science, Ed. Springer, vol. 4190 MICCAI 2006, 25-32

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Zheng, G., Rajamani, K.T., Nolte, L.P. Use of a dense surface point distribution model in a three-stage anatomical shape reconstruction from sparse information fro computer assisted orthopaedic surgery: a preliminary study Lecture Notes in Computer Science, Ed. Springer, vol. 3852 ACCV 2006, 52-60 Zheng, G., Nolte, L.-P. Surface reconstruction of bone from X-ray images and point distribution model incorporating a novel method for 2D-3D correspondence IEEE Computer Society Conference on Computer Vision and Pattern Recognition, vol.2, 2237-2244 Zheng, G., Zhang, X., Nolte, L.-P. Automatic pose recovery of the distal locking holes from single calibrated fluoroscopic image from computer-assisted intramedullary nailing of femoral shaft fractures Lecture Notes in Computer Science, Ed. Springer, vol. 4091 MIAR 2006, 195-202 Zheng, G., Dong, X., Nolte, L.-P. Robust and accurate reconstruction of patient-specific 3D surface models from sparse point sets: a sequential three-stage trimmed optimization approach Lecture Notes in Computer Science, Ed. Springer, vol. 4091 MIAR 2006, 68-75 Zheng, G., Gonzalez Ballester, M.A., Styner, M., Nolte, L.-P. Reconstruction of patient-specific 3D bone surface from 2D calibrated fluoroscopic images and point distribution model Lecture Notes in Computer Science, Ed. Springer, vol. 4190 MICCAI 2006, 25-32 Zheng, G., Zhang, X., Jonic,S., Thévenaz, P., Unser, M., Nolte, L.-P. Point similarity measures based on MRF modeling of difference images for spline-based 2D-3D rigid registration of X-ray fluoroscopy to CT images Lecture Notes in Computer Science, Ed. Springer, vol. 4057 3rd International Workshop on Biomedical Image Registration, 186-194 Zheng, G. A novel 3D/2D correspondence building method for anatomy-based registration Lecture Notes in Computer Science, Ed. Springer, vol. 4057 3rd International Workshop on Biomedical Image Registration, 75-83

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