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Focus Line overview
2 LMTC brief outline Q3-2014 + Focus Line Overview
Objectives of L-MTC
• Increase the efficiency of interdisciplinary
collaboration in Med Tech R&D within KU Leuven and
the Association;
• Support Technology Transfer of research results;
• Increase external visibility of Med Tech R&D within KU
Leuven;
• Support the new Master in Biomedical Technology (Fac.
Engineering) and the Master of Biomedical Sciences (Fac.
Medicine);
• Promote Biomedical Technology R&D at the level of
Association KU Leuven.
3 LMTC brief outline Q3-2014 + Focus Line Overview
Coordinator
Siegfried Jaecques
Int’l affairs
Luc Mortelmans
Chairman
Jos Vander Sloten
Medical Imaging
• Medical Imaging Research Center
Robotics and Automation in Health Care
Controlled Release
Biomaterials & Tissue Regeneration
• Prometheus (Skeletal Tissue Engineering Leuven)
Biomonitoring & Control
Co-chairman
Frank Luyten
Focus themes LMTC
4 LMTC brief outline Q3-2014 + Focus Line Overview
– Integration biological systems – artificial systems
– Personalised approach (« service » approach) =
procedures instead of products, optimisation by functional
simulation
– Scale-up & industrialisation
– New disciplines: biomedical engineer, tissue engineer,
developmental engineer
– Paradigm shift:
• from ‘hospital centric care’ to ‘patient centric care’
• from curative medicine to integrative medicine:
prevention – screening – diagnostics – treatment –
management
(« patient centric care cycle »)
Roadmap/Challenges:
5 LMTC brief outline Q3-2014 + Focus Line Overview
• 40 member groups, 800+ researchers and clinicians
• Distributed center concept
• Full time co-ordinator
• Workshops
• Representation at international events
• Matchmaking internally and externally
• Major grants (EIT, TTC, EC programmes, …)
LMTC facts
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– Computational Medicine (12/09/2011)
– Molecular imaging, a platform for translational medicine (10/10/2011)
– Regenerative medicine in the post-genomic era (28/11/2011)
– Point of Care Diagnostics (14/02/2012)
– Controlled release technologies for drug development (23/04/2012)
– “Large Animal Models in clinical research and training” (07/02/2013)
– European Surgical Robotics Demonstration Day (27/03/2014)
– “The evolutionary path for clinical studies”, 13/5/2014
– Visionary Seminar Assistive Robotics Technology (02/10/2014)
– Spin-off day “Health(y) Entrepreneurship” (06/11/2014)
– Ageing with a Healthy Brain EIT workshops (19-20/01 & 28-
29/04/2015)
– CRAS (Computer/Robot Assisted Surgery) workshop (10-12/09/2015)
(co) Organized Events 2011-2014 (selection)
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• Health for Growth & Leuven Health Metropolis
• Flanders Smart Hub Development (FSH-D) / Sports.Tech
• Care Innovation platform/ “Living Lab” InnovAGE
• Health Axis Europe
Starting Up:
• KIC EIT Health
Strategic Networking and BDS
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EIT – Health network spans across Europe
Co-location centre
EIT Health InnoStars
countries
International Headquarters
Coordinator: Roche
Diagnostics GmbH
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Loco-regional to International
EU/Int’l
Cross-border
Leuven
• EIT Health
• Accelerator/Projects/Campus
• H2020
• Interreg NWE, EU
• RegMed 2.0
• BuSyBee, CrossCare
• RegMed
• HealthHouse, Leuven.Inc, Gezondheidsmetropool Leuven
• InnovAge
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Relation with industry & spin-offs
Academic programmes driven by evolution in the field
MSc Biomedical Engineering
Human-Machine synergy as a key concept (~Human Health Engineering)
Opportunitities for industry and spin-offs
Instrumen
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1. MEDICAL IMAGING
12 LMTC brief outline Q3-2014 + Focus Line Overview
• Exploring and exploiting the potential of novel imaging
technology in medicine and biomedical research:
from “seeing” to “understanding”
1. Medical imaging
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• Radiology
• Nuclear Medicine
• Cardiology
• Radiation Oncology
• ESAT – Medical Image Computing
• > 20 faculty
• > 80 researchers
• engineers, physicians, physicists
• fundamental and applied research
in a clinical setting
Medical Imaging Research Center
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• Radiopharmacy
• Molecular Medicine
• Clinical and Experimental Neurology
• Laboratory of Neuro- and Psychophysiology
• Oral Imaging Center
• Forensic Medicine
• ESAT - SCD - Biomedical Data Processing group
• …
Collaborating groups
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• Centralized research facility
– Core location in the hospital itself (‘Louvre’)
• State of the art clinical imaging equipment
– 3T MRI, 4D & dual energy CT, PET/CT, CBCT, US, …
– Inter-connected via DICOM, PACS, HIS
• Small animal imaging center (SAIC)
– 9T microMRI, microPET, microCT, BLI, dedicated US
– Pre-clinical imaging in animal models (rodents)
• Molecular Imaging Research and Clinic Leuven (MIRACLE)
– Molecular imaging for drug development and clinical trials
– GMP lab in collaboration with industry
• High-performance computing cluster
– Inside the hospital (fire wall)
Facilities
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• Optimization of imaging protocols
– Anatomical, functional and molecular imaging
• Image reconstruction
– Cone beam CT, PET/MRI
• Image quality enhancement
– Resolution, contrast, SNR, artifact reduction
• Imaging probes:
– Contrast agents (CT, MRI)
– Radio-labeled tracers (PET, SPECT)
– (Nano-) particles (MRI, US)
– Reporter genes (pre-clinical imaging)
Image acquisition
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• Registration (‘image fusion’)
• Segmentation (‘object delineation’)
• Quantification (‘image measurements’)
– Contrast
– Structure
– Changes over time
– Inter-subject differences
• Visualization
– Interpretation
– Interaction
Image computing
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2. ROBOTICS AND AUTOMATION
IN HEALTH CARE
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Advanced mechatronic & automation technology for
- increased patient safety
- patient-specific medical devices
- surgical simulators
- better mobility and home care
- logistics in health care
Robotics and automation in health care
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1. Increased patient safety
Smart instrumentation
– Instruments that sense interaction with tissue and
- measure
- analyse
- react
Example 1: pulling aside the renal vein
Example 2: clamping the renal artery
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Experimental results
Stress and damage pattern after 1 N of clamping load for both clamp designs:
Famaey, Sommer, Vander Sloten, Holzapfel (2012) Arterial clamping: finite element simulation
and in vivo validation Mechanical Behaviour of Biological Materials
Detail of an H&E-stained sample crushed
with a mosquito clamp. Stretching of the
fibres is noticed at the edge.
Boxplot of the endothelial cell count.
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Advanced surgical robotics
Follows the surgeon in the
safe zone
Increases the resistance in the
boundary zone
Activates a virtual wall in the
forbidden zone
The teleoperation control:
Willaert (2012) Ph.D. thesis KU Leuven
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2. Custom made devices and procedures
(Corten et al. ORS 2011)
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3. Surgical simulators
Lack of real life representation:
- visual
- haptic, tactile
- bio-response
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4. Smart devices for rehabilitation
• Orthotics to treat spasticity
• Intelligent and adaptive orthotics
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5. Logistics in health care
Patient safety and technical management of medical devices in
hospitals
→ focus on risk assessment
Home care and medical devices:
→ focus on weak user profile, having an impact on risk assessment
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Robotics and automation in health care – member groups
• Experimental Cardiac Surgery
• Abdominal Transplant Surgery
• Mobilab (KHKempen)
• Ergonomics & Occupational Biomechanics
• Orthopaedic Surgery
• Traumatology
• Experimental Urology
• Experimental Neurosurgery and Neuroanatomy
• Endoscopic surgery
• Production Engineering, Machine Design and Automation
(PMA – RAS)
• Industrial Management – Logistics in Health Care
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3. CONTROLLED RELEASE
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3. Controlled release
The study of drug delivery systems that enable controlled release of a
pharmacologically active compound (API) during a specified time
The release kinetics are reproducable and predictable
Controlled release ? slow and prolonged, delayed, pulsed, targeting
increased release rate and extent
Advantages:
1. Reduced intake (advantageous in case of low t1/2)
2. Improved patient compliance and comfort
3. Reduced side effects
4. Controllable release kinetics: less fluctuation in plasma API levels and
uniform therapeutic effect
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Highlights of recent projects
1. Development of a binary polymer matrix system for the prolonged release
of poorly soluble compounds for parenteral administration
2. Understanding the influence of compression forces on the phase
behavior of amorphous solid dispersions
3. Down stream processing evaluation of mesoporous silica
4. Amorphous microporous silica (AMS) for prolonged drug release
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Examples of recent projects
... Down stream processing evaluation of mesoporous silica
Man (n=12)
0 4 8 12 16 20 240.0
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1.0
1.5
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Time (h)
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a c
on
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trati
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(µ
g/m
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Man (n=12)Dose-normalized
0 4 8 12 16 20 240
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33.5 mg Formac capsule
67 mg Lipanthyl (micronized fenofibrate)
silica
Micronized powder
KU Leuven spin off (2007)
Silica drug delivery company
Fenofibrate release (powder in capsules)
Silica typically has/is:
- Poor flow properties (large scale)
- Poor compactibility (tablet)
- Hygroscopic
(commercial product)
Solid dosage form development is challenging!!
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Highlights of recent projects
...Amorphous microporous silica (AMS) for prolonged drug release
AMS180
AMS280
AMS1800
Control of Chlorhexidine release from AMS
Particle size
Release rate
Pore size
Release rate
Oral controlled release
Dental implants
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Controlled release – member groups
• Laboratory of Pharmacotechnology and Biopharmacy
• Centre for Surface Chemistry and Catalysis
• Physical Metallurgy and Materials Engineering
• Applied Rheology and Polymer Processing
Ph.D. projects
• J. Meeus
• Z. Worku
• A. Paudel
• M. Vialpando
• E. Verraedt
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4. BIOMATERIALS AND
TISSUE REGENERATION
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• Prometheus – Interdisciplinary research platform
– Incubator for TE technology
• Rheumatology
• Orthopedics
• BIOMAT Research Cluster
• Abdominal wall tissue engineering
• Laboratory of experimental medicine
and endocrinology
• Biomechanics (BMe)
• Groep T Biomedical Engineering
4. Biomaterials and Tissue Regeneration
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Tissue Regeneration – Prometheus
• Mission statement: Development of consistent and
clinically relevant Tissue Engineering concepts for
skeletal applications
• Participating of other focus line members
• Rheumatology
• Orthopedics
• BIOMAT Research Cluster
• Legendo
• Biomechanics (BMe)
• Groep T Biomedical Engineering
• Blueprint for other tissues
• Link to abdominal wall TE via SCIL Clinical
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Preclinical bone regeneration
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Personalised regenerative therapy
Prof. Eric Legius
Laboratory for
Neurofibromatosis Research
YES ?
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• Large soft tissue regeneration challenges
• Limited experience with expensive biological
meshes, both clinically and preclinically
• No match prosthesis degradation & tissue
regeneration
• Stimulate site specific tissue remodelling
• Addition of growth factors - stem cells -
fibroblasts to the biological scaffolds
• SCIL Clinical as discussion forum
• Projects
• Prospective EU registry biological prostheses
• Treatment of large abdominal wall defects
using collagen prostheses
• Genetic and tissue examination from patients
with inguinal and incisional hernias
Abdominal wall reconstruction & TE
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a ba ba ba bunloaded loaded
unloaded loaded
• Mechanobiology of implant osseointegration
BIOMAT Research Cluster
Low
frequency
bone
chamber
High
frequency
whole body
vibration
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• Optimisation of implant osseointegration in compromised bone
conditions (osteoporosis)
Highlights BIOMAT Research Cluster
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Prometheus biomaterial ‘spin-off’ actions
• Scaffold design
• Ti scaffolds
• Design
• Production
• Surface treatment & characterisation
• Interest biomedical companies
• Testing new biomaterials
• FP7 BioTiNet project
• Novel Ti alloys
• Hydrogel technology
• EPFL - Hubbell technology
• Tenure Track Prof. J. Patterson
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5. BIOMONITORING & CONTROL
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Current trends in technology
• Design of new sensors
• Miniaturisation (micro, nano)
• Wireless communication
• Ubiquitous computing
5. Biomonitoring and control
45 LMTC brief outline Q3-2014 + Focus Line Overview
Current trends in biomedicine
• Poor data rich data
• Standard treatments individually tailored treatments
• Curing prevention
• Fragmented care integrated care
Need
• ‘Intelligence’ in healthcare monitoring and control systems
5. Biomonitoring and control
46 LMTC brief outline Q3-2014 + Focus Line Overview
Bioresponses
(e.g. heart
rate)
Process
inputs
(e.g. drug)
(2) Analyses
& models
(3) Controller/
monitor Desired/expected
output
(1) Sensors (1) Sensors
Actuators
5. Biomonitoring and control
47 LMTC brief outline Q3-2014 + Focus Line Overview
1. Measure bio-responses
– Microsystem technology
• Micro-electronics (e.g. MEMS)
• Micro-mechanics
(e.g. accelerometers)
• Biotelemetry
• Nanotechnology
– Medical imaging
– Biomedical expertise
• Neurology & physiology
(e.g. epilepsy)
• Pneumology (e.g. COPD)
• Oto-rhino-laryngology (ORL)
5. Biomonitoring and control
48 LMTC brief outline Q3-2014 + Focus Line Overview
2. Analyse & model bio-responses
– Biomedical data analysis
• Signal processing
• Bioinformatics
• Medical imaging
– Understand human behaviour
• Audiology
• Psychology
• …
5. Biomonitoring and control
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3. Manage bio-responses
– Monitor and control responses
• Monitoring implant fixation
• Body Area Networks
• Cochlear implants
• Telemedicine
• COPD monitoring
• …
Integrate intelligence in daily life of patients/users
5. Biomonitoring and control
50 LMTC brief outline Q3-2014 + Focus Line Overview
Highlights of recent projects
Neonatal Non-invasive Monitoring
• Non-invasive measurement of the neonatal cerebral circulation and
oxygenation
• Continuous measurement of the cerebral autoregulation
• Non-invasive measurement of the lung function
• Pharmacodynamic measurements
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Epilepsy research
• Collaboration KUL-UZ, KUL-ESAT and IMEC
• Validation of wireless 8ch EEG system
• Use of a wireless monitoring system of autonomic nervous system
(ECG, respiration, galvanic skin response and temperature) in
epilepsy research
Participation in the NeoGuard project
• wireless neonatal EEG monitor with real-time bedside data
visualisation in a realistic head model
• collaboration KUL-UZ and ESAT in automated background analysis
and automated seizure detection
Highlights of recent projects
Developmental Neurophysiology
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Highlights of recent projects
iMinds/Stadius (fka SISTA-BioMed)
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Highlights of recent projects
• TOPICS: in collaboration with UZ Leuven and EU partners
• EMG & HRV signal processing for stress monitoring
• MR Spectroscopic quantitation & brain tumor recognition using MRS(I)
• (Functional) Near-Infrared Spectroscopy & neonatal brain monitoring
• Cardiovascular dynamics, fetal ECG extraction & HRV analysis
• Preoperative cancer diagnosis & prognosis: ovarian, prostate, brain, breast
• EEG based signal processing for epileptic monitoring and ERP analysis
• Video/accelerometry for epileptic seizure monitoring
• Osseoperception, prediction of ectopic pregnancies, renography, …
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Blood glucose control in the Intensive Care Unit
• Tight Glycaemic Control in critically ill patients lowers mortality and
morbidity
• LOGIC-Insulin = algorithm/software that advises the nurse on insulin dose
and time interval for the next blood sample
LOGIC-Insulin
Insulin pump Glucose sensor
Highlights of recent projects
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• Engineering
– Design of algorithm
– Design of graphical user interface
• Clinical validation (Randomized Controlled Trial)
– Comparison LOGIC-Insulin vs. nurse
– 300 patients
• Team (UZ Leuven ~ ESAT-SCD)
– Dr. Ing. Tom Van Herpe ([email protected])
– Prof. Dr. Dieter Mesotten
– Prof. Dr. Greet Van den Berghe
– Prof. Dr. Ir. Bart De Moor
Highlights of recent projects
Blood glucose control in the Intensive Care Unit
56 LMTC brief outline Q3-2014 + Focus Line Overview
Highlights of recent projects – Experimental Oto-rhino-
laryngology & speech processing
• Speech and music processing for cochlear implants
• Noise reduction for improved speech reception with hearing
instruments in adverse and noisy listening environments
• Binaural hearing: signal processing schemes and evaluation
procedures for bilateral acoustical and/or electrical hearing
instruments
• New electrical pulse-waveforms for optimal neural stimulation in
cochlear implants
• Temporal neural processing in the auditory system
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• Activity monitoring for patients with COPD and lung transplantation
to relate daily activity to complications and co-morbid disease
• New surgical techniques to improve pulmonary function for the
treatment of COPD patients
• Tissue bank for relating clinical variables and structural
abnormalities in lung diseases such as COPD
• D-base of lung cancer patients to analyse the effects of treatment on
survival in patients
• Flow-volume characterisation for monitoring COPD evolution (in
collaboration with M3-BIORES)
Highlights of recent projects - Pneumology
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Design, development and evaluation of brain stimulation and recording probes
Rigid probes for recording in the
brain in collaboration with IMEC
(W Eberle, M Welkenhuysen, et al)
Flexible probes for cortex or brain
lesions in collaboration with ESAT - MICAS (B Puers,
F Ceyssens)
In vivo bio- and MRI-compatibility
testing in collaboration with MoSAIC
Highlights of recent projects – Neurosurgery and Neuroanatomy
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Deep brain stimulation in psychiatric disorders
Neuroimaging in collaboration with MoSAIC
Local field potential recording and
single cell recording for closed-
loop stimulation in collaboration with ESAT (S Van Huffel) and
M3-BIORES (JM Aerts)
Highlights of recent projects – Neurosurgery and Neuroanatomy
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Deep brain stimulation in lesion cavities
Brain lesions induce functional
impairment
concept of treatment with recording and
stimulation with electrode contacts
covering the lesion cavity wall
Recording and stimulation in ex-vivo
slices with brain lesions in collaboration with IMEC (W Eberle) and ESAT
(S Van Huffel)
0
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s
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Recording and stimulation in-vivo in
rats with brain lesions
epilepsy, chronic pain, motor deficits in collaboration with M3-BIORES (JM Aerts)
Highlights of recent projects – Neurosurgery and Neuroanatomy
61 LMTC brief outline Q3-2014 + Focus Line Overview
• Early warning infection and inflammation monitoring in
the ICU (in collaboration with UZ Leuven – G. Van den Berghe)
• Monitoring and prediction of nephropathia epidemica
outbreaks caused by bankvoles (in collaboration with UZ
Leuven – M. Van Ranst)
• Reverse engineering of synaptic plasticity in the
hippocampus (in collaboration with D. Balschun)
Time (minutes)
-50 0 50 100 150
Ce
ll re
sp
on
se
40
60
80
100
120
Highlights of recent projects – Measure, Model & Manage Bioresponses
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• Monitoring and control of cell growth in perfusion bioreactors for
bone tissue engineering (in collaboration with Prometheus – J. Schrooten, F.
Luyten)
• Behaviour monitoring and brain signal analysis in rat models for
obsessive-compulsive disorders and anorexia (in collaboration with B.
Nuttin)
0 5 10 15 20 25 30Loca
tion o
f ra
t in
cage in
y-d
irect
ion (
cm)
0
5
10
15
20
25
30
Travelled distance: 7827 cmNumber of drinking sessions: 55
Location of rat in cage in x-direction (cm)
Highlights of recent projects – Measure, Model & Manage Bioresponses
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• Physical condition monitoring for athletes (in collaboration with FABER and
P. Clarys)
• Sleep monitoring (in collaboration with a.o. R. Cluydts,
J. Vander Sloten)
Highlights of recent projects – Measure, Model & Manage Bioresponses
64 LMTC brief outline Q3-2014 + Focus Line Overview
Highlights of recent projects - Sensors and Biotelemetry group
Min. linewidth of Pt wires: 5 mm
Electrode diameter: 15 – 80 mm
Insulation thickness: 3 mm
Embeddded in porous chitosan
Highly flexible neural implants for monitoring and stimulation
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Inductive powering
Image compression
•High-resolution
monitoring of the GI tract
Swallowable camera pill
Highlights of recent projects - Sensors and Biotelemetry group
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Highlights of recent projects – Mechatronics, Biostatistics and Sensors
Microfluid lab-on-a-chip for high-throughput analysis
Glucose monitoring system based on optical sensors
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Biomonitoring and control – member groups
• Neonatal Non-Invasive Monitoring (Gunnar Naulaers)
• Epilepsy research (Wim Van Paesschen)
• Developmental Neurophysiology (Lieven Lagae)
• Biomedical Data Processing (SISTA-BIOMED) (Sabine Van Huffel)
• Bioinformatics (SISTA-Bioi) (Bart De Moor)
• Speech processing (Marc Moonen)
• Experimental oto-rhino-laryngology (Jan Wouters)
• Pneumology (Marc Decramer)
• Neurosurgery and Neuroanatomy (Bart Nuttin)
• Measure, Model & Manage Bioresponses (M3-BIORES) (Jean-Marie Aerts)
• Sensors and Biotelemetry group (Bob Puers)
• Mechatronics, Biostatistics and Sensors (MeBioS) (Bart Nicolaï)
68 LMTC brief outline Q3-2014 + Focus Line Overview
• www.kuleuven.be/lmtc
• Interested in a joint project? First contact:
Dr. ir. Siegfried Jaecques, IOF fellow
Coordinator Leuven Medical Technology Centre (LMTC)
p.a. Celestijnenlaan 300, bus 2419, 3001 Heverlee, Belgium
tel. +32-16-327056 or +32-16-327096 (secr. BMe)
tel. +32-16-326500 or +32-16-326525 (secr. LRD)
fax +32-16-327994
GSM +32-486-498345
More info