Beruflich Dokumente
Kultur Dokumente
26 April 2016
MagnetoTheranostics
Nano Particle Hyperthermia Applicator
Second prototype
PSU
System
Two amplifier
units
Each with 4 x
750W amplifier
modules
Each with 2 x
1.5kW power
supplies
Input 2fo
Power
Cotrol
PSU
PSU
System
System functions
Field coils
characterised
Equivalent circuit
model available
Basic control
software available
Loss resistance
Calramic capacitors had
Tan = 0.002
Loss resistance between
0.23 and 0.30 at 300 kHz
Cooling system
System has been defined, will use split cooling loops with a
liquid liquid heat exchanger.
Manifolds connect to all 8 coils
Coil cooling loop will use transformer oil which has very high
isolation of the high voltages and does not corrode or absorb
ions from the construction materials
The oil is pumped through the coils and heat exchanger in a
sealed and closed loop
Connections for an external water based cooling loop will be
provided the water will cool the oil
Cooling system
Outline
background
method
application
impact:
width
shape
vasculature
conclusions
Background
SPIONS (superparamagnetic iron oxide
nanoparticles)
coated iron oxide core
can be functionalized, e.g., with antibodies
requirements
efficient generation of personalized patient model
(anatomy, physiology, treatment setup)
precise modeling of physics
realistic modeling of physiological reaction
assessment of induced therapeutic effect /
collateral damage
treatment optimization
validation & uncertainty assessment
Method
extend existing HTP platform (Sim4Life)
magneto-quasistatic solver to determine local magnetic field (FEM,
MPI-parallelized, rectilinear mesh)
modeling of in vivo induced magnetic field distribution from
applicator
Method (II)
combine computed field strength with image-based particle density
using derived relationship to determine deposited power
determine temperature increase using Pennes bioheat equation
perfusion impact
non-linear temperature dependence of perfusion
convective/Dirichlet boundary conditions for large vessels
possibility of coupling to advanced models
(body-core heating, vessel trees, CRD...)
Method (IV)
CEM43 thermal dose computation for effect assessment
Impact (I)
varied:
width of particle distribution
sharpness (step vs. gaussian)
proximity of major vessel
(Dirichlet, zero T increase)
observation
dominated by interplay between
diffusion & perfusion heat removal
little T impact when distribution
wider than characteristic Greens
function length
strongly perfused tissue (liver)
quickly reaches perfusion
dominated regime (perfusion &
particle density matter, distribution
only affects width)
Impact (II)
Conclusion
Acknowlegement
Funding
CTI HYCUNEHT
SNF, Nano-Tera.ch
Collaboration
EPFL Powder Lab
University Hospital Geneva
Veterinary Clinic, University Zurich
Centre Hospitalier Universitaire Vaudois
Center for BioMedical Imaging
Inselspital Bern
Magnetotheranostics
From superparamagnetic nanoparticles to tools for the detection and
treatment of cancer
H. Hofmann1, B. von Rechenberg2, H. Thoeny3, M. Stuber4, O. Jordan5, N.
Kuster6, D. Bonvin1, P. Kircher2, H. Richter2, S. Barbieri3, J. Bastiaansen4,
M. Mionic Ebersold4, S. Ehrenberger5, G. Borchart5, M.Capstick6, E.
Neufeld6
1EPFL, 2University of Zurich, 3Inselspital Bern, 4CHUV, 5University of Geneva, 6 ItIS
Project layout
Engineering ; ITIS, ANTIA
Physics, chemistry material
science; EPFL, UNI GE, CHUV
In-vitro, toxicity, imaging
EPFL, ITIS, UNI GE, CHUV
Development
temperatur
simulation
tool
Improvement
of mag
generator
Characterisation
toxicity screening
Functionalisation of
particle with
antibodies
Nanocomposite
formulation
In vitro tests
and heating
capacity
In vivo tests of
and tumor
treatment
Toxicity tests
Hyperthermia
Medical application
CABMM, Inselspital
In vivo tests
theragnosis
Magnetotheranostics Mid Term Report
April 2016
In vitro tests
specific adsorption
at metastasis
In vivo tests of
metastasis
detection
2
MagnetoTheranostics
Mukesh G. Harisinghani, The new england journal of medicine 2003 vol. 348 no. 25, 2491
UTE MRI
novel IRON-UTE
(IRON) MRI
7
Functionalisation
Different types of molecules were used to
increase biocompatibility
higher colloidal stability
Act as linker for further functionalization with targeting molecules
Small biocompatible molecules with min 3 functional groups for:
-
Small urea molecule ACUPA (phase II clinical trial for docetaxel nanoparticles)
(ii)
(iii)
10
aptamer
merged
11
cement
Remaining
tumor tissue
Implant
3D reconstruction
13
50
48
Field strength
Tumoral ET
46
1212
mT
mT
46.2 C
44
1111
mT
mT
43.5 C
42
10.5
10.5mT
mT
42.7 C
40
1010
mT
mT
42.8 C
38
9 mT
9 mT
40.0 C
p<0.05
Fishers LSD
36
34
32
0
10
15
20
Time (min)
Functionalized nanoparticles for biomedical
application MSE 617
14
Implant
15
group
Median
survival
time : tm.
Control
12
1
0.9
n=6
0.7
implante
d control
0.6
12 mT
0.5
0.3
treated
n=7
10.5 mT
12 mT
Control
Implanted control
12
24
36
48
37
treated
n=11
0
0
27
p<0.05
10.5mT
0.1
21
n=7
0.4
0.2
p<0.001 p<0.05
Fractional survival
0.8
60
72
84
200
16
17
18
19
20
Conclusion
Milestones and delivery fulfilled as planned
Engineering part developed so far, that the
biological/medical part can start.
Animal models and antibodies selected and tested
Next steps:
21
Measures (several
partners are involved)
Realized
Acceptance of nanotechnology
*with Prof. S. Krishnan, Director, University of Texas MD Anderson Cancer Center, USA
Institution
Main task
H. Hofmann, D. Bovin,
M Mionic
EPFL
B. von Rechenberg P.
Kircher,
H. Richter
Vetsuisse Zrich
animal experiments
H. Thoeny,
S. Barbieri,
Inselspital, Bern
M. Stuber, J. Bastiaansen,
M. Mionic,
CHUV
O. Jordan, G. Borchart ,
S. Ehrenberger
UNI Geneva,
N. Kuster, M. Clapstick
E. Neufeld
ITIS
23