Eva Oberacker1, Andre Kuehne2, Celal Oezerdem1, Jason M Millward1, Cecilia Diesch1, Thomas Wilhelm Eigentler1, Jacek Nadobny3, Sebastian Zschaeck3, Pirus Ghadjar3, Peter Wust3, Lukas Winter4, and Thoralf Niendorf1,2,5
1Berlin Ultrahigh Field Facility (B.U.F.F.), Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany, 2MRI.TOOLS GmbH, Berlin, Germany, 3Clinic for Radiation Oncology, Charite University Medicine, Berlin, Germany, 4Biomedizinische Magnetresonanz, Physikalisch Technische Bundesanstalt, Berlin, Germany, 5Experimental and Clinical Research Center (ECRC), joint cooperation between the Charité Medical Faculty and the Max Delbrueck Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
Synopsis
There is a pressing
need to implement Thermal MR therapies in the brain, particularly to sensitize
treatment of aggressive cancers like glioblastoma multiforme. Given the high power
transmission regime of Thermal MR therapies, it is crucial to understand the
engineering constraints affecting RF power losses, since inaccurate estimates
could compromise the efficiency and precision of the therapy. Here we conducted
a thorough simulation of five RF applicator designs, using realistic loss
estimates of material and electrical components, and considering antenna
design, position and coupling. Results from simulated and patient-derived data
underscore that clinical requirements must balance with practical engineering
constraints.
Purpose
Localized thermal
therapy has been convincingly demonstrated to potently sensitize chemo- and
radiotherapy for several cancers1-4, and significantly improve
patient survival5. Glioblastoma multiforme (GBM) is an especially attractive target for thermal
therapy, given its aggressive nature and resistance to current treatment
options6. Unfortunately, limitations of steering and energy
deposition restrict the use of conventional thermal therapy approaches in the
brain. Here, Thermal Magnetic Resonance (Thermal MR) has a unique
potential to circumvent these limitations, and provide temperature
manipulation, MR thermometry and imaging and in an integrated applicator. In
the high power transmission regime of thermal MR therapies, it is crucial to
have a comprehensive understanding of the engineering constraints that affect
RF power losses, including material and electric component losses, as well as
RF antenna design, positioning and coupling with respect to each other and the
patient. The consequences of these challenges are too often under-appreciated –
inaccurate estimates of the true RF power loss could compromise the efficiency
and precision of Thermal MR therapy. To address this issue, the current study
carefully investigated five RF applicator designs using realistic loss
estimates, obtained with the power correlation matrix approach7. This work underscores the impact of
real-world engineering constraints, and puts these into context with metrics
used to quantify thermal therapy performance.Methods
We examined the transmit
performance of five thermal MR applicators at f=297MHz (Figure1, Table1, Design
A-E). For the EMF simulations8 a patient model was approximated by
superimposing the human voxel model Duke9 with a spherical tumor. A
more clinically relevant voxel model was generated using radiation therapy (RT)
treatment planning data of a GBM patient, with the target volume (TV) equal to
the clinical target volume10.
For designs A-D, a circuit
co-simulation was performed, optimizing the values of two lossy capacitances
for channel-wise matching and tuning. Channel-wise phase and amplitude
optimization was performed11 to maximize power deposition in the TV under the constraint of
SAR10g,max(healthy)≤40W/kg in healthy tissue10.
The hyperthermia treatment planning (HTP) performance was
assessed considering, i) SAR10g,max(TV), ii) SAR10g,mean(TV)
(i.e. power deposition), iii) SAR
amplification factor SAF=SAR10g,mean(TV)/SAR10g,mean(healthy)
(i.e. quality of the focusing) and iv) volume of the TV exposed to a higher SAR10g
than SAR10g,max(healthy) (VSAR>Lim, i.e. TV coverage).
Combining the measures for power deposition, focusing and coverage, we
introduced the performance indicator PI=SAR10g,max(TV)·SAF·VSAR>Lim.
The tumor coverage at 25% of maximum SAR TC25% was used as an
established measure for hyperthermia treatment planning quality12,13.
We calculated the power balance and compared the power delivered to the TV and
the head, and the energy dissipated in the RF applicator.
Results & Discussion
Figure2 shows S-Matrices (all
scattering parameters <-12.5dB) and HTP results for all designs applied to
the small tumor. The HTP quality increased with each design iteration. For
design D the increased longitudinal extent of the applicator causes high energy
deposition in healthy tissue. Design E showed the best performance for PI, TC25%
and required forward power (Table2).
Figure3 shows S-matrices (all
scattering parameters <-13dB) and HTP results for the GBM patient data. The
best HTP was achieved using design D. Given the large extent of the TV, the
increased head coverage improved performance versus design B. The HTP
performance of design E yielded highly focused energy deposition, leading to a
small hotspot and poor coverage of the TV. Nonetheless it showed the best
transmit efficiency. Conversely, Design D, which would have been chosen based
on the quality of the HTP, required a forward power of >27kW. The high
conductivity of the ceramic slurry induces high dielectric losses, leading to a
transmit efficiency of <1% (PHead/PForward) with ~90% of the energy dissipated in the
dielectric (PCoil/PForward, Designs B+D). The high
forward power required for Designs B+D and the strong heating of the elements
during thermal MR are challenging if not prohibitive for clinical applications.
To address this shortcoming, the required forward power was offset by a factor
of ~80 by adding a water bolus.
This approach increased PHead/PForward to 15% (vs.
0.24%), while <8% of the forward power was dissipated in the bolus. With the
PI of design C being equally high as for design B and a TC25% of
still 75%, design C is better suited for practical realization. However, the
efficiency gain of adding the water bolus (Design C) did not exceed the effect
of better head coverage (Design D).
Conclusion
This work demonstrates that novel
concepts for RF applicators tailored for thermal interventions in the human
brain should balance clinical requirements with engineering constraints and
practical considerations including proper power loss calculations.
Acknowledgements
This work is supported by the German Federal Ministry of
Education and Research (13GW0102) and an advanced ERC grant (DLV-743077).References
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