physics considerations and electromagnetic field simulations up to 23.5 Tesla (1GHz)

Background Glioblastoma multiforme is the most common and most aggressive malign brain tumor. The 5-year survival rate after tumor resection and adjuvant chemoradiation is only 10 %, with almost all recurrences occurring in the initially treated site. Attempts to improve local control using a higher radiation dose were not successful so that alternative additive treatments are urgently needed. Given the strong rationale for hyperthermia as part of a multimodal treatment for patients with glioblastoma, non-invasive radio frequency (RF) hyperthermia might significantly improve treatment results. Methods A non-invasive applicator was constructed utilizing the magnetic resonance (MR) spin excitation frequency for controlled RF hyperthermia and MR imaging in an integrated system, which we refer to as thermal MR. Applicator designs at RF frequencies 300 MHz, 500 MHz and 1GHz were investigated and examined for absolute applicable thermal dose and temperature hotspot size. Electromagnetic field (EMF) and temperature simulations were performed in human voxel models. RF heating experiments were conducted at 300 MHz and 500 MHz to characterize the applicator performance and validate the simulations. Results The feasibility of thermal MR was demonstrated at 7.0 T. The temperature could be increased by ~11 °C in 3 min in the center of a head sized phantom. Modification of the RF phases allowed steering of a temperature hotspot to a deliberately selected location. RF heating was monitored using the integrated system for MR thermometry and high spatial resolution MRI. EMF and thermal simulations demonstrated that local RF hyperthermia using the integrated system is feasible to reach a maximum temperature in the center of the human brain of 46.8 °C after 3 min of RF heating while surface temperatures stayed below 41 °C. Using higher RF frequencies reduces the size of the temperature hotspot significantly. Conclusion The opportunities and capabilities of thermal magnetic resonance for RF hyperthermia interventions of intracranial lesions are intriguing. Employing such systems as an alternative additive treatment for glioblastoma multiforme might be able to improve local control by “fighting fire with fire”. Interventions are not limited to the human brain and might include temperature driven targeted drug and MR contrast agent delivery and help to understand temperature dependent bio- and physiological processes in-vivo

Effects of transmission regime on left ventricle quantification.

<p>Left ventricle (LV) cardiac chamber quantification in a cohort of 11 subjects obtained for all transmission regimes were examined by evaluating a stack of short axis views ranging from apex to base. Bland-Altman plots of (a) LV end-diastolic volume (EDV), (b) LV end-systolic volume (ESV), (c) LV ejection fraction (EF) and (d) LV mass. No statistically significant differences were found between the reference (BC/32RX) and the BC/4RX setup (circles), the 4TX/4RX with phase setting <b>Φ</b>₁ (squares) or the 4TX/4RX with phase setting <b>Φ</b>₂ (stars). Data points of the same subject were marked with identical colors.</p

Simulated local SAR_10g distributions at maximum applicable input power.

<p>Maximum projection images for voxel model Duke (top) and Ella (bottom) in coronal (1^st and 3^rd row) and axial orientation (2^nd and 4^th row) are shown. Formations of SAR hotspots can be seen for every transmission setup, with the dominating SAR hotspots being marked by arrows. Note: At the elbow twice the SAR is allowed to avoid a bias in favor of the 4TX/4RX configuration. Immoderate whole-body SAR limits lead to exceedance of local SAR limits (1^st column). For 4TX/4RX both transmit phase settings Φ₁ (3^rd column) and Φ₂ (4^th column) yield a local SAR_10g hotspot located underneath the shared middle conductor of the loop elements, where the currents can add up and the distance between the RF coil array and the body is minimal (1 cm/2 cm for the anterior/posterior part).</p

SAR and B₁⁺-values derived from EMF simulation.

<p>SAR and B₁⁺-values derived from EMF simulation.</p

Photographs and simulation setups of the used RF coil configurations.

<p>(a) local four-channel TX/RX RF surface coil array (4TX/4RX) and (b) its EMF simulation setup loaded with the truncated human voxel model Duke. The feeding ports of the RF coil are marked in red. (c) basic circuit diagram of the 4TX/4RX RF coil. (d) photograph of the four-channel RX-only RF surface coil (4RX). (e) EMF simulation setup of the body RF coil loaded with the voxel model Duke. The detuned four-channel receive-only surface RF coil (4RX) is included to examine possible field distortions [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0161863#pone.0161863.ref023" target="_blank">23</a>]. (f) photograph of the 32-channel RX-only RF surface coil. In configuration (d) and (f) the body RF coil (BC) transmits.</p

Cardiac images derived from 2D SSFP CINE.

<p>Shown are end-diastolic phases of the cardiac cycle using standard cardiac views (denoted in the left line) of a healthy subject. The employed transmission regime is outlined on top of the figure for each column. Each image was windowed individually and its SNR within the heart is provided. Column 1, 3, 5 and 6 were acquired with the maximum flip angle allowed by SAR limits governed by the IEC guidelines [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0161863#pone.0161863.ref002" target="_blank">2</a>]. Column 2 and 4 were derived by applying local SAR_10g limits for the body RF coil, which results in 30% reduced flip angle compared to whole-body SAR limit (1^st and 3^rd column). Please note the agreement in image quality obtained with the BC/4RX, BC/32RX and the 4TX/4RX RF coil configurations.</p

Effects of transmit efficiency on minimal TR_SSFP.

<p>Shown are flip angle maps and 2D SSFP CINE images of an apical short axis view of the heart. Based on the FA-maps (top row) a target FA of 60° inside the ROI (blue contour) was set for the 2D SSFP CINE technique (bottom row). TR_SSFP was set to minimum so that SAR reached the denoted limits. When operating the body RF coil at whole-body/local SAR limit, the B₀ pass band of 2D SSFP CINE exhibited a width of 212 Hz/120 Hz. Severe banding artifacts can be seen for BC/4RX @ local SAR limit. When using the 4TX/4RX RF coil (<b>Φ</b>₃) a pass band of 263 Hz was achieved for 2D SSFP. This improvement helps to reduce SSFP related banding artifacts across the heart. The denoted SNR_rel is relative to the SNR obtained with the SSFP protocol (BW_RX = 1002 Hz/pixel) used for LV chamber quantification.</p

Validation of EMF simulations.

<p>Comparison of simulated (1^st row) and measured (2^nd row) B₁⁺-maps of a mid-axial slice through a torso phantom (top) filled with a uniform myocardial tissue mimicking solution. Regions with angle-to-noise-ratios lower than 1% were discarded using thresholding. 3^rd row: Absolute difference maps (B₁⁺_simulation - B₁⁺_measurement) demonstrating a good agreement between simulations and experiments.</p