Early effects of neoadjuvant chemotherapy in breast cancer using metabolic MRI

Breast cancer patients undergoing NAC treatment experience side effects, due to the fact that chemotherapy drugs target all cells in the body that grow and divide rapidly. On top of that, in ~30% of the patients, NAC treatment does not result in tumor size reduction. At the moment there is no non-invasive method to evaluate the early effects of systemic treatment. The overall aim of this thesis was to evaluate early effects of NAC treatment in breast cancer patients using metabolic MRI. The first part of this thesis shows that we are able to measure metabolic changes after the first cycle of NAC treatment. In Chapter 2, metabolic ratios measured with 31P-MRSI were correlated to the pathological response. The PMEs and PDEs are known to be important in anabolism and catabolism of the cell membrane. In a small group of patients, it appeared that the PME/PDE ratio in partial and complete responders decreased after the first cycle of NAC treatment and the non-responders showed an increase in the PME/PDE ratio. This shows the potential of using PME/PDE ratio as a biomarker for early prediction of non-response to NAC treatment in breast cancer patients. In Chapter 3, a different contrast mechanism was used to acquire metabolic information about the tumor. Changes in amide signals originating from amide protons attached to the backbone of proteins and peptides, were measured with CEST-MRI. These are of interest as tumors show increased amide signals compared to healthy tissue due to increased cellular proliferation and subsequent accumulation of defective proteins in tumors. Partial and complete responders showed a decrease in amide signal while non-responders showed an increase in amide signal. In Chapter 4, we correlated the amide signal measured with CEST-MRI to the pH measured with 31P-MRSI. A correlation between amide signal and pH in the tumor was found in breast cancer patients. This correlation was opposite from the intrinsic relation between amide signal and pH, as this is base catalyzed. This demonstrates that the contribution of the concentration of mobile amide protons likely supersedes the influence of the exchange rate in the measured amide signal. This also shows that 31P-MRSI and CEST-MRI provide complementary information about the tumor emphasizing the importance of both techniques. In the last part of this thesis in Chapter 5, first steps were taken to merge metabolic imaging with ultra-high resolution MRI of the breasts. A new bilateral breast coil setup was developed. Improved image quality for breast imaging at 7 T was achieved using five meandering dipole antennas in a multi-transmit setup, combined with a high density receive array. The coil generates sufficient B1+ over a larger FOV in the breasts. This makes it possible to acquire T2-weighted images and to image the axillary lymph nodes, which has not been shown in previous studies at high field. The possibility of T2-weighted imaging is a crucial step towards translating routinely used breast imaging protocols from 3 T to 7 T

Homogeneous B\u3csub\u3e1\u3c/sub\u3e\u3csup\u3e+\u3c/sup\u3e for bilateral breast imaging at 7 T using a five dipole transmit array merged with a high density receive loop array

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Homogeneous B1+ for bilateral breast imaging at 7 T using a five dipole transmit array merged with a high density receive loop array

To explore the use of five meandering dipole antennas in a multi-transmit setup, combined with a high density receive array for breast imaging at 7 T for improved penetration depth and more homogeneous B1 field. Five meandering dipole antennas and 30 receiver loops were positioned on two cups around the breasts. Finite difference time domain simulations were performed to evaluate RF safety limits of the transmit setup. Scattering parameters of the transmit setup and coupling between the antennas and the detuned loops were measured. In vivo parallel imaging performance was investigated for various acceleration factors. After RF shimming, a B1 map, a T1-weighted image, and a T2-weighted image were acquired to assess B1 efficiency, uniformity in contrast weighting, and imaging performance in clinical applications. The maximum achievable local SAR10g value was 7.0 W/kg for 5 × 1 W accepted power. The dipoles were tuned and matched to a maximum reflection of −11.8 dB, and a maximum inter-element coupling of −14.2 dB. The maximum coupling between the antennas and the receive loops was −18.2 dB and the mean noise correlation for the 30 receive loops 7.83 ± 8.69%. In vivo measurements showed an increased field of view, which reached to the axilla, and a high transmit efficiency. This coil enabled the acquisition of T1-weighted images with a high spatial resolution of 0.7 mm3 isotropic and T2-weighted spin echo images with uniformly weighted contrast

Homogeneous B1 + for bilateral breast imaging at 7 T using a five dipole transmit array merged with a high density receive loop array

To explore the use of five meandering dipole antennas in a multi-transmit setup, combined with a high density receive array for breast imaging at 7 T for improved penetration depth and more homogeneous B1 field. Five meandering dipole antennas and 30 receiver loops were positioned on two cups around the breasts. Finite difference time domain simulations were performed to evaluate RF safety limits of the transmit setup. Scattering parameters of the transmit setup and coupling between the antennas and the detuned loops were measured. In vivo parallel imaging performance was investigated for various acceleration factors. After RF shimming, a B1 map, a T1-weighted image, and a T2-weighted image were acquired to assess B1 efficiency, uniformity in contrast weighting, and imaging performance in clinical applications. The maximum achievable local SAR10g value was 7.0 W/kg for 5 × 1 W accepted power. The dipoles were tuned and matched to a maximum reflection of −11.8 dB, and a maximum inter-element coupling of −14.2 dB. The maximum coupling between the antennas and the receive loops was −18.2 dB and the mean noise correlation for the 30 receive loops 7.83 ± 8.69%. In vivo measurements showed an increased field of view, which reached to the axilla, and a high transmit efficiency. This coil enabled the acquisition of T1-weighted images with a high spatial resolution of 0.7 mm3 isotropic and T2-weighted spin echo images with uniformly weighted contrast

Homogeneous B1 + for bilateral breast imaging at 7 T using a five dipole transmit array merged with a high density receive loop array

To explore the use of five meandering dipole antennas in a multi-transmit setup, combined with a high density receive array for breast imaging at 7 T for improved penetration depth and more homogeneous B1 field. Five meandering dipole antennas and 30 receiver loops were positioned on two cups around the breasts. Finite difference time domain simulations were performed to evaluate RF safety limits of the transmit setup. Scattering parameters of the transmit setup and coupling between the antennas and the detuned loops were measured. In vivo parallel imaging performance was investigated for various acceleration factors. After RF shimming, a B1 map, a T1-weighted image, and a T2-weighted image were acquired to assess B1 efficiency, uniformity in contrast weighting, and imaging performance in clinical applications. The maximum achievable local SAR10g value was 7.0 W/kg for 5 × 1 W accepted power. The dipoles were tuned and matched to a maximum reflection of −11.8 dB, and a maximum inter-element coupling of −14.2 dB. The maximum coupling between the antennas and the receive loops was −18.2 dB and the mean noise correlation for the 30 receive loops 7.83 ± 8.69%. In vivo measurements showed an increased field of view, which reached to the axilla, and a high transmit efficiency. This coil enabled the acquisition of T1-weighted images with a high spatial resolution of 0.7 mm3 isotropic and T2-weighted spin echo images with uniformly weighted contrast

Amide chemical exchange saturation transfer at 7T : A possible biomarker for detecting early response to neoadjuvant chemotherapy in breast cancer patients

Background: The purpose of this work was to investigate noninvasive early detection of treatment response of breast cancer patients to neoadjuvant chemotherapy (NAC) using chemical exchange saturation transfer (CEST) measurements sensitive to amide proton transfer (APT) at 7T. Methods: CEST images were acquired in 10 tumors of nine breast cancer patients treated with NAC. APT signals in the tumor, before and after the first cycle of NAC, were quantified using a three-pool Lorentzian fit of the z-spectra in the region of interest. The changes in APT were subsequently related to pathological response after surgery defined by the Miller-Payne system. Results: Significant differences (P0.05, Kruskal-Wallis test). Conclusions: This preliminary study shows the feasibility of using APT CEST magnetic resonance imaging as a noninvasive biomarker to assess the effect of NAC in an early stage of NAC treatment of breast cancer patients

Early detection of changes in phospholipid metabolism during neoadjuvant chemotherapy in breast cancer patients using phosphorus magnetic resonance spectroscopy at 7T

The purpose of this work was to investigate whether noninvasive early detection (after the first cycle) of response to neoadjuvant chemotherapy (NAC) in breast cancer patients was possible. 31 P-MRSI at 7 T was used to determine different phosphor metabolites ratios and correlate this to pathological response. 31 P-MRSI was performed in 12 breast cancer patients treated with NAC. 31 P spectra were fitted and aligned to the frequency of phosphoethanolamine (PE). Metabolic signal ratios for phosphomonoesters/phosphodiesters (PME/PDE), phosphocholine/glycerophosphatidylcholine (PC/GPtC), phosphoethanolamine/glycerophosphoethanolamine (PE/GPE) and phosphomonoesters/in-organic phosphate (PME/Pi) were determined from spectral fitting of the individual spectra and the summed spectra before and after the first cycle of NAC. Metabolic ratios were subsequently related to pathological response. Additionally, the correlation between the measured metabolic ratios and Ki-67 levels was determined using linear regression. Four patients had a pathological complete response after treatment, five patients a partial pathological response, and three patients did not respond to NAC. In the summed spectrum after the first cycle of NAC, PME/Pi and PME/PDE decreased by 18 and 13%, respectively. A subtle difference among the different response groups was observed in PME/PDE, where the nonresponders showed an increase and the partial and complete responders a decrease (P = 0.32). No significant changes in metabolic ratios were found. However, a significant association between PE/Pi and the Ki-67 index was found (P = 0.03). We demonstrated that it is possible to detect subtle changes in 31 P metabolites with a 7 T MR system after the first cycle of NAC treatment in breast cancer patients. Nonresponders showed different changes in metabolic ratios compared with partial and complete responders, in particular for PME/PDE; however, more patients need to be included to investigate its clinical value