Clinicians and scientists interested in phosphorus magnetic resonance spectroscopy and breast cancer imaging.Neoadjuvant chemotherapy is increasingly used in the treatment of breast cancer. However, not every patient benefits from neoadjuvant chemotherapy, while she may experience serious side effects. There is a great need to find biomarkers that can assess the early response of an individual patient to neoadjuvant chemotherapy. Previously, we reported changes in the ratio between phosphomonoesters (PME) and phosphodiesters (PDE) and the ratio between PME and inorganic phosphate (Pi) halfway chemotherapy and after the end of neoadjuvant chemotherapy using phosphorus magnetic resonance spectroscopy (³¹P-MRS) [1]. The purpose of this study is to assess the possibility to detect these changes in phospholipid metabolites that are related to the cell membrane synthesis even earlier, directly after the first cycle of neoadjuvant chemotherapy using ³¹P-MRS.After informed consent, six patients who received neoadjuvant chemotherapy were examined before and after the first cycle of chemotherapy with a 2 channel unilateral ¹H/³¹P dual-tuned coil (MR Coils, Drunen, Netherlands) on a 7T MR system (Philips, Cleveland, USA). After B0 shimming, ³¹P-MRS was obtained using the AMESING sequence [2], in which 1 FID and 5 full echoes were acquired with ΔTE = 45 ms; TR = 6 s; FOV 160x160x160 mm³; 8x8x8 voxels; 2x2x2 cm³ nominal resolution; BW = 8200 Hz; sampling matrix size = 256; total scan time 25:36 min. All MRS data were zero-filled and apodized (15Hz Lorentzian) in the time domain and spatially Hamming filtered. Tumor spectra of the group of patients were frequency aligned for PE and weighted averaged based on the PE signal intensity.
The ³¹P-MRS data were analyzed on group level and compared to the spectra obtained in an earlier study in our hospital which acquired ³¹P-MRS halfway the neoadjuvant chemotherapy [1]. Ratios of PME to PDE, PME to inorganic phosphate (Pi), phosphoethanolamine (PE) to phosphodiesters (mobile GPtE and GPtC) and Pi to γ-ATP were determined in the tumor before and after the first cycle of neoadjuvant chemotherapy by means of spectral fitting with JMRUI [3]. Comparing the spectra obtained before and after the first cycle of neoadjuvant chemotherapy, we observed a decrease in PE signal, corresponding with the decrease seen in the earlier study after three cycles of chemotherapy (Figure 1). The ratio of PME over Pi shows the largest decrease in comparison to the other ratios (Figure 2). In this preliminary study, we observed a decrease in PE signal after the first cycle of neoadjuvant chemotherapy which corresponds to our earlier findings (Figure 1). Comparing the metabolite ratios before chemotherapy and after the first cycle of chemotherapy, the PME over Pi ratio shows the largest difference, which in agreement with observations made at later time point of the treatment. However, in contrast to decreased PME/PDE ratios observed after multiple cycles of chemotherapy, this effect could not be observed immediately after the start of the treatment. This could either imply that 1) the level of change cannot be picked up due to limited SNR, 2) the processes that drive a change in PME/PDE are slower than the processes that drive a change in PME/Pi ratio, and/or 3) these ratios differ between responders and non-responders and are averaged out since we do not know yet the pathological response of all patients.We demonstrated that changes in PE signal can be detected after the first cycle of chemotherapy. Moreover, comparing these metabolic changes with a previous study where ³¹P-MRS was performed after the third cycle of neoadjuvant chemotherapy we observed a similar change in PME/Pi ratio but not in PME/PDE ratio.