Detection of alterations in membrane metabolism during neoadjuvant chemotherapy in patients with breast cancer using phosphorus magnetic resonance spectroscopy at 7 Tesla

Here we investigate the feasibility of tumor metabolism monitoring in T1c to T3 breast cancer during neoadjuvant chemotherapy by means of phosphorus ((31)P) magnetic resonance spectroscopy at 7 tesla (T). Five breast cancer patients were examined using a (31)P MRSI sequence, prior to-, halfway-, and after neoadjuvant chemotherapy. The (31)P MRSI data were analyzed on group and individual level and compared to a spectrum of a group of healthy volunteers. Ratios of phosphomonoesters (PME) to phosphodiesters (PDE) and phosphomonoesters to inorganic phosphate (Pi) were determined. Histopathologic assessment showed four partial responders and one complete responder to chemotherapy. The (31)P spectrum of the patient group was distinctly different from the (31)P spectrum of healthy volunteers and transformed its shape during the course of chemotherapy towards the shape of the spectrum of the healthy volunteers. Prior to chemotherapy the PME to PDE signal ratio and the PME to Pi signal ratio were high, and during the course of the chemotherapy these ratios normalized to the value of the healthy volunteers. Metabolite T 2 values in tumor tissue tended to be lower than those for healthy glandular tissue. Assessment of individual patients showed that four out of five had a significant drop of the PME to Pi ratio by a factor of 2 or more. On average, the pH of the tumor, calculated from chemical shift variation of Pi, was 0.19 units lower before chemotherapy. We have demonstrated that the sensitivity of (31)P MRSI in breast cancer at 7 T is sufficient to detect alterations in membrane metabolism during neoadjuvant chemotherapy, which may be used for early assessment of treatment efficacy.