Simultaneous Detection of Choline and Other Metabolites using SEE-SelMQC for Spectroscopic Imaging of Human Breast Cancer

INTRODUCTION. H NMR detection of metabolites and drugs in human breast tissue is challenging due to the intense water and lipid signals that dominate the proton chemical shift range. Since initial observation of increased choline level in breast cancer by Roebuck et. al. using spin-echo MRS techniques, choline has become a potential MR biomarker for breast cancer diagnosis with improve specificity. In most breast MRS studies, the incomplete lipid and water suppression often obscure the quantitative evaluation of tissue choline concentration. Other biochemicals are usually not detectable in breast tissue by MRS due to overlapping lipid and water resonances. In this report, we present data to address this issue with our previously demonstrated SEE-SelMQC (Spin Echo Enhanced Selective Multiple Quantum Coherence transfer) technique developed for multiple metabolite detection in vivo in animal EMT6 tumor models. Complete suppression of lipid and water signals was achieved in a single scan by the Selective Multiple-Quantum Coherence transfer (Sel-MQC) pulse sequence component, which makes it possible to observe metabolites and antineoplastic agents in tissues containing high concentration of mobile lipid. The Sel-MQC method has been adapted for simultaneous detection of lactate and antineoplastic agent Iproplatin in RIF-1 tumors. In addition, the T1and T2-Sel-MQC sequences have also been developed to determine the relaxation times of the edited lactate signals for tissue metabolite quantification. Modified Sel-MQC sequences are available to detect neuronal glucose, GABA and glutamate. 9 Recently, we have developed the volume selective Sel-MQC techniques using 1331 composite pulses, as well as a multi-slice Sel-MQC method for 3D mapping of metabolites using the Hadamard matrix approach. The efficiency for robust multi-slice spectroscopic imaging or 3D volume detection were recently improved for the SelMQC techniques using spatial-spectral (SPSP) selective RF pulses. Here we present the results from a GE 3T clinical scanner for SEE-SelMQC implementation to demonstrate its potential in simultaneous detection of multiple metabolites in human breast tissue or other lipid abundant tissues to study extracranial cancers. Thus, the MRSI studies of breast cancer can be expanded to detect multiple biomolecular markers. Although high-field is preferred for the SEE-SelMQC method, the application of the sequence at lower-field would also enhance lipid and water suppression for choline quantification in the clinical breast MRSI settings.