In vivo lactate signal enhancement using binomial spectral‐selective pulses in selective MQ coherence (SS‐SelMQC) spectroscopy

Abstract

Tumor vasculature and tissue oxygen pressure can influence tumor growth, metastases, and patient survival. Elevated levels of lactate may be observed during the process of aggressive tumor development accompanied by angiogenesis (the evolution of the microenvironment). The noninvasive MR detection of lactate in tumor tissues as a potential biomarker is difficult due to the presence of co-resonating lipids that are present at high concentrations. Methods were previously reported for lactate editing using the SELective Multiple Quantum Coherence (SelMQC) method. Here we report a sequence "SS-SelMQC," Spectral-Selective SelMQC, which is a modified version of SelMQC using binomial pulses. Binomial pulses were employed in this editing sequence for frequency excitation or inversion of selective lactate resonances. Lactate detection has been demonstrated using SS-SelMQC, both in vitro ( In vivo proton MR spectroscopy (MRS) provides a noninvasive, biochemical measure of metabolism which can be used to differentiate healthy tissues from tumor tissues based on the metabolic abnormalities (1-3). Metabolites may be a priori markers of prognosis or metabolic changes can be very sensitive early indicators of treatment response. As such, metabolic approaches show promise for monitoring, and perhaps even ultimately selecting treatments. As tumors are heterogeneous, multivoxel MRS imaging (MRSI) provides a method to investigate therapy response and optimization of individual treatment regime based on various metabolite levels or concentrations within each voxel, which might signify aggressive (or indolent) disease (4 -8) in local regions of the tumor. Among the many detectable metabolites, lactate (Lac) is an important compound that reflects elevated tumor glycolysis and/or poor tissue perfusion, which may result in accelerated tumor growth, malignant transformation, and metastases (9). Lac is the endproduct of glycolysis and the methyl resonance peak is typically a doublet situated at 1.3 ppm. Different levels of tumor lactate in the MR spectrum were reported in the literature (10 -15). High Lac was observed in extracts from biopsy specimens of breast tumors (10,16) and prostate tumors (11). Low extracellular pH and high Lac levels were shown to be indicators of metastatic risk in breast cancer xenografts (12,13). Elevated Lac content in biopsy samples was shown to correlate with increased risk of metastasis and poor patient survival in head and neck cancer (14) and cervical cancer (15), while a decrease in steady-state tumor Lac levels related to tumor response to radiation (17,18) and chemotherapy (19,20). It has also been shown by Shkarin et al. (21) that Lac is likely to be found in malignant breast tumors that may be a marker for tumor diagnosis. Therefore, noninvasively measured Lac may be an additional characteristic metabolic marker for cancer studies and may improve diagnostic specificity, serve as an early marker of tumor response, and provide functional information about prognosis.Reliable measurement and interpret...

Lactate detection in inducible and orthotopic Her2/neu mammary gland tumours in mouse models

“…In vivo MRS detection of lactate is difficult due to overlap of the lactate methyl and lipid methylene signals. Several techniques have been implemented by other investigators to suppress lipid in order to reveal the underlying lactate signals in various tissues . These methods can be broadly divided into two categories.…”

Lactate MRSI and DCE MRI as surrogate markers of prostate tumor aggressiveness

“…Lactate MRSI was performed using the selective multiple quantum coherence (Sel‐MQC) editing sequence with frequency‐selective, 15‐ms, single‐lobe sinc pulses. This sequence provides excellent lipid and water suppression, as shown previously . The selection of the lactate signal was achieved by applying three magnetic field gradients with the same combination and duration as described in refs.…”

Metabolic Tumor Imaging Using Magnetic Resonance Spectroscopy

“…35,36 The CH 2 lipid signal at 1.3 ppm overlaps with the lactate signal at 1.3 ppm, and requires spectral editing for the separation of these two signals. 37–39 Additionally, mobile polyunsaturated fatty acyl chain signals can be detected at 5.4 and 2.8 ppm, and can be used to assess polyunsaturation of mobile lipids. 36 However, the signal at 5.4 ppm may be difficult to detect because of its proximity to the large water signal at 4.7 ppm.…”