In Vivo pi-SSelMQC to Recover 100% Biomarker Signals From Both MQ Coherence Transfer Pathways with Applications in...

The Warburg Effect and lactate production in human cancer have a profound impact on tumor microenvironment modulation and cancer immune evasion. Lactate level changes during cancer therapies have been investigated in animal tumor models as an early predictive biomarker of treatment responses. Previously, non-invasive selective multiple quantum coherence transfer (Sel-MQC) methods were developed for in vivo lactate or polyunsaturated fatty acids (PUFA) imaging in tumors using chemical shift imaging (CSI) or fast Spiral-SelMQC methods. The Sel-MQC offers excellent single-scan suppression of intensive lipid and water signals. In current Sel-MQC imaging, however, only one of the Double-Quantum (DQ)→ Zero-Quantum (ZQ) and ZQ→DQ coherence transfer pathways can be detected at a time, resulting in a loss of biomarker signal by a factor of one-half when imaging lactate in tissues containing high level of mobile lipid. To recover 100% signal and improve in vivo biomarker imaging sensitivity, a fast MRSI imaging technique is needed for simultaneous detection of ZQ→DQ and DQ→ZQ coherence transfer pathways. In this research project, we have developed novel phase-incrementing soft selective multiple quantum coherence transfer (pi-SSelMQC) methods to detect full biomarker signal from both MQ-coherence transfer pathways with excellent water and lipid suppression with demonstrations in phantoms and tumor lactate imaging.

The pi-SSelMQC methods with a single-echo or double-echo acquisitions were demonstrated in phantoms and in vivo in animal tumor models. The biomarker lactate and PUFA images were obtained from yogurt samples and soybean oil phantoms, respectively. In vivo lactate imaging was carried out using the murine 344SQ lung cancer model grown subcutaneously on the right thigh of syngeneic 129X1/SvJ male mouse.

Lactate from both ZQ→DQ and DQ→ZQ coherence transfer pathways was detected in yogurt samples and in vivo in 344SQ tumors by synchronizing the phase-encoding gradient steps with the RF phase incrementations of the selective MQ-excitation 90˚ pulse or the MQ-transfer 90˚ pulse. Opposite imaging offsets were introduced to the lactate signals from the two different MQ-coherence transfer pathways, moving lactate images away from unwanted signals from water, lipid, or other overlapping biochemicals. This permits frequency-encoding to speed up data acquisition by 10-20 times in Cartesian coordinates. The pi-SSelMQC methods were also applied to recover 100% PUFA signals from soybean oil phantoms. In the presence of readout-gradients, the novel double-echo pi-SSelMQC acquisition scheme offers excellent lipid and water suppression, as well as 100% biomarker signal recovery from both MQ-coherence transfer pathways.

The biomarker images from the two different MQ-coherence transfer pathways can be simultaneously detected by the pi-SSelMQC methods with 100% signal recovery using phase-incrementing technique. The fast double-echo acquisition with frequency-encoding gradients may be employed to speed up cancer biomarker imaging with excellent lipid and water suppression. The novel pi-SSelMQC methods may be employed to monitor cancer treatment responses and investigate the relationship of tumor lactate production and cancer immune evasion.