Synopsis

Keywords: Pulse Sequence Design, Spectroscopy

A double-echo pi-SSelMQC method was developed to recover 100% biomarker signals, as compared to spin-echo pulse sequences, with excellent water and lipid suppression. Signals from both ZQ→DQ and DQ→ZQ coherence transfer pathways were detected. By synchronization of phase-encoding steps and RF phase increments of either MQ-preparation or MQ-transfer pulse, the biomarker images from different MQ-pathways were resolved and shifted away from residual lipid and water signals. Full lactate and polyunsaturated fatty acids (PUFA) signals were recovered in pi-SSelMQC imaging using yogurt phantoms, vegetable oil, and murine 344SQ lung tumors grown subcutaneously on the right thigh of syngeneic 129X1/SvJ male mice.

Introduction

The Selective Multiple-Quantum Coherence transfer (Sel-MQC) methods enable in vivo mapping of biomarker distributions in biological tissues containing high-fat content with complete lipid and water suppression in a single-scan [1]. The method was employed in proton detection of the antineoplastic agent Iproplatin in a mouse tumor model [2] and polyunsaturated fatty acids (PUFA) in human breast cancer [3, 4]. However, only one of the ZQ→DQ and DQ→ZQ coherence transfer pathways was detected in order to suppress lipid and water. Half of the biomarker signals was lost as compared to the spin echo pulse sequence. In this report, we present a novel phase-incrementing soft Sel-MQC (pi-SSelMQC) method for simultaneous detection of both ZQ→DQ and DQ→ZQ pathways with full biomarker signal recovery. We have developed the double-echo pi-SSelMQC pulse sequences to achieve excellent lipid and water suppression. The methods are applicable for fast MRSI in extracranial tissues.

Methods

The soft Sel-MQC (SSel-MQC) method [1] was modified into the pi-SSelMQC sequence by incrementing the RF phase of the second or the last 90° pulse for MQ-coherence preparation or transfer, respectively, in synchronization with the phase-encoding gradient (Fig. 1). Since the coherence order of the DQ→ZQ and ZQ→DQ coherence transfer pathways have opposite signs, this procedure introduces opposite image offsets of signals from the two different MQ-coherence transfer pathways, away from unwanted spurious signals of residual water and lipids. The method enables simultaneous detection of both DQ→ZQ and ZQ→DQ pathways for a full recovery of the biomarker signals. Acquiring both pathways in the same acquisition window, however, reintroduced lipid and water signals (Fig. 2a). To address the issue, we have designed the double-echo pi-SSelMQC pulse sequences (Fig. 3) to acquire two separate MQ-coherence transfer echoes from the DQ→ZQ and ZQ→DQ coherence transfer pathways. We have previously observed that the two MQ-transfer echoes in the Sel-MQC experiments were separated by 2t₁ [1], permitting insertion of gradient pulses between the two MQ-coherence transfer echoes to suppress unwanted signals (Fig. 3). The biomarker signals from the two MQ-coherence pathways can be digitally added for full recovery without 50% loss of the biomarker signal. The double-echo pi-SSelMQC achieved excellent lipid and water suppression, similar to the original SSel-MQC experiments.

Results

The pi-SSelMQC pulse sequences were implemented on a Bruker 9.4T BioSpec 94/30USR AVII MRI spectrometer. The system has the BFG-240/120-S13B shielded gradients (12cm bore size) with Integrated Shims (Resonance Research, Inc) and the maximum gradient strengths of 999.63, 1,001.9, and 1,001.6 mT/m respectively in x-, y- and z-directions. We detected yogurt lactate signals from both DQ→ZQ and ZQ→DQ coherence transfer pathways in two-dimensional pi-SSelMQC imaging experiments using a gap resonator RF coil (data will be presented). In one-dimensional (1D) CSI experiments using a single-loop RF coil, we have observed tumor lactate signals in vivo in a mouse lung cancer model simultaneously from both DQ→ZQ and ZQ→DQ coherence pathways (Fig. 2a), and separately from either DQ→ZQ (Fig. 2b) or ZQ→DQ (Fig. 2c) coherence pathway. The mouse tumor was grown into 10.73 mm x 10.72 mm x 8.63 mm size after inoculating mouse lung cancer 344SQ cells (0.5 million in 100 ul of serum-free medium) subcutaneously in the right thigh region of the syngeneic 129X1/SvJ male mice. When both MQ-coherence transfer pathways were detected in the single acquisition window, intense lipid and water signals were reintroduced with gradient ratio g₁:g₂:g₃ = 1: -1: 2 [Fig. 2a]. When using two acquisition windows separately for the two MQ-coherence transfer pathways, excellent lipid and water suppression were achieved for fast imaging of PUFA (Fig. 4) or lactate (Fig. 5) in the presence of read gradient. Fast 3D imaging of these biomarkers were also demonstrated using the double-echo pi-SSelMQC techniques.

Conclusion

When synchronizing RF phase-incrementation and phase-encoding gradients, we have recovered full biomarker signals in pi-SSelMQC imaging in phantoms and in vivo in a mouse tumor model. The fast double-echo pi-SSelMQC imaging methods offer outstanding lipid and water suppression in a single-scan with 100% biomarker signal recovery.

Acknowledgements

We thank the funding support from Linebarger Comprehensive Center (P30 CA016086), Bowles Center for Alcohol Studies (P60 AA011605), and Carolina Institute for Developmental Disabilities (U54 HD079124) for Center for Animal MRI facilities at the University of North Carolina at Chapel Hill.

References

1. He, Q., et al., Single-scan in Vivo Lactate Editing With Complete Lipid and Water Suppression by Selective Multiple-Quantum-Coherence Transfer (Sel-MQC) With Application to Tumors. J. Magn. Reson. B, 1995. 106(3): p. 203-11. 2. He, Q., et al., Proton observation of the antineoplastic agent iproplatin in vivo by selective multiple quantum coherence transfer (Sel-MQC). Magn. Reson. Med., 1995. 33(3): p. 414-416. 3. He, Q., et al., In Vivo MR Spectroscopic Imaging of Polyunsaturated Fatty Acids (PUFA) in Healthy and Cancerous Breast Tissues by Selective Multiple-Quantum Coherence Transfer (Sel-MQC): A Preliminary Study. Magn. Reson. Med., 2007. 58: p. 1079-1085. 4. Zhu, H., D. Rubin, and Q. He, The Fast Spiral-SelMQC Technique for In Vivo MR Spectroscopic Imaging of Polyunsaturated Fatty Acids in Human Breast Tissue. Magn. Reson. Med., 2012. 67: p. 8–19.