In Vivo Intermolecular Double-Quantum Imaging on a Clinical 1.5 T MR Scanner Jianhui Zhong, 1,2 * Zhong Chen, 1 and Edmund Kwok 1 A novel MRI method based on the intermolecular double-quan- tum coherence (DQC) for soft tissues is described. DQC images of human brain were obtained for the first time on a whole-body 1.5 T scanner. The combination of quantum and classical for- malisms was used to characterize multiple-quantum coher- ences, and to aid in the design of a DQC imaging sequence. The theoretical analysis suggests that signals from the intermolec- ular DQCs have higher sensitivity than those from the zero- quantum coherence (ZQC) for human brain, and the sensitivity increases with increased field strength. The DQC signal may provide a new form of contrast for MRI. Magn Reson Med 43: 335–341, 2000. © 2000 Wiley-Liss, Inc. Key words: intermolecular dipole– dipole interaction; double- quantum coherence; MRI; sensitivity Multiple spin echoes (MSEs) and intermolecular multiple- quantum coherences (MQCs) in highly polarized systems have generated tremendous interest but also controversy in the NMR community over the past few years. These phenomena have been described using either classical the- ory for the demagnetizing field (1– 6) or quantum-mechan- ical density matrix treatments (7–11). To date, both treat- ments have led to fully quantitative predictions of the signals for simple sequences, such as correlated 2D spec- troscopy (COSY) or COSY Revamped by Asymmetric Z Gradient Echo Detection (CRAZED) experiments (6 – 8). Warren and co-workers (8) determined the connection be- tween the demagnetizing field and intermolecular dipolar coupling. The residual dipolar couplings between distant spins are responsible for the dipolar demagnetizing field, and give rise to the intermolecular MQCs (7). From the classical viewpoint, these phenomena are due to the de- magnetizing field produced by the spatial modulation of the nuclear magnetization arising in the sample following the second pulse in the CRAZED sequence (6). Though there are still some theoretical issues which remain to be addressed (12), intermolecular dipolar interaction effects have lost much of their mystical character and are becom- ing useful tools in NMR. Recently, there has been great interest in the potential of the MQC or MSE contrast mech- anisms for MRI (13–18), because these contrast mecha- nisms may provide improved detection of tumors and eliminate the need for contrast agent injection. Warren and co-workers (9,10) first proposed intermolecular zero-quan- tum coherence (ZQC) imaging which is insensitive to the magnetic field inhomogeneity and has a relatively higher signal-to-noise ratio (SNR) than other MQCs. They have obtained ZQC images with varying contrast which reveal structural features not seen in conventional MR images (13–15). However, DQC imaging utilizing the prototype sequence 90° – t 1 –{gradient} – 90° – {double-area gradi- ent}– t 2 , was believed to be unable to result in meaningful signals from the DQCs with a long detection time t 2 and a short evolution t 1 , which are the preferred conditions for imaging (14). Navon and co-workers (16) used 1 H double- quantum filtered (DQF) MRI to detect molecules associ- ated with ordered structures, thus identifying a new type of contrast. The method, however, only detects signals from semisolid constituents and is specific for imaging of connective tissues such as cartilage and tendons. This method will not be discussed here. Based on classical demagnetization field theory, van Zijl and co-workers (17) attempted to form an image from the second spin-echo, but found that the image had a very low SNR and no detectable contrast even at the high field strength of 4.7 T. Recently, Bifone et al. (18) showed that MSE spectroscopic signals in a localized volume can be observed in vivo with a 1.5 T clinical MR scanner. However, the sensitivity of the de- tected signal was too low for MRI. It appears from previous results that it may be too difficult to obtain MSE or DQC images. We noticed, however, that the experimental pa- rameters for the acquisition of the signal from the DQCs were not optimized in these previous reports (17,18). The potential applications of the intermolecular MQC as a new image contrast can be properly evaluated only when sig- nals at acceptable levels can be obtained with designs of optimal imaging sequences for the MQC imaging. The purpose of this article is to investigate the charac- teristics of DQCs and their feasibility for human brain imaging using a clinical MRI scanner. We analyzed the behaviors of MQCs using a combination of the quantum and classical formalisms. We calculated the optimal signal sensitivity of the MQCs at different field strengths, and discuss the effect of the multiple-quantum relaxation pro- cesses during the t 1 evolution in the CRAZED-like se- quences, since it may provide a new contrast mechanism in MQC MRI. A DQC imaging sequence with some exper- imental optimization was designed to fully utilize the available signal intensity from DQCs and to improve the contrast in imaging. Multislice human brain DQC images were obtained successfully for the first time at 1.5 T. RELATIVE SIGNAL INTENSITY OF DQC, ZQC, AND SQC FOR IMAGING In order to study the feasibility of in vivo DQC imaging, it is necessary to estimate the relative signal intensities for 1 Department of Radiology, University of Rochester Medical Center, Roches- ter, New York. 2 Biomedical Engineering Program, University of Rochester Medical Center, Rochester, New York. Grant sponsor: US PHS, NIH; Grant number: NS32024. *Correspondence to: Jianhui Zhong, Ph.D., Department of Radiology, Univer- sity of Rochester Medical Center, 601 Elmwood Avenue, Box 648, Rochester, NY 14642-8648. E-mail: jianhui_zhong@urmc.rochester.edu Received 10 September 1999; revised 10 November 1999; accepted 29 November 1999. Magnetic Resonance in Medicine 43:335–341 (2000) © 2000 Wiley-Liss, Inc. 335