Proton observed phosphorus editing (POPE) for in vivo detection of phospholipid metabolites Jannie P. Wijnen a,b *, Dennis W. J. Klomp a , Christine I. H. C. Nabuurs c , Robin A. de Graaf a,d , Irene M. L. van Kalleveen a , Wybe J. M. van der Kemp a , Peter R. Luijten a , Mark C. Kruit b , Andrew Webb b , Hermien E. Kan b and Vincent O. Boer a The purpose of this article was to compare the sensitivity of proton observed phosphorus editing (POPE) with direct 31 P MRS with Ernst angle excitation for 1 H– 31 P coupled metabolites at 7 T. POPE sequences were developed for detecting phosphocholine (PC), phosphoethanolamine (PE), glycerophospho- choline (GPC), and glycerophosphoethanolamine (GPE) on the 1 H channel, thereby using the enhanced sensitivity of the 1 H nuclei over 31 P detection. Five healthy volunteers were examined with POPE and 31 P-MRS. POPE editing showed a more than doubled sensitivity in an ideal phantom experiment as compared with direct 31 P MRS with Ernst angle excitation. In vivo, despite increased relaxation losses, significant gains in signal-to-noise ratio (SNR) of 30–40% were shown for PE and GPE+PC levels in the human brain. The SNR of GPC was lower in the POPE measurement compared with the 31 P-MRS measurement. Furthermore, selective narrowband editing on the 31 P channel showed the ability to separate the overlapping GPE and PE signals in the 1 H spectrum. POPE can be used for enhanced detection of 1 H– 31 P coupled metabolites in vivo. Copyright © 2015 John Wiley & Sons, Ltd. Keywords: proton observed phosphorus editing; POPE; in vivo; brain; phospholipids INTRODUCTION Abnormal metabolism of phospholipids occurs in several brain pathologies. Absolute and relative 31 P MR signals for phospho- choline (PC), phosphoethanolamine (PE), glycerophosphocholine (GPC), and glycerophosphoethanolamine (GPE) have been measured, in research on neoplastic lesions (1,2) in particular, and also in cognitive diseases such as schizophrenia (3). For example, decreased levels of phosphomonoesters (PMEs) and increased levels of phosphodiesters (PDEs) were found in the brains of schizophrenic patients (3,4). Elevated PME levels were found in patients with Alzheimer disease (5). In brain tumor cells a substantially higher PC/GPC ratio (more than twofold) as compared with normal white matter cells has been re- ported, as well as elevated levels of PME in patients with brain tumors (2). However, the sensitivity of 31 P MRS is intrinsically low, due to the gyromagnetic ratio of the 31 P nucleus and the low concentration of phosphorylated metabolites, which hinders the true translation of 31 P MRS to clinical use since very large voxels and long scan times are needed. While 1 H to 31 P polar- ization transfer (6–8), multi-echo acquisitions (9), and ultra-high field (10–12) have been shown to improve the signal-to-noise ratio (SNR) in 31 P MRS, detection via 1 H MRS has an intrinsically higher sensitivity (i.e. (γ 1 H/γ 31 P) 3 ). However, in the 1 H MR spectrum the signals of PME and PDE are completely overlap- ped by signals of other metabolites, and even with LC model fitting techniques (13) these cannot be resolved, even at ultra- high field. * Correspondence to: Jannie P. Wijnen, Department of Radiology, University Medical Centre Utrecht, Utrecht, The Netherlands. E-mail: jwijnen@umcutrecht.nl a J. P. Wijnen, D. W. J. Klomp, R. A. de Graaf, I. M. L. van Kalleveen, W. J. M. van der Kemp, P. R. Luijten, V. O. Boer Department of Radiology, University Medical Centre Utrecht, Utrecht, The Netherlands b J. P. Wijnen, M. C. Kruit, A. Webb, H. E. Kan Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands c C. I. H. C. Nabuurs Department of Radiology, Maastricht University, Maastricht, The Netherlands d R. A. de Graaf Department of Diagnostic Radiology, Yale University, New Haven, CT, USA Abbreviations used: B 0 , static magnetic field; B 1 , applied magnetic field; BIR, B 1 independent rotation; Cho, choline containing compounds; Cr, creatine; GPC, glycerophosphocholine; GPE, glycerophosphoethanolamine; CSI, chemi- cal shift imaging; NAA, N-acetyl aspartate; NOE, nuclear Overhauser enhance- ment; PC, phosphocholine; PDE, phosphodiester; PCr, phosphocreatine; PE, phosphoethanolamine; PME, phosphomonoester; POPE, proton observed phosphorus editing; ppm, parts per million; SAR, specific absorption rate; SNR, signal-to-noise ratio; T E , echo time; T R , repetition time; VAPOR, variable pulse powers and optimized relaxation delays. Special issue research article Received: 17 September 2014, Revised: 3 September 2015, Accepted: 8 October 2015, Published online in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/nbm.3440 NMR Biomed. 2015 Copyright © 2015 John Wiley & Sons, Ltd.