Phosphorous-31 magnetic resonance spectroscopy (31P-MRS), the longest-standing in vivo MRS modality, can be an invaluable tool for probing in vivo metabolites such as phosphocreatine (PCr), inorganic phosphate (Pi), phosphomonoesters (PMEs), phosphodiesters (PDEs), and adenosine triphosphate (ATP) .1,2 As fundamental phospholipids and consitituents of the high-energy phosphate pathway, these 31P metabolites provide noninvasive measures of tissue pH, lipid metabolism, and oxidative bioenergetics.3,4 Thus, 31P-MRS possesses versatile diagnostic and prognostic potential. For instance, elevated PME/PDE ratios and reduced ATP levels have been reported in diseased and cancerous liver tissue, often correlated with classical plasma markers and Child-Pugh scores.5–9 Furthermore, 31P-MRS has been used to assess whole-liver treatment efficacy, monitoring metabolite changes in malignant tissues following therapy.10 Likewise, diminished PCr/ATP ratios and post-exercise PCr recovery rates have been measured in cardiac and skeletal muscles of patients with type 2 diabetes.11 Numerous endeavors have employed 31P MRS in the brain, heart, and muscle, seeking out alterations in neurodegenerative, cardiovascular, metabolic, and oncological diseases.12–20
While relevant 1H-MRS metabolite signals are obscured by background signals such as contaminating fat, water, and macromolecular signals, widely spaced 31P spectral peaks can be easily elucidated due to the absence of these nuisance signals. However, in contrast to 1H-MRS, 31P-MRS is burdened by a lower gyromagnetic ratio and relatively short spin-spin metabolite relaxation times (T2);21,22 these factors engender extremely poor in vivo relative sensitivity and force a delicate balance between SNR, resolution, and scan duration. Low 31P-MRS tissue concentrations (approximately 2 mM γ-ATP in liver23) further exacerbate SNR challenges, so that commonly used acquisition delays (TE > 300 µs) with conventional methods result in prolonged acquisition, phase distortions, baseline roll, and subsequent operator errors during metabolite quantification. Such complications have been severely limiting factors in the clinical feasibility of 31P-MRS. Recent advances in coil engineering and the introduction of ultra-high field (UHF, B0 > 3T) scanners have assisted in mitigating these limiting factors; one experiment demonstrated a 2.8-factor increase in PCr SNR at 7T relative to 3T.24 Conversely, UHF acquisitions also necessitate larger spectral bandwidth (SBW), with a 40 ppm range requiring approximately 2.0 kHz at 3T but 4.8 kHz at 7T. Still, excessive acquisition durations remain the clear barrier to clinical translation without innovative acceleration.
To address these points, we propose a three-dimensional (3D), ultra-short echo time (UTE) sequence with a novel rosette k-space trajectory (previously validated in ultra-short-T2 imaging25,26 and brain iron mapping27,28) for 31P magnetic resonance spectroscopic imaging (MRSI).29 Compared to conventional CSI Cartesian k-space trajectories, rosette’s “petal-like” pattern (Fig. 1) maps 3D k-space far more efficiently. Additionally, rosette’s relatively inchorent data sampling allows the possibility of significant acceleration through higher undersampling factors and compressed sensing (CS) reconstruction; offering better k-space coverage when compared to radial and spiral trajectories, generalized rosette’s curvature affords superior SNR performance under aggressive acceleration.30 Furthermore, UTE acquisitions permit the capture of short-T2 signals before significant transverse signal decay and first-order dephasing occur, enhancing SNR, simplifying spectral pre-processing, and minimizing operator quantification errors.
Substantial efforts have been invested towards clinically feasible 31P-MRSI, experimenting with short repetition times (TR), measuring multiple k-space points per TR, k-space undersampling, enhanced reconstruction via prior knowledge, and their conceivable combinations.31 3D extensions of ISIS have shown promise in UHF preclinical and 3T cardiac studies but remain limited by time resolution and motion artifact sensitivity.32,33 Non-localized or FID acquisitions are often preferred to minimize rapid 31P T2-decay, but also to overcome specific absorption rate (SAR) limitations at UHFs. Thus, variations of spatial-spectral encoding (SSE) schemes and their synergies with k-space undersampling appear to be the more promising avenue forward; several Cartesian and non-Cartesian acquisition designs offer varying degrees of SNR efficiency, k-space weighting, gradient system demands, and undersampling acceleration potential.
Flyback EPSI has been tested in skeletal calf muscle,34 offering considerable time savings over conventional phase-encoded when combined with CS acceleration;35 despite its acceleration potential, EPSI offers lower SNR efficiency and SBW at fine resolutions than other SSE options. Density-weighted concentric ring36 trajectories (CRTs) offer increased SNR efficiency and SBW limits, enabling faster MRSI even with UHF systems. CRTs boast flexibility in weighting and temporal interleaves, allowing tailoring according to acceleration needs and gradient slew rates. Similarly, spiral-encoded 31P-MRSI has exhibited faster dynamic calf muscle mapping than conventional weighting phase-encoded acquisition.37 Though spirals offer high acceleration, SNR efficiency, and customizable weighting, they are also limited by SBW and gradient system hardware.
Conventional CSI FIDs commonly possess TE on the order of 1–2 ms, which is restricted by the duration of constant excitation pulses and phase encoding gradients to reach the outermost k-space points. This acquisition delay can be decreased using variable pulse widths and amplitudes. Sampling throughout gradient transition periods, or ramp sampling, remains an additional option for minimizing TE. Studies have showcased TE as low as 480 µs and 520 µs for EPSI and radial EPSI, respectively.35,38 Acquisitions using such UTE CSI techniques39 have achieved TE = 300 µs at 3T and TE = 500 µs at 7T.40,41 In non-Cartesian center-out k-space trajectories employing ramp sampling, TE is primarily limited by the dead time between coil transmit-receive switching, permitting the shortest possible TE. Despite this possibility, SBW constraints and conventional sequence parameter (TA/FOV) matching have prevented extensive investigation of non-Cartesian UTE 31P-MRSI.
In this study, we evaluate the 3D UTE 31P-MRSI with a novel rosette k-space trajectory by comparing its performance to conventional 3D-weighted 31P CSI in the quadriceps muscle at 3T. We ultimately aim to demonstrate its potential value in clinical spectroscopic acquisitions.