High-Resolution Dynamic ³¹P-MR Spectroscopic Imaging for Mapping Mitochondrial Function

Abstract

To enable non-invasive dynamic metabolic mapping in rodent model studies of mitochondrial function using 31 P-MR spectroscopic imaging (MRSI). Methods: We developed a novel method for high-resolution dynamic 31 P-MRSI. The method synergistically integrates physics-based models of spectral structures, biochemical modeling of molecular dynamics, and subspace learning to capture spatiospectral variations. Fast data acquisition was achieved using rapid spiral trajectories and sparse sampling of (k, t, T)-space; image reconstruction was accomplished using a low-rank tensor-based framework. Results: The proposed method provided high-resolution dynamic metabolic mapping in rat hindlimb at spatial and temporal resolutions of 4 × 4 × 2 mm 3 and 1.28 s, respectively. This allowed for in vivo mapping of the time-constant of phosphocreatine resynthesis, a well established index of mitochondrial oxidative capacity. Multiple rounds of in vivo experiments were performed to demonstrate reproducibility, and in vitro experiments were used to validate the accuracy of the estimated metabolite maps. Conclusions: A new model-based method is proposed to achieve high-resolution dynamic 31 P-MRSI. The proposed method's ability to delineate metabolic heterogeneity was demonstrated in rat hindlimb. Significance: Abnormal mitochondrial metabolism is a key cellular dysfunction in many prevalent diseases such as diabetes and heart disease; however, current understanding of mitochondrial function is mostly gained from studies on isolated mitochondria

Assessment of Bioenergetic Deficits in Patients With Parkinson Disease and Progressive Supranuclear Palsy Using 31 P-MRSI

“…Despite the current methodological disadvantages of 31 P-MRSI, continuing to develop advanced 31 P-MRSI acquisition schemes will foster the applicability of the method in future research and potentially in clinical practice. 45 Such methodological advancements in 31 P-MRSI will allow quantitative measurements to be taken that will enhance intersite reliability, improve spatial and spectral resolution (e.g., when measuring the redox state of nicotinamide adenine dinucleotide), and enable dynamic measurements of the ATP synthesis (iP → ATP or PCr → ATP) rate, which will likely improve the diagnostic capabilities of the method. 42,46,47 In conclusion, we have demonstrated the pronounced presence of bioenergetic differences in these 2 parkinsonian disorders.…”

Whole‐Slab 3D MR Spectroscopic Imaging of the Human Brain With Spiral‐Out‐In Sampling at 7T

“…Increasing the resolution for spiral trajectories at 7T is difficult due to slew rate limitations and long measurement times. To further increase the resolution of spiral trajectories, undersampling techniques such as parallel imaging, 35 compressed sensing, 36 or SPICE 37 are necessary. The coverage in the slice direction was limited to a brain slab of 5 cm due to challenges with B 0 shimming using the standard scanner shimming hardware that has only first‐ and second‐order spherical harmonic shim coils.…”

Quantification of creatine kinase reaction rate in mouse hindlimb using phosphorus‐31 magnetic resonance spectroscopic fingerprinting

“…The electrodes were connected to a Grass stimulator (Grass Technologies, Warwick, RI). Muscle contraction was induced for 4 min by applying 3 Hz square wave pulses with 2 V amplitude and 1 ms pulse duration 38 . 31 P‐MRSF data were acquired before and 16 min after the stimulation.…”