Assessing tissue metabolism by phosphorous-31 magnetic resonance spectroscopy and imaging: a methodology review

Abstract

Many human diseases are caused by an imbalance between energy production and demand.Magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) provide the unique opportunity for in vivo assessment of several fundamental events in tissue metabolism without the use of ionizing radiation. Of particular interest, phosphate metabolites that are involved in ATP generation and utilization can be quantified noninvasively by phosphorous-31 ( 31 P) MRS/MRI. Furthermore, 31 P magnetization transfer (MT) techniques allow in vivo measurement of metabolic fluxes via creatine kinase (CK) and ATP synthase. However, a major impediment for the clinical applications of 31 P-MRS/MRI is the prohibitively long acquisition time and/or the low spatial resolution that are necessary to achieve adequate signal-to-noise ratio. P-MRS/MRI techniques. Applications of these techniques to the investigation of a specific physiology/pathology will be discussed without detailed description. Interested readers are referred to recent review articles on the applications of 31 P-MRS/MRI in metabolic characterization of skeletal muscle (10-12), heart (13), brain (14), and liver (11), as well as in diseases such as cancer (15), heart failure (16), and obesity and diabetes (17,18). Historical perspectiveThe use of 31 P-MRS for metabolic investigations dates back to 1960. Cohn and Hughes were the first to obtain a high-resolution 31 P spectrum of a solution of ATP (19). In addition, they also observed a dependence of the chemical shifts of the phosphorus nuclei of ATP on the pH of the solution. In parallel to the early development of MRI methods by Lauterbur (20), the entire 1970s also witnessed the rapid advance of 31 P-MRS in metabolic investigation of a broad range of biological systems. In 1973, Moon and Richards performed the first 31 P-MRS study that measured intracellular pH in human red blood cells (21). In the following year, Henderson and colleagues obtained the first 31 P spectrum of ATP from human red blood cells (22). At the same time, the Oxford team led by Radda performed the first experiment to acquire 31 P spectra from an intact organ, i.e., the excised and superfused muscle of rat hindlimb (23). The first in vivo 31 P-MRS study was performed on mouse brain by Chance et al. (24). Within the short span of one decade, organelles including mitochondria (25,26) and chromaffin granules (27), cells including Escherichia coli (28), yeast (29), and hepatocytes (30), and organs including skeletal muscle (31,32), heart (33-35), brain (36), kidney (37), and liver (38,39) have all been studied using 31 P-MRS.It is worth noting that most of these organ studies were performed on excised organs to avoid the need for spatial localization. Although Lauterbur has demonstrated the feasibility of imaging water protons (20), it was considered impractical for 31 P imaging of living systems because of the low sensitivity and difficulties with spectral resolution.The 1980s began with the publication of two important studies that aimed a...

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

“…One limitation of the current method is that it leads to a bias in the estimation of the chemical shift of Pi, an indicator of intracellular pH [1], [4]. To capture the changes in both the amplitude and the resonance frequency of Pi during stimulation and recovery, the subspace of Pi needs to be learned from training data acquired both during electrical stimulation and recovery.…”

“…where Ω m is the set of relaxation time-constants and resonance frequencies for the m th molecule [17]- [19]. Further, to exploit the exponential behavior of PCr recovery [1], [3], [4], [20], [21], we also constrained the temporal basis functions as…”

“…M ITOCHONDRIA play a critical role in biological processes by supplying the energy needed for maintaining tissue viability and functional integrity. Abnormal or altered mitochondrial metabolism has been shown to be a key factor in a wide range of diseases, including diabetes and cardiovascular diseases [1]. To date, our understanding of mitochondrial function is mostly gained from in vitro studies on isolated mitochondria under nonphysiological conditions.…”

“…However, due to the inherently low signal-to-noise ratio (SNR) of the 31 P signal, dynamic 31 P-MRSI methods are typically limited to spatial resolutions above 1 cm 3 , which is inadequate for small animal imaging. Hence, preclinical studies have been largely limited to nonlocalized or single voxel MRS studies [1].…”

Graft assessment of the ex vivo perfused porcine kidney using hyperpolarized [1‐13C]pyruvate

“…Alternatively, ex vivo renal viability assessment using 31 P metabolic MRS has been proposed as a novel way to ensure graft viability and increase the donor pool size 14 . Although 31 P MRS has merit, its inherently low SNR could impose restrictions on its use in the clinical setting due to low resolution and long scan times 15 …”