Quantification of J‐resolved proton spectra in two‐dimensions with LCModel using GAMMA‐simulated basis sets at 4 Tesla

Abstract

A two-dimensional, J-resolved magnetic resonance spectroscopic extraction approach was developed employing GAMMA-simulated, LCModel basis-sets. In this approach, a two-dimensional J-resolved (2D-JPRESS) dataset was resolved into a series of one-dimensional spectra where each spectrum was modeled and fitted with its theoretically customized LCModel template. Metabolite levels were derived from the total integral across the J-series of spectra for each metabolite. Phantoms containing physiologic concentrations of the major brain chemicals were used for validation. Varying concentrations of glutamate and glutamine were evaluated at and around their accepted in vivo concentrations in order to compare the accuracy and precision of our method with 30 ms PRESS. We also assessed 2D-JPRESS and 30 ms PRESS in vivo, in a single voxel within the parieto-occipital cortex by scanning ten healthy volunteers once and a single healthy volunteer over nine repeated measures. Phantom studies demonstrated that serial fitting of 2D-JPRESS spectra with simulated LCModel basis sets provided accurate concentration estimates for common metabolites including glutamate and glutamine. Our in vivo results using 2D-JPRESS suggested superior reproducibility in measuring glutamine and glutamate relative to 30 ms PRESS. These novel methods have clear implications for clinical and research studies seeking to understand neurochemical dysfunction.

Rapid Enhancement of Glutamatergic Neurotransmission in Bipolar Depression Following Treatment with Riluzole

“…Conversely, linear addition of the CRLB values across f1 would unfairly bias our final error estimate by the high CRLB values from the low SNR, higher-frequency spectral extractions, resulting in overinflated error estimates. We found that our weighted average calculation best represents the test-retest metabolite variance observed in repeated measures using this J-resolved technique (Jensen et al, 2009), and is thus the best compromise to providing realistic CRLB error estimates for our summed metabolite values. There were no between-scan CRLB differences.…”

“…We have previously described the details of MRS acquisition and data analysis (Jensen et al, 2009;Ö ngür et al, 2008). Briefly, 1 H-MRS acquisitions were conducted on a 4-T scanner (Varian/UnityInova, Varian, Palo Alto, CA, USA), using a volumetric-birdcage coil (Robarts Research Institute, London, Canada).…”

“…Once all of the 64 J-resolved spectral extractions are fitted, the raw, metabolite integrals for each extraction over the central 50-Hz region in f1 are summed up to produce a final metabolite integral. Our serial 1D quantification approach improves spectral quantification by using all available signals rather than by fitting select single J-resolved extractions (Jensen et al, 2009;Schulte and Boesiger, 2006a;Schulte et al, 2006b), and has been shown to greatly improve the accuracy and precision of separate measurements of the coupled and highly overlapped resonances of glutamate and glutamine. Details of our fitting procedure, including GAMMA generation of theoretical spectra for use as basis sets and fitting of individual spectral extractions, were previously reported (Ö ngür et al, 2008).…”

“…As theorized by several other groups, increased Gln/Glu ratios reflect intensified flux through the glutamate-glutamine cycle and an overall increase in glutamatergic neurotransmitter activity (Igarashi et al, 2001;Iltis et al, 2009;Mlynarik et al, 2008;Ö ngür et al, 2008;Theberge et al, 2003Theberge et al, , 2002. It has recently become possible to measure this ratio, using J-resolved proton MRS ( 1 H-MRS), a sequence that acquires spectra at multiple echo times (TEs), allowing improved metabolite quantification (Jensen et al, 2009). Thus, 1 H-MRS can measure glutamate and glutamine levels separately, allowing calculation of Gln/Glu ratios.…”

The case of the missing glutamine

“…3 T), which theoretically allow concentration measurements for metabolites with strongly coupled protons through 1 H MRS, more and more reports of Gln concentrations have started to emerge in normal and diseased states. An overview of such 1 H MRS studies indicates a majority of normal brain Gln concentration measurements in the 2-mM range (or c Gln /c Glu ¼ 0.2) (7)(8)(9)(10)(11), with some reports also in the 4-mM range (or c Gln /c Glu ¼ 0.4) (3,12).…”