Li An^{1}, Shizhe Li^{1}, and Jun Shen^{1}

^{1}National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United States

### Synopsis

**A data acquisition and
quantification approach is proposed for simultaneous measurement of concentration,
T**_{1}, and T_{2} of metabolites. The concentration, T_{1}, and T_{2}
of NAA, creatine, choline, glutamate and myo-inositol were determined reliably in
less than 9 min using single voxel MRS at 7 Tesla.### Introduction

Knowledge of metabolite T

_{1} and T

_{2} relaxation times can be very valuable in the investigation of intracellular
micro-environment changes caused by diseases (1). In this work, we propose to simultaneously
measure metabolite concentrations and relaxation times using a point resolved
spectroscopy (PRESS) sequence with multiple echo times (TEs) and inversion-recovery
times (TIs). The whole set of data acquired with different TIs and TEs are modeled
by linear combinations of a single set of basis functions to compute metabolite
concentrations and relaxation times (T

_{1} and T

_{2}).

### Methods

Two broadband hyperbolic
secant pulses were added to a single-voxel PRESS sequence with a variable TE.
The first hyperbolic secant pulse had a fixed TI of 2500 ms and a flip angle of
90^{°}, while the second one has a variable flip angle and TI. The following nine
TE values were used: 58, 68, 78, 88, 98, 108, 178, 198, and 218 ms. At TE of 68
ms, the second hyperbolic secant pulse
was varied using six different settings: (1) no inversion; (2) TI = 1500 ms, flip angle = 160.2°;
(3) TI = 900 ms, flip angle = 160.2°; (4) TI = 471 ms, flip angle = 160.2°;
(5) TI = 244 ms, flip angle = 142.6°; and (6) TI = 81 ms, flip angle
= 160.2°. The position and
flip angle of the second hyperbolic secant pulse were chosen to provide
sufficiently different T_{1} weighting and to optimize water suppression at the
same time. For TEs other than 68 ms, the second inversion pulse was turned off.
The first 90° hyperbolic secant pulse
was used to ensure that the longitudinal magnetization was zero at 2500 ms
prior to the excitation pulse of the PRESS sequence for all repetitions.

Two healthy
volunteers were recruited for the study. MRS data were collected using the
proposed pulse sequence from the medial prefrontal cortex of the two
volunteers. A repetition time of 3 s and 12 signal averages were used for each (TE,
TI) setting. The total scan time was 8.9 minutes. Basis functions
of ten brain metabolites (see Table 1) at the nine selected TE values were
numerically computed using an in-house developed program based on the GAMMA C++
library. The acquired time domain data were Fourier transformed into the frequency
domain to obtain spectra for all 14 different (TE, TI) settings (see Fig. 1). These
14 spectra were put into one large vector and were fitted together by linear
combinations of the basis functions using an in-house developed fitting program
which models the baseline using a spline function. In the fitting process, mono-exponential
functions were used to model T_{1} and T_{2} relaxations.

### Results

The reconstructed spectra and fitted spectra for
all 14 (TE, TI) settings are displayed in Fig. 1. Metabolite concentrations and
the corresponding Cramer-Rao lower bounds (CRLB) are given in Table 1. Metabolite
T

_{1} and T

_{2} values are given in Table 2. Unreliable metabolite T

_{1} and T

_{2} values
are not listed. The spectrum corresponding to TE of 68 ms without the second hyperbolic
secant pulse was also quantified for comparison. The corresponding metabolite concentrations
and normalized CRLB values are given in Table 3. As shown by the CRLB values in
Table 1 and Table 3, the proposed method resulted in much lower or comparable CRLBs
for most major metabolites (NAA, tCr, tCho, Glu, Gln, GSH, GABA, NAAG, and mI).
Most importantly, the proposed method allows simultaneous determination of T

_{1}
and T

_{2} of the major metabolites which is not possible for a single TE data
acquisition.

### Discussion and Conclusions

A new approach for acquiring and quantifying single
voxel MRS data was proposed to allow simultaneous measurement of metabolite
concentrations and relaxation times. By changing the sequence parameters,
different spectral information is generated with different
metabolite-metabolite and metabolite-baseline interactions. Therefore, the
overall information content is increased over a single sequence with fixed TE
and TI. As a result, it is possible to improve the reliability of measurement
for metabolites of interest without increasing the total scan time. In the meantime,
metabolite T

_{1} and T

_{2} are simultaneously determined.
To
our best knowledge, this is the first time that the concentration, T

_{1} and T

_{2} of
metabolites are simultaneously measured

*in vivo*. Demonstration of this unique feasibility
opens the possibilities of further improving this technique and measuring all
three parameters in patient studies.

### Acknowledgements

This research was supported by
the Intramural Research Program of the National Institute of
Mental Health.### References

1. Bracken
*et al.*,
PsychiatryResearch:Neuroimaging 213 (2013):142–153.