Synopsis

The different relaxation times of the water and the fat compartment in human lumbar vertebrae make it necessary to determine these values for a correct calculation of the fat fraction, which is used as a biomarker for various applications. This study investigates the reproducibility of relaxometry in human lumbar vertebrae to serve as a basis for future studies. Furthermore, factors like age, sex, and physique are investigated for their influence on the derived T₁ and T₂ values to investigate whether relaxation times of the fat and water compartments can serve as biomarkers in addition to the fat fraction.

Purpose

The quantification of the fat content of lumbar vertebrae using ¹H MR spectroscopy (MRS) is used as a tool for the determination of bone quality and the investigation of related parameters. The percentage fat fraction was shown to be connected to bone mineral density¹, osteoporosis², abdominal adipose tissue³ or bone health⁴. If not corrected, the quantification results are influenced by the relaxation times of the fat and water compartments, respectively, which are basically different^5,6. Recently, the need to correct for T₂ decay on MRS-based fat quantification was investigated⁷, concluding that the fat fraction should always be determined using a multi-TE approach.

This study aims to provide a basis for the estimation of the accuracy of relaxometry results provided by MRS measurements by investigating the reproducibility of the method. For this purpose T₁ and T₂ values of human lumbar vertebrae are quantified using a multi-TE/multi-TR MRS protocol and repeated measurements. Furthermore, influences introduced by volunteer sex, age and physique are investigated to identify potential biomarkers in addition to the fat fraction.

Material and Methods

Thirty healthy volunteers (15f, μ=27.19y, σ=6.11y; 15m, μ=30.07y, σ=6.59y) with no history of bone disease or vertebral abnormalities filled out a form on nutrition and exercise and were scanned in supine position on a clinical 3T scanner. The volume of interest was positioned in the center of vertebral bodies L2 and L3 for ¹H-MRS using a STEAM-SVS sequence (20x20x20mm³, TE/TR=20,40,60,80,100/5000ms for T₂ determination, TE/TR=20/600,1000,2000,3000,10 000ms for T₁ determination, AVG=10). After the measurements the subjects were removed from the scanner and registered again to repeat the protocol two times.

Spectra were analyzed in the time-frequency domain using jMRUI software⁸ and the AMARES algorithm⁹. Five resonances were identified in the acquired spectra: CH₃, CH₂, CH₂CH=CH, water, and CH=CH. These five peaks were included in the AMARES algorithm using multiple peaks for the water and the CH₂ resonances to account for the non-Lorentzian shape of the peaks. Values for T₁ and T₂ were obtained fitting $$I=I_0 \cdot \left( 1-e^{-\frac{\text{T}_\text{R}}{\text{T}_1}} \right) e^{-\frac{\text{T}_\text{E}}{T_2}}$$ to the exported data using MATLAB and assuming a common relaxation time for all fat peaks.

Reproducibility was investigated comparing the results of the first measurement to the values derived from the remaining measurements and performing a linear regression. Statistical significance was tested with a paired-sample t-test. Finally, relaxation times were correlated with volunteer age, sex and physical parameters.

Results

Figure 1 compares the relaxation times of the water compartment for each first measurement of each volunteer and vertebra (T_{2,w (first)}, T_{1,w (first)}) with the results of the remaining two measurements (T_{2,w (repeat)}, T_{1,w (repeat)}). Figure 2 shows the same analysis for the fat compartment (values for correlation coefficient r are shown in respective figures).

Figure 3 plots T_2,w, T_1,w and T_2,f against volunteer age separated by sex. Averaged values of men and women differ significantly (p<0.01) for all three relaxation times. The T₂ times of both compartments show a pronounced negative correlation with age for male volunteers.

Figure 4 shows the correlation between relaxation times and volunteer physique. All values show a negative correlation with volunteer height and weight and a positive correlation with sports activities.

Discussion and Conclusion

The presented results show an excellent reproducibility of relaxometry for the water compartment and for T₂ of the fat compartment. For T₁ of fat the correlation factor is decreased and the correlation line deviates noticeably from identity; therefore, this quantity was not investigated further.

Since T₂ effects represent the main influence on MRS data of human lumbar vertebrae, the high reproducibility for these values is an important basis for future studies applying T₂-correction to acquired spectra. Furthermore, the high reproducibility of T_2,w is of special interest, as this quantity is considered to be an additional parameter sensitive to the composition of the water compartment⁷.

Sex-specific differences were found for all three investigated relaxation times. For T₂ only men showed increased correlation with age. As the fat fraction is well-known to increase with age¹⁰, this underlines the necessity to correct for T₂ effects, since not correcting would introduce a sex-dependent bias into the age-related increase of the fat fraction. Additionally, the strong sex-specific difference in T_1,w emphasizes the need for long enough repetition times to avoid different T₁-weighting effects.

The correlations of all relaxation times with volunteer height and weight also suggest that using average T₂ times for correction¹¹ will introduce additional uncertainties. Finally, since more athletic people show higher values for all relaxation times, the presented results suggest that relaxation times may be considered as a marker for bone health.

Acknowledgements

References

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