4-T 7Li 3D MR spectroscopy imaging in the brains of bipolar disorder subjects

Abstract

This work demonstrates the first whole brain "high spatial resolution" (7)Li MR spectroscopy imaging in bipolar disorder subjects. The in vivo quantification is validated by a phantom containing 5 mM lithium salt using the identical radiofrequency sequence and imaging protocol. This study is the first demonstration of the (7)Li distribution in the brain of bipolar disorder patients on lithium therapy using a 3D MR spectroscopy imaging approach. The results show that brain lithium level is strongly correlated with serum lithium concentration. The brain-to-serum lithium ratios for the average brain and the local maximum were 0.39 ± 0.08 (r = 0.93) and 0.92 ± 0.16 (r = 0.90), respectively. The lithium distribution is found to be nonuniform throughout the brain for all patients, which is somewhat unexpected and highly intriguing. This uneven distribution is more evident in subjects at a higher therapeutic serum lithium level. This finding may suggest that lithium targets specific brain tissues and/or certain enzymatic and macromolecular sites that are associated with therapeutic effect. Further investigations of bipolar disorder patients on lithium therapy using 3D (7)Li MR spectroscopy imaging are warranted.

Figure 1

Illustration of the 1D-3D FFT approach used in this study. Lithium MRSI was integrated from each and seven individual points in this case. See details in text.

Figure 2

Brain lithium distribution from two subjects with serum lithium of a) 1.0 mM and b) 0.5 mM. The color bar gives the concentration from 0 to 1 mM. c) Three representative spectra obtained by using a single voxel reconstruction technique to illustrate typical spectra for concentrations of 0.8, 0.5, to 0.2 mM from top to bottom, respectively.

Figure 3

Comparison brain lithium maps of one subject who has been scanned three times in two visits separated by 15 weeks. Lithium map a) was obtained on the first visit when serum level was 0.5 mM, while b) and c) were obtained on the second visit when serum level was 0.8 mM.

Figure 4

The correlation (solid lines) between serum lithium level and a) the brain average lithium concentration and b) the brain local maximum lithium concentration for subjects (n=8) whose blood was drawn within 24 hours of the MRS scan. The correlation between serum lithium level and c) the brain average lithium concentration and d) the brain local maximum lithium concentration for all scans (n=22). Note: the number of data points may seem to be less than n since some data points overlap. Data with serum lithium concentration less than 0.3 mM were excluded from the analysis since the exact concentration was not given in the medical report (i.e. it reads < 0.3 mM). The solid lines represent the linear correlation between brain and serum lithium level and slopes give the brain-to-serum lithium ratios, while the dashed lines show the condition when the brain-to-serum lithium ratio is equal to one.