Transverse relaxation of cerebrospinal fluid depends on glucose concentration

Abstract

Purpose: To evaluate the biophysical processes that generate specific T₂ values and their relationship to specific cerebrospinal fluid (CSF) content.

Materials and methods: CSF T_2s were measured ex vivo (14.1T) from isolated CSF collected from human, rat and non-human primate. CSF T_2s were also measured in vivo at different field strength in human (3 and 7T) and rodent (1, 4.7, 9,4 and 11.7T) using different pulse sequences. Then, relaxivities of CSF constituents were measured, in vitro, to determine the major molecule responsible for shortening CSF T₂ (2s) compared to saline T₂ (3s). The impact of this major molecule on CSF T₂ was then validated in rodent, in vivo, by the simultaneous measurement of the major molecule concentration and CSF T₂.

Results: Ex vivo CSF T₂ was about 2.0s at 14.1T for all species. In vivo human CSF T₂ approached ex vivo values at 3T (2.0s) but was significantly shorter at 7T (0.9s). In vivo rodent CSF T₂ decreased with increasing magnetic field and T₂ values similar to the in vitro ones were reached at 1T (1.6s). Glucose had the largest contribution of shortening CSF T₂in vitro. This result was validated in rodent in vivo, showing that an acute change in CSF glucose by infusion of glucose into the blood, can be monitored via changes in CSF T₂ values.

Conclusion: This study opens the possibility of monitoring glucose regulation of CSF at the resolution of MRI by quantitating T₂.

Keywords: CSF; Human; MRI; Monkey; Relaxation time; Rodent.

Fig. 1.

In vivo human and rodent CSF T₂ measurement. Human imaging was performed on a 3 T Siemens Skyra and rodent imaging on a 4.7 T Bruker. Heavily T₂-w images are shown in panel A (TE = 752 ms) and C (TE = 384 ms). B. Human T₂ mapping was performed using a FSE sequence with TR = 3500 ms, TE(2) = 11/101 ms, in-plane resolution 0.5 mm, and slice thickness 3 mm. D. Rodent T₂ mapping was performed using a MSME sequence, TR = 4000 ms, TE(20) = 10.95/219 ms (intervals of 10.95 ms), in-plane resolution 0.3 mm, and slice thickness 1 mm. ROIs were manually drawn in the lateral ventricles and the resulting T₂ values were 887 ± 50 ms for human CSF and 174 ± 27 for rodent CSF.

Fig. 2.

In vivo human and rodent CSF T₂ measurement at different field strength. A. CSF T₂ was measured at different field strengths. In humans, T₂ mapping was performed at 7 T and 3 T. Images show an apparently longer CSF T₂ at 3 T than at 7 T (according to the color scale). The blue boxes represent the ROIs drown in the lateral ventricles. B. In rodent, spectroscopic sequences were used to measure CSF T₂ of the whole head at 11.7 T, 9.4 T, 4.7 T, and 1 T. There are 3 peaks in the spectra, the first corresponding to parenchyma with very short T₂ (0–0.1 s), the second to fat with short T₂ (0.1–0.2 s), and the last to CSF with the longest T₂ (0.3–2 s). C. Quantification of CSF T₂ in vivo shows longer T₂ values at low field in both Human and rodent. For rodent, CSF T₂ post mortem got longer at higher field likely due to CSF flow in the brain/head gradients.

Fig. 3.

R₂ differences between saline, ex vivo and in vivo rodent and Human CSF at different field. A. Rodent CSF and saline T₂ measurement were performed using a multi-echo CPMG sequence with TR = 10,000 ms at 1 T and TR = 20,000 ms at 4.7 T, 9.4 T and 14.1 T; TE(1024) = 2/2048 ms (intervals of 2 ms) at 1, 4.7 and 9.4 T and TE(2048) = 2/2048 ms (intervals of 1 ms) at 14.1 T. Scans were performed at 1, 4.7. 9.4 and 11.7 T for in vivo data and at 14.1 and 4.7 T for ex vivo data. B. Human CSF T₂ measurements were performed using two different sequences. In vivo CSF T₂ measurements were performed by a multi-contrast spin echo sequence with TR = 10,000 ms and 32 TEs equally spaced between 30.5 and 945.5 ms. Ex vivo CSF and saline T₂ measurements were performed using the same multi-echo CPMG sequence detailed above for rodent.

Fig. 4.

CSF compounds that can substantially change human CSF T₂ relaxivity. All T₂ measurements were performed on a 14.1 T Bruker MRI system at 37 °C using a CPMG sequence with TE(2048) = 2/2048 ms (intervals of 1 ms). A. Example of ΔR₂ plotted against glucose (n = 3) and BSA concentration (n = 3). The regression equation is written for each graph, showing the relaxivity r₂ for each species represented in this figure. B. Table showing the relaxivity r₂, the concentration and the calculated R₂ in human CSF for each element. Relaxivity r₂ was computed for each species (proteins, metals and glucose) from the plot between ΔR₂ and solute concentration. The concentration of metals in human CSF was determined by IC-PMS and the one of BSA and glucose was quantified using colorimetric methods. Using r₂ and concentration values, we calculated the R₂ for each element in human CSF (example for the BSA: R₂ = r₂ × [BSA concentration]; R₂ = 7.6 × 8.9.10⁻³; R₂ = 6.8.10⁻² s⁻¹).

Fig. 5.

Effect of chemical exchange on rodent CSF R₂ values. T₂ measurement of rodent CSF in vivo and ex vivo, saline, glucose and BSA solutions were performed using a multi-echo CPMG sequence with TR = 10,000 ms at 1 T and TR = 20,000 ms at 4.7 T, 9.4 T and 14.1 T; TE(1024) = 2/2048 ms (intervals of 2 ms) at 1, 4.7 and 9.4 T and TE(2048) = 2/2048 ms (intervals of 1 ms) at 14.1 T. Scans were performed at 1, 4.7. 9.4 and 11.7 T for in vivo data and at 14.1 and 4.7 T for ex vivo data as well as for saline, glucose and BSA solutions. Glucose and BSA solutions were prepared in saline at a concentration of 4 mM and 0.01 mM, respectively, to mimic CSF physiological values. The pH of both, glucose and BSA solutions is at 7 and it was changed to be acidic (pH 2) and basic (pH 10).

Fig. 6.

CSF T₂ depends on glycemia A. Experimental scheme. Surgery was performed under anesthesia to catheterize both jugular vein and femoral artery. Black arrow corresponds to serum glucose concentration measurement via the femoral artery. The rat is kept within the MRI scanner (4.7 T Bruker MRI system). B. CSF R₂ values measured at 3 time point as shown in A using the spectroscopy sequence, plotted against serum glucose concentration values (n = 9 rats). C. CSF R₂ values measured at the end of the experiment, just before CSF collection, plotted against CSF glucose concentration values (n = 7). CSF was collected just after the last MRI acquisition and before euthanasia. D. Glycorrhachia as a function of glycemia (n = 7 rats). The ratio of glycorrhachia to glycemia is 0.42.