Article Figures & Data
Figures
- FIG 1.
1H-MR spectra from the DN in 1 patient from both case and control groups. Red lines represent the TARQUIN fits. MRS at TE = 35 ms shows elevated mIns peaks at 3.5 ppm, creatine peaks at 3 ppm, lactate peaks at 1.3 ppm, and Glx peaks at 2.1–2.4 ppm.
- FIG 2.
Boxplots of the metabolites. Differences between case and control groups.
- FIG 3.
The astrocyte-neuron lactate shuttle and glutamate-glutamine cycles. After traveling through the endothelial cells, glucose (Glc) enters the astrocytes via Glc transporter 1 (GlcT1). It is metabolized to pyruvate and then lactate by lactate dehydrogenase (LDH5). The lactate is carried outside the astrocyte and inside the neuron via the monocarboxylate transporters (MCTs). The lactate inside the neuron is metabolized in the oxygen pathway. Glutamate (Glu) molecules released from presynaptic neurons are transported into the astrocytes through Na+-dependent channels. In astrocytes, the Glu is transformed into Glutamine (Gln) or α-ketoglutarate to perform oxygen metabolism in the Krebs cycle. ATP indicates adenosine triphosphate; ADP, adenosine di-phosphate; P, phosphate; GluR, glutamate receptor; OH/HCO3, hydroxide/bicarbonate; K+, potassium; GLT, glutamate transporter; PGK, phosphoglycerate kinase; ATPase, adenosine triphosphatase.
Tables
Variable Case (n = 10) Control 1 (n = 10) Control 2 (n = 10) Control 3 (n = 10) Age (mean) (yr) 43.4 (SD, 8.6) 36.7 (SD, 10.2) 31.7 (SD, 10.0) 30.7 (SD, 2.9) Sex (female) 8 (80%) 7 (70%) 9 (90%) 3 (30%) - Table 2:
Absolute mean metabolite concentrations and calculated ratios in the DN in all 4 studied groups
Variable Studied Groups Comparisons (P Values) Case Control 1 Control 2 Control 3 Among 4 Groups Case vs Control 3 Case vs. Controls 1 and 2 NAA 43.0 (SD, 7.3) 44.8 (SD, 11.7) 45.3 (SD, 10.5) 36.7 (SD, 10.8) .24 .15 .59 Choline 32.8 (SD, 9.7) 25.7 (SD, 11.5) 28.8 (SD, 5.8) 23.5 (SD, 11.8) .20 .07 .27 Cr on short TE 11.6 (SD, 1.3) 9.3 (SD, 4.3) 10.1 (SD, 1.8) 8.9 (SD, 3.3) .21 .04a .06 Lactate on short TE 4.6 (SD, 2.2) 2.3 (SD, 2.1) 2.1 (SD, 1.3) 3.2 (SD, 2.8) .15 .33 .02a mIns 2.7 (SD, 0.7) 1.5 (SD, 0.8) 2.4 (SD, 1.2) 1.7 (SD, 1.2) .04a .04a .51 Glx 3.5 (SD, 1.7) 3.7 (SD, 1.7) 4.9 (SD, 1.8) 4.5 (SD, 2.7) .36 .35 .10 Lipid 0.9 4.8 (SD, 2.0) 3.9 (SD, 2.4) 4.1 (SD, 1.8) 3.5 (SD, 2.2) .65 .22 .44 Lipid 1.3 5.2 (SD, 2.7) 5.8 (SD, 4.1) 6.5 (SD, 3.6) 5.7 (SD, 3.0) .92 .73 .42 NAA/Cr 1.7 (SD, 0.5) 2.1 (SD, 0.9) 1.6 (SD, 0.6) 2.8 (SD, 2.0) .10 .11 .73 Lactate/Cr on short TE 0.4 (SD, 0.2) 0.3 (SD, 0.2) 0.2 (SD, 0.2) 0.3 (SD, 0.2) .25 .50 .04a mIns/Cr 0.2 (SD, 0.1) 0.2 (SD, 0.2) 0.2 (SD, 0.1) 0.2 (SD, 0.1) .68 .16 .99 Glx/Cr 0.3 (SD, 0.1) 0.5 (SD, 0.3) 0.5 (SD, 0.2) 0.5 (SD, 0.3) .35 .08 .04a Lipid 0.9/Cr 0.4 (SD, 0.3) 0.4 (SD, 0.2) 0.4 (SD, 0.1) 0.4 (SD, 0.1) .91 .50 .76 Lipid 1.3/Cr 0.4 (SD, 0.2) 0.9 (SD, 1.0) 0.6 (SD, 0.4) 0.8 (SD, 0.4) .43 .05 .19 ↵a Statistically significant.
- Table 3:
Relative mean metabolite concentrations and calculated ratios in DN/pons in all 4 studied groups
Variable Studied Groups Comparisons (P Values) Case Control 1 Control 2 Control 3 Among 4 Groups Case vs. Control 3 Case vs Controls 1 and 2 NAA 0.7 (SD, 0.1) 1.1 (SD, 0.3) 0.8 (SD, 0.2) 0.9 (SD, 0.5) .13 .38 .36 Choline 0.8 (SD, 0.3) 0.8 (SD, 0.4) 0.9 (SD, 0.3) 0.8 (SD, 0.4) .98 .97 .70 Cr on short TE 1.4 (SD, 0.5) 1.1 (SD, 0.6) 1.0 (SD, 0.2) 1.8 (SD, 2.5) .54 .61 .03a Lactate on short TE 4.3 (SD, 7.4) 1.5 (SD, 2.0) 1.0 (SD, 1.6) 0.2 (SD, 0.4) .32 .25 .26 mIns 0.9 (SD, 0.5) 0.5 (SD, 0.4) 1.3 (SD, 1.5) 1.1 (SD, 1.2) .35 .69 .42 Glx 1.2 (SD, 0.8) 1.0 (SD, 0.6) 1.3 (SD, 1.0) 1.3 (SD, 0.6) .84 .72 .81 Lipid 0.9 1.3 (SD, 0.8) 1.1 (SD, 0.7) 0.8 (SD, 0.5) 1.3 (SD, 1.0) .43 .96 .13 Lipid 1.3 1.4 (SD, 1.0) 1.0 (SD, 1.3) 1.4 (SD, 1.0) 1.0 (SD, 0.5) .74 .33 .93 NAA/Cr 0.7 (SD, 0.2 0.8 (SD, 0.4) 0.6 (SD, 0.3) 0.9 (SD, 0.5) .29 .44 .15 Lactate/Cr on short TE 0.2 (SD, 0.1) 0.2 (SD, 0.1) 0.1 (SD, 0.1) 0.2 (SD, 0.1) .95 .56 .61 mIns/Cr 0.6 (SD, 0.3) 0.4 (SD, 0.2) 1.3 (SD, 1.5) 0.7 (SD, 0.5) .11 .56 .20 Glx/Cr 1.1 (SD, 0.6) 0.9 (SD, 0.6) 1.5 (SD, 1.5) 1.2 (SD, 0.8) .67 .58 .48 Lipid 0.9/Cr 1.0 (SD, 0.6) 1.0 (SD, 0.5) 0.8 (SD, 0.4) 1.0 (SD, 0.7) .68 .83 .33 Lipid 1.3/Cr 1.5 (SD, 0.6) 1.3 (SD, 0.6) 1.8 (SD, 1.0) 0.8 (SD, 0.5) .17 .04a .45 ↵a Statistically significant.
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