Chemical exchange saturation transfer MRI shows low cerebral 2-deoxy-D-glucose uptake in a model of Alzheimer's Disease

Daniele Tolomeo, Edoardo Micotti, Sonia Colombo Serra, Michael Chappell, Anniina Snellman, Gianluigi Forloni, Daniele Tolomeo, Edoardo Micotti, Sonia Colombo Serra, Michael Chappell, Anniina Snellman, Gianluigi Forloni

Abstract

Glucose is the central nervous system's only energy source. Imaging techniques capable to detect pathological alterations of the brain metabolism are useful in different diagnostic processes. Such techniques are also beneficial for assessing the evaluation efficacy of therapies in pre-clinical and clinical stages of diseases. Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) is a possible alternative to positron emission tomography (PET) imaging that has been widely explored in cancer research in humans and animal models. We propose that pathological alterations in brain 2-deoxy-D-glucose (2DG) uptake, typical of neurodegenerative diseases, can be detected with CEST MRI. Transgenic mice overexpressing a mutated form of amyloid precusrsor protein (APP23), a model of Alzheimer's disease, analyzed with CEST MRI showed a clear reduction of 2DG uptake in different brain regions. This was reminiscent of the cerebral condition observed in Alzheimer's patients. The results indicate the feasibility of CEST for analyzing the brain metabolic state, with better image resolution than PET in experimental models.

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Timing of the experiment. (syringe image from https://www.dreamstime.com/stock-illustration-syringe-icon-white-background-image42045561, author: Konstantin Semenov).
Figure 2
Figure 2
Asymmetry enhancement. Mean asymmetry fitted curves over the cortex region of a single WT mouse before and after 2DG injection. Highlighted by the square is the area where the cest enhancement has been evaluated.
Figure 3
Figure 3
Temporal GCE. Group mean ± standard errors (s.e.m.) are visualized and injection time is indicated as zero. ***p 

Figure 4

Graphic representation of the GCE…

Figure 4

Graphic representation of the GCE ( a ) Time course represented as group…

Figure 4
Graphic representation of the GCE (a) Time course represented as group mean images. Baseline is showed as the mean of the first three time points. (b) Voxel wise comparison. T-test on the normalized images representing the GCE 54 minutes after 2DG injection. In red the areas where WT > APP23 with p < 0.05.

Figure 5

DynamicCEST measurements. ( a ,…

Figure 5

DynamicCEST measurements. ( a , b ) Group mean AUC Dyn images normalized…

Figure 5
DynamicCEST measurements. (a,b) Group mean AUCDyn images normalized to the template. (c) group mean dynamic curves obtained by averaging the signal in the cortex. (d) AUCDyn calculated in the cortex area.

Figure 6

Fitting procedure. The left panel…

Figure 6

Fitting procedure. The left panel shows the location of the different compounds. Analysis…

Figure 6
Fitting procedure. The left panel shows the location of the different compounds. Analysis firstly fitted the contribution of water and NOE (part A) and in a second step the other compounds contributions (part B).

Figure 7

Visual comparison of the two…

Figure 7

Visual comparison of the two techniques. ( a ) Single WT mouse PET…

Figure 7
Visual comparison of the two techniques. (a) Single WT mouse PET imagerepresenting 18F-FDG uptake 50–60 minutes after injection with a voxel size of 0.78 × 0.78 × 0.8 mm3; (b) image representing the GCE of a single mouse 1 hour after the 2DG injection, it has a voxel size of 0.35 × 0.35 × 2 mm3; (c) PET image coregistered with computed tomography image and superimposed on a general mouse brain MRI template; (d) GCE image coregistered and superimposed on the in-house template. SUV = standard uptake value; GCE = glucose cest enhancement.
All figures (7)
Figure 4
Figure 4
Graphic representation of the GCE (a) Time course represented as group mean images. Baseline is showed as the mean of the first three time points. (b) Voxel wise comparison. T-test on the normalized images representing the GCE 54 minutes after 2DG injection. In red the areas where WT > APP23 with p < 0.05.
Figure 5
Figure 5
DynamicCEST measurements. (a,b) Group mean AUCDyn images normalized to the template. (c) group mean dynamic curves obtained by averaging the signal in the cortex. (d) AUCDyn calculated in the cortex area.
Figure 6
Figure 6
Fitting procedure. The left panel shows the location of the different compounds. Analysis firstly fitted the contribution of water and NOE (part A) and in a second step the other compounds contributions (part B).
Figure 7
Figure 7
Visual comparison of the two techniques. (a) Single WT mouse PET imagerepresenting 18F-FDG uptake 50–60 minutes after injection with a voxel size of 0.78 × 0.78 × 0.8 mm3; (b) image representing the GCE of a single mouse 1 hour after the 2DG injection, it has a voxel size of 0.35 × 0.35 × 2 mm3; (c) PET image coregistered with computed tomography image and superimposed on a general mouse brain MRI template; (d) GCE image coregistered and superimposed on the in-house template. SUV = standard uptake value; GCE = glucose cest enhancement.

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