Mapping Changes in Mouse Brain Metabolism with PET/CT

Welch, Andrew; Mingarelli, Marco; Riedel, Gernot; Platt, Bettina

doi:10.2967/jnumed.113.121509

Cited by 26 publications

(19 citation statements)

References 37 publications

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“…Given the lower resolution of μPET in comparison to autoradiography, decreased sensitivity may indeed mask small regional decreases in [ 18 F]FDG uptake between genotypes [ 29 ]. However these discrepancies may also be accounted for by methodological factors [ 30 ] in addition to strain differences. More recently in vivo hypometabolism in amyloidosis models has been described [ 31 – 33 ].…”

Section: Introductionmentioning

confidence: 99%

In vivo molecular neuroimaging of glucose utilization and its association with fibrillar amyloid-β load in aged APPPS1-21 mice

et al. 2015

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IntroductionRadioligand imaging is a powerful in vivo method to assess the molecular basis of Alzheimer’s Disease. We therefore aimed to visualize the pathological deposition of fibrillar amyloid-β and neuronal dysfunction in aged double transgenic mice.MethodsUsing non-invasive positron emission tomography (PET) we assessed brain glucose utilization with [18F]FDG and fibrillar amyloidosis with [11C]PiB and [18F]AV45 in 12 month old APPPS1-21 (n = 10) mice and their age-matched wild-type controls (n = 15). PET scans were analyzed with statistical parametric mapping (SPM) to detect significant differences in tracer uptake between genotypes. After imaging, mice were sacrificed and ex vivo measures of amyloid-β burden with immunohistochemistry as well as glucose utilization with [14C]-2DG autoradiography were obtained as gold standards.ResultsVoxel-wise SPM analysis revealed significantly decreased [18F]FDG uptake in aged APPPS1-21 mice in comparison to WT with the thalamus (96.96 %, maxT = 3.35) and striatum (61.21 %, maxT = 3.29) demonstrating the most widespread reductions at the threshold of p < 0.01. [11C]PiB binding was significantly increased in APPPS1-21 mice, most notably in the hippocampus (87.84 %, maxT = 7.15) and cortex (69.08 %, maxT = 7.95), as detected by SPM voxel-wise analysis at the threshold of p < 0.01. Using the same threshold [18F]AV45 uptake was comparably lower with less significant differences. Compared to their respective ex vivo equivalents [18F]FDG demonstrated significant positive correlation to [14C]2-DG autoradiography (r = 0.67, p <0.0001) while [11C]PiB and [18F]AV45 binding did not correlate to ex vivo immunohistochemistry for amyloid-β (r = 0.25, p = 0.07 and r = 0.17, p = 0.26 respectively). Lastly no correlation was observed between regions of high amyloid burden and those with decreased glucose utilization (r = 0.001, p = 0.99).ConclusionsOur findings support that fibrillar amyloid-β deposition and reduced glucose utilization can be visualized and quantified with in vivo μPET imaging in aged APPPS1-21 mice. Therefore, the combined use of [18F]FDG and amyloid μPET imaging can shed light on the underlying relationship between fibrillar amyloid-β pathology and neuronal dysfunction.

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Section: Introductionmentioning

confidence: 99%

In vivo molecular neuroimaging of glucose utilization and its association with fibrillar amyloid-β load in aged APPPS1-21 mice

et al. 2015

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“…The amount of activity in each of the phantom's structures was adjusted to simulate a 100 μCi injection of 18 F-fluorodeoxyglucose. 75 The simulated phantom was scanned for 10 min. Since the ranges of positrons, even those emitted by 18 F (mean and maximum range of ∼0.6 and ∼2.4 mm, respectively 76,77 ), are equivalent to the predicted scanner resolution, it was necessary to correct the images for this effect.…”

Section: Performance Measurementsmentioning

confidence: 99%

Preclinical positron emission tomography scanner based on a monolithic annulus of scintillator: initial design study

et al. 2017

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Abstract. Positron emission tomography (PET) scanners designed for imaging of small animals have transformed translational research by reducing the necessity to invasively monitor physiology and disease progression. Virtually all of these scanners are based on the use of pixelated detector modules arranged in rings. This design, while generally successful, has some limitations. Specifically, use of discrete detector modules to construct PET scanners reduces detection sensitivity and can introduce artifacts in reconstructed images, requiring the use of correction methods. To address these challenges, and facilitate measurement of photon depth-ofinteraction in the detector, we investigated a small animal PET scanner (called AnnPET) based on a monolithic annulus of scintillator. The scanner was created by placing 12 flat facets around the outer surface of the scintillator to accommodate placement of silicon photomultiplier arrays. Its performance characteristics were explored using Monte Carlo simulations and sections of the NEMA NU4-2008 protocol. Results from this study revealed that AnnPET's reconstructed spatial resolution is predicted to be ∼1 mm full width at half maximum in the radial, tangential, and axial directions. Peak detection sensitivity is predicted to be 10.1%. Images of simulated phantoms (mini-hot rod and mouse whole body) yielded promising results, indicating the potential of this system for enhancing PET imaging of small animals.

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“…Voxel‐based analysis also revealed an increase in [ 18 F]MPPF binding in the hippocampus and/or thalamus in M83 vs WT and KO α‐syn mice. However, different brain regions were identified according to the chosen method . This difference would probably fade if the number of animals was increased.…”

Section: Discussionmentioning

confidence: 99%

PET imaging of the influence of physiological and pathological α‐synuclein on dopaminergic and serotonergic neurotransmission in mouse models

et al. 2018

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Mapping Changes in Mouse Brain Metabolism with PET/CT

Cited by 26 publications

References 37 publications

In vivo molecular neuroimaging of glucose utilization and its association with fibrillar amyloid-β load in aged APPPS1-21 mice

In vivo molecular neuroimaging of glucose utilization and its association with fibrillar amyloid-β load in aged APPPS1-21 mice

Preclinical positron emission tomography scanner based on a monolithic annulus of scintillator: initial design study

PET imaging of the influence of physiological and pathological α‐synuclein on dopaminergic and serotonergic neurotransmission in mouse models

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