Elucidating the complementarity of resting-state networks derived from dynamic [18F]FDG and hemodynamic fluctuations using simultaneous small-animal PET/MRI

Functional connectivity (FC) and resting-state network (RSN) analyses using functional magnetic resonance imaging (fMRI) have evolved into a growing field of research and have provided useful biomarkers for the assessment of brain function in neurological disorders. However, the underlying mechanisms of the blood oxygen level-dependant (BOLD) signal are not fully resolved due to its inherent complexity. In contrast, [18F]fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) has been shown to provide a more direct measure of local synaptic activity and may have additional value for the readout and interpretation of brain connectivity. We performed an RSN analysis from simultaneously acquired PET/fMRI data on a single-subject level to directly compare fMRI and [18F]FDG-PET-derived networks during the resting state. Simultaneous [18F]FDG-PET/fMRI scans were performed in 30 rats. Pairwise correlation analysis, as well as independent component analysis (ICA), were used to compare the readouts of both methods. We identified three RSNs with a high degree of similarity between PET and fMRI-derived readouts: the default-mode-like network (DMN), the basal ganglia network and the cerebellar-midbrain network. Overall, [18F]FDG connectivity indicated increased integration between different, often distant, brain areas compared to the results indicated by the more segregated fMRI-derived FC. Additionally, several networks exclusive to either modality were observed using ICA. These networks included mainly bilateral cortical networks of a limited spatial extent for fMRI and more spatially widespread networks for [18F]FDG-PET, often involving several subcortical areas.This is the first study using simultaneous PET/fMRI to report RSNs subject-wise from dynamic [18F]FDG tracer delivery and BOLD fluctuations with both independent component analysis (ICA) and pairwise correlation analysis in small animals. Our findings support previous studies, which show a close link between local synaptic glucose consumption and BOLD-fMRI-derived FC. However, several brain regions were exclusively attributed to either [18F]FDG or BOLD-derived networks underlining the complementarity of this hybrid imaging approach, which may contribute to the understanding of brain functional organization and could be of interest for future clinical applications

Quantitative Correlation at the Molecular Level of Tumor Response to Docetaxel by Multimodal Diffusion-Weighted Magnetic Resonance Imaging and [F-18]FDG/[F-18]FLT Positron Emission Tomography

We aimed to quantitatively characterize the treatment effects of docetaxel in the HCT116 xenograft mouse model, applying diffusion-weighted magnetic resonance imaging (MRI) and positron emission tomography (PET) using 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) and 3′-deoxy-3′-[ 18 F]-fluorothymidine ([ 18 F]FLT). Mice were imaged at four time points over 8 days. Docetaxel (15 mg/kg) was administered after a baseline scan. Voxel-wise scatterplots of PET and apparent diffusion coefficient (ADC) data of tumor volumes were evaluated with a threshold cluster analysis and compared to histology (GLUT1, GLUT3, Ki67, activated caspase 3a). Compared to the extensive tumor growth observed in the vehicle-treated group (from 0.32 ± 0.21 cm 3 to 0.69 ± 0.40 cm 3 ), the administration of docetaxel led to tumor growth stasis (from 0.32 ± 0.20 cm 3 to 0.45 ± 0.23 cm 3 ). The [ 18 F]FDG/ADC cluster analysis and the evaluation of peak histogram values revealed a significant treatment effect matching histology as opposed to [ 18 F]FLT/ADC. [ 18 F]FLT uptake and the Ki67 index were not in good agreement. Our voxel-based cluster analysis uncovered treatment effects not seen in the separate inspection of PET and MRI data and may be used as an independent analysis tool. [ 18 F]FLT/ADC cluster analysis could still point out the treatment effect; however, [ 18 F]FDG/ADC reflected the histology findings in higher agreement

Assessment of murine brain tissue shrinkage caused by different histological fixatives using magnetic resonance and computed tomography imaging

Especially for neuroscience and the development of new biomarkers, a direct correlation between in vivo imaging and histology is essential. However, this comparison is hampered by deformation and shrinkage of tissue samples caused by fixation, dehydration and paraffin embedding. We used magnetic resonance (MR) imaging and computed tomography (CT) imaging to analyze the degree of shrinkage on murine brains for various fixatives. After in vivo imaging using 7 T MRI, animals were sacrificed and the brains were dissected and immediately placed in different fixatives, respectively: zinc-based fixative, neutral buffered formalin (NBF), paraformaldehyde (PFA), Bouin-Holland fixative and paraformaldehyde-lysine-periodate (PLP). The degree of shrinkage based on mouse brain volumes, radiodensity in Hounsfield units (HU), as well as non-linear deformations were obtained. The highest degree of shrinkage was observed for PLP (68.1%, P<0.001), followed by PFA (60.2%, P<0.001) and NBF (58.6%, P<0.001). The zinc-based fixative revealed a low shrinkage with only 33.5% (P<0.001). Compared to NBF, the zinc-based fixative shows a slightly higher degree of deformations, but is still more homogenous than PFA. Tissue shrinkage can be monitored non-invasively with CT and MR. Zinc-based fixative causes the smallest degree of brain shrinkage and only small deformations and is therefore recommended for in vivo ex vivo comparison studies