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

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

One-pot synthesis and characterization of size-controlled bimagnetic FePt-iron oxide heterodimer nanocrystals.

A one-pot, two-step colloidal strategy to prepare bimagnetic hybrid nanocrystals (HNCs), comprising size-tuned fcc FePt and inverse spinel cubic iron oxide domains epitaxially arranged in a heterodimer configuration, is described. The HNCs have been synthesized in a unique surfactant environment by temperature-driven sequential reactions, involving the homogeneous nucleation of FePt seeds and the subsequent heterogeneous growth of iron oxide. This self-regulated mechanism offers high versatility in the control of the geometric features of the resulting heterostructures, circumventing the use of more elaborate seeded growth techniques. It has been found that, as a consequence of the exchange coupling between the two materials, the HNCs exhibit tunable single-phase-like magnetic behavior, distinct from that of their individual components. In addition, the potential of the heterodimers as effective contrast agents for magnetic resonance imaging techniques has been examined

Single severe traumatic brain injury produces progressive pathology with ongoing contralateral white matter damage one year after injury

There is increasing recognition that traumatic brain injury (TBI) may initiate long-term neurodegenerative processes, particularly chronic traumatic encephalopathy. However, insight into the mechanisms transforming an initial biomechanical injury into a neurodegenerative process remain elusive, partly as a consequence of the paucity of informative pre-clinical models. This study shows the functional, whole brain imaging and neuropathological consequences at up to one year survival from single severe TBI by controlled cortical impact in mice. TBI mice displayed persistent sensorimotor and cognitive deficits. Longitudinal T2 weighted magnetic resonance imaging (MRI) showed progressive ipsilateral (il) cortical, hippocampal and striatal volume loss, with diffusion tensor imaging demonstrating decreased fractional anisotropy (FA) at up to one year in the il-corpus callosum (CC: − 30%) and external capsule (EC: − 21%). Parallel neuropathological studies indicated reduction in neuronal density, with evidence of microgliosis and astrogliosis in the il-cortex, with further evidence of microgliosis and astrogliosis in the il-thalamus. One year after TBI there was also a decrease in FA in the contralateral (cl) CC (− 17%) and EC (− 13%), corresponding to histopathological evidence of white matter loss (cl-CC: − 68%; cl-EC: − 30%) associated with ongoing microgliosis and astrogliosis. These findings indicate that a single severe TBI induces bilateral, long-term and progressive neuropathology at up to one year after injury. These observations support this model as a suitable platform for exploring the mechanistic link between acute brain injury and late and persistent neurodegeneration

Quantitative MRI Harmonization to Maximize Clinical Impact: The RIN-Neuroimaging Network

Neuroimaging studies often lack reproducibility, one of the cardinal features of the scientific method. Multisite collaboration initiatives increase sample size and limit methodological flexibility, therefore providing the foundation for increased statistical power and generalizable results. However, multisite collaborative initiatives are inherently limited by hardware, software, and pulse and sequence design heterogeneities of both clinical and preclinical MRI scanners and the lack of benchmark for acquisition protocols, data analysis, and data sharing. We present the overarching vision that yielded to the constitution of RIN-Neuroimaging Network, a national consortium dedicated to identifying disease and subject-specific in-vivo neuroimaging biomarkers of diverse neurological and neuropsychiatric conditions. This ambitious goal needs efforts toward increasing the diagnostic and prognostic power of advanced MRI data. To this aim, 23 Italian Scientific Institutes of Hospitalization and Care (IRCCS), with technological and clinical specialization in the neurological and neuroimaging field, have gathered together. Each IRCCS is equipped with high- or ultra-high field MRI scanners (i.e., ≥3T) for clinical or preclinical research or has established expertise in MRI data analysis and infrastructure. The actions of this Network were defined across several work packages (WP). A clinical work package (WP1) defined the guidelines for a minimum standard clinical qualitative MRI assessment for the main neurological diseases. Two neuroimaging technical work packages (WP2 and WP3, for clinical and preclinical scanners) established Standard Operative Procedures for quality controls on phantoms as well as advanced harmonized quantitative MRI protocols for studying the brain of healthy human participants and wild type mice. Under FAIR principles, a web-based e-infrastructure to store and share data across sites was also implemented (WP4). Finally, the RIN translated all these efforts into a large-scale multimodal data collection in patients and animal models with dementia (i.e., case study). The RIN-Neuroimaging Network can maximize the impact of public investments in research and clinical practice acquiring data across institutes and pathologies with high-quality and highly-consistent acquisition protocols, optimizing the analysis pipeline and data sharing procedures

Longitudinal Tracking of Human Fetal Cells Labeled with Super Paramagnetic Iron Oxide Nanoparticles in the Brain of Mice with Motor Neuron Disease

Stem Cell (SC) therapy is one of the most promising approaches for the treatment of Amyotrophic Lateral Sclerosis (ALS). Here we employed Super Paramagnetic Iron Oxide nanoparticles (SPIOn) and Hoechst 33258 to track human Amniotic Fluid Cells (hAFCs) after transplantation in the lateral ventricles of wobbler (a murine model of ALS) and healthy mice. By in vitro, in vivo and ex vivo approaches we found that: 1) the main physical parameters of SPIOn were maintained over time; 2) hAFCs efficiently internalized SPIOn into the cytoplasm while Hoechst 33258 labeled nuclei; 3) SPIOn internalization did not alter survival, cell cycle, proliferation, metabolism and phenotype of hAFCs; 4) after transplantation hAFCs rapidly spread to the whole ventricular system, but did not migrate into the brain parenchyma; 5) hAFCs survived for a long time in the ventricles of both wobbler and healthy mice; 6) the transplantation of double-labeled hAFCs did not influence mice survival

A systems-level analysis highlights microglial activation as a modifying factor in common forms of human epilepsy

The common human epilepsies are associated with distinct patterns of reduced cortical thickness, detectable on neuroimaging, with important clinical consequences. To explore underlying mechanisms, we layered MRI-based cortical structural maps from a large-scale epilepsy neuroimaging study onto highly spatially-resolved human brain gene expression data, identifying >2,500 genes overexpressed in regions of reduced cortical thickness, compared to relatively-protected regions. The resulting set of differentially-expressed genes shows enrichment for microglial markers, and in particular, activated microglial states. Parallel analyses of cell-specific eQTLs show enrichment in human genetic signatures of epilepsy severity, but not epilepsy causation. Post mortem brain tissue from humans with epilepsy shows excess activated microglia. In an experimental model, depletion of activated microglia prevents cortical thinning, but not the development of chronic seizures. These convergent data strongly implicate activated microglia in cortical thinning, representing a new dimension for concern and disease modification in the epilepsies, potentially distinct from seizure control

A comparative VBM study of longitudinal neuroanatomical changes in AD transgenic mouse models

Purpose/Introduction: Neurodegeneration and signs of atrophy in brain areas such as the hippocampus and entorhinal cortex are typical for Alzheimer’s disease (AD). To various extents, available transgenic (TG) mouse models of AD recapitulate such hallmarks of the disease as amyloid and tangle pathology, cognitive impairment, synaptic and neuronal loss. Less is known, however, about the brain volumetric changes over time in different genetic strains. Voxel-based morphometry (VBM) of structural MRIs is an in vivo method used to study subtle volumetric changes over time in the whole brain longitudinally. Although it has been seldom used in mice, recent developments in automated image analysis algorithms made it a bridgeable gap. Subjects and Methods: In this study, we compared the progression of neurodegeneration in double (TASTPM; amyloid? at 6 m; tangle-) and triple (TAUPS2APP amyloid? ; tangle? ; both at 4 m) TG strains of AD with a longitudinal design. Control (C67/BL6), TG (TASTPM and TAUPS2APP) male and female mice received MRI scan at 4 m, 13 m, and 24 m; (N & 10–20 mice per group). Datapreprocessing was performed with toolkits from the AFNI, FMRIB, and ANTs software libraries; the statistical analysis—in SPM12 and the read-out of anatomical labels—in ITK-snap. Results: The flexible factorial analysis in SPM12 revealed a strong interaction between time and genotype among the 3 groups in the hippocampal formation, entorhinal area, vermis, thalamus, and neostriatum. In paired comparison—‘controls against TASTPM’ a strong interaction between time and genotype was seen in the nucleus accumbens, striatum, thalamus, cerebellum, and olfactory areas. The analogous comparison with TAUPS2APP group showed in triple TG mice this interaction was isolated to the hippocampal formation. Discussion/Conclusion: The present results extend previous evidence obtained from the same database (Micotti et al. 2015; manual tracing) disclosing novel regions of progressive brain atrophy in TASTPM mice (i.e., thalamus, nucleus accumbens, and cerebellum). The effect in the nucleus accumbens corroborated literature about early alterations of mesolimbic dopaminergic systems in Tg2576 TG mice overexpressing the APP695 protein (Nobili et al. 2017), while the alteration in the cerebellum fits previous observation of local AD pathology in early-onset AD patients with PS1 mutation (Larner and Doran 2006). Overall, the present approach was successful to unveil different abnormalities in the brain over time in two common TG strains of AD

Novel spin dynamics in ferrimagnetic molecular chains from 1H NMR and MuSR spin-lattice relaxation measurements

The spin dynamics in the helical chain Co(hfac)(2)NITPhOMe has been investigated by H-1 NMR and muSR relaxation. In the temperature range 15 < T < 60 K, the results are consistent with the relaxation of the homogeneous magnetization. For Tless than or equal to 15 K, NMR and muSR evidence a second spin relaxation mechanism, undetected by the magnetization measurements. From the analysis of these data, insights on this novel relaxation process are derived

Low-energy excitations in the S=1/2 molecular nanomagnet K-6((V15As6O42)-As-IV(H2O)) center dot 8H(2)O from proton NMR and mu SR

Zero- and longitudinal-field muon-spin-rotation (muSR) and 1H NMR measurements on the S= 1/2 molecular nanomagnet K6[V15As6O42(H2O)]·8H2O are presented. In LF experiments, the muon asymmetry P(t) was fitted by the sum of three different exponential components with fixed weights. The different muon relaxation rates l_i (i=1,2,3) and the low-field H=0.23 T 1H NMR spin-lattice relaxation rate 1/T1 show a similar behavior for T>50 K: starting from room temperature they increase as the temperature is decreased. The increase of l_i and 1/T1 can be attributed to the “condensation” of the system toward the lowest-lying energy levels. The gap Delta, around 550 K, between the first and second S= 3/2 excited states was determined experimentally. For T<2 K, the muon relaxation rates l_i stay constant, independently of the field value H<0.15 T. The behavior for T<2 K strongly suggests that, at low T, the spin fluctuations are not thermally driven but rather originate from quasielastic intramolecular or intermolecular magnetic interactions. We suggest that the very-lowtemperature relaxation rates could be driven by energy exchanges between two almost degenerate S= 1/2 ground states and/or by quantum effects