Gold nanoparticles carrying fluorinated ligands in their monolayer are, by themselves, contrast agents for 19F magnetic resonance imaging displaying high sensitivity because of the high density of fluorine nuclei achievable by grafting suitable ligands on the gold core surface. Functionalization of these nanoparticles with Gd(III) chelates allows adding a further functional activity to these systems, developing materials also acting as contrast agents for proton magnetic resonance imaging. These dual mode contrast agents may allow capitalizing on the benefits of 1H and 19F magnetic resonance imaging in a single diagnostic session. In this work, we describe a proof of principle of this approach by studying these nanoparticles in a high field preclinical scanner. The Gd(III) centers within the nanoparticles monolayer shorten considerably the 19F T1 of the ligands but, nevertheless, these systems display strong and sharp NMR signals which allow recording good quality 19F MRI phantom images at nanoparticle concentration of 20 mg/mL after proper adjustment of the imaging sequence. The Gd(III) centers also influence the T1 relaxation time of the water protons and high quality 1H MRI images could be obtained. Gold nanoparticles protected by hydrogenated ligands and decorated with Gd(III) chelates are reported for comparison as 1H MRI contrast agents.

Background and purposeHead down tilt 15° (HDT15°), applied before recanalization, increases collateral flow and improves outcome in experimental ischemic stroke. For its simplicity and low cost, HDT15° holds considerable potential to be developed as an emergency treatment of acute stroke in the prehospital setting, where hemorrhagic stroke is the major mimic of ischemic stroke. In this study, we assessed safety of HDT15° in the acute phase of experimental intracerebral hemorrhage.MethodsIntracerebral hemorrhage was produced by stereotaxic injection of collagenase in Wistar rats. A randomized noninferiority trial design was used to assign rats to HDT15° or flat position (n = 64). HDT15° was applied for 1 h during the time window of hematoma expansion. The primary outcome was hematoma volume at 24 h. Secondary outcomes were mass effect, mortality, and functional deficit in the main study and acute changes of intracranial pressure, hematoma growth, and cardiorespiratory parameters in separate sets of randomized animals (n = 32).ResultsHDT15° achieved the specified criteria of noninferiority for hematoma volume at 24 h. Mass effect, mortality, and functional deficit at 24 h showed no difference in the two groups. HDT15° induced a mild increase in intracranial pressure with respect to the pretreatment values (+2.91 ± 1.76 mmHg). HDT15° had a neutral effect on MRI‐based analysis of hematoma growth and cardiorespiratory parameters.ConclusionsApplication of HDT15° in the hyperacute phase of experimental intracerebral hemorrhage does not worsen early outcome. Further research is needed to implement HDT15° as an emergency collateral therapeutic for acute stroke.

BackgroundThe identification of possible hippocampal alterations is a crucial point for the diagnosis and therapy of patients with unilateral temporal lobe epilepsy (TLE).ObjectiveTo investigate the role of Neurite Orientation Dispersion and Density Imaging (NODDI), compared to Diffusion Tensor Imaging (DTI), in the comprehension of hippocampal microstructure in TLE.MethodsDTI and NODDI metrics were calculated in the hippocampi of adult patients with TLE, with and without histology-confirmed hippocampal sclerosis (HS), and in age/sex-matched healthy controls (HC). Diffusion metrics and hippocampal volumes of pathologic side were compared within subjects and between subjects among HS, non-HS, and HC groups. Diffusion metrics were also correlated with hippocampal volume and patients' clinical features. After surgery, hippocampal specimens were processed for neuropathology examinations.ResultsFifteen patients with TLE (9 with and 6 without HS) and 11 HC were included. Hippocampal analyses resulted in significant increase in FA (fractional anisotropy) and MD (mean diffusivity, mm2/s × 10−3), decrease in ODI (orientation dispersion index) comparing the pathologic side of patients with HS vs: (1) their relative non-pathological side (0.203 vs 0.183, 0.825 vs 0.724, 0.366 vs 0.443, respectively); (2) the pathologic side of patients without HS (0.203 vs 0.169, 0.825 vs 0.745, 0.366 vs 0.453, respectively); (3) HC (0.203 vs 0.172, 0.825 vs 0.729, 0.366 vs 0.447, respectively). Moreover, ND (neurite density) was significantly decreased comparing both hippocampi of patients with HS (0.416 vs 0.460). A significant increase in fiso (free-water isotropic volume fraction) was found in the comparison of pathologic hippocampi of patients with HS vs: (1) non-pathological hippocampi of patients with HS (0.323 vs 0.258); (2) HC (0.323 vs 0.226). Hippocampal volume of all patients with TLE negatively correlated with MD (r = −0.746, p = 0.0145) and positively correlated with ODI (r = 0.719, p = 0.0145). Fiso and ND of sclerotic hippocampi positively correlated with disease duration (r = 0.684, p = 0.0424 and r = 0.670, p = 0.0486, respectively). Immunohistochemistry in sclerotic hippocampal specimens revealed neuronal loss in pyramidal layer and fiber reorganization at the level of stratum lacunosum-moleculare confirming ODI and ND metrics.DiscussionThis study shows the capability of diffusion-MRI metrics to detect hippocampal microstructural alterations. Among them, ODI seems to better highlight the fiber reorganization observed by neuropathology in sclerotic hippocampi.

Hypothermia is a promising therapeutic strategy for severe vasospasm and other types of non-thrombotic cerebral ischemia, but its clinical application is limited by significant systemic side effects. We aimed to develop an intraventricular device for the controlled cooling of the cerebrospinal fluid, to produce a targeted hypothermia in the affected cerebral hemisphere with a minimal effect on systemic temperature. An intraventricular cooling device (acronym: V-COOL) was developed by in silico modelling, in vitro testing, and in vivo proof-of-concept application in healthy Wistar rats (n = 42). Cerebral cortical temperature, rectal temperature, and intracranial pressure were monitored at increasing flow rate (0.2 to 0.8 mL/min) and duration of application (10 to 60 min). Survival, neurological outcome, and MRI volumetric analysis of the ventricular system were assessed during the first 24 h. The V-COOL prototyping was designed to minimize extra-cranial heat transfer and intra-cranial pressure load. In vivo application of the V-COOL device produced a flow rate-dependent decrease in cerebral cortical temperature, without affecting systemic temperature. The target degree of cerebral cooling (− 3.0 °C) was obtained in 4.48 min at the flow rate of 0.4 mL/min, without significant changes in intracranial pressure. Survival and neurological outcome at 24 h showed no significant difference compared to sham-treated rats. MRI study showed a transient dilation of the ventricular system (+ 38%) in a subset of animals. The V-COOL technology provides an effective, rapid, selective, and safe cerebral cooling to a clinically relevant degree of − 3.0 °C.