Impaired synaptic function is linked to cognition in Parkinson's disease

OBJECTIVE: Cognitive impairment is frequent in Parkinson's disease, but the underlying mechanisms are insufficiently understood. Because cortical metabolism is reduced in Parkinson's disease and closely associated with cognitive impairment, and CSF amyloid‐β species are reduced and correlate with neuropsychological performance in Parkinson's disease, and amyloid‐β release to interstitial fluid may be related to synaptic activity; we hypothesize that synapse dysfunction links cortical hypometabolism, reduced CSF amyloid‐β, and presynaptic deposits of α‐synuclein. We expect a correlation between hypometabolism, CSF amyloid‐β, and the synapse related‐markers CSF neurogranin and α‐synuclein. METHODS: Thirty patients with mild‐to‐moderate Parkinson's disease and 26 healthy controls underwent a clinical assessment, lumbar puncture, MRI, 18F‐fludeoxyglucose‐PET, and a neuropsychological test battery (repeated for the patients after 2 years). RESULTS: All subjects had CSF amyloid‐β 1‐42 within normal range. In Parkinson's disease, we found strong significant correlations between cortical glucose metabolism, CSF Aβ, α‐synuclein, and neurogranin. All PET CSF biomarker‐based cortical clusters correlated strongly with cognitive parameters. CSF neurogranin levels were significantly lower in mild‐to‐moderate Parkinson's disease compared to controls, correlated with amyloid‐β and α‐synuclein, and with motor stage. There was little change in cognition after 2 years, but the cognitive tests that were significantly different, were also significantly associated with cortical metabolism. No such correlations were found in the control group. INTERPRETATION: CSF Aβ, α‐synuclein, and neurogranin concentrations are related to cortical metabolism and cognitive decline. Synaptic dysfunction due to Aβ and α‐synuclein dysmetabolism may be central in the evolution of cognitive impairment in Parkinson's disease

T-1- and T-2*-dominant extravasation correction in DSC-MRI:Part II-predicting patient outcome after a single dose of cediranib in recurrent glioblastoma patients

A ‘vascular normalization index' (VNI) based on the changes in the magnetic resonance imaging (MRI) parameters K(trans) and cerebral blood volume (CBV), combined with blood sampling, has been shown to correlate with patient outcome in recurrent glioblastoma after a single dose of antiangiogenic therapy. Here, by applying a novel contrast agent extravasation correction method insensitive to variations in tissue mean transit time, we show that a similar VNI parameter can be derived from a single dynamic susceptibility contrast MR acquisition rather than the three parameters shown previously. Our results show that this new VNI parameter, which combines changes in tumoral CBV and an apparent transfer constant from our leakage correction method, may provide prognostic information in an even simpler manner than prior efforts

A generic support vector machine model for preoperative glioma survival associations

To develop a generic support vector machine (SVM) model by using magnetic resonance (MR) imaging-based blood volume distribution data for preoperative glioma survival associations and to prospectively evaluate the diagnostic effectiveness of this model in autonomous patient data

Magnetic Nanoparticles for Diagnosis and Medical Therapy

Magnetic nanoparticles (MNPs) reveal promising opportunities for biomedical applications, potentially allowing minimally invasive diagnosis and therapeutic usage at several levels of human body organization (cells, tissue and organs). An increasingly broad collection of MNPs has been recently developed not only at the research level but also in some specific cases for medical applications. Superparamagnetic iron oxide (SPIO) nanoparticles are commonly used in clinical practice as contrast agents for magnetic resonance imaging (MRI) of liver and angiography. Carbon nanotubes (CNTs) are another type of nanomaterials with great potential for biomedical applications. Filled with ferromagnetic materials, an ensemble of aligned CNTs displays a highly non-linear, anisotropic and hysteretic magnetization behaviour due to their extremely high aspect ratio (length/diameter >100). The intrinsic properties of such ferromagnetic nanoparticles can potentially improve diagnosis and therapy of numerous diseases. Combining tailored biocompatible ferromagnetic nanomaterials with dedicated detection technology can provide a new approach leading to the exciting perspective of accurate medical imaging and medical therapy (magnetic hyperthermia, targeted drug delivery, etc.) at the cellular level. Elongated Fe-filled CNTs (Fe-CNTs) are foreseen as potential nanotools leading to minimally invasive, highly sensitive, and cost effective novel investigation routes for complete human body systems