Enhancing magnetic resonance imaging with computational fluid dynamics

Quantitative assessment of haemodynamics has been utilised for better understanding of cardiac function and assisting diagnostics of cardiovascular diseases. To study haemodynamics, magnetic resonance imaging (MRI) and computational fluid dynamics (CFD) are widely used because of their non-invasive nature. It has been demonstrated that the two approaches are complementary to each other with their own advantages and limitations. Four dimensional cardiovascular magnetic resonance (4D Flow CMR) imaging enables direct measurement of blood flow velocity in vivo while spatial and temporal resolutions as well as region of image acquisition are limited to achieve a detailed assessment of the haemodynamics. CFD, on the other hand, is a powerful tool that has the potential to expand the image-obtained velocity fields with some problem-specific assumptions such as rigid arterial walls. We suggest a novel approach in which 4D Flow CMR and CFD are integrated synergistically in order to obtain an enhanced 4D Flow CMRI (EMRI). The enhancement will consist in overcoming the spatial-resolution limitations of the original 4D Flow CMRI, which will enable more accurate quantification of flow dependent bio-mechanical quantities (e.g. endothelial shear stress) as well as non-invasive estimation of blood pressure. At the same time, it will reduce a number of assumptions in conventional haemodynamic CFD such as in/outflow conditions including the effect of valves, the impact of patient-specific vessel wall motion and the effect of the surrounding tissues. The approach was first tested on a 2D portion of a pipe, to understand the behaviour of the parameters of the model in this novel framework. Afterwards the methodology was tested on patient specific data, to apply it to the analysis of blood flow in a patient specific human aorta, in 2D. The outcomes of EMRI are assessed by comparing the computed velocities with the 4D Flow CMR one. A fundamental step to allow the translation to clinics of this methodology was the validation. The study was performed on an idealised-simplified model of the human aortic arch – a U bend – with a sinusoidal inflow applied by a pump. Firstly, phase resolved particle image velocimetry (PIV) (an experimental technique enables high spatial-temporal resolution) was performed in 5 different time points of the pump cycle, using a blood alike fluid with the same refractive index matched of the clear silicon phantom, and seeded with silver coated hollow glass spheres. Real time 4D Flow CMR was then performed on the phantom with MRI. Lastly using the pump flow rate and the phantom geometry, a computation of the flow through the U bend was conducted using Ansys CFX. The flow patterns obtained from the 3 methods were compared in the middle plane of the phantom. The methodology was then applied to study a patient specific aorta in 3D, and retrieve flow patterns and flow dependent parameters. Finally, the validated methodology was applied to study atherogenesis, and in particular to investigate the relation between EMRI retrieved flow quantities (e.g. wall shear stress (WSS)) and temperature heterogeneity. A carotid artery phantom was realised and studied with CFD, MRT and EMRI. All the results demonstrate that EMRI preserves flow structures while correcting for experimental noise. Therefore it can provide better insights of the haemodynamics of cardiovascular problems, overcoming the limitations of 4D Flow CMR and CFD, even when considering a small region of interest. These findings were supported by the validation experiment that showed how EMRI retrieved flow patterns were much more consistent with the one measured with high resolution PIV, compensating for 4D Flow CMR errors. These findings lead to the application to the atherogenesis problem, allowing higher resolution flow patterns, more suitable to be compared to the temperature distribution and highlighted how flow patterns exert an influence on the temperature distribution on the vessel wall. EMRI confirmed its potential to provide more accurate non-invasive estimation of flow derived and flow dependent quantities and become a novel diagnostic tool

Brain magnetic resonance findings in 117 children with autism spectrum disorder under 5 years old.

We examined the potential benefits of neuroimaging measurements across the first 5 years of life in detecting early comorbid or etiological signs of autism spectrum disorder (ASD). In particular, we analyzed the prevalence of neuroradiologic findings in routine magnetic resonance imaging (MRI) scans of a group of 117 ASD children younger than 5 years old. These data were compared to those reported in typically developing (TD) children. MRI findings in children with ASD were analyzed in relation to their cognitive level, severity of autistic symptoms, and the presence of electroencephalogram (EEG) abnormalities. The MRI was rated abnormal in 55% of children with ASD with a significant prevalence in the high-functioning subgroup compared to TD children. We report significant incidental findings of mega cisterna magna, ventricular anomalies and abnormal white matter signal intensity in ASD without significant associations between these MRI findings and EEG features. Based on these results we discuss the role that brain MRI may play in the diagnostic procedure of ASD

Terbium to quantum rod Förster resonance energy transfer for homogeneous bioassays with picomolar detection limits

International audienc

Sensitivity Enhancement of Förster Resonance Energy Transfer Immunoassays by Multiple Antibody Conjugation on Quantum Dots

International audienceQuantum dots (QDs) are not only advantageous for color-tuning, improved brightness, and high stability, but their nanoparticle surfaces also allow for the attachment of many biomolecules. Because IgG antibodies (AB) are in the same size range of biocompatible QDs and the AB orientation after conjugation to the QD is often random, it is difficult to predict if few or many AB per QD will lead to an efficient AB-QD conjugate. This is particularly true for homogeneous Förster resonance energy transfer (FRET) sandwich immunoassays, for which the AB on the QD must bind a biomarker that needs to bind a second AB-FRET-conjugate. Here, we investigate the performance of Tb-to-QD FRET immunoassays against total prostate specific antigen (TPSA) by changing the number of AB per QD while leaving all the other assay components unchanged. We first characterize the AB-QD conjugation by various spectroscopic, microscopic, and chromatographic techniques and then quantify the TPSA immunoassay performance regarding sensitivity, limit of detection, and dynamic range. Our results show that an increasing conjugation ratio leads to significantly enhanced FRET immunoassays. These findings will be highly important for developing QD-based immunoassays in which the concentrations of both AB and QDs can significantly influence the assay performance

Analysis of RBFOX1 gene expression in lymphoblastoid cell lines of Italian discordant autism spectrum disorders sib-pairs

Several lines of evidence suggest that RBFOX1 is a key regulator of transcriptional and splicing programs in neural cells during development, and that it is expressed in a neuronal module enriched for known autism susceptibility genes. We have investigated its expression by semiquantitative RT-PCR in accessible nonbrain resources in eighteen autism spectrum disorder sib-pairs belonging to the Italian Autism Network cohort. RBFOX1 gene expression was detected in lymphoblastoid cell lines but not in lymphocytes. No significant differences between autism spectrum disorders and non-affected brothers were found. We were not able to replicate in lymphoblastoid cell lines the previously reported RBFOX1 gene downregulation in autism, even if a trend was observed. This might be due to less pronounced transcription level differences in RBFOX1 gene expression in lymphoblastoid cell lines than in brain samples. \ua9 2014 Elsevier Ltd