Spatio-temporal anomalous diffusion in heterogeneous media by NMR

For the first time, the diffusion phase diagram in highly confined colloidal systems, predicted by Continuous Time Random Walk (CTRW), is experimentally obtained. Temporal and spatial fractional exponents, $\alpha$ and $\mu$, introduced within the framework of CTRW, are simultaneously measured by Pulse Field Gradient Nuclear Magnetic Resonance technique in samples of micro-beads dispersed in water. We find that $\alpha$ depends on the disorder degree of the system. Conversely, $\mu$ depends on both bead sizes and magnetic susceptibility differences within samples. Our findings fully match the CTRW predictions.Comment: 5 pages, 4 figures, submitted to Phys. Rev. Let

Apparent Diffusion Coefficient Assessment of Brain Development in Normal Fetuses and Ventriculomegaly

Diffusion neuro-MRI has benefited significantly from sophisticated pre-processing procedures aimed at improving image quality and diagnostic. In this work, diffusion-weighted imaging (DWI) was used with artifact correction and the apparent diffusion coefficient (ADC) was quantified to investigate fetal brain development. The DWI protocol was designed in order to limit the acquisition time and to estimate ADC without perfusion bias. The ADC in normal fetal brains was compared to cases with isolated ventriculomegaly (VM), a common fetal disease whose DWI studies are still scarce. DWI was performed in 58 singleton fetuses (Gestational age (GA) range: 19–38w) at 1.5T. In 31 cases, VM was diagnosed on ultrasound. DW-Spin Echo EPI with b-values = 50, 200, 700 s/mm2 along three orthogonal axes was used. All images were corrected for noise, Gibbs-ringing, and motion artifacts. The signal-to-noise ratio (SNR) was calculated and the ADC was measured with a linear least-squared algorithm. A multi-way ANOVA was used to evaluate differences in ADC between normal and VM cases and between second and third trimester in different brain regions. Correlation between ADC and GA was assessed with linear and quadratic regression analysis. Noise and artifact correction considerably increased SNR and the goodness-of-fit. ADC measurements were significantly different between second and third trimester in centrum semiovale, frontal white matter, thalamus, cerebellum and pons of both normal and VM brains (p ≤ 0.03). ADC values were significantly different between normal and VM in centrum semiovale and frontal white matter (p ≤ 0.02). ADC values in centrum semiovale, thalamus, cerebellum and pons linearly decreased with GA both in normal and VM brains, while a quadratic relation with GA was found in basal ganglia and occipital white matter of normal brains and in frontal white matter of VM (p ≤ 0.02). ADC values in all fetal brain regions were lower than those reported in literature where DWI with b = 0 was performed. Conversely, they were in agreement with the results of other authors who measured perfusion and diffusion contributions separately. By optimizing our DWI protocol we achieved an unbiased quantification of brain ADC in reasonable scan time. Our findings suggested that ADC can be a useful biomarker of brain abnormalities associated with VM

Wave reflection and transmission in multiply stented blood vessels

Closed circulatory systems display an exquisite balance between vascular elasticity and viscous fluid effects, to induce pulse-smoothing and avoid resonance during the cardiac cycle. Stents in the arterial tree alter this balance through stiffening and because a periodic structure is introduced, capable of interacting with the fluid in a complex way. While the former feature has been investigated, the latter received no attention so far. But periodic structures are the building blocks of metamaterials, known for their ‘non-natural’ behaviour. Thus, the investigation of a stent's periodic microstructure dynamical interactions is crucial to assess possible pathological responses. A one-dimensional fluid–structure interaction model, simple enough to allow an analytical solution for situations of interest involving one or two interacting stents, is introduced. It is determined: (i) whether or not frequency bands exist in which reflected blood pulses are highly increased and (ii) if these bands are close to the characteristic frequencies of arteries and finally, (iii) if the internal structure of the stent can sensibly affect arterial blood dynamics. It is shown that, while the periodic structure of an isolated stent can induce anomalous reflection only in pathological conditions, the presence of two interacting stents is more critical, and high reflection can occur at frequencies not far from the physiological values.This work was supported by the ERC advanced grant ERC-2013-ADG-340561-INSTABILITIES (2014– 2019). T.K.P. acknowledges support from the aforementioned programme for the period from 10 May 2016 to 13 September 2016. A.B.M. acknowledges the support from the aforementioned ERC Advanced Grant during his Visiting Professorship at Trento University in 2016

Apparent diffusion coefficient assessment of brain development in normal fetuses and ventriculomegaly

Diffusion neuro-MRI has benefited significantly from sophisticated pre-processing procedures aimed at improving image quality and diagnostic. In this work, diffusion-weighted imaging (DWI) was used with artifact correction and the apparent diffusion coefficient (ADC) was quantified to investigate fetal brain development. The DWI protocol was designed in order to limit the acquisition time and to estimate ADC without perfusion bias. The ADC in normal fetal brains was compared to cases with isolated ventriculomegaly (VM), a common fetal disease whose DWI studies are still scarce. DWI was performed in 58 singleton fetuses (Gestational age (GA) range: 19–38w) at 1.5T. In 31 cases, VM was diagnosed on ultrasound. DW-Spin Echo EPI with b-values = 50, 200, 700 s/mm2 along three orthogonal axes was used. All images were corrected for noise, Gibbs-ringing, and motion artifacts. The signal-to-noise ratio (SNR) was calculated and the ADC was measured with a linear least-squared algorithm. A multi-way ANOVA was used to evaluate differences in ADC between normal and VM cases and between second and third trimester in different brain regions. Correlation between ADC and GA was assessed with linear and quadratic regression analysis. Noise and artifact correction considerably increased SNR and the goodness-of-fit. ADC measurements were significantly different between second and third trimester in centrum semiovale, frontal white matter, thalamus, cerebellum and pons of both normal and VM brains (p ≤ 0.03). ADC values were significantly different between normal and VM in centrum semiovale and frontal white matter (p ≤ 0.02). ADC values in centrum semiovale, thalamus, cerebellum and pons linearly decreased with GA both in normal and VM brains, while a quadratic relation with GA was found in basal ganglia and occipital white matter of normal brains and in frontal white matter of VM (p ≤ 0.02). ADC values in all fetal brain regions were lower than those reported in literature where DWI with b = 0 was performed. Conversely, they were in agreement with the results of other authors who measured perfusion and diffusion contributions separately. By optimizing our DWI protocol we achieved an unbiased quantification of brain ADC in reasonable scan time. Our findings suggested that ADC can be a useful biomarker of brain abnormalities associated with VM

Quantitative diffusion and perfusion MRI in the evaluation of endometrial cancer. Validation with histopathological parameters

Objectives: To investigate the role of quantitative Magnetic Resonance Imaging (MRI) in preoperative assessment of tumour aggressiveness in patients with endometrial cancer, correlating multiple parameters obtained from diffusion and dynamic contrast-enhanced (DCE) MR sequences with conventional histopathological prognostic factors and inflammatory tumour infiltrate.Methods: Forty-four patients with biopsy-proven endometrial cancer underwent preoperative MR imaging at 3T scanner, including DCE imaging, diffusion-weighted imaging (DWI) and intravoxel incoherent motion imaging (IVIM). Images were analysed on dedicated post-processing workstations and quantitative parameters were extracted: K-trans, K-ep, V-e and AUC from the DCE; ADC from DWI; diffusion D, pseudo diffusion D*, perfusion fraction f from IVIM and tumour volume from DWI. The following histopathological data were obtained after surgery: histological type, grading (G), lympho-vascular invasion (LVI), lymph node status, FIGO stage and inflammatory infiltrate.Results: ADC was significantly higher in endometrioid histology, G1-G2 (low grade), and stage IA. Significantly higher D* were found in endometrioid subptype, negative lymph nodes and stage IA. The absence of LVI is associated with higher f values. K-trans and V-e values were significantly higher in low grade. Higher D*, f and AUC occur with the presence of chronic inflammatory cells, D * was also able to distinguish chronic from mixed type of inflammation. Larger volume was significantly correlated with the presence of mixed-type inflammation, LVI, positive lymph nodes and stage >= IB.Conclusions: Quantitative biomarkers obtained from pre-operative DWI, IVIM and DCE-MR examination are an in vivo representation of the physiological and micro-structural characteristics of endometrial carcinoma allowing to obtain the fundamental parameters for stratification into Risk Classes.Advances in knowledge: Quantitative imaging biomarkers obtained from DWI, DCE and IVIM may improve preoperative prognostic stratification in patients with endometrial cancer leading to a more informed therapeutic choice

L-DOPA preloading increases the uptake of borophenylalanine in C6 glioma rat model: a new strategy to improve BNCT efficacy.

Purpose: Boron neutron capture therapy (BNCT) is a radiotherapeutic modality based on 10B(n,a)7Li reaction, for the treatment of malignant gliomas. One of the main limitations for BNCT effectiveness is the insufficient intake of 10B nuclei in the tumor cells. This work was aimed at investigating the use of L-DOPA as a putative enhancer for 10B-drug 4-dihydroxy-borylphenylalanine (BPA) uptake in the C6-glioma model. The investigation was first per- formed in vitro and then extended to the animal model. Methods and Materials: BPA accumulation in C6-glioma cells was assessed using radiowave dielectric spectros- copy, with and without L-DOPA preloading. Two L-DOPA incubation times (2 and 4 hours) were investigated, and the corresponding effects on BPA accumulation were quantified. C6-glioma cells were also implanted in the brain of 32 rats, and tumor growth was monitored by magnetic resonance imaging. Rats were assigned to two experimental branches: (1) BPA administration; (2) BPA administration after pretreatment with L-DOPA. All an- imals were sacrificed, and assessments of BPA concentrations in tumor tissue, normal brain, and blood samples were performed using high-performance liquid chromatography. Results: L-DOPA preloading induced a massive increase of BPA concentration in C6-glioma cells only after a 4-hour incubation. In the animal model, L-DOPA pretreatment produced a significantly higher accumulation of BPA in tumor tissue but not in normal brain and blood samples. Conclusions: This study suggests the potential use of L-DOPA as enhancer for BPA accumulation in malig- nant gliomas eligible for BNCT. L-DOPA preloading effect is discussed in terms of membrane transport mechanisms