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Diffusion-weighted Magnetic Resonance Imaging (dMRI) has relevant applications in the microstructural characterization of the spinal cord, especially in neurodegenerative diseases. Animal models have a pivotal role in the study of such diseases; however, in vivo spinal dMRI of small animals entails additional challenges that require a systematical investigation of acquisition parameters. The purpose of this study is to compare three acquisition protocols and identify the scanning parameters allowing a robust estimation of the main diffusion quantities and a good sensitivity to neurodegeneration in the mouse spinal cord. For all the protocols, the signal-to-noise and contrast-to noise ratios and the mean value and variability of Diffusion Tensor metrics were evaluated in healthy controls. For the estimation of fractional anisotropy less variability was provided by protocols with more diffusion directions, for the estimation of mean, axial and radial diffusivity by protocols with fewer diffusion directions and higher diffusion weighting. Intermediate features (12 directions, b = 1200 s/mm2) provided the overall minimum inter- and intra-subject variability in most cases. In order to test the diagnostic sensitivity of the protocols, 7 G93A-SOD1 mice (model of amyotrophic lateral sclerosis) at 10 and 17 weeks of age were scanned and the derived diffusion parameters compared with those estimated in age-matched healthy animals. The protocols with an intermediate or high number of diffusion directions provided the best differentiation between the two groups at week 17, whereas only few local significant differences were highlighted at week 10. According to our results, a dMRI protocol with an intermediate number of diffusion gradient directions and a relatively high diffusion weighting is optimal for spinal cord imaging. Further work is needed to confirm these results and for a finer tuning of acquisition parameters. Nevertheless, our findings could be important for the optimization of acquisition protocols for preclinical and clinical dMRI studies on the spinal cord., Competing Interests: The authors have declared that no competing interests exist.

To characterize the anatomy of the venous outflow of the mouse brain using different imaging techniques. Ten C57/black male mice (age range: 7-8 weeks) were imaged with high-frequency Ultrasound, Magnetic Resonance Angiography and ex-vivo Microcomputed tomography of the head and neck. Under general anesthesia, Ultrasound of neck veins was performed with a 20 MHz transducer; head and neck Magnetic Resonance Angiography data were collected on 9.4 T or 7 T scanners, and ex-vivo Microcomputed tomography angiography was obtained by filling the vessels with a radiopaque inert silicone rubber compound. All procedures were approved by the local ethical committee. The dorsal intracranial venous system is quite similar in mice and humans. Instead, the mouse Internal Jugular Veins are tiny vessels receiving the sigmoid sinuses and tributaries from cerebellum, occipital lobe and midbrain, while the majority of the cerebral blood, i.e. from the olfactory bulbs and fronto-parietal lobes, is apparently drained through skull base connections into the External Jugular Vein. Three main intra-extracranial anastomoses, absent in humans, are: 1) the petrosquamous sinus, draining into the posterior facial vein, 2) the veins of the olfactory bulb, draining into the superficial temporal vein through a foramen of the frontal bone 3) the cavernous sinus, draining in the External Jugular Vein through a foramen of the sphenoid bone. The anatomical structure of the mouse cranial venous outflow as depicted by Ultrasound, Microcomputed tomography and Magnetic Resonance Angiography is different from humans, with multiple connections between intra- and extra-cranial veins.

The purpose of this study was to investigate whether artificial neural networks (ANN) are able to decode participants' conscious experience perception from brain activity alone, using complex and ecological stimuli. To reach the aim we conducted pattern recognition data analysis on fMRI data acquired during the execution of a binocular visual rivalry paradigm (BR). Twelve healthy participants were submitted to fMRI during the execution of a binocular non-rivalry (BNR) and a BR paradigm in which two classes of stimuli (faces and houses) were presented. During the binocular rivalry paradigm, behavioral responses related to the switching between consciously perceived stimuli were also collected. First, we used the BNR paradigm as a functional localizer to identify the brain areas involved the processing of the stimuli. Second, we trained the ANN on the BNR fMRI data restricted to these regions of interest. Third, we applied the trained ANN to the BR data as a 'brain reading' tool to discriminate the pattern of neural activity between the two stimuli. Fourth, we verified the consistency of the ANN outputs with the collected behavioral indicators of which stimulus was consciously perceived by the participants. Our main results showed that the trained ANN was able to generalize across the two different tasks (i.e. BNR and BR) and to identify with high accuracy the cognitive state of the participants (i.e. which stimulus was consciously perceived) during the BR condition. The behavioral response, employed as control parameter, was compared with the network output and a statistically significant percentage of correspondences (p-value <0.05) were obtained for all subjects. In conclusion the present study provides a method based on multivariate pattern analysis to investigate the neural basis of visual consciousness during the BR phenomenon when behavioral indicators lack or are inconsistent, like in disorders of consciousness or sedated patients.

Resting state fMRI (rs-fMRI) has recently been considered as a possible complement or alternative to task-based fMRI (tb-fMRI) for presurgical mapping. However, evidence of its usefulness remains scant, because existing studies have investigated relatively small samples and focused primarily on qualitative evaluation. The aim of this study is to investigate the clinical usefulness of rs-fMRI in the context of presurgical mapping of motor functions, and in particular to determine the degree of correspondence with tb-fMRI which, while not a gold-standard, is commonly used in preoperative setting. A group of 13 patients with lesions close to the sensorimotor cortex underwent rs-fMRI and tb-fMRI to localize the hand, foot and mouth motor areas. We assessed quantitatively the degree of correspondence between multiple rs-fMRI analyses (independent-component and seed-based analyses) and tb-fMRI, with reference to sensitivity and specificity of rs-fMRI with respect to tb-fMRI, and centre-of-mass distances. Agreement with electro-cortical stimulation (ECS) was also investigated, and a traditional map thresholding approach based on agreement between two experienced operators was compared to an automatic threshold determination method. Rs-fMRI can localize the sensorimotor cortex successfully, providing anatomical specificity for hand, foot and mouth motor subregions, in particular with seed-based analyses. Agreement with tb-fMRI was only partial and rs-fMRI tended to provide larger patterns of correlated activity. With respect to the ECS data available, rs-fMRI and tb-fMRI performed comparably, even though the shortest distance to stimulation points was observed for the latter. Notably, the results of both were on the whole robust to thresholding procedure. Localization performed by rs-fMRI is not equivalent to tb-fMRI, hence rs-fMRI cannot be considered as an outright replacement for tb-fMRI. Nevertheless, since there is significant agreement between the two techniques, rs-fMRI can be considered with caution as a potential alternative to tb-fMRI when patients are unable to perform the task.

Background: Perfusion weighted imaging (PWI) can be used to measure key aspects of tumor vascularity in vivo and recent studies suggest that perfusion imaging may be useful in the early assessment of response to angiogenesis inhibitors. Aim of this work is to compare Parametric Response Maps (PRMs) with the Region Of Interest (ROI) approach in the analysis of tumor changes induced by bevacizumab and irinotecan in recurrent glioblastomas (rGBM), and to evaluate if changes in tumor blood volume measured by perfusion MRI may predict clinical outcome., Methods: 42 rGBM patients with KPS ≥ 50 were treated until progression, as defined by MRI with RANO criteria. Relative cerebral blood volume (rCBV) variation after 8 weeks of treatment was calculated through semi-automatic ROI placement in the same anatomic region as in baseline. Alternatively, rCBV variations with respect to baseline were calculated into the evolving tumor region using a voxel-by-voxel difference. PRMs were created showing where rCBV significantly increased, decreased or remained unchanged., Results: An increased blood volume in PRM (PRMCBV+) higher than 18% (first quartile) after 8 weeks of treatment was associated with increased progression free survival (PFS; 24 versus 13 weeks, p = 0.045) and overall survival (OS; 38 versus 25 weeks, p = 0.016). After 8 weeks of treatment ROI analysis showed that mean rCBV remained elevated in non responsive patients (4.8 ± 0.9 versus 5.1 ± 1.2, p = 0.38), whereas decreased in responsive patients (4.2 ± 1.3 versus 3.8 ± 1.6 p = 0.04), and re-increased progressively when patients approached tumor progression., Conclusions: Our data suggest that PRMs can provide an early marker of response to antiangiogenic treatment and warrant further confirmation in a larger cohort of GBM patients.

Background: Recent data suggest that circulating endothelial and progenitor cells (CECs and CEPs, respectively) may have predictive potential in cancer patients treated with bevacizumab, the antibody recognizing vascular endothelial growth factor (VEGF). Here we report on CECs and CEPs investigated in 68 patients affected by recurrent glioblastoma (rGBM) treated with bevacizumab and irinotecan and two Independent Datasets of rGBM patients respectively treated with bevacizumab alone (n=32, independent dataset A: IDA) and classical antiblastic chemotherapy (n=14, independent dataset B: IDB)., Methods: rGBM patients with KPS ≥50 were treated until progression, as defined by MRI with RANO criteria. CECs expressing CD109, a marker of tumor endothelial cells, as well as other CEC and CEP subtypes, were investigated by six-color flow cytometry., Results: A baseline count of CD109+ CEC higher than 41.1/ml (1(st) quartile) was associated with increased progression free survival (PFS; 20 versus 9 weeks, P=0.008) and overall survival (OS; 32 versus 23 weeks, P=0.03). Longer PFS (25 versus 8 weeks, P=0.02) and OS (27 versus 17 weeks, P=0.03) were also confirmed in IDA with CD109+ CECs higher than 41.1/ml but not in IDB. Patients treated with bevacizumab with or without irinotecan that were free from MRI progression after two months of treatment had significant decrease of CD109+ CECs: median PFS was 19 weeks; median OS 29 weeks. The presence of two non-contiguous lesions (distant disease) at baseline was an independent predictor of shorter PFS and OS (P<0.001)., Conclusions: Data encourage further studies on the predictive potential of CD109+ CECs in GBM patients treated with bevacizumab.