Time-of-flight MRA of intracranial vessels at 7 T.

BACKGROUND: Three-dimensional time-of-flight magnetic resonance angiography (TOF-MRA) is a largely adopted non-invasive technique for assessing cerebrovascular diseases. We aimed to optimize the 7-T TOF-MRA acquisition protocol, confirm that it outperforms conventional 3-T TOF-MRA, and compare 7-T TOF-MRA with digital subtraction angiography (DSA) in patients with different vascular pathologies. METHODS: Seven-tesla TOF-MRA sequences with different spatial resolutions acquired in four healthy subjects were compared with 3-T TOF-MRA for signal-to-noise and contrast-to-noise ratios as well as using a qualitative scale for vessel visibility and the quantitative Canny algorithm. Four patients with cerebrovascular disease (primary arteritis of the central nervous system, saccular aneurism, arteriovenous malformation, and dural arteriovenous fistula) underwent optimized 7-T TOF-MRA and DSA as reference. Images were compared visually and using the complex-wavelet structural similarity index. RESULTS: Contrast-to-noise ratio was higher at 7 T (4.5 ± 0.8 (mean ± standard deviation)) than at 3 T (2.7 ± 0.9). The mean quality score for all intracranial vessels was higher at 7 T (2.89) than at 3 T (2.28). Angiogram quality demonstrated a better vessel border detection at 7 T than at 3 T (44,166 versus 28,720 pixels). Of 32 parameters used for diagnosing cerebrovascular diseases on DSA, 27 (84%) were detected on 7-T TOF-MRA; the similarity index ranged from 0.52 (dural arteriovenous fistula) to 0.90 (saccular aneurysm). CONCLUSIONS: Seven-tesla TOF-MRA outperformed conventional 3-T TOF-MRA in evaluating intracranial vessels and exhibited an excellent image quality when compared to DSA. Seven-tesla TOF-MRA might improve the non-invasive diagnostic approach to several cerebrovascular diseases. RELEVANCE STATEMENT: An optimized TOF-MRA sequence at 7 T outperforms 3-T TOF-MRA, opening perspectives to its clinical use for noninvasive diagnosis of paradigmatic pathologies of intracranial vessels. KEY POINTS: • An optimized 7-T TOF-MRA protocol was selected for comparison with clinical 3-T TOF-MRA for assessing intracranial vessels. • Seven-tesla TOF-MRA outperformed 3-T TOF-MRA in both quantitative and qualitative evaluation. • Seven-tesla TOF-MRA is comparable to DSA for the diagnosis and characterization of intracranial vascular pathologies.

Case report: Exploring chemoradiotherapy-induced leukoencephalopathy with 7T imaging and quantitative susceptibility mapping.

Chemotherapy and radiotherapy are widely used in the treatment of central nervous system tumors and acute lymphocytic leukemia even in the pediatric population. However, such treatments run the risk of a broad spectrum of cognitive and neurological deficits. Even though the correlation with cognitive decline is still not clear, neuroradiological defects linked to white matter injury and vasculopathies may be identified. Thanks to the use of 7T MRI it is possible to better define the vascular pattern of the brain lesions with the added advantage of identifying their characteristics and anatomical localization, which, however, are not evident with a conventional brain scan. Moreover, the use of Quantitative Susceptibility Mapping (QSM) makes it possible to discriminate between calcium deposits on vessels (chemo-radiation-induced) and hemoglobin deposition in radio-induced cavernomas, speculating, as a result, about the pathophysiology of iatrogenic brain damage. We describe the case of a 9 year-old boy with a T-type acute lymphoid leukemia who had previously been treated with polychemotherapy and high-dose RT. To better define the child's neuroradiological pattern, 7T MRI and QSM were performed in addition to conventional imaging examinations. Our case report suggests the potential usefulness of a QSM study to distinguish radio-induced vascular malformations from mineralizing microangiopathy.

Magnetic resonance fingerprinting-based myelin water fraction mapping for the assessment of white matter maturation and integrity in typical development and leukodystrophies.

A quantitative biomarker for myelination, such as myelin water fraction (MWF), would boost the understanding of normative and pathological neurodevelopment, improving patients' diagnosis and follow-up. We quantified the fraction of a rapidly relaxing pool identified as MW using multicomponent three-dimensional (3D) magnetic resonance fingerprinting (MRF) to evaluate white matter (WM) maturation in typically developing (TD) children and alterations in leukodystrophies (LDs). We acquired DTI and 3D MRF-based R1, R2 and MWF data of 15 TD children and 17 LD patients (9 months-12.5 years old) at 1.5 T. We computed normative maturation curves in corpus callosum and corona radiata and performed WM tract profile analysis, comparing MWF with R1, R2 and fractional anisotropy (FA). Normative maturation curves demonstrated a steep increase for all tissue parameters in the first 3 years of age, followed by slower growth for MWF while R1, R2R2 and FA reached a plateau. Unlike FA, MWF values were similar for regions of interest (ROIs) with different degrees of axonal packing, suggesting independence from fiber bundle macro-organization and higher myelin specificity. Tract profile analysis indicated a specific spatial pattern of myelination in the major fiber bundles, consistent across subjects. LD were better distinguished from TD by MWF rather than FA, showing reduced MWF with respect to age-matched controls in both ROI-based and tract analysis. In conclusion, MRF-based MWF provides myelin-specific WM maturation curves and is sensitive to alteration due to LDs, suggesting its potential as a biomarker for WM disorders. As MRF allows fast simultaneous acquisition of relaxometry and MWF, it can represent a valuable diagnostic tool to study and follow up developmental WM disorders in children.

Fast high-resolution electric properties tomography using three-dimensional quantitative transient-state imaging-based water fraction estimation.

In this study, we aimed to develop a fast and robust high-resolution technique for clinically feasible electrical properties tomography based on water content maps (wEPT) using Quantitative Transient-state Imaging (QTI), a multiparametric transient state-based method that is similar to MR fingerprinting. Compared with the original wEPT implementation based on standard spin-echo acquisition, QTI provides robust electrical properties quantification towards B1 + inhomogeneities and full quantitative relaxometry data. To validate the proposed approach, 3D QTI data of 12 healthy volunteers were acquired on a 1.5 T scanner. QTI-provided T1 maps were used to compute water content maps of the tissues using an empirical relationship based on literature ex-vivo measurements. Assuming that electrical properties are modulated mainly by tissue water content, the water content maps were used to derive electrical conductivity and relative permittivity maps. The proposed technique was compared with a conventional phase-only Helmholtz EPT (HH-EPT) acquisition both within whole white matter, gray matter, and cerebrospinal fluid masks, and within different white and gray matter subregions. In addition, QTI-based wEPT was retrospectively applied to four multiple sclerosis adolescent and adult patients, compared with conventional contrast-weighted imaging in terms of lesion delineation, and quantitatively assessed by measuring the variation of electrical properties in lesions. Results obtained with the proposed approach agreed well with theoretical predictions and previous in vivo findings in both white and gray matter. The reconstructed maps showed greater anatomical detail and lower variability compared with standard phase-only HH-EPT. The technique can potentially improve delineation of pathology when compared with conventional contrast-weighted imaging and was able to detect significant variations in lesions with respect to normal-appearing tissues. In conclusion, QTI can reliably measure conductivity and relative permittivity of brain tissues within a short scan time, opening the way to the study of electric properties in clinical settings.

Brainstem anatomy with 7-T MRI: in vivo assessment and ex vivo comparison.

BACKGROUND: The brainstem contains grey matter nuclei and white matter tracts to be identified in clinical practice. The small size and the low contrast among them make their in vivo visualisation challenging using conventional magnetic resonance imaging (MRI) sequences at high magnetic field strengths. Combining higher spatial resolution, signal- and contrast-to-noise ratio and sensitivity to magnetic susceptibility (χ), susceptibility-weighted 7-T imaging could improve the assessment of brainstem anatomy. METHODS: We acquired high-resolution 7-T MRI of the brainstem in a 46-year-old female healthy volunteer (using a three-dimensional multi-echo gradient-recalled-echo sequence; spatial resolution 0.3 × 0.3 × 1.2 mm3) and in a brainstem sample from a 48-year-old female body donor that was sectioned and stained. Images were visually assessed; nuclei and tracts were labelled and named according to the official nomenclature. RESULTS: This in vivo imaging revealed structures usually evaluated through light microscopy, such as the accessory olivary nuclei, oculomotor nucleus and the medial longitudinal fasciculus. Some fibre tracts, such as the medial lemniscus, were visible for most of their course. Overall, in in vivo acquisitions, χ and frequency maps performed better than T2*-weighted imaging and allowed for the evaluation of a greater number of anatomical structures. All the structures identified in vivo were confirmed by the ex vivo imaging and histology. CONCLUSIONS: The use of multi-echo GRE sequences at 7 T allowed the visualisation of brainstem structures that are not visible in detail at conventional magnetic field and opens new perspectives in the diagnostic and therapeutical approach to brain disorders. RELEVANCE STATEMENT: In vivo MR imaging at UHF provides detailed anatomy of CNS substructures comparable to that obtained with histology. Anatomical details are fundamentals for diagnostic purposes but also to plan a direct targeting for a minimally invasive brain stimulation or ablation. KEY POINTS: • The in vivo brainstem anatomy was explored with ultrahigh field MRI (7 T). • In vivo T2*-weighted magnitude, χ, and frequency images revealed many brainstem structures. • Ex vivo imaging and histology confirmed all the structures identified in vivo. • χ and frequency imaging revealed more brainstem structures than magnitude imaging.

Case report: Clinical and neuroradiological longitudinal follow-up in Leukoencephalopathy with Calcifications and Cysts during treatment with bevacizumab.

Leukoencephalopathy with Calcifications and Cysts (LCC) is a rare genetic microangiopathy exclusively affecting the central nervous system caused by biallelic mutations in SNORD118. Brain magnetic resonance imaging (MRI) is often diagnostic due to the highly characteristic triad of leukoencephalopathy, intracranial calcifications, and brain cysts. Age at onset, presentation and disease evolution can all vary, ranging from pauci-symptomatic disease to rapid evolution of signs with loss of motor and cognitive abilities. No specific therapies for LCC are currently licensed. According to the literature, bevacizumab might represent an effective modality to improve the clinical and MRI features of the disease. However, uncertainty remains as to the true efficacy of this approach, when to begin therapy, appropriate dosing, and the consequences of drug withdrawal. According to CARE guidelines, we describe the long-term clinical and neuro-radiological follow-up of a 10-year-old child with LCC. We report disease evolution following repeated cycles of treatment with bevacizumab. Our case report suggests that repeated cycles of bevacizumab might effectively modify disease progression, possibly indicating a time-dependent effect.

Normative values of the topological metrics of the structural connectome: A multi-site reproducibility study across the Italian Neuroscience network.

PURPOSE: The use of topological metrics to derive quantitative descriptors from structural connectomes is receiving increasing attention but deserves specific studies to investigate their reproducibility and variability in the clinical context. This work exploits the harmonization of diffusion-weighted acquisition for neuroimaging data performed by the Italian Neuroscience and Neurorehabilitation Network initiative to obtain normative values of topological metrics and to investigate their reproducibility and variability across centers. METHODS: Different topological metrics, at global and local level, were calculated on multishell diffusion-weighted data acquired at high-field (e.g. 3 T) Magnetic Resonance Imaging scanners in 13 different centers, following the harmonization of the acquisition protocol, on young and healthy adults. A "traveling brains" dataset acquired on a subgroup of subjects at 3 different centers was also analyzed as reference data. All data were processed following a common processing pipeline that includes data pre-processing, tractography, generation of structural connectomes and calculation of graph-based metrics. The results were evaluated both with statistical analysis of variability and consistency among sites with the traveling brains range. In addition, inter-site reproducibility was assessed in terms of intra-class correlation variability. RESULTS: The results show an inter-center and inter-subject variability of <10%, except for "clustering coefficient" (variability of 30%). Statistical analysis identifies significant differences among sites, as expected given the wide range of scanners' hardware. CONCLUSIONS: The results show low variability of connectivity topological metrics across sites running a harmonised protocol.

Quality assessment, variability and reproducibility of anatomical measurements derived from T1-weighted brain imaging: The RIN-Neuroimaging Network case study.

Initiatives for the collection of harmonized MRI datasets are growing continuously, opening questions on the reliability of results obtained in multi-site contexts. Here we present the assessment of the brain anatomical variability of MRI-derived measurements obtained from T1-weighted images, acquired according to the Standard Operating Procedures, promoted by the RIN-Neuroimaging Network. A multicentric dataset composed of 77 brain T1w acquisitions of young healthy volunteers (mean age = 29.7 ± 5.0 years), collected in 15 sites with MRI scanners of three different vendors, was considered. Parallelly, a dataset of 7 "traveling" subjects, each undergoing three acquisitions with scanners from different vendors, was also used. Intra-site, intra-vendor, and inter-site variabilities were evaluated in terms of the percentage standard deviation of volumetric and cortical thickness measures. Image quality metrics such as contrast-to-noise and signal-to-noise ratio in gray and white matter were also assessed for all sites and vendors. The results showed a measured global variability that ranges from 11% to 19% for subcortical volumes and from 3% to 10% for cortical thicknesses. Univariate distributions of the normalized volumes of subcortical regions, as well as the distributions of the thickness of cortical parcels appeared to be significantly different among sites in 8 subcortical (out of 17) and 21 cortical (out of 68) regions of i nterest in the multicentric study. The Bland-Altman analysis on "traveling" brain measurements did not detect systematic scanner biases even though a multivariate classification approach was able to classify the scanner vendor from brain measures with an accuracy of 0.60 ± 0.14 (chance level 0.33).

Simulated and experimental phantom data for multi-center quality assurance of quantitative susceptibility maps at 3 T, 7 T and 9.4 T.

PURPOSE: To develop methods for quality assurance of quantitative susceptibility mapping (QSM) using MRI at different magnetic field strengths, and scanners, using different MR-sequence protocols, and post-processing pipelines. METHODS: We built a custom phantom based on iron in two forms: homogeneous susceptibility ('free iron') and with fine-scaled variations in susceptibility ('clustered iron') at different iron concentrations. The phantom was measured at 3.0 T (two scanners), 7.0 T and 9.4 T using multi-echo, gradient echo acquisition sequences. A digital phantom analogue to the iron-phantom, tailored to obtain similar results as in experimentation was developed, with similar geometry and susceptibility values. Morphology enabled dipole inversion was applied to the phase images to obtain QSM for experimental and simulated data using the MEDI + 0 approach for background regularization. RESULTS: Across all scanners, QSM-values showed a linear increase with iron concentrations. The QSM-relaxivity was 0.231 ± 0.047 ppm/mM for free and 0.054 ± 0.013 ppm/mM for clustered iron, with adjusted determination coefficients (DoC) ≥ 0.87. Similarly, the simulations yielded linear increases (DoC ≥ 0.99). In both the experimental and digital phantoms, the estimated molar susceptibility was lower with clustered iron, because clustering led to highly localized field effects. CONCLUSION: Our iron phantom can be used to evaluate the capability of QSM to detect local variations in susceptibility across different field strengths, when using different MR-sequence protocols. The devised simulation method captures the effect of iron clustering in QSM as seen experimentally and could be used in the future to optimize QSM processing pipelines and achieve higher accuracy for local field effects, as also seen in Alzheimer's beta-amyloid plaques.

Development of BOLD Response to Motion in Human Infants.

Behavioral studies suggest that motion perception is rudimentary at birth and matures steadily over the first few years. We demonstrated previously that the major cortical associative areas serving motion processing, like middle temporal complex (MT+), visual cortex area 6 (V6), and PIVC in adults, show selective responses to coherent flow in 8-week-old infants. Here, we study the BOLD response to the same motion stimuli in 5-week-old infants (four females and four males) and compare the maturation between these two ages. The results show that MT+ and PIVC areas show a similar motion response at 5 and 8 weeks, whereas response in the V6 shows a reduced BOLD response to motion at 5 weeks, and cuneus associative areas are not identifiable at this young age. In infants and in adults, primary visual cortex (V1) does not show a selectivity for coherent motion but shows very fast development between 5 and 8 weeks of age in response to the appearance of motion stimuli. Resting-state correlations demonstrate adult-like functional connectivity between the motion-selective associative areas but not between primary cortex and temporo-occipital and posterior-insular cortices. The results are consistent with a differential developmental trajectory of motion area respect to other occipital regions, probably reflecting also a different development trajectory of the central and peripheral visual field.SIGNIFICANCE STATEMENT How the cortical visual areas attain the specialization that we observed in human adults in the first few months of life is unknown. However, this knowledge is crucial to understanding the consequence of perinatal brain damage and its outcome. Here, we show that motion selective areas are already functioning well in 5-week-old infants with greater responses for detecting coherent motion over random motion, suggesting that very little experience is needed to attain motion selectivity.

MRI data quality assessment for the RIN - Neuroimaging Network using the ACR phantoms.

PURPOSE: Generating big-data is becoming imperative with the advent of machine learning. RIN-Neuroimaging Network addresses this need by developing harmonized protocols for multisite studies to identify quantitative MRI (qMRI) biomarkers for neurological diseases. In this context, image quality control (QC) is essential. Here, we present methods and results of how the RIN performs intra- and inter-site reproducibility of geometrical and image contrast parameters, demonstrating the relevance of such QC practice. METHODS: American College of Radiology (ACR) large and small phantoms were selected. Eighteen sites were equipped with a 3T scanner that differed by vendor, hardware/software versions, and receiver coils. The standard ACR protocol was optimized (in-plane voxel, post-processing filters, receiver bandwidth) and repeated monthly. Uniformity, ghosting, geometric accuracy, ellipse's ratio, slice thickness, and high-contrast detectability tests were performed using an automatic QC script. RESULTS: Measures were mostly within the ACR tolerance ranges for both T1- and T2-weighted acquisitions, for all scanners, regardless of vendor, coil, and signal transmission chain type. All measurements showed good reproducibility over time. Uniformity and slice thickness failed at some sites. Scanners that upgraded the signal transmission chain showed a decrease in geometric distortion along the slice encoding direction. Inter-vendor differences were observed in uniformity and geometric measurements along the slice encoding direction (i.e. ellipse's ratio). CONCLUSIONS: Use of the ACR phantoms highlighted issues that triggered interventions to correct performance at some sites and to improve the longitudinal stability of the scanners. This is relevant for establishing precision levels for future multisite studies of qMRI biomarkers.

Multi-centre and multi-vendor reproducibility of a standardized protocol for quantitative susceptibility Mapping of the human brain at 3T.

Quantitative Susceptibility Mapping (QSM) is an MRI-based technique allowing the non-invasive quantification of iron content and myelination in the brain. The RIN - Neuroimaging Network established an optimized and harmonized protocol for QSM across ten sites with 3T MRI systems from three different vendors to enable multicentric studies. The assessment of the reproducibility of this protocol is crucial to establish susceptibility as a quantitative biomarker. In this work, we evaluated cross-vendor reproducibility in a group of six traveling brains. Then, we recruited fifty-one volunteers and measured the variability of QSM values in a cohort of healthy subjects scanned at different sites, simulating a multicentric study. Both voxelwise and Region of Interest (ROI)-based analysis on cortical and subcortical gray matter were performed. The traveling brain study yielded high structural similarity (∼0.8) and excellent reproducibility comparing maps acquired on scanners from two different vendors. Depending on the ROI, we reported a quantification error ranging from 0.001 to 0.017 ppm for the traveling brains. In the cohort of fifty-one healthy subjects scanned at nine different sites, the ROI-dependent variability of susceptibility values, of the order of 0.005-0.025 ppm, was comparable to the result of the traveling brain experiment. The harmonized QSM protocol of the RIN - Neuroimaging Network provides a reliable quantification of susceptibility in both cortical and subcortical gray matter regions and it is ready for multicentric and longitudinal clinical studies in neurological and pychiatric diseases.

Evaluation of iron overload in nigrosome 1 via quantitative susceptibility mapping as a progression biomarker in prodromal stages of synucleinopathies.

Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is a prodromal stage of α-synucleinopathies, such as Parkinson's disease (PD), which are characterized by the loss of dopaminergic neurons in substantia nigra, associated with abnormal iron load. The assessment of presymptomatic biomarkers predicting the onset of neurodegenerative disorders is critical for monitoring early signs, screening patients for neuroprotective clinical trials and understanding the causal relationship between iron accumulation processes and disease development. Here, we used Quantitative Susceptibility Mapping (QSM) and 7T MRI to quantify iron deposition in Nigrosome 1 (N1) in early PD (ePD) patients, iRBD patients and healthy controls and investigated group differences and correlation with disease progression. We evaluated the radiological appearance of N1 and analyzed its iron content in 35 ePD, 30 iRBD patients and 14 healthy controls via T2*-weighted sequences and susceptibility (χ) maps. N1 regions of interest (ROIs) were manually drawn on control subjects and warped onto a study-specific template to obtain probabilistic N1 ROIs. For each subject the N1 with the highest mean χ was considered for statistical analysis. The appearance of N1 was rated pathological in 45% of iRBD patients. ePD patients showed increased N1 χ compared to iRBD patients and HC but no correlation with disease duration, indicating that iron load remains stable during the early stages of disease progression. Although no difference was reported in iron content between iRBD and HC, N1 χ in the iRBD group increases as the disease evolves. QSM can reveal temporal changes in N1 iron content and its quantification may represent a valuable presymptomatic biomarker to assess neurodegeneration in the prodromal stages of PD.

Quantitative MRI Harmonization to Maximize Clinical Impact: The RIN-Neuroimaging Network.

Neuroimaging studies often lack reproducibility, one of the cardinal features of the scientific method. Multisite collaboration initiatives increase sample size and limit methodological flexibility, therefore providing the foundation for increased statistical power and generalizable results. However, multisite collaborative initiatives are inherently limited by hardware, software, and pulse and sequence design heterogeneities of both clinical and preclinical MRI scanners and the lack of benchmark for acquisition protocols, data analysis, and data sharing. We present the overarching vision that yielded to the constitution of RIN-Neuroimaging Network, a national consortium dedicated to identifying disease and subject-specific in-vivo neuroimaging biomarkers of diverse neurological and neuropsychiatric conditions. This ambitious goal needs efforts toward increasing the diagnostic and prognostic power of advanced MRI data. To this aim, 23 Italian Scientific Institutes of Hospitalization and Care (IRCCS), with technological and clinical specialization in the neurological and neuroimaging field, have gathered together. Each IRCCS is equipped with high- or ultra-high field MRI scanners (i.e., ≥3T) for clinical or preclinical research or has established expertise in MRI data analysis and infrastructure. The actions of this Network were defined across several work packages (WP). A clinical work package (WP1) defined the guidelines for a minimum standard clinical qualitative MRI assessment for the main neurological diseases. Two neuroimaging technical work packages (WP2 and WP3, for clinical and preclinical scanners) established Standard Operative Procedures for quality controls on phantoms as well as advanced harmonized quantitative MRI protocols for studying the brain of healthy human participants and wild type mice. Under FAIR principles, a web-based e-infrastructure to store and share data across sites was also implemented (WP4). Finally, the RIN translated all these efforts into a large-scale multimodal data collection in patients and animal models with dementia (i.e., case study). The RIN-Neuroimaging Network can maximize the impact of public investments in research and clinical practice acquiring data across institutes and pathologies with high-quality and highly-consistent acquisition protocols, optimizing the analysis pipeline and data sharing procedures.

Short-term plasticity in the human visual thalamus.

While there is evidence that the visual cortex retains a potential for plasticity in adulthood, less is known about the subcortical stages of visual processing. Here, we asked whether short-term ocular dominance plasticity affects the human visual thalamus. We addressed this question in normally sighted adult humans, using ultra-high field (7T) magnetic resonance imaging combined with the paradigm of short-term monocular deprivation. With this approach, we previously demonstrated transient shifts of perceptual eye dominance and ocular dominance in visual cortex (Binda et al., 2018). Here, we report evidence for short-term plasticity in the ventral division of the pulvinar (vPulv), where the deprived eye representation was enhanced over the nondeprived eye. This vPulv plasticity was similar as previously seen in visual cortex and it was correlated with the ocular dominance shift measured behaviorally. In contrast, there was no effect of monocular deprivation in two adjacent thalamic regions: dorsal pulvinar and Lateral Geniculate Nucleus. We conclude that the visual thalamus retains potential for short-term plasticity in adulthood; the plasticity effect differs across thalamic subregions, possibly reflecting differences in their corticofugal connectivity.

Normal Retinotopy in Primary Visual Cortex in a Congenital Complete Unilateral Lesion of Lateral Geniculate Nucleus in Human: A Case Study.

Impairment of the geniculostriate pathway results in scotomas in the corresponding part of the visual field. Here, we present a case of patient IB with left eye microphthalmia and with lesions in most of the left geniculostriate pathway, including the Lateral Geniculate Nucleus (LGN). Despite the severe lesions, the patient has a very narrow scotoma in the peripheral part of the lower-right-hemifield only (beyond 15° of eccentricity) and complete visual field representation in the primary visual cortex. Population receptive field mapping (pRF) of the patient's visual field reveals orderly eccentricity maps together with contralateral activation in both hemispheres. With diffusion tractography, we revealed connections between superior colliculus (SC) and cortical structures in the hemisphere affected by the lesions, which could mediate the retinotopic reorganization at the cortical level. Our results indicate an astonishing case for the flexibility of the developing retinotopic maps where the contralateral thalamus receives fibers from both the nasal and temporal retinae.

Relationship among Connectivity of the Frontal Aslant Tract, Executive Functions, and Speech and Language Impairment in Children with Childhood Apraxia of Speech.

Childhood apraxia of speech (CAS) is a subtype of motor speech disorder usually co-occurring with language impairment. A supramodal processing difficulty, involving executive functions (EFs), might contribute to the cognitive endophenotypes and behavioral manifestations. The present study aimed to profile the EFs in CAS, investigating the relationship between EFs, speech and language severity, and the connectivity of the frontal aslant tract (FAT), a white matter tract involved in both speech and EFs. A total of 30 preschool children with CAS underwent speech, language, and EF assessments and brain MRIs. Their FAT connectivity metrics were compared to those of 30 children without other neurodevelopmental disorders (NoNDs), who also underwent brain MRIs. Alterations in some basic EF components were found. Inhibition and working memory correlated with speech and language severity. Compared to NoND children, a weak, significant reduction in fractional anisotropy (FA) in the left presupplementary motor area (preSMA) FAT component was found. Only speech severity correlated and predicted FA values along with the FAT in both of its components, and visual-spatial working memory moderated the relationship between speech severity and FA in the left SMA. Our study supports the conceptualization of a composite and complex picture of CAS, not limited to the speech core deficit, but also involving high-order cognitive skills.

Modeling brain connectivity dynamics in functional magnetic resonance imaging via particle filtering.

Interest in the studying of functional connections in the brain has grown considerably in the last decades, as many studies have pointed out that alterations in the interaction among brain areas can play a role as markers of neurological diseases. Most studies in this field treat the brain network as a system of connections stationary in time, but dynamic features of brain connectivity can provide useful information, both on physiology and pathological conditions of the brain. In this paper, we propose the application of a computational methodology, named Particle Filter (PF), to study non-stationarities in brain connectivity in functional Magnetic Resonance Imaging (fMRI). The PF algorithm estimates time-varying hidden parameters of a first-order linear time-varying Vector Autoregressive model (VAR) through a Sequential Monte Carlo strategy. On simulated time series, the PF approach effectively detected and enabled to follow time-varying hidden parameters and it captured causal relationships among signals. The method was also applied to real fMRI data, acquired in presence of periodic tactile or visual stimulations, in different sessions. On these data, the PF estimates were consistent with current knowledge on brain functioning. Most importantly, the approach enabled to detect statistically significant modulations in the cause-effect relationship between brain areas, which correlated with the underlying visual stimulation pattern presented during the acquisition.

Neural substrates of neuropsychological profiles in dystrophynopathies: A pilot study of diffusion tractography imaging.

INTRODUCTION: Cognitive difficulties and neuropsychological alterations in Duchenne and Becker muscular dystrophy (DMD, BMD) boys are not yet sufficiently explored, although this topic could have a relevant impact, finding novel biomarkers of disease both at genetics and neuroimaging point of view. The current study aims to: 1) analyze the neuropsychological profile of a group of DMD and BMD boys without cognitive impairment with an assessment of their executive functions; 2) explore the structural connectivity in DMD, BMD, and age-matched controls focusing on cortico-subcortical tracts that connect frontal cortex, basal ganglia, and cerebellum via the thalamus; 3) explore possible correlations between altered structural connectivity and clinical neuropsychological measures. MATERIALS AND METHODS: This pilot study included 15 boys (5 DMD subjects, 5 BMD subjects, and 5 age-matched typically developing, TD). They were assessed using a neuropsychological assessment protocol including cognitive and executive functioning assessment and performed a 1.5T MRI brain exam including advance Diffusion Weighted Imaging (DWI) method for tractography. Structural connectivity measurements were extracted along three specific tracts: Cortico-Ponto-Cerebellar Tract (CPCT), Cerebellar-Thalamic Tract (CTT), and Superior Longitudinal Fasciculus (SLF). Cortical-Spinal Tract (CST) was selected for reference, as control tract. RESULTS: Regarding intellectual functioning, a major impairment in executive functions compared to the general intellectual functioning was observed both for DMD (mean score = 86.20; SD = 11.54) and for BMD children (mean score = 88; SD = 3.67). Mean FA resulted tendentially always lower in DMD compared to both BMD and TD groups for all the examined tracts. The differences in FA were statistically significant for the right CTT (DMD vs BMD, p = 0.002, and DMD vs TD, p = 0.0015) and the right CPCT (DMD vs TD, p = 0.008). Concerning DMD, significant correlations emerged between FA-R-CTT and intellectual quotients (FIQ, p = 0.044; ρs = 0.821), and executive functions (Denomination Total, p = 0.044, ρs = 0.821; Inhibition Total, p = 0.019, ρs = 0.900). BMD showed a significant correlation between FA-R-CPCT and working memory index (p = 0.007; ρs = 0.949). DISCUSSION AND CONCLUSION: In this pilot study, despite the limitation of sample size, the findings support the hypothesis of the involvement of a cerebellar-thalamo-cortical loop for the neuropsychological profile of DMD, as the CTT and the CPCT are involved in the network and the related brain structures are known to be implied in executive functions. Our results suggest that altered WM connectivity and reduced fibre organization in cerebellar tracts, probably due to the lack of dystrophin in the brain, may render less efficient some neuropsychological functions in children affected by dystrophinopathies. The wider multicentric study could help to better establish the role of cerebellar connectivity in neuropsychological profile for dystrophinopathies, identifying possible novel diagnostic and prognostic biomarkers.

Cortical thickness of primary visual cortex correlates with motion deficits in periventricular leukomalacia.

Impairments of visual motion perception and, in particular, of flow motion have been consistently observed in premature and very low birth weight subjects during infancy. Flow motion information is analyzed at various cortical levels along the dorsal pathways, with information mainly provided by primary and early visual cortex (V1, V2 and V3). We investigated the cortical stage of the visual processing that underlies these motion impairments, measuring Grey Matter Volume and Cortical Thickness in 13 children with Periventricular Leukomalacia (PVL). The cortical thickness, but not the grey matter volume of area V1, correlates negatively with motion coherence sensitivity, indicating that the thinner the cortex, the better the performance among the patients. However, we did not find any such association with either the thickness or volume of area MT, MST and areas of the IPS, suggesting damage at the level of primary visual cortex or along the optic radiation.