Comparison between inferior frontal gyrus intrinsic connectivity network and verb-generation task fMRI network for presurgical language mapping in healthy controls and in glioma patients.

Task-based functional MRI (tb-fMRI) represents an extremely valuable approach for the identification of language eloquent regions for presurgical mapping in patients with brain tumors. However, its routinely application is limited by patient-related factors, such as cognitive disability and difficulty in coping with long-time acquisitions, and by technical factors, such as lack of equipment availability for stimuli delivery. Resting-state fMRI (rs-fMRI) instead, allows the identification of distinct language networks in a 10-min acquisition without the need of performing active tasks and using specific equipment. Therefore, to test the feasibility of rs-fMRI as a preoperative mapping tool, we reconstructed a lexico-semantic intrinsic connectivity network (ICN) in healthy controls (HC) and in a case series of patients with gliomas and compared the organization of this language network with the one derived from tb-fMRI in the patient's group. We studied three patients with extra-frontal gliomas who underwent functional mapping with auditory verb-generation (AVG) task and rs-fMRI with a seed in the left inferior frontal gyrus (IFG). First, we identified the functional connected areas to the IFG in HC. We qualitatively compared these areas with those that showed functional activation in AVG task derived from Neurosynth meta-analysis. Last, in each patient we performed single-subject analyses both for rs- and tb-fMRI, and we evaluated the spatial overlap between the two approaches. In HC, the IFG-ICN network showed a predominant left fronto-temporal functional connectivity in regions overlapping with the AVG network derived from a meta-analysis. In two patients, rs- and tb-fMRI showed comparable patterns of activation in left fronto-temporal regions, with different levels of contralateral activations. The third patient could not accomplish the AVG task and thus it was not possible to make any comparison with the ICN. However, in this patient, task-free approach disclosed a consistent network of fronto-temporal regions as in HC, and additional parietal regions. Our preliminary findings support the value of rs-fMRI approach for presurgical mapping, particularly for identifying left fronto-temporal core language-related areas in glioma patients. In a preoperative setting, rs-fMRI approach could represent a powerful tool for the identification of eloquent language areas, especially in patients with language or cognitive impairments.

The effects of the functional interplay between the Default Mode and Executive Control Resting State Networks on cognitive outcome in preterm born infants at 6 months of age.

Preterm birth can affect cognitive functions, such as attention or more generally executive control mechanisms, with severity in impairments proportional to prematurity. The functional cross-talk between the Default Mode (DMN) and Executive Control (ECN) networks mirrors the integrity of cognitive processing and is directly related to brain development. In this study, a cohort of 20 preterm-born infants was investigated using rs-fMRI. First, we addressed biological maturity of the DMN per se and its interplay with the ECN in terms of patterns of increased functional connectivity. Second, we assessed the impact of the degree of prematurity on the DMN-ECN functional interplay development in relation to cognitive outcome at six months. Our results highlighted the emergence of DMN in preterm neonates, with connectivity strength and synchronization between the anterior DMN hub and frontal areas increasing as a function of biological maturity. Further, cognitive scores at 6 months were predicted by mPFC-ECN connectivity strength with degree of prematurity impacting on mPFC-ECN connectivity and triggering differential patterns of functional maturation of the ECN for very early/early and moderate/late preterm neonates. Our findings suggest that the prematurity window allows to observe precursors of functional plasticity that may underlie different developmental trajectories in preterm children.

Along-tract statistics of neurite orientation dispersion and density imaging diffusion metrics to enhance MR tractography quantitative analysis in healthy controls and in patients with brain tumors.

Along-tract statistics analysis enables the extraction of quantitative diffusion metrics along specific white matter fiber tracts. Besides quantitative metrics derived from classical diffusion tensor imaging (DTI), such as fractional anisotropy and diffusivities, new parameters reflecting the relative contribution of different diffusion compartments in the tissue can be estimated through advanced diffusion MRI methods as neurite orientation dispersion and density imaging (NODDI), leading to a more specific microstructural characterization. In this study, we extracted both DTI- and NODDI-derived quantitative microstructural diffusion metrics along the most eloquent fiber tracts in 15 healthy subjects and in 22 patients with brain tumors. We obtained a robust intraprotocol reference database of normative along-tract microstructural metrics, and their corresponding plots, from healthy fiber tracts. Each diffusion metric of individual patient's fiber tract was then plotted and statistically compared to the normative profile of the corresponding metric from the healthy fiber tracts. NODDI-derived metrics appeared to account for the pathological microstructural changes of the peritumoral tissue more accurately than DTI-derived ones. This approach may be useful for future studies that may compare healthy subjects to patients diagnosed with other pathological conditions.

fMRI-Targeted High-Angular Resolution Diffusion MR Tractography to Identify Functional Language Tracts in Healthy Controls and Glioma Patients.

BACKGROUND: MR Tractography enables non-invasive preoperative depiction of language subcortical tracts, which is crucial for the presurgical work-up of brain tumors; however, it cannot evaluate the exact function of the fibers. PURPOSE: A systematic pipeline was developed to combine tractography reconstruction of language fiber bundles, based on anatomical landmarks (Anatomical-T), with language fMRI cortical activations. A fMRI-targeted Tractography (fMRI-T) was thus obtained, depicting the subsets of the anatomical tracts whose endpoints are located inside a fMRI activation. We hypothesized that fMRI-T could provide additional functional information regarding the subcortical structures, better reflecting the eloquent white matter structures identified intraoperatively. METHODS: Both Anatomical-T and fMRI-T of language fiber tracts were performed on 16 controls and preoperatively on 16 patients with left-hemisphere brain tumors, using a q-ball residual bootstrap algorithm based on High Angular Resolution Diffusion Imaging (HARDI) datasets (b = 3000 s/mm2; 60 directions); fMRI ROIs were obtained using picture naming, verbal fluency, and auditory verb generation tasks. In healthy controls, normalized MNI atlases of fMRI-T and Anatomical-T were obtained. In patients, the surgical resection of the tumor was pursued by identifying eloquent structures with intraoperative direct electrical stimulation mapping and extending surgery to the functional boundaries. Post-surgical MRI allowed to identify Anatomical-T and fMRI-T non-eloquent portions removed during the procedure. RESULTS: MNI Atlases showed that fMRI-T is a subset of Anatomical-T, and that different task-specific fMRI-T involve both shared subsets and task-specific subsets - e.g., verbal fluency fMRI-T strongly involves dorsal frontal tracts, consistently with the phonogical-articulatory features of this task. A quantitative analysis in patients revealed that Anatomical-T removed portions of AF-SLF and IFOF were significantly greater than verbal fluency fMRI-T ones, suggesting that fMRI-T is a more specific approach. In addition, qualitative analyses showed that fMRI-T AF-SLF and IFOF predict the exact functional limits of resection with increased specificity when compared to Anatomical-T counterparts, especially the superior frontal portion of IFOF, in a subcohort of patients. CONCLUSION: These results suggest that performing fMRI-T in addition to the 'classic' Anatomical-T may be useful in a preoperative setting to identify the 'high-risk subsets' that should be spared during the surgical procedure.

Functional MRI for Surgery of Gliomas.

PURPOSE OF REVIEW: Advanced neuroimaging techniques such as functional MRI (fMRI) and diffusion MR tractography have been increasingly used at every stage of the surgical management of brain gliomas, as a means to improve tumor resection while preserving brain functions. This review provides an overview of the last advancements in the field of functional MRI techniques, with a particular focus on their current clinical use and reliability in the preoperative and intraoperative setting, as well as their future perspectives for personalized multimodal management of patients with gliomas. RECENT FINDINGS: fMRI and diffusion MR tractography give relevant insights on the anatomo-functional organization of eloquent cortical areas and subcortical connections near or inside a tumor. Task-based fMRI and diffusion tensor imaging (DTI) tractography have proven to be valid and highly sensitive tools for localizing the distinct eloquent cortical and subcortical areas before surgery in glioma patients; they also show good accuracy when compared with intraoperative stimulation mapping data. Resting-state fMRI functional connectivity as well as new advanced HARDI (high angular resolution diffusion imaging) tractography methods are improving and reshaping the role of functional MRI for surgery of gliomas, with potential benefit for personalized treatment strategies. Noninvasive functional MRI techniques may offer the opportunity to perform a multimodal assessment in brain tumors, to be integrated with intraoperative mapping and clinical data for improving surgical management and oncological and functional outcome in patients affected by gliomas.

Abnormal cerebellar functional MRI connectivity in patients with paediatric multiple sclerosis.

OBJECTIVES: We investigated resting state functional connectivity (RSFC) of the cerebellar dentate nuclei in paediatric MS patients and its correlations with clinical, neuropsychological and structural MRI measures. METHODS: RSFC analysis was performed using a seed-region correlation approach and SPM8 from 48 paediatric MS patients and 27 matched healthy controls. RESULTS: In both groups, dentate nuclei RSFC was significantly correlated with RSFC of several cerebellar and extra-cerebellar brain regions. Compared with healthy controls, paediatric MS patients had reduced RSFC between the right dentate nuclei and the bilateral caudate nuclei and left thalamus as well as increased RSFC between the right dentate nuclei and the left precentral and postcentral gyri. Cognitively impaired patients showed a reduced RSFC between the dentate nuclei and bilateral regions located in the parietal, frontal and temporal lobes. Decreased RSFC was correlated with longer disease duration and higher T2 lesion volumes, whereas increased RSFC correlated with shorter disease duration, lower T2 lesion volume and a better motor performance. CONCLUSIONS: Modifications of cerebellar RSFC occur in paediatric MS and are influenced by the duration of the disease and brain focal lesions. Decreased RSFC may reflect early maladaptive plasticity contributing to cognitive impairment.

Maturation of preterm newborn brains: a fMRI-DTI study of auditory processing of linguistic stimuli and white matter development.

To evaluate brain development longitudinally in premature infants without abnormalities as compared to healthy full-term newborns, we assessed fMRI brain activity patterns in response to linguistic stimuli and white matter structural development focusing on language-related fibres. A total sample of 29 preterm newborns and 26 at term control newborns underwent both fMRI and DTI. Griffiths test was performed at 6 months of corrected age to assess development. Auditory fMRI data were analysed in 17 preterm newborns at three time points [34, 41 and 44 weeks of post menstrual age (wPMA)] and in 15 controls, at term. Analysis showed a distinctive pattern of cortical activation in preterm newborns up to 29 wPMA moving from early prevalent left temporal and supramarginal area activation in the preterm period, to a bilateral temporal and frontoopercular activation in the at term equivalent period and to a more fine-grained left pattern of activity at 44 wPMA. At term controls showed instead greater bilateral posterior thalamic activation. The different pattern of brain activity associated to preterm newborns mirrors their white matter maturation delay in peripheral regions of the fibres and thalamo-cortical radiations in subcortical areas of both hemispheres, pointing to different transient thalamo-cortical development due to prematurity. Evidence for functional thalamic activation and more mature subcortical tracts, including thalamic radiations, may represent the substantial gap between preterm and at term infants. The transition between bilateral temporal activations at term age and leftward activations at 44 weeks of PMA is correlated to better neuropsychological results in Griffiths test.