Reliability of quantitative magnetic susceptibility imaging metrics for cerebral cortex and major subcortical structures.

BACKGROUND AND PURPOSE: Susceptibility estimates derived from quantitative susceptibility mapping (QSM) images for the cerebral cortex and major subcortical structures are variably reported in brain magnetic resonance imaging (MRI) studies, as average of all ( µ all ${{{{\mu}}}_{{\mathrm{all}}}}$ ), absolute ( µ abs ${{{{\mu}}}_{{\mathrm{abs}}}}$ ), or positive- ( µ p ${{{{\mu}}}_{\mathrm{p}}}$ ) and negative-only ( µ n ${{{{\mu}}}_{\mathrm{n}}}$ ) susceptibility values using a region of interest (ROI) approach. This pilot study presents a reliability analysis of currently used ROI-QSM metrics and an alternative ROI-based approach to obtain voxel-weighted ROI-QSM metrics ( µ wp ${{{{\mu}}}_{{\mathrm{wp}}}}$ and µ wn ${{{{\mu}}}_{{\mathrm{wn}}}}$ ). METHODS: Ten healthy subjects underwent repeated (test-retest) 3-dimensional multi-echo gradient-echo (3DMEGE) 3 Tesla MRI measurements. Complex-valued 3DMEGE images were acquired and reconstructed with slice thicknesses of 1 and 2 mm (3DMEGE1, 3DMEGE2) along with 3DT1-weighted isometric (voxel 1 mm3) images for independent registration and ROI segmentation. Agreement, consistency, and reproducibility of ROI-QSM metrics were assessed through Bland-Altman analysis, intraclass correlation coefficient, and interscan and intersubject coefficient of variation (CoV). RESULTS: All ROI-QSM metrics exhibited good to excellent consistency and test-retest agreement with no proportional bias. Interscan CoV was higher for µ all ${{{{\mu}}}_{{\mathrm{all}}}}$ in comparison to the other metrics where it was below 15%, in both 3DMEGE1 and 3DMEGE2 datasets. Intersubject CoV for µ all ${{{{\mu}}}_{{\mathrm{all}}}}$ and µ abs ${{{{\mu}}}_{{\mathrm{abs}}}}$ exceeded 50% in all ROIs. CONCLUSIONS: Among the evaluated ROI-QSM metrics, µ all ${{{{\mu}}}_{{\mathrm{all}}}}$ and µ abs ${{{{\mu}}}_{{\mathrm{abs}}}}$ estimates were less reliable, whereas separating positive and negative values (using µ p , µ n , µ wp , µ wn ${{{{\mu}}}_{\mathrm{p}}},\ {{{{\mu}}}_{\mathrm{n}}},\ {{{{\mu}}}_{{\mathrm{wp}}}},\ {{{{\mu}}}_{{\mathrm{wn}}}}$ ) improved the reproducibility within, and the comparability between, subjects, even when reducing the slice thickness. These preliminary findings may offer valuable insights toward standardizing ROI-QSM metrics across different patient cohorts and imaging settings in future clinical MRI studies.

StepBrain: A 3-Dimensionally Printed Multicompartmental Anthropomorphic Brain Phantom to Simulate PET Activity Distributions.

An innovative multicompartmental anatomic brain phantom (StepBrain) is described to simulate the in vivo tracer uptake of gray matter, white matter, and striatum, overcoming the limitations of currently available phantoms. Methods: StepBrain was created by exploiting the potential of fused deposition modeling 3-dimensional printing to replicate the real anatomy of the brain compartments, as modeled through ad hoc processing of healthy-volunteer MR images. Results: A realistic simulation of 18F-FDG PET brain studies, using target activity to obtain the real concentration ratios, was obtained, and the results of postprocessing with partial-volume effect correction tools developed for human PET studies confirmed the accuracy of these methods in recovering the target activity concentrations. Conclusion: StepBrain compartments (gray matter, white matter, and striatum) can be simultaneously filled, achieving different concentration ratios and allowing the simulation of different (e.g., amyloid, tau, or 6-fluoro-l-dopa) tracer distributions, with a potentially valuable role for multicenter PET harmonization studies.

Flexibility of brain dynamics is increased and predicts clinical impairment in relapsing-remitting but not in secondary progressive multiple sclerosis.

Large-scale brain activity has long been investigated under the erroneous assumption of stationarity. Nowadays, we know that resting-state functional connectivity is characterized by aperiodic, scale-free bursts of activity (i.e. neuronal avalanches) that intermittently recruit different brain regions. These different patterns of activity represent a measure of brain flexibility, whose reduction has been found to predict clinical impairment in multiple neurodegenerative diseases such as Parkinson's disease, amyotrophic lateral sclerosis and Alzheimer's disease. Brain flexibility has been recently found increased in multiple sclerosis, but its relationship with clinical disability remains elusive. Also, potential differences in brain dynamics according to the multiple sclerosis clinical phenotypes remain unexplored so far. We performed a brain dynamics study quantifying brain flexibility utilizing the 'functional repertoire' (i.e. the number of configurations of active brain areas) through source reconstruction of magnetoencephalography signals in a cohort of 25 multiple sclerosis patients (10 relapsing-remitting multiple sclerosis and 15 secondary progressive multiple sclerosis) and 25 healthy controls. Multiple sclerosis patients showed a greater number of unique reconfigurations at fast time scales as compared with healthy controls. This difference was mainly driven by the relapsing-remitting multiple sclerosis phenotype, whereas no significant differences in brain dynamics were found between secondary progressive multiple sclerosis and healthy controls. Brain flexibility also showed a different predictive power on clinical disability according to the multiple sclerosis type. For the first time, we investigated brain dynamics in multiple sclerosis patients through high temporal resolution techniques, unveiling differences in brain flexibility according to the multiple sclerosis phenotype and its relationship with clinical disability.

Fully automated measurement of intracranial CSF and brain parenchyma volumes in pediatric hydrocephalus by segmentation of clinical MRI studies.

BACKGROUND: Brain parenchyma (BP) and intracranial cerebrospinal fluid (iCSF) volumes measured by fully automated segmentation of clinical brain MRI studies may be useful for the diagnosis and follow-up of pediatric hydrocephalus. However, previously published segmentation techniques either rely on dedicated sequences, not routinely used in clinical practice, or on spatial normalization, which has limited accuracy when severe brain distortions, such as in hydrocephalic patients, are present. PURPOSE: We developed a fully automated method to measure BP and iCSF volumes from clinical brain MRI studies of pediatric hydrocephalus patients, exploiting the complementary information contained in T2- and T1-weighted images commonly used in clinical practice. METHODS: The proposed procedure, following skull-stripping of the combined volumes, performed using a multiparametric method to obtain a reliable definition of the inner skull profile, maximizes the CSF-to-parenchyma contrast by dividing the T2w- by the T1w- volume after full-scale dynamic rescaling, thus allowing separation of iCSF and BP through a simple thresholding routine. RESULTS: Validation against manual tracing on 23 studies (four controls and 19 hydrocephalic patients) showed excellent concordance (ICC > 0.98) and spatial overlap (Dice coefficients ranging from 77.2% for iCSF to 96.8% for intracranial volume). Accuracy was comparable to the intra-operator reproducibility of manual segmentation, as measured in 14 studies processed twice by the same experienced neuroradiologist. Results of the application of the algorithm to a dataset of 63 controls and 57 hydrocephalic patients (19 with parenchymal damage), measuring volumes' changes with normal development and in hydrocephalic patients, are also reported for demonstration purposes. CONCLUSIONS: The proposed approach allows fully automated segmentation of BP and iCSF in clinical studies, also in severely distorted brains, enabling to assess age- and disease-related changes in intracranial tissue volume with an accuracy comparable to expert manual segmentation.

A polynomial regression-based approach to estimate relaxation rate maps suitable for multiparametric segmentation of clinical brain MRI studies in multiple sclerosis.

BACKGROUND AND OBJECTIVE: Relaxation parameter maps (RPMs) calculated from spin-echo data have provided a basis for the segmentation of normal brain tissues and white matter lesions in multiple sclerosis (MS) MRI studies. However, Conventional Spin-Echo (CSE) sequences, once the core of clinical MRI studies, have been largely replaced by faster ones, which do not allow the calculation a-posteriori of RPMs from clinical studies. Aim of the study was to develop and validate a method to estimate RPMs (pseudo-RPMs) from routine clinical MRI protocols (including 3D-Gradient Echo T1w, FLAIR and fast-T2w sequences), suitable for fully automatic multiparametric segmentation of normal-appearing and pathological brain tissues in MS. METHODS: The proposed method processes spatially normalized clinical MRI studies through a multistep pipeline, to collect a set of data points of matched signal intensities (from MRI studies) and relaxation parameters (from a CSE-derived digital template and an MS lesion database), which are then fitted by a multiple and multivariate 4-th degree polynomial regression, providing pseudo-RPMs. The method was applied to a dataset of 59 clinical MRI studies providing pseudo-RPMs that were segmented through a method originally developed for the CSE-derived RPMs. Results of the segmentation in 12 studies were used to iteratively optimize method parameters. Accuracy of segmentation of normal-appearing brain tissues from the pseudo-RPMs was assessed by comparing their age-related changes, as measured in 47 clinical studies, against those measured acquired using CSE sequences in a comparable dataset of 47 patients. Lesion segmentation was validated against manual segmentation carried out by three neuroradiologists. RESULTS: Age-related changes of normal-appearing brain tissue volumes measured using the pseudo-RPMs substantially overlapped those measured using the RPMs obtained from CSE sequences, and segmentation of MS lesions showed a moderate-high spatial overlap with manual segmentation, comparable to that achieved by the widely used Lesion Segmentation Tool on FLAIR images, with a greater volumetric agreement. CONCLUSIONS: The proposed approach allows calculation from clinical studies of pseudo-RPMs, which are equivalent to those obtainable from CSE sequences, avoiding the need for the acquisition of additional, dedicated sequences for segmentation purposes.

A low-cost open-architecture taste delivery system for gustatory fMRI and BCI experiments.

BACKGROUND: Tasting is a complex process involving chemosensory perception and cognitive evaluation. Different experimental designs and solution delivery approaches may in part explain the variability reported in literature. These technical aspects certainly limit the development of taste-related brain computer interface devices. NEW METHOD: We propose a novel modular, scalable and low-cost device for rapid injection of small volumes of taste solutions during fMRI experiments that gathers the possibility to flexibly increase the number of channels, allowing complex multi-dimensional taste experiments. We provide the full description of the hardware and software architecture and illustrate the application of the working prototype in single-subject event-related fMRI experiments by showing the BOLD responses to basic taste qualities and to five intensities of tastes during the course of perception. RESULTS: The device is shown to be effective in activating multiple clusters within the gustatory pathway and a precise time-resolved event-related analysis is shown to be possible by the impulsive nature of the induced perception. COMPARISON WITH EXISTING METHOD(S): This gustometer represents the first implementation of a low-cost, easily replicable and portable device that is suitable for all kinds of fMRI taste experiments. Its scalability will boost the experimental design of more complex multi-dimensional fMRI studies of the human taste pathway. CONCLUSIONS: The gustometer represents a valid open-architecture alternative to other available devices and its spread and development may contribute to an increased standardization of experimental designs in human fMRI studies of taste perception and pave the way to the development of novel taste-related BCIs.