Graph theory and network modelling have been previously applied to characterize motor network structural topology in multiple sclerosis (MS). However, between‐group differences disclosed by graph ...analysis might be primarily driven by discrepancy in density, which is likely to be reduced in pathologic conditions as a consequence of macroscopic damage and fibre loss that may result in less streamlines properly traced. In this work, we employed the convex optimization modelling for microstructure informed tractography (COMMIT) framework, which, given a tractogram, estimates the actual contribution (or weight) of each streamline in order to optimally explain the diffusion magnetic resonance imaging signal, filtering out those that are implausible or not necessary. Then, we analysed the topology of this ‘COMMIT‐weighted sensory‐motor network’ in MS accounting for network density. By comparing with standard connectivity analysis, we also tested if abnormalities in network topology are still identifiable when focusing on more ‘quantitative’ network properties. We found that topology differences identified with standard tractography in MS seem to be mainly driven by density, which, in turn, is strongly influenced by the presence of lesions. We were able to identify a significant difference in density but also in network global and local properties when accounting for density discrepancy. Therefore, we believe that COMMIT may help characterize the structural organization in pathological conditions, allowing a fair comparison of connectomes which considers discrepancies in network density. Moreover, discrepancy‐corrected network properties are clinically meaningful and may help guide prognosis assessment and treatment choice.
Our aim was to characterize the nature and extent of pathological changes in the normal-appearing white matter (NAWM) of patients with multiple sclerosis (MS) using novel diffusion kurtosis ...imaging-derived white matter tract integrity (WMTI) metrics and to investigate the association between these WMTI metrics and clinical parameters. Thirty-two patients with relapsing–remitting MS and 19 age- and gender-matched healthy controls underwent MRI and neurological examination. Maps of mean diffusivity, fractional anisotropy and WMTI metrics (intra-axonal diffusivity, axonal water fraction, tortuosity and axial and radial extra-axonal diffusivity) were created. Tract-based spatial statistics analysis was performed to assess for differences in the NAWM between patients and controls. A region of interest analysis of the corpus callosum was also performed to assess for group differences and to evaluate correlations between WMTI metrics and measures of disease severity. Mean diffusivity and radial extra-axonal diffusivity were significantly increased while fractional anisotropy, axonal water fraction, intra-axonal diffusivity and tortuosity were decreased in MS patients compared with controls (
p
values ranging from <0.001 to <0.05). Axonal water fraction in the corpus callosum was significantly associated with the expanded disability status scale score (
ρ
= −0.39,
p
= 0.035). With the exception of the axial extra-axonal diffusivity, all metrics were correlated with the symbol digits modality test score (
p
values ranging from 0.001 to <0.05). WMTI metrics are thus sensitive to changes in the NAWM of MS patients and might provide a more pathologically specific, clinically meaningful and practical complement to standard diffusion tensor imaging-derived metrics.
ABSTRACT
BACKGROUND AND PURPOSE
The advent of high and ultra‐high‐field MRI has significantly improved the investigation of infratentorial structures by providing high‐resolution images. However, ...none of the publicly available methods for cerebellar image analysis has been optimized for high‐resolution images yet.
METHODS
We present the implementation of an automated algorithm—SUITer (spatially unbiased infratentorial for enhanced resolution) method for cerebellar lobules parcellation on high‐resolution MR images acquired at both 3 and 7T MRI. SUITer was validated on five manually segmented data and compared with SUIT, FreeSurfer, and convolutional neural networks (CNN). SUITer was then applied to 3 and 7T MR images from 10 multiple sclerosis (MS) patients and 10 healthy controls (HCs).
RESULTS
The difference in volumes estimation for the cerebellar grey matter (GM), between the manual segmentation (ground truth), SUIT, CNN, and SUITer was reduced when computed by SUITer compared to SUIT (5.56 vs. 29.23 mL) and CNN (5.56 vs. 9.43 mL). FreeSurfer showed low volumes difference (3.56 mL). SUITer segmentations showed a high correlation (R2 = .91) and a high overlap with manual segmentations for cerebellar GM (83.46%). SUITer also showed low volumes difference (7.29 mL), high correlation (R2 = .99), and a high overlap (87.44%) for cerebellar GM segmentations across magnetic fields. SUITer showed similar cerebellar GM volume differences between MS patients and HC at both 3T and 7T (7.69 and 7.76 mL, respectively).
CONCLUSIONS
SUITer provides accurate segmentations of infratentorial structures across different resolutions and MR fields.
Magnetic Resonance Elastography (MRE) is a developing imaging technique that enables non-invasive estimation of tissue mechanical properties through the combination of induced mechanical ...displacements in the tissue and Magnetic Resonance Imaging (MRI). The mechanical drivers necessary to produce shear waves in the tissue have been a focus of engineering effort in the development and refinement of MRE. The potential targeting of smaller and stiffer tissues calls for increases in actuation frequency and refinement of mechanical driver positioning. Furthermore, the anisotropic nature of soft tissues results in driver position related changes in observed displacement wave patterns. These challenges motivate the investigation and development of the concept of active MRE driver positioning through visual servoing under MR imaging. Objective: This work demonstrates the initial prototype of an MRE driver positioning system, allowing capture of displacement wave patterns from various mechanical vibration loading angles under different vibration frequencies through MR imaging. Methods: Three different configurations of the MRE driver positioning robot are tested with an intervertebral disc (IVD) shaped gel phantom. Results: Both the octahedral shear stress signal to noise ratio (OSS-SNR) and estimated stiffness show statistically significant dependence on driver configuration in each of the three phantom IVD regions. Conclusion: This dependence demonstrates that driver configuration is a critical factor in MRE, and that the developed robot is capable of producing a range of configurations. Significance: This work presents the first demonstration of an active, imaging guided MRE driver positioning system, with significance for the future application of MRE to a wider range of human tissues.
Measures of fMRI resting-state functional connectivity (rs-FC) are an essential tool for basic and clinical investigations of fronto-limbic circuits. Understanding the relationship between rs-FC and ...the underlying patterns of neural activity in these circuits is therefore vital. Here we introduced inhibitory designer receptors exclusively activated by designer drugs (DREADDs) into the amygdala of two male macaques. We evaluated the causal effect of activating the DREADD receptors on rs-FC and neural activity within circuits connecting amygdala and frontal cortex. Activating the inhibitory DREADD increased rs-FC between amygdala and ventrolateral prefrontal cortex. Neurophysiological recordings revealed that the DREADD-induced increase in fMRI rs-FC was associated with increased local field potential coherency in the alpha band (6.5-14.5 Hz) between amygdala and ventrolateral prefrontal cortex. Thus, our multi-modal approach reveals the specific signature of neuronal activity that underlies rs-FC in fronto-limbic circuits.
Objective
Individuals with eating disorders are theorized to have basic impairments in affective appraisal and social–emotional processing that contribute to pathogenesis of the disease. We aimed to ...determine if facial electromyography could be used to discriminate between happy and disgust emotions during simultaneous acquisition of an fMRI BOLD sequence in efforts to establish a novel tool for investigating emotion‐driven hypotheses about eating pathology. In line with standards for rigor and reproducibility, we provide detailed protocols and code to support each step of this project.
Method
Sixteen adolescents with low‐weight eating disorders viewed emotional faces (Happy or Disgust) and were asked to mimic their facial expression during simultaneous BOLD and EMG (Corrugator supercilli, Lavator lavii, Zygomaticus major) acquisition. Trials were repeated with the scanner off and again with scanner on (i.e., fatigue).
Results
The Levator and Zygomaticus activation patterns discriminated disgust and happy faces successfully. The pattern held between scanner on and off conditions, but muscle activation attenuated in the Fatigue condition, especially for the Zygomaticus.
Discussion
Simultaneous fMRI–EMG is a new tool capable of discriminating specific emotions based on muscle activation patterns and can be leveraged to answer emotion‐driven hypotheses about clinical populations characterized by difficulty labeling or processing emotions.
Objectives
The aim of this study was to evaluate the capability of sequences acquired on a 7-T MRI scanner, within times and anatomical coverage appropriate for clinical studies, to identify cortical ...lesions (CLs) in patients with Multiple Sclerosis (MS). Furthermore, we aimed to confirm the clinical significance of CL, testing the correlations between gray matter (GM) lesions and clinical scores.
Methods
A 7-T MRI protocol included 3D-T1-weighted and T2*-weighted sequences. Images were evaluated independently by three readers of different experience, and the number of CLs was recorded. Between-rater concordance was assessed calculating the intraclass correlation coefficient (ICC). Lin’s concordance correlation coefficient was used to compare CL detection between sequences, while partial correlations and multivariable regression models were used to study the relationship between CL and clinical data.
Results
Forty MS patients (M/F, 17/23; 44.7 ± 12.6 years) were enrolled in this study, and CLs were identified in 35/40 subjects (87.5%). CL detection rate on 3D-T1-weighted images was significantly correlated with the detection rate on T2*-weighted images (
r
= 0.99;
p
< 0.001), with high concordance between readers (ICC ≥ 0.995). CLs were significantly correlated with both motor and cognitive scores (all with
p
≤ 0.04).
Conclusions
CL can be identified over the whole brain at 7-T in MS using a 3D-T1-weighted volume, acquired in a clinically feasible time and with comparable performance to that achievable using the T2*-weighted sequence. Based on the central role of CL in the development of clinical disability, we suggest that 3D-T1-weighted volume may play a role in the evaluation of CL in MS undergoing MRI on ultra-high-field scanners.
Key Points
• Cortical lesions can be identified in a clinically feasible time with a 7-T protocol, which includes a 3D-T1-weighted volume.
• Cortical lesions correlated significantly with both motor and cognitive disability in MS patients.
• Given their correlation with clinical disability, evaluation of a cortical lesion on a 7-T clinical protocol could help in the management of MS patients.
Chemogenetic techniques, such as designer receptors exclusively activated by designer drugs (DREADDs), enable transient, reversible, and minimally invasive manipulation of neural activity
Their ...development in nonhuman primates is essential for uncovering neural circuits contributing to cognitive functions and their translation to humans. One key issue that has delayed the development of chemogenetic techniques in primates is the lack of an accessible drug-screening method. Here, we use resting-state fMRI, a noninvasive neuroimaging tool, to assess the impact of deschloroclozapine (DCZ) on brainwide resting-state functional connectivity in 7 rhesus macaques (6 males and 1 female) without DREADDs. We found that systemic administration of 0.1 mg/kg DCZ did not alter the resting-state functional connectivity. Conversely, 0.3 mg/kg of DCZ was associated with a prominent increase in functional connectivity that was mainly confined to the connections of frontal regions. Additional behavioral tests confirmed a negligible impact of 0.1 mg/kg DCZ on socio-emotional behaviors as well as on reaction time in a probabilistic learning task; 0.3 mg/kg DCZ did, however, slow responses in the probabilistic learning task, suggesting attentional or motivational deficits associated with hyperconnectivity in fronto-temporo-parietal networks. Our study highlights both the excellent selectivity of DCZ as a DREADD actuator, and the side effects of its excess dosage. The results demonstrate the translational value of resting-state fMRI as a drug-screening tool to accelerate the development of chemogenetics in primates.
Chemogenetics, such as designer receptors exclusively activated by designer drugs (DREADDs), can afford control over neural activity with unprecedented spatiotemporal resolution. Accelerating the translation of chemogenetic neuromodulation from rodents to primates requires an approach to screen novel DREADD actuators
Here, we assessed brainwide activity in response to a DREADD actuator deschloroclozapine (DCZ) using resting-state fMRI in macaque monkeys. We demonstrated that low-dose DCZ (0.1 mg/kg) did not change whole-brain functional connectivity or affective behaviors, while a higher dose (0.3 mg/kg) altered frontal functional connectivity and slowed response in a learning task. Our study highlights the excellent selectivity of DCZ at proper dosing, and demonstrates the utility of resting-state fMRI to screen novel chemogenetic actuators in primates.
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