Brain microstructure by multi-modal MRI: Is the whole greater than the sum of its parts?

The MRI signal is dependent upon a number of sub-voxel properties of tissue, which makes it potentially able to detect changes occurring at a scale much smaller than the image resolution. This "microstructural imaging" has become one of the main branches of quantitative MRI. Despite the exciting promise of unique insight beyond the resolution of the acquired images, its widespread application is limited by the relatively modest ability of each microstructural imaging technique to distinguish between differing microscopic substrates. This is mainly due to the fact that MRI provides a very indirect measure of the tissue properties in which we are interested. A strategy to overcome this limitation lies in the combination of more than one technique, to exploit the relative contributions of differing physiological and pathological substrates to selected MRI contrasts. This forms the basis of multi-modal MRI, a broad concept that refers to many different ways of effectively combining information from more than one MRI contrast. This paper will review a range of methods that have been proposed to maximise the output of this combination, primarily falling into one of two approaches. The first one relies on data-driven methods, exploiting multivariate analysis tools able to capture overlapping and complementary information. The second approach, which we call "model-driven", aims at combining parameters extracted by existing biophysical or signal models to obtain new parameters, which are believed to be more accurate or more specific than the original ones. This paper will attempt to provide an overview of the advantages and limitations of these two philosophies

Comparing multiband and singleband EPI in NODDI at 3T: what are the implications for reproducibility and study sample sizes?

Objective The reproducibility of Neurite orientation dispersion and density imaging (NODDI) metrics from time-saving multiband (MB) EPI compared with singleband (SB) has not been considered. This study aims to evaluate the reproducibility of NODDI parameters from SB and MB acquisitions, determine the agreement between acquisitions and estimate the sample sizes required to detect between-group change. Methods Brain diffusion MRI data were acquired using SB and MB (acceleration factors 2 (MB2) and 3 (MB3)) on 8 healthy subjects on 2 separate visits. NODDI maps of isotropic volume fraction (FISO), neurite density (NDI) and orientation dispersion index (ODI) were estimated. Region-of-interest analysis was performed; variability across subjects and visits was measured using coefficients of variation (CoV). Intraclass correlation coefficient and Bland–Altman analysis were performed to assess reproducibility and detect any systematic bias between SB, MB2 and MB3. Power calculations were used to determine sample sizes required to detect group differences. Results Both NDI and ODI were reproducible between visits; however, FISO was variable. All parameters were not reproducible across methods; a systematic bias was observed with the derived values decreasing as the MB factor increases. The number of subjects needed to detect a between-group change is not significantly different between methods; however, ODI needs considerably higher sample sizes than NDI. Conclusions Both SB and MB yield highly reproducible NDI and ODI measures, but direct comparison of these parameters between methods is complicated by systematic differences that exist between the two approaches

Comprehensive Brain Tumour Characterisation with VERDICT-MRI: Evaluation of Cellular and Vascular Measures Validated by Histology

The aim of this work was to extend the VERDICT-MRI framework for modelling brain tumours, enabling comprehensive characterisation of both intra- and peritumoural areas with a particular focus on cellular and vascular features. Diffusion MRI data were acquired with multiple b-values (ranging from 50 to 3500 s/mm2), diffusion times, and echo times in 21 patients with brain tumours of different types and with a wide range of cellular and vascular features. We fitted a selection of diffusion models that resulted from the combination of different types of intracellular, extracellular, and vascular compartments to the signal. We compared the models using criteria for parsimony while aiming at good characterisation of all of the key histological brain tumour components. Finally, we evaluated the parameters of the best-performing model in the differentiation of tumour histotypes, using ADC (Apparent Diffusion Coefficient) as a clinical standard reference, and compared them to histopathology and relevant perfusion MRI metrics. The best-performing model for VERDICT in brain tumours was a three-compartment model accounting for anisotropically hindered and isotropically restricted diffusion and isotropic pseudo-diffusion. VERDICT metrics were compatible with the histological appearance of low-grade gliomas and metastases and reflected differences found by histopathology between multiple biopsy samples within tumours. The comparison between histotypes showed that both the intracellular and vascular fractions tended to be higher in tumours with high cellularity (glioblastoma and metastasis), and quantitative analysis showed a trend toward higher values of the intracellular fraction (fic) within the tumour core with increasing glioma grade. We also observed a trend towards a higher free water fraction in vasogenic oedemas around metastases compared to infiltrative oedemas around glioblastomas and WHO 3 gliomas as well as the periphery of low-grade gliomas. In conclusion, we developed and evaluated a multi-compartment diffusion MRI model for brain tumours based on the VERDICT framework, which showed agreement between non-invasive microstructural estimates and histology and encouraging trends for the differentiation of tumour types and sub-regions

Amplified engagement of prefrontal cortex during control of voluntary action in Tourette syndrome

Tourette syndrome is characterized by ‘unvoluntary’ tics, which are compulsive, yet often temporarily suppressible. The inferior frontal gyrus is implicated in motor control, including inhibition of pre-potent actions through influences on downstream subcortical and motor regions. Although tic suppression in Tourette syndrome also engages the inferior frontal gyrus, it is unclear whether such prefrontal control of action is also dysfunctional: Tic suppression studies do not permit comparison with control groups, and neuroimaging studies of motor inhibition can be confounded by the concurrent expression or suppression of tics. Here, patients with Tourette syndrome were directly compared to control participants when performing an intentional inhibition task during functional MRI. Tic expression was recorded throughout for removal from statistical models. Participants were instructed to make a button press in response to Go cues, withhold responses to NoGo cues, and decide whether to press or withhold to ‘Choose’ cues. Overall performance was similar between groups, for both intentional inhibition rates (% Choose-Go) and reactive NoGo inhibition commission errors. A subliminal face prime elicited no additional effects on intentional or reactive inhibition. Across participants, the task activated prefrontal and motor cortices and subcortical nuclei, including pre-supplementary motor area, inferior frontal gyrus, insula, caudate nucleus, thalamus and primary motor cortex. In Tourette syndrome, activity was elevated in the inferior frontal gyrus, insula and basal ganglia, most notably within the right inferior frontal gyrus during voluntary action and inhibition (Choose-Go and Choose-NoGo), and reactive inhibition (NoGo-correct). Anatomically, the locus of this inferior frontal gyrus hyperactivation during control of voluntary action matched that previously reported for tic suppression. In Tourette syndrome, activity within the caudate nucleus was also enhanced during both intentional (Choose-NoGo) and reactive (NoGo-correct) inhibition. Strikingly, despite the absence of overt motor behaviour, primary motor cortex activity increased in patients with Tourette syndrome but decreased in controls during both reactive and intentional inhibition. Additionally, severity of premonitory sensations scaled with functional connectivity of the pre-supplementary motor area to the caudate nucleus, globus pallidus and thalamus when choosing to respond (Choose-Go). Together, these results suggest that patients with Tourette syndrome use equivalent prefrontal mechanisms to suppress tics and withhold non-tic actions, but require greater inferior frontal gyrus engagement than controls to overcome motor drive from hyperactive downstream regions, notably primary motor cortex. Moreover, premonitory sensations may cue midline motor regions to generate tics through interactions with the basal ganglia

Face perception enhances insula and motor network reactivity in Tourette syndrome

Tourette syndrome is a neurodevelopmental disorder, characterised by motor and phonic tics. Tics are typically experienced as avolitional, compulsive, and associated with premonitory urges. They are exacerbated by stress and can be triggered by external stimuli, including social cues like the actions and facial expressions of others. Importantly, emotional social stimuli, with angry facial stimuli potentially the most potent social threat cue, also trigger behavioural reactions in healthy individuals, suggesting that such mechanisms may be particularly sensitive in people with Tourette syndrome. Twenty-one participants with Tourette syndrome and 21 healthy controls underwent functional magnetic resonance imaging while viewing faces wearing either neutral or angry expressions to quantify group differences in neural activity associated with processing social information. Simultaneous video recordings of participants during neuroimaging enabled us to model confounding effects of tics on task-related responses to the processing of faces. In both Tourette syndrome and control participants, face stimuli evoked enhanced activation within canonical face perception regions, including the occipital face area and fusiform face area. However, the Tourette syndrome group showed additional responses within the anterior insula to both neutral and angry faces. Functional connectivity during face viewing was then examined in a series of psychophysiological interactions. In Tourette syndrome participants, the insula showed functional connectivity with a set of cortical regions previously implicated in tic generation: the pre-supplementary motor area, premotor cortex, primary motor cortex, and the putamen. Furthermore, insula functional connectivity with the globus pallidus and thalamus varied in proportion to tic severity, while supplementary motor area connectivity varied in proportion to premonitory sensations, with insula connectivity to these regions increasing to a greater extent in patients with worse symptom severity. In addition, the occipital face area showed increased functional connectivity in Tourette syndrome participants with posterior cortical regions, including primary somatosensory cortex, and occipital face area connectivity with primary somatosensory and primary motor cortices varied in proportion to tic severity. There were no significant psychophysiological interactions in controls. These findings highlight a potential mechanism in Tourette syndrome through which heightened representation within insular cortex of embodied affective social information may impact the reactivity of subcortical motor pathways, supporting programmed motor actions that are causally implicated in tic generation. Medicinal and psychological therapies that focus on reducing insular hyper-reactivity to social stimuli may have potential benefit for tic reduction in people with Tourette syndrome

Comprehensive brain tumour characterization with VERDICT-MRI: evaluation of cellular and vascular measures validated by histology

The aim of this work is to extend the VERDICT-MRI framework for modelling brain tumours, enabling comprehensive characterization of both intra-tumoural and peri-tumoural areas with a particular focus on cellular and vascular features. Diffusion MRI data were acquired with multiple b-values (ranging from 50 to 3500 s/mm2), diffusion times and echo times, in 21 patients with brain tumours of different types and with a wide range of cellular and vascular features. We fitted a selection of diffusion models that resulted from the combination of different types of intracellular, extracellular, and vascular compartments to the signal. We compared the models using criteria for parsimony while aiming at a good characterization of all the key histological brain tumour components. Finally, we evaluated the parameters of the best-performing model in the differentiation of tumour histotypes, having ADC (apparent diffusion coefficient) as a clinical standard reference, and compared them to histopathology and relevant perfusion MRI metrics. The best-performing model for VERDICT in brain tumours was a three-compartment model accounting for anisotropically hindered and isotropically restricted diffusion and isotropic pseudo-diffusion. VERDICT metrics were compatible with the histological appearance of low-grade gliomas and metastases, and reflected differences found by histopathology between multiple biopsy samples within tumours. The comparison between histotypes showed that both the intracellular and the vascular fractions tend to be higher in tumours with high cellularity (glioblastoma and metastasis), and quantitative analysis showed a trend toward higher values of the intracellular fraction (fic) within the tumour core with increasing glioma grade. We also observed a trend towards higher free water fraction in vasogenic oedemas around metastases compared to infiltrative oedemas around glioblastomas and WHO 3 gliomas and the periphery of low-grade gliomas. In conclusion, we developed and evaluated a multi-compartment diffusion MRI model for brain tumours based on the VERDICT framework and showed agreement of non-invasive microstructural estimates with histology and encouraging trends for differentiation of tumour types and sub-regions

392. Cerebral haemodynamic correlates of altered consciousness states induced by high-ventilation breathwork

No description supplie

Comprehensive brain tumour characterization with VERDICT-MRI: evaluation of cellular and vascular measures validated by histology

The aim of this work is to extend the VERDICT-MRI framework for modelling brain tumours, enabling comprehensive characterization of both intra-tumoural and peri-tumoural areas with a particular focus on cellular and vascular features. Diffusion MRI data were acquired with multiple b-values (ranging from 50 to 3500 s/mm2), diffusion times and echo times, in 21 patients with brain tumours of different types and with a wide range of cellular and vascular features. We fitted a selection of diffusion models that resulted from the combination of different types of intracellular, extracellular, and vascular compartments to the signal. We compared the models using criteria for parsimony while aiming at a good characterization of all the key histological brain tumour components. Finally, we evaluated the parameters of the best-performing model in the differentiation of tumour histotypes, having ADC (apparent diffusion coefficient) as a clinical standard reference, and compared them to histopathology and relevant perfusion MRI metrics. The best-performing model for VERDICT in brain tumours was a three-compartment model accounting for anisotropically hindered and isotropically restricted diffusion and isotropic pseudo-diffusion. VERDICT metrics were compatible with the histological appearance of low-grade gliomas and metastases, and reflected differences found by histopathology between multiple biopsy samples within tumours. The comparison between histotypes showed that both the intracellular and the vascular fractions tend to be higher in tumours with high cellularity (glioblastoma and metastasis), and quantitative analysis showed a trend toward higher values of the intracellular fraction (fic) within the tumour core with increasing glioma grade. We also observed a trend towards higher free water fraction in vasogenic oedemas around metastases compared to infiltrative oedemas around glioblastomas and WHO 3 gliomas and the periphery of low-grade gliomas. In conclusion, we developed and evaluated a multi-compartment diffusion MRI model for brain tumours based on the VERDICT framework and showed agreement of non-invasive microstructural estimates with histology and encouraging trends for differentiation of tumour types and sub-regions