Multimodal Structural Magnetic Resonance Imaging Research Articles

Connectivity defines the distinctive anatomy and function of the hand-knob area.

Control of the hand muscles during fine digit movements requires a high level of sensorimotor integration, which relies on a complex network of cortical and subcortical hubs. The components of this network have been extensively studied in human and non-human primates, but discrepancies in the findings obtained from different mapping approaches are difficult to interpret. In this study, we defined the cortical and connectional components of the hand motor network in the same cohort of 20 healthy adults and 3 neurosurgical patients. We used multimodal structural magnetic resonance imaging (including T1-weighted imaging and diffusion tractography), as well as functional magnetic resonance imaging and navigated transcranial magnetic stimulation (nTMS). The motor map obtained from nTMS compared favourably with the one obtained from functional magnetic resonance imaging, both of which overlapped well within the 'hand-knob' region of the precentral gyrus and in an adjacent region of the postcentral gyrus. nTMS stimulation of the precentral and postcentral gyri led to motor-evoked potentials in the hand muscles in all participants, with more responses recorded from precentral stimulations. We also observed that precentral stimulations tended to produce motor-evoked potentials with shorter latencies and higher amplitudes than postcentral stimulations. Tractography showed that the region of maximum overlap between terminations of precentral-postcentral U-shaped association fibres and somatosensory projection tracts colocalizes with the functional motor maps. The relationships between the functional maps, and between them and the tract terminations, were replicated in the patient cohort. Three main conclusions can be drawn from our study. First, the hand-knob region is a reliable anatomical landmark for the functional localization of fine digit movements. Second, its distinctive shape is determined by the convergence of highly myelinated long projection fibres and short U-fibres. Third, the unique role of the hand-knob area is explained by its direct action on the spinal motoneurons and the access to high-order somatosensory information for the online control of fine movements. This network is more developed in the hand region compared to other body parts of the homunculus motor strip, and it may represent an important target for enhancing motor learning during early development.

QMRI-BIDS: An extension to the brain imaging data structure for quantitative magnetic resonance imaging data

The Brain Imaging Data Structure (BIDS) established community consensus on the organization of data and metadata for several neuroimaging modalities. Traditionally, BIDS had a strong focus on functional magnetic resonance imaging (MRI) datasets and lacked guidance on how to store multimodal structural MRI datasets. Here, we present and describe the BIDS Extension Proposal 001 (BEP001), which adds a range of quantitative MRI (qMRI) applications to the BIDS. In general, the aim of qMRI is to characterize brain microstructure by quantifying the physical MR parameters of the tissue via computational, biophysical models. By proposing this new standard, we envision standardization of qMRI through multicenter dissemination of interoperable datasets. This way, BIDS can act as a catalyst of convergence between qMRI methods development and application-driven neuroimaging studies that can help develop quantitative biomarkers for neural tissue characterization. In conclusion, this BIDS extension offers a common ground for developers to exchange novel imaging data and tools, reducing the entrance barrier for qMRI in the field of neuroimaging.

Imaging gradual neurodegeneration in a basal ganglia model disease.

X-linked dystonia-parkinsonism (XDP) is a neurodegenerative disease with adult onset dystonia and subsequent parkinsonism. Postmortem and imaging studies revealed remarkable striatal pathology, with a predominant involvement of the striosomal compartment in the early phase. Here, we aimed to disentangle sequential neurodegeneration in the striatum of XDP patients, provide evidence for preferential loss of distinct striatal areas in the early phase, and investigate whether iron accumulation is present. We used multimodal structural magnetic resonance imaging (voxel-based morphometry and relaxometry) in 18 male XDP patients carrying a TAF1 mutation and 19 age-matched male controls. Voxel-based relaxometry and morphometry revealed (1) a cluster in the anteromedial putamen showing high iron content and severe atrophy (-55%) and (2) a cluster with reduced relaxation rates as a marker for increased water levels and a lower degree of atrophy (-20%) in the dorsolateral putamen. Iron deposition correlated with the degree of atrophy (ρ = -0.585, p = 0.011) and disease duration (ρ = 0.632, p = 0.005) in the anteromedial putamen. In the dorsolateral putamen, sensorimotor putamen atrophy correlated with disease severity (ρ = -0.649, p = 0.004). This multimodal approach identified a patchy pattern of atrophy within the putamen. Atrophy is advanced and associated with iron accumulation in rostral regions of the striatum, whereas neurodegeneration is moderate and still ongoing in dorsolateral areas. Given the short disease duration and predominant dystonic phenotype, these results are well in line with early and preferential degeneration of striosome-rich striatal areas in XDP. ANN NEUROL 2019;86:517-526.

Added value of multimodal MRI to the clinical diagnosis of primary progressive aphasia variants

ObjectiveTo determine the added value of multimodal structural magnetic resonance imaging (MRI) to language assessment in the differential diagnosis of primary progressive aphasia (PPA) variants. Methods59 PPA patients [29 nonfluent (nfvPPA), 15 semantic (svPPA), 15 logopenic (lvPPA)] and 38 healthy controls underwent 3D T1-weighted and diffusion tensor (DT) MRI. PPA patients also performed a comprehensive language assessment. Cortical thickness measures and DT MRI indices of white matter tract integrity were obtained. A random forest analysis identified MRI features associated with each clinical variant. Using ROC curves, the discriminatory power of the language features alone (“language model”) and the added contribution of multimodal MRI variables were assessed (“language + MRI model”). ResultsThe ‘language model’ alone was able to differentiate svPPA from both nfvPPA and lvPPA patients with high accuracy (area under the curve [AUC] = .95 and .99, respectively). When left inferior parietal cortical thickness and DT MRI metrics of the genu of the corpus callosum and left frontal aslant tract were added to the “language model”, the ability to discriminate between nfvPPA and lvPPA cases increased from AUC .82 (“language model” only) to .94 (“language + MRI model”). ConclusionsLanguage measures alone are able to distinguish svPPA from the other two PPA variants with the highest accuracy. Multimodal structural MRI improves the distinction of nfvPPA and lvPPA, which is challenging in the clinical practice.

White Matter Integrity in Subcortical Vascular Cognitive Impairment: A Multimodal Structural MRI Study.

To investigate the disruption of white matter (WM) integrity in patients with subcortical vascular cognitive impairment (SVCI) with multimodal structural magnetic resonance imaging (MRI), and to explore the relationships between WM damage, structural network disruptions, and general cognitive function decline. Twenty-eight patients with SVCI and twenty control subjects underwent structural MRI scans and neuropsychological assessment. WM volume (WMV), WM hyperintensities (WMH), lacunar infarcts (LI), diffusion tensor imaging parameters and structural network characteristics were compared between two groups. Correlations between these parameters and general cognitive function were calculated. WMV, WMH load, LI number, mean fractional anisotropy (FA), peak height and peak location of mean diffusivity (MD) of normal-appearing WM (NAWM) and structural network characteristics were significantly different between the two groups. Disruption of WM microstructure and network characteristics was widespread. WMV, WMH load, mean FA and peak location of MD of NAWM explained about 70% of the variance in structural network characteristics. Shortest path length with LI number explained 47.5% of the variance in z-scores. SVCI was associated with widespread disruptions of WM integrity in the brain. Network characteristics may be a comprehensive reflection of WM integrity and a superior predictor of general cognitive function, while LI was an independent predictor of cognitive impairment.

Longitudinal Brain Changes Associated with Prophylactic Cranial Irradiation in Lung Cancer

IntroductionThe toxic effects of prophylactic cranial irradiation (PCI) and platinum-based chemotherapy on cognition in the lung cancer population have not yet been well established. In the present study we examined the longitudinal neuropsychological and brain structural changes observed in patients with lung cancer who were undergoing these treatments. MethodsTwenty-two patients with small cell lung cancer (SCLC) who underwent platinum-based chemotherapy and PCI were compared with two control groups: an age- and education-matched group of healthy controls (n = 21) and a group of patients with non-SCLC (NSCLC, n = 13) who underwent platinum-based chemotherapy. All groups were evaluated using a neuropsychological battery and multimodal structural magnetic resonance imaging: T1-weighted and diffusion tensor imaging at baseline (before PCI for SCLC and chemotherapy for NSCLC) and at 3 months after treatment. T1 voxel-based morphometry and tract-based spatial statistics were used to analyze microstructural changes in gray matter (GM) and white matter (WM). The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire—Core Questionnaire was also completed. ResultsPatients with SCLC exhibited cognitive deterioration in verbal fluency over time. Structural magnetic resonance imaging showed decreases in GM at 3 months in the right subcortical regions, bilateral insular cortex, and superior temporal gyrus in patients with SCLC compared with both control groups. Additionally, patients with SCLC showed decreases in GM over time in the aforementioned regions plus in the right parahippocampal gyrus and hippocampus, together with changes in the WM microstructure of the entire corpus callosum. These changes had a limited impact on responses to the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire—Core Questionnaire, however. Patients with NSCLC showed no cognitive or brain structural differences after chemotherapy. ConclusionsThis longitudinal study documents moderate neuropsychological deficits together with notable brain-specific structural changes (in GM and WM) in patients with SCLC after chemotherapy and PCI, suggesting that chemotherapy and especially PCI are associated with the development of cognitive and structural brain toxic effects.

Limited microstructural and connectivity deficits despite subcortical volume reductions in school-aged children born preterm with very low birth weight

Preterm birth and very low birth weight (VLBW, ≤1500g) are worldwide problems that burden survivors with lifelong cognitive, psychological, and physical challenges. In this multimodal structural magnetic resonance imaging (MRI) and diffusion MRI (dMRI) study, we investigated differences in subcortical brain volumes and white matter tract properties in children born preterm with VLBW compared to term-born controls (mean age=8years). Subcortical brain structure volumes and cortical thickness estimates were obtained, and fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were generated for 18 white matter tracts. We also assessed structural relationships between white matter tracts and cortical thickness of the tract endpoints. Compared to controls, the VLBW group had reduced volumes of thalamus, globus pallidus, corpus callosum, cerebral white matter, ventral diencephalon, and brain stem, while the ventricular system was larger in VLBW subjects, after controlling for age, sex, IQ, and estimated total intracranial volume. For the dMRI parameters, group differences were not significant at the whole-tract level, though pointwise analysis found shorter segments affected in forceps minor and left superior longitudinal fasciculus – temporal bundle. IQ did not correlate with subcortical volumes or dMRI measures in the VLBW group. While the deviations in subcortical volumes were substantial, there were few differences in dMRI measures between the two groups, which may reflect the influence of advances in perinatal care on white matter development.

Brain damage following prophylactic cranial irradiation in lung cancer survivors.

Long-term toxic effects of prophylactic cranial irradiation (PCI) on cognition in small cell lung cancer (SCLC) patients have not yet been well-established. The aim of our study was to examine the cognitive toxic effects together with brain structural changes in a group of long-term SCLC survivors treated with PCI. Eleven SCLC patients, who underwent PCI ≥ 2 years before, were compared with an age and education matched healthy control group. Both groups were evaluated using a neuropsychological battery and multimodal structural magnetic resonance imaging. Voxel-based morphometry and Tract-based Spatial Statistics were used to study gray matter density (GMD) and white matter (WM) microstructural changes. Cognitive deterioration was correlated with GMD and Fractional Anisotropy (FA). Finally, we carried out a single-subject analysis in order to evaluate individual structural brain changes. Nearly half of the SCLC met criteria for cognitive impairment, all exhibiting a global worsening of cognitive functioning. Patients showed significant decreases of GMD in basal ganglia bilaterally (putamen and caudate), bilateral thalamus and right insula, together with WM microstructural changes of the entire corpus callosum. Cognitive deterioration scores correlated positively with mean FA values in the corpus callosum. Single-subject analysis revealed that GMD and WM changes were consistently observed in nearly all patients. This study showed neuropsychological deficits together with brain-specific structural differences in long-term SCLC survivors. Our results suggest that PCI therapy, possibly together with platinum-based chemotherapy, was associated to permanent long-term cognitive and structural brain effects in a SCLC population.

Interhemispheric microstructural connectivity in bitemporal lobe epilepsy with hippocampal sclerosis

Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy. The most frequent pathologic finding in this condition is hippocampal sclerosis (HS). In addition, in a small proportion (14–23%) of refractory TLE patients, the presence of HS is bilateral. TLE involves grey matter (GM) and white matter (WM) abnormalities in a wide cortico-subcortical network. However, the impact of neuronal loss on specific WM fiber pathways and associated functional systems as well as seizure propagation pathways remains unclear. There is still much controversy regarding the role of the commissures (corpus callosum, hippocampal commissure and anterior commissure) in interhemispheric seizure propagation. This study aimed to investigate the integrity of WM interhemispheric connectivity in a singular sample of patients with TLE and bilateral HS using structural magnetic resonance imaging (MRI). We performed multimodal structural MRI [high resolution T1-weighted and diffusion tensor imaging (DTI)] analyses of seven patients with medically refractory TLE with bilateral HS, fourteen unilateral left TLE patients and fifteen matched healthy individuals. Whole-brain voxel-wise analysis techniques were used. These patients evidenced WM derangement [reduced fractional anisotropy (FA), increased mean diffusivity (MD) or reduced WM volume] in temporal and extratemporal tracks, but also in commissural pathways, compared to the unilateral left TLE patients and the control group. Presence of reduced FA or increased MD in the fornix, cingulum and uncinate fasciculus in addition to reduced WM volume in the fornix was also encountered. Neuropsychological assessment was performed without significant correlations with structural data. The current results support the idea that commissural pathways play a contributory role in interhemispheric TLE seizure propagation in bilateral HS and offer new perspectives about the long-term effects on interhemispheric connectivity associated with seizure propagation patterns in TLE patients.

O3.04 * COGNITIVE AND STRUCTURAL BRAIN CHANGES ASSOCIATED WITH PROPHYLACTIC CRANIAL IRRADIATION IN LONG TERM SMALL CELL LUNG CANCER SURVIVORS

PURPOSE: The long-term toxic effects of prophylactic cranial irradiation (PCI) on cognition in small cell lung cancer (SCLC) patients have not yet been well-established. The aim of our study was to examine the changes in neuropsychological variables and brain structure in a group of long-term SCLC survivors treated with PCI. PATIENTS AND METHODS: Eleven long-term SCLC patients, who underwent PCI at least two years before were compared to an age and education matched healthy control group. Both groups were evaluated using a neuropsychological battery and multimodal structural magnetic resonance imaging (MRI: T1-weigthed and diffusion-weighted imaging, DTI). Voxel-based morphometry (T1-VBM) and Tract-based Spatial Statistics (DTI-TBSS) were used to analyze gray matter (GM) and white matter (WM) integrity, respectively. RESULTS: Nearly half (45%, n = 5) of the SCLC patients met criteria for cognitive impairment in relation to verbal abilities, processing speed and visual memory. In addition, SCLC patients showed significant decreases of GM in subcortical regions such are the basal ganglia bilaterally (including the putamen and caudate), bilateral thalamus and right insula, together with lower WM integrity of the entire corpus callosum. CONCLUSION: This is the first study to demonstrate neuropsychological deficits together with brain-specific structural differences of both GM and WM in long-term SCLC survivors. Our results suggest that PCI therapy is associated with the development of permanent long-term cognitive and structural brain effects in a SCLC population.