Multimodal Magnetic Resonance Imaging Approach Research Articles

Basis of executive functions in fine-grained architecture of cortical and subcortical human brain networks.

Theoretical models suggest that executive functions rely on both domain-general and domain-specific processes. Supporting this view, prior brain imaging studies have revealed that executive activations converge and diverge within broadly characterized brain networks. However, the lack of precise anatomical mappings has impeded our understanding of the interplay between domain-general and domain-specific processes. To address this challenge, we used the high-resolution multimodal magnetic resonance imaging approach of the Human Connectome Project to scan participants performing 3 canonical executive tasks: n-back, rule switching, and stop signal. The results reveal that, at the individual level, different executive activations converge within 9 domain-general territories distributed in frontal, parietal, and temporal cortices. Each task exhibits a unique topography characterized by finely detailed activation gradients within domain-general territory shifted toward adjacent resting-state networks; n-back activations shift toward the default mode, rule switching toward dorsal attention, and stop signal toward cingulo-opercular networks. Importantly, the strongest activations arise at multimodal neurobiological definitions of network borders. Matching results are seen in circumscribed regions of the caudate nucleus, thalamus, and cerebellum. The shifting peaks of local gradients at the intersection of task-specific networks provide a novel mechanistic insight into how partially-specialized networks interact with neighboring domain-general territories to generate distinct executive functions.

Multimodal imaging of brain reorganization in hearing late learners of sign language.

The neural plasticity underlying language learning is a process rather than a single event. However, the dynamics of training‐induced brain reorganization have rarely been examined, especially using a multimodal magnetic resonance imaging approach, which allows us to study the relationship between functional and structural changes. We focus on sign language acquisition in hearing adults who underwent an 8‐month long course and five neuroimaging sessions. We assessed what neural changes occurred as participants learned a new language in a different modality—as reflected by task‐based activity, connectivity changes, and co‐occurring structural alterations. Major changes in the activity pattern appeared after just 3 months of learning, as indicated by increases in activation within the modality‐independent perisylvian language network, together with increased activation in modality‐dependent parieto‐occipital, visuospatial and motion‐sensitive regions. Despite further learning, no alterations in activation were detected during the following months. However, enhanced coupling between left‐lateralized occipital and inferior frontal regions was observed as the proficiency increased. Furthermore, an increase in gray matter volume was detected in the left inferior frontal gyrus which peaked at the end of learning. Overall, these results showed complexity and temporal distinctiveness of various aspects of brain reorganization associated with learning of new language in different sensory modality.

Effects of Acupuncture on Cancer-Related Cognitive Impairment in Chinese Gynecological Cancer Patients: A Pilot Cohort Study.

Background: Among women in China, gynecological cancers are the second most common cancers after breast cancer. Cancer-related cognitive impairment (CRCI) has emerged as a significant problem affecting gynecological cancer survivors. While acupuncture has been used in different aspects of cancer care, the possible positive effects of acupuncture on cognitive impairment have received little attention. This study hypothesized that patients would demonstrate lower neurocognitive performance and lower structural connectivity compared to healthy controls. This pilot study also hypothesized that acupuncture may potentially be effective in treating CRCI of cancer patients by increasing brain structural connectivity and integrity. Methods: This prospective cohort study consisted of 3 stages: the first stage included a group of gynecological cancer patients and a group of age-matched healthy controls. This baseline stage used a core set of neurocognitive tests to screen patients with cognitive impairment and used a multimodal approach of brain magnetic resonance imaging (MRI) to explore the possible neurobiological mechanism of cognitive impairment in cancer patients, comparing the results with a group of noncancer controls. The second stage involved assigning CRCI patients into the acupuncture intervention group, while patients without CRCI were assigned into the cancer control group. The third stage was a postintervention assessment of neurocognitive function by the same set of neurocognitive tests at baseline. To explore the possible neurobiological basis of acupuncture for treating CRCI, this study also used a multimodal MRI approach to assess changes in brain structural connectivity, and neurochemical properties in patients at pre- and postacupuncture intervention. Results: This study found that the prevalence of cognitive impairment in Chinese gynecological cancer patients at diagnosis was 26.67%. When investigating the microstructural white matter in the brain, diffusion tensor imaging data in this study indicated that premorbid cognitive functioning (before clinical manifestations become evident) has already existed, as the global and local connectome properties in the entire patient group were lower than in the healthy control group. Using magnetic resonance spectroscopy, this study indicated there was a significant reduction of relative concentration of NAA (N-acetyl aspartate) in the left hippocampus, comparing these results with healthy controls. Regarding the effects of acupuncture on reducing CRCI, patients in the acupuncture group reported better neurocognitive test performance after matching for age, menopausal status, cancer stage, and chemotherapy regimen dosage. On a microstructural level, acupuncture’s ability to reduce CRCI may be attributed to a reduction in demyelination and an enhancement of the neuronal viability of white matter in the hippocampus. Conclusion: This pilot study indicates that acupuncture is a promising intervention in treating CRCI in gynecological cancer patients undergoing chemotherapy; however, it requires evaluation in larger randomized controlled studies to definitively assess its benefit. By using a multimodal imaging approach, this pilot study also provides novel insights into the neurobiological basis of cognitive impairment on the human brain that has been induced by cancer and/or its treatment.

Gray Matter Involvement in Radiologically Isolated Syndrome.

The unanticipated magnetic resonance imaging (MRI) detection in the brain of asymptomatic subjects of white matter lesions suggestive of multiple sclerosis has recently been named as radiologically isolated syndrome (RIS). The pathophysiological processes of RIS remain largely unknown and questions as to whether gray matter alterations actually occur in this entity are yet to be investigated in more detail. By means of a 3 T multimodal MRI approach, we searched for cortical and deep gray matter changes in a cohort of RIS patients. Seventeen RIS patients, 17 clinically isolated syndrome (CIS) patients (median disease duration from symptom onset = 12 months), and 17 healthy controls underwent MRI and neuropsychological testing. Normalized deep gray matter volumes and regional cortical thickness were assessed using FreeSurfer. SIENAX was used to obtain normalized global and cortical brain volumes. Voxelwise morphometry analysis was performed by using SPM8 software to localize regions of brain tissue showing significant changes of fractional anisotropy or mean diffusivity. Although no differences were observed between CIS and healthy controls groups, RIS patients showed significantly lower normalized cortical volume (673 ± 27.07 vs 641 ± 35.88 [cm3 × 103, Tukey P test = 0.009) and mean thalamic volume (0.0051 ± 0.4 vs 0.0046 ± 0.4 mm, P = 0.014) compared with healthy controls. RIS patients also showed significant thinning in a number of cortical areas, that were primarily distributed in frontal and temporal lobes (P < 0.05, uncorrected). Strong correlations were observed between T2-white matter lesion volume and regional cortical thickness (rho spearman ranging from 0.60 to 0.80). Our data suggest that white matter lesions on T2-weighted images are not the only hallmark of RIS. Future longitudinal studies with larger samples are warranted to better clarify the effect of RIS-related white matter lesions on gray matter tissue.

T2-Weighted MRI Detects Presymptomatic Pathology in the SOD1 Mouse Model of ALS

Neuroinflammation has been identified as a potential therapeutic target in amyotrophic lateral sclerosis (ALS), but relevant biomarkers are needed. The superoxide dismutase (SOD1)G93A transgenic mouse model of ALS offers a unique opportunity to study and potentially manipulate presymptomatic pathology. While T2-weighted magnetic resonance imaging (MRI) has been shown to be sensitive to pathologic changes at symptom onset, no earlier biomarkers were previously identified and the underlying histopathologic correlates remain uncertain. To address these issues, we used a multimodal MRI approach targeting structural (T2, T1, apparent diffusion coefficient (ADC), magnetization transfer ratio (MTR)), vascular (gadolinium diethylene triamine pentaacetic acid), and endothelial (vascular cell adhesion molecule–microparticles of iron oxide) changes, together with histopathologic analysis from presymptomatic to symptomatic stages of disease. Presymptomatic changes in brainstem nuclei were evident on T2-weighted images from as early as 60 days (P<0.05). Histologic indices of vacuolation, astro- and microglial activation all correlated with T2-weighted changes. Significant reductions in ADC (P<0.01) and MTR (P<0.05) were found at 120 days in the same brainstem nuclei. No changes in T1 relaxation, vascular permeability, or endothelial activation were found at any stage of disease. These findings suggest that T2-weighted MRI offers the strongest biomarker potential in this model, and that MRI has unique potential for noninvasive and longitudinal assessment of presymptomatically applied therapeutic and neuroprotective agents.

Multimodal MRI as a diagnostic biomarker for amyotrophic lateral sclerosis.

ObjectiveReliable biomarkers for amyotrophic lateral sclerosis (ALS) are needed, given the clinical heterogeneity of the disease. Here, we provide proof-of-concept for using multimodal magnetic resonance imaging (MRI) as a diagnostic biomarker for ALS. Specifically, we evaluated the added diagnostic utility of proton magnetic resonance spectroscopy (MRS) to diffusion tensor imaging (DTI).MethodsTwenty-nine patients with ALS and 30 age- and gender-matched healthy controls underwent brain MRI which used proton MRS including spectral editing techniques to measure γ-aminobutyric acid (GABA) and DTI to measure fractional anisotropy of the corticospinal tract. Data were analyzed using logistic regression, t-tests, and generalized linear models with leave-one-out analysis to generate and compare the resulting receiver operating characteristic (ROC) curves.ResultsThe diagnostic accuracy is significantly improved when the MRS data were combined with the DTI data as compared to the DTI data only (area under the ROC curves (AUC) = 0.93 vs. AUC = 0.81; P = 0.05). The combined MRS and DTI data resulted in sensitivity of 0.93, specificity of 0.85, positive likelihood ratio of 6.20, and negative likelihood ratio of 0.08 whereas the DTI data only resulted in sensitivity of 0.86, specificity of 0.70, positive likelihood ratio of 2.87, and negative likelihood ratio of 0.20.InterpretationCombining multiple advanced neuroimaging modalities significantly improves disease discrimination between ALS patients and healthy controls. These results provide an important step toward advancing a multimodal MRI approach along the diagnostic test development pathway for ALS.

The Ins and Outs of the BCCAo Model for Chronic Hypoperfusion: A Multimodal and Longitudinal MRI Approach

Cerebral hypoperfusion induced by bilateral common carotid artery occlusion (BCCAo) in rodents has been proposed as an experimental model of white matter damage and vascular dementia. However, the histopathological and behavioral alterations reported in this model are variable and a full characterization of the dynamic alterations is not available. Here we implemented a longitudinal multimodal magnetic resonance imaging (MRI) design, including time-of-flight angiography, high resolution T1-weighted images, T2 relaxometry mapping, diffusion tensor imaging, and cerebral blood flow measurements up to 12 weeks after BCCAo or sham-operation in Wistar rats. Changes in MRI were related to behavioral performance in executive function tasks and histopathological alterations in the same animals. MRI frequently (70%) showed various degrees of acute ischemic lesions, ranging from very small to large subcortical infarctions. Independently, delayed MRI changes were also apparent. The patterns of MRI alterations were related to either ischemic necrosis or gliosis. Progressive microstructural changes revealed by diffusion tensor imaging in white matter were confirmed by observation of myelinated fiber degeneration, including severe optic tract degeneration. The latter interfered with the visually cued learning paradigms used to test executive functions. Independently of brain damage, BCCAo induced progressive arteriogenesis in the vertebrobasilar tree, a process that was associated with blood flow recovery after 12 weeks. The structural alterations found in the basilar artery were compatible with compensatory adaptive changes driven by shear stress. In summary, BCCAo in rats induces specific signatures in multimodal MRI that are compatible with various types of histological lesion and with marked adaptive arteriogenesis.

Multimodal MRI in Neurodegenerative Disorders

In the last twenty years, advanced magnetic resonance imaging (MRI) techniques have provided fundamental knowledge about neurodegenerative processes underlying several neurological and psychiatric diseases. The native approach in this field of study was the investigation of a single MRI parameter at a time: (a) blood oxygenation-level-dependent (BOLD) images, (b) anatomical 3D T1-weighted images, (c) diffusion-weighted imaging (DWI)/diffusion tensor imaging (DTI), and (d) quantitative relaxometry. (a) The common observation in functional MRI studies is that increasing in the BOLD MRI signal represents increasing of neural activity. Such a neurophysiological “activation” results from elevated oxygen saturation levels (and reduced paramagnetic deoxyhemoglobin contents) of capillary and venous blood. These positive signal changes are considered the basis for the functional organization of the brain. (b) The T1-weighted sequence allows the employment of several neuroanatomical techniques able to describe and quantify macrostructural changes by using probabilistic (voxel-based morphometry analysis) or quantitative research tools (manual/automatic region-of-interest volumetry, cortical thickness measurements). (c) DWI and DTI provide specific quantitative measurement of micro-structural changes within white and gray matter compartments. In particular DTI provides quantitative parameters, such as the mean diffusivity that increases with microscopic barrier disruption and extracellular fluid accumulation and the fractional anisotropy that provides information on the microstructural integrity of highly oriented microstructures (i.e., myelin). (d) Finally, another potential MRI technique is the quantification of mineral levels in the brain. MR relaxometry is a sensitive method to evaluate the brain iron content in vivo. Iron accumulation has been implicated in the pathogenesis of many neurodegenerative diseases. In the last five years, multimodal neuroimaging has became the most popular approach to study pathophysiology of diseased brain. In fact, the aim of this field of study is to quantify the single or combined weight of MRI parameters in describing neurodegenerative processes. In other words, the possibility to measure MR parameters sensitive to complementary tissue characteristics (e.g., volume atrophy, iron deposition, and microstructural damage) could have great potential for investigating pathological changes in several neurologic/psychiatric diseases. At this moment, important new findings have been reported although several issues remain open. In this special edition, we have featured some papers that address such issues. The first paper of this special edition is more forward-looking. In fact, it presents a new experimental multimodal MRI approach to better elucidate interrelated gray and white matter changes in schizophrenic patients. This new method represents a theoretical evolution of the previous and well-known voxel-based analysis of T1-weighted images that generally provides a mixed measure of neuronal “volume” or “density.” The second and third papers provide fundamental overviews of recent findings about neurodegenerative processes underlying Alzheimer's disease (AD) and mild cognitive impairments (MCIs) obtained through a multimodal neuroimaging approach. The subsequent paper addresses the specific advance in functional neuroimaging studies of AD and MCI patients. All these papers highlight the importance of multimodal neuroimaging in enhancing our ability to diagnose MCI and AD in its early stages. Finally, the last two papers present the application of advanced MRI measurements (automatic ROI volumetry, cortical thickness measurements, and T2* iron quantification) to define the presence of new biomarkers able to distinguish AD patients from normal pressure hydrocephalus and to improve the accurate diagnosis of suspect neuroferritinopathy, a neurodegenerative disorder characterized by the deposition of iron and ferritin in the brain. Antonio Cerasa Andrea Cherubini Patrice Peran