Multimodal Multimodal Magnetic Resonance Imaging Research Articles

Radiomic Features from Multi-Modal MRI Combined with Clinical Parameters Predict Molecular Subgroups in Patients with Medulloblastoma

Background: The 2016 WHO Classification of Central Nervous System tumors has included four molecular subgroups under medulloblastoma (MB) as sonic hedgehog (SHH), wingless (WNT), Grade 3 and Group 4. We aimed to develop machine learning models for predicting MB molecular subgroups based on multimodal magnetic resonance imaging (MRI) radiomics, tumor locations and clinical factors. Methods: 122 MB patients were enrolled retrospectively. After selecting robust, nonredundant and relevant features from 5529 extracted radiomics features, a random forest model was constructed based on a training cohort (n = 92) and evaluated on a testing cohort (n = 30). By combining the radiographic features and clinical parameters, two combined prediction models were also built. Findings: The subgroup can be classified using an 11-feature radiomics model with a high area under curve (AUC) of 0.8264 for WNT and modest AUCs of 0.6683, 0.6004 and 0.6979 for SHH, Group 3 and Group 4 in testing cohort, respectively. Incorporating location and hydrocephalus into the radiomics model resulted in improved AUCs of 0.8403 and 0.8317 for WNT and SHH, respectively. After adding gender and age, the AUCs for WNT and SHH were further improved to 0.9097 and 0.8654, while the accuracies were 70% and 86.67% for Group 3 and Group 4, respectively. Interpretation: The prediction performance was excellent for WNT and SHH, while that for Group 3 and Group 4 needs further improvements. Machine learning algorithms offer potentials to non-invasively predict molecular subgroups of MB. Funding Statement: This research was supported by the National Natural Science Foundation of China (No. 81702465, 61571432 and U1804172), the Science and Technology Program of Henan Province (No. 182102310113, 192102310123 and 192102310050). Declaration of Interests: The authors declare no potential conflicts of interest. Ethics Approval Statement: The Human Scientific Ethics Committee of the First Affiliated Hospital of Zhengzhou University has approved the protocol of this study (No. 2019-KY-176).

A nomogram based on bi-regional radiomics features from multimodal magnetic resonance imaging for preoperative prediction of microvascular invasion in hepatocellular carcinoma.

We aimed to develop and validate a nomogram combining bi-regional radiomics features from multimodal magnetic resonance imaging (MRI) and clinicoradiological characteristics to preoperatively predict microvascular invasion (MVI) of hepatocellular carcinoma (HCC). A total of 267 HCC patients were divided into training (n=194) and validation (n=73) cohorts according to MRI data. Bi-regional features were extracted from whole tumors and peritumoral regions in multimodal MRI. The minimum redundancy maximum relevance (mRMR) algorithm was applied to select features and build signatures. The predictive performance of the optimal radiomics signature was further evaluated within subgroups defined by tumor size and alpha fetoprotein (AFP) level. Then, a radiomics nomogram including the optimal radiomics signature, radiographic descriptors, and clinical variables was developed using multivariable regression. The nomogram performance was evaluated based on its discrimination, calibration, and clinical utility. The fusion radiomics signature derived from triphasic dynamic contrast-enhanced (DCE) MR images can effectively classify MVI and non-MVI HCC patients, with an AUC of 0.784 (95% CI: 0.719-0.840) in the training cohort and 0.820 (95% CI: 0.713-0.900) in the validation cohort. The fusion radiomics signature also performed well in the subgroups defined by the two risk factors, respectively. The nomogram, consisting of the fusion radiomics signature, arterial peritumoral enhancement, and AFP level, outperformed the clinicoradiological prediction model in the validation cohort (AUCs: 0.858 vs. 0.729; P=0.022), fitting well in the calibration curves (P>0.05). Decision curves confirmed the clinical utility of the nomogram. The radiomics nomogram can serve as a visual predictive tool for MVI in HCCs, and thus assist clinicians in selecting optimal treatment strategies to improve clinical outcomes.

A multimodal MRI study of the neural mechanisms of emotion regulation impairment in women with obesity

Maladaptive emotion regulation contributes to overeating and impedes weight loss. Our study aimed to compare the voluntary downregulation of negative emotions by means of cognitive reappraisal in adult women with obesity (OB) and female healthy controls (HC) using a data-driven, multimodal magnetic resonance imaging (MRI) approach. Women with OB (n = 24) and HC (n = 25) carried out an emotion regulation task during functional MRI scanning. Seed-to-voxel resting-state connectivity patterns derived from activation peaks identified by this task were compared between groups. Diffusion tensor imaging (DTI) was used to examine white matter microstructure integrity between regions exhibiting group differences in resting-state functional connectivity. Participants in the OB group presented reduced activation in the ventromedial prefrontal (vmPFC) cortex in comparison to the HC group when downregulating negative emotions, along with heightened activation in the extrastriate visual cortex (p < 0.05, AlphaSim-corrected). Moreover, vmPFC peak activity levels during cognitive reappraisal were negatively correlated with self-reported difficulties in emotion regulation. OB patients exhibited decreased functional connectivity between the vmPFC and the temporal pole during rest (peak-pFWE = 0.039). Decreased fractional white-matter track volume in the uncinate fasciculus, which links these two regions, was also found in participants with OB. Taken together, our findings are indicative of emotion regulation deficits in OB being underpinned by dysfunctional hypoactivity in the vmPFC and hyperactivity in the extrastriate visual cortex. Our results provide a potential target circuit for neuromodulatory interventions to improve emotion regulation skills and weight-loss intervention outcomes.

Assessing therapeutic response non-invasively in a neonatal rat model of acute inflammatory white matter injury using high-field MRI

Perinatal infection and inflammatory episodes in preterm infants are associated with diffuse white matter injury (WMI) and adverse neurological outcomes. Inflammation-induced WMI was previously shown to be linked with later hippocampal atrophy as well as learning and memory impairments in preterm infants. Early evaluation of injury load and therapeutic response with non-invasive tools such as multimodal magnetic resonance imaging (MRI) would greatly improve the search of new therapeutic approaches in preterm infants. Our aim was to evaluate the potential of multimodal MRI to detect the response of interleukin-1 receptor antagonist (IL-1Ra) treatment, known for its neuroprotective properties, during the acute phase of injury on a model of neonatal WMI.Rat pups at postnatal day 3 (P3) received intracerebral injection of lipopolysaccharide with systemic IL-1Ra therapy. 24 h later (P4), rats were imaged with multimodal MRI to assess microstructure by diffusion tensor imaging (DTI) and neurochemical profile of the hippocampus with 1H-magnetic resonance spectroscopy. Astrocyte and microglial activation, apoptosis and the mRNA expression of pro-inflammatory and necroptotic markers were assessed.During the acute phase of injury, neonatal LPS exposure altered the concentration of hippocampus metabolites related to neuronal integrity, neurotransmission and membrane integrity and induced diffusivity restriction. Just 24 h after initiation of therapy, early indication of IL-1Ra neuroprotective effect could be detected in vivo by non-invasive spectroscopy and DTI, and confirmed with immunohistochemical evaluation and mRNA expression of inflammatory markers and cell death.In conclusion, multimodal MRI, particularly DTI, can detect not only injury but also the acute therapeutic effect of IL-1Ra suggesting that MRI could be a useful non-invasive tool to follow, at early time points, the therapeutic response in preterm infants.

Monitoring Value of Multimodal Magnetic Resonance Imaging in Disease Progression of Amyotrophic Lateral Sclerosis: A Prospective Observational Study.

Background:Ongoing efforts have been made to identify new neuroimaging markers to track amyotrophic lateral sclerosis (ALS) progression. This study aimed to explore the monitoring value of multimodal magnetic resonance imaging (MRI) in the disease progression of ALS.Methods:From September 2015 to March 2017, ten patients diagnosed with ALS in Peking Union Medical College Hospital completed head MRI scans at baseline and during follow-up. Multimodal MRI analyses, including gray matter (GM) volume measured by voxel-based morphometry; cerebral blood flow (CBF) evaluated by arterial spin labeling; functional connectivity, including low-frequency fluctuation (fALFF) and regional homogeneity (ReHo), measured by resting-state functional MRI; and integrity of white-matter (WM) fiber tracts evaluated by diffusion tensor imaging, were performed in these patients. Comparisons of imaging metrics were made between baseline and follow-up using paired t-test.Results:In the longitudinal comparisons, the brain structure (GM volume of the right precentral gyri, left postcentral gyri, and right thalami) and perfusion (CBF of the bilateral temporal poles, left precentral gyri, postcentral gyri, and right middle temporal gyri) in both motor and extramotor areas at follow-up were impaired to different extents when compared with those at baseline (all P < 0.05, false discovery rate adjusted). Functional connectivity was increased in the motor areas (fALFF of the right precentral gyri and superior frontal gyri, and ReHo of right precentral gyri) and decreased in the extramotor areas (fALFF of the bilateral middle frontal gyri and ReHo of the right precuneus and cingulate gyri) (all P < 0.001, unadjusted). No significant changes were detected in terms of brain WM measures.Conclusion:Multimodal MRI could be used to monitor short-term brain changes in ALS patients.

Combined diffusion tensor imaging and magnetic resonance spectroscopy to predict neurological outcome before transjugular intrahepatic portosystemic shunt.

Hepatic encephalopathy (HE) may occur after transjugular intrahepatic portosystemic shunt (TIPSS) placement. Multimodal magnetic resonance imaging (MRI), combining anatomical sequences, diffusion tensor imaging (DTI) and 1 H magnetic resonance spectroscopy, is modified in cirrhotic patients. To describe multimodal MRI images before TIPSS, to assess if TIPSS induces changes in multimodal MRI, and to find predictors of HE after TIPSS in patients with cirrhosis. Consecutive cirrhotic patients with an indication for TIPSS were prospectively screened. Diagnosis of minimal HE was performed using psychometric HE test score. Multimodal MRI was performed before and 3months after TIPSS placement. Twenty-five consecutive patients were analysed (median age=59, male gender 76%, median Child-Pugh score=8 [5-8], MELD score=12 [9-17], indication for TIPSS placement: ascites/secondary prophylaxis of variceal bleeding/other 20/3/2), no HE/minimal HE/overt HE: 21/4/0. 8/25 patients developed HE after TIPSS. Before TIPSS placement, metabolite concentrations were different in patients with or without minimal HE (lower myo-inositol, mI, higher glutamate/glutamine), but there were no differences in DTI data. TIPSS placement induced changes in metabolite concentrations even in asymptomatic patients, but not in DTI metrics. Baseline fractional anisotropy was significantly lower in patients who developed HE after TIPSS in five regions of interest. TIPSS placement induced significant changes in cerebral metabolites, even in asymptomatic patients. Patients who developed HE after TIPSS displayed lower fractional anisotropy before TIPSS. Brain MRI with DTI acquisition may help selecting patients at risk of HE.

The Processing Time for Recanalization and Size of Ischemic Lesions on DWI is Related With Complete Reperfusion After Mechanical Thrombectomy

Recent studies demonstrated that modified thrombolysis in cerebral infarction (TICI) 3 reperfusion have better functional outcomes than modified TICI 2b after mechanical thrombectomy in acute ischemic stroke with large vessel occlusion. The purpose of this study was to determine significant factors to forecast the presence of complete reperfusion after mechanical thrombectomy based on multimodal magnetic resonance imaging (MRI). We investigated 96 consecutive patients with acute large intracranial artery occlusion of anterior circulation who based on multimodal MRI. Also, we compared clinical and radiologic parameters between patients with modified TICI 3 and those with modified TICI 0-2b. Among 96 eligible subjects received mechanical thrombectomy, 39 patients (40.6%) showed complete reperfusion and 57 partial or nonreperfusion (mTICI 2b-26, mTICI 2a-9, mTICI 1-8, and mTICI 0-14) after mechanical thrombectomy. Patients with mTICI 3 had significantly smaller initial Diffusion weighted images (DWI) lesion volume (P < .01) and much shorter time interval from onset to reperfusion (P < .01) than those patients with mTICI (0-2b). In multivariate analysis, smaller initial DWI volume (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.23-2.57; P < .01) and faster reperfusion time (OR, 1.07; 95% CI 1.01-1.14; P = .015) had an independence significance for complete reperfusion after mechanical thrombectomy. In this study, the ischemic lesion volume on DWI and faster processing time are critical factor to predict the state of complete reperfusion after mechanical thrombectomy.

A Novel Multimodal MRI Analysis for Alzheimer's Disease Based on Convolutional Neural Network.

Recent years, Alzheimer's disease (AD) has become a significant threat to human health while the accurate screening and diagnosis of AD remain a tough problem. Multimodal Magnetic resonance imaging (MRI) can help to identify the variation of brain function and structure in a non-invasive way. Deep learning, especially the convolutional neural networks (CNN), can be utilized to automatically detect appropriate features for classification, which is well adapted for computer-aided AD screening and identification. This paper proposed a multimodal MRI analytical method based on CNN, which is also suitable for single type MRI data analysis. First, the human brain network connectivity matrix were extracted from multimodal MRI data, used as the input data for CNN. Then a novel CNN framework was proposed to process the network matrix and classify AD, amnestic mild cognitive impairment (aMCI) patients and normal controls (NC). The advantage of this method lies in that we combined multimodal MRI information through CNN convolution kernel, and achieved a higher classification accuracy. In our experiments, the comprehensive classification accuracy of AD, aMCI patients and NC was as high as 92.06% when using multimodal MRI data as input, which is effective enough to provide a reference for multimodal MRI data analysis.

Mild cognitive impairment disrupts attention network connectivity in Parkinson's disease: A combined multimodal MRI and meta-analytical study

Mild cognitive impairment (MCI) affects approximately one-third of non-demented Parkinson's Disease (PD) patients. We aimed at investigating the neural correlates of MCI in PD combining multimodal magnetic resonance imaging (MRI) with large-scale data from the literature. We analyzed 31 PD patients and 30 matched controls. The standard neuropsychological assessment of PD-MCI covered memory, attention, executive functions, language and visuospatial abilities. Following validated criteria, 16 patients were classified as showing MCI. Whole-brain functional connectivity and structural volume changes were assessed, respectively, by means of eigenvector centrality (EC) and voxel-based morphometry. To address the involvement of specific functional brain networks, we validated our results by building a meta-analytic co-activation map (MACM) based on the previous literature and then testing its overlap with the parcellation of functional networks derived from 1000 healthy controls. The EC comparison between PD with normal cognition and controls showed a selective decline in interconnectedness in the bilateral lentiform nuclei. Differently, comparing PD with MCI and controls revealed additional changes in non-motor areas. Directly comparing PD with and without MCI, we found a reduced interconnectedness in the bilateral superior parietal lobules and precuneus. No differences in brain volume were detected comparing these patient groups. The MACM and overlap analyses showed that the observed connectivity changes were localized in the hubs of the dorsal attention network. Notably, this aligned with the predominant attention deficit observed in our sample. Overall, functional impairment in the dorsal attention network seems to be the hallmark of MCI due to PD, thus extending previous findings of brain connectivity disruption in non-motor networks.

The effect of glioblastoma heterogeneity on survival stratification: a multimodal MR imaging texture analysis

Background Quantitative evaluation of the effect of glioblastoma (GBM) heterogeneity on survival stratification would be critical for the diagnosis, treatment decision, and follow-up management. Purpose To evaluate the effect of GBM heterogeneity on survival stratification, using texture analysis on multimodal magnetic resonance (MR) imaging. Material and Methods A total of 119 GBM patients (65 in long-term and 54 in short-term survival group, separated by overall survival of 12 months) were selected from the Cancer Genome Atlas, who underwent the T1-weighted (T1W) contrast-enhanced (CE), T1W, T2-weighted (T2W), and FLAIR sequences. For each sequence, the co-occurrence matrix, run-length matrix, and histogram features were extracted to reflect GBM heterogeneity on different scale. The recursive feature elimination based support vector machine was adopted to find an optimal subset. Then the stratification performance of four MR sequences was evaluated, both alone and in combination. Results When each sequence used alone, the T1W-CE sequence performed best, with an area under the receiver operating characteristic curve, accuracy, sensitivity, and specificity of 0.7915, 80.67%, 78.45%, and 83.33%, respectively. When the four sequences combined, the stratification performance was basically equal to that of T1W-CE sequence. In the optimal subset of features extracted from multimodality, those from the T2W sequence weighted the most. Conclusion All the four sequences could reflect heterogeneous distribution of GBM and thereby affect the survival stratification, especially T1W-CE and T2W sequences. However, the stratification performance using only the T1W-CE sequence can be preserved with omission of other three sequences, when investigating the effect of GBM heterogeneity on survival stratification.

Oculomotor Cognitive Control Abnormalities in Australian Rules Football Players with a History of Concussion.

This study used oculomotor, cognitive, and multi-modal magnetic resonance imaging (MRI) measures to assess for neurological abnormalities in current asymptomatic amateur Australian rules footballers (i.e., Australia's most participated collision sport) with a history of sports-related concussion (SRC). Participants were 15 male amateur Australian rules football players with a history of SRC greater than 6 months previously, and 15 sex-, age-, and education-matched athlete control subjects that had no history of neurotrauma or participation in collision sports. Participants completed a clinical interview, neuropsychological measures, and oculomotor measures of cognitive control. MRI investigation involved structural imaging, as well as diffusion tensor imaging and resting-state functional MRI sequences. Despite no group differences on conventional neuropsychological tests and multi-modal MRI measures, Australian rules football players with a history of SRC performed significantly worse on an oculomotor switch task: a measure of cognitive control that interleaves the response of looking towards a target (i.e., a prosaccade) with the response of looking away from a target (i.e., an antisaccade). Specifically, Australian footballers performed significantly shorter latency prosaccades and found changing from an antisaccade trial to a prosaccade trial (switch cost) significantly more difficult than control subjects. Poorer switch cost was related to poorer performance on a number of neuropsychological measures of inhibitory control. Further, when comparing performance on the cognitively more demanding switch task with performance on simpler, antisaccade/prosaccades tasks which require a single response, Australian footballers demonstrated a susceptibility to increased cognitive load, compared to the control group who were unaffected. These initial results suggest that current asymptomatic amateur Australian rules football players with a history of SRC may have persisting, subtle, cognitive changes, which are demonstrable on oculomotor cognitive measures. Future studies are required in order to further elucidate the full nature and clinical relevance of these findings.

Multimodal Magnetic Resonance Imaging of Treatment-Induced Changes to Diffuse Infiltrating Pontine Gliomas in Children and Correlation to Patient Progression-Free Survival

Touse multimodal magnetic resonance imaging (MRI) to quantify treatment-induced changes in the whole volume of diffuse infiltrating pontine gliomas and correlate them with progression-free survival (PFS). This prospective study included 22 children aged 3.3 to 14.7years (median, 5.9years). Multimodal MRI was performed at 3 distinct time points: before treatment, the first week following radiation therapy (RT), and 2months after RT.The imaging protocol included morphologic, multi b-value diffusion; arterial spin labeling; and dynamic susceptibility contrast-enhanced perfusion.Morphologic and multimodal data-lesion volume, diffusion coefficients, relative cerebral blood flow, and relative cerebral blood volume (rCBV)-were recorded at the 3 aforementioned time points.The Wilcoxon test was used to compare each individual parameter variation between time points, and its correlation with PFS was assessed by the Spearman test. Following RT, the tumors' solid component volume decreased by 40% (P<.001). Their median diffusion coefficients decreased by 20% to 40% (P<.001), while median relative cerebral blood flow increased by 60% to 80% (P<.001) and median rCBV increased by 70% (P<.001). PFS was positively correlated with rCBV measured immediately after RT (P=.003), and in patients whose rCBV was above the cutoff value of 2.46, the median PFS was 4.6months longer (P=.001). These indexes tended to return to baseline 2months after RT. Lesion volume before or after RT was not correlated with survival. Multimodal MRI provides useful information about diffuse infiltrating pontine gliomas' response to treatment; rCBV increases following RT, and higher values are correlated with better PFS. High rCBV values following RT should not be mistaken for progression and could be an indicator of response to therapy.

Multimodal magnetic resonance imaging and spectroscopy for prostate cancer screening and staging

Introduction Multi-modal magnetic resonance imaging (MRI) combining T2-weighted imaging with advanced techniques such as diffusion-weighted imaging (DWI), dynamic contrast and proton spectroscopy is a promising tool for prostate cancer screening, staging and treatment planning. Purpose Evaluation and optimization of multi-modal MRI techniques for prostate cancer screening, staging and treatment planning. Materials and methods Participants at high risk of prostate cancer underwent MRI scans including T2-weighted imaging, DWI using echo planar readout, 3D chemical shift imaging (CSI) and dynamic contrast enhanced imaging on a 3T Siemens scanner with data acquisition using spine and surface coils only. The results were analyzed using vendor-supplied and in-house software and scored according to the “Prostate imaging reporting and data system (PI-RADS)” scoring system. Results Despite the promise of spectroscopic biomarkers as a diagnostic tool, the CSI spectra acquired using standard sequences proved generally of insufficient quality for reliable biomarker estimation. Scanner produced metabolite maps proved highly variable and prone to misidentification of metabolites due to poorly resolved peaks. Apparent diffusion coefficient (ADC) maps appeared diagnostically more useful although low signal and noise floor issues at higher b-values also affected the estimation of ADCs and apparent kurtosis observed at low b-values, casting some doubt on the reliability of high kurtosis values reported in the literature for prostate diffusion kurtosis imaging (DKI). Conclusion Reliable quantification of spectroscopic biomarkers for prostate cancer requires improved protocols for CSI and spectroscopy. Apparent kurtosis observed for diffusion weighted images acquired at low maximum b-values are require further validation.

Non-invasive MRI Assessments of Tissue Microstructures and Macromolecules in the Eye upon Biomechanical or Biochemical Modulation.

The microstructural organization and composition of the corneoscleral shell (CSS) determine the biomechanical behavior of the eye, and are important in diseases such as glaucoma and myopia. However, limited techniques can assess these properties globally, non-invasively and quantitatively. In this study, we hypothesized that multi-modal magnetic resonance imaging (MRI) can reveal the effects of biomechanical or biochemical modulation on CSS. Upon intraocular pressure (IOP) elevation, CSS appeared hyperintense in both freshly prepared ovine eyes and living rat eyes using T2-weighted MRI. Quantitatively, transverse relaxation time (T2) of CSS increased non-linearly with IOP at 0–40 mmHg and remained longer than unloaded tissues after being unpressurized. IOP loading also increased fractional anisotropy of CSS in diffusion tensor MRI without apparent change in magnetization transfer MRI, suggestive of straightening of microstructural fibers without modification of macromolecular contents. Lastly, treatments with increasing glyceraldehyde (mimicking crosslinking conditions) and chondroitinase-ABC concentrations (mimicking glycosaminoglycan depletion) decreased diffusivities and increased magnetization transfer in cornea, whereas glyceraldehyde also increased magnetization transfer in sclera. In summary, we demonstrated the changing profiles of MRI contrast mechanisms resulting from biomechanical or biochemical modulation of the eye non-invasively. Multi-modal MRI may help evaluate the pathophysiological mechanisms in CSS and the efficacy of corneoscleral treatments.

The spectrum of structural and functional imaging abnormalities in temporal lobe epilepsy.

Although most temporal lobe epilepsy (TLE) patients show marked hippocampal sclerosis (HS) upon pathological examination, 40% present with no significant cell loss but gliotic changes only. To evaluate effects of hippocampal pathology on brain structure and functional networks, we aimed at dissociating multimodal magnetic resonance imaging (MRI) characteristics in patients with HS (TLE-HS) and those with gliosis only (TLE-G). In 20 TLE-HS, 19 TLE-G, and 25 healthy controls, we carried out a novel MRI-based hippocampal subfield surface analysis that integrated volume, T2 signal intensity, and diffusion markers with seed-based hippocampal functional connectivity. Compared to controls, TLE-HS presented with marked ipsilateral atrophy, T2 hyperintensity, and mean diffusivity increases across all subfields, whereas TLE-G presented with dentate gyrus hypertrophy, focal increases in T2 intensity and mean diffusivity. Multivariate assessment confirmed a more marked ipsilateral load of anomalies across all subfields in TLE-HS, whereas anomalies in TLE-G were restricted to the subiculum. A between-cohort dissociation was independently suggested by resting-state functional connectivity analysis, revealing marked hippocampal decoupling from anterior and posterior default mode hubs in TLE-HS, whereas TLE-G did not differ from controls. Back-projection connectivity analysis from cortical targets revealed consistently decreased network embedding across all subfields in TLE-HS, while changes in TLE-G were limited to the subiculum. Hippocampal disconnectivity strongly correlated to T2 hyperintensity and marginally to atrophy. Multimodal MRI reveals diverging structural and functional connectivity profiles across the TLE spectrum. Pathology-specific modulations of large-scale functional brain networks lend novel evidence for a close interplay of structural and functional disruptions in focal epilepsy. Ann Neurol 2016;80:142-153.

High-Performance Upconversion Nanoprobes for Multimodal MR Imaging of Acute Ischemic Stroke.

Multimodal magnetic resonance (MR) imaging, including MR angiography (MRA) and MR perfusion (MRP), plays a critical role in the diagnosis and surveillance of acute ischemic stroke. However, these techniques are hindered by the low T1 relaxivity, short circulation time, and high leakage rate from vessels of clinical Magnevist. To address these problems, nontoxic polyethylene glycol (PEG)ylated upconversion nanoprobes (PEG-UCNPs) are synthesized and first adopted for excellent MRA and MRP imaging, featuring high diagnostic sensitivity toward acute ischemic stroke in high-resolution imaging. The investigations show that the agent possesses superior advantages over clinical Magnevist, such as much higher relaxivity, longer circulation time, and lower leakage rate, which guarantee much better imaging efficiency. Remarkably, an extremely small dosage (5 mg Gd kg(-1) ) of PEG-UCNPs provides high-resolution MRA imaging with the vascular system delineated much clearer than the Magnevist with clinical dosage as high as 108 mg Gd kg(-1) . On the other hand, the long circulation time of PEG-UCNPs enables the surveillance of the progression of ischemic stroke using MRA or MRP. Once translated, these PEG-UCNPs are expected to be a promising candidate for substituting the clinical Magnevist in MRA and MRP, which will significantly lengthen the imaging time window and improve the overall diagnostic efficiency.

Spatiotemporal characterization of brain infarction by sequential multimodal MR imaging following transient focal ischemia in a Rat model of intra-arterial middle cerebral artery occlusion.

To assess spatiotemporal brain infarction evolution by sequential multimodal magnetic resonance (MR) imaging in an endovascular model of acute stroke in rats. A microwire was selectively placed in the middle cerebral artery (MCA) in 16 consecutives rats during 90minutes occlusion. Longitudinal 7-T MR imaging, including angiography, diffusion, and perfusion was performed during ischemia, immediately after reperfusion, 3h and 24h after subsequent reperfusion. MCA occlusion was complete in 75% and partial in 18.7%. Hypoperfusion (mean ± SD) was observed in all animals during ischemia (-59 ± 18% of contralateral hemisphere, area 31 ± 5mm2). Infarction volume (mean ± SD) was 90 ± 64mm3 during ischemia and 57 ± 67mm3 at 24h. Brain infarction was fronto-parietal cortical in five animals (31%), striatal in four animals (25%), and cortico-striatal in seven animals (44%) at 24h. All rats survived at 24h. This model is suitable to neuroprotection studies because of possible acute and close characterization of spatiotemporal evolution of brain infarction by MR imaging techniques, and evidence of ischemic penumbra, the target of neuroprotection agents. However, optimization of the brain infarct reproducibility needs further technical and neurointerventional tools improvements. • Nitinol microwire is MRI compatible allowing spatiotemporal characterization of brain infarction in rats. • Microwire selective placement in middle cerebral artery allows complete artery occlusion in 75 %. • A diffusion/perfusion mismatch during arterial occlusion is observed in 77 % of rats.

Opportunities in multimodal neuroimaging for optimizing thrombolytic therapy for ischemic stroke

The main purpose of examination of patients before thrombolytic therapy for ischemic stroke (IS) is to timely identify contraindications to the use of recombinant tissue plasminogen activator. Objective: to estimate opportunities and benefits in applying multimodal magnetic resonance imaging (MRI) to improve clinical outcomes in acute stroke, among other processes, by enhancing the efficiency and safety of thrombolytic therapy. Patients and methods . The clinical experience of the S.M. Kirov Military Medical Academy in using multimodal MRI of the brain since 2004 was analyzed in patients with stroke. Results. Comprehensive assessment of the results of perfusion-weighted MRI of the brain and those of transcranial Doppler ultrasound identified five clinically significant variants of perfusion changes in IS: normal perfusion; postischemic hyperemia; persistent hypoperfusion; acute pathological hyperperfusion, and unrecovered perfusion. With an irreversible tissue damage volume of >60 cm3 on day 1 of stroke, as evidenced by diffusion-weighted MRI, the odd ratio for cerebral edema in the acutest period of the disease is 39.4% (95% CI 2.57–2436; p<0.05). The risk of hemorrhagic transformation increases with a measured diffusion coefficient in the area of the nucleus of developing nonlacunar infarct <35×10-5 mm2/sec within the first 24 hours after disease onset (p<0.005). Conclusion. The data of local clinical practice and the results of international clinical trials show that multimodal MRI of the brain is a reliable tool for the detailed evaluation of the expected efficiency and safety of thrombolytic therapy for IS. When persistent hypoperfusion is detected, the determination of perfusion-diffusion mismatch is of no informative value in deciding on whether thrombolytic therapy can be performed. Estimating the volume of pathological changes on diffusion-weighted images and the measured diffusion coefficient in the area of the nucleus of developing nonlacunar infarct in the measured diffusion coefficient maps allows the risk of major intracranial complications due to IS to be identified.

Multimodal Quantitative MR Imaging of the Thalamus in Multiple Sclerosis and Neuromyelitis Optica.

To systematically investigate structural and functional alterations of the thalamus and its subregions through a multimodal magnetic resonance (MR) imaging technique and examine its clinical relevance in multiple sclerosis (MS) and neuromyelitis optica (NMO). The institutional review board approved this study, and written informed consent was obtained from each participant. Thirty-seven patients with MS, 39 patients with NMO, and 40 healthy control subjects were recruited. Six MR imaging measurements were obtained for each participant and compared between groups in the thalamus and its seven subregions, including gray matter (GM) volume, fractional anisotropy, mean diffusivity, amplitude of low-frequency fluctuation, cross-correlation coefficient of spontaneous low frequency, and weighted functional connectivity strength. Partial correlation was used to estimate the MR imaging-clinical relationships. Both MS and NMO exhibited widespread GM atrophy (GM volume in MS, 0.244; NMO, 0.297; and control subjects, 0.329; P < .001) and diffusion abnormalities (fractional anisotropy in MS, 0.293; NMO, 0.323; and control subjects, 0.355; P < .001) in the whole thalamus and several subregions, while MS showed more severe changes than NMO. Decreased cross-correlation coefficient of spontaneous low-frequency and weighted functional connectivity strength was observed in several thalamus subregions in MS (P < .05), but no significant functional abnormalities were identified in NMO. GM volume, fractional anisotropy, and mean diffusivity, not functional changes of the thalamus and thalamic subregions, correlated with the patients' clinical variables and exhibited high discriminative power in distinguishing the three groups. Similar patterns of thalamic structural alteration were identified in MS and NMO, but MS showed more severe pathologic changes. The thalamus is a key node for functional disconnection in MS but not in NMO.

Hypoxia-induced neuroinflammatory white-matter injury reduced by minocycline in SHR/SP.

Hypertensive small vessel disease is a major cause of vascular cognitive impairment (VCI). Spontaneously hypertensive/stroke prone rats (SHR/SP) with unilateral carotid artery occlusion (UCAO) and a Japanese permissive diet (JPD) have white-matter (WM) damage similar to that seen in VCI. We hypothesized that WM injury was due to hypoxia-mediated, blood-brain barrier (BBB) disruption. Twelve-week-old SHR/SP had UCAO/JPD and were studied with immunohistochemistry, biochemistry, multimodal magnetic resonance imaging (MRI), and Morris water maze (MWM) testing. One week after UCAO/JPD, WM showed a significant increase in hypoxia inducible factor-1α (HIF-1α), which increased further by 3 weeks. Prolyl hydroxylase-2 (PHD2) expression decreased at 1 and 3 weeks. Infiltrating T cells and neutrophils appeared around endothelial cells from 1 to 3 weeks after UCAO/JPD, and matrix metalloproteinase-9 (MMP-9) colocalized with inflammatory cells. At 3 weeks, WM immunostained for IgG, indicating BBB leakage. Minocycline (50 mg/kg intraperitoneally) was given every other day from weeks 12 to 20. Multimodal MRI showed that treatment with minocycline significantly reduced lesion size and improved cerebral blood flow. Minocycline improved performance in the MWM and prolonged survival. We propose that BBB disruption occurred secondary to hypoxia, which induced an MMP-9-mediated infiltration of leukocytes. Minocycline significantly reduced WM damage, improved behavior, and prolonged life.