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Like other dangerous pollutants in the air, asbestos has negative and adverse effects on human and animal health. The present study is designed to determine the concentration of asbestos in the air of the most industrial city of Iran (Karaj) in 2018–2019. For this purpose, 4 samples were taken from different areas of the air of Karaj during a year with an SKC pump and flow of 6 L/min for 8 h and in 45 days, and a total of 68 samples of asbestos fibers were collected. Then, the samples were analyzed by phase-contrast microscope (PCM) and scanning electron microscopy (SEM). Eventually, the health effects of asbestos fibers were evaluated by the IRIS EPA method. The average concentration of asbestos fibers was 1.84 f/L PCM and 18.16 f/L SEM. Also, the results of statistical correlation analysis indicated that asbestos fibers are positively correlated with wind speed but negatively correlated with the other three parameters (temperature, relative humidity, and pressure). On the other hand, the average annual risk of asbestos fiber in the ambient air of Karaj for all samples was in the range of 4.32 × 10−6 to 1.81 × 10−4 which in some places had more danger than the recommended risk range. According to the EPA guidelines, carcinogenicity acceptable levels are in the range of 10−4 and 10−6. Values higher than 10−4 have more carcinogenic risk and values lower than 10−6 have a lower carcinogenic risk. [ABSTRACT FROM AUTHOR]

The intervertebral disc's (IVD) annulus fibrosus (AF) retains the hydrostatic pressure of the nucleus pulposus (NP), controls the range of motion, and maintains the integrity of the motion segment. The microstructure of the AF is not yet fully understood and quantitative characterization is lacking, leaving a caveat in modern medicine's ability to prevent and treat disc failure (e.g., disc herniation). In this study, we show a reconstruction of the 3D microstructure of the fibers that constitute the AF via MRI diffusion tensor imaging (DTI) followed by fiber tracking. A quantitative analysis presents an anisotropic structure with significant architectural differences among the annuli along the width of the fibrous belt. These findings indicate that the outer annuli's construction reinforces the IVD while providing a sufficient degree of motion. Our findings also suggest an increased role of the outer annuli in IVD nourishment. [ABSTRACT FROM AUTHOR]

Positron emission tomography (PET) using fluorodeoxyglucose (18F-FDG) combined with magnetic resonance imaging (MR) is an emerging hybrid modality that has shown utility in evaluating abdominal and pelvic disease entities. Together, the high soft tissue contrast and metabolic/functional imaging capabilities make this modality ideal for oncologic imaging in many organ systems. Its clinical utility continues to evolve and future research will help solidify its role in oncologic imaging. In this manuscript, we aim to (1) provide an overview of the various PET/MR systems, describing the strengths and weaknesses of each system, and (2) review the oncologic applications for 18F-FDG PET/MR in the abdomen and pelvis. [ABSTRACT FROM AUTHOR]

Late-life depression (LLD) may increase the risk of Alzheimer's dementia (AD). While amyloidopathy accelerates AD progression, its role in such patients has not yet been elucidated. We hypothesized that cerebral amyloidopathy distinctly affects the alteration of brain network topology and may be associated with distinct cognitive symptoms. We recruited 26 and 27 depressed mild cognitive impairment (MCI) patients with (LLD-MCI-A(+)) and without amyloid accumulation (LLD-MCI-A(−)), respectively, and 21 normal controls. We extracted structural brain networks using their diffusion-weighted images. We aimed to compare the distinct network deterioration in LLD-MCI with and without amyloid accumulation and the relationship with their distinct cognitive decline. Thus, we performed a group comparison of the network topological measures and investigated any correlations with neurocognitive testing scores. Topological features of brain networks were different according to the presence of amyloid accumulation. Disrupted network connectivity was highly associated with impaired recall and recognition in LLD-MCI-A(+) patients. Inattention and dysexecutive function were more influenced by the altered networks involved in fronto-limbic circuitry dysfunction in LLD-MCI-A(−) patients. Our results show that alterations in brain network topology may reflect different cognitive dysfunction depending on amyloid accumulation in depressed older adults with MCI. [ABSTRACT FROM AUTHOR]

To understand brain function it is necessary to characterize both the underlying structural connectivity between neurons and the physiological integrity of these connections. Previous research exploring insect brain connectivity has typically used electron microscopy techniques, but this methodology cannot be applied to living animals and so cannot be used to understand dynamic physiological processes. The relatively large brain of the desert locust, Schistercera gregaria (Forksȧl) is ideal for exploring a novel methodology; micro diffusion magnetic resonance imaging (micro-dMRI) for the characterization of neuronal connectivity in an insect brain. The diffusion-weighted imaging (DWI) data were acquired on a preclinical system using a customised multi-shell diffusion MRI scheme optimized to image the locust brain. Endogenous imaging contrasts from the averaged DWIs and Diffusion Kurtosis Imaging (DKI) scheme were applied to classify various anatomical features and diffusion patterns in neuropils, respectively. The application of micro-dMRI modelling to the locust brain provides a novel means of identifying anatomical regions and inferring connectivity of large tracts in an insect brain. Furthermore, quantitative imaging indices derived from the kurtosis model that include fractional anisotropy (FA), mean diffusivity (MD) and kurtosis anisotropy (KA) can be extracted. These metrics could, in future, be used to quantify longitudinal structural changes in the nervous system of the locust brain that occur due to environmental stressors or ageing. [ABSTRACT FROM AUTHOR]

Since the relatively recent regulatory approval for clinical use in both Europe and North America, 7-Tesla (T) MRI has been adopted for clinical practice at our institution. Based on this experience, this article reviews the unique features of 7-T MRI neuroimaging and addresses the challenges of establishing a 7-T MRI clinical practice. The underlying fundamental physics principals of high-field strength MRI are briefly reviewed. Scanner installation, safety considerations, and artifact mitigation techniques are discussed. Seven-tesla MRI case examples of neurologic diseases including epilepsy, vascular abnormalities, and tumor imaging are presented to illustrate specific applications of 7-T MRI. The advantages of 7-T MRI in conjunction with advanced neuroimaging techniques such as functional MRI are presented. Seven-tesla MRI produces more detailed information and, in some cases, results in specific diagnoses where previous 3-T studies were insufficient. Still, persistent technical issues for 7-T scanning present ongoing challenges for radiologists. [ABSTRACT FROM AUTHOR]

Purpose: Impaired olfactory function is one of the main features of Parkinson's disease. However, how peripheral olfactory structures are involved remains unclear. Using diffusion tensor imaging fiber tracking, we investigated for MRI microstructural changes in the parkinsonian peripheral olfactory system and particularly the olfactory tract, in order to seek a better understanding of the structural alternations underlying hyposmia in Parkinson's disease. Methods: All patients were assessed utilizing by the Italian Olfactory Identification Test for olfactory function and the Unified Parkinson's Disease Rating Scale-III part as well as Hoehn and Yahr rating scale for motor disability. Imaging was performed on a 3 T Clinical MR scanner. MRI data pre-processing was carried out by DTIPrep, diffusion tensor imaging reconstruction, and fiber tracking using Diffusion Toolkit and tractography analysis by TrackVis. The following parameters were used for groupwise comparison: fractional anisotropy, mean diffusivity, radial diffusivity, axial diffusivity, and tract volume. Results: Overall 23 patients with Parkinson's disease (mean age 63.6 ± 9.3 years, UPDRS-III 24.5 ± 12.3, H&Y 1.9 ± 0.5) and 18 controls (mean age 56.3 ± 13.7 years) were recruited. All patients had been diagnosed hyposmic. Diffusion tensor imaging analysis of the olfactory tract showed significant fractional anisotropy, and tract volume decreases for the Parkinson's disease group compared with controls (P < 0.05). Fractional anisotropy and age, in the control group, were significant for multiple correlations (r = − 0.36, P < 0.05, Spearman's rank correlation). Conclusions: Fiber tracking diffusion tensor imaging analysis of olfactory tract was feasible, and it could be helpful for characterizing hyposmia in Parkinson's disease. [ABSTRACT FROM AUTHOR]

Objective: In local SAR compression algorithms, the overestimation is generally not linearly dependent on actual local SAR. This can lead to large relative overestimation at low actual SAR values, unnecessarily constraining transmit array performance. Method: Two strategies are proposed to reduce maximum relative overestimation for a given number of VOPs. The first strategy uses an overestimation matrix that roughly approximates actual local SAR; the second strategy uses a small set of pre-calculated VOPs as the overestimation term for the compression. Result: Comparison with a previous method shows that for a given maximum relative overestimation the number of VOPs can be reduced by around 20% at the cost of a higher absolute overestimation at high actual local SAR values. Conclusion: The proposed strategies outperform a previously published strategy and can improve the SAR compression where maximum relative overestimation constrains the performance of parallel transmission. [ABSTRACT FROM AUTHOR]

Structural and functional neuroimaging studies have shown that brain areas associated with fear and anxiety (defensive system areas) are modulated by individual differences in sensitivity to punishment (SP). However, little is known about how SP is related to brain functional connectivity and the factors that modulate this relationship. In this study, we investigated whether a simple methodological manipulation, such as performing a resting state with eyes open or eyes closed, can modulate the manifestation of individual differences in SP. To this end, we performed an exploratory fMRI resting state study in which a group of participants (n = 88) performed a resting state with eyes closed and another group (n = 56) performed a resting state with eyes open. All participants completed the Sensitivity to Punishment and Sensitivity to Reward Questionnaire. Seed-based functional connectivity analyses were performed in the amygdala, hippocampus, and periaqueductal gray (PAG). Our results showed that the relationship between SP and left amygdala-precuneus and left hippocampus-precuneus functional connectivity was modulated by eye state. Moreover, in the eyes open group, SP was negatively related to the functional connectivity between the PAG and amygdala and between the PAG and left hippocampus, and it was positively related to the functional connectivity between the amygdala and hippocampus. Together, our results may suggest underlying differences in the connectivity between anxiety-related areas based on eye state, which in turn would affect the manifestation of individual differences in SP. [ABSTRACT FROM AUTHOR]

Background: Prognostic significance of troponin-I (T-I) elevation for poor short-term outcome in thrombolyzed ischemic stroke patients remains uncertain. Objectives: To evaluate its role as a predictive biomarker of short-term outcome in thrombolyzed ischemic stroke patients. Methods: This study included 72 acute ischemic stroke patients who were treated with intravenous thrombolytic therapy. All patients were subjected to clinical assessment and measurement of serum T-I level on admission. Outcome was assessed 3 months after stroke onset using the National Institute of Health Stroke Scale (NIHSS) and modified Rankin scale. Results: Thirteen patients had elevated serum T-I level (group 1) and the remaining 59 were classified as group 2. Group 1 had a higher statistically significant older age, history of diabetes mellitus (DM), previous stroke, atrial fibrillation (AF), and admission NIHSS score, with significant decrease in high-density lipoprotein cholesterol (P < 0.05). Regarding the outcome of both groups, good outcome was significantly less common among group 1. Also, death was significantly more common among group I. Poor outcome in group 1 were significantly associated with older age, DM, AF, elevated serum T-I level at admission, and higher admission NIHSS score (P = 0.03, 0.04, 0.02, 0.05, and 0.001 respectively). The predictors of poor outcome in group 1 were elevated serum T-I level at admission, higher admission NIHSS score, and DM (P = 0.001, 0.02, and 0.05 respectively). Conclusion: Elevated serum T-I levels on admission is a reliable prognostic predictor of poor outcome in thrombolyzed ischemic stroke patients. Trial registration: ClinicalTrials.govNCT03925298 (19 April 2019) "retrospectively registered," [ABSTRACT FROM AUTHOR]

Bedside assessment of consciousness and awareness after a severe brain injury might be hampered by confounding clinical factors (i.e., pitfalls) interfering with the production of behavioral or motor responses to external stimuli. Despite the use of validated clinical scales, a high misdiagnosis rate is indeed observed. We retrospectively analyzed a cohort of 49 patients with severe brain injury admitted to an acute neuro-rehabilitation program. Patients' behavior was assessed using the Motor Behavior Tool and Coma Recovery Scale Revised. All patients underwent systematic assessment for pitfalls including polyneuropathy and/or myopathy and/or myelopathy, major cranial nerve palsies, non-convulsive status epilepticus, aphasia (expressive or comprehensive), cortical blindness, thalamic involvement and frontal akinetic syndrome. A high prevalence (75%) of pitfalls potentially interfering with sensory afference (polyneuropathy, myopathy, myelopathy, and sensory aphasia), motor efference (polyneuropathy, myopathy, motor aphasia, and frontal akinetic syndrome), and intrinsic brain activity (thalamic involvement and epilepsy) was found. Nonetheless, the motor behavior tool identified residual cognition (i.e. a cognitive motor dissociation condition) regardless of the presence of these pitfalls in 70% of the patients diagnosed as unresponsive using the Coma Recovery Scale Revised. On one hand, pitfalls might contribute to misdiagnosis. On the other, it could be argued that they are clues for diagnosing cognitive motor dissociation rather than true disorders of consciousness given their prominent effect on the sensory–motor input–output balance. [ABSTRACT FROM AUTHOR]

Cardiac complications post-stroke are common, and diabetes exacerbates post-stroke cardiac injury. In this study, we tested whether treatment with exosomes harvested from human umbilical cord blood derived CD133+ cells (CD133+Exo) improves cardiac function in type 2 diabetes mellitus (T2DM) stroke mice. Adult (3–4 m), male, BKS.Cg-m+/+Leprdb/J (db/db, T2DM) and non-DM (db+) mice were randomized to sham or photothrombotic stroke groups. T2DM-stroke mice were treated with phosphate-buffered saline (PBS) or CD133+Exo (20 μg, i.v.) at 3 days after stroke. T2DM sham and T2DM+CD133+Exo treatment groups were included as controls. Echocardiography was performed, and mice were sacrificed at 28 days after stroke. Cardiomyocyte hypertrophy, myocardial capillary density, interstitial fibrosis, and inflammatory factor expression were measured in the heart. MicroRNA-126 expression and its target gene expression were measured in the heart. T2DM mice exhibit significant cardiac deficits such as decreased left ventricular ejection fraction (LVEF) and shortening fraction (LVSF), increased left ventricular diastolic dimension (LVDD), and reduced heart rate compared to non-DM mice. Stroke in non-DM and T2DM mice significantly decreases LVEF compared to non-DM and T2DM-sham, respectively. Cardiac dysfunction is worse in T2DM-stroke mice compared to non-DM-stroke mice. CD133+Exo treatment of T2DM-stroke mice significantly improves cardiac function identified by increased LVEF and decreased LVDD compared to PBS treated T2DM-stroke mice. In addition, CD133+Exo treatment significantly decreases body weight and blood glucose but does not decrease lesion volume in T2DM-stroke mice. CD133+Exo treatment of T2DM mice significantly decreases body weight and blood glucose but does not improve cardiac function. CD133+Exo treatment in T2DM-stroke mice significantly decreases myocardial cross-sectional area, interstitial fibrosis, transforming growth factor beta (TGF-β), numbers of M1 macrophages, and oxidative stress markers 4-HNE (4-hydroxynonenal) and NADPH oxidase 2 (NOX2) in heart tissue. CD133+Exo treatment increases myocardial capillary density in T2DM-stroke mice as well as upregulates endothelial cell capillary tube formation in vitro. MiR-126 is highly expressed in CD133+Exo compared to exosomes derived from endothelial cells. Compared to PBS treatment, CD133+Exo treatment significantly increases miR-126 expression in the heart and decreases its target gene expression such as Sprouty-related, EVH1 domain-containing protein 1 (Spred-1), vascular cell adhesion protein (VCAM), and monocyte chemoattractant protein 1 (MCP1) in the heart of T2DM-stroke mice. CD133+Exo treatment significantly improves cardiac function in T2DM-stroke mice. The cardio-protective effects of CD133+Exo in T2DM-stroke mice may be attributed at least in part to increasing miR-126 expression and decreasing its target protein expression in the heart, increased myocardial capillary density and decreased cardiac inflammatory factor expression. [ABSTRACT FROM AUTHOR]

Accurate and reproducible automated segmentation of human hippocampal subfields is of interest to study their roles in cognitive functions and disease processes. Multispectral structural MRI methods have been proposed to improve automated hippocampal subfield segmentation accuracy, but the reproducibility in a multicentric setting is, to date, not well characterized. Here, we assessed test–retest reproducibility of FreeSurfer 6.0 hippocampal subfield segmentations using multispectral MRI analysis pipelines (22 healthy subjects scanned twice, a week apart, at four 3T MRI sites). The harmonized MRI protocol included two 3D-T1, a 3D-FLAIR, and a high-resolution 2D-T2. After within-session T1 averaging, subfield volumes were segmented using three pipelines with different multispectral data: two longitudinal ("long_T1s" and "long_T1s_FLAIR") and one cross-sectional ("long_T1s_FLAIR_crossT2"). Volume reproducibility was quantified in magnitude (reproducibility error—RE) and space (DICE coefficient). RE was lower in all hippocampal subfields, except for hippocampal fissure, using the longitudinal pipelines compared to long_T1s_FLAIR_crossT2 (average RE reduction of 0.4–3.6%). Similarly, the longitudinal pipelines showed a higher spatial reproducibility (1.1–7.8% of DICE improvement) in all hippocampal structures compared to long_T1s_FLAIR_crossT2. Moreover, long_T1s_FLAIR provided a small but significant RE improvement in comparison to long_T1s (p = 0.015), whereas no significant DICE differences were found. In addition, structures with volumes larger than 200 mm3 had better RE (1–2%) and DICE (0.7–0.95) than smaller structures. In summary, our study suggests that the most reproducible hippocampal subfield FreeSurfer segmentations are derived from a longitudinal pipeline using 3D-T1s and 3D-FLAIR. Adapting a longitudinal pipeline to include high-resolution 2D-T2 may lead to further improvements. [ABSTRACT FROM AUTHOR]

Objective: To investigate the feasibility of using amide proton transfer (APT) magnetic resonance imaging (MRI) in the liver and to evaluate its ability to characterize focal liver lesions (FLLs).Methods: A total of 203 patients with suspected FLLs who underwent APT imaging at 3T were included. APT imaging was obtained using a single-slice turbo spin-echo sequence to include FLLs through five breath-holds, and its acquisition time was approximately 1 min. APT signals in the background liver and FLL were measured with magnetization transfer ratio asymmetry (MTRasym) at 3.5 ppm. The technical success rate of APT imaging and the reasons for failure to obtain meaningful MTRasym values were assessed. The Mann Whitney U test was used to compare MTRasym values between different FLLs.Results: The technical success rate of APT imaging in the liver was 62.1% (126/203). The reasons for failure were a too large B0 inhomogeneity (n = 43), significant respiratory motion (n = 12), and these two factors together (n = 22), respectively. Among 59 FLLs with analyzable APT images, MTRasym values were compared between 27 patients with liver metastases and 23 patients with hepatocellular carcinomas (HCCs). The MTRasym values of metastases were significantly higher than those of HCC (0.13 ± 2.15% vs. - 1.41 ± 3.68%, p = 0.027).Conclusions: APT imaging could be an imaging biomarker for the differentiation of FLLs. However, further technical improvement is required before APT imaging can be clinically applied to liver MRI.Key Points: • Liver APT imaging was technically feasible, but with a relatively low success rate (62.1%). • Liver metastases showed higher APT values than hepatocellular carcinomas. [ABSTRACT FROM AUTHOR]

This article introduces a new dataset on transnational public-private governance initiatives (TGIs) in world politics. TGIs are institutions in which states and/or intergovernmental organizations cooperate with business and civil society actors to govern transnational problems. Thus, they are a special type of transnational public-private partnership. TGIs have flourished since the late 1990s and, today, govern a broad range of global policy domains, including environmental protection, human rights, health, trade, finance, and security. Yet, existing research lacks the data necessary to map this phenomenon and its variation along dimensions, such as issue areas, governance functions, participation, and institutional design. The Transnational Public-Private Governance Initiatives in World Politics (TGIWP) data is designed for this purpose. It contains detailed information on the scope, functions, participants, and institutional design of 636 TGIs created between 1885 and 2017. I describe the sample generation and discuss coding rules. I also map the proliferation and characteristics of TGIs, and provide an exploratory analysis of the relationship between state participation in TGIs and domestic democracy to show how the new data contributes to enhancing ongoing debates in international relations. The article concludes by discussing how the new dataset may be useful in future research on global governance. [ABSTRACT FROM AUTHOR]

We translocated polymers through pores of different shapes and interaction patterns in three dimensions by Langevin molecular dynamics. There were four simple cylindrical pores of the same length but with different diameters. The results showed that even though decreasing the pore diameter would always decrease the translocation velocity, it was strongly dependent on the shape of the increased pore diameter. Although increasing the pore diameter made the translocation faster in simple cylindrical pores, it was complicated in different pore shapes, e.g. increasing the diameter in the middle decreased the translocation velocity. Investigating polymer shapes through the translocation process and comparing the shapes by the cumulative waiting time for different pore structures reveals the non-equilibrium properties of translocation. Moreover, polymer shape parameters such as gyration radius, polymer center of mass, and average aspect ratio help us to distinguish different pore shapes and/or different polymers. [ABSTRACT FROM AUTHOR]

Objective: For clinical purposes and research projects in neurological disease, it is of interest to evaluate the performance and comparability of available sequences and software packages for brain volume assessment to determine whether they provide equivalent results. This study compares cross-sectional brain volume values derived from images obtained with MP-RAGE or MP2RAGE sequences, using SIENA/X, SPM, or MorphoBox. Materials and methods: MP-RAGE and MP2RAGE T1-weighted images were obtained from 24 healthy volunteers. Back-to-back scans were performed in 12 of them. Brain volumes, coefficients of variation, and concordance coefficients were determined. Results: Significant differences were found for most brain volumes derived from MP-RAGE and MP2RAGE images. MP2RAGE-derived measures showed a non-significant trend to larger coefficients of variation. There were statistical differences between brain volumes determined with the three software packages, whereas coefficients of variation were comparable for most brain volumes. Correlation and concordance values were lower for CSF and brain parenchyma fraction measures. Conclusion: The results obtained advise caution when comparing brain volumes obtained by different sequences and software packages. Of note, for most brain volume measures, the MP2RAGE and MorphoBox coefficients of variation were similar to those obtained with MP-RAGE, SIENA/X or SPM, accepted tools for clinical research. [ABSTRACT FROM AUTHOR]

Cumulative evidence suggests the existence of common processes underlying subjective experience of cognitive and physical fatigue. However, mechanistic understanding of the brain structural connections underlying the experience of fatigue in general, without the influence of clinical conditions, is limited. The purpose of the study was to examine the relationship between structural connectivity and perceived state fatigue in older adults. We enrolled cognitively and physically healthy older individuals (n = 52) and categorized them into three groups (low cognitive/low physical fatigue; low cognitive/high physical fatigue; high cognitive/low physical fatigue; no subjects had high cognitive/high physical fatigue) based on perceived fatigue from cognitive and physical fatigue manipulation tasks. Using sophisticated diffusion tensor imaging processing techniques, we extracted connectome matrices for six different characteristics of whole-brain structural connections for each subject. Tensor network principal component analysis was used to examine group differences in these connectome matrices, and extract principal brain networks for each group. Connected surface area of principal brain networks differentiated the two high fatigue groups from the low cognitive/physical fatigue group (high vs. low physical fatigue, p = 0.046; high vs. low cognitive fatigue, p = 0.036). Greater connected surface area within striatal-frontal-parietal networks was correlated with lower cognitive and physical fatigue, and was predictive of perceived physical and cognitive fatigue measures not used for group categorization (Pittsburgh fatigability physical subscale, R2 = 0.70, p < 0.0001; difference in self-report fatigue before and after gambling tasks, R2 = 0.54, p < 0.0001). There are potentially structural connectomes resilient to both cognitive and physical fatigue in older adults. [ABSTRACT FROM AUTHOR]

The present study and the preceding paper revisit landmark discoveries that paved the way to the definition of the renowned Brodmann areas in the human cerebral cortex, in an attempt to rectify certain undeserved historical neglects. A 'second period of discoveries', from 1893 to 1908, is marked by the work of Carl Hammarberg (1865–1893) in Uppsala, Alfred Walter Campbell (1868–1937) in Liverpool and Grafton Elliot Smith (1871–1937) in Cairo. Their classical findings are placed in a modern perspective. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to investigate hippocampal subfield volumes in patients with hippocampal sclerosis (HS) without visually detectable MRI abnormalities and to determine the diagnostic accuracy using hippocampal subfield volumes. Materials and methods: We examined 46 patients with unilateral HS who had a histopathological diagnosis, and 54 controls. The patients were divided into two groups; visually detectable HS (n = 26) and undetectable HS (n = 20) on MRI. The volumes of hippocampal subfield using FreeSurfer were compared among the three groups. Diagnostic accuracy was calculated as the AUC of ROC using cutoff values for each individual subfield. Results: Compared with the controls, visually detectable HS showed significantly reduced volumes of all the hippocampal subfields and entire hippocampus, whereas visually undetectable HS showed significant atrophy only in the CA3 and hippocampus-amygdala-transition-area. To diagnose visually undetectable HS, the CA3 volumes had AUC of 0.719, which was higher than AUC of 0.614 based on the entire hippocampal volumes. Conclusion: Visually undetectable HS demonstrated volume reductions in the CA3. Further, the CA3 volumes was more useful to diagnose visually undetectable HS compared with the entire hippocampal volumes. [ABSTRACT FROM AUTHOR]

Purpose: SimPET/M7 system is a small-animal dedicated simultaneous positron emission tomography and magnetic resonance imaging (PET/MRI) scanner. The SimPET insert has been upgraded from its prototype with a focus on count rate performance and sensitivity. The M7 scanner is a 1-T permanent magnet-based compact MRI system without any cryogens. Here, we present performance evaluation results of SimPET along with the results of mutual interference evaluation and simultaneously acquired PET/MR imaging. Procedures: Following NEMA NU 4-2008 standard, we evaluated the performance of the SimPET system. The M7 MRI compatibility of SimPET was also assessed by analyzing MRI images of a uniform phantom under different PET conditions and PET count rates with different MRI pulse sequences. Mouse imaging was performed including a whole-body 18F-NaF PET scan and a simultaneous PET/MRI scan with 64Cu-NOTA-ironoxide. Results: The spatial resolution at center based on 3D OSEM without and with warm background was 0.7 mm and 1.45 mm, respectively. Peak sensitivity was 4.21 % (energy window = 250–750 keV). The peak noise equivalent count rate with the same energy window was 151 kcps at 38.4 MBq. The uniformity was 4.42 %, and the spillover ratios in water- and air-filled chambers were 14.6 % and 12.7 %, respectively. In the hot rod phantom image, 0.75-mm-diameter rods were distinguishable. There were no remarkable differences in the SNR and uniformity of MRI images and PET count rates with different PET conditions and MRI pulse sequences. In the whole-body 18F-NaF PET images, fine skeletal structures were well resolved. In the simultaneous PET/MRI study with 64Cu-NOTA-ironoxide, both PET and MRI signals changed before and after injection of the dual-modal imaging probe, which was evident with the exact spatiotemporal correlation. Conclusions: We demonstrated that the SimPET scanner has a high count rate performance and excellent spatial resolution. The combined SimPET/M7 enabled simultaneous PET/MR imaging studies with no remarkable mutual interference between the two imaging modalities. [ABSTRACT FROM AUTHOR]

Recent emerging hybrid technology of positron emission tomography/magnetic resonance (PET/MR) imaging has generated a great need for an accurate MR image-based PET attenuation correction. MR image segmentation, as a robust and simple method for PET attenuation correction, has been clinically adopted in commercial PET/MR scanners. The general approach in this method is to segment the MR image into different tissue types, each assigned an attenuation constant as in an X-ray CT image. Machine learning techniques such as clustering, classification and deep networks are extensively used for brain MR image segmentation. However, only limited work has been reported on using deep learning in brain PET attenuation correction. In addition, there is a lack of clinical evaluation of machine learning methods in this application. The aim of this review is to study the use of machine learning methods for MR image segmentation and its application in attenuation correction for PET brain imaging. Furthermore, challenges and future opportunities in MR image-based PET attenuation correction are discussed. [ABSTRACT FROM AUTHOR]

Exercise improves both physical and mental health and increases neurogenesis in the dendate gyrus (DG) of the hippocampus. The aim of this study was to examine whether exercising, as compared to no change in regular physical activity, would impact on hippocampal volume, and in particular the core hippocampal structures, DG and cornu ammonis (CA) subfields, and whether any changes would be moderated by age. Thirty nine previously sedentary healthy participants were randomized to either a standardized progressive aerobic exercise program or to "no change" for 16 weeks. Mental health including profile of mood states (POMS), was assessed before and every 4 weeks during the program. Magnetic resonance imaging to examine hippocampal subfields was carried out before and after the program. Aerobic exercise resulted in a significant improvement of the POMS item 'vigour' compared to those in the control group. Overall left hippocampal and left CA4-DG volumes increased significantly in the exercise group while no significant changes were seen in the control group. Older adults in the control group demonstrated significant reductions in CA4-DG subfields over the study, whereas older adults in the exercise group did not show volume decline. These findings reinforce the literature that exercise has a beneficial effect on mental health and can prevent age-related volume decline. Exercise to Improve Resilience, https://register.clinicaltrials.gov/prs/app/action/LoginUser?ts=1&cx=-jg9qo4, NCT02541136, Rec Ref 2011/45/13. [ABSTRACT FROM AUTHOR]

The purpose of this study was to noninvasively evaluate the changes of regional cerebral venous oxygen saturation (rSvO2) in hemodialysis patients using quantitative susceptibility mapping (QSM) and investigate the relationship with clinical risk factors and neuropsychological testing. Fifty four (54) hemodialysis patients and 54 age, gender and education matched healthy controls (HCs) were recruited in this prospective study. QSM data were reconstructed from the original phase data of susceptibility weighted imaging to measure the susceptibility of cerebral regional major veins in all subjects and calculate their rSvO2. The differences in rSvO2 between hemodialysis patients and HCs were investigated using analysis of covariance adjusting for age and gender as covariates. Stepwise multiple regression and correlation analysis were performed between the cerebral rSvO2 and clinical factors including neuropsychological testing. The SvO2 of the bilateral cortical, thalamostriate, septal, cerebral internal and basal veins in hemodialysis patients was significantly lower than that in HCs (p < 0.001, Bonferroni corrected). The cerebral rSvO2 in all these veins was reduced by 1.67% to 2.30%. The hematocrit, iron, glucose, pre-and post-dialysis diastolic blood pressure (DBP) were independent predictive factors for the cerebral rSvO2 (all P < 0.05). The Mini-Mental State Examination and Montreal Cognitive Assessment (MoCA) scores were both lower in patients than those in HCs (both P < 0.05). The SvO2 of the left cerebral internal vein correlated with MoCA scores (r = 0.492; P = 0.02, FDR corrected). In conclusion, our study indicated that the cerebral rSvO2 was reduced in hemodialysis patients, which was the risk factor for neurocognitive impairment. The hematocrit, iron, glucose, pre-and post-dialysis DBP were independent risk factors for the cerebral rSvO2. [ABSTRACT FROM AUTHOR]

Hardware/software partitioning is an essential step in hardware/software co-design. For large size problems, it is difficult to consider both solution quality and time. This paper presents an efficient GPU-based parallel tabu search algorithm (GPTS) for HW/SW partitioning. A single GPU kernel of compacting neighborhood is proposed to reduce the amount of GPU global memory accesses theoretically. A kernel fusion strategy is further proposed to reduce the amount of GPU global memory accesses of GPTS. To further minimize the transfer overhead of GPTS between CPU and GPU, an optimized transfer strategy for GPU-based tabu evaluation is proposed, which considers that all the candidates do not satisfy the given constraint. Experiments show that GPTS outperforms state-of-the-art work of tabu search and is competitive with other methods for HW/SW partitioning. The proposed parallelization is significant when considering the ordinary GPU platform. [ABSTRACT FROM AUTHOR]

Background: A brain–heart interaction has been proposed in Takotsubo syndrome (TTS). Structural changes in the limbic system and hypoconnectivity between certain brain areas in the chronic phase of the disease have been reported, but little is known concerning functional neuroimaging in the acute phase. We hypothesized anatomical and functional changes in the central nervous system and investigated whole-brain volumetric and functional connectivity alterations in the acute phase TTS patients compared to controls. Methods: Anatomical and resting-state functional magnetic resonance imaging were performed in postmenopausal females: thirteen in the acute TTS phase and thirteen healthy controls without evidence of coronary artery disease. Voxel-based morphometry and graph theoretical analysis were applied to identify anatomical and functional differences between patients and controls. Results: Significantly lower gray matter volumes were found in TTS patients in the right middle frontal gyrus (p = 0.004) and right subcallosal cortex (p = 0.009) compared to healthy controls. When lower threshold was applied, volumetric changes were noted in the right insular cortex (p = 0.0113), the right paracingulate cortex (p = 0.012), left amygdala (p = 0.018), left central opercular cortex (p = 0.017), right (p = 0.013) and left thalamus (p = 0.017), and left cerebral cortex (p = 0.017). Graph analysis revealed significantly (p < 0.01) lower functional connectivity in TTS patients compared to healthy controls, particularly in the connections originating from the right insular cortex, temporal lobes, and precuneus. Conclusion: In the acute phase of TTS volumetric changes in frontal regions and the central autonomic network (i.e. insula, anterior cingulate cortex, and amygdala) were noted. In particular, the right insula, associated with sympathetic autonomic tone, had both volumetric and functional changes. [ABSTRACT FROM AUTHOR]

Calls to advance the democratization of sustainable development negotiations have recently proliferated. However, the participatory schemes set up by international organizations and governments have fallen short of answering to academic and empirical demands for global democracy, in particular by excluding the most marginalized actors from policymaking. Deliberative democrats argue that discursive representation may, in some contexts, overcome the shortcomings of actor-based representation and advance global democracy. To what extent, then, does discursive representation effectively contribute to the democratization of global policymaking by representing diverse interests, including those of marginalized actors? By performing a qualitative–quantitative discourse analysis of 122 primary documents issued during the formal sessions of negotiations of the Open Working Group on the Sustainable Development Goals, this article explores the extent to which different sustainability discourses that evolve in the public space got represented within authoritative circles of decision-making. While the negotiations on the Sustainable Development Goals involved more than ten million civil society voices and resulted in an agreement that claims to "transform our world" and "leave no-one behind," the study shows that discursive representation was biased toward a progressive sustainability discourse, depicting a state-centric orientation of equity and responsibilities to address global sustainable development challenges. Besides, the coalitions that emerged between state and non-state actors on alternative sustainability discourses failed to increase the saliency of the interests of marginalized actors in the shaping of the goals. As the understandings of transformation and inclusiveness conveyed in the negotiations were biased toward the interests of the most represented actors in the Open Working Group, the article reveals that in the context of the negotiations on the Sustainable Development Goals the effectiveness of discursive representation in democratizing global policymaking was eventually limited. [ABSTRACT FROM AUTHOR]

Ischemic stroke is one of the leading causes of death worldwide. In the post-stroke stage, cardiac dysfunction is common and is known as the brain–heart interaction. Diabetes mellitus worsens the post-stroke outcome. Stroke-induced systemic inflammation is the major causative factor for the sequential complications, but the mechanism underlying the brain–heart interaction in diabetes has not been clarified. The NLRP3 (NLR pyrin domain-containing 3) inflammasome, an important component of the inflammation after stroke, is mainly activated in M1-polarized macrophages. In this study, we found that the cardiac dysfunction induced by ischemic stroke is more severe in a mouse model of type 2 diabetes. Meanwhile, M1-polarized macrophage infiltration and NLRP3 inflammasome activation increased in the cardiac ventricle after diabetic stroke. Importantly, the NLRP3 inflammasome inhibitor CY-09 restored cardiac function, indicating that the M1-polarized macrophage–NLRP3 inflammasome activation is a pathway underlying the brain–heart interaction after diabetic stroke. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to evaluate the capability of sequences acquired on a 7-T MRI scanner, within times and anatomical coverage appropriate for clinical studies, to identify cortical lesions (CLs) in patients with Multiple Sclerosis (MS). Furthermore, we aimed to confirm the clinical significance of CL, testing the correlations between gray matter (GM) lesions and clinical scores. Methods: A 7-T MRI protocol included 3D-T1-weighted and T2*-weighted sequences. Images were evaluated independently by three readers of different experience, and the number of CLs was recorded. Between-rater concordance was assessed calculating the intraclass correlation coefficient (ICC). Lin's concordance correlation coefficient was used to compare CL detection between sequences, while partial correlations and multivariable regression models were used to study the relationship between CL and clinical data. Results: Forty MS patients (M/F, 17/23; 44.7 ± 12.6 years) were enrolled in this study, and CLs were identified in 35/40 subjects (87.5%). CL detection rate on 3D-T1-weighted images was significantly correlated with the detection rate on T2*-weighted images (r = 0.99; p < 0.001), with high concordance between readers (ICC ≥ 0.995). CLs were significantly correlated with both motor and cognitive scores (all with p ≤ 0.04). Conclusions: CL can be identified over the whole brain at 7-T in MS using a 3D-T1-weighted volume, acquired in a clinically feasible time and with comparable performance to that achievable using the T2*-weighted sequence. Based on the central role of CL in the development of clinical disability, we suggest that 3D-T1-weighted volume may play a role in the evaluation of CL in MS undergoing MRI on ultra-high-field scanners. Key Points: • Cortical lesions can be identified in a clinically feasible time with a 7-T protocol, which includes a 3D-T1-weighted volume. • Cortical lesions correlated significantly with both motor and cognitive disability in MS patients. • Given their correlation with clinical disability, evaluation of a cortical lesion on a 7-T clinical protocol could help in the management of MS patients. [ABSTRACT FROM AUTHOR]

Circulation through cerebral collaterals can maintain tissue viability until reperfusion is achieved. However, collateral circulation is time limited, and failure of collaterals is accelerated in the aged. Remote ischemic perconditioning (RIPerC), which involves inducing a series of repetitive, transient peripheral cycles of ischemia and reperfusion at a site remote to the brain during cerebral ischemia, may be neuroprotective and can prevent collateral failure in young adult rats. Here, we demonstrate the efficacy of RIPerC to improve blood flow through collaterals in aged (16–18 months of age) Sprague Dawley rats during a distal middle cerebral artery occlusion. Laser speckle contrast imaging and two-photon laser scanning microscopy were used to directly measure flow through collateral connections to ischemic tissue. Consistent with studies in young adult rats, RIPerC enhanced collateral flow by preventing the stroke-induced narrowing of pial arterioles during ischemia. This improved flow was associated with reduced early ischemic damage in RIPerC treated aged rats relative to controls. Thus, RIPerC is an easily administered, non-invasive neuroprotective strategy that can improve penumbral blood flow via collaterals. Enhanced collateral flow supports further investigation as an adjuvant therapy to recanalization therapy and a protective treatment to maintain tissue viability prior to reperfusion. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a late-onset fatal neurodegenerative disease that causes progressive degeneration of motor neurons in the brain and the spinal cord. Corticospinal tract degeneration is a defining feature of ALS. However, there have been very few longitudinal, controlled studies assessing diffusion MRI (dMRI) metrics in different fiber tracts along the spinal cord in general or the corticospinal tract in particular. Here we demonstrate that a tract-specific analysis, with segmentation of ascending and descending tracts in the spinal cord white matter, substantially increases the sensitivity of dMRI to disease-related changes in ALS. Our work also identifies the tracts and spinal levels affected in ALS, supporting electrophysiologic and pathologic evidence of involvement of sensory pathways in ALS. We note changes in diffusion metrics and cord cross-sectional area, with enhanced sensitivity to disease effects through a multimodal analysis, and with strong correlations between these metrics and spinal components of ALSFRS-R. Pramod Pisharady et al. develop a tract-specific analysis with segmentation of the spinal cord white matter to quantify longitudinal changes in cross-sectional area and fractional anisotropy in patients with Amyotrophic Lateral Sclerosis and control participants. With this highly sensitive analytical tool they identify different tracts and spinal levels affected in ALS, including sensory pathways. [ABSTRACT FROM AUTHOR]

The human visual system is capable of processing visual information from fovea to the far peripheral visual field. Recent fMRI studies have shown a full and detailed retinotopic map in area prostriata, located ventro-dorsally and anterior to the calcarine sulcus along the parieto-occipital sulcus with strong preference for peripheral and wide-field stimulation. Here, we report the anatomical pattern of white matter connections between area prostriata and the thalamus encompassing the lateral geniculate nucleus (LGN). To this end, we developed and utilized an automated pipeline comprising a series of Apps that run openly on the cloud computing platform brainlife.io to analyse 139 subjects of the Human Connectome Project (HCP). We observe a continuous and extended bundle of white matter fibers from which two subcomponents can be extracted: one passing ventrally parallel to the optic radiations (OR) and another passing dorsally circumventing the lateral ventricle. Interestingly, the loop travelling dorsally connects the thalamus with the central visual field representation of prostriata located anteriorly, while the other loop travelling more ventrally connects the LGN with the more peripheral visual field representation located posteriorly. We then analyse an additional cohort of 10 HCP subjects using a manual plane extraction method outside brainlife.io to study the relationship between the two extracted white matter subcomponents and eccentricity, myelin and cortical thickness gradients within prostriata. Our results are consistent with a retinotopic segregation recently demonstrated in the OR, connecting the LGN and V1 in humans and reveal for the first time a retinotopic segregation regarding the trajectory of a fiber bundle between the thalamus and an associative visual area. [ABSTRACT FROM AUTHOR]

Chemical exchange saturation transfer (CEST) enables detection of molecules such as glycogen, whose concentrations are too low to impact the signal intensity of standard MR imaging. Detection of these molecules is achieved by selectively saturating a molecule of interest and by measuring the reduction in water signal due to saturation transfer. CEST effects are dependent on parameters such as CEST agent concentration, pH, temperature, relaxation rate, magnetic field strength as well as on experimental parameters such as repetition time, RF irradiation amplitude, and the imaging readout scheme. Measurement of molecules with exchangeable protons that resonate very close to water, e.g., hydroxyl groups in glycogen, is challenging especially at lower magnetic field strengths, mainly due to the effect of direct water saturation. Therefore, optimal RF irradiation parameters that maximize the CEST signal and reduce the competing factors are important for better quantification of glycogen-weighted CEST effects. In this study, analytical solution of the Bloch-McConnell equations was used to find optimal continuous wave RF irradiation parameters for detection of glycogen. In vivo tests were performed on a human calf muscle at different saturation powers to validate the optimal saturation parameters determined via simulation. The selected parameters were applied in vitro to CEST measurements in a phantom with varying glycogen concentrations and also in vivo in a human calf muscle. Our results show the possibility of detecting glycogen using CEST MRI at 3 T. It is further shown that the glycoCEST signal can be maximized by optimizing the RF pulse irradiation parameters (duration and power) and that different glycogen concentrations can be identified when applying the optimized saturation pulse. [ABSTRACT FROM AUTHOR]

Objective: Cerebral blood flow (CBF) quantification using dynamic-susceptibility contrast MRI can be achieved via model-independent deconvolution, with local arterial input function (AIF) deconvolution methods identifying multiple arterial regions with unique corresponding arterial input functions. The clinical application of local AIF methods necessitates an efficient and fully automated solution. To date, such local AIF methods have relied on the computation of a singular surrogate measure of bolus arrival time or custom arterial scoring functions to infer vascular supply origins. This paper aims to introduce a new local AIF method that alternatively utilises a multi-stage approach to perform AIF selection. Material and methods: A fully automated, multi-stage local AIF method is proposed, leveraging both signal-based cluster analysis and priority flooding to define arterial regions and their corresponding vascular supply origins. The introduced method was applied to data from four patients with cerebrovascular disease who showed significant artefacts when using a prevailing automated local AIF method. Results: The immediately apparent image artefacts found using the pre-existing method due to poor AIF selection were found to be absent when using the proposed method. Conclusion: The results suggest the proposed solution provides a more robust approach to perfusion quantification than currently available fully automated local AIF methods. [ABSTRACT FROM AUTHOR]

Objectives: To consider the tract-based analysis of DTI parameters in human muscle by assessing different fiber tracking stop criteria settings on diffusion parameters. Materials and methods: 30 healthy volunteers underwent a 3 T MRI. Diffusion-weighted images were acquired to perform DTI and fiber tracking analysis for six thigh muscles. Whole thigh muscles were evaluated by fiber tractography using different fiber tracking stop parameters [FA (0.01–0.15) to (0.4–0.99); angle 10°–30°, step size 0.75 mm, 1.5 mm, 3 mm]. Diffusion and tractography-derived parameters per stop criterion were compared using a repeated measure ANOVA including Bonferroni-corrected post hoc tests. Results: We found significant differences in all examined diffusion parameters between different stop criteria (main effect p < 0.001). We showed different influence of tracking parameters on diffusion parameters in examined muscles (main effect p ≤ 0.001). Conclusions: Statistically significant differences in fiber tracking results using different stop criteria were shown. Fiber tracking stop criteria do have an important influence on study results and should be considered in the development of study protocols and comparison of studies. We recommend a FA minimum of 0.10 and a step size lower than voxel size, e.g., a half with a constant ratio between step size and angle of 10°/mm. [ABSTRACT FROM AUTHOR]

Growing evidence has demonstrated widespread brain network alterations in temporal lobe epilepsy (TLE). However, the relatively accurate portrait of the subcortical-cortical relationship for impaired consciousness in TLE remains unclear. We proposed that consciousness-impairing seizures may invade subcortical arousal system and corresponding cortical regions, resulting in functional abnormalities and information flow disturbances between subcortical and cortical networks. We performed resting-state fMRI in 26 patients with TLE and 30 matched healthy controls. All included patients were diagnosed with impaired awareness during focal temporal lobe seizures. Functional connectivity density was adopted to determine whether local or distant network alterations occurred in TLE, and Granger causality analysis (GCA) was utilized to assess the direction and magnitude of causal influence among these altered brain networks further. Patients showed increased local functional connectivity in several arousal structures, such as the midbrain, thalamus, and cortical regions including bilateral prefrontal cortex (PFC), left superior temporal pole, left posterior insula, and cerebellum (P < 0.05, FDR corrected). GCA analysis revealed that the casual effects among these regions in patients were significantly sparser than those in controls (P < 0.05, uncorrected), including decreased excitatory and inhibitory effects among the midbrain, thalamus and PFC, and decreased inhibitory effect from the cerebellum to PFC. These findings suggested that consciousness-impairing seizures in TLE are associated with functional alterations and disruption of information process between the subcortical arousal system and cortical network. Understanding the functional networks and innervation pathway involved in TLE can provide insights into the mechanism underlying seizure-related loss of consciousness. [ABSTRACT FROM AUTHOR]

Hypoxia is a critical component of neuronal death in patients with stroke. Therefore increasing oxygenation of brain tissue seems to be a logical therapy against cerebral ischemia. Oxygen therapy exists in two modalities: normobaric hyperoxia therapy and hyperbaric oxygen therapy (HBO). HBO is a therapeutic procedure in which pure (100%) oxygen is administered at greater than atmospheric pressure in HBO therapy chambers. In this review article, we aimed to summarize the current knowledge regarding the therapeutic use of HBO in acute stroke patients. Literature review and electronic search were performed using PubMed, Medscape, and UpToDate with the keywords stroke, acute stroke, hyperbaric oxygen therapy, and hyperoxia. According to the reviewed literature, the use of HBO as routine stroke therapy cannot be justified in acute stage of stroke. More randomized, controlled studies are needed regarding safety and especially effectives of HBO in stroke patients. Also, standardized definitionof HBO should be proposed and used in all future studies. [ABSTRACT FROM AUTHOR]

With the advent of novel biotherapeutics in indications such as oncology, the attention has moved to making these therapies patient centric, potentially available for self-administration. Given the volume limitations of the other convenient routes of administration such a subcutaneous, intramuscular, there is a need for high concentration drug products. Along with the concerns of inherent protein instability at high concentration, there are other practical challenges during the development of these drug products. This review focuses on the considerations in formulation screening, process development, manufacturing, analytical methods and stability for high concentration liquid drug product. For the scenarios where, high concentration liquid drug product is not feasible, alternate approaches can be undertaken to obtain high concentration drug product during administration. The discussion on the current available alternate technologies with an overview of their advantages and disadvantages are covered here. The scope of the overall discussions is introductory and limited to cautionary notes and experiences as opposed to prescriptive recommendations and detailed literature reviews: our primary goal is to provide a compiled set of considerations that can guide a detailed literature research and a to-do list for high concentration development and manufacturing activities. This manuscript aims to highlight the motivations to develop high concentration parenteral protein drug products, a wide range of -commonly known or sometimes overlooked- challenges associated with their development and manufacturing, as well as some approaches towards mitigation of said challenges. [ABSTRACT FROM AUTHOR]

Purpose: To identify the volume changes of hippocampus subfields in T2DM patients with cognitive impairment and to determine how these atrophy patterns associate with impairments in different cognitive domain. Methods: A total of 117 individuals were recruited, including T2DM patients with cognitive impairment (T2DM-CI) (n = 34), T2DM patients without cognitive impairment (T2DM-non-CI) (n = 36) and normal controls (NC) (n = 47). All subjects went through a 3.0 T magnetic resonance (MR) scan and a neuropsychological assessment. Hippocampal subfield volumes were processed using the FreeSurfer 6.0.0 and compared among the three groups. Partial correlation analyses were used to estimate the relationship between cognitive function and hippocampal subfield volume, with age, sex, education, and eTIV (estimated total intracranial volume) as covariants. Results: The total hippocampal volume had a reduction trend among the three groups, and the significantly statistical difference only was found between T2DM-CI group and NC group. Regarding the hippocampal subfields, the volumes of left subiculum, left presubiculum, left fimbria, right CA1 and right molecular layer HP decreased significantly in the T2DM-CI group (P < 0.05/12). Partial correlation analyses showed that the volumes of the left subiculum, left fimbria, and left presubiculum were significantly related to executive function. The right hippocampal CA1 volume was significantly correlated with memory in the T2DM-CI group (P < 0.05). But in T2DM-non-CI group, the correlation between the left fimbria volume and the memory, the left subiculum volume and MoCA were different with the T2DM-CI group and NC group (P < 0.05). Conclusions: The smaller the volume of left presubiculum, the worse the executive function, and the atrophy of the right CA1 was related to memory impairment in T2DM-CI group. However the result was the opposite in T2DM-non-CI group. There might be a compensation mechanism of hippocampus of T2DM patients before cognitive impairment. [ABSTRACT FROM AUTHOR]

Objective: The current study aimed to evaluate the clinical practice for hemodynamic tissue signature (HTS) method in IDH genotype prediction in three groups derived from high-grade gliomas.Methods: Preoperative MRI examinations of 44 patients with known grade and IDH genotype were assigned into three study groups: glioblastoma multiforme, grade III, and high-grade gliomas. Perfusion parameters were analyzed and were used to automatically draw the four reproducible habitats (high-angiogenic enhancing tumor habitats, low-angiogenic enhancing tumor habitats, infiltrated peripheral edema habitats, vasogenic peripheral edema habitats) related to vascular heterogeneity. These four habitats were then compared between inter-patient with IDH mutation and their wild-type counterparts at these three groups, respectively. The discriminating potential for HTS in assessing IDH mutation status prediction was assessed by ROC curves.Results: Compared with IDH wild type, IDH mutation had significantly decreased relative cerebral blood volume (rCBV) at the high-angiogenic enhancing tumor habitats and low-angiogenic enhancing tumor habitats. ROC analysis revealed that the rCBVs in habitats had great ability to discriminate IDH mutation from their wild type in all groups. In addition, the Kaplan-Meier survival analysis yielded significant differences for the survival times observed from the populations dichotomized by low (< 4.31) and high (> 4.31) rCBV in the low-angiogenic enhancing tumor habitat.Conclusions: The HTS method has been proven to have high prediction capabilities for IDH mutation status in high-grade glioma patients, providing a set of quantifiable habitats associated with tumor vascular heterogeneity.Key Points: • The HTS method has a high accuracy for molecular stratification prediction for all subsets of HGG. • The HTS method can give IDH mutation-related hemodynamic information of tumor-infiltrated and vasogenic edema. • IDH-relevant rCBV difference in habitats will be a great prognosis factor in HGG. [ABSTRACT FROM AUTHOR]

Introduction: Metastatic breast cancer (MBC) with leptomeningeal metastases (LM) has dismal survival. We aim to determine if modern systemic therapy, especially the bevacizumab, cisplatin, and etoposide (BEEP) regimen, is beneficial to MBC LM patients. Methods: We excerpted data from a prospectively collected cytopathology database for MBC patients who were diagnosed with LM by positive cerebrospinal fluid cytology. The primary outcome was OS from cytologically confirmed LM until death. Univariate and multivariate analyses were performed to elucidate prognostic factors. Results: We identified 34 patients with cytologically confirmed LM. Treatments after LM diagnosis included: intrathecal methotrexate (82.4%), systemic chemotherapy (68%; BEEP n = 19, others n = 4), and whole brain radiotherapy (n = 5, 14.7%). Three of seven HER2-positive patients (43%) also received intrathecal trastuzumab. OS was improved in 2014–2016 compared with 2011–2013 (13.57 vs 3.20 months, p = 0.004), when 12/17 (71%) versus 7/17 (41%) patients received BEEP, respectively. In the multivariate model including all treatments, BEEP (HR 0.24, p = 0.003) and intrathecal trastuzumab (HR 0.22, p = 0.035), but not intrathecal methotrexate (HR 0.86, p = 0.78), remained significant prognostic factors. Conclusions: MBC with LM is treatable—systemic BEEP are efficacious and may improve survival. [ABSTRACT FROM AUTHOR]

Background: Simultaneous cardiovascular imaging with positron emission tomography (PET) and magnetic resonance imaging (MRI) requires tools such as radio frequency (RF) phased arrays to achieve high temporal and spatial resolution in the MRI, as well as accurate quantification of PET. Today, high-density phased arrays (> 16 channels) used for cardiovascular PET/MRI are not designed to achieve low PET attenuation, and correcting the PET attenuation they cause requires off-line reconstruction, extra time and resources. Purpose: Motivated by previous work assessing the MRI performance of a novel prospectively designed 32-channel phased array, this study assessed the PET image quality with this array in place. Guided by NEMA standards, PET performance was measured using global PET counts, regional background variation (BV), contrast recovery (CR) and contrast-to-noise ratio (CNR) for both the novel array and standard arrays (mMR 12-channel and MRI 32-channel). Nonattenuation-corrected (NAC) data from all arrays (and each part of the array) were processed and compared to no-array, and relative percentage difference (RPD) of the global means was estimated and reported for each part of the arrays. Attenuation correction (AC) of PET images (water in the phantom) using two approaches, MR-based AC map (MRAC) and dual-energy CT-based map (DCTAC), was performed, and RPD compared for each part of the arrays. Percent mean attenuation within regions of interests of the phantom images from each array were compared using a two-way analysis of variance (ANOVA). Results: The NAC data of the anterior part of the novel array recorded the least PET attenuation (≤ 2%); while the full novel array (anterior and posterior together) AC data, produced by MRAC and DCTAC approaches, recorded attenuation of 1.5 ± 2.9% and 0.0 ± 2.5%, respectively. The novel array PET count loss was significantly lower (p = 0.001) than those caused by the standard arrays. Conclusions: Results of this novel 32-channel cardiac array PET performance evaluation, together with its previously reported MRI performance assessment, suggest the novel array to be a strong alternative to the standard arrays currently used for cardiovascular hybrid PET/MRI imaging. It enables accurate PET quantification and high-temporal and spatial resolution for MR imaging. [ABSTRACT FROM AUTHOR]

Most real-world decisions involve a delicate balance between exploring unfamiliar alternatives and committing to the best known option. Previous work has shown that humans rely on different forms of uncertainty to negotiate this "explore-exploit" trade-off, yet the neural basis of the underlying computations remains unclear. Using fMRI (n = 31), we find that relative uncertainty is represented in right rostrolateral prefrontal cortex and drives directed exploration, while total uncertainty is represented in right dorsolateral prefrontal cortex and drives random exploration. The decision value signal combining relative and total uncertainty to compute choice is reflected in motor cortex activity. The variance of this signal scales with total uncertainty, consistent with a sampling mechanism for random exploration. Overall, these results are consistent with a hybrid computational architecture in which different uncertainty computations are performed separately and then combined by downstream decision circuits to compute choice. Humans explore the world by optimistically directing choices to less familiar options and by choosing more randomly when options are uncertain. Here, the authors show that these two exploration strategies rely on distinct uncertainty estimates represented in different parts of the prefrontal cortex. [ABSTRACT FROM AUTHOR]

Background and Purpose: This study aimed at developing a radiomics signature (R score) as prognostic biomarkers based on penumbra quantification and to validate the radiomics nomogram to predict the clinical outcomes for thrombolysis for acute ischemic stroke (AIS) patients. Methods: In total, 168 patients collected from seven centers were retrospectively included. A score of mismatch was defined as MIS. Based on a short-term clinical label, 456 radiomics features were evaluated with feature selection methods. R score was constructed with the selected features. To compare the predictive capabilities of the clinical factors, MIS, and R score, three nomograms were developed and evaluated, according to the short-term clinical assessment on day 7. Finally, the radiomics nomogram was validated by predicting the 3-month clinical outcomes of AIS patients, in an external cohort. Results: R scores were found to be significantly higher in patients with favorable clinical outcomes in both training and validation datasets. The predictive value of the radiomics nomogram estimating favorable clinical outcomes was modest, with a concordance index (C-index) of 0.695 [95% confidence interval (CI) 0.667–0.723) in an external validation dataset. In addition, the area under curve (AUC) of the radiomics nomogram predicting favorable clinical outcome reached 0.886 (95% CI 0.809–0.963) on day 7 and 0.777 (95% CI 0.666–0.888) at 3 months. Conclusions: The radiomics signature is an independent biomarker for estimating the clinical outcomes in AIS patients. By improving the individualized prediction of the clinical outcome for AIS patients 3 months after onset, the radiomics nomogram adds more value to the current clinical decision-making process. [ABSTRACT FROM AUTHOR]

Angiogenesis is the growth of new capillaries from the preexisting blood vessels. Glioblastoma (GBM) tumors are highly vascularized tumors, and glioma growth depends on the formation of new blood vessels. Angiogenesis is a complex process involving proliferation, migration, and differentiation of vascular endothelial cells (ECs) under the stimulation of specific signals. It is controlled by the balance between its promoting and inhibiting factors. Various angiogenic factors and genes have been identified that stimulate glioma angiogenesis. Therefore, attention has been directed to anti-angiogenesis therapy in which glioma proliferation is inhibited by inhibiting the formation of new tumor vessels using angiogenesis inhibitory factors and drugs. Here, in this review, we highlight and summarize the various molecular mediators that regulate GBM angiogenesis with focus on recent clinical research on the potential of exploiting angiogenic pathways as a strategy in the treatment of GBM patients. [ABSTRACT FROM AUTHOR]

Axon diameter and density are important microstructural metrics that offer valuable insight into the structural organization of white matter throughout the human brain. We report the systematic acquisition and analysis of a comprehensive diffusion MRI data set acquired with 300 mT/m maximum gradient strength in a cohort of 20 healthy human subjects that yields distinct and consistent patterns of axon diameter index in white matter tracts of arbitrary orientation. We use a straightforward, previously validated approach to estimating indices of axon diameter and volume fraction that involves interpolating the diffusion signal perpendicular to the principal fiber orientation and fitting a three-compartment model of intra-axonal, extra-axonal and free water diffusion. The resultant maps confirm the presence of larger diameter indices in the body of corpus callosum compared to the genu and splenium, as previously reported, and show larger axon diameter index in the corticospinal tracts compared to adjacent white matter tracts such as the cingulum. An anterior-to-posterior gradient in axon diameter index is also observed, with smaller diameter indices in the frontal lobes and larger diameter indices in the parieto-occipital white matter. These observations are consistent with known trends from prior histologic studies in humans and non-human primates. Rather than serving as fully quantitative measures of axon diameter and density, our results may be considered as axon diameter- and volume fraction-weighted images that appear to be modulated by the underlying microstructure and may capture broad trends in axonal size and packing density, acknowledging that the precise origin of such modulation requires further investigation that will be facilitated by the availability of high gradient strengths for in vivo human imaging. [ABSTRACT FROM AUTHOR]

Positron emission tomography (PET) is a non-invasive imaging technology employed to describe metabolic, physiological, and biochemical processes in vivo. These include receptor availability, metabolic changes, neurotransmitter release, and alterations of gene expression in the brain. Since the introduction of dedicated small-animal PET systems along with the development of many novel PET imaging probes, the number of PET studies using rats and mice in basic biomedical research tremendously increased over the last decade. This article reviews challenges and advances of quantitative rodent brain imaging to make the readers aware of its physical limitations, as well as to inspire them for its potential applications in preclinical research. In the first section, we briefly discuss the limitations of small-animal PET systems in terms of spatial resolution and sensitivity and point to possible improvements in detector development. In addition, different acquisition and post-processing methods used in rodent PET studies are summarized. We further discuss factors influencing the test-retest variability in small-animal PET studies, e.g., different receptor quantification methodologies which have been mainly translated from human to rodent receptor studies to determine the binding potential and changes of receptor availability and radioligand affinity. We further review different kinetic modeling approaches to obtain quantitative binding data in rodents and PET studies focusing on the quantification of endogenous neurotransmitter release using pharmacological interventions. While several studies have focused on the dopamine system due to the availability of several PET tracers which are sensitive to dopamine release, other neurotransmitter systems have become more and more into focus and are described in this review, as well. We further provide an overview of latest genome engineering technologies, including the CRISPR/Cas9 and DREADD systems that may advance our understanding of brain disorders and function and how imaging has been successfully applied to animal models of human brain disorders. Finally, we review the strengths and opportunities of simultaneous PET/magnetic resonance imaging systems to study drug-receptor interactions and challenges for the translation of PET results from bench to bedside. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of modifiable vascular risk factors is increasing in young adults and may contribute to the growing frequency of stroke in this population. The neuropathology and end-organ damage profile of young adult stroke patients with clinically advanced atherosclerosis or arteriosclerosis has not been studied. Methods: This retrospective study included patients aged 18–60 years admitted to our hospital from 1995 to 2017 with recurrent ischemic or hemorrhagic strokes, fatal stroke, or stroke associated with advanced small vessel disease (SVD) on brain MRI, who had no evidence for structural, genetic, inflammatory, or infectious etiology for stroke, and had adequate pathological materials available for analysis. The presence of atherosclerosis, arteriolosclerosis, left ventricular hypertrophy, and nephrosclerosis was evaluated. Results: Twelve patients (mean age 47 ± 9 years, range 31–57 years, 67% male) met inclusion criteria. Four had fatal intracerebral hemorrhage (ICH), three had recurrent non-fatal ICH, one had ICH with advanced SVD on MRI, and four had recurrent ischemic strokes including two with transient ischemic attacks. Pathological studies showed moderate/severe atherosclerosis in 64% and moderate/severe arteriolosclerosis in 42% of patients. Pathological data to evaluate end-organ damage were available for nine patients; eight showed left ventricular hypertrophy and all showed nephrosclerosis. Conclusion: Young adult stroke patients with recurrent stroke, fatal stroke, or SVD on imaging have advanced atherosclerosis and arteriolosclerosis-related pathological changes in multiple organ systems. Aggressive control of atherosclerosis risk factors is warranted even in young individuals. [ABSTRACT FROM AUTHOR]

Cerebral small vessel disease (SVD) is a major cause of stroke and cognitive impairment. However, the underlying mechanisms behind SVD are still poorly understood. High cerebral arterial pulsatility has been suggested as a possible cause of SVD. In population studies, arterial pulsatility has been linked to white matter hyperintensities (WMH), cerebral atrophy, and cognitive impairment, all features of SVD. In stroke, pulsatility data are scarce and contradictory. The aim of this study was to investigate the relationship between arterial pulsatility and SVD in stroke patients. With a cross-sectional design, 89 patients with acute ischemic stroke or TIA were examined with MRI. A neuropsychological assessment was performed 1 year later. Using 4D flow MRI, pulsatile indices (PI) were calculated for the internal carotid artery (ICA) and middle cerebral artery (M1, M3). Flow volume pulsatility (FVP), a measure corresponding to the cyclic expansion of the arterial tree, was calculated for the same locations. These parameters were assessed for associations with WMH volume, brain volume and cognitive function. ICA-FVP was associated with WMH volume (β = 1.67, 95% CI: [0.1, 3.24], p = 0.037). M1-PI and M1-FVP were associated with decreasing cognitive function (β = − 4.4, 95% CI: [− 7.7, − 1.1], p = 0.009 and β = − 13.15, 95% CI: [− 24.26, − 2.04], p = 0.02 respectively). In summary, this supports an association between arterial pulsatility and SVD in stroke patients, and provides a potential target for further research and preventative treatment. FVP may become a useful biomarker for assessing pulsatile stress with PCMRI and 4D flow MRI. [ABSTRACT FROM AUTHOR]