scholarly journals Tractography Reproducibility Challenge with Empirical Data (TraCED): The 2017 ISMRM Diffusion Study Group Challenge

2018 ◽  
Author(s):  
Vishwesh Nath ◽  
Kurt Schilling ◽  
Prasanna Parvathaneni ◽  
Allison E. Hainline ◽  
Yuankai Huo ◽  
...  
Keyword(s):  
Large Scale ◽  
Fiber Tracking ◽  
Physiological Factors ◽  
Brain White Matter ◽  
Specific Order ◽  
Weighted Magnetic Resonance Imaging ◽  
Phantom Studies ◽  
Brain Connection ◽  
Shell Acquisition

Purpose: Fiber tracking with diffusion weighted magnetic resonance imaging has become an essential tool for estimating in vivo brain white matter architecture. Fiber tracking results are sensitive to the choice of processing method and tracking criteria. Phantom studies provide concrete quantitative comparisons of methods relative to absolute ground truths, yet do not capture variabilities because of in vivo physiological factors. Methods: To date, a large-scale reproducibility analysis has not been performed for the assessment of the newest generation of tractography algorithms with in vivo data. Reproducibility does not assess the validity of a brain connection however it is still of critical importance because it describes the variability for an algorithm in group studies. The ISMRM 2017 TraCED challenge was created to fulfill the gap. The TraCED dataset consists of a single healthy volunteer scanned on two different scanners of the same manufacturer. The multi-shell acquisition included b-values of 1000, 2000 and 3000 s/mm2 with 20, 45 and 64 diffusion gradient directions per shell, respectively. Results: Nine international groups submitted 46 tractography algorithm entries. The top five submissions had high ICC > 0.88. Reproducibility is high within these top 5 submissions when assessed across sessions or across scanners. However, it can be directly attributed to containment of smaller volume tracts in larger volume tracts. This holds true for the top five submissions where they are contained in a specific order. While most algorithms are contained in an ordering there are some outliers. Conclusion: The different methods clearly result in fundamentally different tract structures at the more conservative specificity choices (i.e., volumetrically smaller tractograms). The data and challenge infrastructure remain available for continued analysis and provide a platform for comparison.

scholarly journals Large-Scale Evidence for an Association Between Peripheral Inflammation and White Matter Free Water in Schizophrenia and Healthy Individuals

2020 ◽  
Author(s):  
Maria A Di Biase ◽  
Andrew Zalesky ◽  
Suheyla Cetin-Karayumak ◽  
Yogesh Rathi ◽  
Jinglei Lv ◽  
...  
Keyword(s):  
White Matter ◽  
Large Scale ◽  
Interleukin 2 ◽  
Free Water ◽  
Markers Of Inflammation ◽  
Brain White Matter ◽  
Inflammatory Processes ◽  
Weighted Magnetic Resonance Imaging

Abstract Introduction Clarifying the role of neuroinflammation in schizophrenia is subject to its detection in the living brain. Free-water (FW) imaging is an in vivo diffusion-weighted magnetic resonance imaging (dMRI) technique that measures water molecules freely diffusing in the brain and is hypothesized to detect inflammatory processes. Here, we aimed to establish a link between peripheral markers of inflammation and FW in brain white matter. Methods All data were obtained from the Australian Schizophrenia Research Bank (ASRB) across 5 Australian states and territories. We first tested for the presence of peripheral cytokine deregulation in schizophrenia, using a large sample (N = 1143) comprising the ASRB. We next determined the extent to which individual variation in 8 circulating pro-/anti-inflammatory cytokines related to FW in brain white matter, imaged in a subset (n = 308) of patients and controls. Results Patients with schizophrenia showed reduced interleukin-2 (IL-2) (t = −3.56, P = .0004) and IL-12(p70) (t = −2.84, P = .005) and increased IL-6 (t = 3.56, P = .0004), IL-8 (t = 3.8, P = .0002), and TNFα (t = 4.30, P < .0001). Higher proinflammatory signaling of IL-6 (t = 3.4, P = .0007) and TNFα (t = 2.7, P = .0007) was associated with higher FW levels in white matter. The reciprocal increases in serum cytokines and FW were spatially widespread in patients encompassing most major fibers; conversely, in controls, the relationship was confined to the anterior corpus callosum and thalamic radiations. No relationships were observed with alternative dMRI measures, including the fractional anisotropy and tissue-related FA. Conclusions We report widespread deregulation of cytokines in schizophrenia and identify inflammation as a putative mechanism underlying increases in brain FW levels.

scholarly journals In vivo evidence of microstructural hypo-connectivity of brain white matter in 22q11.2 deletion syndrome

2020 ◽  
Author(s):  
Erika Raven ◽  
Jelle Veraart ◽  
Rogier Kievit ◽  
Sila Genc ◽  
Isobel Ward ◽  
...  
Keyword(s):  
White Matter ◽  
Large Scale ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
Typically Developing ◽  
22Q11.2 Deletion ◽  
Genetic Syndrome ◽  
Brain White Matter ◽  
Axonal Morphology

Abstract 22q11.2 Deletion Syndrome, or 22q11.2DS, is a genetic syndrome associated with high rates of schizophrenia, autism, and attention deficit hyperactivity disorder, in addition to widespread structural and functional abnormalities throughout the brain. Experimental animal models have identified neuronal connectivity deficits, e.g., decreased axonal length and complexity of axonal branching, as a primary mechanism underlying atypical brain development in 22q11.2DS. However, it is still unclear whether deficits in axonal morphology can also be observed in people with 22q11.2DS. Here, we provide an unparalleled in vivo characterisation of white matter microstructure in both typically-developing children and children with 22q11.2DS using a dedicated magnetic resonance imaging scanner which is sensitive to axonal morphology. By extracting a rich array of diffusion metrics, we present microstructural profiles of typical and atypical white matter development, and provide new evidence of connectivity differences between typically-developing and 22q11.2DS children. A recent, large-scale consortium study identified higher diffusion anisotropy and reduced overall mobility of water as hallmark microstructural alterations of white matter in 22q11.2DS, in particular for commissural fibers. We observed similar findings across all white matter tracts in this study, in addition to identifying deficits in axonal morphology. This, in combination with reduced tract volume measurements, supports the hypothesis that microstructural connectivity in 22q11.2DS is mediated by densely packed axons with disproportionately small diameters. Our findings provide insight into the in vivo mechanistic features of 22q11.2DS, and promote further investigation of shared features in neurodevelopmental and psychiatric disorders.

In Vivo Fiber-Tracking der Wadenmuskulatur von Kaninchen basierend auf diffusionsgewichteter STEAM-MR-Bildgebung

2011 ◽  
Vol 183 (S 01) ◽  
Author(s):  
P Hiepe ◽  
D Güllmar ◽  
KH Herrmann ◽  
C Küpper ◽  
T Siebert ◽  
...  
Keyword(s):  
Fiber Tracking

Purification of the Antihemophilic Factor by Gel Filtration on Agarose

1969 ◽  
Vol 22 (03) ◽  
pp. 577-583 ◽  
Author(s):  
M.M.P Paulssen ◽  
A.C.M.G.B Wouterlood ◽  
H.L.M.A Scheffers
Keyword(s):  
Factor Viii ◽  
Plasma Proteins ◽  
Large Scale ◽  
Gel Filtration ◽  
Large Scale Preparation ◽  
Scale Preparation ◽  
Antihemophilic Factor

SummaryFactor VIII can be isolated from plasma proteins, including fibrinogen by chromatography on agarose. The best results were obtained with Sepharose 6B. Large scale preparation is also possible when cryoprecipitate is separated by chromatography. In most fractions containing factor VIII a turbidity is observed which may be due to the presence of chylomicrons.The purified factor VIII was active in vivo as well as in vitro.

The Effect of Active Site-inhibited Factor VIIa on Tissue Factor-initiated Coagulation Using Platelets before and after Aspirin Administration

1997 ◽  
Vol 78 (04) ◽  
pp. 1202-1208 ◽  
Author(s):  
Marianne Kjalke ◽  
Julie A Oliver ◽  
Dougald M Monroe ◽  
Maureane Hoffman ◽  
Mirella Ezban ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Active Site ◽  
Large Scale ◽  
Thrombin Generation ◽  
Factor Viia ◽  
Dependent Manner ◽  
Antithrombotic Agent ◽  
Before And After ◽  
Ic50 Values

SummaryActive site-inactivated factor VIIa has potential as an antithrombotic agent. The effects of D-Phe-L-Phe-L-Arg-chloromethyl ketone-treated factor VIla (FFR-FVIIa) were evaluated in a cell-based system mimicking in vivo initiation of coagulation. FFR-FVIIa inhibited platelet activation (as measured by expression of P-selectin) and subsequent large-scale thrombin generation in a dose-dependent manner with IC50 values of 1.4 ± 0.8 nM (n = 8) and 0.9 ± 0.7 nM (n = 7), respectively. Kd for factor VIIa binding to monocytes ki for FFR-FVIIa competing with factor VIIa were similar (11.4 ± 0.8 pM and 10.6 ± 1.1 pM, respectively), showing that FFR-FVIIa binds to tissue factor in the tenase complex with the same affinity as factor VIIa. Using platelets from volunteers before and after ingestion of aspirin (1.3 g), there were no significant differences in the IC50 values of FFR-FVIIa [after aspirin ingestion, the IC50 values were 1.7 ± 0.9 nM (n = 8) for P-selectin expression, p = 0.37, and 1.4 ± 1.3 nM (n = 7) for thrombin generation, p = 0.38]. This shows that aspirin treatment of platelets does not influence the inhibition of tissue factor-initiated coagulation by FFR-FVIIa, probably because thrombin activation of platelets is not entirely dependent upon expression of thromboxane A2.

Naphthoquinones and derivatives for chemotherapy: perspectives and limitations of their anti-trypanosomatids activities

2020 ◽  
Vol 26 ◽  
Author(s):  
Luíza Dantas-Pereira ◽  
Edézio F. Cunha-Junior ◽  
Valter V. Andrade-Neto ◽  
John F. Bower ◽  
Guilherme A. M. Jardim ◽  
...  
Keyword(s):  
Large Scale ◽  
Neglected Tropical Diseases ◽  
Folk Medicine ◽  
Leishmania Species ◽  
Parasitic Infections ◽  
Mechanistic Analysis ◽  
Leishmania Spp ◽  
Nanomolar Range

: Chagas disease, Sleeping sickness and Leishmaniasis, caused by trypanosomatids Trypanosoma cruzi, Trypanosoma brucei and Leishmania spp., respectively, are considered neglected tropical diseases, and they especially affect impoverished populations in the developing world. The available chemotherapies are very limited and a search for alternatives is still necessary. In folk medicine, natural naphthoquinones have been employed for the treatment of a great variety of illnesses, including parasitic infections. This review is focused on the anti-trypanosomatid activity and mechanistic analysis of naphthoquinones and derivatives. Among all the series of derivatives tested in vitro, naphthoquinone-derived 1,2,3-triazoles were very active on T. cruzi infective forms in blood bank conditions, as well as in amastigotes of Leishmania spp. naphthoquinones containing a CF3 on a phenyl amine ring inhibited T. brucei proliferation in the nanomolar range, and naphthopterocarpanquinones stood out for their activity on a range of Leishmania species. Some of these compounds showed a promising selectivity index (SI) (30 to 1900), supporting further analysis in animal models. Indeed, high toxicity to the host and inactivation by blood components are crucial obstacles to be overcome to use naphthoquinones and/or their derivatives for chemotherapy. Multidisciplinary initiatives embracing medicinal chemistry, bioinformatics, biochemistry, and molecular and cellular biology need to be encouraged to allow the optimization of these compounds. Large scale automated tests are pivotal for the efficiency of the screening step, and subsequent evaluation of both the mechanism of action in vitro and pharmacokinetics in vivo are essential for the development of a novel, specific and safe derivative, minimizing adverse effects.

Implantable neural interfaces

2018 ◽  
Author(s):  
Stefano Vassanelli
Keyword(s):  
Brain Function ◽  
Large Scale ◽  
Ionic Channels ◽  
Patch Clamp Technique ◽  
Advantages And Disadvantages ◽  
Optogenetic Stimulation ◽  
Physical Interfaces ◽  
The Brain

Establishing direct communication with the brain through physical interfaces is a fundamental strategy to investigate brain function. Starting with the patch-clamp technique in the seventies, neuroscience has moved from detailed characterization of ionic channels to the analysis of single neurons and, more recently, microcircuits in brain neuronal networks. Development of new biohybrid probes with electrodes for recording and stimulating neurons in the living animal is a natural consequence of this trend. The recent introduction of optogenetic stimulation and advanced high-resolution large-scale electrical recording approaches demonstrates this need. Brain implants for real-time neurophysiology are also opening new avenues for neuroprosthetics to restore brain function after injury or in neurological disorders. This chapter provides an overview on existing and emergent neurophysiology technologies with particular focus on those intended to interface neuronal microcircuits in vivo. Chemical, electrical, and optogenetic-based interfaces are presented, with an analysis of advantages and disadvantages of the different technical approaches.

What Has Direct Cortical and Subcortical Electrostimulation Taught Us about Neurolinguistics?

2019 ◽  
pp. 185-211
Author(s):  
Hugues Duffau
Keyword(s):  
White Matter ◽  
Large Scale ◽  
Functional Neuroimaging ◽  
Great Accuracy ◽  
Subcortical White Matter ◽  
Cerebral Lesions ◽  
Physiological Basis ◽  
Postoperative Mri ◽  
The Brain

Investigating the neural and physiological basis of language is one of the most important challenges in neurosciences. Direct electrical stimulation (DES), usually performed in awake patients during surgery for cerebral lesions, is a reliable tool for detecting both cortical and subcortical (white matter and deep grey nuclei) regions crucial for cognitive functions, especially language. DES transiently interacts locally with a small cortical or axonal site, but also nonlocally, as the focal perturbation will disrupt the entire subnetwork sustaining a given function. Thus, in contrast to functional neuroimaging, DES represents a unique opportunity to identify with great accuracy and reproducibility, in vivo in humans, the structures that are actually indispensable to the function, by inducing a transient virtual lesion based on the inhibition of a subcircuit lasting a few seconds. Currently, this is the sole technique that is able to directly investigate the functional role of white matter tracts in humans. Thus, combining transient disturbances elicited by DES with the anatomical data provided by pre- and postoperative MRI enables to achieve reliable anatomo-functional correlations, supporting a network organization of the brain, and leading to the reappraisal of models of language representation. Finally, combining serial peri-operative functional neuroimaging and online intraoperative DES allows the study of mechanisms underlying neuroplasticity. This chapter critically reviews the basic principles of DES, its advantages and limitations, and what DES can reveal about the neural foundations of language, that is, the large-scale distribution of language areas in the brain, their connectivity, and their ability to reorganize.

scholarly journals Optimizing Manufacturing and Osseointegration of Ti6Al4V Implants through Precision Casting and Calcium and Phosphorus Ion Implantation? In Vivo Results of a Large-Scale Animal Trial

Materials ◽  
2020 ◽  
Vol 13 (7) ◽  
pp. 1670 ◽  
Author(s):  
Wölfle-Roos JV ◽  
Katmer Amet B ◽  
Fiedler J ◽  
Michels H ◽  
Kappelt G ◽  
...  
Keyword(s):  
Ion Implantation ◽  
Large Scale ◽  
In Vivo Studies ◽  
Control Group ◽  
Implant Surface ◽  
Precision Casting ◽  
Pull Out ◽  
Significant Difference ◽  
Calcium And Phosphorus

Background: Uncemented implants are still associated with several major challenges, especially with regard to their manufacturing and their osseointegration. In this study, a novel manufacturing technique—an optimized form of precision casting—and a novel surface modification to promote osseointegration—calcium and phosphorus ion implantation into the implant surface—were tested in vivo. Methods: Cylindrical Ti6Al4V implants were inserted bilaterally into the tibia of 110 rats. We compared two generations of cast Ti6Al4V implants (CAST 1st GEN, n = 22, and CAST 2nd GEN, n = 22) as well as cast 2nd GEN Ti6Al4V implants with calcium (CAST + CA, n = 22) and phosphorus (CAST + P, n = 22) ion implantation to standard machined Ti6Al4V implants (control, n = 22). After 4 and 12 weeks, maximal pull-out force and bone-to-implant contact rate (BIC) were measured and compared between all five groups. Results: There was no significant difference between all five groups after 4 weeks or 12 weeks with regard to pull-out force (p > 0.05, Kruskal Wallis test). Histomorphometric analysis showed no significant difference of BIC after 4 weeks (p > 0.05, Kruskal–Wallis test), whereas there was a trend towards a higher BIC in the CAST + P group (54.8% ± 15.2%), especially compared to the control group (38.6% ± 12.8%) after 12 weeks (p = 0.053, Kruskal–Wallis test). Conclusion: In this study, we found no indication of inferiority of Ti6Al4V implants cast with the optimized centrifugal precision casting technique of the second generation compared to standard Ti6Al4V implants. As the employed manufacturing process holds considerable economic potential, mainly due to a significantly decreased material demand per implant by casting near net-shape instead of milling away most of the starting ingot, its application in manufacturing uncemented implants seems promising. However, no significant advantages of calcium or phosphorus ion implantation could be observed in this study. Due to the promising results of ion implantation in previous in vitro and in vivo studies, further in vivo studies with different ion implantation conditions should be considered.

scholarly journals Lentiviral Vectors for Delivery of Gene-Editing Systems Based on CRISPR/Cas: Current State and Perspectives

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1288
Author(s):  
Wendy Dong ◽  
Boris Kantor
Keyword(s):  
Large Scale ◽  
Lentiviral Vector ◽  
Clinical Applications ◽  
Scale Production ◽  
Base Editing ◽  
Epigenome Editing ◽  
Vector Systems ◽  
Dividing Cells

CRISPR/Cas technology has revolutionized the fields of the genome- and epigenome-editing by supplying unparalleled control over genomic sequences and expression. Lentiviral vector (LV) systems are one of the main delivery vehicles for the CRISPR/Cas systems due to (i) its ability to carry bulky and complex transgenes and (ii) sustain robust and long-term expression in a broad range of dividing and non-dividing cells in vitro and in vivo. It is thus reasonable that substantial effort has been allocated towards the development of the improved and optimized LV systems for effective and accurate gene-to-cell transfer of CRISPR/Cas tools. The main effort on that end has been put towards the improvement and optimization of the vector’s expression, development of integrase-deficient lentiviral vector (IDLV), aiming to minimize the risk of oncogenicity, toxicity, and pathogenicity, and enhancing manufacturing protocols for clinical applications required large-scale production. In this review, we will devote attention to (i) the basic biology of lentiviruses, and (ii) recent advances in the development of safer and more efficient CRISPR/Cas vector systems towards their use in preclinical and clinical applications. In addition, we will discuss in detail the recent progress in the repurposing of CRISPR/Cas systems related to base-editing and prime-editing applications.

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