Vendor-neutral sequences (VENUS) and fully transparent workflows improve inter-vendor reproducibility of quantitative MRI

Purpose: We developed a transparent end-to-end qMRI workflow that starts with a vendor-neutral acquisition and tested the hypothesis that vendor-neutral sequences (VENUS) decrease inter-vendor variability of T1, MTR and MTsat measurements. Methods: We developed and deployed a vendor-neutral 3D spoiled gradient-echo (SPGR) sequence on three clinical scanners by two MRI vendors and acquired T1 maps on the NIST phantom, as well as T1, MTR and MTsat maps in three healthy participants. We performed hierarchical shift function analysis in vivo to characterize the differences between scanners when VENUS is used instead of commercial vendor implementations. Inter-vendor deviations were compared for statistical significance to test the hypothesis. Results: In the NIST phantom, VENUS reduced inter-vendor differences from 8 - 19.4% to 0.2 - 5% with an overall accuracy improvement, reducing ground truth T1 deviation from 7 - 11% to 0.2 - 4%. In vivo we found that the variability between vendors is significantly reduced (p = 0.015) for all maps (T1, MTR and MTsat) using VENUS. Conclusion: We conclude that vendor-neutral workflows are feasible and compatible with clinical MRI scanners. The significant reduction of inter-vendor variability using VENUS has important implications for qMRI research and for the reliability of multicenter clinical trials.

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Whole-brain 3D MR fingerprinting brain imaging: clinical validation and feasibility to patients with meningioma

Magnetic Resonance Materials in Physics Biology and Medicine ◽

10.1007/s10334-021-00924-1 ◽

2021 ◽

Author(s):

Thomaz R. Mostardeiro ◽

Ananya Panda ◽

Robert J. Witte ◽

Norbert G. Campeau ◽

Kiaran P. McGee ◽

...

Keyword(s):

White Matter ◽

Statistical Significance ◽

Relaxation Times ◽

Brain Structures ◽

Centrum Semiovale ◽

In Vivo Evaluation ◽

Whole Brain ◽

Mean Values ◽

Caudate Head

Abstract Purpose MR fingerprinting (MRF) is a MR technique that allows assessment of tissue relaxation times. The purpose of this study is to evaluate the clinical application of this technique in patients with meningioma. Materials and methods A whole-brain 3D isotropic 1mm3 acquisition under a 3.0T field strength was used to obtain MRF T1 and T2-based relaxometry values in 4:38 s. The accuracy of values was quantified by scanning a quantitative MR relaxometry phantom. In vivo evaluation was performed by applying the sequence to 20 subjects with 25 meningiomas. Regions of interest included the meningioma, caudate head, centrum semiovale, contralateral white matter and thalamus. For both phantom and subjects, mean values of both T1 and T2 estimates were obtained. Statistical significance of differences in mean values between the meningioma and other brain structures was tested using a Friedman’s ANOVA test. Results MR fingerprinting phantom data demonstrated a linear relationship between measured and reference relaxometry estimates for both T1 (r2 = 0.99) and T2 (r2 = 0.97). MRF T1 relaxation times were longer in meningioma (mean ± SD 1429 ± 202 ms) compared to thalamus (mean ± SD 1054 ± 58 ms; p = 0.004), centrum semiovale (mean ± SD 825 ± 42 ms; p < 0.001) and contralateral white matter (mean ± SD 799 ± 40 ms; p < 0.001). MRF T2 relaxation times were longer for meningioma (mean ± SD 69 ± 27 ms) as compared to thalamus (mean ± SD 27 ± 3 ms; p < 0.001), caudate head (mean ± SD 39 ± 5 ms; p < 0.001) and contralateral white matter (mean ± SD 35 ± 4 ms; p < 0.001) Conclusions Phantom measurements indicate that the proposed 3D-MRF sequence relaxometry estimations are valid and reproducible. For in vivo, entire brain coverage was obtained in clinically feasible time and allows quantitative assessment of meningioma in clinical practice.

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Structure-Function Analysis of IntDOT

Journal of Bacteriology ◽

10.1128/jb.01052-09 ◽

2009 ◽

Vol 192 (2) ◽

pp. 575-586 ◽

Cited By ~ 5

Author(s):

Seyeun Kim ◽

Brian M. Swalla ◽

Jeffrey F. Gardner

Keyword(s):

Homology Modeling ◽

Protein Interactions ◽

Active Site ◽

Dna Cleavage ◽

Function Analysis ◽

Indicator Strain ◽

Amino Terminal ◽

Dna Ligation ◽

Polypeptide Backbone

ABSTRACT CTnDOT integrase (IntDOT) is a member of the tyrosine family of site-specific DNA recombinases. IntDOT is unusual in that it catalyzes recombination between nonidentical sequences. Previous mutational analyses centered on mutants with substitutions of conserved residues in the catalytic (CAT) domain or residues predicted by homology modeling to be close to DNA in the core-binding (CB) domain. That work suggested that a conserved active-site residue (Arg I) of the CAT domain is missing and that some residues in the CB domain are involved in catalysis. Here we used a genetic approach and constructed an Escherichia coli indicator strain to screen for random mutations in IntDOT that disrupt integrative recombination in vivo. Twenty-five IntDOT mutants were isolated and characterized for DNA binding, DNA cleavage, and DNA ligation activities. We found that mutants with substitutions in the amino-terminal (N) domain were catalytically active but defective in forming nucleoprotein complexes, suggesting that they have altered protein-protein interactions or altered interactions with DNA. Replacement of Ala-352 of the CAT domain disrupted DNA cleavage but not DNA ligation, suggesting that Ala-352 may be important for positioning the catalytic tyrosine (Tyr-381) during cleavage. Interestingly, our biochemical data and homology modeling of the CAT domain suggest that Arg-285 is the missing Arg I residue of IntDOT. The predicted position of Arg-285 shows it entering the active site from a position on the polypeptide backbone that is not utilized in other tyrosine recombinases. IntDOT may therefore employ a novel active-site architecture to catalyze recombination.

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Simulating a Ground Truth for Transit Time Analysis of Indicator Dilution Curves

Current Directions in Biomedical Engineering ◽

10.1515/cdbme-2020-3068 ◽

2020 ◽

Vol 6 (3) ◽

pp. 268-271

Author(s):

Michael Reiß ◽

Ady Naber ◽

Werner Nahm

Keyword(s):

Transit Time ◽

Sampling Rate ◽

Ground Truth ◽

Indicator Dilution ◽

Cross Sectional ◽

In Vivo Measurements ◽

Multiple Indicator Dilution ◽

Transit Times ◽

Dilution Curves

AbstractTransit times of a bolus through an organ can provide valuable information for researchers, technicians and clinicians. Therefore, an indicator is injected and the temporal propagation is monitored at two distinct locations. The transit time extracted from two indicator dilution curves can be used to calculate for example blood flow and thus provide the surgeon with important diagnostic information. However, the performance of methods to determine the transit time Δt cannot be assessed quantitatively due to the lack of a sufficient and trustworthy ground truth derived from in vivo measurements. Therefore, we propose a method to obtain an in silico generated dataset of differently subsampled indicator dilution curves with a ground truth of the transit time. This method allows variations on shape, sampling rate and noise while being accurate and easily configurable. COMSOL Multiphysics is used to simulate a laminar flow through a pipe containing blood analogue. The indicator is modelled as a rectangular function of concentration in a segment of the pipe. Afterwards, a flow is applied and the rectangular function will be diluted. Shape varying dilution curves are obtained by discrete-time measurement of the average dye concentration over different cross-sectional areas of the pipe. One dataset is obtained by duplicating one curve followed by subsampling, delaying and applying noise. Multiple indicator dilution curves were simulated, which are qualitatively matching in vivo measurements. The curves temporal resolution, delay and noise level can be chosen according to the requirements of the field of research. Various datasets, each containing two corresponding dilution curves with an existing ground truth transit time, are now available. With additional knowledge or assumptions regarding the detection-specific transfer function, realistic signal characteristics can be simulated. The accuracy of methods for the assessment of Δt can now be quantitatively compared and their sensitivity to noise evaluated.

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Bone Regeneration by Novel Bioactive Glasses Containing Strontium and/or Magnesium: A Preliminary In-Vivo Study

Materials ◽

10.3390/ma11112223 ◽

2018 ◽

Vol 11 (11) ◽

pp. 2223 ◽

Cited By ~ 12

Author(s):

Devis Bellucci ◽

Valeria Cannillo ◽

Alexandre Anesi ◽

Roberta Salvatori ◽

Luigi Chiarini ◽

...

Keyword(s):

Statistical Significance ◽

Formation Processes ◽

Complete Dissolution ◽

In Vitro Bioactivity ◽

Bioactive Glasses ◽

Beneficial Effects ◽

Glass Dissolution

In this work, a set of novel bioactive glasses have been tested in vivo in an animal model. The new compositions, characterized by an exceptional thermal stability and high in vitro bioactivity, contain strontium and/or magnesium, whose biological benefits are well documented in the literature. To simulate a long-term implant and to study the effect of the complete dissolution of glasses, samples were implanted in the mid-shaft of rabbits’ femur and analyzed 60 days after the surgery; such samples were in undersized powder form. The statistical significance with respect to the type of bioactive glass was analyzed by Kruskal–Wallis test. The results show high levels of bone remodeling, several new bone formations containing granules of calcium phosphate (sometimes with amounts of strontium and/or magnesium), and the absence of adverse effects on bone processes due to the almost complete glass dissolution. In vivo results confirming the cell culture outcomes of a previous study highlighted that these novel bioglasses had osteostimulative effect without adverse skeletal reaction, thus indicating possible beneficial effects on bone formation processes. The presence of strontium in the glasses seems to be particularly interesting.

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A novel long non-coding RNA GK-IT1 promotes the carcinogenesis and progression of esophageal squamous cell carcinoma via mediating the phosphorylation of MAPK1

10.21203/rs.3.rs-131952/v1 ◽

2020 ◽

Author(s):

Xin Yang ◽

Tian Yang Zeng ◽

Zi Yang Liu ◽

Wan Lun He ◽

Meng Ting Hu ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Mapk Pathway ◽

Statistical Significance ◽

In Situ Hybridisation ◽

Fluorescence In Situ Hybridisation ◽

Normal Tissues

Abstract Background: Recent studies have shown that Long non-coding RNAs (lncRNAs) are crucial in the invasion, angiogenesis, progression, and metastasis of esophageal squamous cell carcinoma (ESCC). However, the biological functions and potential molecular mechanism of LncRNA GK-IT1 in esophageal squamous cell carcinoma has not been reported.Methods: We analysed the expression of GK-IT1 in ESCC and their adjacent normal tissues in the TCGA database. The quantitative real-time-PCR (qRT-PCR) was used to detect the expression of GK-IT1 in Clinical specimens. The Kaplan-Meier method was employed to draw the survival curve and then the statistical significance was calculated using the logarithmic rank test. a range of functional experiments in vivo and in vitro were used to explore the role of GK-IT1 in the carcinogenesis and development of ESCC. RNA pull down assay, RNA immunoprecipitation (RIP), fluorescence in situ hybridisation (FISH), agarose gel electrophoresis and immunofluorescence were all employed to explore the interaction mechanism between GK-IT1 and MAPK1 (mitogen activated protein kinase 1).Results: The expression of GK-IT1 was higher in ESCC than adjacent normal tissues, which was positively correlated with the clinical stage and shorter survival time. The knockout of the GK-IT1 gene significantly attenuated the abilities of ESCC cell proliferation, invasion and migration, induced apoptosis and autophagy in ESCC cells and inhibited tumour growth and tumour metastasis in vivo. on the contrary, the upregulation of GK-IT1 had the opposite effect. Further studies have shown that GK-IT1 can regulate the biological process of ESCC by regulating the phosphorylation of MAPK1.Conclusion: Our study reveals that GK-IT1 mediated the phosphorylation of MAPK1 improve the carcinogenesis and development of esophageal squamous cell carcinoma through ERK/MAPK pathway which indicates that GK-IT1 possesses substantial potential as a novel biomarker for ESCC prognosis and therapy.

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Assessing Variations in Areal Organization for the Intrinsic Brain: From Fingerprints to Reliability

10.1101/035790 ◽

2016 ◽

Cited By ~ 3

Author(s):

Ting Xu ◽

Alexander Opitz ◽

R. Cameron Craddock ◽

Margaret Wright ◽

Xi-Nian Zuo ◽

...

Keyword(s):

Individual Variation ◽

Brain Function ◽

Intraclass Correlation ◽

Resting State Fmri ◽

Single Individual ◽

Initial Application ◽

Novel Approach ◽

Gradient Based ◽

Healthy Participants

AbstractResting state fMRI (R-fMRI) is a powerful in-vivo tool for examining the functional architecture of the human brain. Recent studies have demonstrated the ability to characterize transitions between functionally distinct cortical areas through the mapping of gradients in intrinsic functional connectivity (iFC) profiles. To date, this novel approach has primarily been applied to iFC profiles averaged across groups of individuals, or in one case, a single individual scanned multiple times. Here, we used a publically available R-fMRI dataset, in which 30 healthy participants were scanned 10 times (10 minutes per session), to investigate differences in full-brain transition profiles (i.e., gradient maps, edge maps) across individuals, and their reliability. 10-minute R-fMRI scans were sufficient to achieve high accuracies in efforts to “fingerprint” individuals based upon full-brain transition profiles. Regarding testretest reliability, the image-wise intraclass correlation coefficient (ICC) was moderate, and vertex-level ICC varied depending on region; larger durations of data yielded higher reliability scores universally. Initial application of gradient-based methodologies to a recently published dataset obtained from twins suggested inter-individual variation in areal profiles might have genetic and familial origins. Overall, these results illustrate the utility of gradient-based iFC approaches for studying inter-individual variation in brain function.

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Alterations in articular cartilage T2 star relaxation time following mechanical disorders: in vivo canine supraspinatus tendon resection models

10.21203/rs.3.rs-22995/v2 ◽

2020 ◽

Author(s):

Dokwan Lee ◽

Ki-Taek Hong ◽

Tae Seong Lim ◽

Eugene Lee ◽

Ye Hyun Lee ◽

...

Keyword(s):

Relaxation Time ◽

Articular Cartilage ◽

Motion Tracking ◽

Supraspinatus Tendon ◽

Quantitative Mri ◽

Joint Mechanics ◽

T2 Relaxation Time ◽

T2 Relaxation ◽

Positive Correlations

Abstract Background: The role of altered joint mechanics on cartilage degeneration in in vivo models has not been studied successfully due to a lack of pre-injury information. We aimed 1) to develop an accurate in vivo canine model to measure the changes in joint loading and T2 star (T2*) relaxation time before and after unilateral supraspinatus tendon resections, and 2) to find the relationship between regional variations in articular cartilage loading patterns and T2* relaxation time distributions.Methods: Rigid markers were implanted in the scapula and humerus of tested dogs. The movement of the shoulder bones were measured by a motion tracking system during normal gaits. In vivo cartilage contact strain was measured by aligning 3D shoulder models with the motion tracking data. Articular cartilage T2* relaxation times were measured by quantitative MRI scans. Articular cartilage contact strain and T2* relaxation time were compared in the shoulders before and three months after the supraspinatus tendon resections.Results: Excellent accuracy and reproducibility were found in our in vivo contact strain measurements with less than 1% errors. Changes in articular cartilage contact strain exhibited similar patterns with the changes in the T2* relaxation time after resection surgeries. Regional changes in the articular cartilage T2* relaxation time exhibited positive correlations with regional contact strain variations three months after the supraspinatus resection surgeries.Conclusion: This is the first study to measure in vivo articular cartilage contact strains with high accuracy and reproducibility. Positive correlations between contact strain and T2* relaxation time suggest that the articular cartilage extracellular matrix may responds to mechanical changes in local areas.

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Discrimination study between carcass yield and meat quality by gender in Korean native cattle (Hanwoo)

Asian-Australasian Journal of Animal Sciences ◽

10.5713/ajas.19.0472 ◽

2020 ◽

Vol 33 (7) ◽

pp. 1202-1208

Author(s):

Do-Gyun Kim ◽

Joon-Yong Shim ◽

Byoung-Kwan Cho ◽

Collins Wakholi ◽

Youngwook Seo ◽

...

Keyword(s):

Meat Quality ◽

Function Analysis ◽

Statistical Significance ◽

Significance Test ◽

Carcass Yield ◽

Yield And Quality ◽

Quality Grade ◽

Native Cattle

Objective: The aim of this study was to identify a distribution pattern of meat quality grade (MQG) as a function of carcass yield index (CYI) and the gender of Hanwoo (bull, cow, and steer) to determine the optimum point between both yield and quality. We also attempted to identify how pre- and post-deboning variables affect the gender-specific beef quality of Hanwoo.Methods: A total of 31 deboning variables, consisting of 7 pre-deboning and 24 post-deboning variables from bulls (n = 139), cows (n = 69), and steers (n = 153), were obtained from the National Institute of Animal Science (NIAS) in South Korea. The database was reconstructed to be suitable for a statistical significance test between the CYI and the MQG as well as classification of meat quality. Discriminant function analysis was used for classifying MQG using the deboning parameters of Hanwoo by gender.Results: The means of CYI according to 1+, 1, 2, and 3 of MQG were 68.64±2.02, 68.85±1.94, 68.62±5.88, and 70.99±3.32, respectively. High carcass yield correlated with low-quality grade, while high-quality meat most frequently was obtained from steers. The classification ability of pre-deboning parameters was higher than that of post-deboning parameters. Moisture and the shear force were the common significant parameters in all discriminant functions having a classification accuracy of 80.6%, 71%, and 56.9% for the bull, cow, and steer, respectively.Conclusion: This study provides basic information for predicting the meat quality by gender using pre-deboning variables consistent with the actual grading index.

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Structure–function analysis of full-length midkine reveals novel residues important for heparin binding and zebrafish embryogenesis

Biochemical Journal ◽

10.1042/bj20121622 ◽

2013 ◽

Vol 451 (3) ◽

pp. 407-415 ◽

Cited By ~ 13

Author(s):

Jackwee Lim ◽

Sheng Yao ◽

Martin Graf ◽

Christoph Winkler ◽

Daiwen Yang

Keyword(s):

Function Analysis ◽

Structural Features ◽

Full Length ◽

Domain Growth ◽

Heparin Binding ◽

Cellular Mechanisms ◽

The Individual ◽

Zebrafish Embryogenesis

Midkine is a heparin-binding di-domain growth factor, implicated in many biological processes as diverse as angiogenesis, neurogenesis and tumorigenesis. Elevated midkine levels reflect poor prognosis for many carcinomas, yet the molecular and cellular mechanisms orchestrating its activity remain unclear. At the present time, the individual structures of isolated half domains of human midkine are known and its functionally active C-terminal half domain remains a popular therapeutic target. In the present study, we determined the structure of full-length zebrafish midkine and show that it interacts with fondaparinux (a synthetic highly sulfated pentasaccharide) and natural heparin through a previously uncharacterized, but highly conserved, hinge region. Mutating six consecutive residues in the conserved hinge to glycine strongly abates heparin binding and midkine embryogenic activity. In contrast with previous in vitro studies, we found that the isolated C-terminal half domain is not active in vivo in embryos. Instead, we have demonstrated that the N-terminal half domain is needed to enhance heparin binding and mediate midkine embryogenic activity surprisingly in both heparin-dependent and -independent manners. Our findings provide new insights into the structural features of full-length midkine relevant for embryogenesis, and unravel additional therapeutic routes targeting the N-terminal half domain and conserved hinge.

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The Influence of Bioactive Glass Particles on Osteolysis

Key Engineering Materials ◽

10.4028/www.scientific.net/kem.330-332.193 ◽

2007 ◽

Vol 330-332 ◽

pp. 193-196

Author(s):

Duck Hyun Kim ◽

Kang Sik Lee ◽

Jung Hwa Kim ◽

Jae Suk Chang ◽

Yung Tae Kim

Keyword(s):

Foreign Body ◽

Bioactive Glass ◽

Foreign Body Reaction ◽

Statistical Significance ◽

Giant Cells ◽

In Vivo Test ◽

Micro Particles ◽

Rat Calvaria ◽

Replacement Arthroplasty

We observed the cytotoxicity of human bone marrow stromal cells(hBMSCs) by microparticles of bioactive glass with four particle groups(same chemical composition-45S5 but produced by two different manufacturer and two different size groups). In vivo test using rat calvaria were also carried out. The apoptosis rates of all small particle groups(10-20 ㎛) were increased than large(500-700 ㎛ or 200-900 ㎛) particle groups in any culture time and any amount of particles with statistical significance. In vivo study we observed pathologic signs such as macrophages and foreign-body giant cells in rat calvaria by micro-particles of bioglass. Small(10- 20 ㎛) sized particles induced foreign body reaction and bone resorption. There was proliferation of macrophages and cells in large number. But in large particle groups, only fibroblasts were surrounding the particles. The micro-particles of bioglass induced apoptosis of hBMSC and foreign body reaction in calvaria of rat, therefore micro-particles of bioglass may cause osteolysis if used in replacement arthroplasty.

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