High‐resolution serum proteome trajectories in COVID‐19 reveal patient‐specific seroconversion

Abstract Background The inability to observe relevant biological processes in vivo significantly restricts human neurodevelopmental research. Advances in appropriate in vitro model systems, including patient-specific human brain organoids and human cortical spheroids (hCSs), offer a pragmatic solution to this issue. In particular, hCSs are an accessible method for generating homogenous organoids of dorsal telencephalic fate, which recapitulate key aspects of human corticogenesis, including the formation of neural rosettes—in vitro correlates of the neural tube. These neurogenic niches give rise to neural progenitors that subsequently differentiate into neurons. Studies differentiating induced pluripotent stem cells (hiPSCs) in 2D have linked atypical formation of neural rosettes with neurodevelopmental disorders such as autism spectrum conditions. Thus far, however, conventional methods of tissue preparation in this field limit the ability to image these structures in three-dimensions within intact hCS or other 3D preparations. To overcome this limitation, we have sought to optimise a methodological approach to process hCSs to maximise the utility of a novel Airy-beam light sheet microscope (ALSM) to acquire high resolution volumetric images of internal structures within hCS representative of early developmental time points. Results Conventional approaches to imaging hCS by confocal microscopy were limited in their ability to image effectively into intact spheroids. Conversely, volumetric acquisition by ALSM offered superior imaging through intact, non-clarified, in vitro tissues, in both speed and resolution when compared to conventional confocal imaging systems. Furthermore, optimised immunohistochemistry and optical clearing of hCSs afforded improved imaging at depth. This permitted visualization of the morphology of the inner lumen of neural rosettes. Conclusion We present an optimized methodology that takes advantage of an ALSM system that can rapidly image intact 3D brain organoids at high resolution while retaining a large field of view. This imaging modality can be applied to both non-cleared and cleared in vitro human brain spheroids derived from hiPSCs for precise examination of their internal 3D structures. This process represents a rapid, highly efficient method to examine and quantify in 3D the formation of key structures required for the coordination of neurodevelopmental processes in both health and disease states. We posit that this approach would facilitate investigation of human neurodevelopmental processes in vitro.

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Patient-specific modeling of left heart anatomy, dynamics and hemodynamics from high resolution 4D CT

2010 IEEE International Symposium on Biomedical Imaging: From Nano to Macro ◽

10.1109/isbi.2010.5490298 ◽

2010 ◽

Cited By ~ 13

Author(s):

Viorel Mihalef ◽

Razvan Ionasec ◽

Yang Wang ◽

Yefeng Zheng ◽

Bogdan Georgescu ◽

...

Keyword(s):

High Resolution ◽

Patient Specific ◽

Left Heart ◽

4D Ct ◽

Heart Anatomy ◽

Patient Specific Modeling ◽

Specific Modeling

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SNP array analysis in hematologic malignancies: avoiding false discoveries

Blood ◽

10.1182/blood-2009-11-203182 ◽

2010 ◽

Vol 115 (21) ◽

pp. 4157-4161 ◽

Cited By ~ 64

Author(s):

Stefan Heinrichs ◽

Cheng Li ◽

A. Thomas Look

Keyword(s):

Single Nucleotide Polymorphism ◽

High Resolution ◽

Snp Array ◽

Hematologic Malignancies ◽

Cancer Genome ◽

Patient Specific ◽

Nucleotide Polymorphism ◽

Array Analysis ◽

Single Nucleotide ◽

Therapeutic Decisions

Comprehensive analysis of the cancer genome has become a standard approach to identifying new disease loci, and ultimately will guide therapeutic decisions. A key technology in this effort, single nucleotide polymorphism arrays, has been applied in hematologic malignancies to detect deletions, amplifications, and loss of heterozygosity (LOH) at high resolution. An inherent challenge of such studies lies in correctly distinguishing somatically acquired, cancer-specific lesions from patient-specific inherited copy number variations or segments of homozygosity. Failure to include appropriate normal DNA reference samples for each patient in retrospective or prospective studies makes it difficult to identify small somatic deletions not evident by standard cytogenetic analysis. In addition, the lack of proper controls can also lead to vastly overestimated frequencies of LOH without accompanying loss of DNA copies, so-called copy-neutral LOH. Here we use examples from patients with myeloid malignancies to demonstrate the superiority of matched tumor and normal DNA samples (paired studies) over multiple unpaired samples with respect to reducing false discovery rates in high-resolution single nucleotide polymorphism array analysis. Comparisons between matched tumor and normal samples will continue to be critical as the field moves from high resolution array analysis to deep sequencing to detect abnormalities in the cancer genome.

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Abstract 14839: High-resolution Spatiotemporal Changes in Dominant Frequency and Structural Organization During Persistent Atrial Fibrillation

Circulation ◽

10.1161/circ.142.suppl_3.14839 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Terrence Pong ◽

Joy Aparicio Valenzuela ◽

Kevin J Cyr ◽

Cody Carlton ◽

Sasank Sakhamuri ◽

...

Keyword(s):

Atrial Fibrillation ◽

High Resolution ◽

Structural Organization ◽

Porcine Model ◽

Dominant Frequency ◽

Patient Specific ◽

Structural Remodeling ◽

Atrial Activity ◽

Spatiotemporal Changes ◽

Mapping Arrays

Introduction: Spatiotemporal differences in atrial activity are thought to contribute to the maintenance of atrial fibrillation (AF). While recent evidence has identified changes in dominant frequency (DF) during the transition from paroxysmal to persistent AF, little is known about the frequency characteristics of the epicardium during this transition. The purpose of this study was to perform high-resolution mapping of the atrial epicardium and to characterize changes in frequency activity and structural organization during the transition from paroxysmal to persistent AF. Hypothesis: In a porcine model of persistent AF, we tested the hypothesis that the epicardium undergoes spatiotemporal changes in atrial activity and structural organization during persistent AF. Methods: Paroxysmal and persistent AF was induced in adult Yorkshire swine by atrial tachypacing. Atrial morphology was segmented from magnetic resonance imaging and high-resolution patient-specific flexible mapping arrays were 3D printed to match the epicardial contours of the atria. Epicardial activation and DF mapping was performed in four paroxysmal and four persistent AF animals using personalized mapping arrays. Histological analysis was performed to determine structural differences between paroxysmal and persistent AF. Results: The left atrial epicardium was associated with a significant increase in DF between paroxysmal and persistent AF (6.5 ± 0.2 vs. 7.4 ± 0.5 Hz, P = 0.03). High-resolution spatiotemporal mapping identified organized clusters of DF during paroxysmal AF which were lost during persistent AF. The development of persistent AF led to structural remodeling with increased atrial epicardial fibrosis. The organization index (OI) significantly decreased during persistent AF in both the left atria (0.3 ± 0.03 vs. 0.2 ± 0.03, P = 0.01) and right atria (0.33 ± 0.04 vs. 0.23 ± 0.02, P = 0.02). Conclusions: In the porcine model of persistent AF, the epicardium undergoes structural remodeling with increased epicardial fibrosis, reflected by changes in atrial organization index and dominant frequency.

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Accurate and Efficient Plate and Rod Microfinite Element Models for Whole Bone Segments Based on High-Resolution Peripheral Computed Tomography

Journal of Biomechanical Engineering ◽

10.1115/1.4042680 ◽

2019 ◽

Vol 141 (4) ◽

Cited By ~ 1

Author(s):

Ji Wang ◽

Bin Zhou ◽

Yizhong Jenny Hu ◽

Zhendong Zhang ◽

Y. Eric Yu ◽

...

Keyword(s):

Computed Tomography ◽

Vertebral Fracture ◽

High Resolution ◽

Yield Strength ◽

Musculoskeletal Diseases ◽

Quantitative Computed Tomography ◽

Patient Specific ◽

Clinical Tool ◽

Study Results ◽

Bone Segment

The high-resolution peripheral quantitative computed tomography (HR-pQCT) provides unprecedented visualization of bone microstructure and the basis for constructing patient-specific microfinite element (μFE) models. Based on HR-pQCT images, we have developed a plate-and-rod μFE (PR μFE) method for whole bone segments using individual trabecula segmentation (ITS) and an adaptive cortical meshing technique. In contrast to the conventional voxel approach, the complex microarchitecture of the trabecular compartment is simplified into shell and beam elements based on the trabecular plate-and-rod configuration. In comparison to voxel-based μFE models of μCT and measurements from mechanical testing, the computational and experimental gold standards, nonlinear analyses of stiffness and yield strength using the HR-pQCT-based PR μFE models demonstrated high correlation and accuracy. These results indicated that the combination of segmented trabecular plate-rod morphology and adjusted cortical mesh adequately captures mechanics of the whole bone segment. Meanwhile, the PR μFE modeling approach reduced model size by nearly 300-fold and shortened computation time for nonlinear analysis from days to within hours, permitting broader clinical application of HR-pQCT-based nonlinear μFE modeling. Furthermore, the presented approach was tested using a subset of radius and tibia HR-pQCT scans of patients with prior vertebral fracture in a previously published study. Results indicated that yield strength for radius and tibia whole bone segments predicted by the PR μFE model was effective in discriminating vertebral fracture subjects from nonfractured controls. In conclusion, the PR μFE model of HR-pQCT images accurately predicted mechanics for whole bone segments and can serve as a valuable clinical tool to evaluate musculoskeletal diseases.

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Development of a high resolution MRI intracranial atherosclerosis imaging phantom

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2016-012974 ◽

2017 ◽

Vol 10 (2) ◽

pp. 143-149 ◽

Cited By ~ 4

Author(s):

Ju-Yu Chueh ◽

Kajo van der Marel ◽

Matthew J Gounis ◽

Todd LeMatty ◽

Truman R Brown ◽

...

Keyword(s):

High Resolution ◽

Vessel Wall ◽

Cone Beam Ct ◽

Absolute Difference ◽

Patient Specific ◽

Fibrous Cap ◽

Intracranial Atherosclerotic Disease ◽

High Resolution Mri ◽

Atherosclerosis Imaging ◽

Stenotic Vessel

Background and purposeCurrently, there is neither a standard protocol for vessel wall MR imaging of intracranial atherosclerotic disease (ICAD) nor a gold standard phantom to compare MR sequences. In this study, a plaque phantom is developed and characterized that provides a platform for establishing a uniform imaging approach for ICAD.Materials and methodsA patient specific injection mold was 3D printed to construct a geometrically accurate ICAD phantom. Polyvinyl alcohol hydrogel was infused into the core shell mold to form the stenotic artery. The ICAD phantom incorporated materials mimicking a stenotic vessel and plaque components, including fibrous cap and lipid core. Two phantoms were scanned using high resolution cone beam CT and compared with four different 3 T MRI systems across eight different sites over a period of 18 months. Inter-phantom variability was assessed by lumen dimensions and contrast to noise ratio (CNR).ResultsQuantitative evaluation of the minimum lumen radius in the stenosis showed that the radius was on average 0.80 mm (95% CI 0.77 to 0.82 mm) in model 1 and 0.77 mm (95% CI 0.74 to 0.81 mm) in model 2. The highest CNRs were observed for comparisons between lipid and vessel wall. To evaluate manufacturing reproducibility, the CNR variability between the two models had an average absolute difference of 4.31 (95% CI 3.82 to 5.78). Variation in CNR between the images from the same scanner separated by 7 months was 2.5–6.2, showing reproducible phantom durability.ConclusionsA plaque phantom composed of a stenotic vessel wall and plaque components was successfully constructed for multicenter high resolution MRI standardization.

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Using High Resolution Cardiac CT Data to Model and Visualize Patient-Specific Interactions between Trabeculae and Blood Flow

Lecture Notes in Computer Science - Medical Image Computing and Computer-Assisted Intervention – MICCAI 2011 ◽

10.1007/978-3-642-23623-5_59 ◽

2011 ◽

pp. 468-475 ◽

Cited By ~ 7

Author(s):

Scott Kulp ◽

Mingchen Gao ◽

Shaoting Zhang ◽

Zhen Qian ◽

Szilard Voros ◽

...

Keyword(s):

Blood Flow ◽

High Resolution ◽

Cardiac Ct ◽

Patient Specific ◽

Specific Interactions ◽

Ct Data

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SU-D-141-04: Patient-Specific EPID Based High Resolution 3D VMAT QA

Medical Physics ◽

10.1118/1.4814035 ◽

2013 ◽

Vol 40 (6Part3) ◽

pp. 109-109

Author(s):

S Nicol ◽

C Furstoss ◽

P Munger ◽

W Wierzbicki

Keyword(s):

High Resolution ◽

Patient Specific

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MO-FG-CAMPUS-TeP1-05: Rapid and Efficient 3D Dosimetry for End-To-End Patient-Specific QA of Rotational SBRT Deliveries Using a High-Resolution EPID

Medical Physics ◽

10.1118/1.4957347 ◽

2016 ◽

Vol 43 (6Part32) ◽

pp. 3719-3719

Author(s):

Y M Yang ◽

B Han ◽

L Xing ◽

L Wang

Keyword(s):

High Resolution ◽

Patient Specific ◽

3D Dosimetry ◽

Patient Specific Qa ◽

End To End

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Probing cardiomyocyte mobility with multi-phase cardiac diffusion tensor MRI

PLoS ONE ◽

10.1371/journal.pone.0241996 ◽

2020 ◽

Vol 15 (11) ◽

pp. e0241996

Author(s):

Kévin Moulin ◽

Ilya A. Verzhbinsky ◽

Nyasha G. Maforo ◽

Luigi E. Perotti ◽

Daniel B. Ennis

Keyword(s):

High Resolution ◽

Healthy Volunteers ◽

Diffusion Tensor ◽

Spin Echo ◽

Mean Diffusivity ◽

Helix Angle ◽

Patient Specific ◽

Early Systole ◽

Multi Phase ◽

Late Systole

Purpose Cardiomyocyte organization and performance underlie cardiac function, but the in vivo mobility of these cells during contraction and filling remains difficult to probe. Herein, a novel trigger delay (TD) scout sequence was used to acquire high in-plane resolution (1.6 mm) Spin-Echo (SE) cardiac diffusion tensor imaging (cDTI) at three distinct cardiac phases. The objective was to characterize cardiomyocyte organization and mobility throughout the cardiac cycle in healthy volunteers. Materials and methods Nine healthy volunteers were imaged with cDTI at three distinct cardiac phases (early systole, late systole, and diastasis). The sequence used a free-breathing Spin-Echo (SE) cDTI protocol (b-values = 350s/mm2, twelve diffusion encoding directions, eight repetitions) to acquire high-resolution images (1.6x1.6x8mm3) at 3T in ~7 minutes/cardiac phase. Helix Angle (HA), Helix Angle Range (HAR), E2 angle (E2A), Transverse Angle (TA), Mean Diffusivity (MD), diffusion tensor eigenvalues (λ1-2-3), and Fractional Anisotropy (FA) in the left ventricle (LV) were characterized. Results Images from the patient-specific TD scout sequence demonstrated that SE cDTI acquisition was possible at early systole, late systole, and diastasis in 78%, 100% and 67% of the cases, respectively. At the mid-ventricular level, mobility (reported as median [IQR]) was observed in HAR between early systole and late systole (76.9 [72.6, 80.5]° vs 96.6 [85.9, 100.3]°, p<0.001). E2A also changed significantly between early systole, late systole, and diastasis (27.7 [20.8, 35.1]° vs 45.2 [42.1, 49]° vs 20.7 [16.6, 26.4]°, p<0.001). Conclusion We demonstrate that it is possible to probe cardiomyocyte mobility using multi-phase and high resolution cDTI. In healthy volunteers, aggregate cardiomyocytes re-orient themselves more longitudinally during contraction, while cardiomyocyte sheetlets tilt radially during wall thickening. These observations provide new insights into the three-dimensional mobility of myocardial microstructure during systolic contraction.

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