The fluorescent probes having complete spectral separation between absorption and emission spectra (large Stokes shift) are highly useful for solar concentrators and bioimaging. In bioimaging ...application, NIR fluorescent dyes have a greater advantage in tissue penetration depth compared to visible-emitting organic dyes or inorganic quantum dots. Here we report the design, synthesis, and characterization of an amphiphilic polymer, poly(isobutylene-alt-maleic anhyride)-functionalized near-infrared (NIR) IR-820 dye and its conjugates with iron oxide (Fe3O4) magnetic nanoparticles (MNPs) for optical and magnetic resonance (MR) imaging. Our results demonstrate that the Stokes shift of unmodified dye can be tuned (from ∼106 to 208 nm) by the functionalization of the dye with polymer and MNPs. The fabrication of bimodal probes involves (i) the synthesis of NIR fluorescent dye (IR-820 cyanine) functionalized with ethylenediamine linker in high yield, >90%, (ii) polymer conjugation to the functionalized NIR fluorescent dye, and (iii) grafting the polymer-conjugated dyes on iron oxide MNPs. The resulting uniform, small-sized (ca. 6 nm) NIR fluorescent dye–magnetic hybrid nanoparticles (NPs) exhibit a wider emissive range (800–1000 nm) and minimal cytotoxicity. Our preliminary studies demonstrate the potential utility of these NPs in bioimaging by means of direct labeling of cancerous HeLa cells via NIR fluorescence microscopy and good negative contrast enhancement in T 2-weighted MR imaging of a murine model.
Efforts to engineer new materials inspired by biological structures are hampered by the lack of genomic data from many model organisms studied in biomimetic research. Here we show that biomimetic ...engineering can be accelerated by integrating high-throughput RNA-seq with proteomics and advanced materials characterization. This approach can be applied to a broad range of systems, as we illustrate by investigating diverse high-performance biological materials involved in embryo protection, adhesion and predation. In one example, we rapidly engineer recombinant squid sucker ring teeth proteins into a range of structural and functional materials, including nanopatterned surfaces and photo-cross-linked films that exceed the mechanical properties of most natural and synthetic polymers. Integrating RNA-seq with proteomics and materials science facilitates the molecular characterization of natural materials and the effective translation of their molecular designs into a wide range of bio-inspired materials.
Medical 3D Printing for the Radiologist Mitsouras, Dimitris; Liacouras, Peter; Imanzadeh, Amir ...
Radiographics,
2015 Nov-Dec, Letnik:
35, Številka:
7
Journal Article
Recenzirano
Odprti dostop
While use of advanced visualization in radiology is instrumental in diagnosis and communication with referring clinicians, there is an unmet need to render Digital Imaging and Communications in ...Medicine (DICOM) images as three-dimensional (3D) printed models capable of providing both tactile feedback and tangible depth information about anatomic and pathologic states. Three-dimensional printed models, already entrenched in the nonmedical sciences, are rapidly being embraced in medicine as well as in the lay community. Incorporating 3D printing from images generated and interpreted by radiologists presents particular challenges, including training, materials and equipment, and guidelines. The overall costs of a 3D printing laboratory must be balanced by the clinical benefits. It is expected that the number of 3D-printed models generated from DICOM images for planning interventions and fabricating implants will grow exponentially. Radiologists should at a minimum be familiar with 3D printing as it relates to their field, including types of 3D printing technologies and materials used to create 3D-printed anatomic models, published applications of models to date, and clinical benefits in radiology. Online supplemental material is available for this article.
The risk for aortic dissection is increased among relatively young women with Turner syndrome (TS). It is unknown whether aortic dilatation precedes acute aortic dissection in TS and, if so, what ...specific diameter predicts impending deterioration.
Study subjects included 166 adult volunteers with TS (average age, 36.2 years) who were not selected for cardiovascular disease and 26 healthy female control subjects. Ascending and descending aortic diameters were measured by magnetic resonance imaging at the right pulmonary artery. TS women were on average 20 cm shorter, yet average aortic diameters were identical in the 2 groups. Ascending aortic diameters normalized to body surface area (aortic size index) were significantly greater in TS, and approximately 32% of TS women had values greater than the 95th percentile of 2.0 cm/m2. Ascending diameter/descending diameter ratios also were significantly greater in the TS group. During approximately 3 years of follow-up, aortic dissections occurred in 3 women with TS, for an annualized rate of 618 cases/100,000 woman-years. These 3 subjects had ascending aortic diameters of 3.7 to 4.8 cm and aortic size indices > 2.5 cm/m2.
The risk for aortic dissection is greatly increased in young women with TS. Because of their small stature, ascending aortic diameters of < 5 cm may represent significant dilatation; thus, the use of aortic size index is preferred. Individuals with a dilated ascending aorta defined as aortic size index > 2.0 cm/m2 require close cardiovascular surveillance. Those with aortic size index > or = 2.5 cm/m2 are at highest risk for aortic dissection.
Shiga toxins (Stxs) produced by ingested
can induce hemolytic uremic syndrome after crossing the intact intestinal barrier, entering the bloodstream, and targeting endothelial cells in the kidney. ...The method(s) by which the toxins reach the bloodstream are not fully defined. Here, we used two polarized cell models to evaluate Stx translocation: (i) a single-layer primary colonic epithelial cell model and (ii) a three-cell-layer model with colonic epithelial cells, myofibroblasts, and colonic endothelial cells. We traced the movement of Stx types 1a and 2a across the barrier models by measuring the toxicity of apical and basolateral media on Vero cells. We found that Stx1a and Stx2a crossed both models in either direction. However, approximately 10-fold more Stx translocated in the three-layer model as compared to the single-layer model. Overall, the percentage of toxin that translocated was about 0.01% in the epithelial-cell-only model but up to 0.09% in the three-cell-layer model. In both models, approximately 3- to 4-fold more Stx2a translocated than Stx1a. Infection of the three-cell-layer model with Stx-producing
(STEC) strains showed that serotype O157:H7 STEC reduced barrier function in the model and that the damage was not dependent on the presence of the
gene. Infection of the three-layer model with O26:H11 STEC strain TW08571 (Stx1a+ and Stx2a+), however, allowed translocation of modest amounts of Stx without reducing barrier function. Deletion of stx2a from TW08571 or the use of anti-Stx1 antibody prevented translocation of toxin. Our results suggest that single-cell models may underestimate the amount of Stx translocation and that the more biomimetic three-layer model is suited for Stx translocation inhibitor studies.
p53 tumor suppressor maintains genomic stability, typically acting through cell-cycle arrest, senescence, and apoptosis. We discovered a function of p53 in preventing conflicts between transcription ...and replication, independent of its canonical roles. p53 deficiency sensitizes cells to Topoisomerase (Topo) II inhibitors, resulting in DNA damage arising spontaneously during replication. Topoisomerase IIα (TOP2A)-DNA complexes preferentially accumulate in isogenic p53 mutant or knockout cells, reflecting an increased recruitment of TOP2A to regulate DNA topology. We propose that p53 acts to prevent DNA topological stress originating from transcription during the S phase and, therefore, promotes normal replication fork progression. Consequently, replication fork progression is impaired in the absence of p53, which is reversed by transcription inhibition. Pharmacologic inhibition of transcription also attenuates DNA damage and decreases Topo-II-DNA complexes, restoring cell viability in p53-deficient cells. Together, our results demonstrate a function of p53 that may underlie its role in tumor suppression.
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•p53 loss causes increased topological conflict between transcription and replication•p53 loss impairs normal replication fork progression•Topological conflict and TOP2A recruitment are reversed by transcription inhibition•Transcription inhibition also restores fork progression in p53-deficient cells
Yeo et al. demonstrate that p53 maintains genomic stability during replication by preventing the interference between replication and transcription. Transcription inhibition restores fork progression and attenuates the sensitivity to Topo II inhibitors in p53-deficient cells, providing compelling evidence that transcription causes chronic replication stress in the absence of functional p53.
Micro-computed tomography (microCT) is a common tool for the visualization of the internal composition of organic tissues. Collagen comprises approximately 25-35% of the whole-body protein content in ...mammals, and the structure and arrangement of collagen fibers contribute significantly to the integrity of tissues. Collagen type I is also frequently used as a key structural component in tissue-engineered and bioprinted tissues. However, the imaging of collagenous tissues is limited by their inherently low X-ray attenuation, which makes them indistinguishable from most other soft tissues. An imaging contrast agent that selectively alters X-ray attenuation is thus essential to properly visualize collagenous tissue using a standard X-ray tube microCT scanner. This review compares various contrast-enhanced techniques reported in the literature for MicroCT visualization of collagen-based tissues. An ideal microCT contrast agent would meet the following criteria: (1) it diffuses through the tissue quickly; (2) it does not deform or impair the object being imaged; and (3) it provides sufficient image contrast for reliable visualization of the orientation of individual fibers within the collagen network. The relative benefits and disadvantages of each method are discussed. Lugol's solution (I
K), phosphotungstic acid (H
PW
O
), mercury(II) chloride (HgCl
), and Wells-Dawson polyoxometalates came closest to fitting the criteria. While none of the contrast agents discussed in the literature met all criteria, each one has advantages to consider in the context of specific lab capabilities and imaging priorities.
Purpose
To develop a highly efficient magnetic field gradient coil for head imaging that achieves 200 mT/m and 500 T/m/s on each axis using a standard 1 MVA gradient driver in clinical whole‐body ...3.0T MR magnet.
Methods
A 42‐cm inner diameter head‐gradient used the available 89‐ to 91‐cm warm bore space in a whole‐body 3.0T magnet by increasing the radial separation between the primary and the shield coil windings to 18.6 cm. This required the removal of the standard whole‐body gradient and radiofrequency coils. To achieve a coil efficiency ~4× that of whole‐body gradients, a double‐layer primary coil design with asymmetric x‐y axes, and symmetric z‐axis was used. The use of all‐hollow conductor with direct fluid cooling of the gradient coil enabled ≥50 kW of total heat dissipation.
Results
This design achieved a coil efficiency of 0.32 mT/m/A, allowing 200 mT/m and 500 T/m/s for a 620 A/1500 V driver. The gradient coil yielded substantially reduced echo spacing, and minimum repetition time and echo time. In high b = 10,000 s/mm2 diffusion, echo time (TE) < 50 ms was achieved (>50% reduction compared with whole‐body gradients). The gradient coil passed the American College of Radiology tests for gradient linearity and distortion, and met acoustic requirements for nonsignificant risk operation.
Conclusions
Ultra‐high gradient coil performance was achieved for head imaging without substantial increases in gradient driver power in a whole‐body 3.0T magnet after removing the standard gradient coil. As such, any clinical whole‐body 3.0T MR system could be upgraded with 3‐4× improvement in gradient performance for brain imaging.
.2661 Preamble This document was developed by the American College of Cardiology Foundation (ACCF) Task Force on Clinical Expert Consensus Documents (ECDs) and cosponsored by the American College of ...Radiology (ACR), American Heart Association (AHA), North American Society for Cardiovascular Imaging (NASCI), and the Society for Cardiovascular Magnetic Resonance (SCMR), to provide a perspective on the current state of cardiovascular magnetic resonance (CMR). Often the topic is the subject of ongoing investigation. ...the reader should view the ECD as the best attempt of the ACCF and document cosponsors to inform and guide clinical practice in areas where rigorous evidence may not be available or the evidence to date is not widely accepted. ...some topics covered by ECDs will be addressed subsequently by the ACCF/AHA Practice Guidelines Committee. Peer Reviewer Representation Consultant Speaker Ownership/Partnership/Principal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Dr. James C. Carr Official Reviewer--North American Society for Cardiovascular Imaging None None None None None None Dr. Michael G. Del Core Official Reviewer--ACCF Board of Governors None None None None None None Dr. Andre Duerinckx Official Reviewer--American College of Radiology None None None Philips Medical Systems Schering-Plough None None Dr. Mark J. Eisenberg Official Reviewer--ACCF Task Force on Clinical Expert Consensus Documents None None None None None None Dr. Victor A. Ferrari Official Reviewer-- Society for Cardiovascular Magnetic Resonance Imaging None None None None None None Dr. Gautham Reddy Official Reviewer--American College of Radiology None None None None None None Dr. Orlando Simonetti Official Reviewer--North American Society for Cardiovascular Imaging None None * Siemens Healthcare None None None Dr. James E. Udelson Official Reviewer--ACCF Board of Trustees; American Heart Association None None None None None None Dr. Sanjay Kaul Content Reviewer--ACCF Task Force on Clinical Expert Consensus Documents None None None None None None Dr. Debabrata Mukherjee Content Reviewer--ACCF Task Force on Clinical Expert Consensus Documents None None None None None None Dr. Robert S. Rosenson Content Reviewer--ACCF Task Force on Clinical Expert Consensus Documents Abbott Anthera AstraZeneca* Daiichi Sankyo LipoScience* Roche None LipoScience* None Grain Board None Dr. Jonathan W. Weinsaft Content Reviewer--*Individual None None None Lantheus Medical Imaging None None * This table represents the relevant relationships with industry and other entities that were disclosed by reviewers at the time of peer review. A person is deemed to have a significant interest in a business if the interest represents ownership of 5% or more of the voting stock or share of the business entity, or ownership of $10 000 or more of the fair market value of the business entity; or if funds received by the person from the business entity exceed 5% of the person's gross income for the previous year.
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