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Female, Humans, Pilot Projects, Endoscopes, Fallopian Tubes, Ovarian Neoplasms diagnostic imaging, and Ovarian Neoplasms pathology

Significance: High grade serous ovarian cancer is the most deadly gynecological cancer, and it is now believed that most cases originate in the fallopian tubes (FTs). Early detection of ovarian cancer could double the 5-year survival rate compared with late-stage diagnosis. Autofluorescence imaging can detect serous-origin precancerous and cancerous lesions in ex vivo FT and ovaries with good sensitivity and specificity. Multispectral fluorescence imaging (MFI) can differentiate healthy, benign, and malignant ovarian and FT tissues. Optical coherence tomography (OCT) reveals subsurface microstructural information and can distinguish normal and cancerous structure in ovaries and FTs.
Aim: We developed an FT endoscope, the falloposcope, as a method for detecting ovarian cancer with MFI and OCT. The falloposcope clinical prototype was tested in a pilot study with 12 volunteers to date to evaluate the safety and feasibility of FT imaging prior to standard of care salpingectomy in normal-risk volunteers. In this manuscript, we describe the multiple modifications made to the falloposcope to enhance robustness, usability, and image quality based on lessons learned in the clinical setting.
Approach: The ∼ 0.8    mm diameter falloposcope was introduced via a minimally invasive approach through a commercially available hysteroscope and introducing a catheter. A navigation video, MFI, and OCT of human FTs were obtained. Feedback from stakeholders on image quality and procedural difficulty was obtained.
Results: The falloposcope successfully obtained images in vivo . Considerable feedback was obtained, motivating iterative improvements, including accommodating the operating room environment, modifying the hysteroscope accessories, decreasing endoscope fragility and fiber breaks, optimizing software, improving fiber bundle images, decreasing gradient-index lens stray light, optimizing the proximal imaging system, and improving the illumination.
Conclusions: The initial clinical prototype falloposcope was able to image the FTs, and iterative prototyping has increased its robustness, functionality, and ease of use for future trials.
(© 2023 The Authors.)

Image reconstruction from data collected over full-angular range (FAR) in dual-energy CT (DECT) is well-studied. There exists interest in DECT with advanced scan configurations in which data are collected only over limited-angular ranges (LARs) for meeting unique workflow needs in certain practical imaging applications, and thus in the algorithm development for image reconstruction from such LAR data. The objective of the work is to investigate and prototype image reconstructions in DECT with LAR scans. We investigate and prototype optimization programs with various designs of constraints on the directional-total-variations (DTVs) of virtual monochromatic images and/or basis images, and derive the DTV algorithms to numerically solve the optimization programs for achieving accurate image reconstruction from data collected in a slew of different LAR scans. Using simulated and real data acquired with low- and high-kV spectra over LARs, we conduct quantitative studies to demonstrate and evaluate the optimization programs and their DTV algorithms developed. As the results of the numerical studies reveal, while the DTV algorithms yield images of visual quality and quantitative accuracy comparable to that of the existing algorithms from FAR data, the former reconstruct images with improved visualization, reduced artifacts, and also enhanced quantitative accuracy when applied to LAR data in DECT. Optimization-based, one-step algorithms, including the DTV algorithms demonstrated, can be developed for quantitative image reconstruction from spectral data collected over LARs of extents that are considerably smaller than the FAR in DECT. The theoretical and numerical results obtained can be exploited for prototyping designs of optimization-based reconstructions and LAR scans in DECT, and they may also yield insights into the development of reconstruction procedures in practical DECT applications. The approach and algorithms developed can naturally be applied to investigating image reconstruction from LAR data in multi-spectral and photon-counting CT.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)

Acetyl Coenzyme A metabolism, Cell Extracts, Escherichia coli metabolism, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae metabolism, and Metabolic Engineering

Building and optimizing biosynthetic pathways in engineered cells holds promise to address societal needs in energy, materials, and medicine, but it is often time-consuming. Cell-free synthetic biology has emerged as a powerful tool to accelerate design-build-test-learn cycles for pathway engineering with increased tolerance to toxic compounds. However, most cell-free pathway prototyping to date has been performed in extracts from wildtype cells which often do not have sufficient flux towards the pathways of interest, which can be enhanced by engineering. Here, to address this gap, we create a set of engineered Escherichia coli and Saccharomyces cerevisiae strains rewired via CRISPR-dCas9 to achieve high-flux toward key metabolic precursors; namely, acetyl-CoA, shikimate, triose-phosphate, oxaloacetate, α-ketoglutarate, and glucose-6-phosphate. Cell-free extracts generated from these strains are used for targeted enzyme screening in vitro. As model systems, we assess in vivo and in vitro production of triacetic acid lactone from acetyl-CoA and muconic acid from the shikimate pathway. The need for these platforms is exemplified by the fact that muconic acid cannot be detected in wildtype extracts provided with the same biosynthetic enzymes. We also perform metabolomic comparison to understand biochemical differences between the cellular and cell-free muconic acid synthesis systems (E. coli and S. cerevisiae cells and cell extracts with and without metabolic rewiring). While any given pathway has different interfaces with metabolism, we anticipate that this set of pre-optimized, flux enhanced cell extracts will enable prototyping efforts for new biosynthetic pathways and the discovery of biochemical functions of enzymes.
(Copyright © 2023 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.)