Noninvasive Visualization Research Articles

Spindle shape and volume differ in high- and low-quality metaphase II oocytes.

Optical coherence microscopy non-invasively visualizes metaphase II spindles allowing for quantitative analysis of their volume and shape, which may prove useful in the assessment of the oocyte quality. Using a mouse model, we showed also that analysis of spindle length combined with morphokinetics improves the evaluation of the resulting embryos. The proper development of embryos strongly depends on the quality of oocytes, so the evaluation of oocytes may be a useful initial step in IVF procedures. Additionally, it enables embryologists to make more informed decisions regarding the treatments chosen for the patients and better manage patients' expectations. Optical coherence microscopy (OCM) allows for non-invasive 3D visualization of intracellular structures, such as spindles or nuclei, which have been linked to the success of embryonic development. Here, we applied a mouse model to examine whether OCM imaging could be used in the quality assessment of metaphase II (MII) oocytes. We showed that quantitative parameters describing the shape and volume of the MII spindle were associated with the quality of the resulting embryos, including the likelihood of blastocyst formation and the embryos' ability to differentiate the trophectoderm and primitive endoderm, but not the epiblast. We also created a multivariate linear regression model, combining OCM-based quantification of MII spindles with morphokinetic analysis of the embryos, that allowed for improved evaluation of the embryo quality. Finally, we proved that OCM does not interfere with the viability of the scanned cells, at least during the preimplantation development. Therefore, we believe that OCM-based quantitative assessment of MII spindles can improve the oocyte and embryo selection in IVF procedures.

Scalable manufacture of therapeutic mesenchymal stromal cell products on customizable microcarriers in vertical wheel bioreactors that improve direct visualization, product harvest, and cost

Background aimsHuman mesenchymal stromal cells (hMSCs) and their secreted products show great promise for treatment of musculoskeletal injury and inflammatory or immune diseases. However, the path to clinical utilization is hampered by donor-tissue variation and the inability to manufacture clinically relevant yields of cells or their products in a cost-effective manner. Previously we described a method to produce chemically and mechanically customizable gelatin methacryloyl (GelMA) microcarriers for culture of hMSCs. Herein, we demonstrate scalable GelMA microcarrier-mediated expansion of induced pluripotent stem cell (iPSC)-derived hMSCs (ihMSCs) in 500 mL and 3L vertical wheel bioreactors, offering several advantages over conventional microcarrier and monolayer-based expansion strategies. MethodsHuman mesenchymal stromal cells derived from induced pluripotent cells were cultured on custom-made spherical gelatin methacryloyl microcarriers in single-use vertical wheel bioreactors (PBS Biotech). Cell-laden microcarriers were visualized using confocal microscopy and elastic light scattering methodologies. Cells were assayed for viability and differentiation potential in vitro by standard methods. Osteogenic cell matrix derived from cells was tested in vitro for osteogenic healing using a rodent calvarial defect assay. Immune modulation was assayed with an in vivo peritonitis model using Zymozan A. ResultsThe optical properties of GelMA microcarriers permit noninvasive visualization of cells with elastic light scattering modalities, and harvest of product is streamlined by microcarrier digestion. At volumes above 500 mL, the process is significantly more cost-effective than monolayer culture. Osteogenic cell matrix derived from ihMSCs expanded on GelMA microcarriers exhibited enhanced in vivo bone regenerative capacity when compared to bone morphogenic protein 2, and the ihMSCs exhibited superior immunosuppressive properties in vivo when compared to monolayer-generated ihMSCs. ConclusionsThese results indicate that the cell expansion strategy described here represents a superior approach for efficient generation, monitoring and harvest of therapeutic MSCs and their products.

The Eye as the Window to the Heart: Optical Coherence Tomography Angiography Biomarkers as Indicators of Cardiovascular Disease

Alterations in microvasculature represent some of the earliest pathological processes across a wide variety of human diseases. In many organs, however, inaccessibility and difficulty in directly imaging tissues prevent the assessment of microvascular changes, thereby significantly limiting their translation into improved patient care. The eye provides a unique solution by allowing for the non-invasive and direct visualization and quantification of many aspects of the human microvasculature, including biomarkers for structure, function, hemodynamics, and metabolism. Optical coherence tomography angiography (OCTA) studies have specifically identified reduced capillary densities at the level of the retina in several eye diseases including glaucoma. This narrative review examines the published data related to OCTA-assessed microvasculature biomarkers and major systemic cardiovascular disease. While loss of capillaries is being established in various ocular disease, pilot data suggest that changes in the retinal microvasculature, especially within the macula, may also reflect small vessel damage occurring in other organs resulting from cardiovascular disease. Current evidence suggests retinal microvascular biomarkers as potential indicators of major systemic cardiovascular diseases, including systemic arterial hypertension, atherosclerotic disease, and congestive heart failure.

Non-invasive assessment and visualization of Phytophthora cactorum infection in strawberry crowns using quantitative magnetic resonance imaging

Phytophthora cactorum is an oomycete species that causes enormous losses on horticultural crops, including strawberries. The purpose of this work was to investigate the alterations caused by P. cactorum inoculation in hydroponically grown strawberry plantlets (Fragaria × ananassa Duch.) using quantitative magnetic resonance imaging (qMRI). It was observed that with MRI, spatial and temporal progression of the infection could be observed in the crown using quantitative MR parameters, namely relaxation time maps. Relaxation times are numeric subject-specific properties that describe the MR signal behavior in an examined anatomical region. Elevated T2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$T_{2}$$\\end{document} relaxation time values were observed inside the infected plant crowns with respect to the healthy references. The T2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$T_{2}$$\\end{document} and T2∗\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$T_{2}^{*}$$\\end{document} values of healthy plants were small in the crown region and further diminished during the development of the plant. Furthermore, elevated T1\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$T_{1}$$\\end{document} relaxation time values were seen in regions where P. cactorum progression was observed in corresponding plant dissection photographs. Quantitative susceptibility maps (QSM) were calculated to estimate the local magnetic field inhomogeneities. The QSM suggests magnetic susceptibility differences near the center of the pith. This study provides novel non-invasive information on the structure and development of strawberry plants and the effects caused by the P. cactorum infection.

Non-invasive quantification of corneal vascularization using anterior segment optical coherence tomography angiography

The presence of corneal vascularization (CV) interferes with the angiogenic and immune privilege of the cornea, risking rejection in eyes following keratoplasty. Pre-operative (lymph)-angioregression is a promising therapeutic approach, but objective monitoring by non-invasive CV imaging is needed. The purpose of this study was to investigate anterior-segment optical coherence tomography angiography (AS-OCTA) for CV visualization and quantification, and to show its superiority over slit-lamp photography in high-risk eyes scheduled for keratoplasty. This institutional pilot study included 29 eyes of 26 patients (51 ± 16 years, 8 female) with significant CV scheduled for keratoplasty that were imaged by slit-lamp photography (Zeiss SL 800) and AS-OCTA (Zeiss Plex Elite 9000). After manual corneal layer segmentation correction, CV maximum/relative depth was measured with the inbuilt software. Slit-lamp photographs and AS-OCTA images were compared for visualization of vascular details. Angiotool software allowed a semi-automated determination of CV-related parameters in the vascular complex of AS-OCTA images. The predominant causes of CV were the herpes simplex virus keratitis (n = 7) and chemical burn (n = 4). Visualization of vascular morphology in AS-OCTA was superior to slit-lamp photography in all except one eye. Vascular metrics including total vessel length, number of junctions/endpoints, junction density, lacunarity, and vessel area/density were defined using Angiotool, with CV depth localization despite scarring and opacification. AS-OCTA proved effective for angioregressive treatment monitoring. AS-OCTA enables non-invasive and objective three-dimensional visualization of corneal vascularization superior to slit-lamp photography, and could be a precious tool for monitoring angioregressive preconditioning prior to keratoplasty.

3D visualization and printing: An "Anatomical Engineering" trend revealing underlying morphology via innovation and reconstruction towards future of veterinary anatomy.

The amalgamation of veterinary anatomy, technology and innovation has led to development of latest technological advancement in the field of veterinary medicine, i.e., three-dimensional (3D) imaging and reconstruction. 3D visualization technique followed by 3D reconstruction has been proven to enhance non-destructive 3D visualization grossly or microscopically, e.g., skeletal muscle, smooth muscle, ligaments, cartilage, connective tissue, blood vessels, nerves, lymph nodes, and glands. The core aim of this manuscript is to document non-invasive 3D visualization methods being adopted currently in veterinary anatomy to reveal underlying morphology and to reconstruct them by 3D softwares followed by printing, its applications, current challenges, trends and future opportunities. 3D visualization methods such as MRI, CT scans and micro-CT scans are utilised in revealing volumetric data and underlying morphology at microscopic levels as well. This will pave a way to transform and re-invent the future of teaching in veterinary medicine, in clinical cases as well as in exploring wildlife anatomy. This review provides novel insights into 3D visualization and printing as it is the future of veterinary anatomy, thus making it spread to become the plethora of opportunities for whole veterinary science.

The application of radionuclide therapy for breast cancer.

Radionuclide-mediated diagnosis and therapy have emerged as effective and low-risk approaches to treating breast cancer. Compared to traditional anatomic imaging techniques, diagnostic radionuclide-based molecular imaging systems exhibit much greater sensitivity and ability to precisely illustrate the biodistribution and metabolic processes from a functional perspective in breast cancer; this transitions diagnosis from an invasive visualization to a noninvasive visualization, potentially ensuring earlier diagnosis and on-time treatment. Radionuclide therapy is a newly developed modality for the treatment of breast cancer in which radionuclides are delivered to tumors and/or tumor-associated targets either directly or using delivery vehicles. Radionuclide therapy has been proven to be eminently effective and to exhibit low toxicity when eliminating both primary tumors and metastases and even undetected tumors. In addition, the specific interaction between the surface modules of the delivery vehicles and the targets on the surface of tumor cells enables radionuclide targeting therapy, and this represents an exceptional potential for this treatment in breast cancer. This article reviews the development of radionuclide molecular imaging techniques that are currently employed for early breast cancer diagnosis and both the progress and challenges of radionuclide therapy employed in breast cancer treatment.

Single-image phase retrieval for off-the-shelf Zernike phase-contrast microscopes.

Quantitative phase imaging (QPI), such as digital holography, is considered a promising tool in the field of life science due to its noninvasive and quantitative visualization capabilities without the need for fluorescence labeling. However, the popularity of QPI systems is limited due to the cost and complexity of their hardware. In contrast, Zernike phase-contrast microscopy (ZPM) has been widely used in practical scenarios but has not been categorized as QPI, owing to halo and shade-off artifacts and the weak phase condition. Here, we present a single-image phase retrieval method for ZPM that addresses these issues without requiring hardware modifications. By employing a rigorous physical model of ZPM and a gradient descent algorithm for its inversion, we achieve single-shot QPI with an off-the-shelf ZPM system. Our approach is validated in simulations and experiments, demonstrating QPI of a polymer microbead and biological cells. The quantitative nature of our method for single-cell imaging is confirmed through comparisons with observations from an established QPI technique conducted through digital holography. This study paves the way for transforming non-QPI ZPM systems into QPI systems.

Non-invasive Visualization and Characterization of Bile Canaliculus Formation Using Refractive Index Tomography.

The vital role of bile canaliculus (BC) in liver function is closely related to its morphology. Electron microscopy has contributed to understanding BC morphology; however, its invasiveness limits its use in living specimens. Here, we report non-invasive characterization of BC formation using refractive index (RI) tomography. First, we investigated and characterized the RI distribution of BCs in two-dimensional (2D) cultured HepG2 cells. BCs were identified based on their distinct morphology and functionality, as confirmed using a fluorescence-labeled bile acid analog. The RI distribution of BCs exhibited three common features: (1) luminal spaces with a low RI between adjacent hepatocytes; (2) luminal spaces surrounded by a membranous structure with a high RI; and (3) multiple microvillus structures with a high RI within the lumen. Second, we demonstrated the characterization of BC structures in a three-dimensional (3D) culture model, which is more relevant to the in vivo environment but more difficult to evaluate than 2D cultures. Various BC structures were identified inside HepG2 spheroids with the three features of RI distribution. Third, we conducted comparative analyses and found that the BC lumina of spheroids had higher circularity and lower RI standard deviation than 2D cultures. We also addressed comparison of BC and intracellular lumen-like structures within a HepG2 spheroid, and found that the BC lumina had higher RI and longer perimeter than intracellular lumen-like structures. Our demonstration of the non-destructive, label-free visualization and quantitative characterization of living BC structures will be a basis for various hepatological and pharmaceutical applications.

Non-Invasive Direct Visualization of Luciferase-Luciferin Emitted Light Producing True Images from an Orthotopic Lung Cancer Xenograft Model in Nude Mice Using an Ultra-sensitive Low-light Camera and Optics.

In vivo imaging with luciferase-luciferin has been limited by the inability to visualize the low emitted light, with the signal quantified only by photon counting using a cumbersome highly-cooled CCD camera in a dark room. In the present study, we demonstrate direct visualization of the luciferase-luciferin signal from an orthotopic lung cancer in a nude-mouse xenograft model with a sensitive low-light camera and optics. Mouse Lewis-lung carcinoma cells expressing luciferase (LL/2-Luc2) were injected transcutaneously into the lung of a nude mouse. One week later after cell injection, luciferase imaging for emission at 560 nm was performed using the UVP Biospectrum Advanced system after i.v. injection of D-luciferin potassium salt. The intensity of the visualized light was measured and quantified with the instrument. A week following the implantation of LL/2-Luc2 cells in nude mice, the luciferase-luciferin signal from LL/2-Luc2 tumors in the lung was sufficiently visible through the skin to produce true images. At fifteen minutes, the intensity peaked and then progressively dropped due to clearance of luciferin from the tumor. Using the UVP Biospectrum Advanced system we demonstrated non-invasive visualization of true images from luciferase-luciferin signals from an orthotopic lung-cancer mouse model. The luciferase-luciferin emitted light was directly visible through the skin which is a major improvement over previous photon counting to detect the luciferase-luciferin signal.

A polymeric 1H/19F dual-modal MRI contrast agent with a snowman-like Janus nanostructure.

Magnetic resonance imaging (MRI) has emerged as a pivotal tool in contemporary medical diagnostics, offering non-invasive and high-resolution visualization of internal structures. Contrast agents are essential for enhancing MRI resolution, accurate lesion detection, and early pathology identification. While gadolinium-based contrast agents are widely used in clinics, safety concerns have prompted exploration of metal-free alternatives, including fluorine and nitroxide radical-based MRI contrast agents. Fluorine-containing compounds exhibit excellent MRI capabilities, with 19F MRI providing enhanced resolution and quantitative assessment. Nitroxide radicals, such as PROXYL and TEMPO, offer paramagnetic properties for MRI contrast. Despite their versatility, nitroxide radicals suffer from lower relaxivity values (r1) compared to gadolinium. Dual-modal imaging, combining 1H and 19F MRI, has gained prominence for its comprehensive insights into biological processes and disease states. However, existing dual-modal agents predominantly utilize gadolinium-organic ligands without incorporating nitroxide radicals. Here, we introduce a novel dual-modal MRI contrast agent (J-CA) featuring a Janus asymmetric nanostructure synthesized via seeded emulsion polymerization and post-modification. J-CA demonstrates excellent in vitro and in vivo performance in both 19F and 1H MRI, with a T2 relaxation time of 5 ms and an r1 value of 0.31 mM-1 s-1, ensuring dual-modal imaging capability. Moreover, J-CA exhibits superior biocompatibility and organ targeting, making it a promising candidate for precise lesion imaging and disease diagnosis. This work introduces a new avenue for metal-free dual-modal MRI, addressing safety concerns associated with traditional contrast agents.

Dynamic monitoring of the fibrosis disease by a collagen targeting near infrared probe.

The deposition of the extracellular matrix, especially collagen, and the elevated expression levels of reactive oxygen species, including H2O2, are the main features of fibrosis. Fibrosis can occur in many tissues, such as tumor and liver tissues. The deposition of collagen in the location of lesions not only leads to immunological rejection and supports liver fibrosis and tumor progression, but also provides unique physiological signals with the progression of fibrosis and tumor. However, at present, the detection of fibrosis, especially real time detection, is greatly difficult, making it important to develop noninvasive probes for the dynamic monitoring of fibrosis progression. Herein, we propose a H2O2 responsive macromolecular probe for collagen imaging with high sensitivity and specificity. This probe consists of a collagen-targeting peptide and a H2O2-sensitive and near-infrared (NIR)-emitting macromolecular optical probe, which could effectively bind to collagen both in vitro and in vivo in the region of tumor or fibrotic liver tissues, allowing for high sensitivity and noninvasive visualization of fibrotic tissues and real time monitoring of collagen degradation after anti-fibrotic drug treatment.

Coronary artery wall contrast enhancement imaging impact on disease activity assessment in IgG4-RD: a direct marker of coronary involvement

BackgroundCoronary artery wall contrast enhancement (CE) has been applied to non-invasive visualization of changes to the coronary artery wall in systemic lupus erythematosus (SLE). This study investigated the feasibility of quantifying CE to detect coronary involvement in IgG4-related disease (IgG4-RD), as well as the influence on disease activity assessment. MethodsA total of 93 subjects (31 IgG4-RD; 29 SLE; 33 controls) were recruited in the study. Coronary artery wall imaging was performed in a 3.0 T MRI scanner. Serological markers and IgG4-RD Responder Index (IgG4-RD-RI) scores were collected for correlation analysis. ResultsCoronary wall CE was observed in 29 (94 %) IgG4-RD patients and 22 (76 %) SLE patients. Contrast-to-noise ratio (CNR) and total CE area were significantly higher in patient groups compared to controls (CNR: 6.1 ± 2.7 [IgG4-RD] v. 4.2 ± 2.3 [SLE] v. 1.9 ± 1.5 [control], P < 0.001; Total CE area: 3.0 [3.0–6.6] v. 1.7 [1.5–2.6] v. 0.3 [0.3–0.9], P < 0.001). In the IgG4-RD group, CNR and total CE area were correlated with the RI (CNR: r = 0.55, P = 0.002; total CE area: r = 0.39, P = 0.031). RI´ scored considering coronary involvement by CE, differed significantly from RI scored without consideration of CE (RI v. RI´: 15 ± 6 v. 16 ± 6, P < 0.001). ConclusionsVisualization and quantification of CMR coronary CE by CNR and total CE area could be utilized to detect subclinical and clinical coronary wall involvement, which is prevalent in IgG4-RD. The potential inclusion of small and medium-sized vessel involvements in the assessment of disease activity in IgG4-RD is worthy of further investigation.

Enzyme-responsive, multi-lock optical probes for molecular imaging and disease theranostics.

Optical imaging is an indispensable tool for non-invasive visualization of biomolecules in living organisms, thereby offering a sensitive approach for disease diagnosis and image-guided disease treatment. Single-lock activatable optical probes (SOPs) that specifically switch on optical signals in the presence of biomarkers-of-interest have shown both higher detection sensitivity and imaging quality as compared to conventional "always-on" optical probes. However, such SOPs can still show "false-positive" results in disease diagnosis due to non-specific biomarker expression in healthy tissues. By contrast, multi-lock activatable optical probes (MOPs) that simultaneously detect multiple biomarkers-of-interest could improve detection specificity towards certain biomolecular events or pathological conditions. In this Review, we discuss the recent advancements of enzyme-responsive MOPs, with a focus on their biomedical applications. The higher detection specificity of MOPs could in turn enhance disease diagnosis accuracy and improve treatment efficacy in image-guided disease therapy with minimal toxicity in the surrounding healthy tissues. Finally, we discuss the current challenges and suggest future applications of MOPs.

Multiwavelength laser doppler holography (MLDH) in spatiotemporal optical coherence tomography (STOC-T)

Spatiotemporal optical coherence tomography (STOC-T) is the novel modality for high-speed, crosstalk- and aberration-free volumetric imaging of biological tissue in vivo. STOC-T extends the Fourier-Domain holographic Optical Coherence Tomography by the spatial phase modulation that enables the reduction of spatial coherence of the tunable laser. By reducing the spatial coherence of the laser, we suppress coherent noise, and, consequently, improve the imaging depth. Furthermore, we remove geometrical aberrations computationally in postprocessing. We recently demonstrated high-speed, high-resolution STOC-T of human retinal imaging in vivo. Here, we show that the dataset produced by STOC-T can be processed differently to reveal blood flow in the human retina in vivo. To render the blood flow, we first pre-process STOC-T holographic data to access the approximated information about the Doppler-shifted optical field backscattered from the sample. Then, we analyze it using methods from the laser Doppler flowmetry, namely, by analyzing the Doppler broadening caused by moving light scatterers (red blood cells). However, contrary to conventional approaches, we use multiple illumination wavelengths. This enables us to render the structural volumetric and blood flow images from the same dataset concurrently. Our method, denoted as multiwavelength laser Doppler holography (MLDH), links laser Doppler flowmetry with multiwavelength holographic detection to enable noninvasive visualization and possible blood flow quantification at different human retina layers at high speeds and high transverse resolution in vivo.

Editorial for “Whole-Body Magnetic Resonance Imaging at 0.05 Tesla”

Magnetic Resonance Imaging (MRI) stands as a cornerstone of modern medical diagnostics, offering noninvasive visualization of internal body structures with unparalleled detail. Its ability to produce detailed images with exceptional soft tissue contrast has made it an indispensable tool in various medical specialties, ranging from neurology to oncology. However, the widespread adoption of MRI has been hindered by its high cost and infrastructure requirements, which pose significant challenges, particularly in low-income and developing regions.

Alpha-Synuclein Oligomers Driven T1-T2 Switchable Nanoprobes for Early and Accurate Diagnosis of Parkinson's Disease.

The alpha-synuclein (α-syn) oligomers hold a central role in the pathology of Parkinson's disease (PD). Achieving accurate detection of α-syn oligomers in vivo presents a promising avenue for early and accurate diagnosis of PD. Magnetic resonance imaging (MRI), with non-invasion and exceptional tissue penetration, offers a potent tool for visualizing α-syn oligomers in vivo. Nonetheless, ensuring diagnostic specificity remains a formidable challenge. Herein, a novel MRI probe (ASOSN) is introduced, which encompasses highly sensitive antiferromagnetic nanoparticles functionalized with single-chain fragment variable antibodies, endowing it with the capacity for discerning recognition and binding to α-syn oligomers and triggering a switchable T1-T2 MRI signal. Significantly, ASOSN possesses the unique capability to accurately discriminate α-syn oligomers from neuroinflammation in vivo. Moreover, ASOSN facilitates the non-invasive and precise visualizing of endogenous α-syn oligomers in living systems. This innovative design heralds the development of a non-invasive visualization strategy for α-syn oligomers, marking a pivotal advancement for early and accurate diagnosis of PD.

The role of non-invasive preoperative imaging techniques in predicting the risk of pancreatic fistula development in pancreaticoduodenal tumours

Background. In pancreaticoduodenal tumours, pancreaticoduodenectomy (PDE) is a radical surgical intervention. The most important stage of the operation is the pancreaticojejunoanastomosis (PEA), the admissibility of which depends on many factors: the degree of fibrous changes in the pancreatic parenchyma, the degree of mechanical jaundice, and the operating surgeon’s technique. Identification of factors that reflect changes in the structure of the pancreatic parenchyma and its ductal system, which are important predictors in predicting the risk of developing pancreatic fistula (PF) after PDE, is of great scientific importance. Purpose. Evaluation of changes in the structure of the pancreatic parenchyma and its ductal system using non-invasive preoperative imaging methods in predicting the risk of pancreatic fistula development during pancreaticoduodenectomy. Materials and Methods. This study included 302 patients who underwent pancreaticoduodenectomy. Mechanical jaundice was detected in 246 (81.5%) patients, 56 (18.5%) patients had no jaundice, the age of patients ranged from 31 to 77 years, 178 (58.9%) were men and 124 (41.1%) were women. Ultrasound elastography and multidetector computed tomography were used for preoperative non-invasive visualisation of the degree of changes in the pancreatic parenchyma and its ductal system. The following parameters of visualisation of the pancreatic parenchyma with an assessment of the anatomical features of the isthmus and the duct of Wirsung were identified: diameter and cross-sectional area of the duct of Wirsung (at the level of the isthmus), width and thickness of the pancreas (at the level of the isthmus), cross-sectional area of the pancreatic isthmus (without the area of the duct of Wirsung), native density, and stiffness of the pancreatic parenchyma. Results and discussion. The ROC analysis of the parameters for assessing the state of the parenchyma of the pancreas and the duct of Wirsung obtained from computed tomography made it possible to determine the validity of these indicators in predicting the risk of developing PF. According to the results of the ROC analysis, the following indicators were identified as markers of moderate risk of developing PF: the diameter of the duct of Wirsung is less than 4 mm, the cross-sectional area of the duct of Wirsung is less than 0.23 cm2 , the thickness of the isthmus of the pancreas is greater than 15 mm, the width of the isthmus of the pancreas is greater than 19 mm, the cross-sectional area of the isthmus of the pancreas (without the area of the duct of Wirsung) is greater than 3 cm2 , and the native density is greater than 24 HU. To assess the high risk of developing PF, the use of ROC analysis allowed us to establish the high quality of diagnostic models for such computed tomography parameters as the diameter of the duct of Wirsung – the area under the ROC curve is 0.965, the cross-sectional area of the duct of Wirsung – AUC is 0.894, the cross-sectional area of the isthmus of the pancreas (without the area of the duct of Wirsung) – AUC is 0.873, the width of the isthmus of the pancreas – the area under the ROC curve is 0.859, the native density – AUC is 0.844. Determination of the parameter of stiffness of the pancreatic parenchyma by shear wave elastography in predicting high and moderate risk of developing PF also corresponded to the high quality of the diagnostic model. Conclusions. The use of non-invasive imaging methods allows changes in the structure of the pancreatic parenchyma, anatomical features of the pancreatic isthmus and the duct of Wirsung to be detected at the preoperative stage, the risk of developing a pancreatic fistula to be predicted and the number of complications during pancreaticoduodenectomy to be reduced.

Chronic Pancreatitis in Children

Chronic pancreatitis (CP) in children is a rare condition and its etiology varies; it is mainly associated with genetic abnormalities, autoimmune pancreatitis, and obstruction. Most cases of CP have a history of acute pancreatitis. The magnetic resonance cholangiopancreatography is a diagnostic technique that allows noninvasive multiplanar visualization of the biliary and pancreatic ducts, and does not require contrast administration. In children with CP, the step-up management includes a limited trial of endoscopic interventions, such as endoscopic retrograde cholangiopancreatography, followed by surgery.

Deep learning framework for automated goblet cell density analysis in in-vivo rabbit conjunctiva

Goblet cells (GCs) in the conjunctiva are specialized epithelial cells secreting mucins for the mucus layer of protective tear film and playing immune tolerance functions for ocular surface health. Because GC loss is observed in various ocular surface diseases, GC examination is important for precision diagnosis. Moxifloxacin-based fluorescence microscopy (MBFM) was recently developed for non-invasive high-contrast GC visualization. MBFM showed promise for GC examination by high-speed large-area imaging and a robust analysis method is needed to provide GC information. In this study, we developed a deep learning framework for GC image analysis, named dual-channel attention U-Net (DCAU-Net). Dual-channel convolution was used both to extract the overall image texture and to acquire the GC morphological characteristics. A global channel attention module was adopted by combining attention algorithms and channel-wise pooling. DCAU-Net showed 93.1% GC segmentation accuracy and 94.3% GC density estimation accuracy. Further application to both normal and ocular surface damage rabbit models revealed the spatial variations of both GC density and size in normal rabbits and the decreases of both GC density and size in damage rabbit models during recovery after acute damage. The GC analysis results were consistent with histology. Together with the non-invasive high-contrast imaging method, DCAU-Net would provide GC information for the diagnosis of ocular surface diseases.