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The Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), also known as CD66a, is a member of the immunoglobulin superfamily. CEACAM1 was shown to be a prognostic marker in patients suffering from cancer. In this review, we summarize pre-clinical and clinical evidence linking CEACAM1 to tumorigenicity and cancer progression. Furthermore, we discuss potential CEACAM1-based mechanisms that may affect cancer biology.
Ultra-high-resolution photon-counting detector CT arthrography of the ankle: a feasibility study
(2023)
This study was designed to investigate the image quality of ultra-high-resolution ankle arthrography employing a photon-counting detector CT. Bilateral arthrograms were acquired in four cadaveric specimens with full-dose (10 mGy) and low-dose (3 mGy) scan protocols. Three convolution kernels with different spatial frequencies were utilized for image reconstruction (ρ\(_{50}\); Br98: 39.0, Br84: 22.6, Br76: 16.5 lp/cm). Seven radiologists subjectively assessed the image quality regarding the depiction of bone, hyaline cartilage, and ligaments. An additional quantitative assessment comprised the measurement of noise and the computation of contrast-to-noise ratios (CNR). While an optimal depiction of bone tissue was achieved with the ultra-sharp Br98 kernel (S ≤ 0.043), the visualization of cartilage improved with lower modulation transfer functions at each dose level (p ≤ 0.014). The interrater reliability ranged from good to excellent for all assessed tissues (intraclass correlation coefficient ≥ 0.805). The noise levels in subcutaneous fat decreased with reduced spatial frequency (p < 0.001). Notably, the low-dose Br76 matched the CNR of the full-dose Br84 (p 0.999) and superseded Br98 (p < 0.001) in all tissues. Based on the reported results, a photon-counting detector CT arthrography of the ankle with an ultra-high-resolution collimation offers stellar image quality and tissue assessability, improving the evaluation of miniscule anatomical structures. While bone depiction was superior in combination with an ultra-sharp convolution kernel, soft tissue evaluation benefited from employing a lower spatial frequency.
Recent dissection studies resulted in the introduction of the term “chiasma antebrachii”, which represents an intersection of the flexor digitorum superficialis (FDS) tendons for digits 2 and 3 in the distal third of the forearm. This retrospective investigation aimed to provide an MRI-based morphologic analysis of the chiasma antebrachii. In 89 patients (41 women, 39.3 ± 21.3 years), MRI examinations of the forearm (2010–2021) were reviewed by two radiologists, who evaluated all studies for the presence and length of the chiasma as well as its distance from the distal radioulnar and elbow joint. The chiasma antebrachii was identified in the distal third of the forearm in 88 patients (98.9%), while one intersection was located more proximally in the middle part. The chiasma had a median length of 28 mm (interquartile range: 24–35 mm). Its distances to the distal radioulnar and elbow joint were 16 mm (8–25 mm) and 215 mm (187–227 mm), respectively. T1-weighted post-contrast sequences were found to be superior to T2- or proton-density-weighted sequences in 71 cases (79.8%). To conclude, the chiasma antebrachii is part of the standard FDS anatomy. Knowledge of its morphology is important, e.g., in targeted injections of therapeutics or reconstructive surgery.
Diabetes mellitus is a common disease affecting more than 537 million adults worldwide. The microvascular complications that occur during the course of the disease are widespread and affect a variety of organ systems in the body. Diabetic retinopathy is one of the most common long-term complications, which include, amongst others, endothelial dysfunction, and thus, alterations in the blood-retinal barrier (BRB). This particularly restrictive physiological barrier is important for maintaining the neuroretina as a privileged site in the body by controlling the inflow and outflow of fluid, nutrients, metabolic end products, ions, and proteins. In addition, people with diabetic retinopathy (DR) have been shown to be at increased risk for systemic vascular complications, including subclinical and clinical stroke, coronary heart disease, heart failure, and nephropathy. DR is, therefore, considered an independent predictor of heart failure. In the present review, the effects of diabetes on the retina, heart, and kidneys are described. In addition, a putative common microRNA signature in diabetic retinopathy, nephropathy, and heart failure is discussed, which may be used in the future as a biomarker to better monitor disease progression. Finally, the use of miRNA, targeted neurotrophin delivery, and nanoparticles as novel therapeutic strategies is highlighted.
Hereditary retinal degenerations like retinitis pigmentosa (RP) are among the leading causes of blindness in younger patients. To enable in vivo investigation of cellular and molecular mechanisms responsible for photoreceptor cell death and to allow testing of therapeutic strategies that could prevent retinal degeneration, animal models have been created. In this study, we deeply characterized the transcriptional profile of mice carrying the transgene rhodopsin V20G/P23H/P27L (VPP), which is a model for autosomal dominant RP. We examined the degree of photoreceptor degeneration and studied the impact of the VPP transgene-induced retinal degeneration on the transcriptome level of the retina using next generation RNA sequencing (RNASeq) analyses followed by weighted correlation network analysis (WGCNA). We furthermore identified cellular subpopulations responsible for some of the observed dysregulations using in situ hybridizations, immunofluorescence staining, and 3D reconstruction. Using RNASeq analysis, we identified 9256 dysregulated genes and six significantly associated gene modules in the subsequently performed WGCNA. Gene ontology enrichment showed, among others, dysregulation of genes involved in TGF-β regulated extracellular matrix organization, the (ocular) immune system/response, and cellular homeostasis. Moreover, heatmaps confirmed clustering of significantly dysregulated genes coding for components of the TGF-β, G-protein activated, and VEGF signaling pathway. 3D reconstructions of immunostained/in situ hybridized sections revealed retinal neurons and Müller cells as the major cellular population expressing representative components of these signaling pathways. The predominant effect of VPP-induced photoreceptor degeneration pointed towards induction of neuroinflammation and the upregulation of neuroprotective pathways like TGF-β, G-protein activated, and VEGF signaling. Thus, modulation of these processes and signaling pathways might represent new therapeutic options to delay the degeneration of photoreceptors in diseases like RP.
Blood vessel organoids are an important in vitro model to understand the underlying mechanisms of human blood vessel development and for toxicity testing or high throughput drug screening. Here we present a novel, cost-effective, and easy to manufacture vascular organoid model. To engineer the organoids, a defined number of human induced pluripotent stem cells are seeded in non-adhesive agarose coated wells of a 96-well plate and directed towards a lateral plate mesoderm fate by activation of Wnt and BMP4 signaling. We observe the formation of a circular layer of angioblasts around days 5–6. Induced by VEGF application, CD31\(^+\) vascular endothelial cells appear within this vasculogenic zone at approximately day 7 of organoid culture. These cells arrange to form a primitive vascular plexus from which angiogenic sprouting is observed after 10 days of culture. The differentiation outcome is highly reproducible, and the size of organoids is scalable depending on the number of starting cells. We observe that the initial vascular ring forms at the interface between two cell populations. The inner cellular compartment can be distinguished from the outer by the expression of GATA6, a marker of lateral plate mesoderm. Finally, 14-days-old organoids were transplanted on the chorioallantois membrane of chicken embryos resulting in a functional connection of the human vascular network to the chicken circulation. Perfusion of the vessels leads to vessel wall maturation and remodeling as indicated by the formation of a continuous layer of smooth muscle actin expressing cells enwrapping the endothelium. In summary, our organoid model recapitulates human vasculogenesis, angiogenesis as well as vessel wall maturation and therefore represents an easy and cost-effective tool to study all steps of blood vessel development and maturation directly in the human setting without animal experimentation.
This study evaluated the influence of different vascular reconstruction kernels on the image quality of CT angiographies of the lower extremity runoff using a 1st-generation photon-counting-detector CT (PCD-CT) compared with dose-matched examinations on a 3rd-generation energy-integrating-detector CT (EID-CT). Inducing continuous extracorporeal perfusion in a human cadaveric model, we performed CT angiographies of eight upper leg arterial runoffs with radiation dose-equivalent 120 kVp acquisition protocols (CTDIvol 5 mGy). Reconstructions were executed with different vascular kernels, matching the individual modulation transfer functions between scanners. Signal-to-noise-ratios (SNR) and contrast-to-noise-ratios (CNR) were computed to assess objective image quality. Six radiologists evaluated image quality subjectively using a forced-choice pairwise comparison tool. Interrater agreement was determined by calculating Kendall’s concordance coefficient (W). The intraluminal attenuation of PCD-CT images was significantly higher than of EID-CT (414.7 ± 27.3 HU vs. 329.3 ± 24.5 HU; p < 0.001). Using comparable kernels, image noise with PCD-CT was significantly lower than with EID-CT (p ≤ 0.044). Correspondingly, SNR and CNR were approximately twofold higher for PCD-CT (p < 0.001). Increasing the spatial frequency for PCD-CT reconstructions by one level resulted in similar metrics compared to EID-CT (CNRfat; EID-CT Bv49: 21.7 ± 3.7 versus PCD-CT Bv60: 21.4 ± 3.5). Overall image quality of PCD-CTA achieved ratings superior to EID-CTA irrespective of the used reconstruction kernels (best: PCD-CT Bv60; worst: EID-CT Bv40; p < 0.001). Interrater agreement was good (W = 0.78). Concluding, PCD-CT offers superior intraluminal attenuation, SNR, and CNR compared to EID-CT in angiographies of the upper leg arterial runoff. Combined with improved subjective image quality, PCD-CT facilitates the use of sharper convolution kernels and ultimately bears the potential of improved vascular structure assessability.
In this study, the impact of reconstruction sharpness on the visualization of the appendicular skeleton in ultrahigh-resolution (UHR) photon-counting detector (PCD) CT was investigated. Sixteen cadaveric extremities (eight fractured) were examined with a standardized 120 kVp scan protocol (CTDI\(_{vol}\) 10 mGy). Images were reconstructed with the sharpest non-UHR kernel (Br76) and all available UHR kernels (Br80 to Br96). Seven radiologists evaluated image quality and fracture assessability. Interrater agreement was assessed with the intraclass correlation coefficient. For quantitative comparisons, signal-to-noise-ratios (SNRs) were calculated. Subjective image quality was best for Br84 (median 1, interquartile range 1–3; p ≤ 0.003). Regarding fracture assessability, no significant difference was ascertained between Br76, Br80 and Br84 (p > 0.999), with inferior ratings for all sharper kernels (p < 0.001). Interrater agreement for image quality (0.795, 0.732–0.848; p < 0.001) and fracture assessability (0.880; 0.842–0.911; p < 0.001) was good. SNR was highest for Br76 (3.4, 3.0–3.9) with no significant difference to Br80 and Br84 (p > 0.999). Br76 and Br80 produced higher SNRs than all kernels sharper than Br84 (p ≤ 0.026). In conclusion, PCD-CT reconstructions with a moderate UHR kernel offer superior image quality for visualizing the appendicular skeleton. Fracture assessability benefits from sharp non-UHR and moderate UHR kernels, while ultra-sharp reconstructions incur augmented image noise.
Objectives: This study investigated the feasibility and image quality of ultra-low-dose unenhanced abdominal CT using photon-counting detector technology and tin prefiltration. Materials and Methods: Employing a first-generation photon-counting CT scanner, eight cadaveric specimens were examined both with tin prefiltration (Sn 100 kVp) and polychromatic (120 kVp) scan protocols matched for radiation dose at three different levels: standard-dose (3 mGy), low-dose (1 mGy) and ultra-low-dose (0.5 mGy). Image quality was evaluated quantitatively by means of contrast-to-noise-ratios (CNR) with regions of interest placed in the renal cortex and subcutaneous fat. Additionally, three independent radiologists performed subjective evaluation of image quality. The intraclass correlation coefficient was calculated as a measure of interrater reliability. Results: Irrespective of scan mode, CNR in the renal cortex decreased with lower radiation dose. Despite similar mean energy of the applied x-ray spectrum, CNR was superior for Sn 100 kVp over 120 kVp at standard-dose (17.75 ± 3.51 vs. 14.13 ± 4.02), low-dose (13.99 ± 2.6 vs. 10.68 ± 2.17) and ultra-low-dose levels (8.88 ± 2.01 vs. 11.06 ± 1.74) (all p ≤ 0.05). Subjective image quality was highest for both standard-dose protocols (score 5; interquartile range 5–5). While no difference was ascertained between Sn 100 kVp and 120 kVp examinations at standard and low-dose levels, the subjective image quality of tin-filtered scans was superior to 120 kVp with ultra-low radiation dose (p < 0.05). An intraclass correlation coefficient of 0.844 (95% confidence interval 0.763–0.906; p < 0.001) indicated good interrater reliability. Conclusions: Photon-counting detector CT permits excellent image quality in unenhanced abdominal CT with very low radiation dose. Employment of tin prefiltration at 100 kVp instead of polychromatic imaging at 120 kVp increases the image quality even further in the ultra-low-dose range of 0.5 mGy.