Postoperative Extremity Tomosynthesis-A Superimposition-Free Alternative to Standard Radiography?

RATIONALE AND OBJECTIVES: This study investigates the performance of tomosynthesis in the presence of osteosynthetic implants, aiming to overcome superimposition-induced limitations in conventional radiograms. MATERIALS AND METHODS: After surgical fracture induction and subsequent osteosynthesis, 8 cadaveric fracture models (wrist, metacarpus, ankle, metatarsus) were scanned with the prototypical tomosynthesis mode of a multiuse x-ray system. Tomosynthesis protocols at 60, 80, and 116 kV (sweep angle 10°, 13 FPS) were compared with standard radiograms. Five radiologists independently rated diagnostic assessability based on an equidistant 7-point scale focusing on fracture delineation, intra-articular screw placement, and implant positioning. The intraclass correlation coefficient (ICC) was calculated to analyze interrater agreement. RESULTS: Radiation dose in radiography was 0.48 ± 0.26 dGy·cm2 versus 0.12 ± 0.01, 0.36 ± 0.02, and 1.95 ± 0.11 dGy·cm2 for tomosynthesis scans at 60, 80, and 116 kV. Delineation of fracture lines was superior for 80/116 kV tomosynthesis compared with radiograms (P ≤ 0.003). Assessability of intra-articular screw placement was deemed favorable for all tomosynthesis protocols (P ≤ 0.004), whereas superiority for evaluation of implant positioning could not be ascertained (all P's ≥ 0.599). Diagnostic confidence was higher for 80/116 kV tomosynthesis versus radiograms and 60 kV tomosynthesis (P ≤ 0.002). Interrater agreement was good for fracture delineation (ICC, 0.803; 95% confidence interval [CI], 0.598-0.904), intra-articular screw placement (ICC, 0.802; 95% CI, 0.599-0.903), implant positioning (ICC, 0.855; 95% CI, 0.729-0.926), and diagnostic confidence (ICC, 0.842; 95% CI, 0.556-0.934). CONCLUSIONS: In the postoperative workup of extremity fractures, tomosynthesis allows for superior assessment of fracture lines and intra-articular screw positioning with greater diagnostic confidence at radiation doses comparable to conventional radiograms.

Influence of helical pitch and gantry rotation time on image quality and file size in ultrahigh-resolution photon-counting detector CT.

The goal of this experimental study was to quantify the influence of helical pitch and gantry rotation time on image quality and file size in ultrahigh-resolution photon-counting CT (UHR-PCCT). Cervical and lumbar spine, pelvis, and upper legs of two fresh-frozen cadaveric specimens were subjected to nine dose-matched UHR-PCCT scan protocols employing a collimation of 120 × 0.2 mm with varying pitch (0.3/1.0/1.2) and rotation time (0.25/0.5/1.0 s). Image quality was analyzed independently by five radiologists and further substantiated by placing normed regions of interest to record mean signal attenuation and noise. Effective mAs, CT dose index (CTDIvol), size-specific dose estimate (SSDE), scan duration, and raw data file size were compared. Regardless of anatomical region, no significant difference was ascertained for CTDIvol (p ≥ 0.204) and SSDE (p ≥ 0.240) among protocols. While exam duration differed substantially (all p ≤ 0.016), the lowest scan time was recorded for high-pitch protocols (4.3 ± 1.0 s) and the highest for low-pitch protocols (43.6 ± 15.4 s). The combination of high helical pitch and short gantry rotation times produced the lowest perceived image quality (intraclass correlation coefficient 0.866; 95% confidence interval 0.807-0.910; p < 0.001) and highest noise. Raw data size increased with acquisition time (15.4 ± 5.0 to 235.0 ± 83.5 GByte; p ≤ 0.013). Rotation time and pitch factor have considerable influence on image quality in UHR-PCCT and must therefore be chosen deliberately for different musculoskeletal imaging tasks. In examinations with long acquisition times, raw data size increases considerably, consequently limiting clinical applicability for larger scan volumes.

GPR124 regulates murine brain embryonic angiogenesis and BBB formation by an intracellular domain-independent mechanism.

The GPR124/RECK/WNT7 pathway is an essential regulator of CNS angiogenesis and blood-brain barrier (BBB) function. GPR124, a brain endothelial adhesion 7-pass transmembrane protein, associates with RECK, which binds and stabilizes newly synthesized WNT7, which is transferred to Frizzled (FZD) to initiate canonical b-catenin signaling. GPR124 remains enigmatic; while its extracellular domain (ECD) is essential, the poorly conserved intracellular domain (ICD) appears variably required in mammals versus zebrafish, potentially via adaptor protein bridging of GPR124/FZD ICDs. GPR124 ICD deletion impairs zebrafish angiogenesis, but paradoxically retains WNT7 signaling upon mammalian transfection. We thus investigated GPR124 ICD function by mouse deletion (Gpr124ΔC). Despite inefficiently expressed GPR124ΔC protein, Gpr124ΔC/ΔC mice could be born with normal cerebral cortex angiogenesis, versus Gpr124-/- embryonic lethality, forebrain avascularity and hemorrhage. Gpr124ΔC/ΔC vascular phenotypes were restricted to sporadic ganglionic eminence angiogenic defects, attributable to impaired GPR124ΔC protein expression. Further, Gpr124ΔC and recombinant GPR124 ECD rescued WNT7 signaling in culture upon brain endothelial Gpr124 knockdown. Thus, in mice, GPR124-regulated CNS forebrain angiogenesis and BBB function is exerted by ICD-independent functionality, extending the signaling mechanisms used by adhesion 7-pass transmembrane receptors.

Tomosynthesis of the Appendicular Skeleton on a Twin Robotic X-ray System: A Cadaveric Fracture Study.

RATIONALE AND OBJECTIVES: Aiming to offset image quality limitations in radiographs due to superimposition, this study investigates the diagnostic potential of appendicular skeleton tomosynthesis. MATERIALS AND METHODS: Eight cadaveric extremities (four hands and feet) were examined employing the prototypical tomosynthesis mode of a twin robotic X-ray scanner. 12 protocols with varying sweep angles (10, 20 vs. 40°), frame rates (13 vs. 26 fps), and tube voltages (60 vs. 80 kV) were compared to radiographs. Four radiologists separately evaluated cortical and trabecular bone visualization and fracture patterns. Interreader reliability was assessed based on the intraclass correlation coefficient (ICC). RESULTS: Radiation dose in radiography was 0.59 ± 0.20 dGy * cm2 versus 0.11 ± 0.00 to 2.46 ± 0.17 dGy * cm2 for tomosynthesis. Cortical bone display was inferior for radiographs compared to 40° and 20° tomosynthesis. Best results were ascertained for the 80 kV/40°/26 fps protocol. Trabecular bone depiction was also superior in tomosynthesis (p ≤ 0.009) and best with the 80 kV/10°/26 fps setting. Interreader reliability was moderate for cortical bone display (ICC 0.521, 95% confidence interval 0.356-0.641) and good for trabecular bone (0.759, 0.697-0.810). Diagnostic accuracy for articular involvement and multifragment situations was higher in tomosynthesis (93.8-100%/92.2-100%) vs. radiography (85.9%/82.8%.). Diagnostic confidence was also better in tomosynthesis (p ≤ 0.003). CONCLUSION: Compared to radiography, tomosynthesis allows for superior assessability of cortical and trabecular bone and fracture morphology, especially at high framerates. Operating on a multipurpose X-ray system, tomosynthesis of the appendicular skeleton can be performed without additional scanner hardware.

The Small Pixel Effect in Ultra-High-Resolution Photon-Counting CT of the Lumbar Spine.

OBJECTIVES: Image acquisition in ultra-high-resolution (UHR) scan mode does not impose a dose penalty in photon-counting CT (PCCT). This study aims to investigate the dose saving potential of using UHR instead of standard-resolution PCCT for lumbar spine imaging. MATERIALS AND METHODS: Eight cadaveric specimens were examined with 7 dose levels (5-35 mGy) each in UHR (120 × 0.2 mm) and standard-resolution acquisition mode (144 × 0.4 mm) on a first-generation PCCT scanner. The UHR images were reconstructed with 3 dedicated bone kernels (Br68 [spatial frequency at 10% of the modulation transfer function 14.5 line pairs/cm], Br76 [21.0], and Br84 [27.9]), standard-resolution images with Br68 and Br76. Using automatic segmentation, contrast-to-noise ratios (CNRs) were established for lumbar vertebrae and psoas muscle tissue. In addition, image quality was assessed subjectively by 19 independent readers (15 radiologists, 4 surgeons) using a browser-based forced choice comparison tool totaling 16,974 performed pairwise tests. Pearson's correlation coefficient ( r ) was used to analyze the relationship between CNR and subjective image quality rankings, and Kendall W was calculated to assess interrater agreement. RESULTS: Irrespective of radiation exposure level, CNR was higher in UHR datasets than in standard-resolution images postprocessed with the same reconstruction parameters. The use of sharper convolution kernels entailed lower CNR but higher subjective image quality depending on radiation dose. Subjective assessment revealed high interrater agreement ( W = 0.86; P < 0.001) with UHR images being preferred by readers in the majority of comparisons on each dose level. Substantial correlation was ascertained between CNR and the subjective image quality ranking (all r 's ≥ 0.95; P < 0.001). CONCLUSIONS: In PCCT of the lumbar spine, UHR mode's smaller pixel size facilitates a considerable CNR increase over standard-resolution imaging, which can either be used for dose reduction or higher spatial resolution depending on the selected convolution kernel.

Influence of spectral shaping and tube voltage modulation in ultralow-dose computed tomography of the abdomen.

PURPOSE: Unenhanced abdominal CT constitutes the diagnostic standard of care in suspected urolithiasis. Aiming to identify potential for radiation dose reduction in this frequent imaging task, this experimental study compares the effect of spectral shaping and tube voltage modulation on image quality. METHODS: Using a third-generation dual-source CT, eight cadaveric specimens were scanned with varying tube voltage settings with and without tin filter application (Sn 150, Sn 100, 120, 100, and 80 kVp) at three dose levels (3 mGy: standard; 1 mGy: low; 0.5 mGy: ultralow). Image quality was assessed quantitatively by calculation of signal-to-noise ratios (SNR) for various tissues (spleen, kidney, trabecular bone, fat) and subjectively by three independent radiologists based on a seven-point rating scale (7 = excellent; 1 = very poor). RESULTS: Irrespective of dose level, Sn 100 kVp resulted in the highest SNR of all tube voltage settings. In direct comparison to Sn 150 kVp, superior SNR was ascertained for spleen (p ≤ 0.004) and kidney tissue (p ≤ 0.009). In ultralow-dose scans, subjective image quality of Sn 100 kVp (median score 3; interquartile range 3-3) was higher compared with conventional imaging at 120 kVp (2; 2-2), 100 kVp (1; 1-2), and 80 kVp (1; 1-1) (all p < 0.001). Indicated by an intraclass correlation coefficient of 0.945 (95% confidence interval: 0.927-0.960), interrater reliability was excellent. CONCLUSIONS: In abdominal CT with maximised dose reduction, tin prefiltration at 100 kVp allows for superior image quality over Sn 150 kVp and conventional imaging without spectral shaping.

Training for endovascular therapy of acute arterial disease and procedure-related complication: An extracorporeally-perfused human cadaver model study.

PURPOSE: The aim of this study was to evaluate the usability of a recently developed extracorporeally-perfused cadaver model for training the angiographic management of acute arterial diseases and periprocedural complications that may occur during endovascular therapy of the lower extremity arterial runoff. MATERIALS AND METHODS: Continuous extracorporeal perfusion was established in three fresh-frozen body donors via inguinal and infragenicular access. Using digital subtraction angiography for guidance, both arterial embolization (e.g., embolization using coils, vascular plugs, particles, and liquid embolic agents) and endovascular recanalization procedures (e.g., manual aspiration or balloon-assisted embolectomy) as well as various embolism protection devices were tested. Furthermore, the management of complications during percutaneous transluminal angioplasty, such as vessel dissection and rupture, were exercised by implantation of endovascular dissection repair system or covered stents. Interventions were performed by two board-certified interventional radiologists and one resident with only limited angiographic experience. RESULTS: Stable extracorporeal perfusion was successfully established on both thighs of all three body donors. Digital subtraction angiography could be performed reliably and resulted in realistic artery depiction. The model allowed for repeatable training of endovascular recanalization and arterial embolization procedures with typical tactile feedback in a controlled environment. Furthermore, the handling of more complex angiographic devices could be exercised. Whereas procedural success was be ascertained for most endovascular interventions, thrombectomies procedures were not feasible in some cases due to the lack of inherent coagulation. CONCLUSION: The presented perfusion model is suitable for practicing time-critical endovascular interventions in the lower extremity runoff under realistic but controlled conditions.

Understanding the link between neurotropic viruses, BBB permeability, and MS pathogenesis.

Neurotropic viruses can infiltrate the CNS by crossing the blood-brain barrier (BBB) through various mechanisms including paracellular, transcellular, and "Trojan horse" mechanisms during leukocyte diapedesis. These viruses belong to several families, including retroviruses; human immunodeficiency virus type 1 (HIV-1), flaviviruses; Japanese encephalitis (JEV); and herpesviruses; herpes simplex virus type 1 (HSV-1), Epstein-Barr virus (EBV), and mouse adenovirus 1 (MAV-1). For entering the brain, viral proteins act upon the tight junctions (TJs) between the brain microvascular endothelial cells (BMECs). For instance, HIV-1 proteins, such as glycoprotein 120, Nef, Vpr, and Tat, disrupt the BBB and generate a neurotoxic effect. Recombinant-Tat triggers amendments in the BBB by decreasing expression of the TJ proteins such as claudin-1, claudin-5, and zona occludens-1 (ZO-1). Thus, the breaching of BBB has been reported in myriad of neurological diseases including multiple sclerosis (MS). Neurotropic viruses also exhibit molecular mimicry with several myelin sheath proteins, i.e., antibodies against EBV nuclear antigen 1 (EBNA1) aa411-426 cross-react with MBP and EBNA1 aa385-420 was found to be associated with MS risk haplotype HLA-DRB1*150. Notably, myelin protein epitopes (PLP139-151, MOG35-55, and MBP87-99) are being used to generate model systems for MS such as experimental autoimmune encephalomyelitis (EAE) to understand the disease mechanism and therapeutics. Viruses like Theiler's murine encephalomyelitis virus (TMEV) are also commonly used to generate EAE. Altogether, this review provide insights into the viruses' association with BBB leakiness and MS along with possible mechanistic details which could potentially use for therapeutics.

Upright Tomosynthesis of the Lumbar Spine.

RATIONALE AND OBJECTIVES: This experimental study investigates the potential of lumbar spine tomosynthesis to offset the traditional limitations of radiographic and computed tomography imaging, that is, superimposition of anatomy and disregard of physiological load-bearing. MATERIALS AND METHODS: A gantry-free twin robotic scanner was used to obtain lateral radiographs and tomosyntheses of the lumbar spine under weight-bearing conditions in eight body donors. Tomosynthesis protocols varied in terms of sweep angle (20 versus 40°), scan time (2.4 versus 4.8 seconds), and framerate (16 versus 30 fps). Image quality and vertebral endplate assessability were evaluated by five radiologists with 4-8 years of skeletal imaging experience. Aiming to identify potential diagnostic deterioration near the scan volume margins, readers additionally determined the craniocaudal extent of clinically acceptable image quality. RESULTS: Tomosynthesis scans effectuated a substantial dose reduction compared to standard radiographs (3.8 ± 0.2 to 15.4 ± 0.8 dGy*cm2 versus 77.7 ± 34.8 dGy*cm2; p ≤ 0.021). Diagnostic image quality and endplate assessability were deemed highest for the 30 fps wide-angle tomosynthesis protocol with good to excellent interrater reliability (intraclass correlation coefficients: 0.846 and 0.946). Accordingly, the craniocaudal extent of acceptable image quality was substantially larger compared to radiography (26.9 versus 18.9 cm; p < 0.001), whereas no significant difference was ascertained for the tomosynthesis protocols with 16 fps (15.3-22.1 cm; all p ≥ 0.058). CONCLUSION: Combining minimal radiation dose with superimposition-free visualization, 30 fps wide-angle tomosynthesis superseded radiography in all evaluated aspects. With superior diagnostic assessability despite significant dose reduction, load-bearing tomosynthesis appears promising as an alternative for first-line lumbar spine imaging in the future.

Photon-Counting Detector CT for Femoral Stent Imaging in an Extracorporeally Perfused Human Cadaveric Model.

BACKGROUND AND AIMS: This study aims to compare the performance of first-generation dual-source photon-counting detector computed tomography (PCD-CT) to third-generation dual-source energy-integrating detector (EID-CT) regarding stent imaging in the femoral arterial runoff. METHODS: Continuous extracorporeal perfusion was established in 1 human cadaver using an inguinal and infragenicular access and peristaltic pump. Seven peripheral stents were implanted into both superior femoral arteries by means of percutaneous angioplasty. Radiation dose-equivalent CT angiographies (high-/medium-/low-dose: 10/5/3 mGy) with constant tube voltage of 120 kVp, matching iterative reconstruction algorithm levels, and convolution kernels were used both with PCD-CT and EID-CT. In-stent lumen visibility, luminal and in-stent attenuation as well as contrast-to-noise ratio (CNR) were assessed via region of interest and diameter measurements. Results were compared using analyses of variance and regression analyses. RESULTS: Maximum in-stent lumen visibility achieved with PCD-CT was 94.48% ± 2.62%. The PCD-CT protocol with the lowest lumen visibility (BV40: 78.93% ± 4.67%) performed equal to the EID-CT protocol with the best lumen visibility (BV59: 79.49% ± 2.64%, P > 0.999). Photon-counting detector CT yielded superior CNR compared with EID-CT regardless of kernel and dose level ( P < 0.001). Maximum CNR was 48.8 ± 17.4 in PCD-CT versus 31.28 ± 5.7 in EID-CT (both BV40, high-dose). The theoretical dose reduction potential of PCD-CT over EID-CT was established at 88% (BV40), 83% (BV48/49), and 73% (BV59/60), respectively. In-stent attenuation was not significantly different from luminal attenuation outside stents in any protocol. CONCLUSIONS: With superior lumen visibility and CNR, PCD-CT allowed for noticeable dose reduction over EID-CT while maintaining image quality in a continuously perfused human cadaveric model.

Investigating the Small Pixel Effect in Ultra-High Resolution Photon-Counting CT of the Lung.

OBJECTIVES: The aim of this study was to investigate potential benefits of ultra-high resolution (UHR) over standard resolution scan mode in ultra-low dose photon-counting detector CT (PCD-CT) of the lung. MATERIALS AND METHODS: Six cadaveric specimens were examined with 5 dose settings using tin prefiltration, each in UHR (120 × 0.2 mm) and standard mode (144 × 0.4 mm), on a first-generation PCD-CT scanner. Image quality was evaluated quantitatively by noise comparisons in the trachea and both main bronchi. In addition, 16 readers (14 radiologists and 2 internal medicine physicians) independently completed a browser-based pairwise forced-choice comparison task for assessment of subjective image quality. The Kendall rank coefficient ( W ) was calculated to assess interrater agreement, and Pearson's correlation coefficient ( r ) was used to analyze the relationship between noise measurements and image quality rankings. RESULTS: Across all dose levels, image noise in UHR mode was lower than in standard mode for scan protocols matched by CTDI vol ( P < 0.001). UHR examinations exhibited noise levels comparable to the next higher dose setting in standard mode ( P ≥ 0.275). Subjective ranking of protocols based on 5760 pairwise tests showed high interrater agreement ( W = 0.99; P ≤ 0.001) with UHR images being preferred by readers in the majority of comparisons. Irrespective of scan mode, a substantial indirect correlation was observed between image noise and subjective image quality ranking ( r = -0.97; P ≤ 0.001). CONCLUSIONS: In PCD-CT of the lung, UHR scan mode reduces image noise considerably over standard resolution acquisition. Originating from the smaller detector element size in fan direction, the small pixel effect allows for superior image quality in ultra-low dose examinations with considerable potential for radiation dose reduction.

Mutations in DNAJC19 cause altered mitochondrial structure and increased mitochondrial respiration in human iPSC-derived cardiomyocytes.

BACKGROUND: Dilated cardiomyopathy with ataxia (DCMA) is an autosomal recessive disorder arising from truncating mutations in DNAJC19, which encodes an inner mitochondrial membrane protein. Clinical features include an early onset, often life-threatening, cardiomyopathy associated with other metabolic features. Here, we aim to understand the metabolic and pathophysiological mechanisms of mutant DNAJC19 for the development of cardiomyopathy. METHODS: We generated induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) of two affected siblings with DCMA and a gene-edited truncation variant (tv) of DNAJC19 which all lack the conserved DnaJ interaction domain. The mutant iPSC-CMs and their respective control cells were subjected to various analyses, including assessments of morphology, metabolic function, and physiological consequences such as Ca2+ kinetics, contractility, and arrhythmic potential. Validation of respiration analysis was done in a gene-edited HeLa cell line (DNAJC19tvHeLa). RESULTS: Structural analyses revealed mitochondrial fragmentation and abnormal cristae formation associated with an overall reduced mitochondrial protein expression in mutant iPSC-CMs. Morphological alterations were associated with higher oxygen consumption rates (OCRs) in all three mutant iPSC-CMs, indicating higher electron transport chain activity to meet cellular ATP demands. Additionally, increased extracellular acidification rates suggested an increase in overall metabolic flux, while radioactive tracer uptake studies revealed decreased fatty acid uptake and utilization of glucose. Mutant iPSC-CMs also showed increased reactive oxygen species (ROS) and an elevated mitochondrial membrane potential. Increased mitochondrial respiration with pyruvate and malate as substrates was observed in mutant DNAJC19tv HeLa cells in addition to an upregulation of respiratory chain complexes, while cellular ATP-levels remain the same. Moreover, mitochondrial alterations were associated with increased beating frequencies, elevated diastolic Ca2+ concentrations, reduced sarcomere shortening and an increased beat-to-beat rate variability in mutant cell lines in response to ß-adrenergic stimulation. CONCLUSIONS: Loss of the DnaJ domain disturbs cardiac mitochondrial structure with abnormal cristae formation and leads to mitochondrial dysfunction, suggesting that DNAJC19 plays an essential role in mitochondrial morphogenesis and biogenesis. Moreover, increased mitochondrial respiration, altered substrate utilization, increased ROS production and abnormal Ca2+ kinetics provide insights into the pathogenesis of DCMA-related cardiomyopathy.

The role of carcinoembryonic antigen-related cell adhesion molecule 1 in cancer.

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.

Comparison of ultrahigh and standard resolution photon-counting CT angiography of the femoral arteries in a continuously perfused in vitro model.

BACKGROUND: With the emergence of photon-counting CT, ultrahigh-resolution (UHR) imaging can be performed without dose penalty. This study aims to directly compare the image quality of UHR and standard resolution (SR) scan mode in femoral artery angiographies. METHODS: After establishing continuous extracorporeal perfusion in four fresh-frozen cadaveric specimens, photon-counting CT angiographies were performed with a radiation dose of 5 mGy and tube voltage of 120 kV in both SR and UHR mode. Images were reconstructed with dedicated convolution kernels (soft: Body-vascular (Bv)48; sharp: Bv60; ultrasharp: Bv76). Six radiologists evaluated the image quality by means of a pairwise forced-choice comparison tool. Kendall's concordance coefficient (W) was calculated to quantify interrater agreement. Image quality was further assessed by measuring intraluminal attenuation and image noise as well as by calculating signal-to-noise ratio (SNR) and contrast-to-noise ratios (CNR). RESULTS: UHR yielded lower noise than SR for identical reconstructions with kernels ≥ Bv60 (p < 0.001). UHR scans exhibited lower intraluminal attenuation compared to SR (Bv60: 406.4 ± 25.1 versus 418.1 ± 30.1 HU; p < 0.001). Irrespective of scan mode, SNR and CNR decreased while noise increased with sharper kernels but UHR scans were objectively superior to SR nonetheless (Bv60: SNR 25.9 ± 6.4 versus 20.9 ± 5.3; CNR 22.7 ± 5.8 versus 18.4 ± 4.8; p < 0.001). Notably, UHR scans were preferred in subjective assessment when images were reconstructed with the ultrasharp Bv76 kernel, whereas SR was rated superior for Bv60. Interrater agreement was high (W = 0.935). CONCLUSIONS: Combinations of UHR scan mode and ultrasharp convolution kernel are able to exploit the full image quality potential in photon-counting CT angiography of the femoral arteries. RELEVANCE STATEMENT: The UHR scan mode offers improved image quality and may increase diagnostic accuracy in CT angiography of the peripheral arterial runoff when optimized reconstruction parameters are chosen. KEY POINTS: • UHR photon-counting CT improves image quality in combination with ultrasharp convolution kernels. • UHR datasets display lower image noise compared with identically reconstructed standard resolution scans. • Scans in UHR mode show decreased intraluminal attenuation compared with standard resolution imaging.

Rotational alignment of the lower extremity in the presence of total knee endoprosthesis: Reproducibility of torsion analyses using ultra-low-dose photon-counting CT.

PURPOSE: Leg torsion analysis can provide valuable information in symptomatic patients after total knee arthroplasty. However, extensive beam-hardening and photon-starvation artifacts limit diagnostic assessability and dose reduction potential. For this study, we investigated the reproducibility of rotational measurements in ultra-low-dose photon-counting CT with spectral shaping via tin prefiltration. MATERIAL AND METHODS: Employing a first-generation photon-counting CT, eight cadaveric specimens were examined with an established three-level scan protocol (hip: Sn 140, knee: Sn 100, ankle: Sn 100 kVp). In three body donors with unilateral knee endoprostheses, additional modified settings were applied (Sn 140 kVp at knee level). Protocols were executed with three dose levels (hip-knee-ankle, high-quality: 5.0-3.0-2.0 mGy, low-dose: 0.80-0.30-0.26 mGy, ultra-low-dose: 0.25-0.06-0.06 mGy). Six radiologists performed torsion analyses, additionally reporting their diagnostic confidence. Intraclass correlation coefficients (ICC) were calculated to assess interrater reliability. RESULTS: No significant differences were ascertained for femoral (p = 0.330), tibial (p = 0.177), and overall leg rotation measurements (p = 0.358) among high-quality, low-dose, and ultra-low-dose protocols. Interrater reliability was excellent for torsion of the femur (ICC 0.915, 95% confidence interval 0.871-0.947), tibia (0.960, 0.938-0.976), and overall leg (0.967, 0.945-0.981). In specimens with total knee endoprostheses, absolute rotational measurements were unaffected by dose level and tube voltage despite superior diagnostic confidence on the ipsilateral and contralateral sides with modified settings (p < 0.001). CONCLUSIONS: Combining the advantages of photon-counting CT and spectral shaping, reliable leg torsion analyses are feasible with ultra-low radiation exposure even in the presence of total knee endoprostheses.

Multiorgan recovery in a cadaver body using mild hypothermic ECMO treatment in a murine model.

BACKGROUND: Transplant candidates on the waiting list are increasingly challenged by the lack of organs. Most of the organs can only be kept viable within very limited timeframes (e.g., mere 4-6 h for heart and lungs exposed to refrigeration temperatures ex vivo). Donation after circulatory death (DCD) using extracorporeal membrane oxygenation (ECMO) can significantly enlarge the donor pool, organ yield per donor, and shelf life. Nevertheless, clinical attempts to recover organs for transplantation after uncontrolled DCD are extremely complex and hardly reproducible. Therefore, as a preliminary strategy to fulfill this task, experimental protocols using feasible animal models are highly warranted. The primary aim of the study was to develop a model of ECMO-based cadaver organ recovery in mice. Our model mimics uncontrolled organ donation after an "out-of-hospital" sudden unexpected death with subsequent "in-hospital" cadaver management post-mortem. The secondary aim was to assess blood gas parameters, cardiac activity as well as overall organ state. The study protocol included post-mortem heparin-streptokinase administration 10 min after confirmed death induced by cervical dislocation under full anesthesia. After cannulation, veno-arterial ECMO (V-A ECMO) was started 1 h after death and continued for 2 h under mild hypothermic conditions followed by organ harvest. Pressure- and flow-controlled oxygenated blood-based reperfusion of a cadaver body was accompanied by blood gas analysis (BGA), electrocardiography, and histological evaluation of ischemia-reperfusion injury. For the first time, we designed and implemented, a not yet reported, miniaturized murine hemodialysis circuit for the treatment of severe hyperkalemia and metabolic acidosis post-mortem. RESULTS: BGA parameters confirmed profound ischemia typical for cadavers and incompatible with normal physiology, including extremely low blood pH, profound negative base excess, and enormously high levels of lactate. Two hours after ECMO implantation, blood pH values of a cadaver body restored from < 6.5 to 7.3 ± 0.05, pCO2 was lowered from > 130 to 41.7 ± 10.5 mmHg, sO2, base excess, and HCO3 were all elevated from below detection thresholds to 99.5 ± 0.6%, - 4 ± 6.2 and 22.0 ± 6.0 mmol/L, respectively (Student T test, p < 0.05). A substantial decrease in hyperlactatemia (from > 20 to 10.5 ± 1.7 mmol/L) and hyperkalemia (from > 9 to 6.9 ± 1.0 mmol/L) was observed when hemodialysis was implemented. On balance, the first signs of regained heart activity appeared on average 10 min after ECMO initiation without cardioplegia or any inotropic and vasopressor support. This was followed by restoration of myocardial contractility with a heart rate of up to 200 beats per minute (bpm) as detected by an electrocardiogram (ECG). Histological examinations revealed no evidence of heart injury 3 h post-mortem, whereas shock-specific morphological changes relevant to acute death and consequent cardiac/circulatory arrest were observed in the lungs, liver, and kidney of both control and ECMO-treated cadaver mice. CONCLUSIONS: Thus, our model represents a promising approach to facilitate studying perspectives of cadaveric multiorgan recovery for transplantation. Moreover, it opens new possibilities for cadaver organ treatment to extend and potentiate donation and, hence, contribute to solving the organ shortage dilemma.

Herpesviral interplay with peroxisome: An underexplored viral niche.

The tendency of herpesvirus proteins, such as HCMV-vMIA and KSHV vFLIP, to interact with PEX19 and further interplay with MAVS is crucial. Investigating other herpesviral proteins that tend to interact with PEX19, and MAVS could provide an idea of whether this is a pan-herpesviral strategy.

MRI-Based Evaluation of the Flexor Digitorum Superficialis Anatomy: Investigating the Prevalence and Morphometry of the "Chiasma Antebrachii".

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.

The small molecule fibroblast growth factor receptor inhibitor infigratinib exerts anti-inflammatory effects and remyelination in a model of multiple sclerosis.

BACKGROUND AND PURPOSE: Fibroblast growth factors and receptors (FGFR) have been shown to modulate inflammation and neurodegeneration in multiple sclerosis (MS). The selective FGFR inhibitor infigratinib has been shown to be effective in cancer models. Here, we investigate the effects of infigratinib on prevention and suppression of first clinical episodes of myelin oligodendrocyte glycoprotein (MOG)35-55 -induced experimental autoimmune encephalomyelitis (EAE) in mice. EXPERIMENTAL APPROACH: The FGFR inhibitor infigratinib was given over 10 days from the time of experimental autoimmune encephalomyelitis induction or the onset of symptoms. The effects of infigratinib on proliferation, cytotoxicity and FGFR signalling proteins were studied in lymphocyte cell lines and microglial cells. KEY RESULTS: Administration of infigratinib prevented by 40% and inhibited by 65% first clinical episodes of the induced experimental autoimmune encephalomyelitis. In the spinal cord, infiltration of lymphocytes and macrophages/microglia, destruction of myelin and axons were reduced by infigratinib. Infigratinib enhanced the maturation of oligodendrocytes and increased remyelination. In addition, infigratinib resulted in an increase of myelin proteins and a decrease in remyelination inhibitors. Further, lipids associated with neurodegeneration such as lysophosphatidylcholine and ceramide were decreased as were proliferation of T cells and microglial cells. CONCLUSION AND IMPLICATIONS: This proof of concept study demonstrates the therapeutic potential of targeting FGFRs in a disease model of multiple sclerosis. Application of oral infigratinib resulted in anti-inflammatory and remyelinating effects. Thus, infigratinib may have the potential to slow disease progression or even to improve the disabling symptoms of multiple sclerosis.

Ultra-High-Resolution Photon-Counting Detector CT Arthrography of the Ankle: A Feasibility Study.

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 (ρ50; 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.