Focal and diffuse myocardial fibrosis both contribute to regional hypoperfusion assessed by post-processing quantitative-perfusion MRI techniques.

Introduction: Indications for stress-cardiovascular magnetic resonance imaging (CMR) to assess myocardial ischemia and viability are growing. First pass perfusion and late gadolinium enhancement (LGE) have limited value in balanced ischemia and diffuse fibrosis. Quantitative perfusion (QP) to assess absolute pixelwise myocardial blood flow (MBF) and extracellular volume (ECV) as a measure of diffuse fibrosis can overcome these limitations. We investigated the use of post-processing techniques for quantifying both pixelwise MBF and diffuse fibrosis in patients with clinically indicated CMR stress exams. We then assessed if focal and diffuse myocardial fibrosis and other features quantified during the CMR exam explain individual MBF findings. Methods: This prospective observational study enrolled 125 patients undergoing a clinically indicated stress-CMR scan. In addition to the clinical report, MBF during regadenoson-stress was quantified using a post-processing QP method and T1 maps were used to calculate ECV. Factors that were associated with poor MBF were investigated. Results: Of the 109 patients included (66 ± 11 years, 32% female), global and regional perfusion was quantified by QP analysis in both the presence and absence of visual first pass perfusion deficits. Similarly, ECV analysis identified diffuse fibrosis in myocardium beyond segments with LGE. Multivariable analysis showed both LGE (ß = -0.191, p = 0.001) and ECV (ß = -0.011, p < 0.001) were independent predictors of reduced MBF. In patients without clinically defined first pass perfusion deficits, the microvascular risk-factors of age and wall thickness further contributed to poor MBF (p < 0.001). Discussion: Quantitative analysis of MBF and diffuse fibrosis detected regional tissue abnormalities not identified by traditional visual assessment. Multi-parametric quantitative analysis may refine the work-up of the etiology of myocardial ischemia in patients referred for clinical CMR stress testing in the future and provide a deeper insight into ischemic heart disease.

Extracellular Vesicle-Mediated Metastasis Suppressors NME1 and NME2 Modify Lipid Metabolism in Fibroblasts.

Nowadays, extracellular vesicles (EVs) raise a great interest as they are implicated in intercellular communication between cancer and stromal cells. Our aim was to understand how vesicular NME1 and NME2 released by breast cancer cells influence the tumour microenvironment. As a model, we used human invasive breast carcinoma cells overexpressing NME1 or NME2, and first analysed in detail the presence of both isoforms in EV subtypes by capillary Western immunoassay (WES) and immunoelectron microscopy. Data obtained by both methods showed that NME1 was present in medium-sized EVs or microvesicles, whereas NME2 was abundant in both microvesicles and small-sized EVs or exosomes. Next, human skin-derived fibroblasts were treated with NME1 or NME2 containing EVs, and subsequently mRNA expression changes in fibroblasts were examined. RNAseq results showed that the expression of fatty acid and cholesterol metabolism-related genes was decreased significantly in response to NME1 or NME2 containing EV treatment. We found that FASN (fatty acid synthase) and ACSS2 (acyl-coenzyme A synthetase short-chain family member 2), related to fatty acid synthesis and oxidation, were underexpressed in NME1/2-EV-treated fibroblasts. Our data show an emerging link between NME-containing EVs and regulation of tumour metabolism.

Model systems in SDHx-related pheochromocytoma/paraganglioma.

Pheochromocytoma (PHEO) and paraganglioma (PGL) (together PPGL) are tumors with poor outcomes that arise from neuroendocrine cells in the adrenal gland, and sympathetic and parasympathetic ganglia outside the adrenal gland, respectively. Many follow germline mutations in genes coding for subunits of succinate dehydrogenase (SDH), a tetrameric enzyme in the tricarboxylic acid (TCA) cycle that both converts succinate to fumarate and participates in electron transport. Germline SDH subunit B (SDHB) mutations have a high metastatic potential. Herein, we review the spectrum of model organisms that have contributed hugely to our understanding of SDH dysfunction. In Saccharomyces cerevisiae (yeast), succinate accumulation inhibits alpha-ketoglutarate-dependent dioxygenase enzymes leading to DNA demethylation. In the worm Caenorhabditis elegans, mutated SDH creates developmental abnormalities, metabolic rewiring, an energy deficit and oxygen hypersensitivity (the latter is also found in Drosophila melanogaster). In the zebrafish Danio rerio, sdhb mutants display a shorter lifespan with defective energy metabolism. Recently, SDHB-deficient pheochromocytoma has been cultivated in xenografts and has generated cell lines, which can be traced back to a heterozygous SDHB-deficient rat. We propose that a combination of such models can be efficiently and effectively used in both pathophysiological studies and drug-screening projects in order to find novel strategies in PPGL treatment.

Conserved and Distinct Elements of Phagocytosis in Human and C. elegans.

Endocytosis provides the cellular nutrition and homeostasis of organisms, but pathogens often take advantage of this entry point to infect host cells. This is counteracted by phagocytosis that plays a key role in the protection against invading microbes both during the initial engulfment of pathogens and in the clearance of infected cells. Phagocytic cells balance two vital functions: preventing the accumulation of cell corpses to avoid pathological inflammation and autoimmunity, whilst maintaining host defence. In this review, we compare elements of phagocytosis in mammals and the nematode Caenorhabditis elegans. Initial recognition of infection requires different mechanisms. In mammals, pattern recognition receptors bind pathogens directly, whereas activation of the innate immune response in the nematode rather relies on the detection of cellular damage. In contrast, molecules involved in efferocytosis-the engulfment and elimination of dying cells and cell debris-are highly conserved between the two species. Therefore, C. elegans is a powerful model to research mechanisms of the phagocytic machinery. Finally, we show that both mammalian and worm studies help to understand how the two phagocytic functions are interconnected: emerging data suggest the activation of innate immunity as a consequence of defective apoptotic cell clearance.

COVID 19 pandemic and minimally invasive gynecology: consequences and future perspectives.

The extent of the 2020 pandemic not only extends to the infected patients but also to patients who have been waiting for medical procedures. Reevaluation of the healthcare system is important in order to help assist the needs of intensive care units. The urgency of the gynaecological cases should be aligned based on surgical interventions and minimally invasive methods should be preferred. This will not endanger professional and other resource demands of ICUs. In acute cases, laparoscopy or hysteroscopy (preferring office hysteroscopy) should be chosen, that require no or only short period of hospitalization. Postponing non-acute surgeries is recommended to the post-pandemic period. Abbreviations: ICU: intensive care unit; COVID-19: coronavirus disease; SARS-CoV-2: severe acute respiratory syndrome Coronaviruses; IgM-IgG: immunoglobulin M; GAGP: aerosol generating procedures; PPE: personal protective equipment; ERAS: early recovery after surgery; mESAS: modified elective surgery acuity scale; RPOC: retained product of concept; PMB: postmenopausal bleeding.

Multimodal hyperspectroscopy ­ the use of digital technology in cervical cancer screening / Multimodális hiperspektroszkópia - elorelépés a digitális technológia felé a méhnyakszurésben.

Összefoglaló. Bevezetés: Bevezetés: A citológiai alapú méhnyakrákszurés átmeneti kategóriáinak optimális menedzselése a humán papillomavírus (HPV) szurése és tipizálása ellenére jelenleg is kihívás. Vizsgálatunk célja a modern cervixspektroszkópiának (multimodális hiperspektroszkópia - MHS), egy azonnali eredményt nyújtó, digitális technológiára épülo módszernek a vizsgálata volt a citológiai alapú méhnyakszurés találati biztonságának javítására. Betegek és módszer: Vizsgálatainkat 208, 18 és 75 év közötti nobeteg bevonásával végeztük, akiknél már indikálásra került valamely, a méhnyakon végzendo mutét, citológiai eredményük rendelkezésre állt (a HPV-tesztet, amennyiben nem történt meg, elvégeztük), valamint valamennyi betegnél elvégeztük a mutét elott az MHS-vizsgálatot. A szövettani mintavétel 166 betegnél történt meg. Eredmények: A citológiai vizsgálatot (az összes betegre tekintve) magas álpozitív arány jellemezte (69,28%), amely megfigyelések mindenképpen utalnak az újabb komponens alkalmazásának igényére a triázsban. Az összes citológiai kategóriára nézve az MHS-eredmények közül kiemelendo az álnegatív leletek rendkívül alacsony aránya (3/166 = 1,8%), mely a HPV-teszt esetén ennél magasabb volt (11/165 = 6,66%). A spektroszkópiás vizsgálat álpozitív aránya ugyanakkor kedvezotlenebbnek bizonyult (91/166 = 54,81%) a HPV-vizsgálat álpozitív arányánál (40/165 = 24,24%). Az atípusos laphámsejt (ASC-US/ASC-H) citológiai kategória esetén a spektroszkópia álnegatív eredményeinek aránya (3/126 = 2,38%) szintén kedvezobb volt, mint a HPV-vizsgálaté (9/126 = 7,14%). A cervicalis intraepithelialis neoplasia-2 vagy súlyosabb fokozatú hámelváltozások azonosításában a spektroszkópia szenzitivitása 94% (95% CI = 0,84-0,99), specificitása 22% (95% CI = 0,15-0,31), negatív prediktív értéke 90% (95% CI = 0,73-0,98), pozitív prediktív értéke 34% (95% CI = 0,26-0,43) volt (p = 0,00130). Következtetés: Az MHS fejlett innovatív technológián alapuló, azonnali eredményt adó vizsgálóeljárás, amely kiemelkedoen alacsony álnegatív eredménye miatt nagy segítséget nyújt a citológiai eltéréssel rendelkezo betegek további vizsgálatában. Orv Hetil. 2021; 162(20): 790-799. INTRODUCTION: Despite the use of human papillomavirus (HPV) testing, the management of the transitional categories of cytology-based screening still remains a challenge. The modern multimodal hyperspectroscopy (MHS) of the cervix is a novel digital technology based on artificial intelligence, providing an instant result in the assessment of cytology-based screening abnormalities. PATIENTS AND METHODS: 208 women (age 18-75) were enrolled. The patients already had cytology results and an operation on the cervix indicated at the time of inclusion. HPV and the hyperspectroscopy examination was performed pre-operatively. The pre-indicated operation was performed on 166 patients. RESULTS: Cytology-based screening alone (in the category of all patients) resulted in a high false-positive rate (69.28%). In this category, the MHS had an outstanding false-negative rate (3/166 = 1.80%) compared to the HPV (11/165 = 6.66%). The false-positive rate of the spectroscopy examination (91/166 = 54.81%) was higher than that of the HPV testing (40/165 = 24.24%). In the atypical squamous cell (ASC-US/ASC-H) category, the false-negative rate of the spectroscopy (3/126 = 2.38%) was also lower than that of the HPV test (9/126 = 7.14%). In the detection of high-grade abnormalities (cervical intraepithelial neoplasia 2 and worse), the spectroscopy had a 94% sensitivity (95% CI = 0.84-0.99), with a 22% specificity (95% CI = 0.15-0.31), an 90% negative predictive value (95% CI = 0.73-0.98), and a 34% positive predictive value (95% CI = 0.26-0.43) (p = 0.00130). CONCLUSION: In the case of cytological abnormality, the MHS provides an immediate result based on advanced digital technology, and because of its outstanding false negative rate it is a great aid and should be considered in the triage of such patients. Orv Hetil. 2021; 162(20): 790-799.

The Function of NM23-H1/NME1 and Its Homologs in Major Processes Linked to Metastasis.

Metastasis suppressor genes (MSGs) inhibit different biological processes during metastatic progression without globally influencing development of the primary tumor. The first MSG, NM23 (non-metastatic clone 23, isoform H1) or now called NME1 (stands for non-metastatic) was identified some decades ago. Since then, ten human NM23 paralogs forming two groups have been discovered. Group I NM23 genes encode enzymes with evolutionarily highly conserved nucleoside diphosphate kinase (NDPK) activity. In this review we summarize how results from NDPKs in model organisms converged on human NM23 studies. Next, we examine the role of NM23-H1 and its homologs within the metastatic cascade, e.g. cell migration and invasion, proliferation and apoptosis. NM23-H1 homologs are well known inhibitors of cell migration. Drosophila studies revealed that AWD, the fly counterpart of NM23-H1 is a negative regulator of cell motility by modulating endocytosis of chemotactic receptors on the surface of migrating cells in cooperation with Shibire/Dynamin; this mechanism has been recently confirmed by human studies. NM23-H1 inhibits proliferation of tumor cells by phosphorylating the MAPK scaffold, kinase suppressor of Ras (KSR), resulting in suppression of MAPK signalling. This mechanism was also observed with the C. elegans homolog, NDK-1, albeit with an inverse effect on MAPK activation. Both NM23-H1 and NDK-1 promote apoptotic cell death. In addition, NDK-1, NM23-H1 and their mouse counterpart NM23-M1 were shown to promote phagocytosis in an evolutionarily conserved manner. In summary, inhibition of cell migration and proliferation, alongside actions in apoptosis and phagocytosis are all mechanisms through which NM23-H1 acts against metastatic progression.

Dual-Energy Low-keV or Single-Energy Low-kV CT for Endoleak Detection?: A 6-Reader Study in an Aortic Aneurysm Phantom.

OBJECTIVES: The aim of this study was to compare image quality, conspicuity, and endoleak detection between single-energy low-kV images (SEIs) and dual-energy low-keV virtual monoenergetic images (VMIs+) in computed tomography angiography of the aorta after endovascular repair. MATERIALS AND METHODS: An abdominal aortic aneurysm phantom simulating 36 endoleaks (2 densities; diameters: 2, 4, and 6 mm) in a medium- and large-sized patient was used. Each size was scanned using single-energy at 80 kVp (A) and 100 kVp (B), and dual-energy at 80/Sn150kVp for the medium (C) and 90/Sn150kVp for the large size (D). VMIs+ at 40 keV and 50 keV were reconstructed from protocols C and D. Radiation dose was 3 mGy for the medium and 6 mGy for the large size. Objective image quality and normalized noise power spectrum were determined. Subjective image quality, conspicuity, and sensitivity for endoleaks were independently assessed by 6 radiologists. Sensitivity was compared using Marascuilo procedure and Fisher exact test. Conspicuities were compared using Wilcoxon-matched pairs test, analysis of variance, and Tukey test. RESULTS: The contrast-to-noise-ratio of the aorta was significantly higher for VMI+ compared with SEI (P < 0.001). Noise power spectrum showed a higher noise magnitude and coarser texture in VMI+. Subjective image quality and overall conspicuity was lower for VMI+ compared with SEI (P < 0.05). Sensitivity for endoleaks was overall higher in the medium phantom for SEI (60.9% for A, 62.2% for B) compared with VMI+ (54.2% for C, 49.3% for D) with significant differences between protocols B and D (P < 0.05). In the large phantom, there was no significant difference in sensitivity among protocols (P = 0.79), with highest rates for protocols B (31.4%) and C (31.7%). CONCLUSIONS: Our study indicates that low-keV VMI+ results in improved contrast-to-noise-ratio of the aorta, whereas noise properties, subjective image quality, conspicuity, and sensitivity for endoleaks were overall superior for SEI.

Dose-optimized computed tomography of the cervical spine in patients with shoulder pull-down: Is image quality comparable with a standard dose protocol in an emergency setting?

PURPOSE: Superimposing soft tissue and bony structures in computed tomography (CT) of the cervical spine (C-spine) is a limiting factor in optimizing radiation exposure maintaining an acceptable image quality. Therefore, we assessed image quality of dose-optimized (DO) C-spine CT in patients capable of shoulder pull-down in an emergency setting. METHODS AND MATERIALS: DO-CT (105mAs/120 kVp) of the C-spine in trauma settings was performed in patients with shoulder pull-down if C5 was not superimposed by soft tissue on the lateral topogram, otherwise standard-dose (SD)-CT (195 mAs/120 kVp) was performed. 34 DO (mean age, 68y ±â€¯21; BMI, 24.2 kg/m2 ±â€¯3.2) and 34 SD (mean age 70y ±â€¯19; BMI 25.7 kg/m2 ±â€¯4.4) iterative reconstructed CTs were evaluated at C2/3 and C6/7 by two musculoskeletal radiologists. Qualitative image noise and morphological characteristics of bony structures (cortex, trabeculae) were assessed on a Likert scale. Quantitative image noise was measured and effective dose (ED) was recorded. Parameters were compared using Mann-Whitney-U-test (p < 0.05). RESULTS: At C2/3, DO-CT vs. SD-CT yielded comparable qualitative noise (mean, 1.3 vs. 1.0; p = 0.18) and morphological characteristics, but higher quantitative noise (27.2 ±â€¯8.8HU vs. 19.6 ±â€¯4.5HU; p < 0.001). At C6/7, DO-CT yielded lower subjective noise (1.9; SD-CT 2.2; p = 0.017) and better morphological characteristics with higher visibility scores for cortex (p = 0.001) and trabeculae (p = 0.03). Quantitative noise did not differ (p = 0.24). Radiation dose was 51% lower using DO-CT (EDDO-CT 0.80 ±â€¯0.1 mSv; EDSD-CT 1.63 ±â€¯0.2 mSv; p < 0.001). CONCLUSION: C-spine CT with dose reduction of 51% showed no image quality impairment. Additional pull-down of both shoulders allowed better image quality at lower C-spine segments as compared to a standard protocol.

The nucleoside diphosphate kinase NDK-1/NME1 promotes phagocytosis in concert with DYN-1/Dynamin.

Phagocytosis of various targets, such as apoptotic cells or opsonized pathogens, by macrophages is coordinated by a complex signaling network initiated by distinct phagocytic receptors. Despite the different initial signaling pathways, each pathway ends up regulating the actin cytoskeletal network, phagosome formation and closure, and phagosome maturation leading to degradation of the engulfed particle. Herein, we describe a new phagocytic function for the nucleoside diphosphate kinase 1 (NDK-1), the nematode counterpart of the first identified metastasis inhibitor NM23-H1 (nonmetastatic clone number 23) nonmetastatic clone number 23 or nonmetastatic isoform 1 (NME1). We reveal by coimmunoprecipitation, Duolink proximity ligation assay, and mass spectrometry that NDK-1/NME1 works in a complex with DYN-1/Dynamin (Caenorhabditis elegans/human homolog proteins), which is essential for engulfment and phagosome maturation. Time-lapse microscopy shows that NDK-1 is expressed on phagosomal surfaces during cell corpse clearance in the same time window as DYN-1. Silencing of NM23-M1 in mouse bone marrow-derived macrophages resulted in decreased phagocytosis of apoptotic thymocytes. In human macrophages, NM23-H1 and Dynamin are corecruited at sites of phagosome formation in F-actin-rich cups. In addition, NM23-H1 was required for efficient phagocytosis. Together, our data demonstrate that NDK-1/NME1 is an evolutionarily conserved element of successful phagocytosis.-Farkas, Z., Petric, M., Liu, X., Herit, F., Rajnavölgyi, É., Szondy, Z., Budai, Z., Orbán, T. I., Sándor, S., Mehta, A., Bajtay, Z., Kovács, T., Jung, S. Y., Afaq Shakir, M., Qin, J., Zhou, Z., Niedergang, F., Boissan, M., Takács-Vellai, K. The nucleoside diphosphate kinase NDK-1/NME1 promotes phagocytosis in concert with DYN-1/dynamin.

Large fetal weight alone in Robson-1 parturients doesn't translate into a risk of Caesarean delivery higher then that of a vaginal birth.

OBJECTIVE: The authors analysed the Caesarean section rate as a function of birth weight among Robson-1 parturients and compared with that among the unselected obstetric population. STUDY DESIGN: A retrospective analysis of birth weight, maternal height and the route of delivery was carried out in an unselected obstetric population of 26,012 parturients. The authors compared birth weight centile distributions of vaginally, and that of abdominally delivered fetuses between Robson-1 parturients as well as those of the total obstetric population. RESULTS: The 90th birth weight centile of fetuses delivered at 37, 38, 39, 40, 41, and 42 weeks gestation were 3960 g, 3960 g, 4000 g, 3950 g, 4000 g and 3820 g, respectively. Among Robson-1 parturients, 677 fetuses weighed >4000 g, and 448 patients (66%) were delivered vaginally. Maternal height did not influence either the birth-weight-percentiles or the Caesarean-rates substantially. Above the birth weight of 4000 g, the Caesarean-rate among Robson-1 parturient rose similarly to that of the total obstetric population. In the knowledge of the most accurately estimated fetal weight, the odds of Caesarean delivery among Robson-1 parturients was not different from that of the total obstetric population. Among pregnancies with fetuses weighing less than 5000 g, the Caesarean-rate was below 50% in both Robson-1 parturients and the total obstetric population of 10 years. CONCLUSION: Even the best possible estimation of fetal weight cannot give a valid reason to downplay the intent of vaginal birth based on the fetal size above 3900 g that would be associated with increased odds of Caesarean delivery.

Over-scanning in chest CT: Comparison of practice among six hospitals and its impact on radiation dose.

OBJECTIVES: Compare incidence of over-scanning in chest CT among six hospitals and impact on effective and organ effective radiation dose. METHODS: Scout images of 600 chest CTs from six hospitals (A-F) were retrospectively reviewed using a radiation dose tracking software (RTS). Optimal scan range was determined and compared to the actual scan range. Incidence of cranial and caudal over-scanning was assessed and changes in total and organ effective dose were calculated. Descriptive statistics, Tukey- and Wilcoxon matched pairs test were applied. RESULTS: Simultaneous cranial and caudal over-scanning occurred in 29 of 600 scans (A = 0%, B = 1%, C = 12%, D = 3%, E = 11%, F = 2%). Effective radiation dose increased on average by 0.29 mSv (P < 0.001). Cranial over-scanning was observed in 45 of 600 scans (A = 0%, B = 8%, C = 2%, D = 15%, E = 17%, F = 3%) and increased organ effective dose by 0.35 mSv in the thyroid gland (P < 0.001). Caudal over-scanning occurred in 147 of 600 scans (A = 7%, B = 9%, C = 35%, D = 4%, E = 32%, F = 60%) and increased organ effective doses in the upper abdomen by up to 14% (P < 0.001 for all organs). CONCLUSIONS: Substantial differences in the incidence of over-scanning in chest CT exist among different hospitals. These differences result in excessive effective radiation dose and increased individual organ effective doses in patients.

Comparison of image quality and radiation dose between split-filter dual-energy images and single-energy images in single-source abdominal CT.

OBJECTIVES: To compare image quality and radiation dose of abdominal split-filter dual-energy CT (SF-DECT) combined with monoenergetic imaging to single-energy CT (SECT) with automatic tube voltage selection (ATVS). METHODS: Two-hundred single-source abdominal CT scans were performed as SECT with ATVS (n = 100) and SF-DECT (n = 100). SF-DECT scans were reconstructed and subdivided into composed images (SF-CI) and monoenergetic images at 55 keV (SF-MI). Objective and subjective image quality were compared among single-energy images (SEI), SF-CI and SF-MI. CNR and FOM were separately calculated for the liver (e.g. CNRliv) and the portal vein (CNRpv). Radiation dose was compared using size-specific dose estimate (SSDE). Results of the three groups were compared using non-parametric tests. RESULTS: Image noise of SF-CI was 18% lower compared to SEI and 48% lower compared to SF-MI (p < 0.001). Composed images yielded higher CNRliv over single-energy images (23.4 vs. 20.9; p < 0.001), whereas CNRpv was significantly lower (3.5 vs. 5.2; p < 0.001). Monoenergetic images overcame this inferiority in CNRpv and achieved similar results compared to single-energy images (5.1 vs. 5.2; p > 0.628). Subjective sharpness was equal between single-energy and monoenergetic images and diagnostic confidence was equal between single-energy and composed images. FOMliv was highest for SF-CI. FOMpv was equal for SEI and SF-MI (p = 0.78). SSDE was significant lower for SF-DECT compared to SECT (p < 0.022). CONCLUSIONS: The combined use of split-filter dual-energy CT images provides comparable objective and subjective image quality at lower radiation dose compared to single-energy CT with ATVS. KEY POINTS: • Split-filter dual-energy results in 18% lower noise compared to single-energy with ATVS. • Split-filter dual-energy results in 11% lower SSDE compared to single-energy with ATVS. • Spectral shaping of split-filter dual-energy leads to an increased dose-efficiency.

The dosage-dependent effect exerted by the NM23-H1/H2 homolog NDK-1 on distal tip cell migration in C. elegans.

Abnormal regulation of cell migration and altered rearrangement of the cytoskeleton are fundamental properties of metastatic cells. The first identified metastasis suppressor NM23-H1, which displays nucleoside-diphosphate kinase (NDPK) activity is involved in these processes. NM23-H1 inhibits the migratory and invasive potential of some cancer cells. Correspondingly, numerous invasive cancer cell lines (eg, breast, colon, oral, hepatocellular carcinoma, and melanoma) display low endogenous NM23 levels. In this review, we summarize mechanisms, which are linked to the anti-metastatic activity of NM23. In human cancer cell lines NM23-H1 was shown to regulate cytoskeleton dynamics through inactivation of Rho/Rac-type GTPases. The Drosophila melanogaster NM23 homolog abnormal wing disc (AWD) controls tracheal and border cell migration. The molecular function of AWD is well characterized in both processes as a GTP supplier of Shi/Dynamin whereby AWD regulates the level of chemotactic receptors on the surface of migrating cells through receptor internalization, by its endocytic function. Our group studied the role of the sole group I NDPK, NDK-1 in distal tip cell (DTC) migration in Caenorhabditis elegans. In the absence of NDK-1 the migration of DTCs is incomplete. A half dosage of NDPK as present in ndk-1 (+/-) heterozygotes results in extra turns and overshoots of migrating gonad arms. Conversely, an elevated NDPK level also leads to incomplete gonadal migration owing to a premature stop of DTCs in the third phase of migration, where NDK-1 acts. We propose that NDK-1 exerts a dosage-dependent effect on the migration of DTCs. Our data derived from DTC migration in C. elegans is consistent with data on AWD's function in Drosophila. The combined data suggest that NDPK enzymes control the availability of surface receptors to regulate cell-sensing cues during cell migration. The dosage of NDPKs may be a coupling factor in cell migration by modulating the efficiency of receptor recycling.

Transatlantic Comparison of CT Radiation Doses in the Era of Radiation Dose-Tracking Software.

OBJECTIVE: The purpose of this study is to compare diagnostic reference levels from a local European CT dose registry, using radiation-tracking software from a large patient sample, with preexisting European and North American diagnostic reference levels. MATERIALS AND METHODS: Data (n = 43,761 CT scans obtained over the course of 2 years) for the European local CT dose registry were obtained from eight CT scanners at six institutions. Means, medians, and interquartile ranges of volumetric CT dose index (CTDIvol), dose-length product (DLP), size-specific dose estimate, and effective dose values for CT examinations of the head, paranasal sinuses, thorax, pulmonary angiogram, abdomen-pelvis, renal-colic, thorax-abdomen-pelvis, and thoracoabdominal angiogram were obtained using radiation-tracking software. Metrics from this registry were compared with diagnostic reference levels from Canada and California (published in 2015), the American College of Radiology (ACR) dose index registry (2015), and national diagnostic reference levels from local CT dose registries in Switzerland (2010), the United Kingdom (2011), and Portugal (2015). RESULTS: Our local registry had a lower 75th percentile CTDIvol for all protocols than did the individual internationally sourced data. Compared with our study, the ACR dose index registry had higher 75th percentile CTDIvol values by 55% for head, 240% for thorax, 28% for abdomen-pelvis, 42% for thorax-abdomen-pelvis, 128% for pulmonary angiogram, 138% for renal-colic, and 58% for paranasal sinus studies. CONCLUSION: Our local registry had lower diagnostic reference level values than did existing European and North American diagnostic reference levels. Automated radiation-tracking software could be used to establish and update existing diagnostic reference levels because they are capable of analyzing large datasets meaningfully.

Scan time adapted contrast agent injection protocols with low volume for low-tube voltage CT angiography: An in vitro study.

PURPOSE: The aims of this study were twofold. First, we investigated the extent of changes in arterial peak enhancement and changes in the duration of a diagnostic arterial enhancement when small amounts of CA volumes (≤30mL) were administered at varying tube voltages. Second, we investigated how to optimize CA injection protocols for CT-angiography with long scan times at various tube voltages to achieve optimal vascular enhancement at the lowest reasonable CA dose. MATERIALS AND METHODS: Measurements were performed with a custom-made dynamic flow phantom. For CTA protocols with a short scan time, we investigated the effect of various tube voltages (70-120kVp) on the arterial enhancement profile with very small CA volumes (20 and 30mL of Iobitridol 350mg I/mL) at a flow rate of 5mL/s. For CTA protocols with a long scan time, we utilized an optimized multi-bolus technique switching rapidly between 13 "micro-boli" of CA (total, 60mL) and saline (total, 24mL) at a flow rate of 4mL/s. The peak arterial enhancement (PAE) and the time period of diagnostic aortic enhancement ≥200 HU (T200) were analyzed. RESULTS: For the short scan time protocols, a diagnostic peak enhancement was achieved using 20mL of CA at 70 and 80kVp (PAE: 327±10 and 255±15 HU, respectively) or 30mL of CA at 70, 80 and 100kVp (PAE 451±10, 367±9, and 253±15 HU). For the long scan time, the optimized multi-bolus injection protocol extended T200 at 100kVp by 6s (40%) compared to a linear injection protocol (21±1s and 15±1s, respectively; p<0.001). CONCLUSION: Optimized CTA protocols comprising alternations of tube voltage and the CA injection protocol can save radiation doses and CA volumes at the same time.

Systematic radiation dose optimization of abdominal dual-energy CT on a second-generation dual-source CT scanner: assessment of the accuracy of iodine uptake measurement and image quality in an in vitro and in vivo investigations.

PURPOSE: To assess the accuracy of iodine quantification in a phantom study at different radiation dose levels with dual-energy dual-source CT and to evaluate image quality and radiation doses in patients undergoing a single-energy and two dual-energy abdominal CT protocols. METHODS: In a phantom study, the accuracy of iodine quantification (4.5-23.5 mgI/mL) was evaluated using the manufacturer-recommended and three dose-optimized dual-energy protocols. In a patient study, 75 abdomino-pelvic CT examinations were acquired as follows: 25 CT scans with the manufacturer-recommended dual-energy protocol (protocol A); 25 CT scans with a dose-optimized dual-energy protocol (protocol B); and 25 CT scans with a single-energy CT protocol (protocol C). CTDIvol and objective noise were measured. Five readers scored each scan according to six subjective image quality parameters (noise, contrast, artifacts, visibility of small structures, sharpness, overall diagnostic confidence). RESULTS: In the phantom study, differences between the real and measured iodine concentrations ranged from -8.8% to 17.0% for the manufacturer-recommended protocol and from -1.6% to 20.5% for three dose-optimized protocols. In the patient study, the CTDIvol of protocol A, B, and C were 12.5 ± 1.9, 7.5 ± 1.2, and 6.5 ± 1.7 mGycm, respectively (p < 0.001), and the average image noise values were 6.6 ± 1.2, 7.8 ± 1.4, and 9.6 ± 2.2 HU, respectively (p < 0.001). No significant differences in the six subjective image quality parameters were observed between the dose-optimized dual-energy and the single-energy protocol. CONCLUSION: A dose reduction of 41% is feasible for the manufacturer-recommended, abdominal dual-energy CT protocol, as it maintained the accuracy of iodine measurements and subjective image quality compared to a single-energy protocol.

Impact of model-based iterative reconstruction on low-contrast lesion detection and image quality in abdominal CT: a 12-reader-based comparative phantom study with filtered back projection at different tube voltages.

OBJECTIVES: To evaluate the impact of model-based iterative reconstruction (MBIR) on image quality and low-contrast lesion detection compared with filtered back projection (FBP) in abdominal computed tomography (CT) of simulated medium and large patients at different tube voltages. METHODS: A phantom with 45 hypoattenuating lesions was placed in two water containers and scanned at 70, 80, 100, and 120 kVp. The 120-kVp protocol served as reference, and the volume CT dose index (CTDIvol) was kept constant for all protocols. The datasets were reconstructed with MBIR and FBP. Image noise and contrast-to-noise-ratio (CNR) were assessed. Low-contrast lesion detectability was evaluated by 12 radiologists. RESULTS: MBIR decreased the image noise by 24% and 27%, and increased the CNR by 30% and 29% for the medium and large phantoms, respectively. Lower tube voltages increased the CNR by 58%, 46%, and 16% at 70, 80, and 100 kVp, respectively, compared with 120 kVp in the medium phantom and by 9%, 18% and 12% in the large phantom. No significant difference in lesion detection rate was observed (medium: 79-82%; large: 57-65%; P > 0.37). CONCLUSIONS: Although MBIR improved quantitative image quality compared with FBP, it did not result in increased low-contrast lesion detection in abdominal CT at different tube voltages in simulated medium and large patients. KEY POINTS: • MBIR improved quantitative image quality but not lesion detection compared with FBP. • Increased CNR by low tube voltages did not improve lesion detection. • Changes in image noise and CNR do not directly influence diagnostic accuracy.