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.

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.

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.

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.

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.

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.

Bone subtraction radiography in adult patients with cystic fibrosis.

Background Bone subtraction radiography allows reading pulmonary changes of chest radiographs more accurately without superimposition of bones. Purpose To evaluate the value of bone subtraction chest radiography using dual energy (DE) bone subtracted lung images compared to conventional radiographs (CR) in adult patients with cystic fibrosis (CF). Material and Methods Forty-nine DE radiographs of 24 patients (16 men) with CF (mean age, 32 years; age range, 18-71 years) were included. Lung function tests were performed within 10 days of the radiographs. Two radiologists evaluated all CR, DE, and CR + DE radiographs using the modified Chrispin-Norman score (CNS) and a five-point score for the confidence. Findings were statistically evaluated by Friedman ANOVA and Wilcoxon matched-pairs test. Results There was significant difference of CNS between CR and DE ( P = 0.044) as well as CR and CR + DE ( P < 0.001). CNS of CR images showed moderate correlation with FEV1% (R = 0.287, P = 0.046) while DE and CR + DE correlated poorly with FEV1% (R = 0.023, P = 0.874 and R = 0.04, P = 0.785). A higher confidence was achieved with bone-subtracted radiographs compared to radiographs alone (median, CR 3.3, DE 3.9, CR + DE 4.1, for both P < 0.001). Conclusion DE radiographs are reliable for the evaluation of adult patients with CF in acute exacerbation. For yearly surveillance, CR and DE radiographs may play a limited role. However, in clinical routine, DE radiographs are useful for adult CF patients and may depict more accurately inflammatory changes than CR.

Organ-based tube current modulation in a clinical context: Dose reduction may be largely overestimated in breast tissue.

OBJECTIVES: Organ-based tube current modulation aims to reduce exposure to radiosensitive organs like the breasts by considering their anatomical location and altering tube current during rotation. Former phantom studies demonstrated a dose reduction of 20-37 %. Our study aimed to estimate the potential of dose reduction with this technique in relation to the actual location of breast tissue in a large clinical cohort. METHODS: A 1-year cohort of chest CTs of females (N=1,263) was retrospectively evaluated. To estimate the relative dose effect, breast location was analysed by measuring the angle range of glandular tissue within the different dose zones. Relative exposure compared with constant tube current was calculated. Descriptive statistics and Wilcoxon-test were applied. RESULTS: Only 63 % of angle range of glandular breast tissue was found inside the reduced dose zone. The estimated mean relative dose reduction was lower than observed in former phantom studies(16 % vs. 20-37 %) but still significant compared to constant tube current (p<0.0001). CONCLUSIONS: Although organ-based tube current modulation results in a significant reduction of breast exposure compared to non-modulated irradiation, the technique cannot unfold its full potential, because breast tissue is often located outside the reduced dose zone, resulting in significantly lower dose reduction than expected. KEY POINTS: • OBTCM results in significant dose reduction compared to constant tube current scans. • A substantial portion of glandular tissue lies outside the reduced dose zone. • Potential dose reduction using organ-based tube current modulation may be overestimated.

Feasibility of Dose Optimization in a Second-Generation Dual-Source CT Scanner for a Manufacturer-Recommended Urolithiasis Protocol for Imaging Renal Stones.

OBJECTIVE: The purpose of this article is to investigate the magnitude of dose optimization for a manufacturer-recommended urolithiasis protocol in a second-generation dual-source CT scanner. MATERIALS AND METHODS: Custom renal phantoms with 24 stones were scanned using the manufacturer-provided dual-energy CT protocol (tube A, 100 kVp and 210 reference mAs; tube B, 140 kVp and 162 reference mAs) and seven dose-optimized protocols in which the reference tube current-time product setting of tube A was reduced stepwise by 20 mAs. Detection and characterization of the stones was assessed. In the patient study, 25 patients underwent the manufacturer-provided dual-energy protocol and 25 patients underwent imaging with a dose-optimized protocol (tube A, 100 kVp and 90 reference mAs; tube B, 140 kVp and 70 reference mAs). Dose-length product (DLP), image noise, and contrast-to-noise ratio (CNR) were assessed. Subjective image quality was analyzed by three independent radiologists. RESULTS: In the phantom study, the reference tube current-time product of tube A could be reduced from 210 to 90 mAs without losing the accuracy of detection or characterization of the calculi. In the patient study, the dose-optimized protocol resulted in a significant reduction of the average DLP by 51% compared with the standard protocol (219.4 vs 443.5 mGy·cm, respectively; p = 0.0001). The image noise was higher, and the CNR was lower, in the dose-optimized group than in the standard-dose group (p < 0.05). The subjective overall image quality of the dose-optimized CT examinations was rated as good, and that of the standard-dose CT examinations was rated as excellent (p = 0.001). CONCLUSION: The in vitro and in vivo assessment revealed a potential for a 51% dose reduction of the manufacturer-recommended dual-energy CT protocol for urolithiasis without compromising the accuracy.

Nucleoside diphosphate kinases (NDPKs) in animal development.

In textbooks of biochemistry, nucleoside diphosphate conversion to a triphosphate by nucleoside diphosphate 'kinases' (NDPKs, also named NME or NM23 proteins) merits a few lines of text. Yet this essential metabolic function, mediated by a multimeric phosphotransferase protein, has effects that lie beyond a simple housekeeping role. NDPKs attracted more attention when NM23-H1 was identified as the first metastasis suppressor gene. In this review, we examine these NDPK enzymes from a developmental perspective because of the tractable phenotypes found in simple animal models that point to common themes. The data suggest that NDPK enzymes control the availability of surface receptors to regulate cell-sensing cues during cell migration. NDPKs regulate different forms of membrane enclosure that engulf dying cells during development. We suggest that NDPK enzymes have been essential for the regulated uptake of objects such as bacteria or micronutrients, and this evolutionarily conserved endocytic function contributes to their activity towards the regulation of metastasis.

Combining automated attenuation-based tube voltage selection and iterative reconstruction: a liver phantom study.

OBJECTIVES: To determine the value of combined automated attenuation-based tube-potential selection and iterative reconstructions (IRs) for optimising computed tomography (CT) imaging of hypodense liver lesions. METHODS: A liver phantom containing hypodense lesions was imaged by CT with and without automated attenuation-based tube-potential selection (80, 100 and 120 kVp). Acquisitions were reconstructed with filtered back projection (FBP) and sinogram-affirmed IR. Image noise and contrast-to-noise ratio (CNR) were measured. Two readers marked lesion localisation and rated confidence, sharpness, noise and image quality on a five-point scale (1 = worst, 5 = best). RESULTS: Image noise was lower (31-52%) and CNR higher (43-102%) on IR than on FBP images at all tube voltages. On 100-kVp and 80-kVp IR images, confidence and sharpness were higher than on 120-kVp FBP images. Scores for image quality score and noise as well as sensitivity for 100-kVp IR were similar or higher than for 120-kVp FBP and lower for 80-kVp IR. Radiation dose was reduced by 26% at 100 kVp and 56% at 80 kVp. CONCLUSIONS: Compared with 120-kVp FBP images, the combination of automated attenuation-based tube-potential selection at 100 kVp and IR provides higher image quality and improved sensitivity for detecting hypodense liver lesions in vitro at a dose reduced by 26%. KEY POINTS: • Combining automated tube voltage selection/iterative CT reconstruction improves image quality. • Attenuation values remain stable on IR compared with FBP images. • Lesion detection was highest on 100-kVp IR images.

Prospective randomised comparison of diagnostic confidence and image quality with normal-dose and low-dose CT pulmonary angiography at various body weights.

OBJECTIVES: To find a threshold body weight (BW) below 100 kg above which computed tomography pulmonary angiography (CTPA) using reduced radiation and a reduced contrast material (CM) dose provides significantly impaired quality and diagnostic confidence compared with standard-dose CTPA. METHODS: In this prospectively randomised study of 501 patients with suspected pulmonary embolism and BW <100 kg, 246 were allocated into the low-dose group (80 kVp, 75 ml CM) and 255 into the normal-dose group (100 kVp, 100 ml CM). Contrast-to-noise ratio (CNR) in the pulmonary trunk was calculated. Two blinded chest radiologists independently evaluated subjective image quality and diagnostic confidence. Data were compared between the normal-dose and low-dose groups in five BW subgroups. RESULTS: Vessel attenuation did not differ between the normal-dose and low-dose groups within each BW subgroup (P = 1.0). The CNR was higher with the normal-dose compared with the low-dose protocol (P < 0.006) in all BW subgroups except for the 90-99 kg subgroup (P = 0.812). Subjective image quality and diagnostic confidence did not differ between CT protocols in all subgroups (P between 0.960 and 1.0). CONCLUSIONS: Subjective image quality and diagnostic confidence with 80 kVp CTPA is not different from normal-dose protocol in any BW group up to 100 kg. KEY POINTS: • 80 kVp CTPA is safe in patients weighing <100 kg • Reduced radiation and iodine dose still provide high vessel attenuation • Image quality and diagnostic confidence with low-dose CTPA is good • Diagnostic confidence does not deteriorate in obese patients weighing <100 kg.

Hybrid iterative reconstruction technique for abdominal CT protocols in obese patients: assessment of image quality, radiation dose, and low-contrast detectability in a phantom.

OBJECTIVE: The purpose of this study was to assess the impact of a noise reduction technique on image quality, radiation dose, and low-contrast detectability in abdominal CT for obese patients. MATERIALS AND METHODS: A liver phantom with 12 different tumors was designed, and fat rings were added to mimic intermediately sized and large patients. The intermediate and large phantoms were scanned with our standard abdominal CT protocol (image noise level of 15 HU and filtered back projection [FBP]). The large phantom was scanned with five different noise levels (10, 12.5, 15, 17.5, and 20 HU). All datasets for the large phantom were reconstructed with FBP and the noise reduction technique. The image noise and the contrast-to-noise ratio (CNR) were assessed. Tumor detection was independently performed by three radiologists in a blinded fashion. RESULTS: The application of the noise reduction method to the large phantom decreased the measured image noise (range, -14.5% to -37.0%) and increased the CNR (range, 26.7-70.6%) compared with FBP at the same noise level (p < 0.001). However, noise reduction was unable to improve the sensitivity for tumor detection in the large phantom compared with FBP at the same noise level (p > 0.05). Applying a noise level of 15 HU, the overall sensitivity for tumor detection in the intermediate and large phantoms with FBP measured 75.5% and 87.7% and the radiation doses measured 42.0 and 23.7 mGy, respectively. CONCLUSION: Although noise reduction significantly improved the quantitative image quality in simulated large patients undergoing abdominal CT compared with FBP, no improvement was observed for low-contrast detectability.

Iterative reconstruction algorithm for CT: can radiation dose be decreased while low-contrast detectability is preserved?

PURPOSE: To compare the low-contrast detectability and image quality of computed tomography (CT) at different radiation dose levels reconstructed with iterative reconstruction (IR) and filtered back projection (FBP). MATERIALS AND METHODS: A custom liver phantom with 12 simulated hypoattenuating tumors (diameters of 5, 10, 15, and 20 mm; tumor-to-liver contrast values of -10, -20, and -40 HU) was designed. The phantom was scanned with a standard abdominal CT protocol with a volume CT dose index of 21.6 mGy (equivalent 100% dose) and four low-dose protocols (20%, 40%, 60%, and 80% of the standard protocol dose). CT data sets were reconstructed with IR and FBP. Image noise was measured, and the tumors' contrast-to-noise ratios (CNRs) were calculated. Tumor detection was independently assessed by three radiologists who were blinded to the CT technique used. A total of 840 simulated tumors were presented to the radiologists. Statistical analyses included analysis of variance. RESULTS: IR yielded an image noise reduction of 43.9%-63.9% and a CNR increase of 74.1%-180% compared with FBP at the same dose level (P < .001). The overall sensitivity for tumor detection was 64.7%-85.3% for IR and 66.3%-85.7% for FBP at the 20%-100% doses, respectively. There was no significant difference in the sensitivity for tumor detection between IR and FBP at the same dose level (P = .99). The sensitivity of the protocol at the 20% dose with FBP and IR was significantly lower than that of the protocol at the 100% dose with FBP and IR (P = .019). CONCLUSION: As the radiation dose at CT decreases, the IR algorithm does not preserve the low-contrast detectability. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13122349/-/DC1.

Comparison of dual-energy subtraction and electronic bone suppression combined with computer-aided detection on chest radiographs: effect on human observers' performance in nodule detection.

OBJECTIVE: The objective of our study was to compare the effect of dual-energy subtraction and bone suppression software alone and in combination with computer-aided detection (CAD) on the performance of human observers in lung nodule detection. MATERIALS AND METHODS: One hundred one patients with from one to five lung nodules measuring 5-29 mm and 42 subjects with no nodules were retrospectively selected and randomized. Three independent radiologists marked suspicious-appearing lesions on the original chest radiographs, dual-energy subtraction images, and bone-suppressed images before and after postprocessing with CAD. Marks of the observers and CAD marks were compared with CT as the reference standard. Data were analyzed using nonparametric tests and the jackknife alternative free-response receiver operating characteristic (JAFROC) method. RESULTS: Using dual-energy subtraction alone (p = 0.0198) or CAD alone (p = 0.0095) improved the detection rate compared with using the original conventional chest radiograph. The combination of bone suppression and CAD provided the highest sensitivity (51.6%) and the original nonenhanced conventional chest radiograph alone provided the lowest (46.9%; p = 0.0049). Dual-energy subtraction and bone suppression provided the same false-positive (p = 0.2702) and true-positive (p = 0.8451) rates. Up to 22.9% of lesions were found only by the CAD program and were missed by the readers. JAFROC showed no difference in the performance between modalities (p = 0.2742-0.5442). CONCLUSION: Dual-energy subtraction and the electronic bone suppression program used in this study provided similar detection rates for pulmonary nodules. Additionally, CAD alone or combined with bone suppression can significantly improve the sensitivity of human observers for pulmonary nodule detection.

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.

Extracardiac findings detected by cardiac magnetic resonance imaging.

OBJECTIVE: To determine the prevalence and importance of extracardiac findings (ECF) in patients undergoing clinical CMR and to test the hypothesis that the original CMR reading focusing on the heart may underestimate extracardiac abnormalities. METHODS: 401 consecutive patients (mean age 53 years) underwent CMR at 1.5 T. Main indications were ischaemic heart disease (n = 183) and cardiomyopathy (n = 164). All CMR sequences, including scout images, were reviewed with specific attention to ECF in a second reading by the same radiologist who performed the first clinical reading. Potentially significant findings were defined as abnormalities requiring additional clinical or radiological follow-up. RESULTS: 250 incidental ECF were detected, of which 84 (34%) had potentially significant ECF including bronchial carcinoma (n = 1), lung consolidation (n = 7) and abdominal abnormalities. In 166 CMR studies (41%) non-significant ECF were detected. The number of ECF identified at second versus first reading was higher for significant (84 vs. 47) and non-significant (166 vs. 36) findings (P < 0.00001). CONCLUSIONS: About one fifth of patients undergoing CMR were found to have potentially significant ECF requiring additional work-up. The second dedicated reading detected significantly more ECF compared with the first clinical reading emphasising the importance of active search for extracardiac abnormalities when evaluating CMR studies. KEY POINTS: • Many patients undergoing cardiac MR have significant extracardiac findings (ECF) • These impact on management and require additional work-up. • Wide review of scout and cine sequences will detect most ECFs. • Education of radiologists is important to identify ECFs on CMR studies.