Comparison of automated kidney stone size measurement and volumetry in photon counting CT compared to 3rd generation dual energy CT and physically measurements - an ex vivo study.

PURPOSE: This ex vivo study aimed to compare a newly developed dual-source photon-counting CT (PCCT) with a 3rd generation dual-source dual-energy CT (DECT) for the detection and measurement (stone lengths and volumetrics) of urinary stones. METHODS: 143 urinary stones with a known geometry were physically measured and defined as reference values. Next, urinary stones were placed in an anthropomorphic abdomen-model and were scanned with DECT and PCCT. Images were read by two experienced examiners and automatically evaluated using a specific software. RESULTS: DECT and PCCT showed a high sensitivity for manual stone detection of 97.9% and 94.4%, and for automatic detection of 93.0% and 87.4%, respectively. Compared to that uric acid and xanthine stones were recognized slightly worse by DECT and PCCT with manual stone detection (93.3% and 82.2%), and with automatic detection (77.8% and 60.0%). All other stone entities were completely recognized. By comparing the maximum diameter of the reference value and DECT, Pearson-correlation was 0.96 (p < 0.001) for manual and 0.97 (p < 0.001) for automatic measurement, and for PCCT it was 0.94 (p < 0.001) for manual and 0.97 (p < 0.001) for automatic measurements. DECT and PCCT can also reliably determine volume manually and automatically with a Pearson-correlation of 0.99 (p < 0.001), respectively. CONCLUSION: Both CTs showed comparable results in stone detection, length measurement and volumetry compared to the reference values. Automatic measurement tends to underestimate the maximum diameter. DECT proved to be slightly superior in the recognition of xanthine and uric acid stones.

Diagnosis of acute pulmonary embolism: when photon-counting-detector CT replaces energy-integrating-detector CT in daily routine.

PURPOSE: To compare the diagnostic approach of acute pulmonary embolism (PE) with photon-counting-detector CT (PCD-CT) and energy-integrating-detector CT (EID-CT). MATERIALS AND METHODS: Two cohorts underwent CT angiographic examinations with EID-CT (Group 1; n = 158) and PCD-CT (Group 2; n = 172), (b) with two options in Group 1, dual energy (Group 1a) or single energy (Group 1b) and a single option in Group 2 (spectral imaging with single source). RESULTS: In Group 2, all patients benefited from spectral imaging, only accessible to 105 patients (66.5%) in Group 1, with a mean acquisition time significantly shorter (0.9 ± 0.1 s vs 4.0 ± 0 .3 s; p < 0.001) and mean values of CTDIvol and DLP reduced by 46.3% and 47.7%, respectively. Comparing the quality of 70 keV (Group 2) and averaged (Group 1a) images: (a) the mean attenuation within pulmonary arteries did not differ (p = 0.13); (b) the image noise was significantly higher (p < 0.001) in Group 2 with no difference in subjective image noise (p = 0.29); and (c) 89% of examinations were devoid of artifacts in Group 2 vs 28.6% in Group 1a. The percentage of diagnostic examinations was 95.2% (100/105; Group 1a), 100% (53/53; Group 1b), and 95.3% (164/172; Group 2). There were 4.8% (5/105; Group 1a) and 4.7% (8/172; Group 2) of non-diagnostic examinations, mainly due to the suboptimal quality of vascular opacification with the restoration of a diagnostic image quality on low-energy images. CONCLUSION: Compared to EID-CT, morphology and perfusion imaging were available in all patients scanned with PCD-CT, with the radiation dose reduced by 48%. CLINICAL RELEVANCE STATEMENT: PCD-CT enables scanning patients with the advantages of both spectral imaging, including high-quality morphologic imaging and lung perfusion for all patients, and fast scanning-a combination that is not simultaneously accessible with EID-CT while reducing the radiation dose by almost 50%.

Image quality of lung perfusion with photon-counting-detector CT: comparison with dual-source, dual-energy CT.

PURPOSE: To evaluate the quality of lung perfusion imaging obtained with photon-counting-detector CT (PCD-CT) in comparison with dual-source, dual-energy CT (DECT). METHODS: Seventy-one consecutive patients scanned with PCD-CT were compared to a paired population scanned with dual-energy on a 3rd-generation DS-CT scanner using (a) for DS-CT (Group 1): collimation: 64 × 0.6 × 2 mm; pitch: 0.55; (b) for PCD-CT (Group 2): collimation: 144 × 0.4 mm; pitch: 1.5; single-source acquisition. The injection protocol was similar in both groups with the reconstruction of perfusion images by subtraction of high- and low-energy virtual monoenergetic images. RESULTS: Compared to Group 1, Group 2 examinations showed: (a) a shorter duration of data acquisition (0.93 ± 0.1 s vs 3.98 ± 0.35 s; p < 0.0001); (b) a significantly lower dose-length-product (172.6 ± 55.14 vs 339.4 ± 75.64 mGy·cm; p < 0.0001); and (c) a higher level of objective noise (p < 0.0001) on mediastinal images. On perfusion images: (a) the mean level of attenuation did not differ (p = 0.05) with less subjective image noise in Group 2 (p = 0.049); (b) the distribution of scores of fissure visualization differed between the 2 groups (p < 0.0001) with a higher proportion of fissures sharply delineated in Group 2 (n = 60; 84.5% vs n = 26; 26.6%); (c) the rating of cardiac motion artifacts differed between the 2 groups (p < 0.0001) with a predominance of examinations rated with mild artifacts in Group 2 (n = 69; 97.2%) while the most Group 1 examinations showed moderate artifacts (n = 52; 73.2%). CONCLUSION: PCD-CT acquisitions provided similar morphologic image quality and superior perfusion imaging at lower radiation doses. CLINICAL RELEVANCE STATEMENT: The improvement in the overall quality of perfusion images at lower radiation doses opens the door for wider applications of lung perfusion imaging in clinical practice. KEY POINTS: The speed of data acquisition with PCD-CT accounts for mild motion artifacts. Sharply delineated fissures are depicted on PCD-CT perfusion images. High-quality perfusion imaging was obtained with a 52% dose reduction.

Consistency of Monoenergetic Attenuation Measurements for a Clinical Dual-Source Photon-Counting Detector CT System Across Scanning Paradigms: A Phantom Study.

BACKGROUND. Use of virtual monoenergetic images (VMIs) from multienergy CT scans can mitigate inconsistencies in traditional attenuation measurements that result from variation in scan-related factors. Photon-counting detector (PCD) CT systems produce VMIs as standard image output under flexible scanning conditions. OBJECTIVE. The purpose of this article was to evaluate the consistency of monoenergetic attenuation measurements obtained from a clinical PCD CT scanner across a spectrum of scanning paradigms. METHODS. A phantom with 10 tissue-simulating inserts was imaged using a clinical dual-source PCD CT scanner. Nine scanning paradigms were obtained across combinations of tube voltages (90, 120, and 140 kVp) and image quality (IQ) levels (80, 145, and 180). Images were reconstructed at VMI levels of 50, 60, 70, and 80 keV. Consistency of attenuation measurements was assessed, using the 120 kVp with IQ level of 145 scanning paradigm as the reference scan. RESULTS. For all scanning paradigms, attenuation measurements showed intra-class correlation of 0.999 and higher with respect to the reference scan. Across inserts, mean bias relative to the reference scan ranged from -14.9 to 13.6 HU, -2.7 to 1.7 HU, and -3.9 to 3.8 HU at tube voltages of 90, 120, and 140 kVp, respectively; and from -14.9 to 13.6 HU, -6.4 to 3.8 HU, -3.7 to 1.4 HU, and -7.2 to 4.3 HU at VMI levels of 50, 60, 70, and 80 keV, respectively. Thus, mean bias did not exceed 5 HU for any insert at tube potentials of 120 kVp and 140 kVp, nor for any insert at a VMI level of 70 keV. At a VMI level of 50 keV and tube potential of 90 kVp, mean bias exceeded 5 HU for 14 of 30 possible combinations of inserts and scanning paradigms and exceeded 10 HU for four of 30 such combinations. At VMI levels of both 60 and 80 keV, mean bias exceeded 5 HU for only two combinations of inserts and scanning paradigms, all at a tube potential of 90 kVp. CONCLUSION. PCD CT generally provided consistent attenuation measurements across combinations of scanning paradigms and VMI levels. CLINICAL IMPACT. PCD CT may facilitate quantitative applications of CT data in clinical practice.

Ultra-High-Resolution Photon-Counting Detector CTA of the Head and Neck: Image Quality Assessment and Vascular Kernel Optimization.

Background: Head and neck CTA requires fine detail evaluation, including characterization of potentially very small vessels and intrastent lumens. Blooming artifacts also hinder evaluation. Objectives: To evaluate image quality of ultra-high-resolution (UHR) photon-counting detector (PCD) CTA of the head and neck and to explore variation of such quality across reconstruction kernels. Methods: This prospective study included patients who underwent clinically indicated head and neck CTA from September 2023 to December 2023. Participants underwent PCD CTA in UHR mode. Reconstructions for each examination included a reference reconstruction (reflecting clinical protocols) using 0.8-mm slice thickness and Bv40 kernel, and six UHR reconstructions using 0.2-mm slice thickness and kernels of varying sharpness (Bv48-Bv80). Quantitative measures were recorded. Two radiologists independently evaluated qualitative measures using Likert scales (1=lowest quality; 5=highest quality). Results: The analysis included 103 participants (mean age, 61.3±13.0 years; 56 male, 48 female). Median vessel sharpness (in HU/mm) was 100.9 for reference reconstruction, and for UHR varied from 110.0 for Bv46 to 121.6 for Bv76 and 134.7 for Bv80. Median right internal carotid artery C2 luminal diameter was 3.8 mm for reference reconstruction, and for UHR increased from 4.1 mm for Bv48 to 4.9 mm for Bv80. For both readers, median overall image quality for reference reconstruction was 3, and for UHR was highest for Bv64 (5); calcified plaque blooming artifact for reference reconstruction was 1, and for UHR was highest for Bv72 (5) and Bv76 (5); stent blooming artifact for reference reconstruction was 1, and for UHR was highest for Bv76 (5) and Bv80 (5); soft-plaque delineation for reference reconstruction was 1, and for UHR was highest for Bv76 (5) or Bv80 (5); small-vessel visualization for reference reconstruction was 1, and for UHR was highest for Bv76 (5) or Bv80 (5). Conclusion: UHR-PCD CTA yielded reduced blooming artifact from calcified plaques or stents, and improved softplaque and small-vessel visualization. These advantages were more pronounced for strongest kernels, although subjective image quality was better for a weaker kernel. Clinical impact: The findings indicate benefits from use of UHR-PCD CTA for head and neck evaluation and may help guide such examinations' kernel selection.

Effect of therapeutic plasma exchange on tissue factor and tissue factor pathway inhibitor in septic shock.

BACKGROUND: Coagulopathy is part of the pathological host response to infection in sepsis. Higher plasma concentrations of both tissue factor (TF) and tissue factor pathway inhibitor (TFPI) are associated with occurrence of disseminated intravascular coagulation (DIC), multi-organ dysfunction and increased mortality in patients with sepsis. Currently no treatment approaches specifically targeting this axis are available. We hypothesize that therapeutic plasma exchange (TPE) might limit this coagulopathy by restoring the balance of plasma proteins. METHODS: This was a pooled post-hoc biobank analysis including 51 patients with early (shock onset < 24 h) and severe (norepinephrine dose > 0.4 µg/kg/min) septic shock, who were either receiving standard of care treatment (SOC, n = 14) or SOC + one single TPE (n = 37). Plasma concentrations of TF and TFPI were measured both at- and 6 h after study inclusion. The effect of TPE on concentrations of TF and TFPI was investigated and compared to SOC patients. Further, baseline TF and TFPI concentrations were used to modulate and predict clinical response to adjunctive TPE, indicated by longitudinal reduction of lactate concentrations over the first 24 h following study inclusion. RESULTS: TPE led to a significant reduction in circulating concentrations of both TF and TFPI while no difference was observed in the SOC group. Relative change of TF within 6 h was + 14 (-0.8 to + 30.4) % (p = 0.089) in the SOC and -18.3 (-32.6 to -2.2) % (p < 0.001) in the TPE group (between group p < 0.001). Similarly, relative change of TFPI was + 14.4 (-2.3 to + 30.9) % (p = 0.076) in the SOC and -20 (-32.8 to -7.9) % (p < 0.001) in the TPE group (between group p = 0.022). The ratio of TF to TFPI remained unchanged in both SOC and TPE groups. SOC patients exhibited an increase in lactate over the initial 24 h when TF and TFPI concentrations were higher at baseline. In contrast, patients undergoing TPE experienced a sustained longitudinal reduction of lactate concentrations across all levels of baseline TF and TFPI elevations. In a multivariate mixed-effects model, higher baseline TF (p = 0.003) and TFPI (p = 0.053) levels led to greater longitudinal lactate concentration reduction effects in the TPE group. CONCLUSIONS: Adjunctive TPE in septic shock is associated with a significant removal of both TF and TFPI, which may contribute to the early hemodynamic improvement observed in septic shock patients receiving TPE. Higher baseline TF (and TFPI) plasma concentrations were identified as a putative predictor of treatment response that could be useful for predictive enrichment strategies in future clinical trials.

Physical activity and its impact on cardiovascular health in pediatric kidney transplant recipients.

BACKGROUND: Cardiovascular (CV) morbidity after kidney transplantation (KTx) in childhood is of increasing importance. In light of a high prevalence of CV risk factors, protective measures such as physical activity (PA) come into focus. Our aim was to comprehensively assess PA in pediatric KTx recipients and evaluate its impact on CV health. METHODS: Forty-eight patients were assessed for frequency, duration, intensity, and setting of PA using the "Motorik-Modul" PA questionnaire. Walking-based activity was measured by accelerometer in a subgroup (n = 23). CV risk factors and subclinical CV organ damage were determined. The impact of PA on CV parameters was analyzed using linear regression models. RESULTS: Fifty-two percent of pediatric KTx recipients did not reach WHO recommended PA level; 54% did not engage in PA with vigorous intensity (VPA). Twenty-nine percent indicated an extremely inactive lifestyle (< 120 min/week of moderate to vigorous intensity PA, MVPA). Compared to the healthy German KiGGS cohort, KTx recipients specifically lacked engagement in sport activities (KTx: 129 min/week; 95%CI, 97-162 vs. KiGGS, 242 min/week; 95%CI, 230-253). VPA was associated with lower systolic blood pressure (p = 0.024) and resting heart rate (p = 0.005), MVPA with fewer components of the post-transplant metabolic syndrome (p = 0.037), and better left ventricular diastolic function (p = 0.006). CONCLUSIONS: A considerable lack of PA, especially VPA, exists in young KTx recipients. PA was positively associated with important parameters of CV health. While long-term CV protection through PA seems promising in pediatric KTx recipients, specific educational approaches are most likely needed to increase patients' engagement in sport activities.

Impairment of endothelial progenitor cells in women after kidney transplantation.

OBJECTIVE: The long-term survival of kidney transplant patients has substantially improved. However, there is a higher risk for cardiovascular events after transplantation, partly due to immunosuppression. A diminished number of endothelial progenitor cells (EPCs), which play an important role in angiogenesis and the repair of endothelial damage, are associated with an increased cardiovascular risk. The aim of this study was to evaluate whether kidney transplantation affects EPCs in women. METHODS: Twenty-four healthy women and 22 female kidney transplant recipients were recruited. The ratio of angiogenic and non-angiogenic circulating progenitor cells (CPCs) was determined by multicolor flow cytometry and related to clinical parameters. Cord blood-derived endothelial colony-forming cells (ECFCs), a proliferative subgroup of endothelial progenitor cells, were treated with pooled sera from transplant patients or healthy controls and tested for their functional integrity using in vitro models. RESULTS: Kidney transplant recipients displayed a reduced ratio of angiogenic and non-angiogenic CPCs compared to healthy controls. Differences were especially pronounced in premenopausal women. Exposure to sera of transplanted women led to a significant impairment of ECFC proliferation, migration, and angiogenesis ability. CONCLUSIONS: Alterations of EPC populations may contribute to the higher cardiovascular risks after organ transplantation and should be considered in therapeutic strategies.

Myocardial Characterization with Extracellular Volume Mapping with a First-Generation Photon-counting Detector CT with MRI Reference.

Background Photon-counting detector (PCD) CT provides comprehensive spectral data with every acquisition, but studies evaluating myocardial extracellular volume (ECV) quantification with use of PCD CT compared with an MRI reference remain lacking. Purpose To compare ECV quantification for myocardial tissue characterization between a first-generation PCD CT system and cardiac MRI. Materials and Methods In this single-center prospective study, adults without contraindication to iodine-based contrast media underwent same-day cardiac PCD CT and MRI with native and postcontrast T1 mapping and late gadolinium enhancement for various clinical indications for cardiac MRI (the reference standard) between July 2021 and January 2022. Global and midventricular ECV were assessed with use of three methods: single-energy PCD CT, dual-energy PCD CT, and MRI T1 mapping. Quantitative comparisons among all techniques were performed. Correlation and reliability between different methods of ECV quantification were assessed with use of the Pearson correlation coefficient (r) and the intraclass correlation coefficient. Results The final sample included 29 study participants (mean age ± SD, 54 years ± 17; 15 men). There was a strong correlation of ECV between dual- and single-energy PCD CT (r = 0.91, P < .001). Radiation dose was 40% lower with dual-energy versus single-energy PCD CT (volume CT dose index, 10.1 mGy vs 16.8 mGy, respectively; P < .001). In comparison with MRI, dual-energy PCD CT showed strong correlation (r = 0.82 and 0.91, both P < .001) and good to excellent reliability (intraclass correlation coefficients, 0.81 and 0.90) for midventricular and global ECV quantification, but it overestimated ECV by approximately 2%. Single-energy PCD CT showed similar relationship with MRI but underestimated ECV by 3%. Conclusion Myocardial tissue characterization with photon-counting detector CT-based quantitative extracellular volume analysis showed a strong correlation to MRI. © RSNA, 2023 Supplemental material is available for this article.

Stent imaging on a clinical dual-source photon-counting detector CT system-impact of luminal attenuation and sharp kernels on lumen visibility.

OBJECTIVES: To assess the impact of scan modes and reconstruction kernels using a novel dual-source photon-counting detector CT (PCD-CT) on lumen visibility and sharpness of different stent sizes. METHODS: A phantom containing six balloon-expandable stents (2.5 to 9 mm diameter) in silicone tubing was scanned on a PCD-CT with standard (0.6 mm and 0.4 mm thicknesses) and ultra-high-resolution (0.2 mm thickness) modes. With the use of increasing contrast medium concentrations, densities of 0, 200, 400, and 600 HU were achieved. Standard-resolution scans were reconstructed using increasing sharpness kernels, using both polyenergetic quantitative soft tissue "conventional" ((Qr40c(0.6 mm), Qr40c(0.4 mm), Qr72c(0.2 mm)) and vascular (Bv) virtual monoenergetic reconstructions (Bv44m(0.4 mm), Bv60m(0.4 mm)) at 70 keV. In-stent lumen visibility, sharpness (max. ΔHU of the stent measured in profile plots), and in-stent noise (standard deviation of HU) were measured. RESULTS: In-stent lumen visibility was highest for Qr72c(0.2 mm) (86.5 ± 2.8% to 88.3 ± 2.6%) and in Bv60m(0.4 mm) reconstructions (77.3 ± 2.9 to 82.7 ± 2.5%). Lumen visibility was lowest in the smallest stent (2.5 mm) ranging from 54.1% in Qr40c(0.6 mm) to 74.1% in Qr72c(0.2 mm) and highest in the largest stent (9 mm) ranging from 93.8% in Qr40c(0.6 mm) to 99.1% in the Qr72c(0.2 mm) series. Lumen visibility decreased by 2.1% for every 200-HU increase in lumen attenuation. Max. ΔHU between stents and stent lumen was highest in Qr72c(0.2 mm) (ΔHU 892 ± 504 to 1526 ± 517) and Bv60m(0.4 mm) series (ΔHU 480 ± 357 to 1030 ± 344). Improvement of lumen visibility and sharpness in UHR and Bv60m(0.4 mm) series was strongest in smaller stent sizes. CONCLUSION: UHR acquisition mode and sharp reconstruction kernels on a novel PCD-CT system significantly improve in-stent lumen visibility and sharpness-especially for smaller stent sizes. KEY POINTS: • In-stent lumen visibility and sharpness of stents significantly improve using sharp reconstruction kernels (Bv60) and ultra-high-resolution mode in photon-counting detector computed tomography. • The observed improvement of stent-lumen visibility was highest in smaller stent sizes.

Clinical applications of photon counting detector CT.

The X-ray detector is a fundamental component of a CT system that determines the image quality and dose efficiency. Until the approval of the first clinical photon-counting-detector (PCD) system in 2021, all clinical CT scanners used scintillating detectors, which do not capture information about individual photons in the two-step detection process. In contrast, PCDs use a one-step process whereby X-ray energy is converted directly into an electrical signal. This preserves information about individual photons such that the numbers of X-ray in different energy ranges can be counted. Primary advantages of PCDs include the absence of electronic noise, improved radiation dose efficiency, increased iodine signal and the ability to use lower doses of iodinated contrast material, and better spatial resolution. PCDs with more than one energy threshold can sort the detected photons into two or more energy bins, making energy-resolved information available for all acquisitions. This allows for material classification or quantitation tasks to be performed in conjunction with high spatial resolution, and in the case of dual-source CT, high pitch, or high temporal resolution acquisitions. Some of the most promising applications of PCD-CT involve imaging of anatomy where exquisite spatial resolution adds clinical value. These include imaging of the inner ear, bones, small blood vessels, heart, and lung. This review describes the clinical benefits observed to date and future directions for this technical advance in CT imaging. KEY POINTS: • Beneficial characteristics of photon-counting detectors include the absence of electronic noise, increased iodine signal-to-noise ratio, improved spatial resolution, and full-time multi-energy imaging. • Promising applications of PCD-CT involve imaging of anatomy where exquisite spatial resolution adds clinical value and applications requiring multi-energy data simultaneous with high spatial and/or temporal resolution. • Future applications of PCD-CT technology may include extremely high spatial resolution tasks, such as the detection of breast micro-calcifications, and quantitative imaging of native tissue types and novel contrast agents.

Efficacy of CytoSorb®: a systematic review and meta-analysis.

INTRODUCTION: Cytokine adsorption using the CytoSorb® adsorber has been proposed in various clinical settings including sepsis, ARDS, hyperinflammatory syndromes, cardiac surgery or recovery after cardiac arrest. The aim of this analysis is to provide evidence for the efficacy of the CytoSorb® adsorber with regard to mortality in various settings. METHODS: We searched PubMed, Cochrane Library database and the database provided by Cytosorbents™ (01.1.2010-29.5.2022). We considered randomized controlled trials and observational studies with control groups. The longest reported mortality was defined as the primary endpoint. We computed risk ratios and 95%-confidence intervals and used DerSimonian and Lairds random effects model. We analysed all studies combined and divided them into the subgroups: sepsis, cardiopulmonary bypass surgery (CPB), other severe illness, SARS-CoV-2 infection and recovery from cardiac arrest. The meta-analysis was registered in advance (PROSPERO: CRD42022290334). RESULTS: Of an initial 1295 publications, 34 studies were found eligible, including 1297 patients treated with CytoSorb® and 1314 controls. Cytosorb® intervention did not lower mortality (RR [95%-CI]: all studies 1.07 [0.88; 1.31], sepsis 0.98 [0.74; 1.31], CPB surgery 0.91 [0.64; 1.29], severe illness 0.95 [0.59; 1.55], SARS-CoV-2 1.58 [0.50; 4.94]). In patients with cardiac arrest, we found a significant survival advantage of the untreated controls (1.22 [1.02; 1.46]). We did not find significant differences in ICU length of stay, lactate levels, or IL-6 levels after treatment. Of the eligible 34 studies only 12 were randomized controlled trials. All observational studies showed moderate to serious risk of bias. INTERPRETATION: To date, there is no evidence for a positive effect of the CytoSorb® adsorber on mortality across a variety of diagnoses that justifies its widespread use in intensive care medicine.

The significance of central blood pressure for cardiovascular target organ damage in children and adolescents after kidney transplantation.

BACKGROUND: Cardiovascular (CV) complications are important causes of morbidity and mortality in children after kidney transplantation (KTx). In adults, central blood pressure (cBP) is an accepted predictor of CV sequelae. We aimed to assess the prognostic value of cBP over peripheral blood pressure (pBP) for existing CV damage. METHODS: We measured cBP and pBP in 48 pediatric KTx recipients (mean age: 13.5 ± 4.2 years). Assessment of left ventricular mass index (LVMI) and aortic pulse wave velocity (PWV) allowed detection of CV target organ damage. LVMI and PWV were used as endpoints in multivariable linear regression models, in which cBP and pBP were compared for their predictive value. RESULTS: Using cBP z-scores, we identified a larger number of patients with uncontrolled or untreated hypertension compared to pBP (36% vs. 7%). Central systolic blood pressure (cSBP) was a significant independent predictor of LVMI, while peripheral systolic blood pressure (pSBP) was not. Comparing central (cDBP) and peripheral (pDBP) diastolic blood pressure for their predictive value on PWV revealed a greater estimate for cDBP (0.035 vs. 0.026 for pDBP) along with a slightly better model fit for cDBP. CONCLUSIONS: Our data in a small group of patients provide first evidence that cBP measurements in pediatric KTx recipients might be helpful in identifying patients at risk for the development of CV sequelae. Investigating a larger patient number, ideally repeatedly, is needed to create further evidence supporting our findings. In light of available devices measuring cBP noninvasively, the implementation of such clinical studies post-KTx care should be feasible. A higher resolution version of the Graphical abstract is available as Supplementary information.

Arterial stiffness and blood pressure increase in pediatric kidney transplant recipients.

BACKGROUND: Pulse wave velocity (PWV) is a measure of arterial stiffness. We investigated PWV and blood pressure (BP) to determine to what extent BP changes contribute to arterial stiffness, and secondly, to identify influencing factors on BP in children after kidney transplantation. METHODS: Seventy children ≥ 2.5 years post-transplantation with at least two PWV measurements were included. Changes of systolic (Δ SBP) and diastolic BP (Δ DBP) were classified into "stable/decreasing," "1-10 mmHg increase," and " > 10 mmHg increase." Linear mixed modeling for PWV z-score (PWVz) adjusted either for Δ SBP or Δ DBP was performed. An extended dataset with monthly entries of BP, immunosuppression, and creatinine was obtained in 35 participants over a median of 74 months to perform linear mixed modeling for SBP and DBP. RESULTS: PWVz increased with a rate of 0.11/year (95% CI 0.054 to 0.16). Compared to participants with stable BP, those with 1-10-mmHg SBP and DBP increase showed a higher PWVz of 0.59 (95% CI 0.046 to 1.13) and 0.86 (95% CI 0.43 to 1.30), respectively. A > 10-mmHg BP increase was associated with an even higher PWVz (SBP ß = 0.78, 95% CI 0.22 to 1.34; DBP ß = 1.37, 95% CI 0.80 to 1.94). Female sex and participants with lower eGFR showed higher PWVz. In the extended analysis, DBP was positively associated with cyclosporin A and everolimus trough levels. CONCLUSIONS: A higher increase of PWV is seen in patients with greater BP increase, with higher cyclosporin A and everolimus trough levels associated with higher BP. This emphasizes the role of BP as a modifiable risk factor for the improvement of cardiovascular outcome after transplantation. A higher resolution version of the Graphical abstract is available as Supplementary information.

Is Lumbar Puncture Needed? - Noninvasive Assessment of ICP Facilitates Decision Making in Patients with Suspected Idiopathic Intracranial Hypertension.

PURPOSE: Idiopathic intracranial hypertension (IIH) usually occurs in obese women of childbearing age. Typical symptoms are headache and sight impairment. Lumbar puncture (LP) is routinely used for both diagnosis and therapy (via cerebrospinal fluid drainage) of IIH. In this study, noninvasively assessed intracranial pressure (nICP) was compared to LP pressure (LPP) in order to clarify its feasibility for the diagnosis of IIH. MATERIALS AND METHODS: nICP was calculated using continuous signals of arterial blood pressure and cerebral blood flow velocity in the middle cerebral artery, a method which has been introduced recently. In 26 patients (f = 24, m = 2; age: 33 ±â€Š11 years), nICP was assessed one hour prior to LPP. If LPP was > 20 cmH2O, lumbar drainage was performed, LPP was measured again, and also nICP was reassessed. RESULTS: In total, LPP and nICP correlated with R = 0.85 (p < 0.001; N = 38). The mean difference of nICP-LPP was 0.45 ±â€Š4.93 cmH2O. The capability of nICP to diagnose increased LPP (LPP > 20 cmH2O) was assessed by ROC analysis. The optimal cutoff for nICP was close to 20 cmH2O with both a sensitivity and specificity of 0.92. Presuming 20 cmH2O as a critical threshold for the indication of lumbar drainage, the clinical implications would coincide in both methods in 35 of 38 cases. CONCLUSION: The TCD-based nICP assessment seems to be suitable for a pre-diagnosis of increased LPP and might eliminated the need for painful lumbar puncture if low nICP is detected.

Findings from 4C-T Study demonstrate an increased cardiovascular burden in girls with end stage kidney disease and kidney transplantation.

Mortality in children with kidney failure is higher in girls than boys with cardiovascular complications representing the most common causes of death. Pulse wave velocity (PWV), a measure of vascular stiffness, predicts cardiovascular mortality in adults. Here, PWV in children with kidney failure undergoing kidney replacement therapy was investigated to determine sex differences and potential contributing factors. Two-hundred thirty-five children (80 girls; 34%) undergoing transplantation (150 pre-emptive, 85 with prior dialysis) having at least one PWV measurement pre- and/or post-transplantation from a prospective cohort were analyzed. Longitudinal analyses (median/maximum follow-up time of 6/9 years) were performed for PWV z-scores (PWVz) using linear mixed regression models and further stratified by the categories of time: pre-kidney replacement therapy and post-transplantation. PWVz significantly increased by 0.094 per year and was significantly higher in girls (PWVz +0.295) compared to boys, independent of the underlying kidney disease. During pre-kidney replacement therapy, an average estimated GFR decline of 4 ml/min/1.73 m2 per year was associated with a PWVz increase of 0.16 in girls only. Higher diastolic blood pressure and low density lipoprotein were independently associated with higher PWVz during pre-kidney replacement therapy in both sexes. In girls post-transplantation, an estimated GFR decline of 4ml/min/1.73m2 per year pre-kidney replacement therapy and a longer time (over 12 months) to transplantation were significantly associated with higher PWVz of 0.22 and of 0.57, respectively. PWVz increased further after transplantation and was positively associated with time on dialysis and diastolic blood pressure in both sexes. Thus, our findings demonstrate that girls with advanced chronic kidney disease are more susceptible to develop vascular stiffening compared to boys, this difference persist after transplantation and might contribute to higher mortality rates seen in girls with kidney failure.

Dual-Energy CT Perfusion of Invasive Tumor Front in Non-Small Cell Lung Cancers.

Background Active endothelial cell proliferation occurs at the tumor edge, known as the invading-tumor front. This study focused on perfusion analysis of non-small cell lung cancers. Purpose To analyze dual-phase, dual-energy CT perfusion according to the degree of tumor hypoxia. Materials and Methods This prospective study was performed 2016-2017. A two-phase dual-energy CT protocol was obtained for consecutive participants with operable non-small cell lung cancer. The first pass and delayed iodine concentration within the tumor and normalized iodine uptake, corresponding to the iodine concentration within the tumor normalized to iodine concentration within the aorta, were calculated for the entire tumor and within three peripheral layers automatically segmented (ie, 2-mm-thick concentric subvolumes). The expression of the membranous carbonic anhydrase (mCA) IX, a marker of tumor hypoxia, was assessed in tumor specimens. Comparative analyses according to the histologic subtypes, type of resected tumors, and mCA IX expression were performed. Results There were 33 mCA IX-positive tumors and 16 mCA IX-negative tumors. In the entire tumor, the mean normalized iodine uptake was higher on delayed than on first-pass acquisitions (0.35 ± 0.17 vs 0.13 ± 0.15, respectively; P < .001). A single layer, located at the edge of the tumor, showed higher values of the iodine concentration (median, 0.53 mg/mL vs 0.21 mg/mL, respectively; P = .03) and normalized iodine uptake (0.04 vs 0.02, respectively; P = .03) at first pass in mCA IX-positive versus mCA IX-negative tumors. Within this layer, a functional profile of neovascularization was found in 23 of 33 (70%) of mCA IX-positive tumors, and the median mCA IX score of these tumors was higher than in tumors with a nonfunctional profile of neovascularization (median mCA IX score, 20 vs 2, respectively; P = .03). Conclusion A two-phase dual-energy CT examination depicted higher perfusion between the tumor edge and lung parenchyma in hypoxic tumors. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Murphy and Ryan in this issue.

First Clinical Photon-counting Detector CT System: Technical Evaluation.

Background The first clinical CT system to use photon-counting detector (PCD) technology has become available for patient care. Purpose To assess the technical performance of the PCD CT system with use of phantoms and representative participant examinations. Materials and Methods Institutional review board approval and written informed consent from four participants were obtained. Technical performance of a dual-source PCD CT system was measured for standard and high-spatial-resolution (HR) collimations. Noise power spectrum, modulation transfer function, section sensitivity profile, iodine CT number accuracy in virtual monoenergetic images (VMIs), and iodine concentration accuracy were measured. Four participants were enrolled (between May 2021 and August 2021) in this prospective study and scanned using similar or lower radiation doses as their respective clinical examinations performed on the same day using energy-integrating detector (EID) CT. Image quality and findings from the participants' PCD CT and EID CT examinations were compared. Results All standard technical performance measures met accreditation and regulatory requirements. Relative to filtered back-projection reconstructions, images from iterative reconstruction had lower noise magnitude but preserved noise power spectrum shape and peak frequency. Maximum in-plane spatial resolutions of 125 and 208 µm were measured for HR and standard PCD CT scans, respectively. Minimum values for section sensitivity profile full width at half maximum measurements were 0.34 mm (0.2-mm nominal section thickness) and 0.64 mm (0.4-mm nominal section thickness) for HR and standard PCD CT scans, respectively. In a 120-kV standard PCD CT scan of a 40-cm phantom, VMI iodine CT numbers had a mean percentage error of 5.7%, and iodine concentration had root mean squared error of 0.5 mg/cm3, similar to previously reported values for EID CT. VMIs, iodine maps, and virtual noncontrast images were created for a coronary CT angiogram acquired with 66-msec temporal resolution. Participant PCD CT images showed up to 47% lower noise and/or improved spatial resolution compared with EID CT. Conclusion Technical performance of clinical photon-counting detector (PCD) CT is improved relative to that of a current state-of-the-art CT system. The dual-source PCD geometry facilitated 66-msec temporal resolution multienergy cardiac imaging. Study participant images illustrated the effect of the improved technical performance. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Willemink and Grist in this issue.

Telomere length is associated with intima-media thickness in pediatric liver transplant patients: A prospective cohort study.

Leukocyte telomere length (LTL) is a marker for biological age. Pediatric liver transplant recipients show a high rate of subclinical atherosclerosis, indicated by elevated intima-media thickness (IMT). We hypothesized that atherosclerosis is associated with biological age in these patients and investigated the course of LTL over time. We measured LTL from peripheral blood leukocytes by quantitative polymerase chain reaction and IMT from 97 pediatric patients after liver transplantation in a prospective cohort study. Of the patients, 71% (n = 69) had two or more assessments (total, 228 observations; median follow-up, 1.1 years). Lower LTL was associated with higher IMT (ß = -0.701, p = 0.01) and higher aspartate aminotransferase (ß = -0.001, p = 0.02), adjusted for age, sex, and age at transplantation. Of the patients, 45% showed decreasing LTL over time, whereas 55% exhibited stable LTL. Patients with stable LTL showed a decrease in IMT (median, -0.02 mm/year) and a decrease of tacrolimus trough levels (median, -0.08 µg/L/year). LTL is associated with IMT independent of age in pediatric liver transplant patients, suggesting that early aging contributes to the high burden of subclinical cardiovascular damage and may furthermore negatively affect the graft.

Renal events in patients receiving neprilysin inhibitors: a systematic review and meta-analysis.

BACKGROUND: While it is well known that angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARBs) increase the risk of acute renal failure, the role of neprilysin inhibition (NEPi) is unclear and some physicians are reluctant to prescribe sacubitril/valsartan because of safety concerns. This meta-analysis aimed to examine the risk for renal events, progression of chronic kidney disease (CKD) or progression to dialysis on combined NEPi and ACEi/ARBs compared with ACEi or ARBs. METHODS: We performed a systematic meta-analysis including 17 randomized controlled trials (study drug sacubitril/valsartan or omapatrilat), involving a total of 23 569 patients, after searching PubMed, Cochrane, ClinicalTrials.org and Embase for eligible studies. From the included trials, all renal endpoints, including long- and short-term outcomes and hyperkalemia, were extracted. Pooled odds ratios (ORs) were calculated using the DerSimonian and Laird method. The study was registered at PROSPERO. RESULTS: Overall, treatment with sacubitril/valsartan or omapatrilat showed a slightly lower risk of any renal event [OR 0.82 (0.7-0.97)] compared with treatment with an ACEi or ARB alone. Also, there was a decreased risk of severe acute renal events [OR 0.8 (0.69-0.93)] and a decrease in estimated glomerular filtration rate decline [mean difference -0.58 mL/min (-0.83 to -0.33 mL/min)]. There was no difference in chronic renal events [OR 0.92 (0.8-1.05)] or hyperkalemia [OR 1.02 (0.84-1.23)]. CONCLUSION: NEPi + ACEi/ARBs are safe in terms of renal adverse events. Longer trials focusing on CKD are needed to evaluate the effect of NEPi on decreasing progression of CKD.