Assessing bolus peak position in CT perfusion: High variance persisting despite age-dependency in a large cohort.

PURPOSE: CT perfusion (CTP) is a valuable tool in suspected acute ischemic stroke. A substantial variability of the delay between contrast injection and bolus arrival in the brain is conceivable. We investigated the distribution of the peak positions of the concentration time curves measured in an artery (arterial input function, AIF) and - in cases with ischemia - also measured in the penumbra. METHODS: We report on 2624 perfusion scans (52 % female, mean age 72.2 ± 14.4 years) with stroke present in 1636 cases. From the attenuation time curves of the AIF and the penumbra, we calculated the respective bolus peak positions and investigated the distribution of the peak positions. Further, we analyzed the bolus peak positions for associations with age. RESULTS: The bolus peaked significantly later in older patients, both in the AIF and in the penumbra (all p < 0.001). In the whole cohort, we found a significant association of age with the bolus peak position of the AIF (ρ = 0.334; p < 0.001). In patients with stroke, age was also associated to the peak position of the AIF (ρ = 0.305; p < 0.001), and the penumbra (ρ = 0.246, p < 0.001). However, a substantial range of peak positions of the AIF and penumbra was noted across all age ranges. CONCLUSIONS: This study revealed a strong age-dependency of the contrast bolus arrival in both healthy and ischemic tissue. This variability makes non-uniform sampling schemes, which have been suggested to reduce radiation dose, problematic, as they might not always optimally capture the bolus in all cases.

Impact of temporal resolution on perfusion metrics, therapy decision, and radiation dose reduction in brain CT perfusion in patients with suspected stroke.

PURPOSE: CT perfusion of the brain is a powerful tool in stroke imaging, though the radiation dose is rather high. Several strategies for dose reduction have been proposed, including increasing the intervals between the dynamic scans. We determined the impact of temporal resolution on perfusion metrics, therapy decision, and radiation dose reduction in brain CT perfusion from a large dataset of patients with suspected stroke. METHODS: We retrospectively included 3555 perfusion scans from our clinical routine dataset. All cases were processed using the perfusion software VEOcore with a standard sampling of 1.5 s, as well as simulated reduced temporal resolution of 3.0, 4.5, and 6.0 s by leaving out respective time points. The resulting perfusion maps and calculated volumes of infarct core and mismatch were compared quantitatively. Finally, hypothetical decisions for mechanical thrombectomy following the DEFUSE-3 criteria were compared. RESULTS: The agreement between calculated volumes for core (ICC = 0.99, 0.99, and 0.98) and hypoperfusion (ICC = 0.99, 0.99, and 0.97) was excellent for all temporal sampling schemes. Of the 1226 cases with vascular occlusion, 14 (1%) for 3.0 s sampling, 23 (2%) for 4.5 s sampling, and 63 (5%) for 6.0 s sampling would have been treated differently if the DEFUSE-3 criteria had been applied. Reduction of temporal resolution to 3.0 s, 4.5 s, and 6.0 s reduced the radiation dose by a factor of 2, 3, or 4. CONCLUSION: Reducing the temporal sampling of brain perfusion CT has only a minor impact on image quality and treatment decision, but significantly reduces the radiation dose to that of standard non-contrast CT.

Adipose tissue is associated with kidney function parameters.

Obesity is characterized by the accumulation of adipose tissue in different body compartments. Whether adipose tissue directly affects kidney function is still unknown. We aimed to investigate the role of the adipose tissue and circulating creatinine, cystatin C and kidney function in subjects free of cardio-renal diseases. In the KORA-MRI population-based study, 377 subjects (mean age 56.2 ± 9.2 years; 41.6% female) underwent whole-body 3T-MRI examination. Adipose tissue defined as visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were quantified from T1-DIXON sequence using a semi-automatic algorithm. Serum creatinine and cystatin C were measured using standard laboratory and estimated glomerular filtration rate (e-GFR) was performed based on creatinine (e-GFRcrea), cystatin C (e-GFRcys) and creatinine-cystatin C (e-GFRcc). Linear regression analysis, adjusted for risk factors, was used to investigate the relationship between adipose tissue and circulating creatinine, cystatin C, and kidney function. In multivariate analyses VAT was inversely associated with eGFRcys (ß = - 4.88, p = < 0.001), and positively associated with serum cystatin C (ß = 0.05, p = < 0.001), respectively. No association was found between other adipose parameters such as total adipose tissue (TAT) and subcutaneous adipose tissue (SAT) and serum creatinine, urine microalbumin and eGFRcrea. Stratified analyses according to BMI revealed confirmatory results for category of BMI > 30. VAT is positively associated with serum cystatin C and inversely with eGFR based on cystatin C, suggesting a direct involvement of visceral adipose tissue in increased metabolism of cystatin C and consequently decreased kidney function.

Pulmonary computed tomographic manifestations of COVID-19 in vaccinated and non-vaccinated patients.

This study aimed to analyze computed tomographic (CT) imaging features of vaccinated and non-vaccinated COVID-19 patients. The study population of this retrospective single-center cohort study consisted of hospitalized COVID-19 patients who received a chest CT at the study site between July 2021 and February 2022. Qualitative scoring systems (RSNA, CO-RADS, COV-RADS), imaging pattern analysis and semi-quantitative scoring of lung changes were assessed. 105 patients (70,47% male, 62.1 ± 16.79 years, 53.3% fully vaccinated) were included in the data analysis. A significant association between vaccination status and the presence of the crazy-paving pattern was observed in univariate analysis and persisted after step-wise adjustment for possible confounders in multivariate analysis (RR: 2.19, 95% CI: [1.23, 2.62], P = 0.024). Scoring systems for probability assessment of the presence of COVID-19 infection showed a significant correlation with the vaccination status in univariate analysis; however, the associations were attenuated after adjustment for virus variant and stage of infection. Semi-quantitative assessment of lung changes due to COVID-19 infection revealed no association with vaccination status. Non-vaccinated patients showed a two-fold higher probability of the crazy-paving pattern compared to vaccinated patients. COVID-19 variants could have a significant impact on the CT-graphic appearance of COVID-19.

Computed Tomographic Imaging Features of COVID-19 Pneumonia Caused by the Delta (B.1.617.2) and Omicron (B.1.1.529) Variant in a German Nested Cohort Pilot Study Group.

BACKGROUND: The aim of this study was to evaluate CT (computed tomography) imaging differences for the Delta and the Omicron variant in COVID-19 infection. METHODS: The study population was derived from a retrospective study cohort investigating chest CT imaging patterns in vaccinated and nonvaccinated COVID-19 patients. CT imaging patterns of COVID-19 infection were evaluated by qualitative and semiquantitative scoring systems, as well as imaging pattern analysis. RESULTS: A total of 60 patients (70.00% male, 62.53 ± 17.3 years, Delta: 43 patients, Omicron: 17 patients) were included. Qualitative scoring systems showed a significant correlation with virus variants; "typical appearance" and "very high" degrees of suspicion were detected more often in patients with Delta (RSNA: p = 0.003; CO-RADS: p = 0.002; COV-RADS: p = 0.001). Semiquantitative assessment of lung changes revealed a significant association with virus variants in univariate (Delta: 6.3 ± 3.5; Omicron: 3.12 ± 3.2; p = 0.002) and multivariate analysis. The vacuolar sign was significantly associated with the Delta variant (OR: 14.74, 95% CI: [2.32; 2094.7], p = 0.017). CONCLUSION: The Delta variant had significantly more extensive lung involvement and showed changes classified as "typical" more often than the Omicron variant, while the Omicron variant was more likely associated with CT findings such as "absence of pulmonary changes". A significant correlation between the Delta variant and the vacuolar sign was observed.

White matter hyperintensity volume in pre-diabetes, diabetes and normoglycemia.

INTRODUCTION: As white matter hyperintensities (WMHs) of the brain are associated with an increased risk of stroke, cognitive decline, and depression, elucidating the associated risk factors is important. In addition to age and hypertension, pre-diabetes and diabetes may play important roles in the development of WMHs. Previous studies have, however, shown conflicting results. We aimed to investigate the effect of diabetes status and quantitative markers of glucose metabolism on WMH volume in a population-based cohort without prior cardiovascular disease. RESEARCH DESIGN AND METHODS: 400 participants underwent 3 T MRI. WMHs were manually segmented on 3D fluid-attenuated inversion recovery images. An oral glucose tolerance test (OGTT) was administered to all participants not previously diagnosed with diabetes to assess 2-hour serum glucose concentrations. Fasting glucose concentrations and glycated hemoglobin (HbA1c) levels were measured. Zero-inflated negative binomial regression analyses of WMH volume and measures of glycemic status were performed while controlling for cardiovascular risk factors and multiple testing. RESULTS: The final study population comprised 388 participants (57% male; age 56.3±9.2 years; n=98 with pre-diabetes, n=51 with diabetes). Higher WMH volume was associated with pre-diabetes (p=0.001) and diabetes (p=0.026) compared with normoglycemic control participants after adjustment for cardiovascular risk factors. 2-hour serum glucose (p<0.001), but not fasting glucose (p=0.389) or HbA1c (p=0.050), showed a significant positive association with WMH volume after adjustment for cardiovascular risk factors. CONCLUSION: Our results indicate that high 2-hour serum glucose concentration in OGTT, but not fasting glucose levels, may be an independent risk factor for the development of WMHs, with the potential to inform intensified prevention strategies in individuals at risk of WMH-associated morbidity.

Case Report: Refusal of an Veno-Arterial Extracorporeal Membrane Oxygenation Due to Malignant Disease? - An Extremely Rare Form of Cardiac Involvement in Acute Myeloid Leukemia.

We report here on a 61-year-old patient with acute right heart failure of unclear etiology. Echocardiography revealed a myocardial mass infiltrating the heart, though, we assumed a cardiac lymphoma. A VA-ECMO was implanted as bridging for diagnosis and therapy. Our patient received chemotherapy, under which the tumor (of unknown etiology at this point) reached a partial remission. Nine months after first admission the patient developed acute myeloid leukemia with DNMT3a and TET2 mutations. Retrospective analysis of the cardiac biopsy revealed the identical mutations and matched with the diagnosis of an extremely rare primary extramedullary manifestation of an AML (myelosarcoma). The patient received induction-chemotherapy and was planned for consolidating allogeneic stem cell transplantation. From this case, we conclude that an extracorporeal therapy should be discussed in selected patients even in case of an initially fatal appearing prognosis. In selected cases, extracorporeal support can generate enough time for diagnosis and therapy. However, transparent planning, including discussion of best supportive care strategies involving the patient's family are indispensable requirements for starting ECMO in such patients.

Associated factors of white matter hyperintensity volume: a machine-learning approach.

To identify the most important parameters associated with cerebral white matter hyperintensities (WMH), in consideration of potential collinearity, we used a data-driven machine-learning approach. We analysed two independent cohorts (KORA and SHIP). WMH volumes were derived from cMRI-images (FLAIR). 90 (KORA) and 34 (SHIP) potential determinants of WMH including measures of diabetes, blood-pressure, medication-intake, sociodemographics, life-style factors, somatic/depressive-symptoms and sleep were collected. Elastic net regression was used to identify relevant predictor covariates associated with WMH volume. The ten most frequently selected variables in KORA were subsequently examined for robustness in SHIP. The final KORA sample consisted of 370 participants (58% male; age 55.7 ± 9.1 years), the SHIP sample comprised 854 participants (38% male; age 53.9 ± 9.3 years). The most often selected and highly replicable parameters associated with WMH volume were in descending order age, hypertension, components of the social environment (i.e. widowed, living alone) and prediabetes. A systematic machine-learning based analysis of two independent, population-based cohorts showed, that besides age and hypertension, prediabetes and components of the social environment might play important roles in the development of WMH. Our results enable personal risk assessment for the development of WMH and inform prevention strategies tailored to the individual patient.

Combining lung ultrasound and Wells score for diagnosing pulmonary embolism in critically ill COVID-19 patients.

Subpleural consolidations have been found in lung ultrasound in patients with COVID-19, possibly deriving from pulmonary embolism (PE). The diagnostic utility of impact of lung ultrasound in critical-ill patients with COVID-19 for PE diagnostics however is unclear. We retrospectively evaluated all SARS-CoV2-associated ARDS patients admitted to our ICU between March 8th and May 31th 2020. They were enrolled in this study, when a lung ultrasound and a computed tomography pulmonary angiography (CTPA) were documented. In addition, wells score was calculated to estimate the probability of PE. The CTPA was used as the gold standard for the detection of PE. Twenty out of 25 patients met the inclusion criteria. In 12/20 patients (60%) (sub-) segmental PE were detected by CT-angiography. Lung ultrasound found subpleural consolidations in 90% of patients. PE-typical large supleural consolidations with a size ≥ 1 cm were detectable in 65% of patients and were significant more frequent in patients with PE compared to those without (p = 0.035). Large consolidations predicted PE with a sensitivity of 77% and a specificity of 71%. The Wells score was significantly higher in patients with PE compared to those without (2.7 ± 0.8 and 1.7 ± 0.5, respectively, p = 0.042) and predicted PE with an AUC of 0.81. When combining the two modalities, comparing patients with considered/probable PE using LUS plus a Wells score ≥ 2 to patients with possible/unlikely PE in LUS plus a Wells score < 2, PE could be predicted with a sensitivity of 100% and a specificity of 80%. Large consolidations detected in lung ultrasound were found frequently in COVID-19 ARDS patients with pulmonary embolism. In combination with a Wells score > 2, this might indicate a high-risk for PE in COVID-19.

Pulmonary artery thrombi are co-located with opacifications in SARS-CoV2 induced ARDS.

PURPOSE: Patients hospitalized for infection with SARS-CoV-2 typically present with pneumonia. The respiratory failure is frequently complicated by pulmonary embolism in segmental pulmonary arteries. The distribution of pulmonary embolism in regard to lung parenchymal opacifications has not been investigated yet. METHODS: All patients with COVID-19 treated at a medical intensive care unit between March 8th and April 15th, 2020 undergoing computed tomography pulmonary angiography (CTPA) were included. All CTPA were assessed by two radiologists independently in respect to parenchymal changes and pulmonary embolism on a lung segment basis. RESULTS: Out of 22 patients with severe COVID-19 treated within the observed time period, 16 (age 60.4 ± 10.2 years, 6 female SAPS2 score 49.2 ± 13.9) underwent CT. A total of 288 lung segment were analyzed. Thrombi were detectable in 9/16 (56.3%) patients, with 4.4 ± 2.9 segments occluded per patient and 40/288 (13.9%) segments affected in the whole cohort. Patients with thrombi had significantly worse segmental opacifications in CT (p < 0.05) and all thrombi were located in opacitated segments. There was no correlation between d-dimer level and number of occluded segmental arteries. CONCLUSIONS: Thrombi in segmental pulmonary arteries are common in COVID-19 and are located in opacitated lung segments. This might suggest local clot formation.

Adrenal and Ovarian Phenotype of a Tissue-Specific Urocortin 2-Overexpressing Mouse Model.

Urocortin 2 (UCN2) is a neuropeptide of the CRH family, involved in homeostatic mechanisms, the stress response, and control of anxiety. To elucidate the effects of UCN2 on steroidogenesis, we developed a mouse model that allows a Cre recombinase-determined conditional overexpression of UCN2 (UCN2-COE). In these mice SF1-Cre-driven overexpression of UCN2 was restricted to the adrenal glands, gonads, and parts of the hypothalamus. UCN2-COE animals of both sexes revealed significantly higher plasma UCN2 levels and significantly higher UCN2 expression levels in the adrenals and ovaries. In contrast, the baseline expression of UCN2 was already high in the testes of control mice with no further increase achievable in UCN2-COE animals. Adrenal steroidogenesis of UCN2-COE animals was investigated under baseline conditions, upon an ACTH stimulation test, and following a restraint stress test. A tendency toward lower expression of steroidogenic enzymes was detectable in UCN2-COE animals of both sexes with slight differences between males and females. A similar reduction in the expression levels of the final steps of ovarian steroidogenesis, accompanied by reduced plasma estradiol levels, was observed in female UCN2-COE animals. Thus, adrenal UCN2 overexpression resulted in down-regulation of adrenal steroidogenesis, suggesting a reduction in the stress response in the mouse (stress coping behavior). Similarly, UCN2 overexpression in the ovaries caused a decrease in steroidogenesis and reduction of follicles that had undergone ovulation. Nevertheless, this finding was not associated with reduced fertility.