Characterisation of cold-induced mitochondrial fission in porcine aortic endothelial cells

BACKGROUND Previously, we observed that hypothermia, widely used for organ preservation, elicits mitochondrial fission in different cell types. However, temperature dependence, mechanisms and consequences of this cold-induced mitochondrial fission are unknown. Therefore, we here study cold-induced mitochondrial fission in endothelial cells, a cell type generally displaying a high sensitivity to cold-induced injury. METHODS Porcine aortic endothelial cells were incubated at 4-25 °C in modified Krebs-Henseleit buffer (plus glucose to provide substrate and deferoxamine to prevent iron-dependent hypothermic injury). RESULTS Cold-induced mitochondrial fission occurred as early as after 3 h at 4 °C and at temperatures below 21 °C, and was more marked after longer cold incubation periods. It was accompanied by the formation of unusual mitochondrial morphologies such as donuts, blobs, and lassos. Under all conditions, re-fusion was observed after rewarming. Cellular ATP content dropped to 33% after 48 h incubation at 4 °C, recovering after rewarming. Drp1 protein levels showed no significant change during cold incubation, but increased phosphorylation at both phosphorylation sites, activating S616 and inactivating S637. Drp1 receptor protein levels were unchanged. Instead of increased mitochondrial accumulation of Drp1 decreased mitochondrial localization was observed during hypothermia. Moreover, the well-known Drp1 inhibitor Mdivi-1 showed only partial protection against cold-induced mitochondrial fission. The inner membrane fusion-mediating protein Opa1 showed a late shift from the long to the fusion-incompetent short isoform during prolonged cold incubation. Oma1 cleavage was not observed. CONCLUSIONS Cold-induced mitochondrial fission appears to occur over almost the whole temperature range relevant for organ preservation. Unusual morphologies appear to be related to fission/auto-fusion. Fission appears to be associated with lower mitochondrial function/ATP decline, mechanistically unusual, and after cold incubation in physiological solutions reversible at 37 °C

Impact of Bayesian penalized likelihood reconstruction on quantitative and qualitative aspects for pulmonary nodule detection in digital 2-[18F]FDG-PET/CT

To evaluate the impact of block sequential regularized expectation maximization (BSREM) reconstruction on quantitative and qualitative aspects of 2-[18F]FDG-avid pulmonary nodules compared to conventional ordered subset expectation maximization (OSEM) reconstruction method. Ninety-one patients with 144 2-[18F]FDG-avid pulmonary nodules (all ≤ 20 mm) undergoing PET/CT for oncological (re-)staging were retrospectively included. Quantitative parameters in BSREM and OSEM (including point spread function modelling) were measured, including maximum standardized uptake value (SUVmax). Nodule conspicuity in BSREM and OSEM images was evaluated by two readers. Wilcoxon matched pairs signed-rank test was used to compare quantitative and qualitative parameters in BSREM and OSEM. Pulmonary nodule SUVmax was significantly higher in BSREM images compared to OSEM images [BSREM 5.4 (1.2–20.7), OSEM 3.6 (0.7–17.4); p = 0.0001]. In a size-based analysis, the relative increase in SUVmax was more pronounced in smaller nodules (≤ 7 mm) as compared to larger nodules (8–10 mm, or > 10 mm). Lesion conspicuity was higher in BSREM than in OSEM (p < 0.0001). BSREM reconstruction results in a significant increase in SUVmax and a significantly improved conspicuity of small 2-[18F]FDG-avid pulmonary nodules compared to OSEM reconstruction. Digital 2-[18F]FDG-PET/CT reading may be enhanced with BSREM as small lesion conspicuity is improved

Leukoencephalopathy after prophylactic whole-brain irradiation with or without hippocampal sparing: a longitudinal magnetic resonance imaging analysis

PURPOSE Neurocognitive changes are well described after prophylactic or therapeutic whole-brain radiotherapy (WBRT) and have been reported as early as 3 months after radiotherapy (RT). Therefore, WBRT with protection of the hippocampal region (hippocampal avoidance, HA) has been proposed to preserve neurocognition. Our aim was to compare the risk of leukoencephalopathy after prophylactic cranial irradiation (PCI) with or without HA. METHODS Patients with small-cell lung cancer who received either lateral-opposed field PCI (non-HA-PCI; n = 9) or hippocampus avoidance PCI (HA-PCI; n = 9) with available magnetic resonance imaging (MRI) follow-up were identified and age matched. Pre-therapeutic and follow-up MRI after RT was analysed for leukoencephalopathy based on the Fazekas score. Bilateral cortical and subcortical brain structures were segmented and analysed for alterations in dosimetric parameters and volumes. RESULTS There was no significant difference of Fazekas scores between groups at baseline. Fazekas score differed in post-treatment with a median of 1 in the HA-PCI group and 2 in the non-HA-PCI group (p = 0.007). Significant increase of Fazekas score over time after RT was observed for HA-PCI patients (p = 0.001) but not for non-HA-PCI patients. Dmax (highest radiation dose) and brain volume receiving doses >25Gy were higher in HA-PCI patients. There were no significant volumetric differences for segmented brain structures between groups. CONCLUSION Radiological changes are more prominent after HA-PCI than after non-HA-PCI. Although no standardised neurocognitive testing was performed, the significantly increased Fazekas scores after HA-PCI are expected to interfere with neurocognitive function. Prospective long-term neurocognitive studies are warranted before HA-PCI is implemented in routine clinical practice

Circle of Willis variants and their association with outcome in patients with middle cerebral artery-M1-occlusion stroke

BACKGROUND: An incomplete circle of Willis (CoW) has been associated with a higher risk of stroke and might affect collateral flow in large vessel occlusion (LVO) stroke. We aimed to investigate the distribution of CoW variants in a LVO stroke and transient ischemic attack (TIA) cohort and analyze their impact on 3-month functional outcome. METHODS: CoW anatomy was assessed with time-of-flight magnetic resonance angiography (TOF-MRA) in 193 stroke patients with acute middle cerebral artery (MCA)-M1-occlusion receiving endovascular treatment (EVT) and 73 TIA patients without LVO. The main CoW variants were categorized into four vascular models of presumed collateral flow via the CoW. RESULTS: 82.4% (n = 159) of stroke and 72.6% (n = 53) of TIA patients had an incomplete CoW. Most variants affected the posterior circulation (stroke: 77.2%, n = 149; TIA: 58.9%, n = 43; p = 0.004). Initial stroke severity defined by the National Institutes of Health Stroke Scale (NIHSS) on admission was similar for patients with and without CoW variants. CoW integrity did not differ between groups with favorable (modified Rankin Scale [mRS]): 0-2) and unfavorable (mRS: 3-6) 3-month outcome. However, we found trends towards a higher mortality in patients with any type of CoW variant (p = 0.08) and a higher frequency of incomplete CoW among patients dying within 3 months after stroke onset (p = 0.119). In a logistic regression analysis adjusted for the potential confounders age, sex and atrial fibrillation, neither the vascular models nor anterior or posterior variants were independently associated with outcome. CONCLUSION: Our data provide no evidence for an association of CoW variants with clinical outcome in LVO stroke patients receiving EVT

Circle of Willis variants and their association with outcome in patients with middle cerebral artery-M1-occlusion stroke.

BACKGROUND An incomplete circle of Willis (CoW) has been associated with a higher risk of stroke and might affect collateral flow in large vessel occlusion (LVO) stroke. We aimed to investigate the distribution of CoW variants in a LVO stroke and transient ischemic attack (TIA) cohort and analyze their impact on 3-month functional outcome. METHODS CoW anatomy was assessed with time-of-flight magnetic resonance angiography (TOF-MRA) in 193 stroke patients with acute middle cerebral artery (MCA)-M1-occlusion receiving endovascular treatment (EVT) and 73 TIA patients without LVO. The main CoW variants were categorized into four vascular models of presumed collateral flow via the CoW. RESULTS 82.4% (n = 159) of stroke and 72.6% (n = 53) of TIA patients had an incomplete CoW. Most variants affected the posterior circulation (stroke: 77.2%, n = 149; TIA: 58.9%, n = 43; p = 0.004). Initial stroke severity defined by the National Institutes of Health Stroke Scale (NIHSS) on admission was similar for patients with and without CoW variants. CoW integrity did not differ between groups with favorable (modified Rankin Scale [mRS]): 0-2) and unfavorable (mRS: 3-6) 3-month outcome. However, we found trends towards a higher mortality in patients with any type of CoW variant (p = 0.08) and a higher frequency of incomplete CoW among patients dying within 3 months after stroke onset (p = 0.119). In a logistic regression analysis adjusted for the potential confounders age, sex and atrial fibrillation, neither the vascular models nor anterior or posterior variants were independently associated with outcome. CONCLUSION Our data provide no evidence for an association of CoW variants with clinical outcome in LVO stroke patients receiving EVT

Acute Disseminated Encephalomyelitis in FET PET/MR

After 3 weeks of daily headache, a 28-year-old, otherwise healthy woman was admitted to the emergency department with a first-time generalized seizure. CT showed a left frontal mass with perifocal edema. Brain MRI raised the suspicion of cerebral lymphoma. Cerebrospinal fluid analysis revealed mononuclear pleocytosis of 14 cells/μL without malignant cells, normal protein levels, and absence of oligoclonal bands. FET PET/MRI of the lesion showed FET characteristics of inflammatory disease, and acute disseminated encephalomyelitis was suggested as diagnosis. Final histopathological results from brain biopsy confirmed acute disseminated encephalomyelitis

Virtual Monoenergetic Images of Dual-Energy CT-Impact on Repeatability, Reproducibility, and Classification in Radiomics

The purpose of this study was to (i) evaluate the test-retest repeatability and reproducibility of radiomic features in virtual monoenergetic images (VMI) from dual-energy CT (DECT) depending on VMI energy (40, 50, 75, 120, 190 keV), radiation dose (5 and 15 mGy), and DECT approach (dual-source and split-filter DECT) in a phantom (ex vivo), and (ii) to assess the impact of VMI energy and feature repeatability on machine-learning-based classification in vivo in 72 patients with 72 hypodense liver lesions. Feature repeatability and reproducibility were determined by concordance-correlation-coefficient (CCC) and dynamic range (DR) ≥0.9. Test-retest repeatability was high within the same VMI energies and scan conditions (percentage of repeatable features ranging from 74% for SFDE mode at 40 keV and 15 mGy to 86% for DSDE at 190 keV and 15 mGy), while reproducibility varied substantially across different VMI energies and DECTs (percentage of reproducible features ranging from 32.8% for SFDE at 5 mGy comparing 40 with 190 keV to 99.2% for DSDE at 15 mGy comparing 40 with 50 keV). No major differences were observed between the two radiation doses (<10%) in all pair-wise comparisons. In vivo, machine learning classification using penalized regression and random forests resulted in the best discrimination of hemangiomas and metastases at low-energy VMI (40 keV), and for cysts at high-energy VMI (120 keV). Feature selection based on feature repeatability did not improve classification performance. Our results demonstrate the high repeatability of radiomics features when keeping scan and reconstruction conditions constant. Reproducibility diminished when using different VMI energies or DECT approaches. The choice of optimal VMI energy improved lesion classification in vivo and should hence be adapted to the specific task

VEXAS Syndrome With Tracheal Involvement but Absence of Vasculitis in FDG PET/CT

In early 2022, a 77-year-old man presented with weight loss and recurrent subfebrile temperatures since 6 months. Workup with CT revealed a lung infiltrate. Despite antibiotic treatment, serum inflammation markers remained high. The patient further developed eczematous skin changes, uveitis (sequentially on both eyes), and macrocytic anemia. Finally, an autoinflammatory disease was suspected, and FDG PET/CT was performed. The examination revealed metabolically active foci in several tissues (tracheal cartilage, bone marrow, muscles). Bone marrow aspiration revealed an UBA1 mutation, which is pathognomonic for VEXAS syndrome

Leptomeningeal collateral activation indicates severely impaired cerebrovascular reserve capacity in patients with symptomatic unilateral carotid artery occlusion

For patients with symptomatic unilateral internal carotid artery (ICA) occlusion, impaired cerebrovascular reactivity (CVR) indicates increased stroke risk. Here, the role of collateral activation remains a matter of debate, whereas angio-anatomical collateral abundancy does not necessarily imply sufficient compensatory flow provided. We aimed to further elucidate the role of collateral activation in the presence of impaired CVR. From a prospective database, 62 patients with symptomatic unilateral ICA occlusion underwent blood oxygenation-level dependent (BOLD) fMRI CVR imaging and a transcranial Doppler (TCD) investigation for primary and secondary collateral activation. Descriptive statistic and multivariate analysis were used to evaluate the relationship between BOLD-CVR values and collateral activation. Patients with activated secondary collaterals exhibited more impaired BOLD-CVR values of the ipsilateral hemisphere (p = 0.02). Specifically, activation of leptomeningeal collaterals showed severely impaired ipsilateral hemisphere BOLD-CVR values when compared to activation of ophthalmic collaterals (0.05 ± 0.09 vs. 0.12 ± 0.04, p = 0.005). Moreover, the prediction analysis showed leptomeningeal collateral activation as a strong independent predictor for ipsilateral hemispheric BOLD-CVR. In our study, ipsilateral leptomeningeal collateral activation is the sole collateral pathway associated with severely impaired BOLD-CVR in patients with symptomatic unilateral ICA occlusion

Virtual Monoenergetic Images of Dual-Energy CT-Impact on Repeatability, Reproducibility, and Classification in Radiomics

Simple Summary Virtual monoenergetic images from dual-energy CT are incrementally used in routine clinical practice. Thus, radiomic analysis will be more often performed on these images in the future. This study characterized the test-retest repeatability and reproducibility of radiomic features from virtual monoenergetic images and their impact on machine-learning-based lesion classification. The results of this study provide a basis to improve radiomic analyses and identify the role of feature stability in classification tasks when using virtual monoenergetic imaging with different scan or reconstruction parameters in multicenter clinical studies. The purpose of this study was to (i) evaluate the test-retest repeatability and reproducibility of radiomic features in virtual monoenergetic images (VMI) from dual-energy CT (DECT) depending on VMI energy (40, 50, 75, 120, 190 keV), radiation dose (5 and 15 mGy), and DECT approach (dual-source and split-filter DECT) in a phantom (ex vivo), and (ii) to assess the impact of VMI energy and feature repeatability on machine-learning-based classification in vivo in 72 patients with 72 hypodense liver lesions. Feature repeatability and reproducibility were determined by concordance-correlation-coefficient (CCC) and dynamic range (DR) >= 0.9. Test-retest repeatability was high within the same VMI energies and scan conditions (percentage of repeatable features ranging from 74% for SFDE mode at 40 keV and 15 mGy to 86% for DSDE at 190 keV and 15 mGy), while reproducibility varied substantially across different VMI energies and DECTs (percentage of reproducible features ranging from 32.8% for SFDE at 5 mGy comparing 40 with 190 keV to 99.2% for DSDE at 15 mGy comparing 40 with 50 keV). No major differences were observed between the two radiation doses (<10%) in all pair-wise comparisons. In vivo, machine learning classification using penalized regression and random forests resulted in the best discrimination of hemangiomas and metastases at low-energy VMI (40 keV), and for cysts at high-energy VMI (120 keV). Feature selection based on feature repeatability did not improve classification performance. Our results demonstrate the high repeatability of radiomics features when keeping scan and reconstruction conditions constant. Reproducibility diminished when using different VMI energies or DECT approaches. The choice of optimal VMI energy improved lesion classification in vivo and should hence be adapted to the specific task