Small vessel disease in primary familial brain calcification with novel truncating PDGFB variants.

INTRODUCTION: Primary familial brain calcification (PFBC) is a neurodegenerative disease characterised by bilateral calcification in the brain, especially in the basal ganglia, leading to neurological and neuropsychiatric manifestations. White matter hyperintensities (WMH) have been described in patients with PFBC and pathogenic variants in the gene for platelet-derived growth factor beta polypeptide (PDGFB), suggesting a manifest cerebrovascular process. We present below the cases of two PFBC families with PDGFB variants and stroke or transient ischaemic attack (TIA) episodes. We examine the possible correlation between PFBC and vascular events as stroke/TIA, and evaluate whether signs for vascular disease in this condition are systemic or limited to the cerebral vessels. MATERIAL AND METHODS: Two Swedish families with novel truncating PDGFB variants, p.Gln140* and p.Arg191*, are described clinically and radiologically. Subcutaneous capillary vessels in affected and unaffected family members were examined by light and electron microscopy. RESULTS: All mutation carriers showed WMH and bilateral brain calcifications. The clinical presentations differed, with movement disorder symptoms dominating in family A, and psychiatric symptoms in family B. However, affected members of both families had stroke, TIA, and/or asymptomatic intracerebral ischaemic lesions. Only one of the patients had classical vascular risk factors. Skin microvasculature was normal. CONCLUSIONS: Patients with these PDGFB variants develop microvascular changes in the brain, but not the skin. PDGFB-related small vessel disease can manifest radiologically as cerebral haemorrhage or ischaemia, and may explain TIA or stroke in patients without other vascular risk factors.

Incidence of intracranial hemorrhagic complications after anterior circulation endovascular thrombectomy in relation to occlusion site: a nationwide observational register study.

BACKGROUND: Intracranial hemorrhage (ICH) is a potentially severe complication of endovascular thrombectomy (EVT). However, the relationship between the incidence and severity of ICH and vascular occlusion location is not well described. OBJECTIVE: To present a comprehensive analysis of subtypes of ICHs and their relationship to the occlusion site following EVT in the anterior circulation. METHODS: All patients with anterior circulation vessel occlusion stroke (internal carotid (ICA) and middle cerebral artery's first (M1) and later segments (M2 and beyond)) registered in the two Swedish national quality registers for stroke care and endovascular therapy during 2015-2020 were included. Hemorrhagic complications identified on imaging within 36 hours post-EVT were classified according to Heidelberg Bleeding Classification and further divided into symptomatic (sICH) or non-symptomatic (non-sICH). RESULTS: Of the 3077 patients, ICH frequency was 24.2%, which included 4.5% sICH. Subarachnoid hemorrhage (SAH) was the most frequent subtype of hemorrhage (10.9%). The hemorrhagic subtypes differed significantly by occlusion site, but the frequency of any bleed did not. EVT performed in and beyond the M2 more often resulted in SAH, frequently classified as non-sICH. EVT performed in the ICA was associated with more severe hemorrhages, such as intraventricular and large parenchymal hematomas, that were more often classified as sICH. CONCLUSION: In this nationwide unselected EVT cohort we found that ICH severity significantly differed between different vessel occlusion sites.

Endovascular thrombectomy for anterior circulation stroke beyond 6 hours of onset in Sweden 2015 to 2020: rates and outcomes in a nationwide register-based study.

BACKGROUND: Endovascular thrombectomy (EVT) for ischemic stroke (IS) beyond 6 hours has been proven effective in randomized controlled trials. We present data on implementation and outcomes for EVT beyond 6 hours in Sweden. METHODS: We included all cases of anterior circulation IS caused by occlusion of the intracranial carotid artery, and the M1 or M2 segment of the middle cerebral artery, registered in two nationwide quality registers for stroke in 2015-2020. Three groups were defined from onset-to-groin-puncture (OTG) time: early window (<6 hours), late window (6-24 hours) known onset, late window last seen well (LSW). Favorable outcome (modified Rankin Scale (mRS) 0-2) and all-cause mortality at 90 days were the main outcomes, and symptomatic intracerebral hemorrhage (sICH) was the safety outcome. RESULTS: Late window EVT increased from 0.3% of all IS in 2015 to 1.8% in 2020, and from 17.4% of all anterior circulation EVTs in 2015 to 32.9% in 2020. Of 2199 patients, 76.9% (n=1690) were early window EVTs and 23.1% late window EVTs (n=509; 141 known onset, 368 LSW). Median age was 73 years, and 46.2% were female, with no differences between groups. Favorable outcome did not differ between groups (early window 42.4%, late window known onset 38.9%, late window LSW 37.3% (p=0.737)) and remained similar when adjusted for baseline differences. sICH rates did not differ (early window 4.0%, late window known onset 2.1%, late window LSW 4.9% (p=0.413)). CONCLUSION: Late window EVTs have increased substantially over time, and currently account for one third of anterior circulation treatments. Early and late window patients had similar outcomes.

Accuracy of automated intracerebral hemorrhage volume measurement on non-contrast computed tomography: a Swedish Stroke Register cohort study.

PURPOSE: Hematoma volume is the strongest predictor of patient outcome after intracerebral hemorrhage (ICH). The aim of this study was to validate novel fully automated software for quantification of ICH volume on non-contrast computed tomography (CT). METHODS: The population was defined from the Swedish Stroke Register (RS) and included all patients with an ICH diagnosis during 2016-2019 in Region Skåne. Hemorrhage volume on their initial head CT was measured using ABC/2 and manual segmentation (Sectra IDS7 volume measurement tool) and the automated volume quantification tool (qER-NCCT) by Qure.ai. The first 500 were examined by two independent readers. RESULTS: A total of 1649 ICH patients were included. The qER-NCCT had 97% sensitivity in identifying ICH. In total, there was excellent agreement between volumetric measurements of ICH volumes by qER-NCCT and manual segmentation by interclass correlation (ICC = 0.96), and good agreement (ICC = 0.86) between qER-NCCT and ABC/2 method. The qER-NCCT showed volume underestimation, mainly in large (> 30 ml) heterogenous hemorrhages. Interrater agreement by (ICC) was 0.996 (95% CI: 0.99-1.00) for manual segmentation. CONCLUSION: Our study showed excellent agreement in volume quantification between the fully automated software qER-NCCT and manual segmentation of ICH on NCCT. The qER-NCCT would be an important additive tool by aiding in early diagnostics and prognostication for patients with ICH and in provide volumetry on a population-wide level. Further refinement of the software should address the underestimation of ICH volume seen in a portion of large, heterogenous, irregularly shaped ICHs.

Radiomics-Derived Brain Age Predicts Functional Outcome After Acute Ischemic Stroke.

BACKGROUND AND OBJECTIVES: While chronological age is one of the most influential determinants of poststroke outcomes, little is known of the impact of neuroimaging-derived biological "brain age." We hypothesized that radiomics analyses of T2-FLAIR images texture would provide brain age estimates and that advanced brain age of patients with stroke will be associated with cardiovascular risk factors and worse functional outcomes. METHODS: We extracted radiomics from T2-FLAIR images acquired during acute stroke clinical evaluation. Brain age was determined from brain parenchyma radiomics using an ElasticNet linear regression model. Subsequently, relative brain age (RBA), which expresses brain age in comparison with chronological age-matched peers, was estimated. Finally, we built a linear regression model of RBA using clinical cardiovascular characteristics as inputs and a logistic regression model of favorable functional outcomes taking RBA as input. RESULTS: We reviewed 4,163 patients from a large multisite ischemic stroke cohort (mean age = 62.8 years, 42.0% female patients). T2-FLAIR radiomics predicted chronological ages (mean absolute error = 6.9 years, r = 0.81). After adjustment for covariates, RBA was higher and therefore described older-appearing brains in patients with hypertension, diabetes mellitus, a history of smoking, and a history of a prior stroke. In multivariate analyses, age, RBA, NIHSS, and a history of prior stroke were all significantly associated with functional outcome (respective adjusted odds ratios: 0.58, 0.76, 0.48, 0.55; all p-values < 0.001). Moreover, the negative effect of RBA on outcome was especially pronounced in minor strokes. DISCUSSION: T2-FLAIR radiomics can be used to predict brain age and derive RBA. Older-appearing brains, characterized by a higher RBA, reflect cardiovascular risk factor accumulation and are linked to worse outcomes after stroke.

Swedish trial on embolization of middle meningeal artery versus surgical evacuation in chronic subdural hematoma (SWEMMA)-a national 12-month multi-center randomized controlled superiority trial with parallel group assignment, open treatment allocation and blinded clinical outcome assessment.

BACKGROUND: Chronic subdural hematoma (cSDH) is one of the most common neurosurgical disorders and the incidence is rising. The routine treatment is neurosurgical hematoma evacuation, which is associated with recurrence rates up to 10-25%. In recent years, endovascular embolization of the middle meningeal artery (eMMA) has garnered much attention due to recurrence rates as low as < 5%. Several randomized controlled trials are planned or ongoing. In most of these trials, conventional neurosurgical treatment with or without adjunctive endovascular embolization is compared. The proposed trial aims to conduct a head-to-head comparison between neurosurgical and endovascular treatment as stand-alone treatments. METHODS: The trial is academically driven and funded within existing public healthcare systems and infrastructure. Patients with uni- or bilateral cSDH, presenting with mild-to moderate symptoms, and admitted to neurosurgery on clinical grounds will be offered participation. Subjects are randomized 1:1 between conventional neurosurgical treatment (control) and endovascular embolization of the middle meningeal artery (intervention). Primary endpoint is reoperation due to clinically and/or radiologically significant recurrence within 3 months. Secondary endpoints include safety, technical success rate, neurological disability, and quality of life. DISCUSSION: There are mounting retrospective data suggesting eMMA, as sole treatment or as an adjunctive to neurosurgery for cSDH, is safe and effective with a reoperation rate lower than neurosurgical hematoma evacuation alone. If randomized controlled trials confirm these findings, there is a potential for a paradigm shift in the treatment of cSDH where a minimally invasive procedure can replace open surgery in a large and oftentimes old and fragile patient cohort. TRIAL REGISTRATION: ClinicalTrials.gov, ClinicalTrials.gov Identifier NCT05267184 . Registered March 4, 2022.

Sub-micrometer morphology of human atherosclerotic plaque revealed by synchrotron radiation-based µCT-A comparison with histology.

Histology is a long standing and well-established gold standard for pathological characterizations. In recent years however, synchrotron radiation-based micro-computed tomography (SRµCT) has become a tool for extending the imaging of two-dimensional thin sections into three-dimensional imaging of tissue blocks, enabling so-called virtual histology with arbitrary clipping planes, volumetric rendering and automatic segmentation. In this study, we present a thorough characterization of human carotid plaques after endarterectomy of patients with stroke or transient ischemic attack (TIA), investigating several different pathologic structures using both SRµCT and histology. Phase-contrast SRµCT was performed with two different magnifications (voxel sizes 6.5 µm and 0.65 µm, respectively), and histology was performed with multiple different stainings (Alpha-actin, Glycophorin A, von Kossa, Movat, CD68). The 0.65 µm high-resolution SRµCT was performed on selected areas with plaque typical relevant morphology, identified on the 6.5 µm low-resolution SRµCT. The tomography datasets were reconstructed with additional 3D volume rendering and compared to histology. In total, nine different regions with typical pathologic structures were identified and imaged with high-resolution SRµCT. The results show many characteristics typical for advanced atherosclerotic plaques, clinically relevant, namely ruptures with thrombosis, neo-vascularization, inflammatory infiltrates in shoulder regions, lipid rich necrotic cores (LRNC), thin fibrous cap, calcifications, lumen irregularities, and changes in vessel wall structures such as the internal elastic membrane. This method's non-destructive nature renders details of micro-structures with an excellent visual likeness to histology, with the additional strength of multiplanar and 3D visualization and the possibility of multiple re-scans.

Excessive White Matter Hyperintensity Increases Susceptibility to Poor Functional Outcomes After Acute Ischemic Stroke.

Objective: To personalize the prognostication of post-stroke outcome using MRI-detected cerebrovascular pathology, we sought to investigate the association between the excessive white matter hyperintensity (WMH) burden unaccounted for by the traditional stroke risk profile of individual patients and their long-term functional outcomes after a stroke. Methods: We included 890 patients who survived after an acute ischemic stroke from the MRI-Genetics Interface Exploration (MRI-GENIE) study, for whom data on vascular risk factors (VRFs), including age, sex, atrial fibrillation, diabetes mellitus, hypertension, coronary artery disease, smoking, prior stroke history, as well as acute stroke severity, 3- to-6-month modified Rankin Scale score (mRS), WMH, and brain volumes, were available. We defined the unaccounted WMH (uWMH) burden via modeling of expected WMH burden based on the VRF profile of each individual patient. The association of uWMH and mRS score was analyzed by linear regression analysis. The odds ratios of patients who achieved full functional independence (mRS < 2) in between trichotomized uWMH burden groups were calculated by pair-wise comparisons. Results: The expected WMH volume was estimated with respect to known VRFs. The uWMH burden was associated with a long-term functional outcome (ß = 0.104, p < 0.01). Excessive uWMH burden significantly reduced the odds of achieving full functional independence after a stroke compared to the low and average uWMH burden [OR = 0.4, 95% CI: (0.25, 0.63), p < 0.01 and OR = 0.61, 95% CI: (0.42, 0.87), p < 0.01, respectively]. Conclusion: The excessive amount of uWMH burden unaccounted for by the traditional VRF profile was associated with worse post-stroke functional outcomes. Further studies are needed to evaluate a lifetime brain injury reflected in WMH unrelated to the VRF profile of a patient as an important factor for stroke recovery and a plausible indicator of brain health.

MRI Radiomic Signature of White Matter Hyperintensities Is Associated With Clinical Phenotypes.

OBJECTIVE: Neuroimaging measurements of brain structural integrity are thought to be surrogates for brain health, but precise assessments require dedicated advanced image acquisitions. By means of quantitatively describing conventional images, radiomic analyses hold potential for evaluating brain health. We sought to: (1) evaluate radiomics to assess brain structural integrity by predicting white matter hyperintensities burdens (WMH) and (2) uncover associations between predictive radiomic features and clinical phenotypes. METHODS: We analyzed a multi-site cohort of 4,163 acute ischemic strokes (AIS) patients with T2-FLAIR MR images with total brain and WMH segmentations. Radiomic features were extracted from normal-appearing brain tissue (brain mask-WMH mask). Radiomics-based prediction of personalized WMH burden was done using ElasticNet linear regression. We built a radiomic signature of WMH with stable selected features predictive of WMH burden and then related this signature to clinical variables using canonical correlation analysis (CCA). RESULTS: Radiomic features were predictive of WMH burden (R 2 = 0.855 ± 0.011). Seven pairs of canonical variates (CV) significantly correlated the radiomics signature of WMH and clinical traits with respective canonical correlations of 0.81, 0.65, 0.42, 0.24, 0.20, 0.15, and 0.15 (FDR-corrected p-values CV 1 - 6 < 0.001, p-value CV 7 = 0.012). The clinical CV1 was mainly influenced by age, CV2 by sex, CV3 by history of smoking and diabetes, CV4 by hypertension, CV5 by atrial fibrillation (AF) and diabetes, CV6 by coronary artery disease (CAD), and CV7 by CAD and diabetes. CONCLUSION: Radiomics extracted from T2-FLAIR images of AIS patients capture microstructural damage of the cerebral parenchyma and correlate with clinical phenotypes, suggesting different radiographical textural abnormalities per cardiovascular risk profile. Further research could evaluate radiomics to predict the progression of WMH and for the follow-up of stroke patients' brain health.

White matter hyperintensity burden in acute stroke patients differs by ischemic stroke subtype.

OBJECTIVE: To examine etiologic stroke subtypes and vascular risk factor profiles and their association with white matter hyperintensity (WMH) burden in patients hospitalized for acute ischemic stroke (AIS). METHODS: For the MRI Genetics Interface Exploration (MRI-GENIE) study, we systematically assembled brain imaging and phenotypic data for 3,301 patients with AIS. All cases underwent standardized web tool-based stroke subtyping with the Causative Classification of Ischemic Stroke (CCS). WMH volume (WMHv) was measured on T2 brain MRI scans of 2,529 patients with a fully automated deep-learning trained algorithm. Univariable and multivariable linear mixed-effects modeling was carried out to investigate the relationship of vascular risk factors with WMHv and CCS subtypes. RESULTS: Patients with AIS with large artery atherosclerosis, major cardioembolic stroke, small artery occlusion (SAO), other, and undetermined causes of AIS differed significantly in their vascular risk factor profile (all p < 0.001). Median WMHv in all patients with AIS was 5.86 cm3 (interquartile range 2.18-14.61 cm3) and differed significantly across CCS subtypes (p < 0.0001). In multivariable analysis, age, hypertension, prior stroke, smoking (all p < 0.001), and diabetes mellitus (p = 0.041) were independent predictors of WMHv. When adjusted for confounders, patients with SAO had significantly higher WMHv compared to those with all other stroke subtypes (p < 0.001). CONCLUSION: In this international multicenter, hospital-based cohort of patients with AIS, we demonstrate that vascular risk factor profiles and extent of WMH burden differ by CCS subtype, with the highest lesion burden detected in patients with SAO. These findings further support the small vessel hypothesis of WMH lesions detected on brain MRI of patients with ischemic stroke.

Brain Volume: An Important Determinant of Functional Outcome After Acute Ischemic Stroke.

OBJECTIVE: To determine whether brain volume is associated with functional outcome after acute ischemic stroke (AIS). PATIENTS AND METHODS: This study was conducted between July 1, 2014, and March 16, 2019. We analyzed cross-sectional data of the multisite, international hospital-based MRI-Genetics Interface Exploration study with clinical brain magnetic resonance imaging obtained on admission for index stroke and functional outcome assessment. Poststroke outcome was determined using the modified Rankin Scale score (0-6; 0 = asymptomatic; 6 = death) recorded between 60 and 190 days after stroke. Demographic characteristics and other clinical variables including acute stroke severity (measured as National Institutes of Health Stroke Scale score), vascular risk factors, and etiologic stroke subtypes (Causative Classification of Stroke system) were recorded during index admission. RESULTS: Utilizing the data from 912 patients with AIS (mean ± SD age, 65.3±14.5 years; male, 532 [58.3%]; history of smoking, 519 [56.9%]; hypertension, 595 [65.2%]) in a generalized linear model, brain volume (per 155.1 cm3) was associated with age (ß -0.3 [per 14.4 years]), male sex (ß 1.0), and prior stroke (ß -0.2). In the multivariable outcome model, brain volume was an independent predictor of modified Rankin Scale score (ß -0.233), with reduced odds of worse long-term functional outcomes (odds ratio, 0.8; 95% CI, 0.7-0.9) in those with larger brain volumes. CONCLUSION: Larger brain volume quantified on clinical magnetic resonance imaging of patients with AIS at the time of stroke purports a protective mechanism. The role of brain volume as a prognostic, protective biomarker has the potential to forge new areas of research and advance current knowledge of the mechanisms of poststroke recovery.

Comparing Arterial- and Venous-Phase Acquisition for Optimization of Virtual Noncontrast Images From Dual-Energy Computed Tomography Angiography.

BACKGROUND: Follow-up with computed tomographic angiography is recommended after endovascular aneurysm repair, exposing patients to significant levels of radiation and iodine contrast medium. Dual-energy computed tomography allows virtual noncontrast (VNC) images to be reconstructed from contrast-enhanced images using a software algorithm. If the VNC images are a good-enough approximation of true noncontrast (TNC) images, a reduction in radiation dose can be ensured through omitting a TNC scan. PURPOSE: To compare image quality of VNC images reconstructed from arterial phase and venous phase dual-energy computed tomographic angiography to TNC images and to assess which one is more suitable to replace TNC images. METHODS: Sixty-three consecutive patients were examined using a dual-energy computed tomography as elective follow-up after endovascular aneurysm repair. The examination protocol included 1 unenhanced and 2 contrast-enhanced scans (80 kV/Sn140 kV) of the aorta. Virtual noncontrast data sets were reconstructed from the arterial (A-VNC) and venous (V-VNC) phase scans, respectively. Mean attenuation and image noise were measured for TNC, A-VNC, and V-VNC images within regions of interest at 2 levels in the aorta, the liver, retroperitoneal fat, and psoas muscle. Subjective image quality was assessed on a 4-point scale by 2 blinded readers. RESULTS: The differences between A-VNC and TNC, and between A-VNC and V-VNC, were substantial aorta at the level of diaphragm and aorta at the level of renal arteries. The difference between V-VNC and TNC was, on the other hand, very small and not statistically significant for the renal artery aorta. For liver, fat, and muscle tissue, there were significant differences between both A-VNC and V-VNC compared with TNC, but findings were similar between A-VNC and V-VNC. CONCLUSIONS: Virtual noncontrast images based on venous-phase scans appear to be a more accurate representation of TNC scans than VNC images based on arterial-phase scans.

Postoperative CT Evaluation After EVAR: A Comparison of Image Assessment.

PURPOSE: To compare the postoperative computed tomography angiography (CTA) assessment made by vascular surgeons and interventional radiologists after endovascular aneurysm repair (EVAR) at a tertiary vascular clinic to an outside core review facility. METHODS: One hundred patients (mean age 78.7 years, range 88-55; 84 men) with consecutive, elective, routine CTA controls after EVAR were retrospectively studied. Consultant vascular surgeons or radiologists had evaluated all original scans and written the original report. All scans were then reevaluated by an independent core clinic. Findings were classified as vascular or extravascular and stratified as clinically significant or clinically nonsignificant by an independent external reviewer. RESULTS: The number of vascular findings detected by the vascular clinic was 72 vs 69 by the core clinic. The vascular clinic reported more clinically significant findings (primarily stent compression or kinks) as well as endoleaks and their origin. The core clinic reported more pseudoaneurysms (24 vs 12). None of the patients with puncture complications needed reintervention. Interrater analysis of all findings between the 2 clinics showed good agreement when comparing endoleaks overall (without subclassification) and moderate agreement when assessing aneurysm growth. The core clinic reported extravascular findings in 58 patients; 37 of these were classified as clinically significant. The vascular clinic reported extravascular findings in 23 patients; 7 of these were clinically significant. The core clinic also reported 2 cases of suspected malignancies, which had not been reported by the vascular clinic. CONCLUSION: During routine CTA follow-up after EVAR, a significant number of vascular and nonvascular findings are detected. Whereas a highly dedicated vascular clinic identifies most vascular findings regardless of the specialty of the reader, some extravascular findings are missed. However, the frequency of clinically significant findings or findings that might warrant reintervention was low in this study.

80-kVp CT angiography for endovascular aneurysm repair follow-up with halved contrast medium dose and preserved diagnostic quality.

BACKGROUND: Follow-up of endovascular aneurysm repair (EVAR) with life-long computed tomography angiography (CTA) surveillance exposes patients with impaired renal function to repeated risks of contrast medium-induced nephropathy (CIN). PURPOSE: To retrospectively compare vascular attenuation, image noise, contrast-to-noise ratio (CNR), subjective image quality and effective radiation dose (mSv) for CTA with a 16-multirow detector CT (MDCT) equipment at 80 kVp after EVAR using a contrast medium (CM) dose that is half of that used at 120 kVp. MATERIAL AND METHODS: Forty patients with estimated glomerular filtration rate (eGFR) <45 mL/min underwent 80-kVp CTA with 160 mg I/kg, and 40 patients with eGFR ≥45 mL/min 120-kVp CTA with 320 mg I/kg (maximum dose weight, 80 kg). Arterial phase analysis included vascular attenuation, image noise and CNR, and calculated effective dose. Subjective image quality was assessed on a 4-point scale by two blinded readers at three different levels as well as overall. RESULTS: Median values in the 80/120 kVp cohorts were: age, 74-75 years; body weight, 77/80 kg; BMI 24/27 kg/m(2); CM dose, 13/25 gram-iodine; gram-iodine/GFR ratio, 0.35/0.38; mean aortic attenuation, 313/326 HU; image noise, 26/32 HU; CNR 10-11; subjective image quality score, 3.0-3.5 (Reader 1) and 3.0-3.3 (Reader 2); number of non-diagnostic examinations, 0/1; and effective dose, 4.5/5.1 mSv. There was no statistically significant difference in aortic CNR and effective dose between the 80 and 120 kVp cohorts. CONCLUSION: 80 kVp 16-MDCT with halved CM dose tailored to body weight for CTA follow-up of EVAR may provide satisfactory diagnostic results compared to common standards and be beneficial for patients at risk of CIN, though the present CT equipment may limit the use of the method to patients below 90 kg or with a BMI below 35 kg/m(2).

Treatment of mesenteric vein thrombosis with transjugular mechanical thrombectomy and subsequent simultaneous arterial and venous thrombolysis.

Mesenteric vein thrombosis may induce intestinal ischemia and gangrene. In severe cases, it is necessary to restore venous outflow from the small intestine rapidly. We describe a severe case of mesenteric vein thrombosis that was resolved successfully by mechanical thrombectomy from a transjugular approach followed by selective simultaneous venous and arterial thrombolysis via the superior mesenteric vein and artery. In conclusion, the transjugular intrahepatic portosystemic approach was a feasible and safe access for mechanical thrombectomy and thrombolysis of the mesenteric vein in our patient.

Cystatins--Extra- and intracellular cysteine protease inhibitors: High-level secretion and uptake of cystatin C in human neuroblastoma cells.

Cystatins are present in mammals, birds, fish, insects, plants, fungi and protozoa and constitute a large protein family, with most members sharing a cysteine protease inhibitory function. In humans 12 functional cystatins exist, forming three groups based on molecular organisation and distribution in the organism. The type 1 cystatins (A and B) are known as intracellular, type 2 cystatins (C, D, E/M, F, G, S, SN and SA) extracellular and type 3 cystatins (L- and H-kininogen) intravascular proteins. The present paper is focused on the human cystatins and especially those of type 2, which are directed (with signal peptides) for cellular export following translation. Results indicating existence of systems for significant internalisation of type 2 cystatins from the extracellular to intracellular compartments are reviewed. Data showing that human neuroblastoma cell lines generally secrete high levels, but also contain high amounts of cystatin C are presented. Culturing of these cells in medium containing cystatin C at concentrations found in body fluids resulted in increased intracellular cystatin C, as a result of an uptake process. At immunofluorescence cytochemistry a pronounced vesicular cystatin C staining was observed. The simplistic denotation of the type 2 cystatins as extracellular inhibitors is thus challenged, and possible biological functions of the internalised cystatins are discussed. To illustrate the special case of high cellular cystatin content seen in cells of patients with hereditary cystatin C amyloid angiopathy, expression vectors for wild-type and L68Q mutated cystatin C were used to transfect SK-N-BE(2) cells. Clones overexpressing the two variants showed increased secreted levels of cystatin C. Within the cells the L68Q variant appeared to mainly localise to the endoplasmic reticulum rather than to acidic vesicular organelles, indicating limitations in the transport out from the cell rather than increased uptake as explanation for the elevated cellular cystatin levels seen in hereditary cystatin C amyloid angiopathy.

FDG-accumulating atherosclerotic plaques identified with 18F-FDG-PET/CT in 141 patients.

PURPOSE: The aim of this study was to describe the prevalence of atherosclerotic plaques based on [(18)F]-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in a large population characterized by high risk of cardiovascular disease. PROCEDURES: One hundred forty-one patients referred to our department for FDG-PET/CT for suspected lung cancer were re-evaluated for atherosclerotic lesions. Cardiovascular risk factors were analyzed based on patient records. RESULTS: Forty-two percent of the patients had three cardiovascular risk factors or more. Nine percent of all plaques were assessed as active FDG-accumulating plaques, 88% were inactive calcified plaques, and 2% were mixed. The abdominal aorta was the vessel with the highest plaque count. Patients with one risk factor had significantly less active and inactive plaques. CONCLUSIONS: The observed association between the numbers of cardiovascular risk factors and the numbers of FDG-accumulating plaques as well as calcified plaques further supports the validity and value of FDG-PET/CT in the non-invasive identification and characterization of atherosclerotic disease.

Time-to-time correlation of high-risk atherosclerotic lesions identified with [(18)F]-FDG-PET/CT.

OBJECTIVE: It has been shown that [(18)F]-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) can identify macrophage-rich high-risk atherosclerotic plaques in animal models as well as in patients with atherosclerotic plaques in the carotid arteries. The development of inflamed macrophage-rich plaques over time is not well known. This study was performed to determine the variability of such FDG-accumulating plaques between consecutive PET/CT examinations. METHODS: Twenty-eight patients who underwent two whole-body FDG-PET/CT examinations within 7 months for malignant diseases were re-evaluated for atherosclerotic lesions in major arterial segments. The plaques were identified as active, inactive, or mixed depending on their appearance on PET and CT. Every identified plaque was compared with that of the other examination to evaluate the time-to-time correlation. RESULTS: The time-to-time correlation was close to 100% for calcified inactive plaques and about 50% for FDG-accumulating active plaques, with a high consistency between all examined arterial segments in this material. CONCLUSIONS: A large proportion of FDG-accumulating plaques can be identified on consecutive FDG-PET/CT examinations within 7 months.

High 18F-FDG Uptake in synthetic aortic vascular grafts on PET/CT in symptomatic and asymptomatic patients.

UNLABELLED: Graft infection is a serious complication to vascular surgery. The aim of this study was to assess (18)F-FDG uptake in vascular grafts in patients with or without symptoms of graft infection. METHODS: In all 2,045 patients examined by PET/CT at our clinic, 16 patients with synthetic aortic grafts were identified and reevaluated for (18)F-FDG accumulation. Clinical and biochemical data were obtained from patient records. RESULTS: High (18)F-FDG uptake was found in 10 of 12 grafts in the patients who underwent open surgery and in 1 of 4 grafts in patients who underwent endovascular aneurysm repair. On the basis of biochemical and clinical data, it was concluded that 1 of the 16 patients had a graft infection at the time of investigation. CONCLUSION: (18)F-FDG uptake in vascular grafts was found in the vast majority of patients without graft infection. The risk of a false-positive diagnosis of graft infection by (18)F-FDG PET/CT is evident.

Cystatin C uptake in the eye.

BACKGROUND: As a secreted protein, cystatin C is assumed to play its role in the extracellular compartment, where it can inhibit virtually all cysteine proteases of families C1 (cathepsin B, L, S) and C13 (mammalian legumain-related proteases). Since many of its potential target enzymes in the eye reside in intracellular compartments, we sought evidence for a cellular uptake of the inhibitor in ocular tissues. METHODS: Fluorescence-labeled human cystatin C was injected intravitreally into normal rat eyes. Ocular tissues were subsequently examined using ELISA, fluorescence microscopy, and immunohistochemistry. Cystatin C uptake was additionally studied in an in vitro retina model. RESULTS: Cystatin C administered intravitreally in vivo is taken up into cells of the corneal endothelium and epithelium, the epithelial cells lining the ciliary processes, and into cells in the neuroretina (mostly ganglion cells) and the retinal pigment epithelium. The uptake is demonstrable also in vitro and was, in the neuroretina, found to be a high-affinity system, inhibited by cooling the specimens or by adding the microfilament polymerization inhibitor, cytochalasin D, to the medium. CONCLUSIONS: There is an active, temperature-dependent uptake system for cystatin C into several cell types in the cornea, ciliary body, and retina. The cell types that take up cystatin C are generally the same that contain endogenous cystatin C, suggesting that much or all cystatin C seen intracellularly in the normal eye may have been taken up from the surrounding extracellular space. The uptake indicates that the inhibitor may exert biological functions in intracellular compartments. It is also possible that this uptake system may regulate the extracellular levels of cystatin C in the eye.