Thrombus imaging in acute stroke: correlation of thrombus length on susceptibility-weighted imaging with endovascular reperfusion success

OBJECTIVES Susceptibility-weighted imaging (SWI) enables visualization of thrombotic material in acute ischemic stroke. We aimed to validate the accuracy of thrombus depiction on SWI compared to time-of-flight MRA (TOF-MRA), first-pass gadolinium-enhanced MRA (GE-MRA) and digital subtraction angiography (DSA). Furthermore, we analysed the impact of thrombus length on reperfusion success with endovascular therapy. METHODS Consecutive patients with acute ischemic stroke due to middle cerebral artery (MCA) occlusions undergoing endovascular recanalization were screened. Only patients with a pretreatment SWI were included. Thrombus visibility and location on SWI were compared to those on TOF-MRA, GE-MRA and DSA. The association between thrombus length on SWI and reperfusion success was studied. RESULTS Eighty-four of the 88 patients included (95.5 %) showed an MCA thrombus on SWI. Strong correlations between thrombus location on SWI and that on TOF-MRA (Pearson's correlation coefficient 0.918, P < 0.001), GE-MRA (0.887, P < 0.001) and DSA (0.841, P < 0.001) were observed. Successful reperfusion was not significantly related to thrombus length on SWI (P = 0.153; binary logistic regression). CONCLUSIONS In MCA occlusion thrombus location as seen on SWI correlates well with angiographic findings. In contrast to intravenous thrombolysis, thrombus length appears to have no impact on reperfusion success of endovascular therapy. KEY POINTS • SWI helps in assessing location and length of thrombi in the MCA • SWI, MRA and DSA are equivalent in detecting the MCA occlusion site • SWI is superior in identifying the distal end of the thrombus • Stent retrievers should be deployed over the distal thrombus end • Thrombus length did not affect success of endovascular reperfusion guided by SWI.

Leptomeningeal collateralization in acute ischemic stroke: Impact on prominent cortical veins in susceptibility-weighted imaging.

BACKGROUND The extent of hypoperfusion is an important prognostic factor in acute ischemic stroke. Previous studies have postulated that the extent of prominent cortical veins (PCV) on susceptibility-weighted imaging (SWI) reflects the extent of hypoperfusion. Our aim was to investigate, whether there is an association between PCV and the grade of leptomeningeal arterial collateralization in acute ischemic stroke. In addition, we analyzed the correlation between SWI and perfusion-MRI findings. METHODS 33 patients with acute ischemic stroke due to a thromboembolic M1-segment occlusion underwent MRI followed by digital subtraction angiography (DSA) and were subdivided into two groups with very good to good and moderate to no leptomeningeal collaterals according to the DSA. The extent of PCV on SWI, diffusion restriction (DR) on diffusion-weighted imaging (DWI) and prolonged mean transit time (MTT) on perfusion-imaging were graded according to the Alberta Stroke Program Early CT Score (ASPECTS). The National Institutes of Health Stroke Scale (NIHSS) scores at admission and the time between symptom onset and MRI were documented. RESULTS 20 patients showed very good to good and 13 patients poor to no collateralization. PCV-ASPECTS was significantly higher for cases with good leptomeningeal collaterals versus those with poor leptomeningeal collaterals (mean 4.1 versus 2.69; p=0.039). MTT-ASPECTS was significantly lower than PCV-ASPECTS in all 33 patients (mean 1.0 versus 3.5; p<0.00). CONCLUSIONS In our small study the grade of leptomeningeal collateralization correlates with the extent of PCV in SWI in acute ischemic stroke, due to the deoxyhemoglobin to oxyhemoglobin ratio. Consequently, extensive PCV correlate with poor leptomeningeal collateralization while less pronounced PCV correlate with good leptomeningeal collateralization. Further SWI is a very helpful tool in detecting tissue at risk but cannot replace PWI since MTT detects significantly more ill-perfused areas than SWI, especially in good collateralized subjects.

Focal hemodynamic patterns of status epilepticus detected by susceptibility weighted imaging (SWI).

OBJECTIVE To investigate pathological findings in the susceptibility weighted imaging (SWI) of patients experiencing convulsive (CSE) or non-convulsive status epilepticus (NCSE) with focal hyperperfusion in the acute setting. METHODS Twelve patients (six with NCSE confirmed by electroencephalogram (EEG) and six patients with CSE with seizure event clinically diagnosed) underwent MRI in this acute setting (mean time between onset of symptoms and MRI was 3 h 8 min), including SWI, dynamic susceptibility contrast MR imaging (DSC) and diffusion-weighted imaging (DWI). MRI sequences were retrospectively evaluated and compared with EEG findings (10/12 patients), and clinical symptoms. RESULTS Twelve out of 12 (100 %) patients showed a focal parenchymal area with pseudo-narrowed cortical veins on SWI, associated with focal hyperperfused areas (increased cerebral blood flow (CBF) and mean transit time (MTT) shortening), and cortical DWI restriction in 6/12 patients (50 %). Additionally, these areas were associated with ictal or postical EEG patterns in 8/10 patients (80 %). Most frequent acute clinical findings were aphasia and/or hemiparesis in eight patients, and all of them showed pseudo-narrowed veins in those parenchymal areas responsible for these symptoms. CONCLUSION In this study series with CSE and NCSE patients, SWI showed focally pseudo-narrowed cortical veins in hyperperfused and ictal parenchymal areas. Therefore, SWI might have the potential to identify an ictal region in CSE/NCSE. KEY POINTS • The focal ictal brain regions show hyperperfusion in DSC MR-perfusion imaging. • SWI shows focally diminished cortical veins in hyperperfused ictal regions. • SWI has the potential to identify a focal ictal region in CSE/NCSE.

The IFNL3/4 ΔG variant increases susceptibility to cytomegalovirus retinitis among HIV-infected patients.

BACKGROUND Cytomegalovirus (CMV) retinitis is a major cause of visual impairment and blindness among patients with uncontrolled HIV infections. Whereas polymorphisms in interferon-lambda 3 (IFNL3, previously named IL28B) strongly influence the clinical course of hepatitis C, few studies examined the role of such polymorphisms in infections due to viruses other than hepatitis C virus. OBJECTIVES To analyze the association of newly identified IFNL3/4 variant rs368234815 with susceptibility to CMV-associated retinitis in a cohort of HIV-infected patients. DESIGN AND METHODS This retrospective longitudinal study included 4884 white patients from the Swiss HIV Cohort Study, among whom 1134 were at risk to develop CMV retinitis (CD4 nadir <100 /μl and positive CMV serology). The association of CMV-associated retinitis with rs368234815 was assessed by cumulative incidence curves and multivariate Cox regression models, using the estimated date of HIV infection as a starting point, with censoring at death and/or lost follow-up. RESULTS A total of 40 individuals among 1134 patients at risk developed CMV retinitis. The minor allele of rs368234815 was associated with a higher risk of CMV retinitis (log-rank test P = 0.007, recessive mode of inheritance). The association was still significant in a multivariate Cox regression model (hazard ratio 2.31, 95% confidence interval 1.09-4.92, P = 0.03), after adjustment for CD4 nadir and slope, HAART and HIV-risk groups. CONCLUSION We reported for the first time an association between an IFNL3/4 polymorphism and susceptibility to AIDS-related CMV retinitis. IFNL3/4 may influence immunity against viruses other than HCV.

IL1B and DEFB1 Polymorphisms Increase Susceptibility to Invasive Mold Infection After Solid Organ Transplantation.

BACKGROUND  Single nucleotide polymorphisms (SNPs) in immune genes have been associated with susceptibility to invasive mold infection (IMI) among hematopoietic stem cell (HSCT) but not solid organ transplant (SOT) recipients. METHODS  24 SNPs from systematically selected genes were genotyped among 1101 SOT recipients (715 kidneys, 190 liver, 102 lungs, 79 hearts, 15 other) from the Swiss Transplant Cohort Study. Association between SNPs and the endpoint were assessed by log-rank test and Cox regression models. Cytokine production upon Aspergillus stimulation was measured by ELISA in PBMCs from healthy volunteers and correlated with relevant genotypes. RESULTS  Mold colonization (N=45) and proven/probable IMI (N=26) were associated with polymorphisms in interleukin-1 beta (IL1B, rs16944; log-rank test, recessive mode, colonization P=0.001 and IMI P=0.00005), interleukin-1 receptor antagonist (IL1RN, rs419598; P=0.01 and P=0.02) and β-defensin-1 (DEFB1, rs1800972; P=0.001 and P=0.0002, respectively). The associations with IL1B and DEFB1 remained significant in a multivariate regression model (IL1B rs16944 P=0.002; DEFB1 rs1800972 P=0.01). Presence of two copies of the rare allele of rs16944 or rs419598 was associated with reduced Aspergillus-induced IL-1β and TNFα secretion by PBMCs. CONCLUSIONS  Functional polymorphisms in IL1B and DEFB1 influence susceptibility to mold infection in SOT recipients. This observation may contribute to individual risk stratification.

The value of susceptibility-weighted imaging (SWI) in patients with non-neonatal hypoxic-ischemic encephalopathy

OBJECTIVE In susceptibility-weighted imaging (SWI) in the normal brain, cortical veins appear hypointense due to paramagnetic properties of deoxy-hemoglobin. Global cerebral anoxia decreases cerebral oxygen metabolism, thereby increasing oxy-hemoglobin levels in cerebral veins. We hypothesized that a lower cerebral oxygen extraction fraction in comatose patients with non-neonatal hypoxic ischemic encephalopathy (IHE) produce a pattern of global rarefied or pseudo-diminished cortical veins due to higher oxy-hemoglobin. PURPOSE 1. To investigate the topographic relationship between susceptibility effects in cortical veins and related diffusion restrictions on diffusion-weighted imaging (DWI) in patients with IHE. 2. To relate imaging findings to patterns of altered resting activity on surface EEG. METHODS Twenty-three IHE patients underwent MRI. EEG patterns were used to classify the depth of coma. Regional vs. global susceptibility changes on SWI and patterns of DWI restrictions were compared with the depth of coma. RESULTS All patients exhibited areas of restricted cortical diffusion and SWI abnormalities. The dominant DWI restrictions encompassed widespread areas along the precuneus, frontal and parietal association cortices and basal ganglia. For SWI, nineteen patients had generalized bi-hemispherical patterns, the EEG patterns correlated with coma grades III to V. Four patients had focal decreases of deoxy-hemoglobin following DWI restrictions; associated with normal EEGs. CONCLUSION Focal patterns of diamagnetic effects on SWI according to relative decreases in deoxy-hemoglobin due to reduced metabolic demand are associated with normal EEG in IHE patients. Global patterns indicated increased depth of coma and widespread cortical damage. CLINICAL RELEVANCE The results indicate a potential diagnostic value of SWI in patients with IHE.

Personality, risky health behavior, and perceived susceptibility to health risks

We examined the relations between personality (Five-Factor Model), risky health behaviours, and perceptions of susceptibility to health risks among 683 university students. The hypothesis was that personality would affect perceptions of susceptibility to health risks in two ways: directly, irrespective of risky health behaviours, and indirectly, through the effects of personality on risky health behaviours. The students were surveyed about smoking, being drunk, drunk driving, risky sexual behaviour, and perceptions of susceptibility to related health risks. In path-analytical models we found the expected direct and indirect effects. The personality dimensions of Agreeableness and Conscientiousness had negative direct effects on perceptions of susceptibility as well as negative indirect effects through risky health behaviours. Neuroticism was the only personality dimension to show positive direct effects on perceptions of susceptibility as well as negative indirect effects.

Prevalence, genetic diversity and antimicrobial susceptibility of Listeria monocytogenes isolated from open-air food markets in Greece

A total of 210 food samples originating from milk products, ready-to-eat salads, raw meat and raw meat products purchased in ten open-air market places in Thessaloniki, Greece, were analyzed for the presence of Listeria monocytogenes. Thirty (14.3%) contained L. monocytogenes with the highest prevalence in raw meat (27.5%), raw meat products (18%) and cheese (8%). The strains were susceptible to 16 antimicrobials as determined by microbroth dilution, except one strain which displayed resistance to tetracycline (MIC > 32 μg/ml). This strain carried the tetracycline resistance gene tet(M). Pulsed-field gel electrophoresis (PFGE) revealed a low genetic diversity among the isolates, irrespective of their origin. This suggests that dominant L. monocytogenes clones are widespread in different food product types in open-air food markets in Greece. The high prevalence of L. monocytogenes in these products indicates that appropriate hygienic measures and periodic bacteriological controls are also necessary in open-air food markets to reduce contamination with food-borne pathogens. Greek specialties made with raw meat and raw milk may contain L. monocytogenes and should not be consumed by persons at risk.

Strain typing and antimicrobial susceptibility of methicillin-resistant coagulase-positive staphylococcal species in dogs and people associated with dogs in Thailand

AIMS This study was to investigate and to characterize methicillin-resistant coagulase-positive staphylococci (MRCoPS) harboring in dogs and people associated with dogs in Thailand. METHODS AND RESULTS Staphylococci were collected from 100 dogs, 100 dog owners, 200 small animal veterinarians and 100 people without pet association. Species of MRCoPS were identified phenotypically and genotypically. Molecular characteristics were determined by multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE) and SCCmec typing, and antimicrobial susceptibility was assayed by broth microdilution and by microarray analysis for resistance genes. Methicillin-resistant Staphylococcus pseudintermedius (MRSP), methicillin-resistant Staphylococcus schleiferi subsp. coagulans (MRSSc) and methicillin-resistant Staphylococcus aureus (MRSA) were isolated from dogs (45, 17 and 1%, respectively), veterinarians (8, 2 and 1·5%, respectively) and dog owners (3, 2 and 0%, respectively). Seventeen sequence types (STs) were identified among 83 MRSP isolates which specifically carried SCCmec V, II-III, ΨSCCmec57395 and three uncharacterized SCCmec types. MRSP ST 45, 68 and novel STs including 169, 178, 181 and 183 were shared among canine and human isolates. Most of MRSA ST398 and MRSSc carried SCCmec type V. The MRCoPS commonly displayed multiple resistances to tested antimicrobials and carried various resistance genes. CONCLUSION Variety of MRCoPS, especially new MRSP clones, distributed in dogs and people in Thailand. SIGNIFICANCE AND IMPACT OF THE STUDY The existence of MRCoPS circulating between dogs and humans in Thailand provides indirect evidence of interspecies transmission and represents a potential public health hazard.

Sex-Specific Differences in Pathogen Susceptibility in Honey Bees (Apis mellifera)

Sex-related differences in susceptibility to pathogens are a common phenomenon in animals. In the eusocial Hymenoptera the two female castes, workers and queens, are diploid and males are haploid. The haploid susceptibility hypothesis predicts that haploid males are more susceptible to pathogen infections compared to females. Here we test this hypothesis using adult male (drone) and female (worker) honey bees (Apis mellifera), inoculated with the gut endoparasite Nosema ceranae and/or black queen cell virus (BQCV). These pathogens were chosen due to previously reported synergistic interactions between Nosema apis and BQCV. Our data do not support synergistic interactions between N. ceranae and BQCV and also suggest that BQCV has limited effect on both drone and worker health, regardless of the infection level. However, the data clearly show that, despite lower levels of N. ceranae spores in drones than in workers, Nosema-infected drones had both a higher mortality and a lower body mass than non-infected drones, across all treatment groups, while the mortality and body mass of worker bees were largely unaffected by N. ceranae infection, suggesting that drones are more susceptible to this pathogen than workers. In conclusion, the data reveal considerable sex-specific differences in pathogen susceptibility in honey bees and highlight the importance of ultimate measures for determining susceptibility, such as mortality and body quality, rather than mere infection levels

Whole-Brain Susceptibility-Weighted Thrombus Imaging in Stroke: Fragmented Thrombi Predict Worse Outcome.

BACKGROUND AND PURPOSE The prevalence and clinical importance of primarily fragmented thrombi in patients with acute ischemic stroke remains elusive. Whole-brain SWI was used to detect multiple thrombus fragments, and their clinical significance was analyzed. MATERIALS AND METHODS Pretreatment SWI was analyzed for the presence of a single intracranial thrombus or multiple intracranial thrombi. Associations with baseline clinical characteristics, complications, and clinical outcome were studied. RESULTS Single intracranial thrombi were detected in 300 (92.6%), and multiple thrombi, in 24 of 324 patients (7.4%). In 23 patients with multiple thrombi, all thrombus fragments were located in the vascular territory distal to the primary occluding thrombus; in 1 patient, thrombi were found both in the anterior and posterior circulation. Only a minority of thrombus fragments were detected on TOF-MRA, first-pass gadolinium-enhanced MRA, or DSA. Patients with multiple intracranial thrombi presented with more severe symptoms (median NIHSS scores, 15 versus 11; P = .014) and larger ischemic areas (median DWI ASPECTS, 5 versus 7; P = .006); good collaterals, rated on DSA, were fewer than those in patients with a single thrombus (21.1% versus 44.2%, P = .051). The presence of multiple thrombi was a predictor of unfavorable outcome at 3 months (P = .040; OR, 0.251; 95% CI, 0.067-0.939). CONCLUSIONS Patients with multiple intracranial thrombus fragments constitute a small subgroup of patients with stroke with a worse outcome than patients with single thrombi.

SIRT2 deficiency modulates macrophage polarization and susceptibility to experimental colitis

BACKGROUND SIRT2 belongs to a highly conserved family of NAD+-dependent deacylases, consisting of seven members (SIRT1-SIRT7), which vary in subcellular localizations and have substrates ranging from histones to transcription factors and enzymes. Recently SIRT2 was revealed to play an important role in inflammation, directly binding, deacetylating, and inhibiting the p65 subunit of NF-κB. METHODS A Sirt2 deficient mouse line (Sirt2-/-) was generated by deleting exons 5-7, encoding part of the SIRT2 deacetylase domain, by homologous recombination. Age- and sex-matched Sirt2-/- and Sirt2+/+ littermate mice were subjected to dextran sulfate sodium (DSS)-induced colitis and analyzed for colitis susceptibility. RESULTS Sirt2-/- mice displayed more severe clinical and histological manifestations after DSS colitis compared to wild type littermates. Notably, under basal condition, Sirt2 deficiency does not affect the basal phenotype and intestinal morphology Sirt2 deficiency, however, affects macrophage polarization, creating a pro-inflammatory milieu in the immune cells compartment. CONCLUSION These data confirm a protective role for SIRT2 against the development of inflammatory processes, pointing out a potential role for this sirtuin as a suppressor of colitis. In fact, SIRT2 deletion promotes inflammatory responses by increasing NF-κB acetylation and by reducing the M2-associated anti-inflammatory pathway. Finally, we speculate that the activation of SIRT2 may be a potential approach for the treatment of inflammatory bowel disease.

Anisotropy of magnetic susceptibility in natural olivine single crystals

Mantle flow dynamics can cause preferential alignment of olivine crystals that results in anisotropy of physical properties. To interpret anisotropy in mantle rocks, it is necessary to understand the anisotropy of olivine single crystals. We determined anisotropy of magnetic susceptibility (AMS) for natural olivine crystals. High-field AMS allows for the isolation of the anisotropy due to olivine alone. The orientations of the principal susceptibility axes are related to the olivine’s crystallographic structure as soon as it contains >3 wt % FeO. The maximum susceptibility is parallel to the c axis both at room temperature (RT) and at 77 K. The orientation of the minimum axis at RT depends on iron content; it is generally parallel to the a axis in crystals with 3–5 wt % FeO, and along b in samples with 6–10 wt % FeO. The AMS ellipsoid is prolate and the standard deviatoric susceptibility, k0, is on the order of 8*10210 m3/kg for the samples with <1wt % FeO, and ranges from 3.1*1029 m3/kg to 5.7*1029 m3/kg for samples with 3–10 wt % FeO. At 77 K, the minimum susceptibility is along b, independent of iron content. The shape of the AMS ellipsoid is prolate for samples with <5 wt % FeO, but can be prolate or oblate for higher iron content. The degree of anisotropy increases at 77 K with p0 7757.160.5. The results from this study will allow AMS fabrics to be used as a proxy for olivine texture in ultramafic rocks with high olivine content.