Nanoparticles (MIPs) specifically detect and target senescent cells by binding to a surface protein, showing also specificity in vivo.

BackgroundThousands of air bubbles enter the cerebral circulation during cardiac surgery, but whether high numbers of bubbles explain post-operative cognitive decline is currently controversial. This study estimates the size distribution of air bubbles and volume of air entering the cerebral arteries intra-operatively based on analysis of transcranial Doppler ultrasound data.MethodsTranscranial Doppler ultrasound recordings from ten patients undergoing heart surgery were analysed for the presence of embolic signals. The backscattered intensity of each embolic signal was modelled based on ultrasound scattering theory to provide an estimate of bubble diameter. The impact of showers of bubbles on cerebral blood-flow was then investigated using patient-specific Monte-Carlo simulations to model the accumulation and clearance of bubbles within a model vasculature.ResultsAnalysis of Doppler ultrasound recordings revealed a minimum of 371 and maximum of 6476 bubbles entering the middle cerebral artery territories during surgery. This was estimated to correspond to a total volume of air ranging between 0.003 and 0.12 mL. Based on analysis of a total of 18667 embolic signals, the median diameter of bubbles entering the cerebral arteries was 33 μm (IQR: 18 to 69 μm). Although bubble diameters ranged from ~5 μm to 3.5 mm, the majority (85%) were less than 100 μm. Numerous small bubbles detected during cardiopulmonary bypass were estimated by Monte-Carlo simulation to be benign. However, during weaning from bypass, showers containing large macro-bubbles were observed, which were estimated to transiently affect up to 2.2% of arterioles.ConclusionsDetailed analysis of Doppler ultrasound data can be used to provide an estimate of bubble diameter, total volume of air, and the likely impact of embolic showers on cerebral blood flow. Although bubbles are alarmingly numerous during surgery, our simulations suggest that the majority of bubbles are too small to be harmful.

Background and purpose Cerebral microbleeds (CMBs) have been observed using MRI in patients with cardiovascular risk factors, cognitive deterioration, small vessel disease and dementia. They are a well-known consequence of cerebral amyloid angiopathy, chronic hypertension, and diffuse axonal injury, amongst other causes. However, the frequency and location of new CMBs post adult cardiac surgery, in association with cognition and perioperative risk factors, have yet to be studied. Methods Pre- and post-surgery MR susceptibility-weighted images (SWI) and neuropsychological tests were analysed from a total of 75 patients undergoing cardiac surgery (70 men; mean age: 63±10 years). CMBs were identified by a neuroradiologist blinded to clinical details who independently assessed the presence and location of CMBs using standardised criteria. Results New CMBs were identified in 76% of patients after cardiac surgery. The majority of new CMBs were located in the frontal lobe (46%) followed by the parietal lobe (15%), cerebellum (13%), occipital lobe (12%) and temporal lobe (8%). Patients with new CMBs typically began with a higher prevalence of pre-existing CMBs [p=0.02]. New CMBs were associated with longer cardiopulmonary bypass (CPB) times [p=0.003] and there was a borderline association with lower percentage haematocrit [p=0.04]. Logistic regression analysis suggested a ~2% increase in the odds of acquiring new CMBs during cardiac surgery for every minute of bypass time (odds ratio: 1.02; 95% CI, 1.00 – 1.05; p=0.04). Post-operative neuropsychological decline was observed in 44% of patients and appeared to be unrelated to new CMBs. Conclusions New CMBs identified using SWI were found in 76% of patients who underwent cardiac surgery. CMBs were globally distributed with highest numbers in the frontal and parietal lobes. Our regression analysis indicated that length of CPB time and lowered haematocrit may be significant predictors for new CMBs after cardiac surgery. Clinical Trials Registration URL: http://www.isrctn.com/search?q=66022965. Unique ISRCTN identifier: 66022965.

T he relative contributions of chronic cerebrovascular disease and perioperative stressors in generating postoperative cognitive decline after cardiac surgery are currently not well understood. Previous MRI studies of brain injury after cardiac surgery have focused primarily on identifying acute ischemic lesions using diffusion-weighted (DW) MRI. [1][2][3][4][5][6][7][8][9][10][11][12] Acute ischemic changes are visible in 32% to 61% of patients undergoing DW-MRI, 1,13 and new chronic ischemic lesions are found in ≈13% of patients.14 Some studies report an association between the presence, size, or number of new acute lesions and postoperative cognitive decline, 3,9 whereas others do not. 2,7,11,14 Lesions are typically multiple, small, and spherical, whose radiographic appearance is strongly suggestive of embolization. 3,5,7 However, few studies have attempted to quantify the accumulation of new ischemic injuries against a backdrop of chronic preexisting cerebrovascular disease. Because cognitive impairment is often transient, and new lesions can occur without any discernable decline in cognitive function, whether new ischemic lesions contribute to postoperative cognitive decline after cardiac surgery remains unclear. This is the first study to use 3-T fluid attenuated inversion recovery (FLAIR) MRI to assess the relative contribution of new ischemic lesions to preexisting cerebrovascular disease in patients undergoing cardiac surgery. We also performed neuropsychological testing at the same time points as the MRI scans to investigate whether the presence, number, or volume of new lesions significantly alters cognition.Modern MRI techniques, such as FLAIR, enable confident identification of ischemic white matter disease. 15 Here, we present the spatial distribution and dimensions of new ischemic lesions observed after surgery, quantified against levels of preexisting cerebrovascular disease, alongside the results of neuropsychological testing conducted at the same time point as the MRI scans, to investigate whether the presence, number, or size of new lesions affect neuropsychological test performance.Background and Purpose-Brain injury after cardiac surgery is a serious concern for patients and their families. The purpose of this study was to use 3-T fluid attenuated inversion recovery MRI to characterize new and preexisting cerebral ischemic lesions in patients undergoing cardiac surgery and to test whether the accumulation of new ischemic lesions adversely affects cognition. Methods-Digital comparison of before and after fluid attenuated inversion recovery MRI images was performed for 77 cardiac surgery patients. Patients and MethodsAll patients requiring coronary artery bypass graft or valve surgery at our institution were eligible for inclusion in this study. Data were collected as part of a larger study investigating brain injury after cardiac surgery funded by the British Heart Foundation. Patients were excluded if they had contraindications to MRI (eg, a cardiac pacemaker), or if their first l...