Stroke, Ahead of Print. BACKGROUND:The effects of lipid-lowering drug targets on different ischemic stroke subtypes are not fully understood. We aimed to explore the mechanisms by which lipid-lowering drug targets differentially affect the risk of ischemic stroke subtypes and their underlying pathophysiology.METHODS:Using a 2-sample Mendelian randomization approach, we assessed the effects of genetically proxied low-density lipoprotein cholesterol (LDL-c) and 3 clinically approved LDL-lowering drugs (HMGCR [3-hydroxy-3-methylglutaryl-CoA reductase], PCSK9 [proprotein convertase subtilisin/kexin type 9], and NPC1L1 [Niemann-Pick C1-Like 1]) on stroke subtypes and brain imaging biomarkers associated with small vessel stroke (SVS), including white matter hyperintensity volume and perivascular spaces.RESULTS:In genome-wide Mendelian randomization analyses, lower genetically predicted LDL-c was significantly associated with a reduced risk of any stroke, ischemic stroke, and large artery stroke, supporting previous findings. Significant associations between genetically predicted LDL-c and cardioembolic stroke, SVS, and biomarkers, perivascular space and white matter hyperintensity volume, were not identified in this study. In drug-target Mendelian randomization analysis, genetically proxied reduced LDL-c through NPC1L1 inhibition was associated with lower odds of perivascular space (odds ratio per 1-mg/dL decrease, 0.79 [95% CI, 0.67–0.93]) and with lower odds of SVS (odds ratio, 0.29 [95% CI, 0.10–0.85]).CONCLUSIONS:This study provides supporting evidence of a potentially protective effect of LDL-c lowering through NPC1L1 inhibition on perivascular space and SVS risk, highlighting novel therapeutic targets for SVS.
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Il ruolo dell’imaging nel sanguinamento gastrointestinale: linea guida
Portuguese observational cross-sectional clinical imaging study protocol to investigate central dopaminergic mechanisms of successful weight loss through bariatric surgery
Introduction
Bariatric surgery (BS) is the treatment of choice for refractory obesity. Although weight loss (WL) reduces the prevalence of obesity-related comorbidities, not all patients maintain it. It has been suggested that central mechanisms involving dopamine receptors may play a role in successful WL. This protocol describes an observational cross-sectional study to test if the binding of central dopamine receptors is similar in individuals who responded successfully to BS and age- and gender-matched normal-weight healthy individuals (controls). As secondary goals, the protocol will investigate if this binding correlates with key parameters such as age, hormonal status, anthropometric metrics and neurobehavioural scores. Finally, as exploratory goals, we will include a cohort of individuals with obesity before and after BS to explore whether obesity and type of BS (sleeve gastrectomy and Roux-en-Y gastric bypass) yield distinct binding values and track central dopaminergic changes resulting from BS.
Methods and analysis
To address the major research question of this observational study, positron emission tomography (PET) with [11C]raclopride will be used to map brain dopamine type 2 and 3 receptors (D2/3R) non-displaceable binding potential (BPND) of individuals who have successfully responded to BS. Mean regional D2/3R BPND values will be compared with control individuals by two one-sided test approaches. The sample size (23 per group) was estimated to demonstrate the equivalence between two independent group means. In addition, these binding values will be correlated with key parameters to address secondary goals. Finally, for exploratory analysis, these values will be compared within the same individuals (before and after BS) and between individuals with obesity and controls and types of BS.
Ethics and dissemination
The project and informed consent received ethical approval from the Faculty of Medicine and the Coimbra University Hospital ethics committees. Results will be disseminated in international peer-reviewed journals and conferences.
Intravascular Imaging for Guiding Percutaneous Coronary Intervention: What Does the Totality of Data Suggest, and Where Should We Go?
Circulation, Volume 149, Issue 14, Page 1087-1089, April 2, 2024.
How AI Might Improve Cardiac Imaging
In this Medical News interview, University of California, San Francisco, cardiologist Rima Arnaout, joins JAMA Editor in Chief Kirsten Bibbins-Domingo to discuss the transformative potential of AI on cardiac imaging.
Three-dimensional imaging of the enteric nervous system in human pediatric colon reveals new features of Hirschsprung disease
Hirschsprung disease is defined by the absence of enteric nervous system (ENS) from distal bowel. Primary treatment is “pull-through” surgery to remove bowel that lacks ENS with re-anastomosis of “normal” bowel near the anal verge. Problems after pull-through are common and some may be due to retained hypoganglionic bowel (i.e., low ENS density). Testing this hypothesis has been difficult because counting enteric neurons in tissue sections is unreliable even for experts. Tissue clearing and 3-dimensional imaging provides better data about ENS structure than sectioning.
Imaging Biomarkers of VCI: A Focused Update
Stroke, Ahead of Print. Vascular cognitive impairment is common after stroke, in memory clinics, medicine for the elderly services, and undiagnosed in the community. Vascular disease is said to be the second most common cause of dementia after Alzheimer disease, yet vascular dysfunction is now known to predate cognitive decline in Alzheimer disease, and most dementias at older ages are mixed. Neuroimaging has a major role in identifying the proportion of vascular versus other likely pathologies in patients with cognitive impairment. Here, we aim to provide a pragmatic but evidence-based summary of the current state of potential imaging biomarkers, focusing on magnetic resonance imaging and computed tomography, which are relevant to diagnosing, estimating prognosis, monitoring vascular cognitive impairment, and incorporating our own experiences. We focus on markers that are well-established, with a known profile of association with cognitive measures, but also consider more recently described, including quantitative tissue markers of vascular injury. We highlight the gaps in accessibility and translation to more routine clinical practice.
PET imaging of unruptured intracranial aneurysm inflammation (PET-IA) study: a feasibility study protocol
Introduction
Positron emission tomography (PET) imaging can be used to evaluate arterial wall inflammation in extracranial vascular diseases. However, the application of PET imaging in unruptured intracranial aneurysms (UIA) remains unexplored. Our objective is to investigate feasibility of PET imaging using 18F-FDG and 68Ga-DOTANOC tracers to evaluate arterial wall inflammation in UIA.
Methods and analysis
This PET imaging feasibility study will enrol patients scheduled for surgical treatment of UIA. The study subjects will undergo PET imaging of the intracranial arteries within 1 month before planned surgery. The imaging protocol includes 18F-FDG PET MRI, MRA with gadolinium enhancement, and 68Ga-DOTANOC PET CT. The study will also involve preoperative blood samples, intraoperative cerebrospinal fluid (CSF) samples, and aneurysm sac biopsy. Planned sample size is at least 18 patients. Primary outcome is uptake of 18F-FDG or 68Ga-DOTANOC in intracranial arterial aneurysms compared with contralateral normal vessel as maximum standardised uptake value or target-to-blood pool ratio and correlation of uptake of 18F-FDG or 68Ga-DOTANOC to aneurysm histological findings. Secondary outcomes include estimating the correlations between uptake of 18F-FDG or 68Ga-DOTANOC and histological findings with blood and CSF miRNA-levels, arterial wall enhancement in gadolinium enhanced MRA, aneurysm size and shape, smoking, hypertension, and location of the aneurysm.
Ethics and dissemination
This study is approved by the Human Research Ethics Committee of the Hospital District of Southwest Finland, Finnish Medicines Agency Fimea, and Turku University Hospital. Findings will be disseminated through peer-reviewed journal articles and presentations at national and international conferences.
Trial registration number
NCT04715503
Exploring the safety and quality of mobile X-ray imaging in a new infectious disease biocontainment unit: an in situ simulation and video-reflexive study
Objectives
During a precommissioning inspection of a new biocontainment centre, radiographers noted structural features of quarantine rooms that could compromise staff and patient safety and the X-ray image quality, even after significant modifications had been made to an earlier radiography protocol. The aim of this study was to explore the safety and effectiveness of the modified protocol, in the new space, and identify improvements, if required.
Design
A qualitative study using in situ simulation and video-reflexive methods.
Setting
A newly built biocontainment centre, prior to its commissioning in 2021, in a large, tertiary hospital in Sydney, Australia.
Participants
Five radiographers, and a nurse and a physician from the biocontainment centre, consented to participate. All completed the study.
Interventions
Two simulated mobile X-ray examinations were conducted in the unit prior to its commissioning; simulations were videoed. Participants and other stakeholders analysed video footage, collaboratively, and sessions were audio recorded, transcribed and analysed thematically. Problems and potential solutions identified were collated and communicated to the hospital executive, for endorsement and actioning, if possible.
Results
Four themes were identified from the data: infection exposure risks, occupational health and exposure risks, communication and X-ray image quality. Facilitated group reviews of video footage identified several important issues, across these four areas of risk, which had not been identified previously.
Conclusions
In situ simulation is used, increasingly, to evaluate and improve healthcare practices. This study confirmed the added value of video-reflexive methods, which provided experienced participants with a richer view of a familiar protocol, in a new setting. Video footage can be examined immediately, or later if required, by a broader group of stakeholders, with diverse experience or expertise. Using video reflexivity, clinicians identified potential safety risks, which were collated and reported to the hospital executive, who agreed to implement modifications.
Multimodal Imaging Evidence for Optimized Blood Pressure Control Following Hypertensive Pregnancy: Mechanistic Insights Into Beneficial Cardiac Remodeling From the POP-HT Trial
Circulation, Volume 149, Issue 7, Page 542-544, February 13, 2024.
Tenecteplase for Stroke at 4.5 to 24 Hours with Perfusion-Imaging Selection
New England Journal of Medicine, Ahead of Print.
Pilot study of paediatric regional lung function assessment via X-ray velocimetry (XV) imaging in children with normal lungs and in children with cystic fibrosis
Introduction
Cystic fibrosis (CF) is a life-limiting autosomal recessive genetic condition. It is caused by mutations in the gene that encodes for a chloride and bicarbonate conducting transmembrane channel. X-ray velocimetry (XV) is a novel form of X-ray imaging that can generate lung ventilation data through the breathing cycle. XV technology has been validated in multiple animal models, including the β-ENaC mouse model of CF lung disease. It has since been assessed in early-phase clinical trials in adult human subjects; however, there is a paucity of data in the paediatric cohort, including in CF. The aim of this pilot study was to investigate the feasibility of performing a single-centre cohort study in paediatric patients with CF and in those with normal lungs to demonstrate the appropriateness of proceeding with further studies of XV in these cohorts.
Methods and analysis
This is a cross-sectional, single-centre, pilot study. It will recruit children aged 3–18 years to have XV lung imaging performed, as well as paired pulmonary function testing. The study will aim to recruit 20 children without CF with normal lungs and 20 children with CF. The primary outcome will be the feasibility of recruiting children and performing XV testing. Secondary outcomes will include comparisons between XV and current assessments of pulmonary function and structure.
Ethics and dissemination
This project has ethical approval granted by The Women’s and Children’s Hospital Human Research Ethics Committee (HREC ID 2021/HRE00396). Findings will be disseminated through peer-reviewed publication and conferences.
Trial registration number
ACTRN12623000109606.
Abstract 144: Value of CT Perfusion Imaging Among Patients With Minor Stroke
Stroke, Volume 55, Issue Suppl_1, Page A144-A144, February 1, 2024. Introduction:CTP has increasingly been incorporated into the evaluation of all patients with suspected acute ischemic stroke (AIS), including those with minor symptoms. We aimed to assess the incremental value of CTP in acute treatment decision-making among patients with low NIHSS.Methods:We performed a retrospective cohort study of all patients who underwent CTP upon presentation to the ED at three academic, urban hospitals in Philadelphia, PA between January 1, 2022 and December 31, 2022. We collected data on initial NIHSS score, AIS treatment decisions, subsequent neuroimaging, and final diagnosis.Results:There were 531 patients with a median age of 64.5 years (IQR 54-73) and 56% were women. 73% were Black or African American, 20% White, and 4% Asian. Frequency of CTP imaging by initial NIHSS score is presented in the Figure. Among 90 patients (16.9%) with NIHSS≤2, CTP imaging was cited as justification for AIS treatment (thrombolysis, thrombectomy, or both) in 0 (0%, 95% CI: 0-4%). Specifically, among 41 patients (7.7%) with NIHSS≤1, 0 received thrombolysis or thrombectomy, and 12 (29.2%) were ultimately diagnosed with AIS on CT/MRI. Among 49 with NIHSS=2 (9.2%), 2 patients received thrombolysis (based on clinical exam, CTP was normal) and one later underwent thrombectomy based on clinical decompensation with repeat NIHSS=7, and 28.6% had AIS on CT/MRI. Meanwhile, among 33 patients with NIHSS=3, acute treatment was given to 3 and CTP influenced AIS treatment decisions in 2 (6.1%). Among 59 patients with NIHSS=4, acute treatment was given to 4 and CTP influenced decision-making in 3 (5.1%). CTP mismatch ratio was > 1.7 in all 5 patients who received acute treatment and had NIHSS of 3 or 4.Conclusions:CTP is frequently performed in patients with low NIHSS. It had limited impact on acute treatment decisions, notably none among those with NIHSS≤2, suggesting that CTP may be over-utilized in this subset of patients with AIS.
Abstract TP131: Computed Tomography Perfusion Imaging Patterns Are Similar Before and After Interfacility Transfer of Ischemic Stroke Patients
Stroke, Volume 55, Issue Suppl_1, Page ATP131-ATP131, February 1, 2024. Background:Large vessel occlusion (LVO) stroke patients are often transferred from regional hospitals to comprehensive stroke centers (CSC) for thrombectomy. The need for repeat imaging at CSCs prior to intervention is unclear. We compared regional hospital and CSC perfusion imaging results for interfacility transfers in a single health system.Methods:We analyzed a cohort of patients in western Michigan who received CT perfusion imaging before and after transfer to a CSC. Perfusion mismatch (MM), core infarct volume (CIV), and favorability of imaging for mechanical thrombectomy (MT) candidacy were compared between the regional and CSC studies. A favorable imaging profile was defined as the presence of LVO, MM volume >10 mL, and MM/CIV ratio of >1.2. Linear regression was used to examine predictors of infarct growth during transfer.Results:Over a 10-month period, 25 patients met inclusion criteria. The median age was 76 (IQR 66-81), 60% were male, median NIHSS was 11 (IQR 2-18), and most patients had occlusion of the internal carotid or middle cerebral arteries (72%). The median time from last known well to initial CT was 250 minutes (IQR 85-620). Regional median MM volume was 52 mL (IQR 8-97), CIV was 0 mL (IQR 0-13), and hypoperfusion intensity ratio (HIR) was 0.25 (IQR 0-0.34). The median time between CTs was 152 minutes (IQR 139-226). The median change in MM volume was -3 mL (IQR -27-3) and median CIV growth rate was 0 mL/hr (IQR 0-2.0). In a multivariable regression model, higher HIR (β=23.2, p=0.012) and minutes between imaging studies (β=0.10, p=0.021) were associated with CIV growth. Sixteen patients (64%) had favorable imaging profiles for MT at the regional hospital. Of these, 15 (93.8%) continued to have a favorable CSC imaging profiles and 9 (56.2%) underwent MT. Of the 9 patients without favorable regional imaging profiles, 1 (11.1%) had a favorable CSC imaging profile and 2 (22.2%) underwent MT.Conclusion:In our sample, regional and CSC perfusion imaging patterns were similar and patients infrequently crossed thresholds for MT candidacy between studies. Initial HIR and longer delays between were independently associated with infarct growth during transfers, however overall infarct growth was very small.
Abstract 128: Multi-Direction Diffusion Weighted Imaging on Portable, Low-Field Magnetic Resonance Imaging
Stroke, Volume 55, Issue Suppl_1, Page A128-A128, February 1, 2024. Background and aims:Portable, low-field (LF) MRI has the potential to improve access to expeditious, definitive brain imaging and facilitate diagnosis of acute stroke. Currently available diffusion-weighted imaging (DWI) protocols at LF are limited to a single diffusion direction due to acquisition duration. However, single-direction diffusion has reduced sensitivity for detecting acute ischemic infarcts, particularly small lesions residing in white matter tracts. The purpose of this study was to establish the feasibility of acquiring multi-direction DWI compared with single-direction counterparts on LF-MRI.Methods:Patients presenting with a diagnosis of acute ischemic stroke between July and September 2023 were eligible. Consented patients underwent DWI acquisition on a 0.064T LF-MRI (Mk1.9; Hyperfine Research Inc). Three diffusion directions (x, y, and z) were acquired with abweighting of 900 s/mm2and a single acquisition with ab0 s/mm2. Theb900 images were co-registered to theb0, trace and apparent diffusion coefficient (ADC) maps calculated, and the final images interpolated at 1 mm3.Results:Ten patients presenting to the Massachusetts General Hospital with acute ischemic stroke were consented and imaged within 72 hours of last known well. The total acquisition time was 14 minutes, with all subjects able to tolerate the scan duration. Ischemic lesions as small as 0.1 mL were detectable on the LF-MRI (17.5 +/- 18.2 mL). An example of each diffusion direction individually, the combined trace, and corresponding ADC maps are shown in Figure 1, compared with conventional high-field (HF) diffusion images acquired within 30 minutes of the LF acquisition.Conclusion:Multi-direction DWI imaging is feasible on a 0.064T LF-MRI scanner. Our experience suggests further modifications to the pulse sequence and scanner configuration may facilitate a reduction in acquisition time, improve resolution, or both.
Abstract WP118: Ischemic Core Volumes and Collateral Status Have Diurnal Fluctuations – A Retrospective Cohort Study of 18137 Patients Using Automated Perfusion Imaging
Stroke, Volume 55, Issue Suppl_1, Page AWP118-AWP118, February 1, 2024. Introduction:Circadian rhythms have recently been shown to influence stroke incidence and progression of infarct. We aimed to describe the diurnal variations in the incidence and perfusion profiles of patients with ischemic stroke using a large, multi-center, automated imaging database.Methods:The RAPID Insights database was queried from 02/01/2016 to 01/31/2022 for patients with perfusion imaging and automated detection of an ischemic stroke due to a presumed large vessel occlusion. Exclusion criteria included: patient age ≤25, mismatch volume of 10s]/[Tmax >6s]), where a higher HIR suggests poorer collateral status. All perfusion parameters were analyzed on a 24-hour continuous cycle. Statistical significance was tested using a sinusoidal regression analysis.Results:A total of 18,137 cases were analyzed. The peak incidence of ischemic stroke occurred around noon. A sinusoidal pattern was present, with larger ischemic core volumes and higher HIR during the night compared to the day: peak ischemic core volume of 23.40 cc occurred with imaging performed at 3:56 AM (p