Large-scale pretrained frame generative model enables real-time low-dose DSA imaging: An AI system development and multi-center validation study.

BACKGROUND: Digital subtraction angiography (DSA) devices are commonly used in numerous interventional procedures across various parts of the body, necessitating multiple scans per procedure, which results in significant radiation exposure for both doctors and patients. Inspired by generative artificial intelligence techniques, this study proposes GenDSA, a large-scale pretrained multi-frame generative model-based real-time and low-dose DSA imaging system. METHODS: GenDSA was developed to generate 1-, 2-, and 3-frame sequences following each real frame. A large-scale dataset comprising ∼3 million DSA images from 27,117 patients across 10 hospitals was constructed to pretrain, fine-tune, and validate GenDSA. Two other datasets from 25 hospitals were used for evaluation. Objective evaluations included SSIM and PSNR. Five interventional radiologists independently assessed the quality of the generated frames using the Likert scale and visual Turing test. Scoring consistency among the radiologists was measured using the Kendall coefficient of concordance (W). The Fleiss' kappa values were used for inter-rater agreement analysis for visual Turing tests. FINDINGS: Using only one-third of the clinical radiation dose, videos generated by GenDSA were perfectly consistent with real videos. Objective evaluations demonstrated that GenDSA's performance (PSNR = 36.83, SSIM = 0.911, generation time = 0.07 s/frame) surpassed state-of-the-art algorithms. Subjective ratings and statistical results from five doctors indicated no significant difference between real and generated videos. Furthermore, the generated videos were comparable to real videos in overall quality (4.905 vs. 4.935) and lesion assessment (4.825 vs. 4.860). CONCLUSIONS: With clear clinical and translational values, the developed GenDSA can significantly reduce radiation damage to both doctors and patients during DSA-guided procedures. FUNDING: This study was supported by the National Key R&D Program and the National Natural Science Foundation of China.

Assessment of automated TICI scoring during endovascular treatment in patients with an ischemic stroke.

BACKGROUND: The extended Thrombolysis in Cerebral Infarction (eTICI) score is used in digital subtraction angiography (DSA) to quantify reperfusion grade in patients with an ischemic stroke who undergo endovascular thrombectomy (EVT). A previously developed automatic TICI score (autoTICI), which quantifies the ratio of reperfused pixels after EVT, demonstrates good correlation with eTICI. OBJECTIVE: To evaluate the autoTICI model in a large multicenter registry of patients with an ischemic stroke, investigate the association with visual eTICI, and compare prediction of functional outcome between autoTICI and eTICI. METHODS: Patients in the MR CLEAN Registry with an internal carotid artery, M1, and M2 occlusion were selected if both anteroposterior and lateral views were present in pre- and post-EVT DSA scans. The autoTICI score was compared with eTICI in predicting favorable functional outcome (modified Rankin Scale score 0-2), using area under the receiver operating characteristics curve (AUC) with a multivariable logistic regression model including known prognostic characteristics. RESULTS: In total 421 of 3637 patients were included. AutoTICI was significantly associated with eTICI non-linearly (below 70% cOR=2.3 (95% CI 2.1 to 2.5), above 70% cOR=1.6 (95% CI 1.6 to 1.7) per 10% increment). The AUC of the model predicting favorable functional outcome was similar for autoTICI and eTICI (0.86, 95% CI 0.82 to 0.92 vs 0.86, 95% CI 0.83 to 0.90, P=0.73) and was higher than for a model with prognostic patient characteristics alone (0.86 vs 0.84, P=0.01). CONCLUSION: Automatic quantitative assessment of reperfusion after EVT is associated with eTICI, and prediction of functional outcome is similar to that with visual eTICI. Therefore, autoTICI could be used as an alternative or additional review for visual reperfusion assessment to facilitate reproducible and uniform reporting.

Collaterals at angiography guide clinical outcomes after endovascular stroke therapy in HERMES.

BACKGROUND: Robust collateral circulation has been linked with better reperfusion and clinical outcomes. It remains unclear how individual assessments of collateral circulation may be translated into clinical practice. METHODS: The pooled Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials (HERMES) angiography dataset was analyzed by a centralized, independent imaging core blinded to other clinical data. Conventional angiography was acquired immediately prior to endovascular therapy. Collaterals were graded with the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN) system and associated with baseline patient characteristics, reperfusion, and day 90 modified Rankin Score (mRS). Both 90-day all-cause mortality and day 90 mRS were modeled via multivariable logistic regression. RESULTS: Angiography was available in 376/605 (62%) patients. Baseline ASPECTS (Alberta Stroke Program Early CT Score) (p=0.043), history of diabetes mellitus (p=0.048), site of occlusion (p<0.001), and degree of subsequent Thrombolysis in Cerebral Infarction (TICI) reperfusion (p<0.001) were associated with collateral grades. ASITN collateral grade was strongly associated with ordinal mRS from baseline to 90 days in an unadjusted analysis (p<0.001). Multivariable regression demonstrated that collateral status is a strong determinant of mRS outcome in the presence of other predictors (OR=1.37 per grade, 95% CI [1.05 to 1.74], p=0.018). By comparing ORs, 1 unit of ASITN was determined to be approximately equivalent to 4.5 points of NIHSS, 11 years of age, 1.5 points of ASPECTS, or 100 min less delay from onset to puncture, in terms of impact on mRS. CONCLUSIONS: Individual collateral physiology may contribute significantly to reperfusion success and clinical outcomes after acute ischemic stroke. Building a consensus for the role of angiographic collateral assessment in the allocation of adjuvant reperfusion therapies may help galvanize a precision medicine approach in stroke.

Collateral-based selection for endovascular treatment of acute ischaemic stroke in the late window (MR CLEAN-LATE): 2-year follow-up of a phase 3, multicentre, open-label, randomised controlled trial in the Netherlands.

BACKGROUND: The MR CLEAN-LATE trial provided evidence for the safety and efficacy of endovascular treatment for acute ischaemic stroke within the late window (after 6-24 h) in patients who were preselected based on the presence of collateral flow on CT angiography. We aimed to evaluate clinical outcomes 2 years after randomisation. METHODS: MR CLEAN-LATE was a phase 3, multicentre, open-label, blinded-endpoint, randomised controlled trial conducted at 18 stroke intervention centres in the Netherlands. If endovascular treatment could be initiated within 6-24 h of symptom onset or last seen well, patients (aged 18 years or older) with an acute ischaemic stroke due to a large vessel occlusion in the anterior circulation and at least some collateral flow in the affected middle cerebral artery territory on CT angiography were randomly assigned (1:1) to either endovascular treatment with best medical treatment (endovascular treatment group) or best medical treatment alone (control group). Web-based randomisation, stratified by centre, was performed with the use of permuted blocks (block size eight to 20). The researchers who collected clinical outcomes and analysed the results were masked to treatment allocation; treating physicians, local investigators, and patients were aware of the received treatment. The primary outcome of MR CLEAN-LATE was the modified Rankin Scale (mRS) score at 90 days after randomisation. For this 2-year prespecified analysis, the primary outcome was mRS score at 2 years (minus 3 months to plus 6 months). Primary and safety analyses were performed based on the modified intention-to-treat principle, and included patients who provided (deferred) consent or died before consent could be obtained. Missing data were handled with multiple imputation by chained equations. The trial is completed and is registered at ISRCTN, ISRCTN19922220. FINDINGS: Between Feb 2, 2018, and Jan 27, 2022, 535 patients were randomly assigned in the MR CLEAN-LATE trial, of whom 502 (94%) gave deferred consent and comprised the modified intention-to-treat population (255 in the endovascular treatment group and 247 in the control group). 261 (52%) patients were female and 241 (48%) were male. Data for mRS score at 2 years were available for 226 (89%) patients in the endovascular treatment group and for 202 (82%) patients in the control group. The median mRS score at 2 years was 4 (IQR 2-6) in the endovascular treatment group and 6 (2-6) in the control group. The endovascular treatment group demonstrated a shift towards better functional outcomes on the mRS (adjusted common odds ratio 1·41 [95% CI 1·00-1·99]; p=0·049). All-cause mortality at 2 years was 34% (87 of 255) in the endovascular treatment group and 41% (101 of 247) in the control group (adjusted hazard ratio 0·81 [95% CI 0·60-1·08]; p=0·15). Major vascular events (ie, transient ischaemic attack, ischaemic stroke, haemorrhagic stroke, and cardiac events) were reported between 90 days and 2 years in 23 patients in the endovascular treatment group and 13 patients in the control group. INTERPRETATION: Our results show that the effectiveness of late-window (after 6-24 h) endovascular treatment in improving clinical outcomes is sustained for up to 2 years in a population preselected based on the presence of collateral flow on CT angiography. This finding might be important for prompting further evaluations of cost-effectiveness, health-care policy development, and clinical decision making. FUNDING: The Dutch Organization for Health Research and Health Innovation (ZonMW), Collaboration for New Treatments of Acute Stroke Consortium, Dutch Heart Foundation, Stryker, Medtronic, Cerenovus, Health Holland Top Sector Life Sciences & Health, and the Netherlands Brain Foundation.

CAVE: Cerebral artery-vein segmentation in digital subtraction angiography.

Cerebral X-ray digital subtraction angiography (DSA) is a widely used imaging technique in patients with neurovascular disease, allowing for vessel and flow visualization with high spatio-temporal resolution. Automatic artery-vein segmentation in DSA plays a fundamental role in vascular analysis with quantitative biomarker extraction, facilitating a wide range of clinical applications. The widely adopted U-Net applied on static DSA frames often struggles with disentangling vessels from subtraction artifacts. Further, it falls short in effectively separating arteries and veins as it disregards the temporal perspectives inherent in DSA. To address these limitations, we propose to simultaneously leverage spatial vasculature and temporal cerebral flow characteristics to segment arteries and veins in DSA. The proposed network, coined CAVE, encodes a 2D+time DSA series using spatial modules, aggregates all the features using temporal modules, and decodes it into 2D segmentation maps. On a large multi-center clinical dataset, CAVE achieves a vessel segmentation Dice of 0.84 (±0.04) and an artery-vein segmentation Dice of 0.79 (±0.06). CAVE surpasses traditional Frangi-based k-means clustering (P < 0.001) and U-Net (P < 0.001) by a significant margin, demonstrating the advantages of harvesting spatio-temporal features. This study represents the first investigation into automatic artery-vein segmentation in DSA using deep learning. The code is publicly available at https://github.com/RuishengSu/CAVE_DSA.

Relating pre-treatment non-Gaussian intravoxel incoherent motion diffusion-weighted imaging to human papillomavirus status and response in oropharyngeal carcinoma.

Background and purpose: Diffusion-weighted imaging (DWI) is a promising technique for response assessment in head-and-neck cancer. Recently, we optimized Non-Gaussian Intravoxel Incoherent Motion Imaging (NG-IVIM), an extension of the conventional apparent diffusion coefficient (ADC) model, for the head and neck. In the current study, we describe the first application in a group of patients with human papillomavirus (HPV)-positive and HPV-negative oropharyngeal squamous cell carcinoma. The aim of this study was to relate ADC and NG-IVIM DWI parameters to HPV status and clinical treatment response. Materials and methods: Thirty-six patients (18 HPV-positive, 18 HPV-negative) were prospectively included. Presence of progressive disease was scored within one year. The mean pre-treatment ADC and NG-IVIM parameters in the gross tumor volume were compared between HPV-positive and HPV-negative patients. In HPV-negative patients, ADC and NG-IVIM parameters were compared between patients with and without progressive disease. Results: ADC, the NG-IVIM diffusion coefficient D, and perfusion fraction f were significantly higher, while pseudo-diffusion coefficient D* and kurtosis K were significantly lower in the HPV-negative compared to HPV-positive patients. In the HPV-negative group, a significantly lower D was found for patients with progressive disease compared to complete responders. No relation with ADC was observed. Conclusion: The results of our single-center study suggest that ADC is related to HPV status, but not an independent response predictor. The NG-IVIM parameter D, however, was independently associated to response in the HPV-negative group. Noteworthy in the opposite direction as previously thought based on ADC.

Value of Automatically Derived Full Thrombus Characteristics: An Explorative Study of Their Associations with Outcomes in Ischemic Stroke Patients.

(1) Background: For acute ischemic strokes caused by large vessel occlusion, manually assessed thrombus volume and perviousness have been associated with treatment outcomes. However, the manual assessment of these characteristics is time-consuming and subject to inter-observer bias. Alternatively, a recently introduced fully automated deep learning-based algorithm can be used to consistently estimate full thrombus characteristics. Here, we exploratively assess the value of these novel biomarkers in terms of their association with stroke outcomes. (2) Methods: We studied two applications of automated full thrombus characterization as follows: one in a randomized trial, MR CLEAN-NO IV (n = 314), and another in a Dutch nationwide registry, MR CLEAN Registry (n = 1839). We used an automatic pipeline to determine the thrombus volume, perviousness, density, and heterogeneity. We assessed their relationship with the functional outcome defined as the modified Rankin Scale (mRS) at 90 days and two technical success measures as follows: successful final reperfusion, which is defined as an eTICI score of 2b-3, and successful first-pass reperfusion (FPS). (3) Results: Higher perviousness was significantly related to a better mRS in both MR CLEAN-NO IV and the MR CLEAN Registry. A lower thrombus volume and lower heterogeneity were only significantly related to better mRS scores in the MR CLEAN Registry. Only lower thrombus heterogeneity was significantly related to technical success; it was significantly related to a higher chance of FPS in the MR CLEAN-NO IV trial (OR = 0.55, 95% CI: 0.31-0.98) and successful reperfusion in the MR CLEAN Registry (OR = 0.88, 95% CI: 0.78-0.99). (4) Conclusions: Thrombus characteristics derived from automatic entire thrombus segmentations are significantly related to stroke outcomes.

Contribution of Red Blood Cells and Platelets to Blood Clot Computed Tomography Imaging and Compressive Mechanical Characteristics.

Thrombus computed tomography (CT) imaging characteristics may correspond with thrombus mechanical properties and thus predict thrombectomy success. The impact of red blood cell (RBC) content on these properties (imaging and mechanics) has been widely studied. However, the additional effect of platelets has not been considered. The objective of the current study was to examine the individual and combined effects of blood clot RBC and platelet content on resultant CT imaging and mechanical characteristics. Human blood clot analogues were prepared from a combination of preselected RBC volumes and platelet concentrations to decouple their contributions. The resulting clot RBC content (%) and platelet content (%) were determined using Martius Scarlet Blue and CD42b staining, respectively. Non-contrast and contrast-enhanced CT (NCCT and CECT) scans were performed to measure the clot densities. CECT density increase was taken as a proxy for clinical perviousness. Unconfined compressive mechanics were analysed by performing 10 cycles of 80% strain. RBC content is the major determinant of clot NCCT density. However, additional consideration of the platelet content improves the association. CECT density increase is influenced by clot platelet and not RBC content. Platelet content is the dominant component driving clot stiffness, especially at high strains. Both RBC and platelet content contribute to the clot's viscoelastic and plastic compressive properties. The current in vitro results suggest that CT density is reflective of RBC content and subsequent clot viscoelasticity and plasticity, and that perviousness reflects the clot's platelet content and subsequent stiffness. However, these indications should be confirmed in a clinical stroke cohort.

Non-contrast short MRI surveillance for HCC screening: the study protocol of the SMS-HCC prospective multicenter study.

Hepatocellular carcinoma (HCC) comprises 75 to 85% of all primary liver cancers. Current guidelines recommend a biannual HCC surveillance using ultrasound (US) for high-risk patients. However, due to its low sensitivity for detection of early-stage HCC lesions, there is an urgency for more sensitive surveillance tools. Here, we describe the potential of a short MRI surveillance (SMS) protocol for HCC, including axial T1-weighted in-out phase, fat-saturated T2-weighted, and diffusion-weighted sequences. In this prospective, multicenter, patient cohort study, patients will be recruited from existing HCC surveillance cohorts of six medical centers in The Netherlands. Surveillance patients who undergo biannual US, will be invited for SMS on the same day for 3 years. In case of a suspicious finding on either US or SMS, patients will be invited for a full MRI liver protocol including gadolinium-based contrast agent intravenous injection within 2 weeks. To our knowledge, this will be the first study to perform a head-to-head comparison with a paired US-MRI design. We hypothesize that the sensitivity of SMS for detection of early-stage HCC will be higher than that of US leading to improved survival of surveillance patients through timely HCC diagnosis. Furthermore, we hypothesize that the SMS-HCC protocol will prove cost-effective.Relevance statement The US sensitivity for detecting early-stage HCC has been reported to be less than 50%. We expect that the proposed SMS will detect at least twice as many early-stage HCC lesions and therefore prove to be cost-effective. Key points • The low sensitivity of US necessitates better imaging tools for HCC screening.• This is the first study with a paired US-MRI design.• This design will allow a head-to-head comparison in both diagnostics and patient-acceptance.• We expect that SMS can contribute to a higher survival rate.

Update of the Minimum Information About BIobank Data Sharing (MIABIS) Core Terminology to the 3rd Version.

Introduction: The Minimum Information About BIobank Data Sharing (MIABIS) is a biobank-specific terminology enabling the sharing of biobank-related data for different purposes across a wide range of database implementations. After 4 years in use and with the first version of the individual-level MIABIS component Sample, Sample donor, and Event, it was necessary to revise the terminology, especially to include biobanks that work more in the data domain than with samples. Materials & Methods: Nine use-cases representing different types of biobanks, studies, and networks participated in the development work. They represent types of data, specific sample types, or levels of organization that were not included earlier in MIABIS. To support our revision of the Biobank entity, we conducted a survey of European biobanks to chart the services they provide. An important stakeholder group for biobanks include researchers as the main users of biobanks. To be able to render MIABIS more researcher-friendly, we collected different sample/data requests to analyze the terminology adjustment needs in detail. During the update process, the Core terminology was iteratively reviewed by a large group of experts until a consensus was reached. Results: With this update, MIABIS was adjusted to encompass data-driven biobanks and to include data collections, while also describing the services and capabilities biobanks offer to their users, besides the retrospective samples. The terminology was also extended to accommodate sample and data collections of nonhuman origin. Additionally, a set of organizational attributes was compiled to describe networks. Discussion: The usability of MIABIS Core v3 was increased by extending it to cover more topics of the biobanking domain. Additionally, the focus was on a more general terminology and harmonization of attributes with the individual-level entities Sample, Sample donor, and Event to keep the overall terminology minimal. With this work, the internal semantics of the MIABIS terminology was improved.

Burden of intracranial artery calcification in white patients with ischemic stroke.

INTRODUCTION: The diagnostic workup of stroke doesn't identify an underlying cause in two-fifths of ischemic strokes. Intracranial arteriosclerosis is acknowledged as a cause of stroke in Asian and Black populations, but is underappreciated as such in whites. We explored the burden of Intracranial Artery Calcification (IAC), a marker of intracranial arteriosclerosis, as a potential cause of stroke among white patients with recent ischemic stroke or TIA. PATIENTS AND METHODS: Between December 2005 and October 2010, 943 patients (mean age 63.8 (SD ± 14.0) years, 47.9% female) were recruited, of whom 561 had ischemic stroke and 382 a TIA. CT-angiography was conducted according to stroke analysis protocols. The burden of IAC was quantified on these images, whereafter we assessed the presence of IAC per TOAST etiology underlying the stroke and assessed associations between IAC burden, symptom severity, and short-term functional outcome. RESULTS: IAC was present in 62.4% of patients. Furthermore, IAC was seen in 84.8% of atherosclerotic strokes, and also in the majority of strokes with an undetermined etiology (58.5%). Additionally, patients with larger IAC burden presented with heavier symptoms (adjusted OR 1.56 (95% CI [1.06-2.29]), but there was no difference in short-term functional outcome (1.14 [0.80-1.61]). CONCLUSION: IAC is seen in the majority of white ischemic stroke patients, aligning with findings from patient studies in other ethnicities. Furthermore, over half of patients with a stroke of undetermined etiology presented with IAC. Assessing IAC burden may help identify the cause in ischemic stroke of undetermined etiology, and could offer important prognostic information.

Advancements in diagnostic and interventional radiology for stroke treatment: the path from trial to bedside through the pre-MR CLEAN, MR CLEAN, and MR CLEAN II eras.

The stroke field is inevitably connected with imaging in which radiologists fulfill a central role. Our landmark MR CLEAN trial led to the implementation of baseline computed tomography angiography or magnetic resonance angiography in the acute stroke workup and subsequent endovascular treatment (EVT) for ischemic stroke patients with a large vessel occlusion in the anterior circulation, resulting in numerous patients worldwide currently being treated often successfully. A reversal of the pathophysiologic process behind an acute cerebrovascular event was made possible. Subsequently, in the MR CLEAN II trials, the clinical impact of both diagnostic and interventional radiologists remained a cornerstone of our research, which means value-based radiology. Within these MR CLEAN II trials, we proved that aspirin and heparin during EVT should be avoided due to increased symptomatic intracranial hemorrhage risk (MR CLEAN-MED). We concluded there is additional benefit of EVT in the 6-to-24-h window after stroke in the presence of good collaterals on baseline CTA (MR CLEAN-LATE). The impactful success of our stroke trials that changed many guidelines was mainly attributable to (1) the societal burden of the disease, with two thirds of patients dying or being independent at 3 months; (2) the fact that stroke is a common disease, (3) the relatively simple and pragmatic approach of the trials resembling real-world setting; (4) the acceleration of implementation in clinical practice facilitated by a structured approach to guideline development and conditional funding; and foremost (5) the excellent collaboration on a professional level between-disciplines, i.e., diagnostic radiologists, interventionalists, and neurologists.Critical relevance statement The MR CLEAN and MR CLEAN II trials have had tremendous impact on clinical practice, directly by more patients being treated with an effective intervention and indirectly through adoption of evidence-based guidelines. It is in this setting of stroke treatment that diagnostic and interventional radiologists have played a crucial role and created clinical impact.

Implications of Post-recanalization Perfusion Deficit After Acute Ischemic Stroke: a Scoping Review of Clinical and Preclinical Imaging Studies.

The goal of reperfusion therapy for acute ischemic stroke (AIS) is to restore cerebral blood flow through recanalization of the occluded vessel. Unfortunately, successful recanalization does not always result in favorable clinical outcome. Post-recanalization perfusion deficits (PRPDs), constituted by cerebral hypo- or hyperperfusion, may contribute to lagging patient recovery rates, but its clinical significance remains unclear. This scoping review provides an overview of clinical and preclinical findings on post-ischemic reperfusion, aiming to elucidate the pattern and consequences of PRPD from a translational perspective. The MEDLINE database was searched for quantitative clinical and preclinical studies of AIS reporting PRPD based on cerebral circulation parameters acquired by translational tomographic imaging methods. PRPD and stroke outcome were mapped on a charting table, creating an overview of PRPD after AIS. Twenty-two clinical and twenty-two preclinical studies were included. Post-recanalization hypoperfusion is rarely reported in clinical studies (4/22) but unequivocally associated with detrimental outcome. Post-recanalization hyperperfusion is more commonly reported (18/22 clinical studies) and may be associated with positive or negative outcome. PRPD has been replicated in animal studies, offering mechanistic insights into causes and consequences of PRPD and allowing delineation of possible courses of PRPD. Complex relationships exist between PRPD and stroke outcome. Diversity in methods and lack of standardized definitions in reperfusion studies complicate the characterization of reperfusion patterns. Recommendations are made to advance the understanding of PRPD mechanisms and to further disentangle the relation between PRPD and disease outcome.

Automated image registration of cerebral digital subtraction angiography.

PURPOSE: Our aim is to automatically align digital subtraction angiography (DSA) series, recorded before and after endovascular thrombectomy. Such alignment may enable quantification of procedural success. METHODS: Firstly, we examine the inherent limitations for image registration, caused by the projective characteristics of DSA imaging, in a representative set of image pairs from thrombectomy procedures. Secondly, we develop and assess various image registration methods (SIFT, ORB). We assess these methods using manually annotated point correspondences for thrombectomy image pairs. RESULTS: Linear transformations that account for scale differences are effective in aligning DSA sequences. Two anatomical landmarks can be reliably identified for registration using a U-net. Point-based registration using SIFT and ORB proves to be most effective for DSA registration and are applicable to recordings for all patient sub-types. Image-based techniques are less effective and did not refine the results of the best point-based registration method. CONCLUSION: We developed and assessed an automated image registration approach for cerebral DSA sequences, recorded before and after endovascular thrombectomy. Accurate results were obtained for approximately 85% of our image pairs.

Cerebrovascular Abnormalities in Adults Born SGA at 12 Years After Growth Hormone Cessation Compared to Controls.

CONTEXT: Increased cerebrovascular morbidity was reported in adults born small for gestational age (SGA) who were treated with growth hormone (GH) during childhood compared to the general population. However, previous studies did not have an appropriate control group, which is a major limitation. OBJECTIVE: To study cerebrovascular abnormalities (aneurysms, previous intracerebral hemorrhages and microbleeds) using magnetic resonance imaging (MRI) in adults born SGA at 12 years after cessation of childhood GH treatment (SGA-GH) compared to appropriate controls. METHODS: In this single-center, prospective study, brain MRIs were performed between May 2016 and December 2020 on a 3T MRI system. MRI images were scored by 2 neuroradiologists who were blinded to patient groupings. Participants included adults born SGA previously treated with GH and 3 untreated control groups: adults born SGA with persistent short stature (SGA-S), adults born SGA with spontaneous catch-up growth to a normal height (SGA-CU) and adults born appropriate for gestational age with a normal height (AGA). The intervention was long-term GH treatment during childhood and the main outcome measure was cerebrovascular abnormalities. RESULTS: A total of 301 adults were investigated. Aneurysms were found in 6 adults: 3 (3.6%) SGA-GH, 1 (2.9%) SGA-S and 2 (2.2%) AGA adults, without differences between SGA-GH adults and the controls. Previous intracerebral hemorrhages were only found in 2 SGA-S adults (4.8%). Microbleeds were found in 17 adults: 4 (4.3%) SGA-GH, 4 (9.5%) SGA-S, 3 (4.3%) SGA-CU and 6 (6.3%) AGA adults, without differences between SGA-GH adults and the controls. CONCLUSION: Our findings suggest that SGA-GH adults at 12 years after GH cessation have no increased prevalence of cerebrovascular abnormalities compared to appropriate controls. Further research is needed to confirm our findings.

Carotid Plaque-RADS: A Novel Stroke Risk Classification System.

BACKGROUND: Carotid artery atherosclerosis is highly prevalent in the general population and is a well-established risk factor for acute ischemic stroke. Although the morphological characteristics of vulnerable plaques are well recognized, there is a lack of consensus in reporting and interpreting carotid plaque features. OBJECTIVES: The aim of this paper is to establish a consistent and comprehensive approach for imaging and reporting carotid plaque by introducing the Plaque-RADS (Reporting and Data System) score. METHODS: A panel of experts recognized the necessity to develop a classification system for carotid plaque and its defining characteristics. Using a multimodality analysis approach, the Plaque-RADS categories were established through consensus, drawing on existing published reports. RESULTS: The authors present a universal classification that is applicable to both researchers and clinicians. The Plaque-RADS score offers a morphological assessment in addition to the prevailing quantitative parameter of "stenosis." The Plaque-RADS score spans from grade 1 (indicating complete absence of plaque) to grade 4 (representing complicated plaque). Accompanying visual examples are included to facilitate a clear understanding of the Plaque-RADS categories. CONCLUSIONS: Plaque-RADS is a standardized and reliable system of reporting carotid plaque composition and morphology via different imaging modalities, such as ultrasound, computed tomography, and magnetic resonance imaging. This scoring system has the potential to help in the precise identification of patients who may benefit from exclusive medical intervention and those who require alternative treatments, thereby enhancing patient care. A standardized lexicon and structured reporting promise to enhance communication between radiologists, referring clinicians, and scientists.

Development and validation of a prediction model for failure of the transfemoral approach of endovascular treatment for large vessel occlusion acute ischemic stroke.

INTRODUCTION: Extracranial vascular characteristics determine the accessibility of the large vessel intracranial occlusion for endovascular treatment (EVT) in acute ischemic stroke. We developed and validated a prediction model for failure of the transfemoral approach to aid clinical decision making regarding EVT. METHODS: A prediction model was developed from data of patients included in the Dutch multicenter MR CLEAN Registry (March 18th 2014 until June 15th 2016) with penalized logistic regression. Predictor variables were available prior to the EVT procedure and included age, hypertension and extracranial vascular characteristics assessed on baseline CTA. The prediction model was internally validated, temporally validated within a second MR CLEAN Registry cohort (June 15th 2016 until November 1st 2017) and updated by re-estimating the coefficients using the combined cohort. RESULTS: Failure of the transfemoral approach occurred in 7% of patients, in both cohorts (derivation cohort: n=887, median age 71 years, interquartile range [IQR] 60-80, 52% men; validation cohort: n=1111, median age 73 years, IQR 62-81, 51% men). The prediction model had a c-statistic of 0.81 (95%CI: 0.76-0.86) in the derivation cohort, 0.69 (95%CI: 0.62-0.75) at temporal validation, and 0.75 (95%CI: 0.71-0.79) in the final prediction model, with the following penalized ß-coefficients for predictors age (per decade): 0.26, hypertension: -0.16, severe aortic arch elongation: 1.45, bovine aortic arch: 0.44, elongation of the supra-aortic arteries: 0.72, cervical ICA elongation: 0.44, and high-grade stenosis of the cervical ICA: 0.78. CONCLUSION: Our prediction model showed good performance for prediction of failure to reach the intracranial occlusion by the transfemoral approach.

Identifying lipid traces of atherogenic mechanisms in human carotid plaque.

BACKGROUND AND AIMS: Lipids play an important role in atherosclerotic plaque development and are interesting candidate predictive biomarkers. However, the link between circulating lipids, accumulating lipids in the vessel wall, and plaque destabilization processes in humans remains largely unknown. This study aims to provide new insights into the role of lipids in atherosclerosis using lipidomics and mass spectrometry imaging to investigate lipid signatures in advanced human carotid plaque and plasma samples. METHODS: We used lipidomics and desorption electrospray ionization mass spectrometry imaging (DESI-MSI) to investigate lipid signatures of advanced human carotid plaque and plasma obtained from patients who underwent carotid endarterectomy (n = 14 out of 17 whose plaque samples were analyzed by DESI-MSI). Multivariate data analysis and unsupervised clustering were applied to identify lipids that were the most discriminative species between different patterns in plaque and plasma. These patterns were interpreted by quantitative comparison with conventional histology. RESULTS: Lipidomics detected more than 300 lipid species in plasma and plaque, with markedly different relative abundances. DESI-MSI visualized the spatial distribution of 611 lipid-related m/z features in plaques, of which 330 m/z features could be assigned based on exact mass, comparison to the lipidomic data, and high mass resolution MSI. Matching spatial lipid patterns to histological areas of interest revealed several molecular species that were colocalized with pertinent disease processes in plaque including specific sphingomyelin and ceramide species with calcification, phospholipids and free fatty acids with inflammation, and triacylglycerols and phosphatidylinositols with fibrin-rich areas. CONCLUSIONS: By comparing lipid species in plaque and plasma, we identified those circulating species that were also prominently present in plaque. Quantitative comparison of lipid spectral patterns with histology revealed the presence of specific lipid species in destabilized plaque areas, corroborating previous in vitro and animal studies.