Perfusion Imaging and Clinical Outcome in Acute Ischemic Stroke with Large Core.

OBJECTIVE: Mechanical thrombectomy (MT) is not recommended for acute stroke with large vessel occlusion (LVO) and a large volume of irreversibly injured tissue ("core"). Perfusion imaging may identify a subset of patients with large core who benefit from MT. METHODS: We compared two cohorts of LVO-related patients with large core (>50 ml on diffusion-weighted-imaging or CT-perfusion using RAPID), available perfusion imaging, and treated within 6 hours from onset by either MT + Best Medical Management (BMM) in one prospective study, or BMM alone in the pre-MT era from a prospective registry. Primary outcome was 90-day modified Rankin Scale ≤2. We searched for an interaction between treatment group and amount of penumbra as estimated by the mismatch ratio (MMRatio = critical hypoperfusion/core volume). RESULTS: Overall, 107 patients were included (56 MT + BMM and 51 BMM): Mean age was 68 ± 15 years, median core volume 99 ml (IQR: 72-131) and MMRatio 1.4 (IQR: 1.0-1.9). Baseline clinical and radiological variables were similar between the two groups, except for a higher intravenous thrombolysis rate in the BMM group. The MMRatio strongly modified the clinical outcome following MT (pinteraction < 0.001 for continuous MMRatio); MT was associated with a higher rate of good outcome in patients with, but not in those without, MMRatio>1.2 (adjusted OR [95% CI] = 6.8 [1.7-27.0] vs 0.7 [0.1-6.2], respectively). Similar findings were present for MMRatio ≥1.8 in the subgroup with core ≥70 ml. Parenchymal hemorrhage on follow-up imaging was more frequent in the MT + BMM group regardless of the MMRatio. INTERPRETATION: Perfusion imaging may help select which patients with large core should be considered for MT. Randomized studies are warranted. ANN NEUROL 2021;90:417-427.

Endovascular Therapy in Mild Ischemic Strokes Presenting Under 6 hours: An International Survey.

BACKGROUND: Endovascular therapy (EVT) for patients with mild ischemic stroke (NIHSS ≤5) and visible intracranial occlusion remains controversial, including within 6 hours of symptom onset. We conducted a survey to evaluate global practice patterns of EVT in this population. METHODS: Vascular stroke clinicians and neurointerventionalists were invited to participate through professional stroke listservs. The survey consisted of six clinical vignettes of mild stroke patients with intracranial occlusion. Cases varied by NIHSS, neurological symptoms and occlusion site. All had the same risk factors, time from symptom onset (5h) and unremarkable head CT. Advanced imaging data was available upon request. We explored independent case and responder specific factors associated with advanced imaging request and EVT decision. RESULTS: A total of 482/492 responders had analyzable data ([median age 44 (IQR 11.25)], 22.7% women, 77% attending, 22% interventionalist). Participants were from USA (45%), Europe (32%), Australia (12%), Canada (6%), and Latin America (5%). EVT was offered in 48% (84% M1, 29% M2 and 19% A2) and decision was made without advanced imaging in 66% of cases. In multivariable analysis, proximal occlusion (M1 vs. M2 or A2, p<0.001), higher NIHSS (p<0.001) and fellow level training (vs. attending; p=0.001) were positive predictors of EVT. Distal occlusions (M2 and A2) and higher age of responders were independently associated with increased advanced imaging requests. Compared to US and Australian responders, Canadians were less likely to offer EVT, while those in Europe and Latin America were more likely (p<0.05). CONCLUSIONS: Treatment patterns of EVT in mild stroke vary globally. Our data suggest wide equipoise exists in current treatment of this important subset of mild stroke.

Comparing the outcomes of two independent computed tomography perfusion softwares and their impact on therapeutic decisions in acute ischemic stroke.

BACKGROUND: To compare the computed tomography perfusion (CTP) outcomes derived from two commercial CTP processing software and evaluate their concordance in terms of eligibility for mechanical thrombectomy (MT) in acute ischemic stroke (AIS), based on DEFUSE III criteria. METHODS: A total of 118 patients (62 patients in the MT group and 56 patients in the non-MT (NMT) group) were included. Volumetric perfusion outputs were compared between Syngo.via (package A) and RAPID (package B). Influence on proceeding or not-proceeding with MT was based on DEFUSE III imaging eligibility criteria. RESULTS: Median core infarct/hypoperfusion volumes were 12.3/126 mL in the MT group and 7.7/29.3 ml in the NMT group with package A and 10.5/138 mL and 1.9/24.5 mL with package B, respectively. In the MT group (n=62), concordant perfusion results in terms of patient triage were noted in all but two cases. Of these, one patient would not have qualified (low ASPECTS), while the other qualified based on package A results. For the NMT group (n=56), there was discordance in terms of MT eligibility in seven cases. However, none of these patients qualified for MT based on DEFUSE III criteria. CONCLUSIONS: Both perfusion softwares showed high concordance in correctly triaging patients in the MT versus NMT groups (110/118, 93.2%), which further improved when all DEFUSE III imaging criteria were considered (117/118, 99.1%). The core/hypoperfusion volumes in the NMT group and core infarct volumes in the MT groups were comparable. The hypoperfusion volumes in the MT group varied slightly but did not affect triage between groups.

Patient-Level, Institutional, and Temporal Variations in Use of Imaging Modalities to Confirm Pulmonary Embolism.

BACKGROUND: The choice of the imaging modality for diagnosis of pulmonary embolism (PE) could be influenced by provider, patient or hospital characteristics, or over time. However, little is known about the choice of the diagnostic modalities in practice. The aim of this study was to evaluate the variations in the use of imaging modalities for patients with acute PE. METHODS: Using the data from Registro Informatizado Enfermedad TromboEmbolica (RIETE), a prospective international registry of patients with venous thromboembolism (March 2001-January 2019), we explored the imaging modalities used in patients with acute PE. The imaging modalities included computed tomography pulmonary angiography, ventilation/perfusion scanning, pulmonary angiography, a combination of these tests, or PE signs and symptoms plus imaging-confirmed proximal deep vein thrombosis but no chest imaging. RESULTS: Among 38 025 patients with confirmed PE (53.1% female, age: 67.3±17 years), computed tomography pulmonary angiography was the dominant modality of diagnosis in all RIETE enrollees (78.2% [99% CI, 77.6-78.7]); including pregnant patients (58.9% [99% CI, 47.7%-69.4%]) and patients with severe renal insufficiency (62.5% [99% CI, 59.9-65.0]). A greater proportion of patients underwent ventilation/perfusion scanning in larger hospitals compared with smaller hospitals (13.1% versus 7.3%, P<0.001). The use of computed tomography pulmonary angiography varied between 13.3% and 98.3% across the countries, and its use increased over time (46.5% in 2002 to 91.7% in 2018, P<0.001). CONCLUSIONS: In a large multinational PE registry, variations were observed in the use of imaging modalities according to patient or institutional factors and over time. However, computed tomography pulmonary angiography was the dominant modality of diagnosis, even in pregnancy and severe renal insufficiency. The safety, costs, and downstream effects of these tests on PE-related and non-PE-related outcomes warrant further investigation.

Triage imaging and outcome measures for large core stroke thrombectomy - a systematic review and meta-analysis.

BACKGROUND: Trials of endovascular thrombectomy (EVT) mostly excluded patients with large core strokes so the safety and efficacy of EVT is not well established in such patients. Moreover, the definition of large core and its measurement differ between semi-quantitative (ASPECTS) and quantitative (core volume) imaging modalities. We evaluated functional and safety outcomes in studies reporting large core stroke patients treated with EVT and compared them with patients treated with medical management (MM) only. METHODS: A systemic search using three large databases was performed to identify studies evaluating functional and safety outcomes in patients with large core strokes (ASPECTS<6 or core volume ≥50 cc) on CT, MRI, and Perfusion imaging according to PRISMA guidelines. A random-effect meta-analysis model was used to pool reported outcomes. RESULTS: Twelve studies reporting outcomes for patients treated with EVT compared with MM in large core strokes were included. A pooled random-effect meta-analysis of large core patients by either definition (ASPECTS <6 or ischemic core volume ≥50 cc or both) demonstrated increased functional independence (mRS-scores 0-2) rates with EVT (EVT: 122/491 (25%), MM: 45/691 (7%), pooled OR: 4.39 [95% CI: 2.53 to 7.64], overall effect Z-score: 5.25, P<0.00001, I2=37%, P for Cochran Q:0.15) and decreased mortality (EVT: 101/439 (23%), MM: 215/645 (33%), pooled OR:0.53 [95% CI: 0.40 to 0.71], overall effect Z-score:4.32, P<0.0001, I2=0%, P for Cochran Q:0.78) at 90 days, without significant increase in symptomatic intracranial hemorrhage (ICH) (EVT: 42/462 (9%), MM: 35/663 (5%), pooled OR: 1.68 [95% CI: 0.92 to 3.09], overall effect Z-score:1.68, P=0.09, I2=26%, P for Cochran Q:0.24). Similar effects were observed in studies reporting large core outcomes based on ASPECTS <6 and ischemic core volume ≥50 cc. We observed no heterogeneity between quantitative vs semi-quantitative large core definitions, different ischemic core thresholds, and studies reporting outcomes over different time windows in subgroup analyses. CONCLUSION: In large core stroke patients, EVT is associated with improved functional independence and lower mortality at 90 days without significant increase in symptomatic ICH across various definitions, thresholds of large core size, and time windows. Further randomized evidence is warranted to establish EVT efficacy and safety in this population.

Recanalization following Endovascular treatment and imaging of PErfusion, Regional inFarction and atrophy to Understand Stroke Evolution-NA1 (REPERFUSE-NA1).

RATIONALE: Following endovascular treatment, poor clinical outcomes are more frequent if the initial infarct core or volume of irreversible brain damage is large. Clinical outcomes may be improved using neuroprotective agents that reduce stroke volume and improve recovery. AIM: The aim of the REPERFUSE NA1 was to replicate the preclinical neuroprotection study that significantly reduced infarct volume in a primate model of ischemia reperfusion. Specifically, REPERFUSE NA1 will determine if administration of the neuroprotectant NA1 prior to endovascular therapy can significantly reduce early (Day 2 subtract Day 1 diffusion-weighted imaging volume) and delayed secondary infarct (90-day whole brain atrophy plus FLAIR volume-Day 1 diffusion-weighted imaging volume) growth, as measured by magnetic resonance imaging. METHODS AND DESIGN: REPERFUSE-NA1 is a magnetic resonance imaging observational substudy of ESCAPE-NA1 (ClinicalTrialGov NCT02930018). A total of 150 acute stroke patients will be recruited (including 20% attrition) that have been randomized to either NA1 or placebo in the ESCAPE-NA1 trial. STUDY OUTCOMES: Primary-Early infarct growth measured using diffusion-weighted imaging will be at least 30% smaller in patients receiving NA1 compared to placebo. Secondary-Delayed secondary stroke injury at 90 days will be significantly reduced in patients receiving NA1 compared to placebo, as well as delayed secondary growth at 90 days. CONCLUSION: REPERFUSE-NA1 will demonstrate the effect of NA1 neuroprotection on reducing the early and delayed stroke injury after reperfusion treatment.

Over-Testing for Suspected Pulmonary Embolism in American Emergency Departments: The Continuing Epidemic.

BACKGROUND: No recent data have investigated rates of diagnostic testing for pulmonary embolism (PE) in US emergency departments (EDs), and no data have examined computed tomographic pulmonary angiography (CTPA) rates in subgroups at high risk for adverse imaging outcomes, including young women and children. We hypothesized that over-testing for PE remains a problem. METHODS AND RESULTS: We used electronic health record and billing data for 16 EDs in Indiana and 11 hospitals in the Dallas-Fort Worth area from 2016 to 2019 to locate ED patients who had any of the following: D-dimer, CTPA, scintillation ventilation perfusion lung scanning or formal pulmonary angiography. The primary outcomes were ED encounter volume-adjusted CTPA rate, PE yield rate with subgroup reporting for children (<18 years) and women under 45 years. We also examined the most frequent diagnoses. From a total visit volume of 1 828 010 patient encounters, 97 125 (5.3% of the total volume) had a diagnostic test for PE, including 25 870 patients who had CTPA order without D-dimer (59% of all tests for PE). The yield rate for PE from CTPA scans was 1.3% (1.1%-1.5%) in Indiana and 4.8% (4.2%-5.1%) in Dallas-Fort Worth (pooled rate 3.1%). Linear regression showed that increased D-dimer ordering correlated with increased PE yield rate (Pearson's R2=0.43; P<0.001). From the pooled sample, 59% of CTPAs done were in women, with 21% of all CTPAs performed on women under 45 years of age, and 1.4% (1.3%-1.5%) on children. The most frequent diagnoses were symptom-based descriptions of chest pain (34%) and shortness of breath (6.5%) and the condition-based diagnosis of pneumonia (4.1%). CONCLUSIONS: Over-testing for PE in American EDs remains a major public health problem. Centers with higher D-dimer ordering had higher yield of PE on CTPA. These data suggest the potential for implementation of D-dimer based protocols to reduce low-yield CTPA ordering.

In vivo magnetic resonance imaging and spectroscopy. Technological advances and opportunities for applications continue to abound.

Over the past decades, the field of in vivo magnetic resonance (MR) has built up an impressive repertoire of data acquisition and analysis technologies for anatomical, functional, physiological, and molecular imaging, the description of which requires many book volumes. As such it is impossible for a few authors to have an authoritative overview of the field and for a brief article to be inclusive. We will therefore focus mainly on data acquisition and attempt to give some insight into the principles underlying current advanced methods in the field and the potential for further innovation. In our view, the foreseeable future is expected to show continued rapid progress, for instance in imaging of microscopic tissue properties in vivo, assessment of functional and anatomical connectivity, higher resolution physiologic and metabolic imaging, and even imaging of receptor binding. In addition, acquisition speed and information content will continue to increase due to the continuous development of approaches for parallel imaging (including simultaneous multi-slice imaging), compressed sensing, and MRI fingerprinting. Finally, artificial intelligence approaches are becoming more realistic and will have a tremendous effect on both acquisition and analysis strategies. Together, these developments will continue to provide opportunity for scientific discovery and, in combination with large data sets from other fields such as genomics, allow the ultimate realization of precision medicine in the clinic.

A longitudinal characterization of perfusion in the aging brain and associations with cognition and neural structure.

Cerebral perfusion declines across the lifespan and is altered in the early stages of several age-related neuropathologies. Little is known, however, about the longitudinal evolution of perfusion in healthy older adults, particularly when perfusion is quantified using magnetic resonance imaging with arterial spin labeling (ASL). The objective was to characterize longitudinal perfusion in typically aging adults and elucidate associations with cognition and brain structure. Adults who were functionally intact at baseline (n = 161, ages 47-89) underwent ASL imaging to quantify whole-brain gray matter perfusion; a subset (n = 136) had repeated imaging (average follow-up: 2.3 years). Neuropsychological testing at each visit was summarized into executive function, memory, and processing speed composites. Global gray matter volume, white matter microstructure (mean diffusivity), and white matter hyperintensities were also quantified. We assessed baseline associations among perfusion, cognition, and brain structure using linear regression, and longitudinal relationships using linear mixed effects models. Greater baseline perfusion, particularly in the left dorsolateral prefrontal cortex and right thalamus, was associated with better executive functions. Greater whole-brain perfusion loss was associated with worsening brain structure and declining processing speed. This study helps validate noninvasive MRI-based perfusion imaging and underscores the importance of cerebral blood flow in cognitive aging.

Hypoperfusion ratio predicts infarct growth during transfer for thrombectomy.

We hypothesized that automated assessment of collaterals on computed tomography perfusion can predict the rate of infarct growth during transfer from a primary to a comprehensive stroke center for endovascular stroke treatment. We identified consecutive patients (N = 28) and assessed their collaterals based on the hypoperfusion intensity ratio (HIR) prior to transfer. Infarct growth rate was strongly correlated with HIR (r = 0.78, p < 0.001). Receiver operating characteristic analysis identified HIR ≥ 0.5 as optimal for predicting infarct growth. Patients with HIR ≥ 0.5 had a median infarct growth rate of 10.1ml/h (interquartile range [IQR] = 6.4-18.4) compared with 0.9ml/h (IQR = 0-2.8; p < 0.001) in patients with HIR < 0.5. Patients with HIR ≥ 0.5 had an 83% probability of significant core growth, whereas patients with HIR < 0.5 had an 88% probability of core stability. These preliminary data have the potential to guide decision making regarding whether repeat brain imaging should be performed after transfer to a comprehensive stroke center. Ann Neurol 2018;84:616-620.

Time-Resolved C-Arm Computed Tomographic Angiography Derived From Computed Tomographic Perfusion Acquisition: New Capability for One-Stop-Shop Acute Ischemic Stroke Treatment in the Angiosuite.

BACKGROUND AND PURPOSE: Multimodal imaging using cone beam C-arm computed tomography (CT) may shorten the delay from ictus to revascularization for acute ischemic stroke patients with a large vessel occlusion. Largely because of limited temporal resolution, reconstruction of time-resolved CT angiography (CTA) from these systems has not yielded satisfactory results. We evaluated the image quality and diagnostic value of time-resolved C-arm CTA reconstructed using novel image processing algorithms. METHODS: Studies were done under an Institutional Review Board approved protocol. Postprocessing of data from 21 C-arm CT dynamic perfusion acquisitions from 17 patients with acute ischemic stroke were done to derive time-resolved C-arm CTA images. Two observers independently evaluated image quality and diagnostic content for each case. ICC and receiver-operating characteristic analysis were performed to evaluate interobserver agreement and diagnostic value of this novel imaging modality. RESULTS: Time-resolved C-arm CTA images were successfully generated from 20 data sets (95.2%, 20/21). Two observers agreed well that the image quality for large cerebral arteries was good but was more limited for small cerebral arteries (distal to M1, A1, and P1). receiver-operating characteristic curves demonstrated excellent diagnostic value for detecting large vessel occlusions (area under the curve=0.987-1). CONCLUSIONS: Time-resolved CTAs derived from C-arm CT perfusion acquisitions provide high quality images that allowed accurate diagnosis of large vessel occlusions. Although image quality of smaller arteries in this study was not optimal ongoing modifications of the postprocessing algorithm will likely remove this limitation. Adding time-resolved C-arm CTAs to the capabilities of the angiography suite further enhances its suitability as a one-stop shop for care for patients with acute ischemic stroke.

The Year in Cardiology 2012: imaging, computed tomography, and cardiovascular magnetic resonance.

The year of 2012 has seen many significant publications in cardiac imaging, particularly in the modalities of cardiovascular magnetic resonance and cardiac computed tomography. This article will review in brief some of the most important studies with a particular emphasis on the new evidence base for perfusion imaging both by cardiovascular magnetic resonance and computed tomography.

Emerging trends in CV flow visualization.

Blood flow patterns are closely linked to the morphology and function of the cardiovascular system. These patterns reflect the exceptional adaptability of the cardiovascular system to maintain normal blood circulation under a wide range of workloads. Accurate retrieval and display of flow-related information remains a challenge because of the processes involved in mapping the flow velocity fields within specific chambers of the heart. We review the potentials and pitfalls of current approaches for blood flow visualization, with an emphasis on acquisition, display, and analysis of multidirectional flow. This document is divided into 3 sections. First, we provide a descriptive outline of the relevant concepts in cardiac fluid mechanics, including the emergence of rotation in flow and the variables that delineate vortical structures. Second, we elaborate on the main methods developed to image and visualize multidirectional cardiovascular flow, which are mainly based on cardiac magnetic resonance, ultrasound Doppler, and contrast particle imaging velocimetry, with recommendations for developing dedicated imaging protocols. Finally, we discuss the potential clinical applications and technical challenges with suggestions for further investigations.