Penumbral Imaging Research Articles

基于X光微点源的半影成像技术

基于X光微点源的半影成像技术

Prediction of infarction and reperfusion in stroke by flow- and volume-weighted collateral signal in MR angiography.

In proximal anterior circulation occlusive strokes, collateral flow is essential for good outcome. Collateralized vessel intensity in TOF- and contrast-enhanced MRA is variable due to different acquisition methods. Our purpose was to quantify collateral supply by using flow-weighted signal in TOF-MRA and blood volume-weighted signal in contrast-enhanced MRA to determine each predictive contribution to tissue infarction and reperfusion. Consecutively (2009-2013), 44 stroke patients with acute proximal anterior circulation occlusion met the inclusion criteria with TOF- and contrast-enhanced MRA and penumbral imaging. Collateralized vessels in the ischemic hemisphere were assessed by TOF- and contrast-enhanced MRA using 2 methods: 1) visual 3-point collateral scoring, and 2) collateral signal quantification by an arterial atlas-based collateral index. Collateral measures were tested by receiver operating characteristic curve and logistic regression against 2 imaging end points of tissue-outcome: final infarct volume and percentage of penumbra saved. Visual collateral scores on contrast-enhanced MRA but not TOF were significantly higher in patients with good outcome. Visual collateral scoring on contrast-enhanced MRA was the best rater-based discriminator for final infarct volume < 90 mL (area under the curve, 0.81; P < .01) and percentage of penumbra saved >50% (area under the curve, 0.67; P = .04). Atlas-based collateral index of contrast-enhanced MRA was the overall best independent discriminator for final infarct volume of <90 mL (area under the curve, 0.94; P < .01). Atlas-based collateral index combining the signal of TOF- and contrast-enhanced MRA was the overall best discriminator for effective reperfusion (percentage of penumbra saved >50%; area under the curve, 0.89; P < .001). Visual scoring of contrast-enhanced but not TOF-MRA is a reliable predictor of infarct outcome in stroke patients with proximal arterial occlusion. By atlas-based collateral assessment, TOF- and contrast-enhanced MRA both contain predictive signal information for penumbral reperfusion. This could improve risk stratification in further studies.

Self characterization of a coded aperture array for neutron source imaging.

The neutron imaging system at the National Ignition Facility (NIF) is an important diagnostic tool for measuring the two-dimensional size and shape of the neutrons produced in the burning deuterium-tritium plasma during the stagnation stage of inertial confinement fusion implosions. Since the neutron source is small (∼100 μm) and neutrons are deeply penetrating (>3 cm) in all materials, the apertures used to achieve the desired 10-μm resolution are 20-cm long, triangular tapers machined in gold foils. These gold foils are stacked to form an array of 20 apertures for pinhole imaging and three apertures for penumbral imaging. These apertures must be precisely aligned to accurately place the field of view of each aperture at the design location, or the location of the field of view for each aperture must be measured. In this paper we present a new technique that has been developed for the measurement and characterization of the precise location of each aperture in the array. We present the detailed algorithms used for this characterization and the results of reconstructed sources from inertial confinement fusion implosion experiments at NIF.

79.: EXtending the time for Thombolysis in Emergency Neurological Deficits: The EXTEND Trial

Current clinical application of thrombolysis in stroke is limited by the 4.5 hour time window and not applicable to patients with wake up stroke (WUS). Patient selection using advanced penumbral imaging criteria may allow extension of the therapeutic window. The EXtending the time for Thombolysis in Emergency Neurological Deficits (EXTEND) trial aims to test the hypothesis that perfusion-core mismatch can be used to select patients with favourable response to thrombolysis beyond conventional time windows. EXTEND is an investigator initiated, randomised, double-blind, placebo controlled phase 3 trial of intravenous alteplase versus placebo in patients with ischemic stroke 4.5–9 hours from stroke onset and WUS (defined as the midpoint between time to sleep and awakening with the stroke symptoms 6 seconds and a perfusion:core ratio of >1.2 with core volume

Wake-up stroke and stroke of unknown onset: a critical review.

Patients, who wake up with an ischemic stroke, account for a large number of the total stroke population, due to circadian morning predominance of stroke. Currently, this subset of patients is excluded from revascularization-therapy since no exact time of onset is known. A large group of these patients might be eligible for therapy. In this review, we assessed the current literature about the hypothesis that wake-up-strokes occur just prior on awakening and if this subgroup differs in characteristics compared to the overall stroke population. We looked at the safety and efficacy of thrombolysis and interventional techniques in the group of patients with unknown stroke-onset. We performed a meta-analysis of the diagnostic accuracy of the diffusion-FLAIR mismatch in identifying stroke within 3 and 4.5 h. The different imaging-selection criteria that can be used to treat these patients are discussed. Additional research on imaging findings associated with recent stroke and penumbral imaging will eventually lead to a shift from a rigid time-frame based therapy to a tissue-based individualized treatment approach.

Using penumbral imaging to measure micrometer size plasma hot spots in Gbar equation of state experiments on the National Ignition Facility.

We have developed an experimental platform for absolute equation of state measurements up to Gbar pressures on the National Ignition Facility (NIF) within the Fundamental Science Program. We use a symmetry-tuned hohlraum drive to launch a spherical shock wave into a solid CH sphere. Streaked radiography is the primary diagnostic to measure the density change at the shock front as the pressure increases towards smaller radii. At shock stagnation in the center of the capsule, we observe a short and bright x-ray self emission from high density (∼50 g/cm(3)) plasma at ∼1 keV. Here, we present results obtained with penumbral imaging which has been carried out to characterize the size of the hot spot emission. This allows extending existing NIF diagnostic capabilities for spatial resolution (currently ∼10 μm) at higher sensitivity. At peak emission we find the hot spot radius to be as small as 5.8 +/- 1 μm, corresponding to a convergence ratio of 200.

Assessment of image quality in x-ray radiography imaging using a small plasma focus device

This paper offers a comprehensive investigation of image quality parameters for a small plasma focus as a pulsed hard x-ray source for radiography applications. A set of images were captured from some metal objects and electronic circuits using a low energy plasma focus at different voltages of capacitor bank and different pressures of argon gas. The x-ray source focal spot of this device was obtained to be about 0.6mm using the penumbra imaging method. The image quality was studied by several parameters such as image contrast, line spread function (LSF) and modulation transfer function (MTF). Results showed that the contrast changes by variations in gas pressure. The best contrast was obtained at a pressure of 0.5mbar and 3.75kJ stored energy. The results of x-ray dose from the device showed that about 0.6mGy is sufficient to obtain acceptable images on the film. The measurements of LSF and MTF parameters were carried out by means of a thin stainless steel wire 0.8mm in diameter and the cut-off frequency was obtained to be about 1.5cycles/mm.

Wake-up stroke: clinical characteristics, imaging findings, and treatment option - an update.

About 25% of all strokes occur during sleep, i.e., without knowledge of exact time of symptom onset. According to licensing criteria, this large group of patients is excluded from treatment with received tissue-plasminogen activator, the only specific stroke treatment proven effective in large randomized trials. This paper reviews clinical and imaging characteristics of wake-up stroke and gives an update on treatment options for these patients. From clinical and imaging studies, there is evidence suggesting that many wake-up strokes occur close to awakening and thus, patients might be within the approved time-window of thrombolysis when presenting to the emergency department. Several imaging approaches are suggested to identify wake-up stroke patients likely to benefit from thrombolysis, including non-contrast CT, CT-perfusion, penumbral MRI, and the recent concept of diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR). A number of small case series and observational studies report results of thrombolysis in wake-up stroke, and no safety concerns have occurred, while conclusions on efficacy cannot be drawn from these studies. To this end, there are ongoing clinical trials enrolling wake-up stroke patients based on imaging findings, i.e., the DWI-FLAIR-mismatch (WAKE-UP) or penumbral imaging (EXTEND). The results of these trials will provide evidence to guide thrombolysis in wake-up stroke and thus, expand treatment options for this large group of stroke patients.

Blind deconvolution for spatial distribution of Kα emission from ultraintense laser-plasma interaction

The spatial distributions of the Kα emission from foil targets irradiated with ultra-intensity laser pulses have been studied using the x-ray coded imaging technique. Due to the effect of hard x-ray background contamination, noise as well as imperfection of imaging system, it is hard to determine the PSF analytically or measure it experimentally. Therefore, we propose a blind deconvolution method to restore both the spatial distributions of the Kα emission and the system's PSF from the coded images based on the maximum-likelihood scheme. Experimental restoration results from penumbral imaging and ring coded imaging demonstrated that both the structure integrity and the rich detail information can be well preserved.

Acute extracranial occlusion of the internal carotid artery: emergent surgery remains a viable option

Acute symptomatic occlusion of extracranial internal carotid artery (eICA) can lead to a critical and potentially devastating stroke associated with high morbidity and mortality. Optimal treatment remains unclear. We analyzed our institutional experience with emergent surgical recanalization of acutely occluded eICA. Retrospective analysis of hospital records, surgical reports, imaging studies and outpatient records. Final outcome was assessed according to modified Rankin Scale (mRS). Between January 2010 and September 2013, 22 patients underwent emergent surgical recanalization. There were 17 men and five women, mean age 65.4years (range 37-85). Mean admission National Institute of Health Stroke Scale (NIHSS) was 12 (range 6-21). All patients had evidence of salvageable penumbra on perfusion computed tomography. Tandem intracranial lesion was present in nine patients. Surgical recanalization was successful in 16 patients (72.7%). Twenty-four hours after surgery, 17 patients (77.2%) improved by a minimum of 1 point on NIHSS, 14 patients (63.6%) improved by three and more points; two patients deteriorated by two and five points, the latter treated initially with systemic thrombolysis due to intracranial hemorrhage. No other intracranial hematoma was observed. During 30days following surgery, two patients died (9% mortality rate) due to severity of initial stroke. On discharge, four patients were classified as mRS 0, five patients as mRS 1, five patients as mRS 2 and six patients as mRS 4. Favorable recovery (mRS 0-2) was achieved in 14 patients (63.6%). No change in mRS was observed at threemonths. Our results suggest that emergent surgical desobliteration of occluded eICA can lead to favorable recovery in a majority of patients. Patient selection based on penumbra imaging is crucial. Given the popularity and simplicity of carotid endarterectomy, the procedure should by no means be abandoned in the treatment of acute eICA occlusion.

Abstract 147: Time to Angiographic Reperfusion Predicts Good Clinical Outcome in the Penumbra Studies

BACKGROUND: Faster time to reperfusion (TTR) is associated with better clinical outcome in the IMS trials and other cohorts. We tested this association in the Penumbra-sponsored studies of exclusively mechanical embolectomy cases. METHODS: We pooled prospective (125 Pivotal, 289 PICS, 146 START) and retrospective/registry (157 POST, 225 RetroSTART) Penumbra cases. All were IV tPA-ineligible/refractory with treatment at &lt;8 hours. Penumbral imaging selection was based on local practice. Pivotal and PICS revascularization results were core lab-adjudicated. Outcome assessments were not necessarily blinded. For this analysis, we included the subcohort achieving TICI 2-3 reperfusion of either ICA, M1, or M2 occlusions. We tested the association of TTR (based on time of procedure completion) and good clinical outcome (mRS 0-2 at 90 days) in both unadjusted and adjusted analyses. Tested covariates [age (per 10 years), gender, NIHSS strata (10-19 vs 20+), glucose, target vessel (MCA vs ICA), ASPECTS (0-4 vs 5-10)] with p&lt;0.20 were considered in the multivariable model. RESULTS: Among 942 subjects, 75 were excluded due to occlusion site and 186 due to missing key data (141 mRS, 75 TICI, 38 TTP). Reperfusion was achieved in 563 (83%) of 681 cases. Among these 563 cases, TTR was associated with mRS 0-2 (OR 0.95; 95% CI 0.91-1.00; p=0.045); see graph. In the final model with complete covariate data (n=347; 69 Pivotal, 0 POST, 133 PICS, 88 START, 57 Retro), TTR remained associated with mRS 0-2 (OR 0.92; 95% CI 0.86-0.98; p=0.01). Missing data did not appear to influence the results. CONCLUSION: In this pooled cohort of Penumbra cases, TTR significantly predicted good clinical outcome. This is despite the possibility that registry data and local multimodal imaging selection methods could have favored inclusion of cases with better outcomes. Our findings suggest that rapid treatment should be emphasized regardless of the reperfusion and selection modality chosen.

Abstract T MP9: Analysis of MR RESCUE Dataset Employing DEFUSE 2 Target Mismatch Criteria for Defining Penumbra

Background: The MR RESCUE trial failed to show a benefit of endovascular therapy over standard medical care for first generation thrombectomy devices within 8 hours of onset of acute ischemic stroke. We now report a subset analysis of patients enrolled with MRI, employing DEFUSE 2 criteria to define favorable penumbral pattern (target mismatch) which differed from MR RESCUE penumbral prediction criteria. Methods: Patients with large vessel, anterior circulation strokes were randomized to mechanical embolectomy (Merci Retriever or Penumbra System) or standard care. Patients were categorized as having a favorable penumbral or non-penumbral pattern employing the DEFUSE 2 criteria for target mismatch ([Tmax &gt; 6s / thresholded ADC &lt; 600 х 10 −6 mm 2 /s] &gt; 1.8, thresholded ADC &lt; 70 cc, and Tmax &gt; 10 s &lt; 100 cc). Results: Among 118 total patients, 94 qualified for this analysis. Mean age was 65.8, mean time to enrollment 5.6 hours, median NIHSS 17, and 47% had target mismatch. Predicted core volume using DEFUSE 2 criteria (thresholded ADC volume &lt; 600 х 10 −6 mm 2 /s) was 18.8 cc (target mismatch) and 64.3 cc (non-target mismatch; p&lt;0.001). Revascularization in the embolectomy group was achieved in 62% (TICI 2a-3), and 21% (TICI 2b-3). Among all patients, mean 90-day mRS scores did not differ between embolectomy and standard care (3.8 vs 3.8; p=0.92). In patients with target mismatch, embolectomy was not superior to standard care (mean mRS 3.5 vs 3.3, p=0.78). Similarly, in patients without target mismatch, embolectomy was not superior (4.1 vs 4.3, p=0.67). Furthermore, there was no interaction between pretreatment penumbral imaging pattern employing DEFUSE 2 target mismatch criteria and treatment assignment in these 90-day mRS scores (p=0.11). Conclusions: In this analysis MR RESCUE patients enrolled with pretreatment MRI, use of the DEFUSE 2 criteria for target mismatch as a definition of penumbral pattern failed to identify a subset of patients with improved outcomes when treated with embolectomy. Further randomized, controlled studies employing new generation thrombectomy devices are needed to validate target mismatch as a selection criterion for acute stroke treatments.

Thrombolysis in acute ischemic stroke: issues and options

China is one of the countries with highest incidence of stroke in the world. However, the rate of intravenous thrombolysis for ischemic stroke is extremely low in China, which is related to traditional triage system and inefficient management, the potential of hemorrhagic transformation, and narrow therapeutic time window. In order to improve the clinical implementation of thrombolysis, it is necessary to look at the related issues and to refine the therapeutic protocol according to the international experiences. Careful screening of eligible patients is crucial to reduce the rate of symptomatic intracranial hemorrhage. The advanced penumbral imaging is believed to enhance patient selection and extend the therapeutic time window. In addition, endovascular therapy is increasingly utilized to raise the recanalization rate. All these measures would enhance the improvement of the clinical management for acute stroke patients.

R-L Method and BLS-GSM Denoising for Penumbra Image Reconstruction

When neutron yield is very low, reconstruction of coding penumbra image is rather difficult. In this paper, low-yield (109) 14 MeV neutron penumbra imaging was simulated by Monte Carlo method. The Richardson Lucy (R-L) iteration method was proposed to incorporated with Bayesian least square-Gaussian scale mixture model (BLS-GSM) wavelet denoising for the simulated image. Optimal number of R-L iterations was gotten by a large number of tests. The results show that compared with Wiener method and median filter denoising, this method is better in restraining background noise, the correlation coefficient Rsr between the reconstructed and the real images is larger, and the reconstruction result is better.

Treating Wake-Up Stroke Patients

In 20–25 % of stroke patients, stroke occurs during sleep. Due to the missing information on time of symptom onset, these patients with “wake-up stroke” are excluded from treatment with intravenous thrombolysis based on licensing criteria. Within the past years, however, new approaches to guide treatment in wake-up stroke patients have been suggested and are currently being tested in clinical trials. This article gives an overview of imaging and clinical characteristics of wake-up stroke patients and recent approaches to guide treatment in these patients. Penumbral imaging using multiparametric MRI including diffusion-weighted imaging (DWI) and perfusion imaging or multiparametric CT including CT perfusion is hypothesized to identify stroke patients with tissue at risk independent from time of symptom onset who might benefit from reperfusion treatment. This approach is currently being tested in the EXTEND trial, which also allows for randomization of wake-up stroke patients. A different approach is the use of multiparametric MRI to estimate lesion age in patients with unknown time of symptom onset based on the characteristic course of signal changes and MR parameter changes. The mismatch between a visible lesion on DWI and normal FLAIR (DWI–FLAIR mismatch) identifies patients that are likely to be within a time window of 4.5 h of symptom onset and thus likely to benefit from intravenous thrombolysis. This concept is used to enroll patients in the European randomized controlled WAKE-UP trial of MRI-based thrombolysis in patients with unknown time of symptom onset. The results of these clinical trials are expected to change clinical practice and to improve the treatment of wake-up stroke patients in the near future.

Diffusion and perfusion correlates of the 18F-MISO PET lesion in acute stroke: pilot study

Mapping the ischaemic penumbra in acute stroke is of considerable clinical interest. For this purpose, mapping tissue hypoxia with (18)F-misonidazole (FMISO) PET is attractive, and is straightforward compared to (15)O PET. Given the current emphasis on penumbra imaging using diffusion/perfusion MR or CT perfusion, investigating the relationships between FMISO uptake and abnormalities with these modalities is important. According to a prospective design, three patients (age 54-81 years; admission NIH stroke scale scores 16-22) with an anterior circulation stroke and extensive penumbra on CT- or MR-based perfusion imaging successfully completed FMISO PET, diffusion-weighted imaging and MR angiography 6-26 h after stroke onset, and follow-up FLAIR to map the final infarction. All had persistent proximal occlusion and a poor outcome despite thrombolysis. Significant FMISO trapping was defined voxel-wise relative to ten age-matched controls and mapped onto coregistered maps of the penumbra and irreversibly damaged ischaemic core. FMISO trapping was present in all patients (volume range 18-119 ml) and overlapped mainly with the penumbra but also with the core in each patient. There was a significant (p ≤ 0.001) correlation in the expected direction between FMISO uptake and perfusion, with a sharp FMISO uptake bend around the expected penumbra threshold. FMISO uptake had the expected overlap with the penumbra and relationship with local perfusion. However, consistent with recent animal data, our study suggests FMISO trapping may not be specific to the penumbra. If confirmed in larger samples, this preliminary finding would have potential implications for the clinical application of FMISO PET in acute ischaemic stroke.

Acute Stroke Imaging Research Roadmap II

The recent "Advanced Neuroimaging for Acute Stroke Treatment" meeting on September 7 and 8, 2007 in Washington DC, brought together stroke neurologists, neuroradiologists, emergency physicians, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute of Biomedical Imaging and Bioengineering (NIBIB), industry representatives, and members of the US Food and Drug Administration (FDA) to discuss the role of advanced neuroimaging in acute stroke treatment. The goals of the meeting were to assess state-of-the-art practice in terms of acute stroke imaging research and to propose specific recommendations regarding: (1) the standardization of perfusion and penumbral imaging techniques, (2) the validation of the accuracy and clinical utility of imaging markers of the ischemic penumbra, (3) the validation of imaging biomarkers relevant to clinical outcomes, and (4) the creation of a central repository to achieve these goals. The present article summarizes these recommendations and examines practical steps to achieve them.

Admission insular infarction >25% is the strongest predictor of large mismatch loss in proximal middle cerebral artery stroke.

Previous univariate analyses have suggested that proximal middle cerebral artery infarcts with insular involvement have greater severity and are more likely to progress into surrounding penumbral tissue at risk. We hypothesized that a practical, simple scoring method to assess percent insular ribbon infarction (PIRI score) would improve prediction of penumbral loss over other common imaging biomarkers. Of consecutive acute stroke patients from 2003 to 2008, 45 with proximal middle cerebral artery-only occlusion met inclusion criteria, including available penumbral imaging. Infarct (diffusion-weighted imaging), tissue at risk (magnetic resonance mean transit time), and final infarct volume (magnetic resonance/computed tomography) were manually segmented. Diffusion-weighted imaging images were rated according to the 5-point PIRI score (0, normal; 1, <25%; 2, 25%-49%; 3, 50%-74%; 4, ≥75% insula involvement). Percent mismatch loss was calculated as an outcome measure of infarct progression. Receiver operating characteristic curve and multivariate analyses were performed. Mean admission diffusion-weighted imaging infarct volume was 30.9 (±38.8) mL and median (interquartile range) PIRI score was 3 (0.75-4). PIRI score was significantly correlated with percent mismatch loss (P<0.0001). When percent mismatch loss was dichotomized based on its median value (30.0%), receiver operating characteristic curve area under curve was 0.89 (P=0.0001) with a 25% insula infarction optimal threshold. After adjusting for time to imaging and treatment, binary logistic regression, including dichotomized PIRI (25% threshold), age, National Institutes of Health Stroke Scale score, diffusion-weighted imaging infarct volume, and computed tomography angiography collateral score as covariates, revealed that only dichotomized insula score (P=0.03) and age (P=0.02) were independent predictors of large (68.2%) versus small (8.1%) mismatch loss. There was excellent interobserver agreement for dichotomized PIRI scoring (κ=0.91). Admission insular infarction >25% is the strongest predictor of large mismatch loss in this cohort of proximal middle cerebral artery occlusive stroke. This outcome marker may help to identify treatment-eligible patients who are in greatest need of rapid reperfusion therapy.

Commonly asked questions: thrombolytic therapy in the management of acute stroke

Questions about thrombolytic management arise frequently, often with the intent of ascertaining safety and efficacy in specific situations. Thrombolytic therapy is generally safe, even if a nonruptured intracranial aneurysm is present. The risk of cardiac rupture with tamponade is low, except for the first 7 weeks following myocardial infarction. Over this duration, there is an increased risk of intravenous thrombolytic therapy in specific patient groups. Stroke infrequently occurs during cardiac catheterization. Its infrequent occurrence has limited large treatment trials. Basilar artery occlusion management will be reviewed. Thrombolytic therapy is generally safe in the context of pre-existing cerebral microhemorrhages and cervical artery dissections. Additionally, the role of multimodal penumbral imaging in planning stroke therapy will be reviewed.

Advanced imaging to extend the therapeutic time window of acute ischemic stroke

Reperfusion therapy for acute stroke has evolved from the initial use of intravenous tissue plasminogen activator (tPA) within 3 hours of symptom onset to more recent guideline-recommended use up to 4.5 hours. In addition, endovascular therapy is increasingly utilized for stroke treatment and is typically initiated up to 8 hours after onset. Recent studies demonstrate that imaging of the ischemic penumbra with diffusion/perfusion magnetic resonance imaging (MRI) can identify subgroups of patients who are likely to improve following successful reperfusion (Target Mismatch profile) and others who are at increased risk for hemorrhage and poor clinical outcomes (Malignant profile). New data indicate that stent retriever devices provide better recanalization efficacy and clinical outcomes than the previously available mechanical thrombectomy devices. Going forward, we believe that the use of penumbral imaging with validated MRI techniques, as well as the currently less well-validated computed tomography (CT) perfusion approach, will maximize benefit and reduce the risk of adverse events and poor outcomes when used both early after stroke onset and at later time points. New trials that feature diffusion/perfusion MRI or CT perfusion-based patient selection for treatment with intravenous tPA and or endovascular therapies versus nonreperfused control groups are planned or in progress. We predict that these trials will confirm the hypothesis that penumbral imaging can enhance patient selection and extend the therapeutic time window for acute ischemic stroke.