George W.J. Harston

Identifying the ischaemic penumbra using pH-weighted magnetic resonance imaging

Harston et al. establish proof of principle for clinical use of pH-weighted MRI in patients with acute ischaemic stroke. Detailed tissue-level analysis reveals that cerebral intracellular pH, a marker of metabolic stress, is associated with eventual tissue outcome, and complements established imaging modalities.

Comparing different analysis methods for quantifying the MRI amide proton transfer (APT) effect in hyperacute stroke patients.

Amide proton transfer (APT) imaging is a pH mapping method based on the chemical exchange saturation transfer phenomenon that has potential for penumbra identification following stroke. The majority of the literature thus far has focused on generating pH‐weighted contrast using magnetization transfer ratio asymmetry analysis instead of quantitative pH mapping. In this study, the widely used asymmetry analysis and a model‐based analysis were both assessed on APT data collected from healthy subjects (n = 2) and hyperacute stroke patients (n = 6, median imaging time after onset = 2 hours 59 minutes). It was found that the model‐based approach was able to quantify the APT effect with the lowest variation in grey and white matter (≤ 13.8 %) and the smallest average contrast between these two tissue types (3.48 %) in the healthy volunteers. The model‐based approach also performed quantitatively better than the other measures in the hyperacute stroke patient APT data, where the quantified APT effect in the infarct core was consistently lower than in the contralateral normal appearing tissue for all the patients recruited, with the group average of the quantified APT effect being 1.5 ± 0.3 % (infarct core) and 1.9 ± 0.4 % (contralateral). Based on the fitted parameters from the model‐based analysis and a previously published pH and amide proton exchange rate relationship, quantitative pH maps for hyperacute stroke patients were generated, for the first time, using APT imaging.

Imaging Biomarkers in Acute Ischemic Stroke Trials: A Systematic Review

BACKGROUND AND PURPOSE: Imaging biomarkers are increasingly used to provide a better understanding of the pathophysiology of acute ischemic stroke. However, this approach of routinely using imaging biomarkers to inform treatment decisions has yet to be translated into successful randomized trials. The aim of this study was to systematically review the use of imaging biomarkers in randomized controlled trials in patients with acute ischemic stroke, exploring the purposes for which the imaging biomarkers were used. MATERIALS AND METHODS: We performed a systematic review of imaging biomarkers used in randomized controlled trials of acute ischemic stroke, in which a therapeutic intervention was trialed within 48 hours of symptom onset. Data bases searched included MEDLINE, EMBASE, strokecenter.org, and the Virtual International Stroke Trials Archive (1995–2014). RESULTS: Eighty-four studies met the criteria, of which 49 used imaging to select patients; 31, for subgroup analysis; and 49, as an outcome measure. Imaging biomarkers were broadly used for 8 purposes. There was marked heterogeneity in the definitions and uses of imaging biomarkers and significant publication bias among post hoc analyses. CONCLUSIONS: Imaging biomarkers offer the opportunity to refine the trial cohort by minimizing participant variation, to decrease sample size, and to personalize treatment approaches for those who stand to benefit most. However, within imaging modalities, there has been little consistency between stroke trials. Greater effort to prospectively use consistent imaging biomarkers should help improve the development of novel treatment strategies in acute stroke and improve comparison between studies.

Quantification of amide proton transfer effect pre- and post-gadolinium contrast agent administration.

To compare quantification of the amide proton transfer (APT) effect pre‐ and post‐gadolinium contrast agent (Gd) administration in order to establish to what extent Gd alters quantification of the APT effect.

Quantification of Serial Cerebral Blood Flow in Acute Stroke Using Arterial Spin Labeling

Background and Purpose— Perfusion-weighted imaging is used to select patients with acute ischemic stroke for intervention, but knowledge of cerebral perfusion can also inform the understanding of ischemic injury. Arterial spin labeling allows repeated measurement of absolute cerebral blood flow (CBF) without the need for exogenous contrast. The aim of this study was to explore the relationship between dynamic CBF and tissue outcome in the month after stroke onset. Methods— Patients with nonlacunar ischemic stroke underwent ⩽5 repeated magnetic resonance imaging scans at presentation, 2 hours, 1 day, 1 week, and 1 month. Imaging included vessel-encoded pseudocontinuous arterial spin labeling using multiple postlabeling delays to quantify CBF in gray matter regions of interest. Receiver–operator characteristic curves were used to predict tissue outcome using CBF. Repeatability was assessed in 6 healthy volunteers and compared with contralateral regions of patients. Diffusion-weighted and T2-weighted fluid attenuated inversion recovery imaging were used to define tissue outcome. Results— Forty patients were included. In contralateral regions of patients, there was significant variation of CBF between individuals, but not between scan times (mean±SD: 53±42 mL/100 g/min). Within ischemic regions, mean CBF was lowest in ischemic core (17±23 mL/100 g/min), followed by regions of early (21±26 mL/100 g/min) and late infarct growth (25±35 mL/100 g/min; ANOVA P<0.0001). Between patients, there was marked overlap in presenting and serial CBF values. Conclusions— Knowledge of perfusion dynamics partially explained tissue fate. Factors such as metabolism and tissue susceptibility are also likely to influence tissue outcome.

Lacunar infarction associated with anabolic steroids and polycythemia: a case report.

Lacunar infarction is traditionally ascribed to lipohyalinosis or microatheroma. We report the case of 40-year-old man, without traditional risk factors for ischemic stroke, who presented to the Emergency Department with recurrent episodes of transient right-sided weakness and paresthesia. Lacunar infarction was confirmed on diffusion-weighted MRI and blood tests showed a marked polycythemia. Quantitative magnetic resonance perfusion imaging demonstrated dramatically abnormal perfusion throughout both cerebral hemispheres, and transcranial Doppler revealed reduced cerebral artery velocities, both consistent with the proposed mechanism of hyperviscosity. His symptoms settled with treatment of the polycythemia and workup did not find another cause of ischemic stroke. We propose that hyperviscosity secondary to steroid-induced polycythemia caused ischemia in this case and not lipohyalinosis or microatheroma, to which lacunar disease is commonly attributed.

Serial quantification of brain oxygenation in acute stroke using streamlined-qBOLD

It has been proposed that metabolic markers of baseline brain oxygenation have a role to play in the early identification of the ischemic penumbra. Streamlined-qBOLD is a magnetic resonance imaging technique that does not require exogenous contrast. It is a refinement of the quantitative BOLD methodology that provides a simplified approach to mapping and quantifying baseline brain oxygenation related parameters (reversible transverse relaxation rate (R2′), deoxygenated blood volume (DBV) and deoxyhaemoglobin concentration ([dHb])) in a clinically relevant manner. Streamlined-qBOLD was applied to an exploratory cohort of acute stroke patients in a serial imaging study. Detailed voxel-level analysis was used to quantify the metabolic profile of ischaemic tissue on presentation and investigate these metrics in relation to tissue outcome. Individual patient examples illustrate the appropriate interpretation of R2′, DBV and [dHb] in acute stroke and demonstrate the ability of this method to deliver regional information related to oxygen metabolism in the ischaemic tissue. Regional analysis confirms that R2′, DBV and [dHb] vary between regions of ischaemia with different tissue outcomes.

Ventricular extension of intracerebral hemorrhage during intravenous thrombolysis.

Acknowledgements and Sources of Funding The research was supported by the National Institute for Health Research Oxford Biomedical Research Centre Programme, the Dunhill Medical Trust (grant No. OSRP1/1006) and the Centre of Excellence for Personalized Healthcare funded by the Wellcome Trust and Engineering and Physical Sciences Research Council under grant No. WT 088877/Z/09/Z. We wish to acknowledge the facilities provided by the Oxford Acute Vascular Imaging Centre.