Prediction of subsequent hemorrhage in acute ischemic stroke using permeability CT imaging and a distributed parameter tracer kinetic model

Bisdas, Sotirios; Hartel, Marcin; Cheong, L.H.; Koh, Tong San; Vogl, Thomas J.

doi:10.1016/j.neurad.2007.02.003

Cited by 35 publications

(48 citation statements)

References 12 publications

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“…Several studies have shown that the extent of BBB disruption as assessed with DCE-MRI correlates with the risk of developing HT. 6,41,[46][47][48] A multicenter study with 296 patients incorporated DCE-MRI into a multivariable model to predict the risk of HT with high sensitivity and specificity. 6 The therapeutic window of recombinant tissue-type plasminogen activator is currently constrained to 4.5 hours because of the risks associated with delivering recombinant tissue-type plasminogen activator at a later time point.…”

Section: Translational Potential: Bbb Assessment In the Clinicmentioning

confidence: 99%

Assessment of Blood–Brain Barrier Disruption in Stroke

Kassner

Merali

2015

Stroke

126

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T he disease burden of acute ischemic stroke (AIS) is rising in the United States and Canada. It is estimated that in the United States 795 000 people have a stroke each year, which amounts to $34 billion in medical expenses and lost productivity.1 Recent trials have shown the potential benefit of procedural thrombectomy in the management of AIS. 2 However, despite substantial research expenditures over the past 2 decades, there have been no new pharmacological agents for the initial treatment of AIS since the approval of recombinant tissue-type plasminogen activator in 1996. Recently, the role of the blood-brain barrier (BBB) in the pathogenesis of AIS has emerged as a focus for new therapeutic strategies. After the onset of AIS, the BBB is rapidly disrupted and this disruption persists for days through the acute and early subacute phases of AIS. The disruption of the BBB can be quantified as an increase in the permeability of the BBB (Figure 1). 4 In the setting of AIS, disruption of the BBB is thought to be a precursor to serious clinical consequences such as hemorrhagic transformation (HT), 5-7 which refers to the development of a hemorrhage within the ischemic brain tissue. Current research is attempting to elucidate the mechanisms of BBB disruption after AIS and develop therapeutic strategies to mitigate the clinical consequences of BBB disruption.Given these developments, a greater number of preclinical and clinical studies are incorporating assessment of BBB disruption into their study designs. Although assessment of BBB disruption may once have been technically difficult, a plethora of methods now exist to assess BBB disruption with relative ease in animal models and humans. When taken together, these methods cover a wide range of temporal and spatial resolutions and permit simultaneous assessment of cell morphology, protein expression and localization, cell electrophysiology, and gross neurological function. An awareness of the specifications and limitations of the methods of assessing BBB disruption is necessary to design effective studies and evaluate the literature.In the present review, we summarize the available methods of assessing BBB permeability in animal models and humans. We strive to highlight the relative strengths and weaknesses of these methods and provide suggestions for study design in stroke research. Finally, we discuss recent translational developments in assessing BBB disruption for the treatment of AIS. Ex Vivo Assessment of BBB DisruptionThe pioneering experiments of Max Lewandowsky first defined the BBB as a dynamic barrier separating the intravascular and extravascular compartments. This laid the groundwork for current methods of assessing BBB disruption in AIS animal models and human trials.8 All methods of assessing BBB disruption are common in their use of tracers, which can be either endogenous if they are naturally found in the blood or exogenous if introduced into the circulation by the experimenter. Table I in the online-only Data Supplement summarizes methods of ass...

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Section: Translational Potential: Bbb Assessment In the Clinicmentioning

confidence: 99%

Assessment of Blood–Brain Barrier Disruption in Stroke

Kassner

Merali

2015

Stroke

126

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“…More recently, a promising new approach involving BBBP imaging has been proposed. [15][16][17][18][19][20][21][22] It models the extravasation of a contrast agent from the intravascular space to the extravascular space and can demonstrate elevated BBBP as an indicator of ischemia-induced vascular damage in stroke. BBBP imaging provides a physiologic individualized measurement intimately connected to the underlying pathophysiology of PH-2 (ischemia-induced vascular damage followed by reperfusion) 23 and may, therefore, offer excellent sensitivity and specificity.…”

mentioning

confidence: 99%

“…Abnormally elevated BBBP measurements extracted from both PCT [15][16][17][18][19] and MR imaging studies [20][21][22] have been explored as physiologic predictors of SHT. Notably, most of the prior PCT studies have used first-pass data, [15][16][17][18] though a recent study has shown that using first-pass rather than delayedacquisition data results in inaccurate BBBP measurements.…”

mentioning

confidence: 99%

“…Notably, most of the prior PCT studies have used first-pass data, [15][16][17][18] though a recent study has shown that using first-pass rather than delayedacquisition data results in inaccurate BBBP measurements. 24 One recent PCT study used delayed-acquisition data 19 ; the study involved a quantitative model that had promising predictive power for HT in general but was unable to differentiate between patients destined for PH-2, the only form of hemorrhage definitively linked to poor outcomes in major stroke trials, 6 and more minor forms of hemorrhage of the petechial variety.…”

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confidence: 99%

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Blood-Brain Barrier Permeability Assessed by Perfusion CT Predicts Symptomatic Hemorrhagic Transformation and Malignant Edema in Acute Ischemic Stroke

Hom

Dankbaar

Soares

et al. 2010

AJNR Am J Neuroradiol

146

102

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“…The scans were acquired using a Philips Brilliance iCT scanner (Philips Healthcare) at 80 kVp and 150 mAs/rot and a field-of-view of B200 Â 200 mm 2 with an axial coverage of 65 mm at most. The total acquisition time was 210 seconds, divided into 25 frames with a 2-second interval, followed by 6 frames with a 30-second interval ( Figure 1A).…”

Section: Computed Tomography Brain Perfusion Scansmentioning

confidence: 99%

A Fast Nonlinear Regression Method for Estimating Permeability in CT Perfusion Imaging

Bennink

Riordan

Horsch

et al. 2013

J Cereb Blood Flow Metab

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Blood-brain barrier damage, which can be quantified by measuring vascular permeability, is a potential predictor for hemorrhagic transformation in acute ischemic stroke. Permeability is commonly estimated by applying Patlak analysis to computed tomography (CT) perfusion data, but this method lacks precision. Applying more elaborate kinetic models by means of nonlinear regression (NLR) may improve precision, but is more time consuming and therefore less appropriate in an acute stroke setting. We propose a simplified NLR method that may be faster and still precise enough for clinical use. The aim of this study is to evaluate the reliability of in total 12 variations of Patlak analysis and NLR methods, including the simplified NLR method. Confidence intervals for the permeability estimates were evaluated using simulated CT attenuation-time curves with realistic noise, and clinical data from 20 patients. Although fixating the blood volume improved Patlak analysis, the NLR methods yielded significantly more reliable estimates, but took up to 12 Â longer to calculate. The simplified NLR method was B4 Â faster than other NLR methods, while maintaining the same confidence intervals (CIs). In conclusion, the simplified NLR method is a new, reliable way to estimate permeability in stroke, fast enough for clinical application in an acute stroke setting.

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Prediction of subsequent hemorrhage in acute ischemic stroke using permeability CT imaging and a distributed parameter tracer kinetic model

Cited by 35 publications

References 12 publications

Assessment of Blood–Brain Barrier Disruption in Stroke

Assessment of Blood–Brain Barrier Disruption in Stroke

Blood-Brain Barrier Permeability Assessed by Perfusion CT Predicts Symptomatic Hemorrhagic Transformation and Malignant Edema in Acute Ischemic Stroke

A Fast Nonlinear Regression Method for Estimating Permeability in CT Perfusion Imaging

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