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Sources of systematic error in DCE‐MRI estimation of low‐level blood‐brain barrier leakage.

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Title: Sources of systematic error in DCE‐MRI estimation of low‐level blood‐brain barrier leakage.
Authors: Manning, Cameron1,2 (AUTHOR), Stringer, Michael1,2 (AUTHOR), Dickie, Ben3 (AUTHOR), Clancy, Una1,2 (AUTHOR), Valdés Hernandez, Maria C.1,2 (AUTHOR), Wiseman, Stewart J.1,2 (AUTHOR), Garcia, Daniela Jaime1,2 (AUTHOR), Sakka, Eleni1,2 (AUTHOR), Backes, Walter H.4 (AUTHOR), Ingrisch, Michael5 (AUTHOR), Chappell, Francesca1,2 (AUTHOR), Doubal, Fergus1,2 (AUTHOR), Buckley, Craig6 (AUTHOR), Parkes, Laura M.3 (AUTHOR), Parker, Geoff J. M.7 (AUTHOR), Marshall, Ian1,2,8 (AUTHOR), Wardlaw, Joanna M.1,2,8 (AUTHOR), Thrippleton, Michael J.1,2,8 (AUTHOR) m.j.thrippleton@ed.ac.uk
Source: Magnetic Resonance in Medicine. Oct2021, Vol. 86 Issue 4, p1888-1903. 16p.
Subjects: Blood-brain barrier, Ischemic stroke, Contrast media, Cerebral circulation, Blood products
Abstract: Purpose: Dynamic contrast‐enhanced (DCE) ‐MRI with Patlak model analysis is increasingly used to quantify low‐level blood‐brain barrier (BBB) leakage in studies of pathophysiology. We aimed to investigate systematic errors due to physiological, experimental, and modeling factors influencing quantification of the permeability‐surface area product PS and blood plasma volume vp, and to propose modifications to reduce the errors so that subtle differences in BBB permeability can be accurately measured. Methods: Simulations were performed to predict the effects of potential sources of systematic error on conventional PS and vp quantification: restricted BBB water exchange, reduced cerebral blood flow, arterial input function (AIF) delay and B1+ error. The impact of targeted modifications to the acquisition and processing were evaluated, including: assumption of fast versus no BBB water exchange, bolus versus slow injection of contrast agent, exclusion of early data from model fitting and B1+ correction. The optimal protocol was applied in a cohort of recent mild ischaemic stroke patients. Results: Simulation results demonstrated substantial systematic errors due to the factors investigated (absolute PS error ≤ 4.48 × 10−4 min−1). However, these were reduced (≤0.56 × 10−4 min−1) by applying modifications to the acquisition and processing pipeline. Processing modifications also had substantial effects on in‐vivo normal‐appearing white matter PS estimation (absolute change ≤ 0.45 × 10−4 min−1). Conclusion: Measuring subtle BBB leakage with DCE‐MRI presents unique challenges and is affected by several confounds that should be considered when acquiring or interpreting such data. The evaluated modifications should improve accuracy in studies of neurodegenerative diseases involving subtle BBB breakdown. [ABSTRACT FROM AUTHOR]
Copyright of Magnetic Resonance in Medicine is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Sources of systematic error in DCE‐MRI estimation of low‐level blood‐brain barrier leakage.
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  Data: <searchLink fieldCode="AR" term="%22Manning%2C+Cameron%22">Manning, Cameron</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Stringer%2C+Michael%22">Stringer, Michael</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Dickie%2C+Ben%22">Dickie, Ben</searchLink><relatesTo>3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Clancy%2C+Una%22">Clancy, Una</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Valdés+Hernandez%2C+Maria+C%2E%22">Valdés Hernandez, Maria C.</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wiseman%2C+Stewart+J%2E%22">Wiseman, Stewart J.</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Garcia%2C+Daniela+Jaime%22">Garcia, Daniela Jaime</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Sakka%2C+Eleni%22">Sakka, Eleni</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Backes%2C+Walter+H%2E%22">Backes, Walter H.</searchLink><relatesTo>4</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Ingrisch%2C+Michael%22">Ingrisch, Michael</searchLink><relatesTo>5</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Chappell%2C+Francesca%22">Chappell, Francesca</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Doubal%2C+Fergus%22">Doubal, Fergus</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Buckley%2C+Craig%22">Buckley, Craig</searchLink><relatesTo>6</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Parkes%2C+Laura+M%2E%22">Parkes, Laura M.</searchLink><relatesTo>3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Parker%2C+Geoff+J%2E+M%2E%22">Parker, Geoff J. M.</searchLink><relatesTo>7</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Marshall%2C+Ian%22">Marshall, Ian</searchLink><relatesTo>1,2,8</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wardlaw%2C+Joanna+M%2E%22">Wardlaw, Joanna M.</searchLink><relatesTo>1,2,8</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Thrippleton%2C+Michael+J%2E%22">Thrippleton, Michael J.</searchLink><relatesTo>1,2,8</relatesTo> (AUTHOR)<i> m.j.thrippleton@ed.ac.uk</i>
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  Data: <searchLink fieldCode="JN" term="%22Magnetic+Resonance+in+Medicine%22">Magnetic Resonance in Medicine</searchLink>. Oct2021, Vol. 86 Issue 4, p1888-1903. 16p.
– Name: Subject
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  Data: <searchLink fieldCode="DE" term="%22Blood-brain+barrier%22">Blood-brain barrier</searchLink><br /><searchLink fieldCode="DE" term="%22Ischemic+stroke%22">Ischemic stroke</searchLink><br /><searchLink fieldCode="DE" term="%22Contrast+media%22">Contrast media</searchLink><br /><searchLink fieldCode="DE" term="%22Cerebral+circulation%22">Cerebral circulation</searchLink><br /><searchLink fieldCode="DE" term="%22Blood+products%22">Blood products</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Purpose: Dynamic contrast‐enhanced (DCE) ‐MRI with Patlak model analysis is increasingly used to quantify low‐level blood‐brain barrier (BBB) leakage in studies of pathophysiology. We aimed to investigate systematic errors due to physiological, experimental, and modeling factors influencing quantification of the permeability‐surface area product PS and blood plasma volume vp, and to propose modifications to reduce the errors so that subtle differences in BBB permeability can be accurately measured. Methods: Simulations were performed to predict the effects of potential sources of systematic error on conventional PS and vp quantification: restricted BBB water exchange, reduced cerebral blood flow, arterial input function (AIF) delay and B1+ error. The impact of targeted modifications to the acquisition and processing were evaluated, including: assumption of fast versus no BBB water exchange, bolus versus slow injection of contrast agent, exclusion of early data from model fitting and B1+ correction. The optimal protocol was applied in a cohort of recent mild ischaemic stroke patients. Results: Simulation results demonstrated substantial systematic errors due to the factors investigated (absolute PS error ≤ 4.48 × 10−4 min−1). However, these were reduced (≤0.56 × 10−4 min−1) by applying modifications to the acquisition and processing pipeline. Processing modifications also had substantial effects on in‐vivo normal‐appearing white matter PS estimation (absolute change ≤ 0.45 × 10−4 min−1). Conclusion: Measuring subtle BBB leakage with DCE‐MRI presents unique challenges and is affected by several confounds that should be considered when acquiring or interpreting such data. The evaluated modifications should improve accuracy in studies of neurodegenerative diseases involving subtle BBB breakdown. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Magnetic Resonance in Medicine is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1002/mrm.28833
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        Text: English
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      – SubjectFull: Ischemic stroke
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