26 May 21. Featured Paper

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

Link to paper on Magnetic Resonance in Medicine

Authors

Cameron Manning, Michael Stringer, Ben Dickie, Una Clancy, Maria C. Valdés Hernandez, Stewart J. Wiseman, Daniela Jaime Garcia,  Eleni Sakka, Walter H. Backes, Michael Ingrisch, Francesca Chappell, Fergus Doubal, Craig Buckley, Laura M. Parkes, Geoff J. M. Parker, Ian Marshall, Joanna M. Wardlaw, Michael J. Thrippleton

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, & modeling factors influencing quantification of the permeability-surface area product PS & blood plasma volume v_p, & 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 & v_p quantification: restricted BBB water exchange, reduced cerebral blood flow, arterial input function (AIF) delay & B1+ error.

The impact of targeted modifications to the acquisition & 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 & 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 & 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 & 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.

Keywords

• Blood-brain barrier
• DCE-MRI
• Dementia
• Gadolinium
• Small vessel disease