Quantification of blood-to-brain transfer rate in multiple sclerosis

Abstract

Blood–brain barrier (BBB) disruption visualized in lesions by MRI is a major biomarker of disease activity in multiple sclerosis (MS). However, in MS, destruction occurs to a variable extent in lesions as well as in gray matter (GM) and in the normal appearing white matter (NAWM). A method to quantify the BBB disruption in lesions as well as in non-lesion areas would be useful for assessment of MS progression and treatments. The objective of this study was to quantify the BBB transfer rate (Ki) in WM lesions, in the NAWM, and in the full-brain of MS patients. Thirteen MS patients with active lesions and 10 healthy controls with age and gender matching were recruited for full-brain and WM Ki studies. Dynamic contrast-enhanced MRI (DCEMRI) scans were conducted using T1 mapping with partial inversion recovery (TAPIR), a fast T1 mapping technique, following administration of a quarter-dose of the contrast agent Gadolinium-DTPA (Gd-DTPA). The Patlak modeling technique was used to derive a voxel-based map of Ki. In all patients contrast-enhanced lesions, quantified by Ki maps, were observed. Compared with controls, patients with MS exhibited an increase in mean Ki of the full-brain (P-value<0.05) but no significant difference in mean Ki of NAWM. The identified increase in full-brain Ki of MS patients suggests a global vascular involvement associated with MS disease. The lack of observed significant decrease in Ki in NAWM suggests lower involvement of WM vasculature than full-brain vasculature in MS. Ki maps constructed from time series data acquired by DCEMRI provide additional information about BBB that could be used for evaluation of vascular involvement in MS and monitoring treatment effectiveness.

Blood–brain barrier permeability measured using dynamic contrast‐enhanced magnetic resonance imaging: a validation study

“…However, a number of observations suggest caution in interpreting K i as a BBB permeability marker. First, other studies using variations of DCE-MRI have only shown insignificant trends for higher K i values in MS subjects (Silver et al 2001;Lund et al 2013;Taheri et al 2013). Secondly, we reported a correlation between K i , CSF leukocyte count, and matrix metalloprotease 9 (Cramer et al 2015), an enzyme involved in leukocyte infiltration, in MS patients.…”

“…; Taheri et al . ). Secondly, we reported a correlation between K i , CSF leukocyte count, and matrix metalloprotease 9 (Cramer et al .…”

Blood-Brain Barrier Breakdown in the Aging Human Hippocampus

“…1C). We determined in each individual the arterial input function (AIF) from the common carotid artery instead of using an average value from the superior sagittal venous sinus to determine tracer concentration in blood (Taheri et al, 2011a, 2011b, 2013; Larsson et al, 2009). Individual AIF measurements are important particularly if the studied population diverges by age as changes in blood volume and flow may affect AIF and the K trans measurements.…”

“…Compared to a previous approach limited to measurements of BBB permeability in the white matter (WM) (Taheri et al, 2011a, 2011b, 2013), the current method allows simultaneous measurements of BBB K trans permeability in different grey and WM regions. Additionally, we analyzed CSF biomarkers of BBB breakdown, injury to brain vascular cells including pericytes and endothelial cells, inflammatory response, neuronal injury ( i.e.…”

Accurate Determination of Blood–Brain Barrier Permeability Using Dynamic Contrast-Enhanced T1-Weighted MRI: A Simulation and in vivo Study on Healthy Subjects and Multiple Sclerosis Patients

“…In two more recent studies, the BBB permeability measured as K i was estimated in healthy human subjects using the Patlak method. The first study reported a mean permeability for a conventional MRI contrast agent of 0.013 ml/100 g/min based on measurements on 10 healthy subjects 30 and the second study found an upper limit of normal permeability of 0.03 ml/ 100 g/min 23 based on 20 healthy controls. This is in good agreement with our findings and also show that subtle changes in the BBB permeability can be detected in patients with vascular cognitive impairment and MS patients.…”