Quantitative analysis of blood-brain barrier permeability in the human brain

R Veksler, GS Pell, Y Roth, A Zangen, Y Chassidim, I Shelef, R Raccah, M Inghilleri, A Friedman

Research output: Chapter in Book/Report/Conference proceedingConference contribution


Background: The delivery of toxins and most drugs into
the brain is restricted by the complex blood–brain-barrier
(BBB), which maintains a constant extracellular environment within the brain. Here we present a novel method for
the quantitative evaluation of BBB permeability using
human MRI and its potential use for diagnosis and
treatment evaluation in patients with brain tumors.
Methods and Results: The method is based on dynamic
contrast enhanced (DCE) MRI. 7–10 Spin echo T1-weighted
scans were acquired (TE\TR=8\660 ms, ~3.5 min scan time)
after an injection of Gadolinium-DTPA. The time between
injection and scanning was about 5–10 min so the bolus effect
was not visible. Pre-processing was carried out using SPM
8 and included co-registration, segmentation and normalization. After additional normalization to the signal intensity in
the superior sagittal sinus, intensity at each voxel was fitted to
a linear model. This additional normalization significantly
improved the linear fit, allowing intra and inter-subject
comparison. Analysis of scans from 13 subjects showed the
slope of the linear curve as the most representative parameter
for BBB permeability, showing negative (close to zero) values
in intact brain and positive values in extra-brain tissue as well
as in abnormal brain regions (tumors and surrounding region).
In a preliminary study, the protocol was performed in 11
patients ›1y after surgical resection of malignant brain tumors
following deep transcranial magnetic stimulation (TMS).
Sham stimulation was used as control. 2 patients were
excluded due to lack of enhancement; 7 of the remaining 9
showed enhanced brain region around the tumor area and a
significant increase in permeability following TMS.
Conclusions: The proposed imaging approach reliably
detects pathological increase in vessels permeability. Our
preliminary results suggest that TMS may be efficient as
the first non-invasive
Original languageEnglish GB
StatePublished - 2012


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