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Published in: Fluids and Barriers of the CNS 1/2013

Open Access 01-12-2013 | Review

Quantitative imaging assessment of blood-brain barrier permeability in humans

Authors: Yoash Chassidim, Ronel Veksler, Svetlana Lublinsky, Gaby S Pell, Alon Friedman, Ilan Shelef

Published in: Fluids and Barriers of the CNS | Issue 1/2013

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Abstract

The blood–brain barrier (BBB) is a functional and structural barrier separating the intravascular and neuropil compartments of the brain. It characterizes the vascular bed and is essential for normal brain functions. Dysfunction in the BBB properties have been described in most common neurological disorders, such as stroke, traumatic injuries, intracerebral hemorrhage, tumors, epilepsy and neurodegenerative disorders. It is now obvious that the BBB plays an important role in normal brain activity, stressing the need for applicable imaging and assessment methods. Recent advancements in imaging techniques now make it possible to establish sensitive and quantitative methods for the assessment of BBB permeability. However, most of the existing techniques require complicated and demanding dynamic scanning protocols that are impractical and cannot be fulfilled in some cases. We review existing methods for the evaluation of BBB permeability, focusing on quantitative magnetic resonance-based approaches and discuss their drawbacks and limitations. In light of those limitations we propose two new approaches for BBB assessment with less demanding imaging sequences: the “post-pre” and the “linear dynamic” methods, both allow semi-quantitative permeability assessment and localization of dysfunctional BBB with simple/partial dynamic imaging protocols and easy-to-apply analysis algorithms. We present preliminary results and show an example which compares these new methods with the existing standard assessment method. We strongly believe that the establishment of such “easy to use” and reliable imaging methods is essential before BBB assessment can become a routine clinical tool. Large clinical trials are awaited to fully understand the significance of BBB permeability as a biomarker and target for treatment in neurological disorders.
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Literature
1.
go back to reference Shlosberg D, Benifla M, Kaufer D, Friedman A: Blood–brain barrier breakdown as a therapeutic target in traumatic brain injury. Nat Rev Neurol. 2010, 6: 393-403. 10.1038/nrneurol.2010.74.PubMedCentralPubMedCrossRef Shlosberg D, Benifla M, Kaufer D, Friedman A: Blood–brain barrier breakdown as a therapeutic target in traumatic brain injury. Nat Rev Neurol. 2010, 6: 393-403. 10.1038/nrneurol.2010.74.PubMedCentralPubMedCrossRef
2.
go back to reference Abbot NJ, Friedman A: Overview and introduction: The blood–brain barrier in health and disease. Epilepsia. 2012, 53 (Suppl. 6): 1-6.CrossRef Abbot NJ, Friedman A: Overview and introduction: The blood–brain barrier in health and disease. Epilepsia. 2012, 53 (Suppl. 6): 1-6.CrossRef
3.
go back to reference Tomkins O, Shelef I, Kaizerman I, Eliushin A, Afawi Z, Misk A, Gidon M, Cohen A, Zumsteg D, Friedman A: Blood–brain barrier disruption in post-traumatic epilepsy. J Neurol Neurosurg Psychiat. 2008, 79: 774-777. 10.1136/jnnp.2007.126425.PubMedCrossRef Tomkins O, Shelef I, Kaizerman I, Eliushin A, Afawi Z, Misk A, Gidon M, Cohen A, Zumsteg D, Friedman A: Blood–brain barrier disruption in post-traumatic epilepsy. J Neurol Neurosurg Psychiat. 2008, 79: 774-777. 10.1136/jnnp.2007.126425.PubMedCrossRef
4.
go back to reference Tomkins O, Feintuch A, Benifla M, Cohen A, Friedman A, Shelef I: Blood–brain barrier breakdown following traumatic brain injury: a possible role in posttraumatic epilepsy. Cardiovasc Psychiatry Neurol. 2011, 765923: 1-11.CrossRef Tomkins O, Feintuch A, Benifla M, Cohen A, Friedman A, Shelef I: Blood–brain barrier breakdown following traumatic brain injury: a possible role in posttraumatic epilepsy. Cardiovasc Psychiatry Neurol. 2011, 765923: 1-11.CrossRef
5.
go back to reference Schoknecht K, Shalev H: Blood–brain barrier dysfunction in brain diseases: Clinical experience. Epilepsia. 2012, 53 (Suppl. 6): 7-13.PubMedCrossRef Schoknecht K, Shalev H: Blood–brain barrier dysfunction in brain diseases: Clinical experience. Epilepsia. 2012, 53 (Suppl. 6): 7-13.PubMedCrossRef
6.
go back to reference Rebeles F, Fink J, Anzai Y, Maravilla KR: Blood–brain barrier imaging and therapeutic potentials. Top Magn Reson Imaging. 2006, 17: 107-116. 10.1097/RMR.0b013e31802f5df9.PubMedCrossRef Rebeles F, Fink J, Anzai Y, Maravilla KR: Blood–brain barrier imaging and therapeutic potentials. Top Magn Reson Imaging. 2006, 17: 107-116. 10.1097/RMR.0b013e31802f5df9.PubMedCrossRef
7.
go back to reference Nagaraja TN, Knight RA, Ewing JR, Karki K, Nagesh V, Fenstermacher JD: Multiparametric Magnetic Resonance Imaging and Repeated Measurements of Blood–brain Barrier Permeability to Contrast Agents. The blood–brain and other neural barriers. Edited by: Sukriti N. 2011, New York: Humana Press, 193-212.CrossRef Nagaraja TN, Knight RA, Ewing JR, Karki K, Nagesh V, Fenstermacher JD: Multiparametric Magnetic Resonance Imaging and Repeated Measurements of Blood–brain Barrier Permeability to Contrast Agents. The blood–brain and other neural barriers. Edited by: Sukriti N. 2011, New York: Humana Press, 193-212.CrossRef
8.
go back to reference Schellenberg AE, Buist R, Yong VW, Del Bigio MR, Peeling J: Magnetic resonance imaging of blood-spinal cord barrier disruption in mice with experimental autoimmune encephalomyelitis. J Magn Reson Med. 2007, 58: 298-305. 10.1002/mrm.21289.CrossRef Schellenberg AE, Buist R, Yong VW, Del Bigio MR, Peeling J: Magnetic resonance imaging of blood-spinal cord barrier disruption in mice with experimental autoimmune encephalomyelitis. J Magn Reson Med. 2007, 58: 298-305. 10.1002/mrm.21289.CrossRef
9.
go back to reference Knight RA, Nagaraja TN, Ewing JR, Nagesh V, Whitton PA, Bershad E, Fagan SC, Fenstermacher JD: Quantitation and localization of blood-to-brain influx by magnetic resonance imaging and quantitative autoradiography in a model of transient focal ischemia. J Magn Reson Med. 2005, 54: 813-821. 10.1002/mrm.20629.CrossRef Knight RA, Nagaraja TN, Ewing JR, Nagesh V, Whitton PA, Bershad E, Fagan SC, Fenstermacher JD: Quantitation and localization of blood-to-brain influx by magnetic resonance imaging and quantitative autoradiography in a model of transient focal ischemia. J Magn Reson Med. 2005, 54: 813-821. 10.1002/mrm.20629.CrossRef
10.
go back to reference Sourbron SP, Buckley DL: Tracer kinetic modelling in MRI: estimating perfusion and capillary permeability. Phys Med Biol. 2012, 57: R1-R33. 10.1088/0031-9155/57/2/R1.PubMedCrossRef Sourbron SP, Buckley DL: Tracer kinetic modelling in MRI: estimating perfusion and capillary permeability. Phys Med Biol. 2012, 57: R1-R33. 10.1088/0031-9155/57/2/R1.PubMedCrossRef
11.
go back to reference Benjamini Y: Discovering the false discovery rate. Journal of the Royal Statistical Society Series B. 2010, 72: 405-416. 10.1111/j.1467-9868.2010.00746.x.CrossRef Benjamini Y: Discovering the false discovery rate. Journal of the Royal Statistical Society Series B. 2010, 72: 405-416. 10.1111/j.1467-9868.2010.00746.x.CrossRef
12.
go back to reference Jelescu IO, Leppert IR, Narayanan S, Araújo D, Arnold DL, Pike GB: Dual-temporal resolution dynamic contrast-enhanced MRI protocol for blood–brain barrier permeability measurement in enhancing multiple sclerosis lesions. J Magn Reson Imaging. 2011, 33: 1291-1300. 10.1002/jmri.22565.PubMedCrossRef Jelescu IO, Leppert IR, Narayanan S, Araújo D, Arnold DL, Pike GB: Dual-temporal resolution dynamic contrast-enhanced MRI protocol for blood–brain barrier permeability measurement in enhancing multiple sclerosis lesions. J Magn Reson Imaging. 2011, 33: 1291-1300. 10.1002/jmri.22565.PubMedCrossRef
13.
go back to reference Brix G, Kiessling F, Lucht R, Darai S, Wasser K, Delorme S, Griebel J: Microcirculation and microvasculature in breast tumors: pharmacokinetic analysis of dynamic MR image series. J Magn Reson Med. 2004, 52: 420-429. 10.1002/mrm.20161.CrossRef Brix G, Kiessling F, Lucht R, Darai S, Wasser K, Delorme S, Griebel J: Microcirculation and microvasculature in breast tumors: pharmacokinetic analysis of dynamic MR image series. J Magn Reson Med. 2004, 52: 420-429. 10.1002/mrm.20161.CrossRef
14.
go back to reference Tofts PS, Kermode AG: Measurement of the blood–brain barrier permeability and leakage space using dynamic MR imaging-Fundamental concepts. J Magn Reson Med. 1991, 17: 357-367. 10.1002/mrm.1910170208.CrossRef Tofts PS, Kermode AG: Measurement of the blood–brain barrier permeability and leakage space using dynamic MR imaging-Fundamental concepts. J Magn Reson Med. 1991, 17: 357-367. 10.1002/mrm.1910170208.CrossRef
15.
go back to reference Tofts PS, Brix G, Buckley DL: Estimating kinetic parameters from dynamic contrast-enhanced T1-weighted MRI of a diffusible tracer: standardized quantities and symbols. J Magn Reson Imaging. 1999, 10: 223-232. 10.1002/(SICI)1522-2586(199909)10:3<223::AID-JMRI2>3.0.CO;2-S.PubMedCrossRef Tofts PS, Brix G, Buckley DL: Estimating kinetic parameters from dynamic contrast-enhanced T1-weighted MRI of a diffusible tracer: standardized quantities and symbols. J Magn Reson Imaging. 1999, 10: 223-232. 10.1002/(SICI)1522-2586(199909)10:3<223::AID-JMRI2>3.0.CO;2-S.PubMedCrossRef
16.
go back to reference Tofts PS: Modeling tracer kinetics in dynamic Gd-DTPA MR imaging. J Magn Reson Imaging. 1997, 7: 91-101. 10.1002/jmri.1880070113.PubMedCrossRef Tofts PS: Modeling tracer kinetics in dynamic Gd-DTPA MR imaging. J Magn Reson Imaging. 1997, 7: 91-101. 10.1002/jmri.1880070113.PubMedCrossRef
17.
go back to reference Sourbron S: Technical aspects of MR perfusion. Eur J Radiol. 2010, 76: 304-313. 10.1016/j.ejrad.2010.02.017.PubMedCrossRef Sourbron S: Technical aspects of MR perfusion. Eur J Radiol. 2010, 76: 304-313. 10.1016/j.ejrad.2010.02.017.PubMedCrossRef
18.
go back to reference Parker GJ, Roberts C, Macdonald A, Buonaccorsi GA, Cheung S, Buckley DL, Jackson A, Watson Y, Davies K, Jayson GC: Experimentally-derived functional form for a population-averaged high-temporal-resolution arterial input function for dynamic contrast-enhanced MRI. J Magn Reson Med. 2006, 56: 993-1000. 10.1002/mrm.21066.CrossRef Parker GJ, Roberts C, Macdonald A, Buonaccorsi GA, Cheung S, Buckley DL, Jackson A, Watson Y, Davies K, Jayson GC: Experimentally-derived functional form for a population-averaged high-temporal-resolution arterial input function for dynamic contrast-enhanced MRI. J Magn Reson Med. 2006, 56: 993-1000. 10.1002/mrm.21066.CrossRef
Metadata
Title
Quantitative imaging assessment of blood-brain barrier permeability in humans
Authors
Yoash Chassidim
Ronel Veksler
Svetlana Lublinsky
Gaby S Pell
Alon Friedman
Ilan Shelef
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Fluids and Barriers of the CNS / Issue 1/2013
Electronic ISSN: 2045-8118
DOI
https://doi.org/10.1186/2045-8118-10-9

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