Vascular permeability and iron deposition biomarkers in longitudinal follow-up of cerebral cavernous malformations

Romuald Girard; Maged D Fam; Hussein A Zeineddine; Huan Tan; Abdul Ghani Mikati; Changbin Shi; Michael Jesselson; Robert Shenkar; Meijing Wu; Ying Cao; Nicholas Hobson; Henrik B W Larsson; Gregory A Christoforidis; Issam A Awad

doi:10.3171/2016.5.JNS16687

Vascular permeability and iron deposition biomarkers in longitudinal follow-up of cerebral cavernous malformations

Romuald Girard, Maged D Fam, Hussein A Zeineddine, Huan Tan, Abdul Ghani Mikati, Changbin Shi, Michael Jesselson, Robert Shenkar, Meijing Wu, Ying Cao, Nicholas Hobson, Henrik B W Larsson, Gregory A Christoforidis, Issam A Awad

Department of Clinical Medicine

21 Citations (Scopus)

Abstract

OBJECTIVE Vascular permeability and iron leakage are central features of cerebral cavernous malformation (CCM) pathogenesis. The authors aimed to correlate prospective clinical behavior of CCM lesions with longitudinal changes in biomarkers of dynamic contrast-enhanced quantitative permeability (DCEQP) and quantitative susceptibility mapping (QSM) assessed by MRI. METHODS Forty-six patients with CCMs underwent 2 or more permeability and/or susceptibility studies in conjunction with baseline and follow-up imaging and clinical surveillance during a mean 12.05 months of follow-up (range 2.4-31.27 months). Based on clinical and imaging features, cases/lesions were classified as stable, unstable, or recovering. Associated and predictive changes in quantitative permeability and susceptibility were investigated. RESULTS Lesional mean permeability and QSM values were not significantly different in stable versus unstable lesions at baseline. Mean lesional permeability in unstable CCMs with lesional bleeding or growth increased significantly (+85.9% change; p = 0.005), while mean permeability in stable and recovering lesions did not significantly change. Mean lesional QSM values significantly increased in unstable lesions (+44.1% change; p = 0.01), decreased slightly with statistical significance in stable lesions (-3.2% change; p = 0.003), and did not significantly change in recovering lesions. Familial cases developing new lesions during the follow-up period showed a higher background brain permeability at baseline (p = 0.001), as well as higher regional permeability (p = 0.003) in the area that would later develop a new lesion as compared with the homologous contralateral brain region. CONCLUSIONS In vivo assessment of vascular permeability and iron deposition on MRI can serve as objective and quantifiable biomarkers of disease activity in CCMs. This may be applied in natural history studies and may help calibrate clinical trials. The 2 techniques are likely applicable in other disorders of vascular integrity and iron leakage such as aging, hemorrhagic microangiopathy, and traumatic brain injury.

Original language	English
Journal	Journal of Neurosurgery
Volume	127
Issue number	1
Pages (from-to)	102-110
Number of pages	9
ISSN	0022-3085
DOIs	https://doi.org/10.3171/2016.5.JNS16687
Publication status	Published - Jul 2017

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Girard, R., Fam, M. D., Zeineddine, H. A., Tan, H., Mikati, A. G., Shi, C., Jesselson, M., Shenkar, R., Wu, M., Cao, Y., Hobson, N., Larsson, H. B. W., Christoforidis, G. A., & Awad, I. A. (2017). Vascular permeability and iron deposition biomarkers in longitudinal follow-up of cerebral cavernous malformations. Journal of Neurosurgery, 127(1), 102-110. https://doi.org/10.3171/2016.5.JNS16687

Girard, R, Fam, MD, Zeineddine, HA, Tan, H, Mikati, AG, Shi, C, Jesselson, M, Shenkar, R, Wu, M, Cao, Y, Hobson, N, Larsson, HBW, Christoforidis, GA & Awad, IA 2017, 'Vascular permeability and iron deposition biomarkers in longitudinal follow-up of cerebral cavernous malformations', Journal of Neurosurgery, vol. 127, no. 1, pp. 102-110. https://doi.org/10.3171/2016.5.JNS16687

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title = "Vascular permeability and iron deposition biomarkers in longitudinal follow-up of cerebral cavernous malformations",

abstract = "OBJECTIVE Vascular permeability and iron leakage are central features of cerebral cavernous malformation (CCM) pathogenesis. The authors aimed to correlate prospective clinical behavior of CCM lesions with longitudinal changes in biomarkers of dynamic contrast-enhanced quantitative permeability (DCEQP) and quantitative susceptibility mapping (QSM) assessed by MRI. METHODS Forty-six patients with CCMs underwent 2 or more permeability and/or susceptibility studies in conjunction with baseline and follow-up imaging and clinical surveillance during a mean 12.05 months of follow-up (range 2.4-31.27 months). Based on clinical and imaging features, cases/lesions were classified as stable, unstable, or recovering. Associated and predictive changes in quantitative permeability and susceptibility were investigated. RESULTS Lesional mean permeability and QSM values were not significantly different in stable versus unstable lesions at baseline. Mean lesional permeability in unstable CCMs with lesional bleeding or growth increased significantly (+85.9% change; p = 0.005), while mean permeability in stable and recovering lesions did not significantly change. Mean lesional QSM values significantly increased in unstable lesions (+44.1% change; p = 0.01), decreased slightly with statistical significance in stable lesions (-3.2% change; p = 0.003), and did not significantly change in recovering lesions. Familial cases developing new lesions during the follow-up period showed a higher background brain permeability at baseline (p = 0.001), as well as higher regional permeability (p = 0.003) in the area that would later develop a new lesion as compared with the homologous contralateral brain region. CONCLUSIONS In vivo assessment of vascular permeability and iron deposition on MRI can serve as objective and quantifiable biomarkers of disease activity in CCMs. This may be applied in natural history studies and may help calibrate clinical trials. The 2 techniques are likely applicable in other disorders of vascular integrity and iron leakage such as aging, hemorrhagic microangiopathy, and traumatic brain injury.",

author = "Romuald Girard and Fam, {Maged D} and Zeineddine, {Hussein A} and Huan Tan and Mikati, {Abdul Ghani} and Changbin Shi and Michael Jesselson and Robert Shenkar and Meijing Wu and Ying Cao and Nicholas Hobson and Larsson, {Henrik B W} and Christoforidis, {Gregory A} and Awad, {Issam A}",

year = "2017",

month = jul,

doi = "10.3171/2016.5.JNS16687",

language = "English",

volume = "127",

pages = "102--110",

journal = "Journal of Neurosurgery",

issn = "0022-3085",

publisher = "American Association of Neurological Surgeons",

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TY - JOUR

T1 - Vascular permeability and iron deposition biomarkers in longitudinal follow-up of cerebral cavernous malformations

AU - Girard, Romuald

AU - Fam, Maged D

AU - Zeineddine, Hussein A

AU - Tan, Huan

AU - Mikati, Abdul Ghani

AU - Shi, Changbin

AU - Jesselson, Michael

AU - Shenkar, Robert

AU - Wu, Meijing

AU - Cao, Ying

AU - Hobson, Nicholas

AU - Larsson, Henrik B W

AU - Christoforidis, Gregory A

AU - Awad, Issam A

PY - 2017/7

Y1 - 2017/7

N2 - OBJECTIVE Vascular permeability and iron leakage are central features of cerebral cavernous malformation (CCM) pathogenesis. The authors aimed to correlate prospective clinical behavior of CCM lesions with longitudinal changes in biomarkers of dynamic contrast-enhanced quantitative permeability (DCEQP) and quantitative susceptibility mapping (QSM) assessed by MRI. METHODS Forty-six patients with CCMs underwent 2 or more permeability and/or susceptibility studies in conjunction with baseline and follow-up imaging and clinical surveillance during a mean 12.05 months of follow-up (range 2.4-31.27 months). Based on clinical and imaging features, cases/lesions were classified as stable, unstable, or recovering. Associated and predictive changes in quantitative permeability and susceptibility were investigated. RESULTS Lesional mean permeability and QSM values were not significantly different in stable versus unstable lesions at baseline. Mean lesional permeability in unstable CCMs with lesional bleeding or growth increased significantly (+85.9% change; p = 0.005), while mean permeability in stable and recovering lesions did not significantly change. Mean lesional QSM values significantly increased in unstable lesions (+44.1% change; p = 0.01), decreased slightly with statistical significance in stable lesions (-3.2% change; p = 0.003), and did not significantly change in recovering lesions. Familial cases developing new lesions during the follow-up period showed a higher background brain permeability at baseline (p = 0.001), as well as higher regional permeability (p = 0.003) in the area that would later develop a new lesion as compared with the homologous contralateral brain region. CONCLUSIONS In vivo assessment of vascular permeability and iron deposition on MRI can serve as objective and quantifiable biomarkers of disease activity in CCMs. This may be applied in natural history studies and may help calibrate clinical trials. The 2 techniques are likely applicable in other disorders of vascular integrity and iron leakage such as aging, hemorrhagic microangiopathy, and traumatic brain injury.

AB - OBJECTIVE Vascular permeability and iron leakage are central features of cerebral cavernous malformation (CCM) pathogenesis. The authors aimed to correlate prospective clinical behavior of CCM lesions with longitudinal changes in biomarkers of dynamic contrast-enhanced quantitative permeability (DCEQP) and quantitative susceptibility mapping (QSM) assessed by MRI. METHODS Forty-six patients with CCMs underwent 2 or more permeability and/or susceptibility studies in conjunction with baseline and follow-up imaging and clinical surveillance during a mean 12.05 months of follow-up (range 2.4-31.27 months). Based on clinical and imaging features, cases/lesions were classified as stable, unstable, or recovering. Associated and predictive changes in quantitative permeability and susceptibility were investigated. RESULTS Lesional mean permeability and QSM values were not significantly different in stable versus unstable lesions at baseline. Mean lesional permeability in unstable CCMs with lesional bleeding or growth increased significantly (+85.9% change; p = 0.005), while mean permeability in stable and recovering lesions did not significantly change. Mean lesional QSM values significantly increased in unstable lesions (+44.1% change; p = 0.01), decreased slightly with statistical significance in stable lesions (-3.2% change; p = 0.003), and did not significantly change in recovering lesions. Familial cases developing new lesions during the follow-up period showed a higher background brain permeability at baseline (p = 0.001), as well as higher regional permeability (p = 0.003) in the area that would later develop a new lesion as compared with the homologous contralateral brain region. CONCLUSIONS In vivo assessment of vascular permeability and iron deposition on MRI can serve as objective and quantifiable biomarkers of disease activity in CCMs. This may be applied in natural history studies and may help calibrate clinical trials. The 2 techniques are likely applicable in other disorders of vascular integrity and iron leakage such as aging, hemorrhagic microangiopathy, and traumatic brain injury.

U2 - 10.3171/2016.5.JNS16687

DO - 10.3171/2016.5.JNS16687

M3 - Journal article

C2 - 27494817

SN - 0022-3085

VL - 127

SP - 102

EP - 110

JO - Journal of Neurosurgery

JF - Journal of Neurosurgery

IS - 1

ER -

Vascular permeability and iron deposition biomarkers in longitudinal follow-up of cerebral cavernous malformations

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