Contributions
Abstract: P1123
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Inflammation, demyelination and axonal degeneration are the main pathological changes in Multiple Sclerosis (MS). Perfusion changes throughout the brain have also been described in MS pathology. However, specific biomarkers for MS pathology are still under investigation. Acute demyelinated lesions, with a disrupted blood brain barrier (BBB) and gadolinium enhancement, exhibit an increased perfusion, possibly reflecting the inflammatory process, whereas chronic lesions show reduced perfusion. In contrast, lesions detected through T2-weighted images might show either hyper- or hypo-perfusion suggesting that they can be acute, sub-acute or chronic. The combination of perfusion and diffusion imaging might classify lesions according to their stage, possibly detecting the residual inflammatory activity even in presence of an intact BBB.
We investigated the relationship between diffusion and perfusion alterations in MS.
Twenty-five relapsing-remitting MS patients (EDSS = 3.18 ± 1.42 and annualized relapse rate = 0.63 ± 0.34), and 22 age- and gender-matched healthy controls (HCs) were enrolled. All participants underwent clinical assessments and MRI scans, including diffusion tensor imaging to measure fractional anisotropy (FA) and arterial spin labeling to measure the cerebral blood flow.
Compared to HCs' white matter, the outer and the inner T2 perilesional layer (8 to 4 mm and 4 to 0 mm from lesion border, respectively), T2 and T1 lesions showed reduced cerebral blood flow (-15.8%, -21.6%, -28.7% and -31.2%, respectively; P< 0.001). Highly perfused T2 lesions showed a lower FA compared to T2 lesions with a reduced perfusion (0.29 ± 0.11 and 0.32 ± 0.11, respectively; P=0.004). Higher cerebral blood flow was correlated with lower FA in T2 lesions (coeff. = - 17.22, P< 0.001). Perfusion within T2 lesions was inversely correlated with California verbal learning test scores (coeff. = - 0.17; P< 0.001) and directly related with Hamilton Depression rating scale scores (coeff. = 0.04; P< 0.001).
We demonstrated that a combined perfusion and diffusion imaging approach might differentiate chronic lesions from lesions with an on-going residual inflammatory process even in the absence of a disrupted BBB and gadolinium enhancement. These lesions might represent the targets for anti-inflammatory treatments to prevent their evolution toward a chronic and irreversible stage, ultimately, reducing the burden of clinical disability.
Disclosure: Antonio Carotenuto, Heather Wilson, Beniamino Giordano, Zachary Chappell, George Dervenoulas, Steven C.R. Williams and Alexander Hammers declare no potential conflicts of interest with respect to the research, authorship and/or publication of this abstract. Dr Eli Silber and Peter Brex received travel funding, research support and lecture from Biogen. Dr. Eli silber is the principal investigator and Dr. Peter A Brex is the sub-investigator for the anti-lingo study sponsored by Biogen. Professor Marios Politis research is supported by Parkinson's UK, Lily and Edmond J. Safra Foundation, Michael J Fox Foundation (MJFF) for Parkinson's research, and CHDI Foundation.
Funding: This work is supported by the Wellcome EPSRC Centre for Medical Engineering at King's College London (WT 203148/Z/16/Z) and the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust.
Abstract: P1123
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Inflammation, demyelination and axonal degeneration are the main pathological changes in Multiple Sclerosis (MS). Perfusion changes throughout the brain have also been described in MS pathology. However, specific biomarkers for MS pathology are still under investigation. Acute demyelinated lesions, with a disrupted blood brain barrier (BBB) and gadolinium enhancement, exhibit an increased perfusion, possibly reflecting the inflammatory process, whereas chronic lesions show reduced perfusion. In contrast, lesions detected through T2-weighted images might show either hyper- or hypo-perfusion suggesting that they can be acute, sub-acute or chronic. The combination of perfusion and diffusion imaging might classify lesions according to their stage, possibly detecting the residual inflammatory activity even in presence of an intact BBB.
We investigated the relationship between diffusion and perfusion alterations in MS.
Twenty-five relapsing-remitting MS patients (EDSS = 3.18 ± 1.42 and annualized relapse rate = 0.63 ± 0.34), and 22 age- and gender-matched healthy controls (HCs) were enrolled. All participants underwent clinical assessments and MRI scans, including diffusion tensor imaging to measure fractional anisotropy (FA) and arterial spin labeling to measure the cerebral blood flow.
Compared to HCs' white matter, the outer and the inner T2 perilesional layer (8 to 4 mm and 4 to 0 mm from lesion border, respectively), T2 and T1 lesions showed reduced cerebral blood flow (-15.8%, -21.6%, -28.7% and -31.2%, respectively; P< 0.001). Highly perfused T2 lesions showed a lower FA compared to T2 lesions with a reduced perfusion (0.29 ± 0.11 and 0.32 ± 0.11, respectively; P=0.004). Higher cerebral blood flow was correlated with lower FA in T2 lesions (coeff. = - 17.22, P< 0.001). Perfusion within T2 lesions was inversely correlated with California verbal learning test scores (coeff. = - 0.17; P< 0.001) and directly related with Hamilton Depression rating scale scores (coeff. = 0.04; P< 0.001).
We demonstrated that a combined perfusion and diffusion imaging approach might differentiate chronic lesions from lesions with an on-going residual inflammatory process even in the absence of a disrupted BBB and gadolinium enhancement. These lesions might represent the targets for anti-inflammatory treatments to prevent their evolution toward a chronic and irreversible stage, ultimately, reducing the burden of clinical disability.
Disclosure: Antonio Carotenuto, Heather Wilson, Beniamino Giordano, Zachary Chappell, George Dervenoulas, Steven C.R. Williams and Alexander Hammers declare no potential conflicts of interest with respect to the research, authorship and/or publication of this abstract. Dr Eli Silber and Peter Brex received travel funding, research support and lecture from Biogen. Dr. Eli silber is the principal investigator and Dr. Peter A Brex is the sub-investigator for the anti-lingo study sponsored by Biogen. Professor Marios Politis research is supported by Parkinson's UK, Lily and Edmond J. Safra Foundation, Michael J Fox Foundation (MJFF) for Parkinson's research, and CHDI Foundation.
Funding: This work is supported by the Wellcome EPSRC Centre for Medical Engineering at King's College London (WT 203148/Z/16/Z) and the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust.