Contributions
Abstract: P1112
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: Diffuse white matter (WM) injury is prominent in primary progressive multiple sclerosis (PPMS) pathology and is a potential biomarker of disease progression. Diffusion Kurtosis Imaging (DKI) allows the quantification of non-Gaussian water diffusion, providing metrics with higher WM pathological specificity.
Objectives: To characterize the nature and extent of pathological changes in the WM of PPMS patients at baseline and at 1-year follow-up and to correlate WM tract integrity (WMTI) metrics with clinical disability.
Methods: 26 PPMS patients (14F, mean age 50.92±10.30 years, median EDSS score 4.0, range 1.5-6.0) and 20 healthy controls (HC) (11F, mean age 51.05±9.80 years) were prospectively enrolled. DKI single-shot EPI was acquired on a 3T Philips scanner, with a voxel size of 2×2×2 mm3, 30 directions for each b-values=1000, 2000 s/mm2 and one b=0s/mm2. A 2-compartment biophysical model of WMTI was used to derive spatial maps of axonal water fraction (AWF), intra-axonal diffusivity (Daxon), extra-axonal axial diffusivity (De,axial), extra-axonal radial diffusivity (De,radial) and tortuosity (τ) from the following WM tracts: corpus callosum (CC), cortico-spinal tract (CST), posterior thalamic radiation (PTR). Clinical disability was evaluated with EDSS, 9-hole peg test, 25-foot walk test (T25FW), visual acuity (VA) and z-SDMT.
Results: Compared to HC, PPMS showed widespread significant decrease in AWF, τ and De,axial and an increase of and De,radial , in CC, CST and PTR. At 1-year FU, a significant decrease in AWF was detected in the body of CC (p=0.048), PTR (p=0.008) and in De,axial of the CST (p=0.044). At baseline, CC and CST AWF correlated negatively with EDSS (p=0.033 r=-0.314; p=0.028 r=-0.323). With the exception of Daxon and De,axial, all metrics derived from the CC correlated with z-SDMT. PTR AWF was negatively correlated with VA (p=0.014 r=-0.476). Over one year, CST De,axial correlated positively with T25FW (p=0.048 and r=0.447) while CC AWF correlated negatively with EDSS and z-SMDT (p=0.026 r=-0.496; p=0.044 r=-0.454).
Conclusions: Our results show the prevalence of diffuse chronic axonal damage as measured by AWF over demyelination as measured by τ, De,radial, De,axial in PPMS in line with histopathological studies. Based on the change over time and correlations with clinical disability, AWF is the most sensitive metric to tissue damage in PPMS and therefore it could be considered as a marker in monitoring disease progression.
Disclosure: Monica Margoni: nothing to disclose.
Maria Petracca: nothing to disclose.
Simona Schiavi: nothing to disclose.
Michelle Fabian: nothing to disclose.
Matilde Inglese: grants from Novartis Pharmaceuticals, National Multiple Sclerosis Society, Noto Foundation, NIH and TEVA Neuroscience.
Abstract: P1112
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: Diffuse white matter (WM) injury is prominent in primary progressive multiple sclerosis (PPMS) pathology and is a potential biomarker of disease progression. Diffusion Kurtosis Imaging (DKI) allows the quantification of non-Gaussian water diffusion, providing metrics with higher WM pathological specificity.
Objectives: To characterize the nature and extent of pathological changes in the WM of PPMS patients at baseline and at 1-year follow-up and to correlate WM tract integrity (WMTI) metrics with clinical disability.
Methods: 26 PPMS patients (14F, mean age 50.92±10.30 years, median EDSS score 4.0, range 1.5-6.0) and 20 healthy controls (HC) (11F, mean age 51.05±9.80 years) were prospectively enrolled. DKI single-shot EPI was acquired on a 3T Philips scanner, with a voxel size of 2×2×2 mm3, 30 directions for each b-values=1000, 2000 s/mm2 and one b=0s/mm2. A 2-compartment biophysical model of WMTI was used to derive spatial maps of axonal water fraction (AWF), intra-axonal diffusivity (Daxon), extra-axonal axial diffusivity (De,axial), extra-axonal radial diffusivity (De,radial) and tortuosity (τ) from the following WM tracts: corpus callosum (CC), cortico-spinal tract (CST), posterior thalamic radiation (PTR). Clinical disability was evaluated with EDSS, 9-hole peg test, 25-foot walk test (T25FW), visual acuity (VA) and z-SDMT.
Results: Compared to HC, PPMS showed widespread significant decrease in AWF, τ and De,axial and an increase of and De,radial , in CC, CST and PTR. At 1-year FU, a significant decrease in AWF was detected in the body of CC (p=0.048), PTR (p=0.008) and in De,axial of the CST (p=0.044). At baseline, CC and CST AWF correlated negatively with EDSS (p=0.033 r=-0.314; p=0.028 r=-0.323). With the exception of Daxon and De,axial, all metrics derived from the CC correlated with z-SDMT. PTR AWF was negatively correlated with VA (p=0.014 r=-0.476). Over one year, CST De,axial correlated positively with T25FW (p=0.048 and r=0.447) while CC AWF correlated negatively with EDSS and z-SMDT (p=0.026 r=-0.496; p=0.044 r=-0.454).
Conclusions: Our results show the prevalence of diffuse chronic axonal damage as measured by AWF over demyelination as measured by τ, De,radial, De,axial in PPMS in line with histopathological studies. Based on the change over time and correlations with clinical disability, AWF is the most sensitive metric to tissue damage in PPMS and therefore it could be considered as a marker in monitoring disease progression.
Disclosure: Monica Margoni: nothing to disclose.
Maria Petracca: nothing to disclose.
Simona Schiavi: nothing to disclose.
Michelle Fabian: nothing to disclose.
Matilde Inglese: grants from Novartis Pharmaceuticals, National Multiple Sclerosis Society, Noto Foundation, NIH and TEVA Neuroscience.