Papers by Marios Yiannakas
Frontiers in Neurology, Nov 25, 2021
Background: Multiple sclerosis (MS) has traditionally been regarded as a disease confined to the ... more Background: Multiple sclerosis (MS) has traditionally been regarded as a disease confined to the central nervous system (CNS). However, neuropathological, electrophysiological, and imaging studies have demonstrated that the peripheral nervous system (PNS) is also involved, with demyelination and, to a lesser extent, axonal degeneration representing the main pathophysiological mechanisms.
Journal of Neurology, Neurosurgery & Psychiatry
ObjectivesTo evaluate white matter and grey matter T1-weighted (w)/T2w ratio (T1w/T2w ratio) in h... more ObjectivesTo evaluate white matter and grey matter T1-weighted (w)/T2w ratio (T1w/T2w ratio) in healthy controls and patients with multiple sclerosis, and its association with clinical disability.MethodsIn this cross-sectional study, 270 healthy controls and 434 patients with multiple sclerosis were retrospectively selected from 7 European sites. T1w/T2w ratio was obtained from brain T2w and T1w scans after intensity calibration using eyes and temporal muscle.ResultsIn healthy controls, T1w/T2w ratio increased until 50–60 years both in white and grey matter. Compared with healthy controls, T1w/T2w ratio was significantly lower in white matter lesions of all multiple sclerosis phenotypes, and in normal-appearing white matter and cortex of patients with relapsing-remitting and secondary progressive multiple sclerosis (p≤0.026), but it was significantly higher in the striatum and pallidum of patients with relapsing-remitting, secondary progressive and primary progressive multiple scler...
Brain, 2019
Spinal cord lesions detected on MRI hold important diagnostic and prognostic value for multiple s... more Spinal cord lesions detected on MRI hold important diagnostic and prognostic value for multiple sclerosis. Previous attempts to correlate lesion burden with clinical status have had limited success, however, suggesting that lesion location may be a contributor. Our aim was to explore the spatial distribution of multiple sclerosis lesions in the cervical spinal cord, with respect to clinical status. We included 642 suspected or confirmed multiple sclerosis patients (31 clinically isolated syndrome, and 416 relapsingremitting, 84 secondary progressive, and 73 primary progressive multiple sclerosis) from 13 clinical sites. Cervical spine lesions were manually delineated on T 2-and T 2 *-weighted axial and sagittal MRI scans acquired at 3 or 7 T. With an automatic publiclyavailable analysis pipeline we produced voxelwise lesion frequency maps to identify predilection sites in various patient groups characterized by clinical subtype, Expanded Disability Status Scale score and disease duration. We also measured absolute and normalized lesion volumes in several regions of interest using an atlas-based approach, and evaluated differences within and between groups. The lateral funiculi were more frequently affected by lesions in progressive subtypes than in relapsing in voxelwise analysis (P 5 0.001), which was further confirmed by absolute and normalized lesion volumes (P 5 0.01). The central cord area was more often affected by lesions in primary progressive than relapse-remitting patients (P 5 0.001). Between white and grey matter, the absolute lesion volume in the white matter was greater than in the grey matter in all phenotypes (P 5 0.001); however when normalizing by each region, normalized lesion volumes were comparable between white and grey matter in primary progressive patients. Lesions appearing in the lateral funiculi and central cord area were significantly correlated with Expanded Disability Status Scale score (P 5 0.001). High lesion frequencies were observed in patients with a more aggressive disease course, rather than long disease duration. Lesions located in the lateral funiculi and central cord area of the cervical spine may influence clinical status in multiple sclerosis. This work shows the added value of cervical spine lesions, and provides an avenue for evaluating the distribution of spinal cord lesions in various patient groups.
Journal of Bone and Mineral Research, 2009
BMD is commonly obtained with DXA, but this is confounded by the length and composition of tissue... more BMD is commonly obtained with DXA, but this is confounded by the length and composition of tissues that the X-ray must traverse. Subpixel enhancement of nonuniform tissue (SPENT) is a novel MRI technique that can provide (direction specific) information based on the subvoxel structural uniformity of a sample. We hypothesized that the SPENT signal would be related to BMD. This hypothesis was tested using (1) 2D computer simulation of a simplified bone structure and (2) in vitro experiments. Simulation results suggested that a resolution of 610-800 microm was required for SPENT to be correlated well with the simulated bone volume fraction (BVF) and, at this resolution, a modest signal-to-noise ratio (SNR > 5) was required for reasonable data quality. For the experiments, 15-mm(3) human trabecular bone samples were used (1) to quantify BMD (through both physical measurement and DXA) and (2) to perform MRI on a 7T system. Standard and SPENT images were obtained. Normalized SPENT (NSPENT) images were calculated by pixel-by-pixel division of the SPENT images by the standard proton density images to remove any dependence on proton density and coil uniformity from the SPENT images. The average NSPENT values were determined over the sample volume and compared with the reference BMD measurements. Each of the individual NSPENT directions was highly correlated with BMD (x-NSPENT, R (2) = 0.73, p < 0.001; y-NSPENT, R (2) = 0.76, p < 0.001; z-NSPENT, R (2) = 0.89, p < 0.001). With all three individual NSPENT directions combined, the correlation with BMD was found to be the highest (xyz-NSPENT, R (2) = 0.95, p < 0.001). The results suggest that the SPENT technique can provide a noninvasive measure of BMD at resolution and SNR levels achievable in vivo.
The spinal cord is frequently affected by atrophy and/or lesions in multiple sclerosis (MS) patie... more The spinal cord is frequently affected by atrophy and/or lesions in multiple sclerosis (MS) patients. Segmentation of the spinal cord and lesions from MRI data provides measures of damage, which are key criteria for the diagnosis, prognosis, and longitudinal monitoring in MS. Automating this operation eliminates inter-rater variability and increases the efficiency of large-throughput analysis pipelines. Robust and reliable segmentation across multi-site spinal cord data is challenging because of the large variability related to acquisition parameters and image artifacts. The goal of this study was to develop a fully-automatic framework, robust to variability in both image parameters and clinical condition, for segmentation of the spinal cord and intramedullary MS lesions from conventional MRI data. Scans of 1,042 subjects (459 healthy controls, 471 MS patients, and 112 with other spinal pathologies) were included in this multi-site study (n=30). Data spanned three contrasts (T1-, T2...
Multiple sclerosis (MS) is a pathologically and clinically complex and chronic disease of the cen... more Multiple sclerosis (MS) is a pathologically and clinically complex and chronic disease of the central nervous system. It usually presents in young adults and although it follows a highly variable course within and between individual sufferers, it results in serious long-term neurological disabilities in a majority of patients. Disease-modifying treatments have emerged in the last 15 years that-to a greater or lesser extent-ameliorate the early relapsing-remitting phase of the disease, which is characterized pathologically by recurrent, multifocal inflammatory demyeli-nating white matter lesions in the brain, spinal cord and optic nerves. The later progressive phase of the disease is as yet untreatable, and is characterized by a more widespread pathological process that involves both gray and white matter, brain and spinal cord, and exhibits limited or low-grade inflammation but prominent neurodegenera-tion.
Neurology, 2016
Objective We investigated possible associations between baseline clinical, electrophysiological a... more Objective We investigated possible associations between baseline clinical, electrophysiological and imaging measurements of acute optic neuritis (AON), and the extent of axonal loss after 6 months. Background AON is a common manifestation of multiple sclerosis in which neuroaxonal degeneration can lead to persistent visual impairment. The clinical and pathological factors which determine prognosis at onset have not been fully characterized. Design/Methods 86 participants in a phase II trial of neuroprotection with phenytoin in AON were investigated a mean of 8 days after symptom onset. Visual function (logMAR, low contrast acuity, Farnsworth-Munsell 100 hue measured color perception), optical coherence tomography (retinal nerve fiber layer [RNFL] thickness, macular volume), electrophysiology (VEP latency, amplitude), and optic nerve MRI (optic nerve lesional length, cross-sectional area) were obtained at baseline, and after 6 months. Pearson correlation coefficients and multiple lin...
The spinal cord is frequently affected by atrophy and/or lesions in multiple sclerosis (MS) patie... more The spinal cord is frequently affected by atrophy and/or lesions in multiple sclerosis (MS) patients. Segmentation of the spinal cord and lesions from MRI data provides measures of damage, which are key criteria for the diagnosis, prognosis, and longitudinal monitoring in MS. Automating this operation eliminates inter-rater variability and increases the efficiency of large-throughput analysis pipelines. Robust and reliable segmentation across multi-site spinal cord data is challenging because of the large variability related to acquisition parameters and image artifacts. The goal of this study was to develop a fully-automatic framework, robust to variability in both image parameters and clinical condition, for segmentation of the spinal cord and intramedullary MS lesions from conventional MRI data. Scans of 1,042 subjects (459 healthy controls, 471 MS patients, and 112 with other spinal pathologies) were included in this multi-site study (n=30). Data spanned three contrasts (T1-, T2...
INTRODUCTION: Certain pathologies of the central nervous system (CNS) are known to affect the WM ... more INTRODUCTION: Certain pathologies of the central nervous system (CNS) are known to affect the WM and GM of the spinal cord (SC). Diseases like leucodystrophies and Friedrich’s ataxia, affect the WM tracts [1], while multiple sclerosis (MS) and amyotrophic lateral sclerosis (ASL) affect both the WM and GM components of the SC [2-5]. This therefore establishes the need for an appropriate method of studying WM and GM independently within the SC. In a previous study WM and GM volumes were obtained and MTR was measured within the upper cervical cord by means of commercially available MRI sequence [6] but similar investigations at other levels of the spinal cord, like the lumbar spine, pose new challenges that merit investigation in their own right. For example, differences in physiological motion at this level would require the use of regional saturation (REST) slabs to be used, with a consequent negative effect on the measurable MTR. This work presents preliminary results from a pilot s...
Multiple sclerosis (MS) is a pathologically and clinically complex and chronic disease of the cen... more Multiple sclerosis (MS) is a pathologically and clinically complex and chronic disease of the central nervous system. It usually presents in young adults and although it follows a highly variable course within and between individual sufferers, it results in serious long-term neurological disabilities in a majority of patients. Disease-modifying treatments have emerged in the last 15 years that-to a greater or lesser extent-ameliorate the early relapsing-remitting phase of the disease, which is characterized pathologically by recurrent, multifocal inflammatory demyeli-nating white matter lesions in the brain, spinal cord and optic nerves. The later progressive phase of the disease is as yet untreatable, and is characterized by a more widespread pathological process that involves both gray and white matter, brain and spinal cord, and exhibits limited or low-grade inflammation but prominent neurodegenera-tion.
Neurology, 2015
Background: Previous studies have demonstrated retinal nerve fiber layer swelling(RNFL) in acute ... more Background: Previous studies have demonstrated retinal nerve fiber layer swelling(RNFL) in acute optic neuritis(AON). In this cohort of patients, within 2 weeks of visual loss,we confirm and extend these findings, showing novel early changes in the outer retinal layers. Objectives: To examine the effect of AON on the retinal layers in the macular and papillo-macular bundle(PMB). Methods: 46 AON patients(33 men, 13 women, mean age 35) were recruited within 14 days of visual loss. Peripapillary RNFL thickness, macular volume and PMB scans were obtained. Retinal segmentation analysis was carried out. Average thickness measures for RNFL, ganglion cell and inner plexiform layer(GC/IPL), inner nuclear +outer plexiform layer(IN/OPL). In addition composite measures of ganglion cell complex(GCC= GC/IPL +NFL), outer retinal complex(ORC=outer nuclear layer + photoreceptor layer) and total retinal thickness were obtained. Results: Total macular retinal thickness was significantly greater in the...
Neurology, 2016
Objective We investigated possible associations between baseline clinical, electrophysiological a... more Objective We investigated possible associations between baseline clinical, electrophysiological and imaging measurements of acute optic neuritis (AON), and the extent of axonal loss after 6 months. Background AON is a common manifestation of multiple sclerosis in which neuroaxonal degeneration can lead to persistent visual impairment. The clinical and pathological factors which determine prognosis at onset have not been fully characterized. Design/Methods 86 participants in a phase II trial of neuroprotection with phenytoin in AON were investigated a mean of 8 days after symptom onset. Visual function (logMAR, low contrast acuity, Farnsworth-Munsell 100 hue measured color perception), optical coherence tomography (retinal nerve fiber layer [RNFL] thickness, macular volume), electrophysiology (VEP latency, amplitude), and optic nerve MRI (optic nerve lesional length, cross-sectional area) were obtained at baseline, and after 6 months. Pearson correlation coefficients and multiple lin...
Conventional MRI of the multiple sclerosis (MS) spinal cord offers low specificity to underlying ... more Conventional MRI of the multiple sclerosis (MS) spinal cord offers low specificity to underlying pathological processes taking place. Quantitative MRI metrics able to characterize damage at the microstructural level are required. Of particular interest are those known to be sensitive to myelin content, which can be generated via various different contrast mechanisms. It is important to assess the specificity of such prospective myelin biomarkers to MS spinal cord pathology and validation studies comparing MRI with histological findings are essential for this purpose. Here a comparison of myelinsensitive quantitative MRI metrics measured in MS and healthy ex vivo cord are presented.
INTRODUCTION: Certain pathologies of the central nervous system (CNS) are known to affect the WM ... more INTRODUCTION: Certain pathologies of the central nervous system (CNS) are known to affect the WM and GM of the spinal cord (SC). Diseases like leucodystrophies and Friedrich’s ataxia, affect the WM tracts [1], while multiple sclerosis (MS) and amyotrophic lateral sclerosis (ASL) affect both the WM and GM components of the SC [2-5]. This therefore establishes the need for an appropriate method of studying WM and GM independently within the SC. In a previous study WM and GM volumes were obtained and MTR was measured within the upper cervical cord by means of commercially available MRI sequence [6] but similar investigations at other levels of the spinal cord, like the lumbar spine, pose new challenges that merit investigation in their own right. For example, differences in physiological motion at this level would require the use of regional saturation (REST) slabs to be used, with a consequent negative effect on the measurable MTR. This work presents preliminary results from a pilot s...
Neurology, 2015
Background: Previous studies have demonstrated retinal nerve fiber layer swelling(RNFL) in acute ... more Background: Previous studies have demonstrated retinal nerve fiber layer swelling(RNFL) in acute optic neuritis(AON). In this cohort of patients, within 2 weeks of visual loss,we confirm and extend these findings, showing novel early changes in the outer retinal layers. Objectives: To examine the effect of AON on the retinal layers in the macular and papillo-macular bundle(PMB). Methods: 46 AON patients(33 men, 13 women, mean age 35) were recruited within 14 days of visual loss. Peripapillary RNFL thickness, macular volume and PMB scans were obtained. Retinal segmentation analysis was carried out. Average thickness measures for RNFL, ganglion cell and inner plexiform layer(GC/IPL), inner nuclear +outer plexiform layer(IN/OPL). In addition composite measures of ganglion cell complex(GCC= GC/IPL +NFL), outer retinal complex(ORC=outer nuclear layer + photoreceptor layer) and total retinal thickness were obtained. Results: Total macular retinal thickness was significantly greater in the...
The spinal cord is frequently affected by atrophy and/or lesions in multiple sclerosis (MS) patie... more The spinal cord is frequently affected by atrophy and/or lesions in multiple sclerosis (MS) patients. Segmentation of the spinal cord and lesions from MRI data provides measures of damage, which are key criteria for the diagnosis, prognosis, and longitudinal monitoring in
Conventional MRI of the multiple sclerosis (MS) spinal cord offers low specificity to underlying ... more Conventional MRI of the multiple sclerosis (MS) spinal cord offers low specificity to underlying pathological processes taking place. Quantitative MRI metrics able to characterize damage at the microstructural level are required. Of particular interest are those known to be sensitive to myelin content, which can be generated via various different contrast mechanisms. It is important to assess the specificity of such prospective myelin biomarkers to MS spinal cord pathology and validation studies comparing MRI with histological findings are essential for this purpose. Here a comparison of myelinsensitive quantitative MRI metrics measured in MS and healthy ex vivo cord are presented.
Brain
Many studies report an overlap of MRI and clinical findings between patients with relapsing-remit... more Many studies report an overlap of MRI and clinical findings between patients with relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS), which in part is reflective of inclusion of subjects with variable disease duration and short periods of follow-up. To overcome these limitations, we examined the differences between RRMS and SPMS and the relationship between MRI measures and clinical outcomes 30 years after first presentation with clinically isolated syndrome suggestive of multiple sclerosis. Sixty-three patients were studied 30 years after their initial presentation with a clinically isolated syndrome; only 14% received a disease modifying treatment at any time point. Twenty-seven patients developed RRMS, 15 SPMS and 21 experienced no further neurological events; these groups were comparable in terms of age and disease duration. Clinical assessment included the Expanded Disability Status Scale, 9-Hole Peg Test and Timed 25-Foot Walk and...
The spinal cord is frequently affected by atrophy and/or lesions in multiple sclerosis (MS) patie... more The spinal cord is frequently affected by atrophy and/or lesions in multiple sclerosis (MS) patients. Segmentation of the spinal cord and lesions from MRI data provides measures of damage, which are key criteria for the diagnosis, prognosis, and longitudinal monitoring in
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Papers by Marios Yiannakas