Contributions
Abstract: 181
Type: Hot Topic
Abstract Category: N/A
Over the last two decades, combined post mortem imaging and histopathology verification has played a central role in elucidating pathological characteristics of abnormalities visible on magnetic resonance imaging (MRI). In the early years, these studies were limited to white matter (WM) lesions. T2-hyperintensities were shown to reflect a heterogeneous underlying pathology. T1 'black holes' were found to be more pathologically specific, as they tend to reflect lesions with more profound axonal loss. Slowly resolving black holes, on the other hand, represent various degrees of remyelination. Normal-appearing WM on MRI was demonstrated widely abnormal in terms of histopathology, with varying degrees of axon and myelin loss, and with multiple pre-active foci of microglial clustering. Diffusely abnormal WM areas on MRI were found to correspond to Wallerian degeneration, following initial axonal transection in multiple sclerosis (MS) lesions. As it became clear that some crucial clinical characteristics, such as cognitive impairment, could not be sufficiently explained by imaging of WM lesions, post mortem studies started focusing on the grey matter (GM). It was shown that GM lesions are numerous, though severely underrepresented by conventional imaging at standard field-strengths. Efforts over the years to improve upon imaging techniques and field strengths have resulted in better, though not perfect, GM lesion detection rates. Recent post mortem imaging work has increasingly focused on identifying underlying morphological substrates of abnormalities found with more advanced imaging techniques. For example, regional GM atrophy, an increasingly important measure in clinical and pharmaceutical trial settings, was shown to be dependent on axonal loss and neuronal shrinkage. Additionally, increases of fractional anisotropy in cortical GM lesions could be explained by an increase of matrix directionality following cortical axonal degeneration. Contemporary structural network analysis shows abnormalities that can be linearly retraced to specific neuronal changes in the MS cortex. Post mortem imaging and histopathology correlation requires a dedicated donor program, as well as a multidisciplinary team, and a complex pipeline, optimized to guarantee ultra-short post mortem delays and highest quality of tissue and imaging. The Amsterdam protocol, as well as some of the major findings of this research line over the last twenty years will be highlighted in this lecture.
Disclosure: Jeroen Geurts is Editor for Europe at Multiple Sclerosis Journal; he has served as a consultant and/or has received research grants from Biogen Idec, Novartis Pharma and Sanofi-Genzyme over the last three years.
Abstract: 181
Type: Hot Topic
Abstract Category: N/A
Over the last two decades, combined post mortem imaging and histopathology verification has played a central role in elucidating pathological characteristics of abnormalities visible on magnetic resonance imaging (MRI). In the early years, these studies were limited to white matter (WM) lesions. T2-hyperintensities were shown to reflect a heterogeneous underlying pathology. T1 'black holes' were found to be more pathologically specific, as they tend to reflect lesions with more profound axonal loss. Slowly resolving black holes, on the other hand, represent various degrees of remyelination. Normal-appearing WM on MRI was demonstrated widely abnormal in terms of histopathology, with varying degrees of axon and myelin loss, and with multiple pre-active foci of microglial clustering. Diffusely abnormal WM areas on MRI were found to correspond to Wallerian degeneration, following initial axonal transection in multiple sclerosis (MS) lesions. As it became clear that some crucial clinical characteristics, such as cognitive impairment, could not be sufficiently explained by imaging of WM lesions, post mortem studies started focusing on the grey matter (GM). It was shown that GM lesions are numerous, though severely underrepresented by conventional imaging at standard field-strengths. Efforts over the years to improve upon imaging techniques and field strengths have resulted in better, though not perfect, GM lesion detection rates. Recent post mortem imaging work has increasingly focused on identifying underlying morphological substrates of abnormalities found with more advanced imaging techniques. For example, regional GM atrophy, an increasingly important measure in clinical and pharmaceutical trial settings, was shown to be dependent on axonal loss and neuronal shrinkage. Additionally, increases of fractional anisotropy in cortical GM lesions could be explained by an increase of matrix directionality following cortical axonal degeneration. Contemporary structural network analysis shows abnormalities that can be linearly retraced to specific neuronal changes in the MS cortex. Post mortem imaging and histopathology correlation requires a dedicated donor program, as well as a multidisciplinary team, and a complex pipeline, optimized to guarantee ultra-short post mortem delays and highest quality of tissue and imaging. The Amsterdam protocol, as well as some of the major findings of this research line over the last twenty years will be highlighted in this lecture.
Disclosure: Jeroen Geurts is Editor for Europe at Multiple Sclerosis Journal; he has served as a consultant and/or has received research grants from Biogen Idec, Novartis Pharma and Sanofi-Genzyme over the last three years.