PDF(Pubmed)
Abstract：
BACKGROUND: Multiple sclerosis (MS) is a clinically heterogeneous disease underpinned by inflammatory, demyelinating and neurodegenerative processes, the extent of which varies between individuals and over the course of the disease. Recognising the clinicopathological features that most strongly associate with disease outcomes will inform future efforts at patient phenotyping.
OBJECTIVE: We used a digital pathology workflow, involving high-resolution image acquisition of immunostained slides and opensource software for quantification, to investigate the relationship between clinical and neuropathological features in an autopsy cohort of progressive MS.
METHODS: Sequential sections of frontal, cingulate and occipital cortex, thalamus, brain stem (pons) and cerebellum including dentate nucleus (n = 35 progressive MS, females = 28, males = 7; age died = 53.5 years; range 38-98 years) were immunostained for myelin (anti-MOG), neurons (anti-HuC/D) and microglia/macrophages (anti-HLA). The extent of demyelination, neurodegeneration, the presence of active and/or chronic active lesions and quantification of brain and leptomeningeal inflammation was captured by digital pathology.
RESULTS: Digital analysis of tissue sections revealed the variable extent of pathology that characterises progressive MS. Microglia/macrophage activation, if found at a higher level in a single block, was typically elevated across all sampled blocks. Compartmentalised (perivascular/leptomeningeal) inflammation was associated with age-related measures of disease severity and an earlier death.
CONCLUSIONS: Digital pathology identified prognostically important clinicopathological correlations in MS. This methodology can be used to prioritise the principal pathological processes that need to be captured by future MS biomarkers.
OBJECTIVE: We used a digital pathology workflow, involving high-resolution image acquisition of immunostained slides and opensource software for quantification, to investigate the relationship between clinical and neuropathological features in an autopsy cohort of progressive MS.
METHODS: Sequential sections of frontal, cingulate and occipital cortex, thalamus, brain stem (pons) and cerebellum including dentate nucleus (n = 35 progressive MS, females = 28, males = 7; age died = 53.5 years; range 38-98 years) were immunostained for myelin (anti-MOG), neurons (anti-HuC/D) and microglia/macrophages (anti-HLA). The extent of demyelination, neurodegeneration, the presence of active and/or chronic active lesions and quantification of brain and leptomeningeal inflammation was captured by digital pathology.
RESULTS: Digital analysis of tissue sections revealed the variable extent of pathology that characterises progressive MS. Microglia/macrophage activation, if found at a higher level in a single block, was typically elevated across all sampled blocks. Compartmentalised (perivascular/leptomeningeal) inflammation was associated with age-related measures of disease severity and an earlier death.
CONCLUSIONS: Digital pathology identified prognostically important clinicopathological correlations in MS. This methodology can be used to prioritise the principal pathological processes that need to be captured by future MS biomarkers.
摘要：
背景：多发性硬化症（MS）是一种临床异质性疾病，由炎症性疾病，脱髓鞘和神经退行性过程，其程度因个体和整个疾病过程而异。认识到与疾病结果最密切相关的临床病理特征将为未来的患者表型鉴定工作提供信息。
目的：我们使用了数字病理学工作流程，涉及免疫染色载玻片的高分辨率图像采集和用于定量的开源软件，研究进行性MS尸检队列中临床和神经病理学特征之间的关系。
方法：额叶，扣带和枕骨皮质，丘脑,脑干（脑桥）和小脑，包括齿状核（n=35进行性MS，女性=28，男性=7；死亡年龄=53.5岁；范围38-98岁）对髓磷脂（抗MOG）进行免疫染色，神经元（抗HuC/D）和小胶质细胞/巨噬细胞（抗HLA）。脱髓鞘的程度，神经变性,通过数字病理学记录了活动性和/或慢性活动性病变的存在以及脑和软脑膜炎症的定量。
结果：组织切片的数字分析显示了进行性MS的病理程度不同。小胶质细胞/巨噬细胞活化，如果在单个块中的更高级别的位置找到，通常在所有采样块中都是升高的。分区（血管周围/软脑膜）炎症与疾病严重程度的年龄相关指标和较早死亡有关。
结论：数字病理学确定了MS的预后重要临床病理相关性。该方法可用于优先考虑需要由未来的MS生物标志物捕获的主要病理过程。
目的：我们使用了数字病理学工作流程，涉及免疫染色载玻片的高分辨率图像采集和用于定量的开源软件，研究进行性MS尸检队列中临床和神经病理学特征之间的关系。
方法：额叶，扣带和枕骨皮质，丘脑,脑干（脑桥）和小脑，包括齿状核（n=35进行性MS，女性=28，男性=7；死亡年龄=53.5岁；范围38-98岁）对髓磷脂（抗MOG）进行免疫染色，神经元（抗HuC/D）和小胶质细胞/巨噬细胞（抗HLA）。脱髓鞘的程度，神经变性,通过数字病理学记录了活动性和/或慢性活动性病变的存在以及脑和软脑膜炎症的定量。
结果：组织切片的数字分析显示了进行性MS的病理程度不同。小胶质细胞/巨噬细胞活化，如果在单个块中的更高级别的位置找到，通常在所有采样块中都是升高的。分区（血管周围/软脑膜）炎症与疾病严重程度的年龄相关指标和较早死亡有关。
结论：数字病理学确定了MS的预后重要临床病理相关性。该方法可用于优先考虑需要由未来的MS生物标志物捕获的主要病理过程。
