Michelutti Marco, Huppertz Hans-Jürgen, Volkmann Heiko, Anderl-Straub Sarah, Urso Daniele, Tafuri Benedetta, Nigro Salvatore, Manganotti Paolo, Werner Leonie, Lombardi Jolina, Otto Markus, Logroscino Giancarlo, Müller Hans-Peter, Kassubek Jan
Neurology Unit, Department of Medical, Surgical and Health Sciences, University of Trieste, Strada di Fiume 447, 34149, Trieste, Italy.
Department of Neurology, University Hospital Ulm, Ulm, Germany.
J Neurol. 2025 Jul 2;272(8):490. doi: 10.1007/s00415-025-13215-9.
The non-fluent (nfPPA) and semantic (svPPA) variants of primary progressive aphasia exhibit distinct clinical features. We investigated whether diffusion tensor imaging (DTI) and atlas-based volumetry (ABV) could reveal divergent patterns of longitudinal changes in brain white matter microstructure and gray matter volumes.
MRI datasets from 29 nfPPA, 27 svPPA, and 39 controls were analyzed. White matter fractional anisotropy (FA) differences were assessed using unbiased Whole Brain-based Spatial Statistics (WBSS) and Tract-Wise Fractional Anisotropy Statistics (TFAS). Gray matter volumetric differences were calculated by Atlas-Based Volumetry (ABV). A subset of 10 nfPPA and 6 svPPA patients underwent longitudinal MRI at 12 months. FA maps were correlated with disease severity (FTLD-CDR sum of boxes). A random forest classifier validated tracts of interest (TOI) and structures of interest (SOIs) selection as a proof-of-concept.
At baseline, nfPPA showed frontal, callosal, and temporal white matter degeneration, while the left inferior longitudinal fasciculus (ILF) was predominantly involved in svPPA. Longitudinally, nfPPA exhibited frontal, callosal, and posterior temporal progression, while svPPA showed localized antero-posterior ILF progression. ABV aligned with the DTI analyses, demonstrating volumetric reductions in the frontal lobe for nfPPA and in temporal lobe and subcortical limbic structures in svPPA. Sub-clusters of white matter damage progression correlated with worsening FTLD-CDR scores. Random forest analysis identified the most discriminative TOIs and SOIs.
Distinct degeneration patterns emerged across nfPPA and svPPA, supporting early differential diagnosis and correlating with disease worsening. These findings support the utility of combined DTI and ABV in tracking disease progression.
原发性进行性失语的非流利型（nfPPA）和语义型（svPPA）变体具有不同的临床特征。我们研究了扩散张量成像（DTI）和基于图谱的体积测量（ABV）是否能揭示脑白质微观结构和灰质体积纵向变化的不同模式。
分析了来自29例nfPPA、27例svPPA和39例对照的MRI数据集。使用无偏全脑空间统计（WBSS）和逐束分数各向异性统计（TFAS）评估白质分数各向异性（FA）差异。通过基于图谱的体积测量（ABV）计算灰质体积差异。10例nfPPA和6例svPPA患者的一个亚组在12个月时接受了纵向MRI检查。FA图与疾病严重程度（FTLD-CDR框总和）相关。随机森林分类器验证了感兴趣区域（TOI）和感兴趣结构（SOI）的选择作为概念验证。
在基线时，nfPPA表现为额叶、胼胝体和颞叶白质变性，而左侧下纵束（ILF）主要累及svPPA。纵向来看，nfPPA表现为额叶、胼胝体和颞叶后部进展，而svPPA表现为局部前后ILF进展。ABV与DTI分析结果一致，显示nfPPA的额叶体积减少，svPPA的颞叶和皮质下边缘结构体积减少。白质损伤进展的亚组与FTLD-CDR评分恶化相关。随机森林分析确定了最具鉴别性的TOI和SOI。
nfPPA和svPPA出现了不同的变性模式，支持早期鉴别诊断并与疾病恶化相关。这些发现支持联合使用DTI和ABV追踪疾病进展的实用性。
