Arrow Research search

Author name cluster

Dorothée Lulé

Possible papers associated with this exact author name in Arrow. This page groups case-insensitive exact name matches and is not a full identity disambiguation profile.

3 papers
1 author row

Possible papers

3

YNICL Journal 2023 Journal Article

Structural and microstructural neuroimaging signature of C9orf72-associated ALS: A multiparametric MRI study

  • Maximilian Wiesenfarth
  • Hans-Jürgen Huppertz
  • Johannes Dorst
  • Dorothée Lulé
  • Albert C. Ludolph
  • Hans-Peter Müller
  • Jan Kassubek

BACKGROUND: ALS patients with hexanucleotide expansion in C9orf72 are characterized by a specific clinical phenotype, including more aggressive disease course and cognitive decline. Computerized multiparametric MRI with gray matter volumetry and diffusion tensor imaging (DTI) to analyze white matter structural connectivity is a potential in vivo biomarker. OBJECTIVE: The objective of this study was to develop a multiparametric MRI signature in a large cohort of ALS patients with C9orf72 mutations. The aim was to investigate how morphological features of C9orf72-associated ALS differ in structural MRI and DTI compared to healthy controls and ALS patients without C9orf72 mutations. METHODS: Atlas-based volumetry (ABV) and whole brain-based DTI-based analyses were performed in a cohort of n = 51 ALS patients with C9orf72 mutations and compared with both n = 51 matched healthy controls and n = 51 C9orf72 negative ALS patients, respectively. Subsequently, Spearman correlation analysis of C9orf72 ALS patients' data with clinical parameters (age of onset, sex, ALS-FRS-R, progression rate, survival) as well as ECAS and p-NfH in CSF was performed. RESULTS: The whole brain voxel-by-voxel comparison of fractional anisotropy (FA) maps between C9orf72 ALS patients and controls showed significant bilateral alterations in axonal structures of the white matter at group level, primarily along the corticospinal tracts and in fibers projecting to the frontal lobes. For the frontal lobes, these alterations were also significant between C9orf72 positive and C9orf72 negative ALS patients. In ABV, patients with C9orf72 mutations showed lower volumes of the frontal, temporal, and parietal lobe, with the lowest values in the gray matter of the superior frontal and the precentral gyrus, but also in hippocampi and amygdala. Compared to C9orf72 negative ALS, the differences were shown to be significant for cerebral gray matter (p = 0.04), especially in the frontal (p = 0.01) and parietal lobe (p = 0.01), and in the thalamus (p = 0.004). A correlation analysis between ECAS and averaged regional FA values revealed significant correlations between cognitive performance in ECAS and frontal association fibers. Lower FA values in the frontal lobes were associated with worse performance in all cognitive domains measured (language, verbal fluency, executive functions, memory and spatial perception). In addition, there were significant negative correlations between age of onset and atlas-based volumetry results for gray matter. CONCLUSIONS: This study demonstrates a distinct pattern of DTI alterations of the white matter and ubiquitous volume reductions of the gray matter early in the disease course of C9orf72-associated ALS. Alterations were closely linked to a more aggressive cognitive phenotype. These results are in line with an expected pTDP43 propagation pattern of cortical affection and thus strengthen the hypothesis that an underlying developmental disorder is present in ALS with C9orf72 expansions. Thus, multiparametric MRI could contribute to the assessment of the disease as an in vivo biomarker even in the early phase of the disease.

Details DOI

YNICL Journal 2022 Journal Article

A multivariate Bayesian classification algorithm for cerebral stage prediction by diffusion tensor imaging in amyotrophic lateral sclerosis

  • Anna Behler
  • Hans-Peter Müller
  • Albert C. Ludolph
  • Dorothée Lulé
  • Jan Kassubek

BACKGROUND AND OBJECTIVE: Diffusion tensor imaging (DTI) can be used to tract-wise map correlates of the sequential disease progression and, therefore, to assess disease stages of amyotrophic lateral sclerosis (ALS) in vivo. According to a threshold-based sequential scheme, a classification of ALS patients into disease stages is possible, however, several patients cannot be staged for methodological reasons. This study aims to implement a multivariate Bayesian classification algorithm for disease stage prediction at an individual ALS patient level based on DTI metrics of involved tract systems to improve disease stage mapping. METHODS: The analysis of fiber tracts involved in each stage of ALS was performed in 325 ALS patients and 130 age- and gender-matched healthy controls. Based on Bayes' theorem and in accordance with the sequential disease progression, a multistage classifier was implemented. Patients were categorized into in vivo DTI stages using the threshold-based method and the Bayesian algorithm. By the margin of confidence, the reliability of the Bayesian categorizations was accessible. RESULTS: Based on the Bayesian multistage classifier, 88% of all ALS patients could be assigned into an ALS stage compared to 77% using the threshold-based staging scheme. Additionally, the confidence of all classifications could be estimated. CONCLUSIONS: By the application of the multi-stage Bayesian classifier, an individualized in vivo cerebral staging of ALS patients was possible based on the sequentially involved tract systems and, furthermore, the reliability of the respective classifications could be determined. The Bayesian classification algorithm is an improvement of the threshold-based staging method and could provide a framework for extending the DTI-based in vivo cerebral staging in ALS.

Details DOI

YNICL Journal 2020 Journal Article

In vivo histopathological staging in C9orf72-associated ALS: A tract of interest DTI study

  • Hans-Peter Müller
  • Kelly Del Tredici
  • Dorothée Lulé
  • Kathrin Müller
  • Jochen H. Weishaupt
  • Albert C. Ludolph
  • Jan Kassubek

BACKGROUND: Diffusion tensor imaging (DTI) can identify amyotrophic lateral sclerosis (ALS)-associated patterns of brain alterations at the group level according to a neuropathological staging system. OBJECTIVE: The study was designed to investigate the in vivo staging in ALS patients with the C9orf72 expansion and potential differences to ALS patients with the SOD1 mutation. METHODS: DTI-based white matter mapping was performed both by an unbiased voxel-wise statistical comparison and by a hypothesis-guided tract-wise analysis of fractional anisotropy (FA) maps according to the ALS-staging pattern for 27 ALS patients with C9orf72 expansion vs 15 ALS patients with SOD1 mutation vs 32 matched healthy controls. Clinical and neuropsychological data were acquired and correlated to DTI data. RESULTS: The analysis of white matter integrity demonstrated regional FA reductions along the CST and also in frontal and prefrontal brain areas according to the proposed propagation pattern for the ALS patients with C9orf72 expansion and sporadic patients. This pattern could not be identified for the SOD1 mutation at the group level. In contrast, in the tract-specific analysis according to the neuropathological ALS-staging pattern, C9orf72 expansion ALS patients showed significant alterations of ALS-related tract systems similar to sporadic patients. CONCLUSIONS: The DTI study including the tract-of-interest-based analysis showed a microstructural corticoefferent involvement pattern according to the staging scheme in C9orf72-associated ALS patients but not in the SOD1 mutation.

Details DOI