Mark J.R.J. Bouts

YNICL Journal 2020 Journal Article

Pre-trained MRI-based Alzheimer's disease classification models to classify memory clinic patients

• Frank de Vos
• Tijn M. Schouten
• Marisa Koini
• Mark J.R.J. Bouts
• Rogier A. Feis
• Anita Lechner
• Reinhold Schmidt
• Mark A. van Buchem

Anatomical magnetic resonance imaging (MRI), diffusion MRI and resting state functional MRI (rs-fMRI) have been used for Alzheimer's disease (AD) classification. These scans are typically used to build models for discriminating AD patients from control subjects, but it is not clear if these models can also discriminate AD in diverse clinical populations as found in memory clinics. To study this, we trained MRI-based AD classification models on a single centre data set consisting of AD patients (N = 76) and controls (N = 173), and used these models to assign AD scores to subjective memory complainers (N = 67), mild cognitive impairment (MCI) patients (N = 61), and AD patients (N = 61) from a multi-centre memory clinic data set. The anatomical MRI scans were used to calculate grey matter density, subcortical volumes and cortical thickness, the diffusion MRI scans were used to calculate fractional anisotropy, mean, axial and radial diffusivity, and the rs-fMRI scans were used to calculate functional connectivity between resting state networks and amplitude of low frequency fluctuations. Within the multi-centre memory clinic data set we removed scan site differences prior to applying the models. For all models, on average, the AD patients were assigned the highest AD scores, followed by MCI patients, and later followed by SMC subjects. The anatomical MRI models performed best, and the best performing anatomical MRI measure was grey matter density, separating SMC subjects from MCI patients with an AUC of 0.69, MCI patients from AD patients with an AUC of 0.70, and SMC patients from AD patients with an AUC of 0.86. The diffusion MRI models did not generalise well to the memory clinic data, possibly because of large scan site differences. The functional connectivity model separated SMC subjects and MCI patients relatively good (AUC = 0.66). The multimodal MRI model did not improve upon the anatomical MRI model. In conclusion, we showed that the grey matter density model generalises best to memory clinic subjects. When also considering the fact that grey matter density generally performs well in AD classification studies, this feature is probably the best MRI-based feature for AD diagnosis in clinical practice.

YNICL Journal 2019 Journal Article

Corrigendum to ‘Single-subject classification of presymptomatic frontotemporal dementia mutation carriers user multimodal MRI’ NeuroImage: Clinical 20 (2018) 188–196

• Rogier A. Feis
• Mark J.R.J. Bouts
• Jessica L. Panman
• Lize C. Jiskoot
• Elise G.P. Dopper
• Tijn M. Schouten
• Frank de Vos
• Jeroen van der Grond

YNICL Journal 2019 Journal Article

Single-subject classification of presymptomatic frontotemporal dementia mutation carriers using multimodal MRI

• Rogier A. Feis
• Mark J.R.J. Bouts
• Jessica L. Panman
• Lize C. Jiskoot
• Elise G.P. Dopper
• Tijn M. Schouten
• Frank de Vos
• Jeroen van der Grond

Background: Classification models based on magnetic resonance imaging (MRI) may aid early diagnosis of frontotemporal dementia (FTD) but have only been applied in established FTD cases. Detection of FTD patients in earlier disease stages, such as presymptomatic mutation carriers, may further advance early diagnosis and treatment. In this study, we aim to distinguish presymptomatic FTD mutation carriers from controls on an individual level using multimodal MRI-based classification. Methods: Anatomical MRI, diffusion tensor imaging (DTI) and resting-state functional MRI data were collected in 55 presymptomatic FTD mutation carriers (8 microtubule-associated protein Tau, 35 progranulin, and 12 chromosome 9 open reading frame 72) and 48 familial controls. We calculated grey and white matter density features from anatomical MRI scans, diffusivity features from DTI, and functional connectivity features from resting-state functional MRI. These features were applied in a recently introduced multimodal behavioural variant FTD (bvFTD) classification model, and were subsequently used to train and test unimodal and multimodal carrier-control models. Classification performance was quantified using area under the receiver operator characteristic curves (AUC). Results: The bvFTD model was not able to separate presymptomatic carriers from controls beyond chance level (AUC = 0.582, p = 0.078). In contrast, one unimodal and several multimodal carrier-control models performed significantly better than chance level. The unimodal model included the radial diffusivity feature and had an AUC of 0.642 (p = 0.032). The best multimodal model combined radial diffusivity and white matter density features (AUC = 0.684, p = 0.004). Conclusions: FTD mutation carriers can be separated from controls with a modest AUC even before symptom-onset, using a newly created carrier-control classification model, while this was not possible using a recent bvFTD classification model. A multimodal MRI-based classification score may therefore be a useful biomarker to aid earlier FTD diagnosis. The exclusive selection of white matter features in the best performing model suggests that the earliest FTD-related pathological processes occur in white matter.

YNICL Journal 2018 Journal Article

Single-subject classification of presymptomatic frontotemporal dementia mutation carriers using multimodal MRI

• Rogier A. Feis
• Mark J.R.J. Bouts
• Jessica L. Panman
• Lize C. Jiskoot
• Elise G.P. Dopper
• Tijn M. Schouten
• Frank de Vos
• Jeroen van der Grond

BACKGROUND: Classification models based on magnetic resonance imaging (MRI) may aid early diagnosis of frontotemporal dementia (FTD) but have only been applied in established FTD cases. Detection of FTD patients in earlier disease stages, such as presymptomatic mutation carriers, may further advance early diagnosis and treatment. In this study, we aim to distinguish presymptomatic FTD mutation carriers from controls on an individual level using multimodal MRI-based classification. METHODS: Anatomical MRI, diffusion tensor imaging (DTI) and resting-state functional MRI data were collected in 55 presymptomatic FTD mutation carriers (8 microtubule-associated protein Tau, 35 progranulin, and 12 chromosome 9 open reading frame 72) and 48 familial controls. We calculated grey and white matter density features from anatomical MRI scans, diffusivity features from DTI, and functional connectivity features from resting-state functional MRI. These features were applied in a recently introduced multimodal behavioural variant FTD (bvFTD) classification model, and were subsequently used to train and test unimodal and multimodal carrier-control models. Classification performance was quantified using area under the receiver operator characteristic curves (AUC). RESULTS: The bvFTD model was not able to separate presymptomatic carriers from controls beyond chance level (AUC = 0.582, p = 0.078). In contrast, one unimodal and several multimodal carrier-control models performed significantly better than chance level. The unimodal model included the radial diffusivity feature and had an AUC of 0.642 (p = 0.032). The best multimodal model combined radial diffusivity and white matter density features (AUC = 0.684, p = 0.004). CONCLUSIONS: FTD mutation carriers can be separated from controls with a modest AUC even before symptom-onset, using a newly created carrier-control classification model, while this was not possible using a recent bvFTD classification model. A multimodal MRI-based classification score may therefore be a useful biomarker to aid earlier FTD diagnosis. The exclusive selection of white matter features in the best performing model suggests that the earliest FTD-related pathological processes occur in white matter.