Differentiation between Subtypes of Primary Progressive Aphasia by Using Cortical Thickness and Diffusion-Tensor MR Imaging Measures.
OBJECTIVE
To test a multimodal magnetic resonance (MR) imaging-based approach composed of cortical thickness and white matter (WM) damage metrics to discriminate between variants of primary progressive aphasia (PPA) that are nonfluent and/or agrammatic (NFVPPA) and semantic (SVPPA).


METHODS
This study was approved by the local ethics committees on human studies, and written informed consent from all patients was obtained before their enrollment. T1-weighted and diffusion-tensor (DT) MR images were obtained from 13 NFVPPA patients, 13 SVPPA patients, and 23 healthy control participants. Cortical thickness and DT MR imaging indices from the long-associative and interhemispheric WM tracts were obtained. A random forest (RF) analysis was used to identify the image features associated with each clinical syndrome. Individual patient classification was performed by using receiver operator characteristic curve analysis with cortical thickness, DT MR imaging, and a combination of the two modalities. RESULTS RF analysis showed that the best markers to differentiate the two PPA variants at an individual patient level among cortical thickness and DT MR imaging metrics were diffusivity abnormalities of the left inferior longitudinal and uncinate fasciculi and cortical thickness measures of the left temporal pole and inferior frontal gyrus. A combination of cortical thickness and DT MR imaging measures (the so-called gray-matter-and-WM model) was able to distinguish patients with NFVPPA and SVPPA with the following classification pattern: area under the curve, 0.91; accuracy, 0.89; sensitivity, 0.92; specificity, 0.85. Leave-one-out analysis demonstrated that the gray matter and WM model is more robust than the single MR modality models to distinguish PPA variants (accuracy was 0.86, 0.73, and 0.68 for the gray matter and WM model, the gray matter-only model, and the WM-only model, respectively).


CONCLUSIONS
A combination of structural and DT MR imaging metrics may provide a quantitative procedure to distinguish NFVPPA and SVPPA patients at an individual patient level. The discrimination accuracies obtained suggest that the gray matter and WM model is potentially relevant for the differential diagnosis of the PPA variants in clinical practice.
From the Neuroimaging Research Unit (F.A., P.M.F., E.C., S.G., P.V., A.S., M.F.), Department of Neurology, Institute of Experimental Neurology (G.M., G.C., M.F.), Department of Clinical Neurosciences (A.M.), and Department of Neuroradiology and CERMAC, Division of Neuroscience (A.F.), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy; and Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy (M.C.).
Federica
F
Agosta
From the Neuroimaging Research Unit (F.A., P.M.F., E.C., S.G., P.V., A.S., M.F.), Department of Neurology, Institute of Experimental Neurology (G.M., G.C., M.F.), Department of Clinical Neurosciences (A.M.), and Department of Neuroradiology and CERMAC, Division of Neuroscience (A.F.), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy; and Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy (M.C.).
Pilar M
PM
Ferraro
From the Neuroimaging Research Unit (F.A., P.M.F., E.C., S.G., P.V., A.S., M.F.), Department of Neurology, Institute of Experimental Neurology (G.M., G.C., M.F.), Department of Clinical Neurosciences (A.M.), and Department of Neuroradiology and CERMAC, Division of Neuroscience (A.F.), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy; and Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy (M.C.).
Elisa
E
Canu
From the Neuroimaging Research Unit (F.A., P.M.F., E.C., S.G., P.V., A.S., M.F.), Department of Neurology, Institute of Experimental Neurology (G.M., G.C., M.F.), Department of Clinical Neurosciences (A.M.), and Department of Neuroradiology and CERMAC, Division of Neuroscience (A.F.), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy; and Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy (M.C.).
Massimiliano
M
Copetti
From the Neuroimaging Research Unit (F.A., P.M.F., E.C., S.G., P.V., A.S., M.F.), Department of Neurology, Institute of Experimental Neurology (G.M., G.C., M.F.), Department of Clinical Neurosciences (A.M.), and Department of Neuroradiology and CERMAC, Division of Neuroscience (A.F.), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy; and Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy (M.C.).
Sebastiano
S
Galantucci
From the Neuroimaging Research Unit (F.A., P.M.F., E.C., S.G., P.V., A.S., M.F.), Department of Neurology, Institute of Experimental Neurology (G.M., G.C., M.F.), Department of Clinical Neurosciences (A.M.), and Department of Neuroradiology and CERMAC, Division of Neuroscience (A.F.), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy; and Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy (M.C.).
Giuseppe
G
Magnani
From the Neuroimaging Research Unit (F.A., P.M.F., E.C., S.G., P.V., A.S., M.F.), Department of Neurology, Institute of Experimental Neurology (G.M., G.C., M.F.), Department of Clinical Neurosciences (A.M.), and Department of Neuroradiology and CERMAC, Division of Neuroscience (A.F.), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy; and Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy (M.C.).
Alessandra
A
Marcone
From the Neuroimaging Research Unit (F.A., P.M.F., E.C., S.G., P.V., A.S., M.F.), Department of Neurology, Institute of Experimental Neurology (G.M., G.C., M.F.), Department of Clinical Neurosciences (A.M.), and Department of Neuroradiology and CERMAC, Division of Neuroscience (A.F.), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy; and Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy (M.C.).
Paola
P
Valsasina
From the Neuroimaging Research Unit (F.A., P.M.F., E.C., S.G., P.V., A.S., M.F.), Department of Neurology, Institute of Experimental Neurology (G.M., G.C., M.F.), Department of Clinical Neurosciences (A.M.), and Department of Neuroradiology and CERMAC, Division of Neuroscience (A.F.), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy; and Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy (M.C.).
Alessandro
A
Sodero
From the Neuroimaging Research Unit (F.A., P.M.F., E.C., S.G., P.V., A.S., M.F.), Department of Neurology, Institute of Experimental Neurology (G.M., G.C., M.F.), Department of Clinical Neurosciences (A.M.), and Department of Neuroradiology and CERMAC, Division of Neuroscience (A.F.), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy; and Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy (M.C.).
Giancarlo
G
Comi
From the Neuroimaging Research Unit (F.A., P.M.F., E.C., S.G., P.V., A.S., M.F.), Department of Neurology, Institute of Experimental Neurology (G.M., G.C., M.F.), Department of Clinical Neurosciences (A.M.), and Department of Neuroradiology and CERMAC, Division of Neuroscience (A.F.), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy; and Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy (M.C.).
Andrea
A
Falini
From the Neuroimaging Research Unit (F.A., P.M.F., E.C., S.G., P.V., A.S., M.F.), Department of Neurology, Institute of Experimental Neurology (G.M., G.C., M.F.), Department of Clinical Neurosciences (A.M.), and Department of Neuroradiology and CERMAC, Division of Neuroscience (A.F.), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy; and Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy (M.C.).
Massimo
M
Filippi
D000368:Aged; D018888:Aphasia, Primary Progressive / Q000145:classification* / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology*; D003937:Diagnosis, Differential; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged