Johannes Rosskopf

Ex post facto assessment of diffusion tensor imaging metrics from different MRI protocols: Preparing for multicentre studies in ALS

Abstract Diffusion tensor imaging (DTI) for assessing ALS-associated white matter alterations has still not reached the level of a neuroimaging biomarker. Since large-scale multicentre DTI studies in ALS may be hampered by differences in scanning protocols, an approach for pooling of DTI data acquired with different protocols was investigated. Three hundred and nine datasets from 170 ALS patients and 139 controls were collected ex post facto from a monocentric database reflecting different scanning protocols. A 3D correction algorithm was introduced for a combined analysis of DTI metrics despite different acquisition protocols, with the focus on the CST as the tract correlate of ALS neuropathological stage 1. A homogenous set of data was obtained by application of 3D correction matrices. Results showed that a fractional anisotropy (FA) threshold of 0.41 could be defined to discriminate ALS patients from controls (sensitivity/specificity, 74%/72%). For the remaining test sample, sensitivity/specificity values of 68%/74% were obtained. In conclusion, the objective was to merge data recorded with different DTI protocols with 3D correction matrices for analyses at group level. These post processing tools might facilitate analysis of large study samples in a multicentre setting for DTI analysis at group level to aid in establishing DTI as a non-invasive biomarker for ALS.

Frontal Corpus Callosum Alterations in Progressive Supranuclear Palsy but Not in Parkinson's Disease

Background: Frontal lobe involvement is considered a clinical and magnetic resonance imaging (MRI) feature in later stages of progressive supranuclear palsy (PSP). Objective: Diffusion tensor imaging (DTI) was used to investigate the integrity of frontal pathways in PSP and Parkinsons disease (PD) patients. Methods: DTI and 3-D MRI were performed in 15 PSP patients (parkinsonism subtype: n = 8; Richardson subtype: n = 7), 15 PD patients, and 18 matched controls. DTI analysis was performed in order to identify differences along frontal white matter structures including the corpus callosum (CC) and was complemented by atlas-based volumetry and planimetry. Results: Significantly reduced regional fractional anisotropy was observed for PSP patients versus controls and PSP versus PD patients, respectively, in frontal areas including the area II of the CC and bilaterally in the callosal radiation. The DTI findings correlated with frontal lobe volumes. These differences were not observed between PD patients and controls. Conclusion: DTI identified a PSP-associated microstructural alteration pattern in the frontal lobes and in the CC area II including the corresponding bilateral callosal radiation tracts that could not be identified in both control samples, supporting the prominent PSP-associated frontal involvement as a potential neuroimaging marker.

Intrinsic functional connectivity alterations in progressive supranuclear palsy: Differential effects in frontal cortex, motor, and midbrain networks

The topography of functional network changes in progressive supranuclear palsy can be mapped by intrinsic functional connectivity MRI. The objective of this study was to study functional connectivity and its clinical and behavioral correlates in dedicated networks comprising the cognition‐related default mode and the motor and midbrain functional networks in patients with PSP.

FV7. Tract of interest-based DTI analysis in upper and lower motor neuron disease variants of ALS

Background It is still a topic of research if specific clinical presentations of motoneuron disease (MND) patients should be classified as amyotrophic lateral sclerosis (ALS) variants, i.e. primary lateral sclerosis (PLS) with predominant upper motor neuron on the one hand and pure lower motor neuron disease (LMND) on the other hand. Objective markers for ALS are to be investigated in these patients. Objective The aim of the study was to investigate white matter damage by a hypothesis-guided tract-of-interest-based approach in patients with classical ALS, LMND, and PLS in contrast to healthy controls in order to challenge the hypothesis that brain structural changes according to the neuropathologically defined ALS affectation pattern ( Kassubek et al., 2014 ) can be observed. LMND data were pooled from previous studies at two different study sites (Ulm, Germany and Milano, Italy). Methods DTI-based white matter integrity mapping was performed by voxelwise statistical comparison and by a tractwise analysis of fractional anisotropy (FA) maps according to the ALS-staging pattern for 65 LMND patients (clinically differentiated in fast and slow progressors), 42 PLS patients, and 101 ALS patients with a ’classical’ phenotype vs 92 matched controls to identify white matter structural alterations. Results The analysis of predefined tracts-of-interest according to the neuropathological spreading pattern demonstrated regional characteristic alteration patterns (FA reductions) fast LMND progressors and in ALS compared to controls. ( Muller et al., 2018 ) The degree of involvement correlated with the clinical phenotype. PLS also presented substantial tract involvement in the tract-of-interest-based approach. Conclusion In the tract-specific analysis according to the ALS-staging pattern, upper (PLS) as well as lower motor neuron disease (LMND) pathology showed alterations of ALS-related corticoefferent fibers. The neuroimaging results confirm the clinical approach to these phenotypes as ALS variants, in accordance with the latest revision of the El Escorial criteria for ALS, in favour of the consequence to treat these patients like ALS and also to include them into clinical trials of ALS.

PB1. Functional network alterations in multisystem atrophy (MSA)

Background In multisystem atrophy (MSA), the functional brain connectivity within cortical and subcortical networks and its clinical correlates is a challenging topic of research. Objective Assessment of functional brain connectivity alterations in MSA. Methods Whole-brain based ‘intrinsic functional connectivity’ MRI data were obtained from 22 MSA patients and 22 matched healthy controls, together with standardized clinical assessment and video-oculographic recordings (EyeLink®). Results MSA patients vs. controls showed significantly increased ponto-cerebellar functional connectivity and decreased default mode network connectivity ( p 0.05 , corrected). No differences were observed in the motor network. Saccadized smooth pursuit significantly correlated with increased functional ponto-cerebellar connectivity ( p 0.05 , corrected). Conclusion This intrinsic functional connectivity analysis supports a network-dependent combination of hyper- and hypoconnectivity states in MSA, in agreement with adaptive compensatory responses (hyperconnectivity) and a function disconnection syndrome (hypoconnectivity) ( Gorges et al., 2017 ) that may occur in a consecutive sequence.