Purpose
Tauopathy and transactive response DNA binding protein 43 (TDP-43) proteinopathy are associated with neurodegenerative diseases. These proteinopathies are difficult to detect
in vivo
. This ...study examined if spectral-domain optical coherence tomography (SD-OCT) can differentiate
in vivo
the difference in peripapillary retinal nerve fibre layer (pRNFL) thickness and macular retinal thickness between participants with presumed tauopathy (progressive supranuclear palsy) and those with presumed TDP-43 proteinopathy (amyotrophic lateral sclerosis and semantic variant primary progressive aphasia).
Study design
Prospective, multi-centre, observational study.
Materials and methods
pRNFL and macular SD-OCT images were acquired in both eyes of each participant using Heidelberg Spectralis SD-OCT. Global and pRNFL thickness in 6 sectors were analyzed, as well as macular thickness in a central 1 mm diameter zone and 4 surrounding sectors. Linear mixed model methods adjusting for baseline differences between groups were used to compare the two groups with respect to pRNFL and macular thickness.
Results
A significant difference was found in mean pRNFL thickness between groups, with the TDP-43 group (
n
= 28 eyes) having a significantly thinner pRNFL in the temporal sector than the tauopathy group (
n
= 9 eyes; mean difference = 15.46 μm, SE = 6.98,
p
= 0.046), which was not significant after adjusting for multiple comparisons. No other significant differences were found between groups for pRNFL or macular thickness.
Conclusion
The finding that the temporal pRNFL in the TDP-43 group was on average 15.46 μm thinner could potentially have clinical significance. Future work with larger sample sizes, longitudinal studies, and at the level of retinal sublayers will help to determine the utility of SD-OCT to differentiate between these two proteinopathies.
Alterations in tissue microstructure in normal-appearing white matter (NAWM), specifically measured by diffusion tensor imaging (DTI) fractional anisotropy (FA), have been associated with cognitive ...outcomes following stroke. The purpose of this study was to comprehensively compare conventional DTI measures of tissue microstructure in NAWM to diverse vascular brain lesions in people with cerebrovascular disease (CVD) and to examine associations between FA in NAWM and cerebrovascular risk factors. DTI metrics including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were measured in cerebral tissues and cerebrovascular anomalies from 152 people with CVD participating in the Ontario Neurodegenerative Disease Research Initiative (ONDRI). Ten cerebral tissue types were segmented including NAWM, and vascular lesions including stroke, periventricular and deep white matter hyperintensities, periventricular and deep lacunar infarcts, and perivascular spaces (PVS) using T1-weighted, proton density-weighted, T2-weighted, and fluid attenuated inversion recovery MRI scans. Mean DTI metrics were measured in each tissue region using a previously developed DTI processing pipeline and compared between tissues using multivariate analysis of covariance. Associations between FA in NAWM and several CVD risk factors were also examined. DTI metrics in vascular lesions differed significantly from healthy tissue. Specifically, all tissue types had significantly different MD values, while FA was also found to be different in most tissue types. FA in NAWM was inversely related to hypertension and modified Rankin scale (mRS). This study demonstrated the differences between conventional DTI metrics, FA, MD, AD, and RD, in cerebral vascular lesions and healthy tissue types. Therefore, incorporating DTI to characterize the integrity of the tissue microstructure could help to define the extent and severity of various brain vascular anomalies. The association between FA within NAWM and clinical evaluation of hypertension and disability provides further evidence that white matter microstructural integrity is impacted by cerebrovascular function.
Change in empathy is an increasingly recognised symptom of neurodegenerative diseases and contributes to caregiver burden and patient distress. Empathy impairment has been associated with brain ...atrophy but its relationship to white matter hyperintensities (WMH) is unknown. We aimed to investigate the relationships amongst WMH, brain atrophy, and empathy deficits in neurodegenerative and cerebrovascular diseases. Five hundred thirteen participants with Alzheimer’s disease/mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia (FTD), Parkinson’s disease, or cerebrovascular disease (CVD) were included. Empathy was assessed using the Interpersonal Reactivity Index. WMH were measured using a semi-automatic segmentation and FreeSurfer was used to measure cortical thickness. A heterogeneous pattern of cortical thinning was found between groups, with FTD showing thinning in frontotemporal regions and CVD in left superior parietal, left insula, and left postcentral. Results from both univariate and multivariate analyses revealed that several variables were associated with empathy, particularly cortical thickness in the fronto-insulo-temporal and cingulate regions, sex (female), global cognition, and right parietal and occipital WMH. Our results suggest that cortical atrophy and WMH may be associated with empathy deficits in neurodegenerative and cerebrovascular diseases. Future work should consider investigating the longitudinal effects of WMH and atrophy on empathy deficits in neurodegenerative and cerebrovascular diseases.
Obtaining in vivo human brain tissue volumetrics from MRI is often complicated by various technical and biological issues. These challenges are exacerbated when significant brain atrophy and ...age-related white matter changes (e.g. Leukoaraiosis) are present. Lesion Explorer (LE) is an accurate and reliable neuroimaging pipeline specifically developed to address such issues commonly observed on MRI of Alzheimer's disease and normal elderly. The pipeline is a complex set of semi-automatic procedures which has been previously validated in a series of internal and external reliability tests(1,2). However, LE's accuracy and reliability is highly dependent on properly trained manual operators to execute commands, identify distinct anatomical landmarks, and manually edit/verify various computer-generated segmentation outputs. LE can be divided into 3 main components, each requiring a set of commands and manual operations: 1) Brain-Sizer, 2) SABRE, and 3) Lesion-Seg. Brain-Sizer's manual operations involve editing of the automatic skull-stripped total intracranial vault (TIV) extraction mask, designation of ventricular cerebrospinal fluid (vCSF), and removal of subtentorial structures. The SABRE component requires checking of image alignment along the anterior and posterior commissure (ACPC) plane, and identification of several anatomical landmarks required for regional parcellation. Finally, the Lesion-Seg component involves manual checking of the automatic lesion segmentation of subcortical hyperintensities (SH) for false positive errors. While on-site training of the LE pipeline is preferable, readily available visual teaching tools with interactive training images are a viable alternative. Developed to ensure a high degree of accuracy and reliability, the following is a step-by-step, video-guided, standardized protocol for LE's manual procedures.
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