Thalamic nuclei in frontotemporal dementia: Mediodorsal nucleus involvement is universal but pulvinar atrophy is unique to C9orf72

Thalamic atrophy is a common feature across all forms of FTD but little is known about specific nuclei involvement. We aimed to investigate in vivo atrophy of the thalamic nuclei across the FTD spectrum. A cohort of 402 FTD patients (age: mean(SD) 64.3(8.2) years; disease duration: 4.8(2.8) years) was compared with 104 age‐matched controls (age: 62.5(10.4) years), using an automated segmentation of T1‐weighted MRIs to extract volumes of 14 thalamic nuclei. Stratification was performed by clinical diagnosis (180 behavioural variant FTD (bvFTD), 85 semantic variant primary progressive aphasia (svPPA), 114 nonfluent variant PPA (nfvPPA), 15 PPA not otherwise specified (PPA‐NOS), and 8 with associated motor neurone disease (FTD‐MND), genetic diagnosis (27 MAPT, 28 C9orf72, 18 GRN), and pathological confirmation (37 tauopathy, 38 TDP‐43opathy, 4 FUSopathy). The mediodorsal nucleus (MD) was the only nucleus affected in all FTD subgroups (16–33% smaller than controls). The laterodorsal nucleus was also particularly affected in genetic cases (28–38%), TDP‐43 type A (47%), tau‐CBD (44%), and FTD‐MND (53%). The pulvinar was affected only in the C9orf72 group (16%). Both the lateral and medial geniculate nuclei were also affected in the genetic cases (10–20%), particularly the LGN in C9orf72 expansion carriers. Use of individual thalamic nuclei volumes provided higher accuracy in discriminating between FTD groups than the whole thalamic volume. The MD is the only structure affected across all FTD groups. Differential involvement of the thalamic nuclei among FTD forms is seen, with a unique pattern of atrophy in the pulvinar in C9orf72 expansion carriers.

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Brain volumes and their ratios in Alzheimer´s disease on magnetic resonance imaging segmented using Freesurfer 6.0

• Study shows 44 brain regions volume changes with Alzheimer's disease. 
• Volumes were calculated both in absolute values and ratios to the whole brain volume. 
• The hippocampo-horn proportion is effective for hippocampal atrophy evaluation. 
• This method can be simplified for visual assessment.

Abstract

Yearly Rates of Relative Atrophy

Yearly rates of Relative Atrophy (yrRA) are useful to compare the progression of the atrophy of a given brain structure in comparison with the progression of global brain atrophy. These methods are useful in the diagnosis and follow up of several neurodegenerative conditions, such as Alzheimer's disease (1) and Multiple Sclerosis (2). Thus, yrRA can be referenced to the ventricular system or referenced to the whole brain:

Global brain atrophy can be assessed well directly, measuring the loss of volume of the whole brain, well indirectly, measuring the enlargement of the volume of the ventricular system that correlates with the extent of brain atrophy. Thus, yearly rates of relative atrophy can be referenced to the ventricular system or referenced to the whole brain:

VENTRICULAR-REFERENCED

For telencephalic structures, one can compute the yearly rate of relative atrophy, comparing the change in the volume of ROIs, with the change of volume in the lateral ventricle system

yrR*A= (A1-A2) x 1200 / (B2-B1) x (#months between MRI studies)
where * is the ROI
A1 is the volume of the ROI in the first MRI and A2 the volume of the ROI in the second MRI
B1 is the volume of the ventricular system in the first MRI and B2 the volume of the ventricular system in the second MRI

These methods can be computed for each hemisphere separately, or for both brain hemispheres together (taking the addition of volumes of A on both hemispheres and the addition of volumes of B on both hemispheres).

For diencephalic structures, one can compute the yearly rate of relative atrophy, comparing the change in the volume of ROIs, with the change of volume in the lateral ventricles plus the third ventricle

yrR*A= (A1-A2) x 1200 / (B2-B1) x (#months between MRI studies)
where * is the ROI
A1 is the volume of the ROI in the first MRI and A2 the volume of the ROI in the second MRI
B1 is the volume of the ventricular system in the first MRI and B2 the volume of the ventricular system in the second MRI

For structures in the posterior fossa, one can compute the yearly rate of relative atrophy, comparing the change in the volume of ROIs, with the change of volume in the fourth ventricle.

yrR*A= (A1-A2) x 1200 / (B2-B1) x (#months between MRI studies)
where * is the ROI
A1 is the volume of the ROI in the first MRI and A2 the volume of the ROI in the second MRI
B1 is the volume of the forth ventricle in the first MRI and B2 the volume of the forth ventricle in the second MRI

WHOLE BRAIN-REFERENCED

For telencephalic and diencephalic structures, one can compute the yearly rate of relative atrophy, comparing the change in the volume of ROIs, with the change of volume in the brain hemisphere.

yrR*A= (A1-A2) x 1200 / (B2-B1) x (#months between MRI studies)
where * is the ROI
A1 is the volume of the ROI in the first MRI and A2 the volume of the ROI in the second MRI
B1 is the volume of the the brain hemisphere in the first MRI and B2 the volume of the the brain hemisphere in the second MRI

These methods can be computed for each hemisphere separately, or for both brain hemispheres together (taking the addition of volumes of A on both hemispheres and the addition of volumes of B on both hemispheres).


For structures in the posterior fossa, one can compute the yearly rate of relative atrophy, comparing the change in the volume of ROIs, with the change of volume in parenchyma located in the posterior fossa, including the cerebellum and the brain stem.

These methods can be computed for each side separately: 

yrR*A= (A1-A2) x 1200 / (B1-B2) x (#months between MRI studies)
where * is the ROI
A1 is the volume of the ROI in the first MRI and A2 the volume of the ROI in the second MRI. 
B1 is the volume of the parenchyma located in the posterior fossain the first MRI and B2 the volume of the parenchyma located in the posterior fossa in the second MRI

The yearly rate of Relative Thalamic Atrophy (yrRTA): a simple 2D/3D method for estimating deep gray matter atrophy in Multiple Sclerosis

Despite a strong correlation to outcome, the measurement of gray matter (GM) atrophy is not being used in daily clinical practice as a prognostic factor and monitor the effect of treatments in Multiple Sclerosis (MS). This is mainly because the volumetric methods available to date are sophisticated and difficult to implement for routine use in most hospitals. In addition, the meaning of raw results from volumetric studies on regions of interest are not always easy to understand. Thus, there is a huge need of a methodology suitable to be applied in daily clinical practice in order to estimate GM atrophy in a convenient and comprehensive way. Given the thalamus is the brain structure found to be more consistently implied in MS both in terms of extent of atrophy and in terms of prognostic value, we propose a solution based in this structure. In particular, we propose to compare the extent of thalamus atrophy (TA) with the extent of unspecific, global brain atrophy, represented by ventricular enlargement. We name this ratio the “yearly rate of Relative Thalamic Atrophy” (yrRTA). In this report we aim to describe the concept of yrRTA and the guidelines for computing it under 2D and 3D approaches and explain the rationale behind this method. We have also conducted a very short crossectional retrospective study to proof the concept of yrRTA. However, we do not seek to describe here the validity of this parameter since these researches are being conducted currently and results will be addressed in future publications.

yrRTA= (A1+A’1)-(A2+A’2) x 120 / (B2-B1) x 
(#months between MRI studies) 

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