Exploring quantitative MRI contrast in posterior cortical atrophy using ex vivo imaging

Poster No:

1489 

Submission Type:

Abstract Submission 

Authors:

Luke Edwards1, Carsten Jäger1, Evgeniya Kirilina1,2, Karl-Heinz Herrmann3, Kerrin Pine1, Patrick Scheibe1, Jürgen Reichenbach3, Nikolaus Weiskopf1,4

Institutions:

1Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, 2Center for Cognitive Neuroscience Berlin, Freie Universität Berlin, Berlin, Germany, 3University Clinic Jena, Jena, Germany, 4Felix Bloch Institute for Solid State Physics, Leipzig University, Leipzig, Germany

First Author:

Luke Edwards  
Max Planck Institute for Human Cognitive and Brain Sciences
Leipzig, Germany

Co-Author(s):

Carsten Jäger  
Max Planck Institute for Human Cognitive and Brain Sciences
Leipzig, Germany
Evgeniya Kirilina  
Max Planck Institute for Human Cognitive and Brain Sciences|Center for Cognitive Neuroscience Berlin, Freie Universität Berlin
Leipzig, Germany|Berlin, Germany
Karl-Heinz Herrmann  
University Clinic Jena
Jena, Germany
Kerrin Pine  
Max Planck Institute for Human Cognitive and Brain Sciences
Leipzig, Germany
Patrick Scheibe  
Max Planck Institute for Human Cognitive and Brain Sciences
Leipzig, Germany
Jürgen Reichenbach  
University Clinic Jena
Jena, Germany
Nikolaus Weiskopf  
Max Planck Institute for Human Cognitive and Brain Sciences|Felix Bloch Institute for Solid State Physics, Leipzig University
Leipzig, Germany|Leipzig, Germany

Introduction:

Posterior cortical atrophy (PCA) is a rare variant of Alzheimer's disease (AD) where degeneration begins in the occipital lobe rather than the hippocampus/temporal lobe [Crutch2016]. Recent work has found MRI-visible breakdown of cortical lamination in AD neurodegeneration [Kenkuis2019]. We scanned post mortem samples of PCA, AD, and control tissue with quantitative MRI metrics (R1, R2*, mean diffusivity (MD), mean kurtosis (MK), and fractional anisotropy (FA)) sensitive to cortical microstructure [Edwards2018] to investigate whether similar cortical changes occur in PCA and whether these changes qualitatively differ from those in AD. With this we aim to inform in vivo applications.

Methods:

We used formalin-fixed tissue blocks containing primary visual cortex (V) and superior temporal gyrus (T) from a donor with PCA (PCA1, 75y m) provided by the Queen Square Brain Bank, UCL London (QSBB); a healthy control donor (CTRL) and 2 donors with AD (Braak V–VI; AD1 77y f, AD2 81y m) provided by the Brain Banking Centre Leipzig, Leipzig University; and a V-block from another donor with PCA (PCA2 71y m; QSBB). Before MRI, remnant fixative was washed out with PBS and blocks were placed in 20 mm syringes in Fomblin.

Multiparameter mapping (MPM) data [Weiskopf2013] was recorded on a 7T Siemens Magnetom scanner with custom CP transceive coil (220 µm isotropic resolution (iso.), 12 equispaced echoes TE 4–41 ms, TR 95 ms, PDw flip angle 12°, T1w 60°). B1 maps (1.5 mm iso.) were measured as per [Sacolick2010]. R2* was computed as per [Weiskopf2014], and R1 using an analytical solution of the Ernst equation (Eq. 17 in [Dathe2010]). A 50 µm iso. T2*w image (TE 19 ms, TR 200 ms, flip angle 50°) was also recorded.

Diffusion weighted imaging (DWI) data was recorded on a Bruker BioSpec 94/20 9.4T preclinical scanner with cryocoil (spin echo segmented EPI DWI sequence, 200 µm iso., 16 averages, b [0.3,2,4,8,12] ms/µm², 60 directions per b, TR 4 s, TE 25 ms). Kurtosis tensors fits using MDT (https://github.com/robbert-harms/MDT) gave MD, MK and FA.

MPMs were registered to DWI space. Initial GM/WM masks were estimated by thresholding and k-means clustering of the PDw echoes. Gross errors in the masks were manually corrected (by LJE).

Cortex was segmented into 20 equivolume layers in Nighres (https://github.com/nighres/nighres). Visual inspection of the V images showed the stria of Gennari (layer IVb) was mostly found in layers 8–13. We thus binned each parameter into layers 2–7 (lower), 8–13 (mid), and 14–19 (upper) so "mid" approximates layer IV. Areas showing artefacts were manually masked out (by LJE) before binning.

For histology, tissue blocks were paraffin-embedded, cut into 8 µm sections, and processed, alternating Nissl stain and immunohistochemistry for myelin basic protein (MBP) and Aβ deposits. Microscope images were recorded on a Zeiss Axioscan Z1. Layers I–III (upper), IV (mid), and V–VI (lower) were manually segmented (by CJ) on Nissl sections, projected onto the nearest MBP and Aβ sections, and used to bin the average optical density.

Box plots for all metrics were plotted in Matlab.

Results:

Fig. 1 shows cortical lamination degradation relative to CTRL in MRI contrasts, in line with previous R2* observations in post mortem AD tissue [Nabuurs2013,Kenkuis2019].

Fig. 2 suggests that multimodal combination of regional differences in R2*, MD, and FA profiles could differentiate between AD and PCA. This differentiation could reflect differences in Aβ, myelin, or iron distribution, but could also reflect minor differences in tissue preparation. Quantitative iron measurements and in vivo experiments will allow further investigation.
Supporting Image: Fig1.png
   ·Fig. 1
Supporting Image: Fig2.png
   ·Fig. 2
 

Conclusions:

We have shown that AD cortical lamination disturbances previously seen in R2* [Nabuurs2013] can be seen in other quantitative maps and in PCA. Observed differences in MRI contrast between PCA and AD may reflect their different progression, but the small number of samples calls for caution when extrapolating the results.

Disorders of the Nervous System:

Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1

Neuroanatomy, Physiology, Metabolism and Neurotransmission:

Cortical Anatomy and Brain Mapping 2

Novel Imaging Acquisition Methods:

Anatomical MRI
Diffusion MRI

Keywords:

ADULTS
Cortex
Cortical Layers
Degenerative Disease
DISORDERS
HIGH FIELD MR
MRI
Neurological
STRUCTURAL MRI

1|2Indicates the priority used for review

My abstract is being submitted as a Software Demonstration.

No

Please indicate below if your study was a "resting state" or "task-activation” study.

Other

Healthy subjects only or patients (note that patient studies may also involve healthy subjects):

Patients

Was any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.

Yes

Was any animal research approved by the relevant IACUC or other animal research panel? NOTE: Any animal studies without IACUC approval will be automatically rejected.

Not applicable

Please indicate which methods were used in your research:

Structural MRI
Optical Imaging
Diffusion MRI
Postmortem anatomy

For human MRI, what field strength scanner do you use?

7T
If Other, please list  -   9.4T

Which processing packages did you use for your study?

SPM
FSL
Other, Please list  -   Advanced Normalization Tools (ANTs), Microstructure Diffusion Toolbox (MDT), Nighres

Provide references using author date format

Crutch, SJ et al. (2016), Looking but Not Seeing: Recent Perspectives on Posterior Cortical Atrophy, Current Directions in Psychological Science, doi:10.1177/0963721416655999
Dathe, H et al. (2010), Exact algebraization of the signal equation of spoiled gradient echo MRI, Phys. Med. Biol., doi:10.1088/0031-9155/55/15/003
Edwards, LJ et al. (2018), Microstructural imaging of human neocortex in vivo, Neuroimage, doi:10.1016/j.neuroimage.2018.02.055
Henf, J et al. (2018), Mean diffusivity in cortical gray matter in Alzheimer's disease: The importance of partial volume correction, Neuroimage, doi:10.1016/j.nicl.2017.10.005
Kenkuis, B et al. (2019), 7T MRI allows detection of disturbed cortical lamination of the medial temporal lobe in patients with Alzheimer's disease, Neuroimage Clinical, doi:10.1016/j.nicl.2019.101665
Nabuurs, RJA et al. (2013), MR Microscopy of Human Amyloid-β Deposits: Characterization of Parenchymal Amyloid, Diffuse Plaques, and Vascular Amyloid, Journal of Alzheimer's Disease, doi:10.3233/JAD-122215
Sacolick, LI et al. (2010), B1 mapping by Bloch‐Siegert shift, Magn. Reson. Med., doi:10.1002/mrm.22357
Weiskopf, N et al. (2013), Quantitative multi-parameter mapping of R1, PD*, MT, and R2* at 3T: a multi-center validation, Front. Neurosci., doi:10.3389/fnins.2013.00095
Weiskopf, N et al. (2014), Estimating the apparent transverse relaxation time (R2*) from images with different contrasts (ESTATICS) reduces motion artifacts, Front. Neurosci., doi:10.3389/fnins.2014.00278