Carsten Stueber1,2, Alexey Dimov1, Kofi Deh1, David Pitt2, and Yi Wang1
1Weill Cornell Medical College, New York, NY, United States, 2Yale School of Medicine, Yale University, New Haven, CT, United States
Synopsis
Quantitative
susceptibility mapping (QSM) provides a quantitative MRI contrast, which reflects
the local iron concentration. Thus, QSM allows to determine the geometries of iron-rich
deep grey matter nuclei including substantia nigra (SN) and subthalamic nucleus
(STN). These basal nuclei are of particular interest in Parkinson’s disease. However,
the measured dimensions need to be validated in histology using post-mortem
human brain tissue. In this work, we show the concordance of the geometries
measured in QSM and histology using Perls’ iron stain, which opens the door to
use QSM as a pre-surgical mapping for deep brain stimulation targeting the STN.Target audience
All
MRI researchers and medical doctors interested in investigating
neurodegenerative diseases, in particular Parkinson’s disease.
Purpose
In
recent years, quantitative susceptibility mapping (QSM) has been introduced
1, which allows for in vivo imaging
of iron in brain tissue
2. Furthermore, the imaging
technique can provide quantitative measurements of brain structures
3. However, the
spatial iron difference
in deep grey matter of Parkinson's disease (PD) patients has not been investigated in a clinical
setting using QSM. The aim of this study was to determine
whether QSM is appropriate
to define geometries of basal nuclei of PD patients on a clinical 3T MR
scanner.
Methods
This
study utilizes QSM maps and histological stains of three different post-mortem
specimens containing deep grey matter nuclei, which were obtained from the
Rocky Mountains MS Center (RMMSC). The brain slabs (66 y, f / 53 y, m / 60 y, m)
were embedded in agar, scanned on a 3 T SIEMENS scanner using a GRE sequence (resolution:
0.6 mm3/TE1=7ms/ΔTE=4.1ms/10 echos/TR=49 ms). QSM maps
were calculated using a multiple orientation reconstruction from tissue fields
applying COSMOS, which allows exact calculation of susceptibility
4. Adjacent to scanning, brain
blocks were cut, sliced and stained employing Perls’ Prussian blue for
trivalent ferric iron (Fe
3+), which reflects the iron distribution
in post-mortem brain tissue. Additionally, Sudan Black B lipid stain was done
on one specimen to aid delineating the nuclei from adjacent structures. The
dimensions of the basal nuclei in QSM were measured using ImageJ (NIH,
Bethesda, MD), whereas the dimensions in histology were measured using Leica LAS
X (Leica Microsystems, Wetzlar, Germany). Both, histology images and QSM maps
were registered applying the thin plate spline approach in MIPAV (NIH,
Bethesda, MD).
Results
Coronally
oriented QSM maps and coronally sliced histological stains of brain samples
were acquired, which contain the substantia nigra (SN), subthalamic nucleus (STN)
and red nucleus (RN) (Fig. 1-3). The major and minor axis of these
ellipsoid-shaped basal ganglia nuclei were measured in both modalities, QSM
maps and histological stains. The basal ganglia contain a high iron
concentration in comparison to adjacent regions and thus can be easily
delineated in both image modalities. The dimensions of the nuclei vary depending
on the spatial location within the human brain. Nevertheless, the dimensions
measured in QSM and histology at different spatial location are in concordance
with each other in all three samples (Fig. 4). The slope is slightly smaller
than 1 indicating a slightly larger appearance of these nuclei in QSM images.
Discussion
We
could show that the dimensions of SN, STN and RN are almost identical in QSM and
histology, confirming that QSM can be used as a reliable measure for deep grey
matter nuclei dimensions and geometries. The larger dimensions measured in QSM
can be attributed to the voxels at the boundary of the measured structure.
These voxels appear paramagnetic and thus being part of the nucleus,
although a voxel might not fully cover the object of interest.
Conclusion
This
data suggests that the STN geometries defined on QSM can be used in pre-surgical
mapping for deep brain stimulation targeting STN. Additionally, further
improvements in QSM imaging alleviate the detection of iron accumulations in
Parkinson’s disease brains. We believe that this research will very likely lead to an
impactful outcome, establishing QSM based nigral iron mapping as a biomarker
for PD progression.
Acknowledgements
We acknowledge support from NIH grants RO1 EB013443 and RO1 NS090464. Furthermore, we thank Insil Kim for the help of processing the brain tissue.
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