Geometry of Basal Ganglia nuclei in QSM and Histology in Parkinson’s disease brains
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 introduced1, which allows for in vivo imaging of iron in brain tissue2. Furthermore, the imaging technique can provide quantitative measurements of brain structures3. 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 susceptibility4. Adjacent to scanning, brain blocks were cut, sliced and stained employing Perls’ Prussian blue for trivalent ferric iron (Fe3+), 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.

References

1. Wang , Liu T. Quantitative susceptibility mapping (QSM): Decoding MRI data for a tissue magnetic biomarker. Magn. Reson. Med. 2014;73(1):82-101.

2. Langkammer C, Schweser F, Krebs N, Deistung A, Goessler W, et al. Quantitative susceptibility mapping (QSM) as a means to measure brain iron? A post mortem validation study. Neuroimage 2012;62(3):1593-1599.

3. Liu T, Wisnieff C, Lou M, Chen W, Spincemaille P, et al. Nonlinear formulation of the magnetic field to source relationship for robust quantitative susceptibility mapping. Magn. Reson. Med. 2013;69(2):467-476.

4. Liu T, Spincemaille P, de Rochefort L, Kressler B, Wang Y. Calculation of susceptibility through multiple orientation sampling (COSMOS): A method for conditioning the inverse problem from measured magnetic field map to susceptibility source image in MRI. Magn. Reson. Med. 2009;61(1):196-204.

Figures

Fig. 4: Measured dimensions in QSM and histology (Perls' stain). The slope is slightly smaller than one indicating larger dimensions measured in QSM.

Fig. 1: QSM image showing iron-rich basal nuclei, which appear paramagnetic. The Perls’ stain shows high concentrations of Fe3+ (brown) in the substantia nigra (SN), subthalamic nucleus (STN) and red nucleus (RN). The Sudan B Lipid stain clearly shows the boundaries between white matter fibers and the deep grey matter nuclei.

Fig. 2: Coronal section of the human brain, showing the substantia nigra (SN) and subthalamic nucleus (STN) in QSM (left) and Perls’ stain (right). Other iron-rich structures are visible, including the external globus pallidus (EGP), the internal globus pallidus (IGP) and the comb system (comb).

Fig. 3: Coronal section of the human brain, showing the substantia nigra (SN), subthalamic nucleus (STN) and red nucleus (RN) in QSM (left) and Perls’ stain (right).



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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