Dimitrios G. Gkotsoulias1, Roland Müller 1, Torsten Schlumm1, Niklas Alsleben1, Carsten Jäger1, Jennifer Jaffe2,3, André Pampel1, Catherine Crockford2,3, Roman Wittig2,3, and Harald Möller1
1Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, 2Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany, 3Tai Chimpanzee Project, Centre Suisse de Recherches Scientifiques en Cote d'Ivoire, Abidjan, Cote D'ivoire
Synopsis
Calculation
Of Susceptibility through Multiple Orientation Sampling (COSMOS) is assessed comparing the optimal, a clinically feasible and multiple-orientation
schemes. The optimal COSMOS estimation is used as a gold standard and is compared
to the other schemes using the similarity index (SSIM), mean absolute error (MAE) and Pearson’s coefficient (PC).
Further comparisons include Thresholded
K-space Division (TKD) quantitative
susceptibility mapping. For selected white-matter regions,
linear regression is used to assess the similarities between the different
estimations.
Introduction
Brain
pathologies are often linked to local alterations of iron or myelin, making
their quantitation highly important. Multiple methods have been proposed for
this purpose, including Quantitative Susceptibility Mapping
(QSM)1,2. There are two major problems with single-orientation
QSM: (i) inversion from local tissue phase
to susceptibility is intrinsically ill-posed; (ii) anisotropy of magnetic susceptibility in brain tissue is typically
ignored3.
Most
QSM applications employ post-acquisition solutions to the first problem, with Thresholded K-space Division (TKD)4 being a prominent example. Regarding acquisition-based
approaches, Calculation Of Susceptibility through Multiple
Orientation Sampling (COSMOS) has been
introduced, which requires sampling at three or more orientations of the object
inside the magnetic field. 3 An estimation of the optimal scheme suggests
rotations by 0°, 60° and 120° about the (physical) x- or y-axes. This selection
is believed to yield excellent susceptibility estimates by fully addressing the
ill-posed inversion problem and, additionally, partially addressing the
anisotropy problem. However, the feasibility of COSMOS in in-vivo human brain imaging is challenging
because achievable head rotations are limited to a small range of ±20°, which
deviates substantially from the ideal rotation scheme. In the current study, we
compared the optimal COSMOS scheme to one that considers constraints under in vivo conditions as well as to TKD-QSM.
Acquisitions using more than 3 orientations (4 to 10) were also included to evaluate
the potential impact from additional orientation information in susceptibility
estimations.Methods
Complex 3D multi-echo GRE data (1mm isotropic nominal
resolution) were acquired with a 32-channel headcoil on a 3T MAGNETOM Skyra Connectom
(Siemens, Erlangen Germany) in fixed chimpanzee brain. The animal had died from
natural causes in Tai National Park, Ivory Coast. The brain was immersed in Fomblin
and positioned in a 3D-printed container adapted to its individual anatomy. Acquisitions
at TE=30 ms and a subset of 11 reorientations of the specimen within the main
magnetic field from a total dataset comprising 60 evenly distributed independent
orientations were used for the current study. ESPIRiT-SVD was used for coil combination.5,6
Multi-orientation phase volumes were registered to a
reference employing transformations that were derived by registering the corresponding
magnitude volumes using FSL7.
The 11 phase volumes used in different combinations were selected to ensure
significant rotation (>15°) about the (physical) y-axis, whereas rotations about the remaining axes always remained
below 10° (Figure 1).
Laplacian phase
unwrapping and background-phase removal using V-SHARP8 were
performed on the selected registered phase volumes. All further image processing
routines were implemented in Matlab comprising the COSMOS model, the TKD-QSM estimate,
and the statistical analysis pipelines, which included the 3D-Similarity Index
(SSIM), Mean Absolute Error (MAE) and Pearson’s Coefficient (PC) performed on a
large region of interest (ROI) with combined gray matter (GM) and white matter
(WM) (Figure 4B) as well as linear regression in selected WM ROIs (Figure 5B).Results
Fixed brain specimens permit arbitrary rotations to
overcome restrictions of in vivo
experiments. The availability of a chimpanzee brain further supported more
efficient high-resolution acquisitions compared to a human brain while still showing
a complex WM architecture.
Visual inspection of the susceptibility maps obtained
with optimal COSMOS, in vivo-feasible
COSMOS and TKD-QSM (Figure 3A) indicate differences in WM and GM regions. The high-angular
COSMOS implementations (4 to 10 orientations; Figure 3B) exhibit higher
resemblance to the optimal-scheme results when limiting the number of
orientations (4 and 5).
The visual observations are corroborated by the
different comparison metrics PC, SSIM and MAE. Using the optimal 3-orientation
COSMOS scheme as reference, the 4-orientation COSMOS estimates indicate the smallest
error in addition to higher PC and SSIM values, while higher angular-resolution
schemes yielded slightly increased error and decreased PC/SSIM until a plateau was
reached around 8 orientations. TKD-QSM yielded the highest errors and lowest PC
and SSIM. However, its accuracy was still is comparable to the in vivo-feasible COSMOS scheme (Figure 4A).
In exemplarily selected WM ROIs, linear regression of
the optimal COSMOS susceptibility estimates with TKD-QSM and the in vivo-feasible COSMOS results indicate
similar dispersion (Figure 5), validating the other statistical comparisons.
Higher angular-resolution COSMOS schemes in the same WM ROIs also followed the
trend observed in the general statistical comparisons, with 4- and
5-orientation schemes indicating the least dispersion. Again, with more than 5
orientations, the dispersion increased without significant differences in the
estimations beyond 7 orientations. Discussion
Our results indicate limitations of the COSMOS model in
in-vivo applications, which only
slightly outperforms single-orientation TKD-QSM, when both are compared to the
optimal COSMOS reference scheme. Considering the added complexity of COSMOS
acquisitions and registration, this challenges the suitability of the model,
which has been used as gold standard in comparisons of QSM pipelines.9
Our results further indicate that the theoretical minimum of 3 orientations (rotations
with 60° increments) that is required to stabilize the inverse problem, is
already the optimal choice, whereas sets of more orientations with smaller
angle increments did not achieve significant improvements. This is probably due
to an accumulation of registration errors. We note that even the optimal COSMOS
scheme for estimating susceptibility can induce bias as it does not consider
internal anisotropy of the magnetic susceptibility, in particular in WM. Acknowledgements
This work was funded by the EU through the ITN
“INSPiRE-MED” (H2020-MSCA-ITN-2018, #813120).
We are
grateful to the Evolution of Brain Connectivity (EBC) project, the
Ministère de l’Enseignement Supérieur et de la Recherche Scientifique, the Ministère
de Eaux et Fôrests in Côte d’Ivoire, and the Office Ivoirien des Parcs et Réserves for permitting the
study, and to the staff
of the Taï
Chimpanzee Project.
References
1. Möller HE, Bossoni L, Connor JR, et al. Iron,
myelin, and the brain: Neuroimaging meets neurobiology. Trends Neurosci. 2019; 42:
384-401.
2. Deistung A, Schweser F, Reichenbach JR. Overview of quantitative
susceptibility mapping. NMR Biomed. 2017; 30: e3569.
3. Liu T,
Spincemaille P, de Rochefort L, et al. 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: 196-204.
4. Wharton S, Schäfer A,
Bowtell R. Susceptibility mapping in the human brain using threshold-based
k-space division. Magn Res Med. 2010; 63: 1292-1304.
5. Uecker M, Lustig M. Estimating absolute-phase maps using ESPIRiT and
virtual conjugate coils. Magn Reson Med. 2017; 77: 1201-1207.
6. Bilgic B, Polimeni JR, Wald LL, et al. Automated tissue phase and QSM
estimation from multichannel data. Proceedings of the 24th Annual
Meeting of ISMRM. Singapore 2016; 2849.
7. Jenkinson M, Beckmann CF, Behrens TE, et al. FSL. NeuroImage. 2012; 62: 782-790.
8. Özbay PS, Deistung A, Feng
X, et al. A comprehensive numerical analysis of background phase correction
with V-SHARP. NMR Biomed. 2017; 30: e3550.
9. Langkammer C, Schweser F, Shmueli K, et al. Quantitative susceptibility
mapping: Report from the 2016 reconstruction challenge. Magn Reson Med. 2018;
79: 1661-1673.