Dogu Baran Aydogan1
1Department of Neuroscience and Biomedical Engineering, Aalto University, Helsinki, Finland
Synopsis
Transcranial magnetic stimulation (TMS) is a
non-invasive brain stimulation technique that is widely used in both
research and clinical settings. However, state-of-the-art TMS
guidance systems do not leverage the valuable structural connectivity
in real-time applications. This is mainly due to the limitations of
tractography which has been increasingly pointed out in validation
studies. In order to address this problem, in this work we propose a
novel visualization approach that is capable of providing information
about the uncertainty of obtained streamlines. Our technique offers
an easy and intuitive way for the TMS operator to interpret the
displayed streamlines in real-time.
Introduction
Tractography
is a non-invasive and in vivo technique that is capable of revealing
structural connections in the human brain based on diffusion MRI
(dMRI). Real-time information about the structural connections in the
brain would be highly valuable when performing transcranial magnetic
stimulation (TMS). Currently, with the state-of-the-art TMS
navigation systems, operators can see the TMS coil with respect to
subject’s brain MRI and the affected area on a computer screen.
However, these systems do not show which connections are affected by
the stimulation. With the advancements in rapid imaging techniques,
preprocessing, modeling of dMRI and fiber tracking algorithms,
tractography has become a widely used tool but not for TMS in
real-time settings. One major reason behind this is the limitations
of tractography, which have increasingly been pointed out in the
results of validation studies as well as international tractography
challenges [1-5].
Owing
largely to the validation experiments conducted by Thomas et.al. [1],
using receiver operator characteristic (ROC) curves has become a
widely adopted approach to study the performance of fiber tracking
results. Using false positive rate and true positive rate (or bundle
overreach and bundle overlap), several
groups presented reports on the performance of tractography. Based on
a simulated dataset, as a result of 2015 ISMRM tractography
challenge, Maier-Hein et.al. highlighted that tractograms contain
large numbers of false positive fiber bundles [2]. On the other hand,
by comparing tracer injections against dMRI-based tractograms,
Aydogan et.al. showed that tractography also suffers from a false
negative problem [5]. Importantly, using ROC curves, Aydogan et.al.
studied the trends in tractography performance with respect to
changes in several fiber tracking parameters [5].
In
this work, we present a new visualization approach based on the
observation in [5], which states that the confidence in tractography
results can be increased by repeating the experiments with multiple
different parameter combinations. In our study, we leverage this
approach for the navigation of TMS for real-time applications where
we locally seed tracks within the area that is affected by the TMS
pulse. The novelty of the proposed system is that we not only show
the connections that may be affected by the TMS pulse, but also at
the same time, we color code the connections with respect to
previously known performance of parameter combinations on the ROC
curve. By taking into account the uncertainty in the accuracy of
fiber tracking, our approach helps the TMS operator to better interpret streamlines.Method
We
propose to use transfer functions that map each streamline a color or
opacity/transparency value based on the fiber tracking parameter used
to obtain that streamline. To that end, we make use of prior
knowledge of ROC curves that provide information about previously
known performance of tracking parameter combination choices, e.g.,
it is shown in [5] that when pivoting around a parameter combination,
decreasing the FOD threshold leads to more false positives (increased
amount of connections that do not exist), whereas increasing it leads
to more false negatives (increased amount of actual connections that
are missed). Similar trends exist for other parameters as well.
Fig.1
shows the overall pipeline for the proposed system to guide the TMS
operator with structural connectivity of the brain in real-time.
Streamlines are continuously updated and displayed with respect to
the affected area by the TMS pulse that is estimated based on the
location of the TMS coil. Fig.2 shows two transfer functions that we
use for the visualization of streamlines and corresponding tracking
parameter combinations. Tractography is done using an in-house,
customized, version of Trekker that implements a
state-of-the-art probabilistic fiber tracking algorithm based on
parallel transport frames [6]. Parameter combinations used for
tracking are determined with experiments on
the ISMRM 2015 tractography challenge dataset [2].Results and discussion
Fig.3 shows
results obtained by varying parameters which smoothly traverse the
ROC curve. It also shows that the choice for the default pivot point as well as the
ranges for parameters score highly competitive against other
submissions in the ISMRM 2015 challenge.
For
our real-time experiments, data from a healthy male (age 37) is
acquired and processed using the pipeline shown in Fig.1. Fig.4 shows
side-by-side visual comparison of the proposed uncertainty
visualization method against the case where it is not used. The
neighborhood of the shown stimulation location (the red dot) is a
commonly used region in TMS-based speech mapping applications for
neurosurgical planning [7]. Results are shown both using opacity and
color mapping approaches. Tracks that are more likely to be false
positives are easily recognizable by the operator with both
approaches.
Our
tracking approach is related to ensemble tractography [8], where
streamlines obtained with different parameters are combined together.
In our visualization technique, however, we additionally treat
streamlines differently based on how they are obtained.Conclusion
While
our approach does not solve tractography’s false negative and false
positive problems, in contrast to using a single parameter
combination choice and a single color mapping scheme for all
streamlines, the proposed method offers a more reliable way to use
fiber tracking for TMS applications.
Furthermore,
our
approach provides a quick,
easy
and intuitive way for the TMS
operator
to visually make
judgments about the streamlines in
real-time.Acknowledgements
References
[1]
Thomas C, Ye FQ, Irfanoglu MO, Modi P, Saleem KS, Leopold DA, et al.
Anatomical accuracy of brain connections derived from diffusion MRI
tractography is inherently limited. PNAS. 2014 Nov
18;111(46):16574–9.
[2]
Maier-Hein KH, Neher PF, Houde J-C, Côté M-A, Garyfallidis E, Zhong
J, et al. The challenge of mapping the human connectome based on
diffusion tractography. Nat Commun. 2017 Nov 7;8(1):1–13.
[3]
Nath V, Schilling K, Parvathaneni P, Hainline AE, Huo Y, Blaber JA,
et al. Tractography Reproducibility Challenge with Empirical Data
(TraCED): The 2017 ISMRM Diffusion Study Group Challenge. bioRxiv.
2018 Dec 3;484543.
[4]
Schilling KG, Nath V, Hansen C, Parvathaneni P, Blaber J, Gao Y, et
al. Limits to anatomical accuracy of diffusion tractography using
modern approaches. NeuroImage. 2019 Jan 15;185:1–11.
[5]
Aydogan DB, Jacobs R, Dulawa S, Thompson SL, Francois MC, Toga AW, et
al. When tractography meets tracer injections: a systematic study of
trends and variation sources of diffusion-based connectivity. Brain
Struct Funct. 2018 Jul 1;223(6):2841–58.
[6]
Aydogan DB, Shi Y. A novel fiber tracking algorithm using parallel
transport frames. ISMRM 2019, Montreal.
[7]
Lioumis P, Zhdanov A, Mäkelä N, Lehtinen H, Wilenius J, Neuvonen T,
et al. A novel approach for documenting naming errors induced by
navigated transcranial magnetic stimulation. Journal of Neuroscience
Methods. 2012 Mar 15;204(2):349–54.
[8]
Takemura H, Caiafa CF, Wandell BA, Pestilli F. Ensemble Tractography.
PLOS Computational Biology. 2016 Feb 4;12(2):e1004692.
[9]
Veraart J, Novikov DS, Christiaens D, Ades-aron B, Sijbers J,
Fieremans E. Denoising of diffusion MRI using random matrix theory.
NeuroImage. 2016 Nov 15;142:394–406.
[10]
Kellner E, Dhital B, Kiselev VG, Reisert M. Gibbs-ringing artifact
removal based on local subvoxel-shifts. Magnetic Resonance in
Medicine. 2016 Nov 1;76(5):1574–81.
[11]
Andersson JLR, Sotiropoulos SN. An integrated approach to correction
for off-resonance effects and subject movement in diffusion MR
imaging. NeuroImage. 2016 Jan 15;125:1063–78.
[12]
Smith SM. Fast robust automated brain extraction. Human Brain
Mapping. 2002;17(3):143–55.
[13]
Tran G, Shi Y. Adaptively constrained convex optimization for
accurate fiber orientation estimation with high order spherical
harmonics. Med Image Comput Comput Assist Interv. 2013;16(Pt
3):485–92.
[14]
Tustison NJ, Avants BB, Cook PA, Zheng Y, Egan A, Yushkevich PA, et
al. N4ITK: improved N3 bias correction. IEEE Trans Med Imaging. 2010
Jun;29(6):1310–20.