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Article ; Online: The Rostral Zona Incerta: A Subcortical Integrative Hub and Potential Deep Brain Stimulation Target for Obsessive-Compulsive Disorder.

Haber, Suzanne N / Lehman, Julia / Maffei, Chiara / Yendiki, Anastasia

2023 Volume 93, Issue 11, Page(s) 1010–1022

Abstract: Background: The zona incerta (ZI) is involved in mediating survival behaviors and is connected to a wide range of cortical and subcortical structures, including key basal ganglia nuclei. Based on these connections and their links to behavioral ... ...

Abstract	Background: The zona incerta (ZI) is involved in mediating survival behaviors and is connected to a wide range of cortical and subcortical structures, including key basal ganglia nuclei. Based on these connections and their links to behavioral modulation, we propose that the ZI is a connectional hub for mediating between top-down and bottom-up control and a possible target for deep brain stimulation for obsessive-compulsive disorder. Methods: We analyzed the trajectory of cortical fibers to the ZI in nonhuman and human primates based on tracer injections in monkeys and high-resolution diffusion magnetic resonance imaging in humans. The organization of cortical and subcortical connections within the ZI were identified in the nonhuman primate studies. Results: Monkey anatomical data and human diffusion magnetic resonance imaging data showed a similar trajectory of fibers/streamlines to the ZI. Prefrontal cortex/anterior cingulate cortex terminals all converged within the rostral ZI, with dorsal and lateral areas being most prominent. Motor areas terminated caudally. Dense subcortical reciprocal connections included the thalamus, medial hypothalamus, substantia nigra/ventral tegmental area, reticular formation, and pedunculopontine nucleus and a dense nonreciprocal projection to the lateral habenula. Additional connections included the amygdala, dorsal raphe nucleus, and periaqueductal gray. Conclusions: Dense connections with dorsal and lateral prefrontal cortex/anterior cingulate cortex cognitive control areas and the lateral habenula and the substantia nigra/ventral tegmental area, coupled with inputs from the amygdala, hypothalamus, and brainstem, suggest that the rostral ZI is a subcortical hub positioned to modulate between top-down and bottom-up control. A deep brain stimulation electrode placed in the rostral ZI would not only involve connections common to other deep brain stimulation sites but also capture several critically distinctive connections.
MeSH term(s)	Animals ; Humans ; Zona Incerta ; Deep Brain Stimulation ; Cerebral Cortex ; Thalamus ; Obsessive-Compulsive Disorder/diagnostic imaging ; Obsessive-Compulsive Disorder/therapy
Language	English
Publishing date	2023-01-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	209434-4
ISSN	1873-2402 ; 0006-3223
ISSN (online)	1873-2402
ISSN	0006-3223
DOI	10.1016/j.biopsych.2023.01.006
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Article: Self-supervised segmentation and characterization of fiber bundles in anatomic tracing data.

Sundaresan, Vaanathi / Lehman, Julia F / Maffei, Chiara / Haber, Suzanne N / Yendiki, Anastasia

bioRxiv : the preprint server for biology

2023

Abstract: Anatomic tracing is the gold standard tool for delineating brain connections and for validating more recently developed imaging approaches such as diffusion MRI tractography. A key step in the analysis of data from tracer experiments is the careful, ... ...

Abstract	Anatomic tracing is the gold standard tool for delineating brain connections and for validating more recently developed imaging approaches such as diffusion MRI tractography. A key step in the analysis of data from tracer experiments is the careful, manual charting of fiber trajectories on histological sections. This is a very time-consuming process, which limits the amount of annotated tracer data that are available for validation studies. Thus, there is a need to accelerate this process by developing a method for computer-assisted segmentation. Such a method must be robust to the common artifacts in tracer data, including variations in the intensity of stained axons and background, as well as spatial distortions introduced by sectioning and mounting the tissue. The method should also achieve satisfactory performance using limited manually charted data for training. Here we propose the first deeplearning method, with a self-supervised loss function, for segmentation of fiber bundles on histological sections from macaque brains that have received tracer injections. We address the limited availability of manual labels with a semi-supervised training technique that takes advantage of unlabeled data to improve performance. We also introduce anatomic and across-section continuity constraints to improve accuracy. We show that our method can be trained on manually charted sections from a single case and segment unseen sections from different cases, with a true positive rate of ~0.80. We further demonstrate the utility of our method by quantifying the density of fiber bundles as they travel through different white-matter pathways. We show that fiber bundles originating in the same injection site have different levels of density when they travel through different pathways, a finding that can have implications for microstructure-informed tractography methods. The code for our method is available at https://github.com/v-sundaresan/fiberbundle_seg_tracing.
Language	English
Publishing date	2023-10-02
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.09.30.560310
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Article: A Missing Connection: A Review of the Macrostructural Anatomy and Tractography of the Acoustic Radiation.

Maffei, Chiara / Sarubbo, Silvio / Jovicich, Jorge

Frontiers in neuroanatomy

2019 Volume 13, Page(s) 27

Abstract: The auditory system of mammals is dedicated to encoding, elaborating and transporting acoustic information from the auditory nerve to the auditory cortex. The acoustic radiation (AR) constitutes the thalamo-cortical projection of this system, conveying ... ...

Abstract	The auditory system of mammals is dedicated to encoding, elaborating and transporting acoustic information from the auditory nerve to the auditory cortex. The acoustic radiation (AR) constitutes the thalamo-cortical projection of this system, conveying the auditory signals from the medial geniculate nucleus (MGN) of the thalamus to the transverse temporal gyrus on the superior temporal lobe. While representing one of the major sensory pathways of the primate brain, the currently available anatomical information of this white matter bundle is quite limited in humans, thus constituting a notable omission in clinical and general studies on auditory processing and language perception. Tracing procedures in humans have restricted applications, and the
Language	English
Publishing date	2019-03-07
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2452969-2
ISSN	1662-5129
ISSN	1662-5129
DOI	10.3389/fnana.2019.00027
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Article ; Online: Diffusion-based tractography atlas of the human acoustic radiation.

Maffei, Chiara / Sarubbo, Silvio / Jovicich, Jorge

Scientific reports

2019 Volume 9, Issue 1, Page(s) 4046

Abstract: Diffusion MRI tractography allows in-vivo characterization of white matter architecture, including the localization and description of brain fibre bundles. However, some primary bundles are still only partially reconstructed, or not reconstructed at all. ...

Abstract	Diffusion MRI tractography allows in-vivo characterization of white matter architecture, including the localization and description of brain fibre bundles. However, some primary bundles are still only partially reconstructed, or not reconstructed at all. The acoustic radiation (AR) represents a primary sensory pathway that has been largely omitted in many tractography studies because its location and anatomical features make it challenging to reconstruct. In this study, we investigated the effects of acquisition and tractography parameters on the AR reconstruction using publicly available Human Connectome Project data. The aims of this study are: (i) using a subgroup of subjects and a reference AR for each subject, define an optimum set of parameters for AR reconstruction, and (ii) use the optimum parameters set on the full group to build a tractography-based atlas of the AR. Starting from the same data, the use of different acquisition and tractography parameters lead to very different AR reconstructions. Optimal results in terms of topographical accuracy and correspondence to the reference were obtained for probabilistic tractography, high b-values and default tractography parameters: these parameters were used to build an AR probabilistic tractography atlas. A significant left-hemispheric lateralization was found in the AR reconstruction of the 34 subjects.
MeSH term(s)	Acoustics ; Adult ; Auditory Pathways/diagnostic imaging ; Auditory Pathways/physiology ; Brain/anatomy & histology ; Brain/diagnostic imaging ; Brain/physiology ; Connectome ; Diffusion Magnetic Resonance Imaging/methods ; Diffusion Tensor Imaging/methods ; Humans ; Image Processing, Computer-Assisted/methods ; Nerve Fibers/physiology ; White Matter/anatomy & histology ; White Matter/diagnostic imaging ; White Matter/physiology
Language	English
Publishing date	2019-03-11
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-40666-8
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Article ; Online: High-fidelity approximation of grid- and shell-based sampling schemes from undersampled DSI using compressed sensing: Post mortem validation.

Jones, Robert / Maffei, Chiara / Augustinack, Jean / Fischl, Bruce / Wang, Hui / Bilgic, Berkin / Yendiki, Anastasia

NeuroImage

2021 Volume 244, Page(s) 118621

Abstract: While many useful microstructural indices, as well as orientation distribution functions, can be obtained from multi-shell dMRI data, there is growing interest in exploring the richer set of microstructural features that can be extracted from the full ... ...

Abstract	While many useful microstructural indices, as well as orientation distribution functions, can be obtained from multi-shell dMRI data, there is growing interest in exploring the richer set of microstructural features that can be extracted from the full ensemble average propagator (EAP). The EAP can be readily computed from diffusion spectrum imaging (DSI) data, at the cost of a very lengthy acquisition. Compressed sensing (CS) has been used to make DSI more practical by reducing its acquisition time. CS applied to DSI (CS-DSI) attempts to reconstruct the EAP from significantly undersampled q-space data. We present a post mortem validation study where we evaluate the ability of CS-DSI to approximate not only fully sampled DSI but also multi-shell acquisitions with high fidelity. Human brain samples are imaged with high-resolution DSI at 9.4T and with polarization-sensitive optical coherence tomography (PSOCT). The latter provides direct measurements of axonal orientations at microscopic resolutions, allowing us to evaluate the mesoscopic orientation estimates obtained from diffusion MRI, in terms of their angular error and the presence of spurious peaks. We test two fast, dictionary-based, L2-regularized algorithms for CS-DSI reconstruction. We find that, for a CS acceleration factor of R=3, i.e., an acquisition with 171 gradient directions, one of these methods is able to achieve both low angular error and low number of spurious peaks. With a scan length similar to that of high angular resolution multi-shell acquisition schemes, this CS-DSI approach is able to approximate both fully sampled DSI and multi-shell data with high accuracy. Thus it is suitable for orientation reconstruction and microstructural modeling techniques that require either grid- or shell-based acquisitions. We find that the signal-to-noise ratio (SNR) of the training data used to construct the dictionary can have an impact on the accuracy of CS-DSI, but that there is substantial robustness to loss of SNR in the test data. Finally, we show that, as the CS acceleration factor increases beyond R=3, the accuracy of these reconstruction methods degrade, either in terms of the angular error, or in terms of the number of spurious peaks. Our results provide useful benchmarks for the future development of even more efficient q-space acceleration techniques.
MeSH term(s)	Adult ; Aged ; Algorithms ; Benchmarking ; Brain/diagnostic imaging ; Computer Systems ; Diffusion Magnetic Resonance Imaging/methods ; Female ; Humans ; Male ; Signal-To-Noise Ratio
Language	English
Publishing date	2021-09-26
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1147767-2
ISSN	1095-9572 ; 1053-8119
ISSN (online)	1095-9572
ISSN	1053-8119
DOI	10.1016/j.neuroimage.2021.118621
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Article ; Online: Automated detection of axonal damage along white matter tracts in acute severe traumatic brain injury.

Maffei, Chiara / Gilmore, Natalie / Snider, Samuel B / Foulkes, Andrea S / Bodien, Yelena G / Yendiki, Anastasia / Edlow, Brian L

NeuroImage. Clinical

2022 Volume 37, Page(s) 103294

Abstract: New techniques for individualized assessment of white matter integrity are needed to detect traumatic axonal injury (TAI) and predict outcomes in critically ill patients with acute severe traumatic brain injury (TBI). Diffusion MRI tractography has the ... ...

Abstract	New techniques for individualized assessment of white matter integrity are needed to detect traumatic axonal injury (TAI) and predict outcomes in critically ill patients with acute severe traumatic brain injury (TBI). Diffusion MRI tractography has the potential to quantify white matter microstructure in vivo and has been used to characterize tract-specific changes following TBI. However, tractography is not routinely used in the clinical setting to assess the extent of TAI, in part because focal lesions reduce the robustness of automated methods. Here, we propose a pipeline that combines automated tractography reconstructions of 40 white matter tracts with multivariate analysis of along-tract diffusion metrics to assess the presence of TAI in individual patients with acute severe TBI. We used the Mahalanobis distance to identify abnormal white matter tracts in each of 18 patients with acute severe TBI as compared to 33 healthy subjects. In all patients for which a FreeSurfer anatomical segmentation could be obtained (17 of 18 patients), including 13 with focal lesions, the automated pipeline successfully reconstructed a mean of 37.5 ± 2.1 white matter tracts without the need for manual intervention. A mean of 2.5 ± 2.1 tracts resulted in partial or failed reconstructions and needed to be reinitialized upon visual inspection. The pipeline detected at least one abnormal tract in all patients (mean: 9.1 ± 7.9) and accurately discriminated between patients and controls (AUC: 0.91). The number and neuroanatomic location of abnormal tracts varied across patients and levels of consciousness. The premotor, temporal, and parietal sections of the corpus callosum were the most commonly damaged tracts (in 10, 9, and 8 patients, respectively), consistent with prior histopathological studies of TAI. TAI measures were not associated with concurrent behavioral measures of consciousness. In summary, we provide proof-of-principle evidence that an automated tractography pipeline has translational potential to detect and quantify TAI in individual patients with acute severe TBI.
MeSH term(s)	Humans ; White Matter/diagnostic imaging ; White Matter/pathology ; Brain Injuries/pathology ; Brain Injuries, Traumatic/diagnostic imaging ; Brain Injuries, Traumatic/pathology ; Axons/pathology ; Diffusion Tensor Imaging/methods
Language	English
Publishing date	2022-12-13
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2701571-3
ISSN	2213-1582 ; 2213-1582
ISSN (online)	2213-1582
ISSN	2213-1582
DOI	10.1016/j.nicl.2022.103294
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Article: Quantitative imaging of three-dimensional fiber orientation in the human brain via two illumination angles using polarization-sensitive optical coherence tomography.

Liu, Chao J / Ammon, William / Jones, Robert J / Nolan, Jackson C / Gong, Dayang / Maffei, Chiara / Edlow, Brian L / Augustinack, Jean C / Magnain, Caroline / Yendiki, Anastasia / Villiger, Martin / Fischl, Bruce / Wang, Hui

bioRxiv : the preprint server for biology

2023

Abstract: The accurate measurement of three-dimensional (3D) fiber orientation in the brain is crucial for reconstructing fiber pathways and studying their involvement in neurological diseases. Optical imaging methods such as polarization-sensitive optical ... ...

Abstract	The accurate measurement of three-dimensional (3D) fiber orientation in the brain is crucial for reconstructing fiber pathways and studying their involvement in neurological diseases. Optical imaging methods such as polarization-sensitive optical coherence tomography (PS-OCT) provide important tools to directly quantify fiber orientation at micrometer resolution. However, brain imaging based on the optic axis by PS-OCT so far has been limited to two-dimensional in-plane orientation, preventing the comprehensive study of connectivity in 3D. In this work, we present a novel method to obtain the 3D fiber orientation in full angular space with only two illumination angles. We measure the optic axis orientation and the apparent birefringence by PS-OCT from a normal and a 15 deg tilted illumination, and then apply a computational method yielding the 3D optic axis orientation and true birefringence. We verify that our method accurately recovers a large range of through-plane orientations from -85 deg to 85 deg with a high angular precision. We further present 3D fiber orientation maps of entire coronal sections of human cerebrum and brainstem with 10 μm in-plane resolution, revealing unprecedented details of fiber configurations. We envision that further development of our method will open a promising avenue towards large-scale 3D fiber axis mapping in the human brain and other complex fibrous tissues at microscopic level.
Language	English
Publishing date	2023-10-23
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.10.20.563298
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Article ; Online: Eddy current-induced artifact correction in high b-value ex vivo human brain diffusion MRI with dynamic field monitoring.

Ramos-Llordén, Gabriel / Park, Daniel J / Kirsch, John E / Scholz, Alina / Keil, Boris / Maffei, Chiara / Lee, Hong-Hsi / Bilgic, Berkin / Edlow, Brian L / Mekkaoui, Choukri / Yendiki, Anastasia / Witzel, Thomas / Huang, Susie Y

Magnetic resonance in medicine

2023 Volume 91, Issue 2, Page(s) 541–557

Abstract: Purpose: To investigate whether spatiotemporal magnetic field monitoring can correct pronounced eddy current-induced artifacts incurred by strong diffusion-sensitizing gradients up to 300 mT/m used in high b-value diffusion-weighted (DW) EPI.: Methods! ...

Abstract	Purpose: To investigate whether spatiotemporal magnetic field monitoring can correct pronounced eddy current-induced artifacts incurred by strong diffusion-sensitizing gradients up to 300 mT/m used in high b-value diffusion-weighted (DW) EPI. Methods: A dynamic field camera equipped with 16 Results: Phase perturbations in the readout induced by residual eddy currents from strong diffusion gradients are highly nonlinear in space and time, vary among diffusion directions, and interfere significantly with the image encoding gradients, changing the k-space trajectory. During the readout, phase modulations between odd and even EPI echoes become non-static and diffusion encoding direction-dependent. Superior reduction of ghosting and geometric distortion was achieved with dynamic field monitoring compared to ghosting reduction approaches such as navigator- and structured low-rank-based methods or MUSE followed by image-based distortion correction with the FSL tool "eddy." Conclusion: Strong eddy current artifacts characteristic of high-gradient strength DW-EPI can be well corrected with dynamic field monitoring-based image reconstruction.
MeSH term(s)	Humans ; Image Processing, Computer-Assisted/methods ; Artifacts ; Diffusion Magnetic Resonance Imaging/methods ; Brain/diagnostic imaging ; Imaging, Three-Dimensional/methods ; Echo-Planar Imaging/methods
Language	English
Publishing date	2023-09-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	605774-3
ISSN	1522-2594 ; 0740-3194
ISSN (online)	1522-2594
ISSN	0740-3194
DOI	10.1002/mrm.29873
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Article: Eddy current-induced artifacts correction in high gradient strength diffusion MRI with dynamic field monitoring: demonstration in ex vivo human brain imaging.

Ramos-Llordén, Gabriel / Park, Daniel / Kirsch, John E / Scholz, Alina / Keil, Boris / Maffei, Chiara / Lee, Hong-Hsi / Bilgiç, Berkin / Edlow, Brian L / Mekkaoui, Choukri / Yendiki, Anastasia / Witzel, Thomas / Huang, Susie Y

bioRxiv : the preprint server for biology

2023

Abstract: Purpose: To demonstrate the advantages of spatiotemporal magnetic field monitoring to correct eddy current-induced artifacts (ghosting and geometric distortions) in high gradient strength diffusion MRI (dMRI).: Methods: A dynamic field camera with 16 ...

Abstract	Purpose: To demonstrate the advantages of spatiotemporal magnetic field monitoring to correct eddy current-induced artifacts (ghosting and geometric distortions) in high gradient strength diffusion MRI (dMRI). Methods: A dynamic field camera with 16 NMR field probes was used to characterize eddy current fields induced from diffusion gradients for different gradients strengths (up to 300 mT/m), diffusion directions, and shots in a 3D multi-shot EPI sequence on a 3T Connectom scanner. The efficacy of dynamic field monitoring-based image reconstruction was demonstrated on high-resolution whole brain ex vivo dMRI. A 3D multi-shot image reconstruction framework was informed with the actual nonlinear phase evolution measured with the dynamic field camera, thereby accounting for high-order eddy currents fields on top of the image encoding gradients in the image formation model. Results: Eddy current fields from diffusion gradients at high gradient strength in a 3T Connectom scanner are highly nonlinear in space and time, inducing high-order spatial phase modulations between odd/even echoes and shots that are not static during the readout. Superior reduction of ghosting and geometric distortion was achieved with dynamic field monitoring compared to ghosting approaches such as navigator- and structured low-rank-based methods or MUSE, followed by image-based distortion correction with eddy. Improved dMRI analysis is demonstrated with diffusion tensor imaging and high-angular resolution diffusion imaging. Conclusion: Strong eddy current artifacts characteristic of high gradient strength dMRI can be well corrected with dynamic field monitoring-based image reconstruction, unlike the two-step approach consisting of ghosting correction followed by geometric distortion reduction with eddy.
Language	English
Publishing date	2023-02-16
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.02.15.528684
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Article ; Online: Domain-agnostic segmentation of thalamic nuclei from joint structural and diffusion MRI.

Tregidgo, Henry F J / Soskic, Sonja / Olchanyi, Mark D / Althonayan, Juri / Billot, Benjamin / Maffei, Chiara / Golland, Polina / Yendiki, Anastasia / Alexander, Daniel C / Bocchetta, Martina / Rohrer, Jonathan D / Iglesias, Juan Eugenio

ArXiv

2023

Abstract: The human thalamus is a highly connected subcortical grey-matter structure within the brain. It comprises dozens of nuclei with different function and connectivity, which are affected differently by disease. For this reason, there is growing interest in ... ...

Abstract	The human thalamus is a highly connected subcortical grey-matter structure within the brain. It comprises dozens of nuclei with different function and connectivity, which are affected differently by disease. For this reason, there is growing interest in studying the thalamic nuclei in vivo with MRI. Tools are available to segment the thalamus from 1 mm T1 scans, but the contrast of the lateral and internal boundaries is too faint to produce reliable segmentations. Some tools have attempted to incorporate information from diffusion MRI in the segmentation to refine these boundaries, but do not generalise well across diffusion MRI acquisitions. Here we present the first CNN that can segment thalamic nuclei from T1 and diffusion data of any resolution without retraining or fine tuning. Our method builds on a public histological atlas of the thalamic nuclei and silver standard segmentations on high-quality diffusion data obtained with a recent Bayesian adaptive segmentation tool. We combine these with an approximate degradation model for fast domain randomisation during training. Our CNN produces a segmentation at 0.7 mm isotropic resolution, irrespective of the resolution of the input. Moreover, it uses a parsimonious model of the diffusion signal at each voxel (fractional anisotropy and principal eigenvector) that is compatible with virtually any set of directions and b-values, including huge amounts of legacy data. We show results of our proposed method on three heterogeneous datasets acquired on dozens of different scanners. An implementation of the method is publicly available at https://freesurfer.net/fswiki/ThalamicNucleiDTI.
Language	English
Publishing date	2023-05-05
Publishing country	United States
Document type	Preprint
ISSN	2331-8422
ISSN (online)	2331-8422
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