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Review: Using diffusion-weighted magnetic resonance imaging techniques to explore the microstructure and connectivity of subcortical white matter tracts in the human auditory system
Abstract
Since its inception 30 years ago, diffusion-weighted magnetic resonance imaging (dMRI) has advanced to become a common component of routine clinical MRI examinations. Diffusion-weighted magnetic resonance offers a way to measure anisotropic diffusion in-vivo, which has led to the development of techniques capable of characterising the orientation of diffusion within living tissue. These modelling techniques can be used to investigate the microstructure and connectivity of white matter tracts within the human brain. Such techniques have been used to study many neural networks within the human body. There is, however, a notable paucity of research utilising dMRI techniques to investigate the white matter tracts of the auditory brainstem. In this review we provide a brief introduction to the basic principles of dMRI analysis and consider some of the difficulties associated with applying dMRI techniques to study the auditory pathways of the brainstem. We also consider aspects of current dMRI methodologies relevant to the auditory brainstem to inform future research in this area.
... Given the minute size and complex structures of these brainstem nuclei and tracts, high-resolution imaging is required. Recent methodologies in adults have employed either ex vivo 3T MRI [75] or in vivo imaging with 7T scanners [74] [76] . For infants, additional challenges arise. ...
Infants exhibit remarkable language acquisition abilities, supported by highly plastic neural substrates that dynamically interact with early speech experiences. However, the developmental mechanisms of these neural substrates and their specific role in speech acquisition remain incompletely understood. Here, we present NeoAudi Tract (NAT), a robust automated toolbox for extracting the full set of auditory tracts in infants from birth to 24 months using 3T diffusion MRI data. By characterizing the microstructural changes in these tracts, we demonstrate a gradual and continuous maturation process of the auditory system. Additionally, we identify significant correlations between auditory tract maturation and both _fine-motor skills_ and _expressive language T_-scores from the Mullen Scales of Early Learning tests. Our findings highlight the role of the auditory system in speech production and indicate the intertwined development of auditory and motor systems that underlies speech acquisition, particularly during perceptual reorganization.
... Brainstem anatomy is characterized by a mixture of white matter bundles and subcortical nuclei, and dMRI tractography performance is inhibited by the polysynaptic nature of the auditory pathway (Mori and Tournier 2013;Wakana et al. 2004). In order to mitigate the inherent difficulties of delineating the auditory pathway from the brainstem to the auditory cortex (AC), we utilize state-of-the-art diffusion analysis techniques, including a high angular resolution diffusion imaging (HARDI) acquisition with a higher order modeling approach to enhance detail to auditory microstructure (Zanin et al. 2019). In particular, we employed multicompartment modeling techniques including DTI with free-water elimination diffusion tensor imaging (fwe-DTI) and NODDI, which are made possible with a multishell (or multi-b-value) acquisition, and this provides a way to characterize tissue microstructure properties and reduce partial volume effects that arise from the mixing of distinct tissue compartments. ...
Auditory perception is established through experience‐dependent stimuli exposure during sensitive developmental periods; however, little is known regarding the structural development of the central auditory pathway in humans. The present study characterized the regional developmental trajectories of the ascending auditory pathway from the brainstem to the auditory cortex from infancy through adolescence using a novel diffusion MRI‐based tractography approach and along‐tract analyses. We used diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) to quantify the magnitude and timing of auditory pathway microstructural maturation. We found spatially varying patterns of white matter maturation along the length of the tract, with inferior brainstem regions developing earlier than thalamocortical projections and left hemisphere tracts developing earlier than the right. These results help to characterize the processes that give rise to functional auditory processing and may provide a baseline for detecting abnormal development.
... Because auditory capacity is determined by the degree to which neural firing patterns are disrupted, dMRI may provide crucial information (not attainable with other imaging techniques of the auditory system [Zanin et al. 2019]) and could play a pivotal role in guiding management recommendations. However, while the dMRI metric of AFD is recordable in infants (Dhollander et al. 2018;Pannek et al. 2018), further research is needed to determine whether long-term outcomes can be predicted from AFD findings in babies. ...
Objective
Auditory neuropathy (AN), a complex hearing disorder, presents challenges in diagnosis and management due to limitations of current diagnostic assessment. This study aims to determine whether diffusion-weighted magnetic resonance imaging (MRI) can be used to identify the site and severity of lesions in individuals with AN.
Methods
This case-control study included 10 individuals with AN of different etiologies, 7 individuals with neurofibromatosis type 1 (NF1), 5 individuals with cochlear hearing loss, and 37 control participants. Participants were recruited through the University of Melbourne’s Neuroaudiology Clinic and the Murdoch Children’s Research Institute specialist outpatient clinics. Diffusion-weighted MRI data were collected for all participants and the auditory pathways were evaluated using the fixel-based analysis metric of apparent fiber density. Data on each participant’s auditory function were also collected including hearing thresholds, otoacoustic emissions, auditory evoked potentials, and speech-in-noise perceptual ability.
Results
Analysis of diffusion-weighted MRI showed abnormal white matter fiber density in distinct locations within the auditory system depending on etiology. Compared with controls, individuals with AN due to perinatal oxygen deprivation showed no white matter abnormalities ( p > 0.05), those with a neurodegenerative conditions known/predicted to cause VIII cranial nerve axonopathy showed significantly lower white matter fiber density in the vestibulocochlear nerve ( p < 0.001), while participants with NF1 showed lower white matter fiber density in the auditory brainstem tracts ( p = 0.003). In addition, auditory behavioral measures of speech perception in noise and gap detection were correlated with fiber density results of the VIII nerve.
Conclusions
Diffusion-weighted MRI reveals different patterns of anatomical abnormality within the auditory system depending on etiology. This technique has the potential to guide management recommendations for individuals with peripheral and central auditory pathway abnormality.
... Furthermore, the brainstem is characterized by a mixture of white matter bundles and subcortical nuclei, and dMRI tractography performance is inhibited by the polysynaptic nature of the auditory pathway (Mori and Tournier, 2013;Wakana et al., 2004). In order to mitigate the inherent difficulties of delineating the auditory pathway from the brainstem to the auditory cortex, we utilize state-of-the-art diffusion analysis techniques, including a high angular resolution diffusion imaging (HARDI) acquisition with a higher order modeling approach to enhance detail to auditory microstructure (Zanin et al., 2019). In particular, we employed multi-compartment modeling techniques including DTI with free-water elimination and NODDI, which are made possible with a multi-shell (or multi-b-value) acquisition, and this provides a way to characterize tissue microstructure properties and reduce partial volume effects that arise from the mixing of distinct tissue compartments. ...
Auditory perception is established through experience-dependent stimuli exposure during sensitive developmental periods; however, little is known regarding the structural development of the central auditory pathway in humans. The present study characterized the regional developmental trajectories of the ascending auditory pathway from the brainstem to the auditory cortex from infancy through adolescence using a novel diffusion MRI-based tractography approach and along-tract analyses. We used diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) to quantify the magnitude and timing of auditory pathway microstructural maturation. We found spatially varying patterns of white matter maturation along the length of the tract, with inferior brainstem regions developing earlier than thalamocortical projections and left hemisphere tracts developing earlier than the right. These results help to characterize the processes that give rise to functional auditory processing and may provide a baseline for detecting abnormal development.
Highlights
We characterize the microstructural maturation of the auditory pathway
We show structural development of the auditory pathway is dynamic and heterogeneous
Diffusion metrics AD, RD and MD reach adult-like levels earlier than FA and NDI
Brainstem microstructure matures earlier than the subcortical white matter
Maturation of the right auditory pathway continues later than the left
... However, there are several challenges in this field. Firstly, the human auditory pathway is difficult to inspect non-invasively due to its delicate nodes connected by curving and crossing fibres, especially the parts that are buried deep in the brainstem (Zanin et al., 2019). Functional MRI (fMRI) responses to natural sounds have been used to locate subcortical auditory structures (Sitek et al., 2019), but this method is not applicable to patients with profound hearing loss as no auditory brainstem responses (ABRs) can be detected in these individuals, making it impossible to capture corresponding blood oxygen signals in fMRI. ...
Profound congenital sensorineural hearing loss (SNHL) prevents children from developing spoken language. Cochlear implantation and auditory brainstem implantation can provide partial hearing sensation, but language development outcomes can vary, particularly for patients with inner ear malformations and/or cochlear nerve deficiency (IEM&CND). Currently, the peripheral auditory structure is evaluated through visual inspection of clinical imaging, but this method is insufficient for surgical planning and prognosis. The central auditory pathway is also challenging to examine in vivo due to its delicate subcortical structures. Previous attempts to locate subcortical auditory nuclei using fMRI responses to sounds are not applicable to patients with profound hearing loss as no auditory brainstem responses can be detected in these individuals, making it impossible to capture corresponding blood oxygen signals in fMRI. In this study, we developed a new pipeline for mapping the auditory pathway using structural and diffusional MRI. We used a fixel-based approach to investigate the structural development of the auditory-language network for profound SNHL children with normal peripheral structure and those with IEM&CND under 6 years old. Our findings indicate that the language pathway is more sensitive to peripheral auditory condition than the central auditory pathway, highlighting the importance of early intervention for profound SNHL children to provide timely speech inputs. We also propose a comprehensive pre-surgical evaluation extending from the cochlea to the auditory-language network, showing significant correlations between age, gender, Cn.VIII median contrast value, and the language network with post-implant qualitative outcomes.
... Additionally, hearing and language outcomes 33 (categories of auditory performance) six to twelve months following CI were positively correlated 34 with preoperative auditory pathway FA values (Chang et al., 2012;Huang et al., 2015; However, there are several challenges in this field. Firstly, the human auditory pathway is 44 difficult to inspect non-invasively due to its delicate nodes connected by curving and crossing fibres, 45 especially the parts that are buried deep in the brainstem (Zanin et al., 2019). Functional MRI (fMRI) 46 responses to natural sounds have been used to locate subcortical auditory structures (Sitek et al., 47 2019), but this method is not applicable to patients with profound hearing loss. ...
Profound congenital sensorineural hearing loss (SNHL) prevents children from developing spoken language. Cochlear implantation and auditory brainstem implantation can provide hearing sensation, but language development outcomes can vary, particularly for patients with inner ear malformations and/or cochlear nerve deficiency (IEM&CND). Currently, the peripheral auditory structure is evaluated through visual inspection of clinical imaging, but this method is insufficient for surgical planning and prognosis. The central auditory pathway is also challenging to examine in vivo due to its delicate subcortical structures. Previous attempts to locate subcortical auditory nuclei using fMRI responses to sounds are not applicable to deaf patients. In this study, we developed a new pipeline for mapping the auditory pathway using structural and diffusional MRI. We used a fixel-based approach to investigate the structural development of the auditory-language network for profound SNHL children with normal peripheral structure and those with IEM&CND under six years old. Our findings indicate that the language pathway is more sensitive to peripheral auditory condition than the central auditory pathway, highlighting the importance of early intervention for profound SNHL children to provide timely speech inputs. We also propose a comprehensive pre-surgical evaluation extending from the cochlea to the auditory-language network, which has promising clinical potential.
... Electrophysiological examinations of the cochlear nerve indicated that lesions would be located on the auditory pathway from postsynapses to acoustic fibers [3]. Further, the diffusion-weighted MRI (dMRI) analysis techniques may contribute to the microstructure of the auditory tracts in vivo in individuals with AN [3,46]; from the dMRI of some patients, we can see a reduction in apparent fiber density within the auditory brainstem tracts, which is consistent with the assumed pathophysiological mechanism of postsynapses to acoustic fibers (unpublished data). Thus, AN patients with AIFM1 mutation may have poor efficiency from cochlear implantation. ...
To decipher the genotype-phenotype correlation of auditory neuropathy (AN) caused by AIFM1 variations, as well as the phenotype progression of these patients, exploring the potential molecular pathogenic mechanism of AN. A total of 36 families of individuals with AN (50 cases) with AIFM1 variations were recruited and identified by Sanger sequencing or next-generation sequencing; the participants included 30 patients from 16 reported families and 20 new cases. We found that AIFM1 -positive cases accounted for 18.6% of late-onset AN cases. Of the 50 AN patients with AIFM1 variants, 45 were male and 5 were female. The hotspot variation of this gene was p.Leu344Phe, accounting for 36.1%. A total of 19 AIFM1 variants were reported in this study, including 7 novel ones. A follow-up study was performed on 30 previously reported AIFM1- positive subjects, 16 follow-up cases (53.3%) were included in this study, and follow-up periods were recorded from 1 to 23 years with average 9.75 ± 9.89 years. There was no hearing threshold increase during the short-term follow-up period (1-10 years), but the low-frequency and high-frequency hearing thresholds showed a significant increase with the prolongation of follow-up time. The speech discrimination score progressed gradually and significantly along with the course of the disease and showed a more serious decline, which was disproportionately worse than the pure tone threshold. In addition to the X-linked recessive inheritance pattern, the X-linked dominant inheritance pattern is also observed in AIFM1 -related AN and affects females. In conclusion, we confirmed that AIFM1 is the primary related gene among late-onset AN cases, and the most common recurrent variant is p.Leu344Phe. Except for the X-linked recessive inheritance pattern, the X-linked dominant inheritance pattern is another probability of AIFM1 -related AN, with females affected. Phenotypical features of AIFM1 -related AN suggested that auditory dyssynchrony progressively worsened over time.
... The images are taken sequentially to create non-invasive assays of neural activity. A full description of MRI is beyond the scope of this review but the reader unfamiliar with this technology is encouraged to read an excellent overview of diffusion-weighted MRI by Zanin et al. (2019). ...
Rats make excellent models for the study of medical, biological, genetic, and behavioral phenomena given their adaptability, robustness, survivability, and intelligence. The rat's general anatomy and physiology of the auditory system is similar to that observed in humans, and this has led to their use for investigating the effect of noise overexposure on the mammalian auditory system. The current paper provides a review of the rat model for studying noise-induced hearing loss and highlights advancements that have been made using the rat, particularly as these pertain to noise dose and the hazardous effects of different experimental noise types. In addition to the traditional loss of auditory function following acoustic trauma, recent findings have indicated the rat as a useful model in observing alterations in neuronal processing within the central nervous system following noise injury. Furthermore, the rat provides a second animal model when investigating noise-induced cochlear synaptopathy, as studies examining this in the rat model resemble the general patterns observed in mice. Together, these findings demonstrate the relevance of this animal model for furthering the authors' understanding of the effects of noise on structural, anatomical, physiological, and perceptual aspects of hearing.
... While affected by similar confounds as functional MRI (e.g. partial voluming effects, physiological noise, and relative signal weighting), this technique faces additional complications introduced by the number of orientations required, the gradient strength (bvalue) selected, the modeling of diffusion or fiber orientations within each voxel, and the estimation of streamlines across brain regions, especially within the subcortical auditory system (Zanin et al., 2019). The post mortem and in vivo diffusion MRI datasets in this study each implemented state-ofthe-art acquisition techniques to optimize the MRI signal-to-noise ratio and minimize MRI modeling errors. ...
***[This paper is now published in eLife journal. See https://elifesciences.org/articles/48932]***
Studying the human subcortical auditory system non-invasively is challenging due to its small structures deep within the brain. Additionally, the elaborate three-dimensional (3-D) structure of the system can be diZcult to understand based on currently available 2-D schematics and animal models. To address these issues, we measured functional magnetic resonance imaging (fMRI) responses from the human subcortical auditory system at 7 Tesla and validated the results by creating an atlas based on state of the art human histology (BigBrain) and post mortem MRI. Furthermore, using diffusion MRI tractography, we revealed structural connectivity maps of the human subcortical auditory pathway both in vivo (1050 μm isotropic resolution) and post mortem (200 μm isotropic resolution). This work contributes novel tools for researching the human auditory system to understand its structural organization as well as facilitates dissemination of this knowledge by making the created atlases openly available.
Objectives:
Auditory neuropathy (AN) is the term used to describe a group of hearing disorders, in which the hearing impairment occurs as a result of abnormal auditory nerve function. While our understanding of this condition has advanced significantly over recent years, the ability to determine the site of lesion and the extent of dysfunction in affected individuals remains a challenge. To this end, we investigated potential axonal degeneration in the white matter tracts of the brainstem in individuals with X-linked AN. We hypothesized that individuals with X-linked AN would show focal degeneration within the VIII nerve and/or auditory brainstem tracts, and the degree of degeneration would correlate with the extent of auditory perceptual impairment.
Design:
This was achieved using a higher-order diffusion magnetic resonance imaging (dMRI)-based quantitative measure called apparent fiber density as obtained from a technique called single-shell 3-tissue constrained spherical deconvolution and analyzed with the fixel-based analysis framework. Eleven subjects with genetically confirmed X-linked AN and 11 controls with normal hearing were assessed using behavioral and objective auditory measures. dMRI data were also collected for each participant.
Results:
Fixel-based analysis of the brainstem region showed that subjects with X-linked AN had significantly lower apparent fiber density in the VIII nerve compared with controls, consistent with axonal degeneration in this region. Subsequent analysis of the auditory brainstem tracts specifically showed that degeneration was also significant in these structures overall. The apparent fiber density findings were supported by objective measures of auditory function, such as auditory brainstem responses, electrocochleography, and otoacoustic emissions, which showed VIII nerve activity was severely disrupted in X-linked AN subjects while cochlear sensory hair cell function was relatively unaffected. Moreover, apparent fiber density results were significantly correlated with temporal processing ability (gap detection task) in affected subjects, suggesting that the degree of VIII nerve degeneration may impact the ability to resolve temporal aspects of an acoustic signal. Auditory assessments of sound detection, speech perception, and the processing of binaural cues were also significantly poorer in the X-linked AN group compared with the controls with normal hearing.
Conclusions:
The results of this study suggest that the dMRI-based measure of apparent fiber density may provide a useful adjunct to existing auditory assessments in the characterization of the site of lesion and extent of dysfunction in individuals with AN. Additionally, the ability to determine the degree of degeneration has the potential to guide rehabilitation strategies in the future.
Studying the human subcortical auditory system non-invasively is challenging due to its small, densely packed structures deep within the brain. Additionally, the elaborate three-dimensional (3-D) structure of the system can be difficult to understand based on currently available 2-D schematics and animal models. We addressed these issues using a combination of histological data, post mortem magnetic resonance imaging (MRI), and in vivo MRI at 7 Tesla. We created anatomical atlases based on state-of-the-art human histology (BigBrain) and post mortem MRI (50 μm). We measured functional MRI (fMRI) responses to natural sounds and demonstrate that the functional localization of subcortical structures is reliable within individual participants who were scanned in two different experiments. Further, a group functional atlas derived from the functional data locates these structures with a median distance below 2mm. Using diffusion MRI tractography, we revealed structural connectivity maps of the human subcortical auditory pathway both in vivo (1050 μm isotropic resolution) and post mortem (200 μm isotropic resolution). This work captures current MRI capabilities for investigating the human subcortical auditory system, describes challenges that remain, and contributes novel, openly available data, atlases, and tools for researching the human auditory system.
Anatomical white matter bundles vary in shape, size, length, and complexity, making diffusion MRI tractography reconstruction of some bundles more difficult than others. As a result, bundles reconstruction often suffers from a poor spatial extent recovery. To fill-up the white matter volume as much and as best as possible, millions of streamlines can be generated and filtering techniques applied to address this issue. However, well-known problems and biases are introduced such as the creation of a large number of false positives and over-representation of easy-to-track parts of bundles and under-representation of hard-to-track. To address these challenges, we developed a Bundle-Specific Tractography (BST) algorithm. It incorporates anatomical and orientational prior knowledge during the process of streamline tracing to increase reproducibility, sensitivity, specificity and efficiency when reconstructing certain bundles of interest. BST outperforms classical deterministic, probabilistic, and global tractography methods. The increase in anatomically plausible streamlines, with larger spatial coverage, helps to accurately represent the full shape of bundles, which could greatly enhance and robustify tract-based and connectivity-based neuroimaging studies.
Since the realization that diffusion MRI can probe the microstructural organization and orientation of biological tissue in vivo and non‐invasively, a multitude of diffusion imaging methods have been developed and applied to study the living human brain. Diffusion tensor imaging was the first model to be widely adopted in clinical and neuroscience research, but it was also clear from the beginning that it suffered from limitations when mapping complex configurations, such as crossing fibres. In this review, we highlight the main steps that have led the field of diffusion imaging to move from the tensor model to the adoption of diffusion and fibre orientation density functions as a more effective way to describe the complexity of white matter organization within each brain voxel. Among several techniques, spherical deconvolution has emerged today as one of the main approaches to model multiple fibre orientations and for tractography applications. Here we illustrate the main concepts and the reasoning behind this technique, as well as the latest developments in the field. The final part of this review provides practical guidelines and recommendations on how to set up processing and acquisition protocols suitable for spherical deconvolution. Diffusion MRI can probe non‐invasively and in vivo the microstructural organization and the orientation of white matter in the human brain. Diffusion tensor imaging was the first model to be widely adopted in clinical and research applications, but it has also shown important limitations. Alternative methods have been developed to extract and better describe multiple populations of fibre orientations in the brain. Here we review these techniques, focusing particularly on spherical deconvolution, its principles and how this method can be practically applied in real studies.
The aim of this article is to illustrate the principal challenges, from the medical and technical point of view, associated with the use of ultrahigh field (UHF) scanners in the clinical setting and to present available solutions to circumvent these limitations.
We would like to show the differences between UHF scanners and those used routinely in clinical practice, the principal advantages, and disadvantages, the different UHFs that are ready be applied to routine clinical practice such as susceptibility‐weighted imaging, fluid‐attenuated inversion recovery, 3‐dimensional time of flight, magnetization‐prepared rapid acquisition gradient echo, magnetization‐prepared 2 rapid acquisition gradient echo, and diffusion‐weighted imaging, the technical principles of these sequences, and the particularities of advanced techniques such as diffusion tensor imaging, spectroscopy, and functional imaging at 7TMR.
Finally, the main clinical applications in the field of the neuroradiology are discussed and the side effects are reported.
The ability of fiber tractography to delineate non-invasively the white matter fiber pathways of the brain raises possibilities for clinical applications and offers enormous potential for neuroscience. In the last decade, fiber tracking has become the method of choice to investigate quantitative MRI parameters in specific bundles of white matter. For neurosurgeons, it is quickly becoming an invaluable tool for the planning of surgery, allowing for visualization and localization of important white matter pathways before and even during surgery. Fiber tracking has also claimed a central role in the field of “connectomics,” a technique that builds and studies comprehensive maps of the complex network of connections within the brain, and to which significant resources have been allocated worldwide. Despite its unique abilities and exciting applications, fiber tracking is not without controversy, in particular when it comes to its interpretation. As neuroscientists are eager to study the brain's connectivity, the quantification of tractography-derived “connection strengths” between distant brain regions is becoming increasingly popular. However, this practice is often frowned upon by fiber-tracking experts. In light of this controversy, this paper provides an overview of the key concepts of tractography, the technical considerations at play, and the different types of tractography algorithm, as well as the common misconceptions and mistakes that surround them. We also highlight the ongoing challenges related to fiber tracking. While recent methodological developments have vastly increased the biological accuracy of fiber tractograms, one should be aware that, even with state-of-the-art techniques, many issues that severely bias the resulting structural “connectomes” remain unresolved.
Voxel-based analysis of diffusion MRI data is increasingly popular. However, most white matter voxels contain contributions from multiple fibre populations (often referred to as crossing fibres), and therefore voxel-averaged quantitative measures (e.g. fractional anisotropy) are not fibre-specific and have poor interpretability. Using higher-order diffusion models, parameters related to fibre density can be extracted for individual fibre populations within each voxel (‘fixels’), and recent advances in statistics enable the multi-subject analysis of such data. However, investigating within-voxel microscopic fibre density alone does not account for macroscopic differences in the white matter morphology (e.g. the calibre of a fibre bundle). In this work, we introduce a novel method to investigate the latter, which we call fixel-based morphometry (FBM). To obtain a more complete measure related to the total number of white matter axons, information from both within-voxel microscopic fibre density and macroscopic morphology must be combined. We therefore present the FBM method as an integral piece within a comprehensive fixel-based analysis framework to investigate measures of fibre density, fibre-bundle morphology (cross-section), and a combined measure of fibre density and cross-section. We performed simulations to demonstrate the proposed measures using various transformations of a numerical fibre bundle phantom. Finally, we provide an example of such an analysis by comparing a clinical patient group to a healthy control group, which demonstrates that all three measures provide distinct and complementary information. By capturing information from both sources, the combined fibre density and cross-section measure is likely to be more sensitive to certain pathologies and more directly interpretable.
To overcome the fact that the fibre orientation distribution (FOD) from constrained spherical deconvolution (CSD) assumes a single-fibre white matter (WM) response function—and is thus inappropriate and distorted in voxels containing grey matter (GM) or cerebrospinal fluid (CSF)—multi-shell multi-tissue CSD (MSMT-CSD) was proposed. MSMT-CSD can resolve WM, GM and CSF signal contributions, but requires multi-shell data. Very recently, we proposed a novel method that can achieve the same results using just single-shell data. We refer to this method as "single-shell 3-tissue CSD" (SS3T-CSD). Both MSMT-CSD and SS3T-CSD require WM, GM and CSF response functions. These can be obtained from manually selected exemplary voxels of the tissue classes, or via the procedure described initially in the MSMT-CSD paper, which relies on a highly accurately co-registered T1 image. We propose an unsupervised procedure that does not depend on a T1 image, nor registration, and works for both single-shell and multi-shell data.
Background and purpose:
Vestibular schwannomas cause progressive hearing loss by direct damage to the vestibulocochlear nerve. The cerebral mechanisms of degeneration or plasticity are not well-understood. Therefore, the goal of our study was to show the feasibility of probabilistic fiber-tracking of the auditory pathway in patients with vestibular schwannomas and to compare the ipsi- and contralateral volume and integrity, to test differences between the hemispheres.
Materials and methods:
Fifteen patients with vestibular schwannomas were investigated before surgery. Diffusion-weighted imaging (25 directions) was performed on a 3T MR imaging system. Probabilistic tractography was performed for 3 partial sections of the auditory pathway. Volume and fractional anisotropy were determined and compared ipsilaterally and contralaterally. The laterality ratio was correlated with the level of hearing loss.
Results:
Anatomically reasonable tracts were depicted in all patients for the acoustic radiation. Volume was significantly decreased on the hemisphere contralateral to the tumor side for the acoustic radiation and diencephalic section, while fractional anisotropy did not differ significantly. Tracking did not yield meaningful tracts in 3 patients for the thalamocortical section and in 5 patients for the diencephalic section. No statistically significant correlations between the laterality quotient and classification of hearing loss were found.
Conclusions:
For the first time, this study showed that different sections of the auditory pathway between the inferior colliculus and the auditory cortex can be visualized by using probabilistic tractography. A significant volume decrease of the auditory pathway on the contralateral hemisphere was observed and may be explained by transsynaptic degeneration of the crossing auditory pathway.
Constrained spherical deconvolution (CSD) is a robust approach to resolve the fibre orientation distribution (FOD) from diffusion MRI data. However, the FOD from CSD only aims to represent "pure" white matter (WM) and is inappropriate/distorted in regions of (partial voluming with) grey matter (GM) or cerebrospinal fluid (CSF). Multi-shell multi-tissue CSD was proposed to solve this issue by estimating WM/GM/CSF components, but requires multi-shell data to do so. In this work, we provide the first proof that similar results can also be obtained from only simple single-shell (+b=0) data, and propose a novel specialised optimiser that achieves this goal.
Diffusion tensor imaging (DTI) has revolutionized the visualization of white matter in vivo. However, it is far more than a qualitative tool and can also be used to generate quantitative measures related to diffusion magnitude and its degree of anisotropy, which indirectly reflect microstructural organisation. Although highly sensitive to microstructural change, DTI measures lack specificity and are influenced by a wide range of biological and methodological factors. This makes the interpretation of DTI metric changes extremely challenging.
This chapter introduces the most common DTI measures and how they relate to tissue microstructure. Important confounds are addressed, including how DTI metrics are influenced by biological factors such as ageing and pathology, and by methodological factors such as data acquisition, modeling, and analysis.
In this paper we describe a method for retrospective estimation and correction of eddy current (EC)-induced distortions and subject movement in diffusion imaging. In addition a susceptibility-induced field can be supplied and will be incorporated into the calculations in a way that accurately reflects that the two fields (susceptibility- and EC-induced) behave differently in the presence of subject movement. The method is based on registering the individual volumes to a model free prediction of what each volume should look like, thereby enabling its use on high b-value data where the contrast is vastly different in different volumes. In addition we show that the linear EC-model commonly used is insufficient for the data used in the present paper (high spatial and angular resolution data acquired with Stejskal–Tanner gradients on a 3 T Siemens Verio, a 3 T Siemens Connectome Skyra or a 7 T Siemens Magnetome scanner) and that a higher order model performs significantly better.
The method is already in extensive practical use and is used by four major projects (the WU-UMinn HCP, the MGH HCP, the UK Biobank and the Whitehall studies) to correct for distortions and subject movement.
Although conventional structural MRI provides vital information in the evaluation of congenital sensorineural hearing loss (SNHL), it is relatively insensitive to white matter microstructure. Our objective was to evaluate possible changes in microstructure of the auditory pathway in children with congenital sensorineural hearing loss (SNHL), and the possible distinction between good and poor outcome of cochlear implantation (CI) patients by using diffusion tensor imaging (DTI). Twenty-four patients with congenital SNHL and 20 healthy controls underwent conventional MRI and DTI examination using a 1.5T MR scanner. The DTI metrics of fractional anisotropy (FA) and mean diffusivity (MD) of six regions of interest (ROIs) positioned along the auditory pathway-the trapezoid body, superior olivary nucleus, inferior colliculus, medial geniculate body, auditory radiation and white matter of Heschl's gyrus-was measured in all subjects. Among the 24 patients, 8 patients with a categorie of auditory performance (CAP) score over 6 were classified into the good outcome group, and 16 patients with a CAP score below 6 were classified into the poor outcome group. A significant decrease was observed in FA values while MD values remained unchanged at the six ROIs of SNHL patients compared with healthy controls. Compared to good outcome subjects, poor outcome subjects displayed decreased FA values at all of the ROIs. No changes were observed in MD values. Correlation analyses only revealed strong correlations between FA values and CAP scores, and strong correlations between CAP scores and age at implant were also found. No correlations of FA values with age at implant were observed. Our results show that preoperative DTI can be used to evaluate microstructural alterations in the auditory pathway that are not detectable by conventional MR imaging, and may play an important role in evaluating the outcome of CI. Early cochlear implantation might be more effectively to restore hearing in SNHL patients.
The optic radiation (OR) is one of the major components of the visual system and a key structure at risk in white matter diseases such as multiple sclerosis (MS). However, it is challenging to perform track reconstruction of the OR using diffusion MRI due to a sharp change of direction in the Meyer's loop and the presence of kissing and crossing fibers along the pathway. As such, we aimed to provide a highly precise and reproducible framework for tracking the OR from thalamic and visual cortex masks. The framework combined the generation of probabilistic streamlines by high order fiber orientation distributions estimated with constrained spherical deconvolution and an automatic post-processing based on anatomical exclusion criteria (AEC) to compensate for the presence of anatomically implausible streamlines. Specifically, those ending in the contralateral hemisphere, cerebrospinal fluid or grey matter outside the visual cortex were automatically excluded. We applied the framework to two distinct high angular resolution diffusion weighted imaging (HARDI) acquisition protocols on one cohort, comprised of ten healthy volunteers and five MS patients. The OR was successfully delineated in both HARDI acquisitions in the healthy volunteers and MS patients. Quantitative evaluation of the OR position was done by comparing the results with histological reference data. Compared with histological mask, the OR reconstruction into a template (OR-TCT) was highly precise (percentage of voxels within the OR-TCT correctly defined as OR), ranging from 0.71 to 0.83. The sensitivity (percentage of voxels in histological reference mask correctly defined as OR in OR-TCT) ranged from 0.65 to 0.81 and the accuracy (measured by F1 score) was 0.73 to 0.77 in healthy volunteers. When AEC was not applied the precision and accuracy decreased. The absolute agreement between both HARDI datasets measured by the intraclass correlation coefficient was 0.73. This improved framework allowed us to reconstruct the OR with high reliability and accuracy independently of the acquisition parameters. Moreover, the reconstruction was possible even in
Since its introduction over a decade ago, diffusion tractography has come a long way from local, deterministic methods, over probabilistic approaches, towards global tractography. Yet, the development of tractography methods has been largely focused on single subject data, and very little on cross-population analysis and inter-subject variability. In this work, we extend global tractography with a prior on the local track orientation distribution (TOD), derived from 20 normal subjects. The proposed method is evaluated in 5 independent subjects. Results show that adding such prior regularizes the reconstructed track distribution, although registration errors can induce local artefacts. We conclude that atlas-guided global tractography can improve the fibre reconstruction and ultimately detect and quantify inter-subject differences in tractography. D. Christiaens () · T. Dhollander · F. Maes · P. Suetens Medical Image Computing,
The "traditional" directionally-encoded colour (DEC) FA map is an icon of DTI, but is also affected by its inherent flaws. The first eigenvector is known to be ill-defined in regions of crossing fibres, resulting in misleading specific DEC values as well as "false edges" in the overall map. Additionally, the FA shows naturally low values in these regions. In a clinical setting, this might potentially lead to false positive findings; but also to false negative ones in case these false features mask out or otherwise distract from real pathological features. We propose an FOD-based DEC map that solves these issues.
Diffusion weighted imaging (DWI) acquisitions typically suffer from a lower spatial resolution, compared to their T1 structural counterparts, but provide unique angular information. Researchers and clinical users may often find themselves switching back and forth between the "traditional" directionally-encoded colour (DEC) FA map and a T1 map to navigate anatomy, or try to overlay them using (partial) transparency. We propose a panchromatic sharpening approach tailored to (FOD-based) DEC and (T1) structural information to create a single fused image. The resulting contrast is striking and allows for easy identification of various anatomical structures beyond the resolution of the DWI data.
Purpose:
To develop a fast and stable method for correcting the gibbs-ringing artifact.
Methods:
Gibbs-ringing is a well-known artifact which manifests itself as spurious oscillations in the vicinity of sharp image gradients at tissue boundaries. The origin can be seen in the truncation of k-space during MRI data-acquisition. Correction techniques like Gegenbauer reconstruction or extrapolation methods aim at recovering these missing data. Here, we present a simple and robust method which exploits a different view on the Gibbs-phenomenon: The truncation in k-space can be interpreted as a convolution of the underlying image with a sinc-function. As the image is reconstructed on a discretized grid, the severity of the ringing artifacts depends on how this grid is located with respect to the edge and the oscillation pattern of the function. We propose to reinterpolate the image based on local, subvoxel-shifts to sample the ringing pattern at the zero-crossings of the oscillating sinc-function.
Results:
With the proposed method, the artifact can simply, effectively, and robustly be removed with a minimal amount of image smoothing.
Conclusions:
The robustness of the method suggests it as a suitable candidate for an implementation in the standard image processing pipeline in clinical routine. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.
Tractography algorithms provide us with the ability to non-invasively reconstruct fiber pathways in the white matter (WM) by exploiting the directional information described with diffusion magnetic resonance. These methods could be divided into two major classes, local and global. Local methods reconstruct each fiber tract iteratively by considering only directional information at the voxel level and its neighborhood. Global methods, on the other hand, reconstruct all the fiber tracts of the whole brain simultaneously by solving a global energy minimization problem. The latter have shown improvements compared to previous techniques but these algorithms still suffer from an important shortcoming that is crucial in the context of brain connectivity analyses. As no anatomical priors are usually considered during the reconstruction process, the recovered fiber tracts are not guaranteed to connect cortical regions and, as a matter of fact, most of them stop prematurely in the WM; this violates important properties of neural connections, which are known to originate in the gray matter (GM) and develop in the WM. Hence, this shortcoming poses serious limitations for the use of these techniques for the assessment of the structural connectivity between brain regions and, de facto, it can potentially bias any subsequent analysis. Moreover, the estimated tracts are not quantitative, every fiber contributes with the same weight toward the predicted diffusion signal. In this work, we propose a novel approach for global tractography that is specifically designed for connectivity analysis applications which: (i) explicitly enforces anatomical priors of the tracts in the optimization and (ii) considers the effective contribution of each of them, i.e., volume, to the acquired diffusion magnetic resonance imaging (MRI) image. We evaluated our approach on both a realistic diffusion MRI phantom and in vivo data, and also compared its performance to existing tractography algorithms.
Introduction:
Diffusion MRI tractography has been increasingly used to delineate white matter pathways in vivo for which the leading clinical application is presurgical mapping of eloquent regions. However, there is rare opportunity to quantify the accuracy or sensitivity of these approaches to delineate white matter fiber pathways in vivo due to the lack of a gold standard. Intraoperative electrical stimulation (IES) provides a gold standard for the location and existence of functional motor pathways that can be used to determine the accuracy and sensitivity of fiber tracking algorithms. In this study we used intraoperative stimulation from brain tumor patients as a gold standard to estimate the sensitivity and accuracy of diffusion tensor MRI (DTI) and q-ball models of diffusion with deterministic and probabilistic fiber tracking algorithms for delineation of motor pathways.
Methods:
We used preoperative high angular resolution diffusion MRI (HARDI) data (55 directions, b = 2000 s/mm(2)) acquired in a clinically feasible time frame from 12 patients who underwent a craniotomy for resection of a cerebral glioma. The corticospinal fiber tracts were delineated with DTI and q-ball models using deterministic and probabilistic algorithms. We used cortical and white matter IES sites as a gold standard for the presence and location of functional motor pathways. Sensitivity was defined as the true positive rate of delineating fiber pathways based on cortical IES stimulation sites. For accuracy and precision of the course of the fiber tracts, we measured the distance between the subcortical stimulation sites and the tractography result. Positive predictive rate of the delineated tracts was assessed by comparison of subcortical IES motor function (upper extremity, lower extremity, face) with the connection of the tractography pathway in the motor cortex.
Results:
We obtained 21 cortical and 8 subcortical IES sites from intraoperative mapping of motor pathways. Probabilistic q-ball had the best sensitivity (79%) as determined from cortical IES compared to deterministic q-ball (50%), probabilistic DTI (36%), and deterministic DTI (10%). The sensitivity using the q-ball algorithm (65%) was significantly higher than using DTI (23%) (p < 0.001) and the probabilistic algorithms (58%) were more sensitive than deterministic approaches (30%) (p = 0.003). Probabilistic q-ball fiber tracks had the smallest offset to the subcortical stimulation sites. The offsets between diffusion fiber tracks and subcortical IES sites were increased significantly for those cases where the diffusion fiber tracks were visibly thinner than expected. There was perfect concordance between the subcortical IES function (e.g. hand stimulation) and the cortical connection of the nearest diffusion fiber track (e.g. upper extremity cortex).
Discussion:
This study highlights the tremendous utility of intraoperative stimulation sites to provide a gold standard from which to evaluate diffusion MRI fiber tracking methods and has provided an object standard for evaluation of different diffusion models and approaches to fiber tracking. The probabilistic q-ball fiber tractography was significantly better than DTI methods in terms of sensitivity and accuracy of the course through the white matter. The commonly used DTI fiber tracking approach was shown to have very poor sensitivity (as low as 10% for deterministic DTI fiber tracking) for delineation of the lateral aspects of the corticospinal tract in our study. Effects of the tumor/edema resulted in significantly larger offsets between the subcortical IES and the preoperative fiber tracks. The provided data show that probabilistic HARDI tractography is the most objective and reproducible analysis but given the small sample and number of stimulation points a generalization about our results should be given with caution. Indeed our results inform the capabilities of preoperative diffusion fiber tracking and indicate that such data should be used carefully when making pre-surgical and intra-operative management decisions.
The auditory tracts in the human brain connect the inferior colliculus (IC) and medial geniculate body (MGB) to various components of the auditory cortex (AC). While in non-human primates and in humans, the auditory system is differentiated in core, belt and parabelt areas, the correspondence between these areas and anatomical landmarks on the human superior temporal gyri is not straightforward, and at present not completely understood. However it is not controversial that there is a hierarchical organization of auditory stimuli processing in the auditory system. The aim of this study was to demonstrate that it is possible to non-invasively and robustly identify auditory projections between the auditory thalamus/brainstem and different functional levels of auditory analysis in the cortex of human subjects in vivo combining functional magnetic resonance imaging (fMRI) with diffusion MRI, and to investigate the possibility of differentiating between different components of the auditory pathways (e.g. projections to areas responsible for sound, pitch and melody processing). We hypothesized that the major limitation in the identification of the auditory pathways is the known problem of crossing fibers and addressed this issue acquiring DTI with b-values higher than commonly used and adopting a multi-fibre ball-and-stick analysis model combined with probabilistic tractography. Fourteen healthy subjects were studied. Auditory areas were localized functionally using an established hierarchical pitch processing fMRI paradigm. Together fMRI and diffusion MRI allowed the successful identification of tracts connecting IC with AC in 64 to 86% of hemispheres and left sound areas with homologous areas in the right hemisphere in 86% of hemispheres. The identified tracts corresponded closely with a three-dimensional stereotaxic atlas based on postmortem data. The findings have both neuroscientific and clinical implications for delineation of the human auditory system in vivo.
The human brainstem is critical for the control of many life-sustaining functions, such as consciousness, respiration, sleep, and transfer of sensory and motor information between the brain and the spinal cord. Most of our knowledge about structure and organization of white and gray matter within the brainstem is derived from ex vivo dissection and histology studies. However, these methods cannot be applied to study structural architecture in live human participants. Tractography from diffusion-weighted magnetic resonance imaging (MRI) may provide valuable insights about white matter organization within the brainstem in vivo. However, this method presents technical challenges in vivo due to susceptibility artifacts, functionally dense anatomy, as well as pulsatile and respiratory motion. To investigate the limits of MR tractography, we present results from high angular resolution diffusion imaging of an intact excised human brainstem performed at 11.1 T using isotropic resolution of 0.333, 1, and 2 mm, with the latter reflecting resolution currently used clinically. At the highest resolution, the dense fiber architecture of the brainstem is evident, but the definition of structures degrades as resolution decreases. In particular, the inferred corticopontine/corticospinal tracts (CPT/CST), superior (SCP) and middle cerebellar peduncle (MCP), and medial lemniscus (ML) pathways are clearly discernable and follow known anatomical trajectories at the highest spatial resolution. At lower resolutions, the CST/CPT, SCP, and MCP pathways are artificially enlarged due to inclusion of collinear and crossing fibers not inherent to these three pathways. The inferred ML pathways appear smaller at lower resolutions, indicating insufficient spatial information to successfully resolve smaller fiber pathways. Our results suggest that white matter tractography maps derived from the excised brainstem can be used to guide the study of the brainstem architecture using diffusion MRI in vivo.
Rapid progress in neurobiology and genetics demands knowledge of fundamental aspects of brain development including the connectivity patterns within developing and adult brains. The primary focus of this chapter is on neuroanatomical tract-tracing using carbocyanine dyes which have several advantages over traditional tracing methods. First utilized for in vitro studies, a major breakthrough in the late 1980s was the demonstration that carbocyanine dyes act as anterograde and retrograde tracers in fixed tissue, eliminating the need for diffusion of tracers in vivo. Moreover, carbocyanine dyes are more efficacious than classical tracing methodologies especially during early stages of development, and consequently have been used to reveal the spatiotemporal patterns of axonal development in different species. Furthermore, the unique properties of the carbocyanine dye tracing method have opened up new avenues for tracing connections in human postmortem specimens. This is a key step in determining the precise connectivity of neural circuits in the human brain, and subsequently to relate this knowledge to pathological cases.
The success of carbocyanine dyes as tracers, both in vitro and in fixed material, is reflected in the flurry of publications throughout the 1990s and into the present. However, there are relatively few systematic studies that have tested parameters to optimize their use or to give practical advice to enhance their efficacy. This chapter aims to bring together some of our experiences with the carbocyanine dye tracing method drawn from our studies in mammalian, reptilian, and human and nonhuman primate specimens.
Objective
The radiologic evaluation of patients with hearing loss includes computed tomography and magnetic resonance imaging (MRI) to highlight temporal bone and cochlear nerve anatomy. The central auditory pathways are often not studied for routine clinical evaluation. Diffusion tensor imaging (DTI) is an emerging MRI-based modality that can reveal microstructural changes in white matter. In this systematic review, we summarize the value of DTI in the detection of structural changes of the central auditory pathways in patients with sensorineural hearing loss.
Data Sources
PubMed, Embase, and Cochrane.
Review Methods
We used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement checklist for study design. All studies that included at least 1 sensorineural hearing loss patient with DTI outcome data were included.
Results
After inclusion and exclusion criteria were met, 20 articles were analyzed. Patients with bilateral hearing loss comprised 60.8% of all subjects. Patients with unilateral or progressive hearing loss and tinnitus made up the remaining studies. The auditory cortex and inferior colliculus (IC) were the most commonly studied regions using DTI, and most cases were found to have changes in diffusion metrics, such as fractional anisotropy, compared to normal hearing controls. Detectable changes in other auditory regions were reported, but there was a higher degree of variability.
Conclusion
White matter changes based on DTI metrics can be seen in patients with sensorineural hearing loss, but studies are few in number with modest sample sizes. Further standardization of DTI using a prospective study design with larger sample sizes is needed.
Streamline tractography algorithms infer connectivity from diffusion MRI (dMRI) by following diffusion directions which are similarly aligned between neighboring voxels. However, not all white matter (WM) fascicles are organized in this manner. For example, Meyer's loop is a highly curved portion of the optic radiation (OR) that exhibits a narrow turn, kissing and crossing pathways, and changes in fascicle dispersion. From a neurosurgical perspective, damage to Meyer's loop carries a potential risk of inducing vision deficits to the patient, especially during temporal lobe resection surgery. To prevent such impairment, achieving an accurate delineation of Meyer's loop with tractography is thus of utmost importance. However, current algorithms tend to under-estimate the full extent of Meyer's loop, mainly attributed to the aforementioned rule for connectivity which requires a direction to be chosen across a field of orientations. In this article, it was demonstrated that MAGNEtic Tractography (MAGNET) can benefit Meyer's loop delineation by incorporating anatomical knowledge of the expected fiber orientation to overcome local ambiguities. A new ROI-mechanism was proposed which supplies additional information to streamline reconstruction algorithms by the means of oriented priors. Their results showed that MAGNET can accurately generate Meyer's loop in all of our 15 child subjects (8 males; mean age 10.2 years ± 3.1). It effectively improved streamline coverage when compared with deterministic tractography, and significantly reduced the distance between the anterior-most portion of Meyer's loop and the temporal pole by 16.7 mm on average, a crucial landmark used for preoperative planning of temporal lobe surgery.
We introduce and evaluate a post-processing technique for fast denoising diffusion-weighted MR images. By exploiting the intrinsic redundancy in diffusion MRI using universal properties of the eigenspectrum of random covariance matrices, we remove noise-only principal components, thereby enabling signal-to-noise ratio enhancements, yielding parameter maps of improved quality for visual, quantitative, and statistical interpretation. By studying statistics of residuals, we demonstrate that the technique suppresses local signal fluctuations that solely originate from thermal noise rather than from other sources such as anatomical detail. Furthermore, we achieve improved precision in the estimation of diffusion parameters and fiber orientations in the human brain without compromising the accuracy and/or spatial resolution.
Despite its great potential in studying brain anatomy and structure, diffusion magnetic resonance imaging (dMRI) is marred by artefacts more than any other commonly used MRI technique. In this paper we present a non-parametric framework for detecting and correcting dMRI outliers (signal loss) caused by subject motion. Signal loss (dropout) affecting a whole slice, or a large connected region of a slice, is frequently observed in diffusion weighted images, leading to a set of unusable measurements. This is caused by bulk (subject or physiological) motion during the diffusion encoding part of the imaging sequence. We suggest a method to detect slices affected by signal loss and replace them by a non-parametric prediction, in order to minimise their impact on subsequent analysis. The outlier detection and replacement, as well as correction of other dMRI distortions (susceptibility-induced distortions, eddy currents (EC) and subject motion) are performed within a single framework, allowing the use of an integrated approach for distortion correction. Highly realistic simulations have been used to evaluate the method with respect to its ability to detect outliers (types 1 and 2 errors), the impact of outliers on retrospective correction of movement and distortion and the impact on estiation of commonly used diffusion tensor metrics, such as fractional anisotropy (FA) and mean diffusivity (MD). Data from a large imaging project studying older adults (the Whitehall Imaging sub-study) was used to demonstrate the utility of the method when applied to datasets with severe subject movement. The results indicate high sensitivity and specificity for detecting outliers and that their deleterious effects on FA and MD can be almost completely corrected.
Diffusion-weighted imaging (DWI) is among the most commonly performed type of MR study in the clinic. A more complex variant of DWI is Diffusion Tensor Imaging (DTI), which helps the physician to interrogate tissue with anisotropic (direction-specific) diffusion behavior that may be useful in rendering a diagnosis for a patient. In this chapter we will discuss images for common DTI acquisitions along with their strengths and weaknesses. We will show distorted and artifacted images to demonstrate typical pitfalls in standard DTI, and we will provide suggestions to resolve the artifacts, which are presented in order to accustom the reader to viewing and evaluating diffusion tensor images. To help with this, we will present a checklist to aid troubleshooting and it is intended to be a starting point for the puzzled operator. To aid you in navigating and understanding each section’s main points, you will find a short summary called “To review” which outlines the major take-home messages from that section. In summary, this chapter is intended to help with standard DTI acquisitions, improve and optimize image quality of such exams, and is presented in a way to help ensure the acquisition is robust and reproducible. In the case that artifacts occur, we will show how to best change the scan parameters to avoid and minimize their recurrence.
Fibre tracking is a powerful method for obtaining estimates of global structural connections between brain regions from local measurements of diffusion. By post-processing diffusion weighted MRI data, virtual dissections of white matter fibre bundles can be obtained in vivo. Reconstructed fibre tracts are therefore in no way a direct representation of single axons but only represent an integrative pathway of continuous smoothly curved diffusion orientation information. Prior anatomical knowledge on the trajectory of the bundle of interest is indispensable and can be exploited to define regions of interest (ROIs) for tract delineation. This chapter discusses the data requirements and scanning parameters required for reliable tracking results. It introduces the different methods that are available including deterministic, probabilistic, higher order model, automated and global tractography, and how to use them optimally. Finally, strengths and limitations of connectivity analysis based on tractography-derived measures are discussed. If performed and interpreted correctly, fibre tracking may provide useful complementary information in preclinical research and has potential future utility in routine clinical practice.
There are many approaches for extracting useful visual and quantitative information from diffusion MRI imaging data reconstructed using the diffusion tensor imaging (DTI) method, including whole-brain, regional, and voxel-based approaches. However, the broad range of analysis approaches available and heterogeneous functionality in software tools developed to apply them make analyzing and interpreting DTI data particularly challenging.
This chapter provides an overview of the major DTI analysis techniques, including region-of-interest, tractography, and voxel-based analysis (VBA), as well as their strengths and weaknesses. Additionally, the chapter provides practical guidance on considerations that should be taken into account when choosing how to analyze DTI data, supported by a visual decision scheme and software checklist.
Crossing fibers are increasingly acknowledged to be a significant problem, affecting both tractography and tensor-derived measures of anisotropy. Moreover, typical human scans have been shown to contain a significant proportion of voxels with crossing fibers. Thankfully, there is information in the diffusion-weighted signal that can be used to resolve these crossing fibers. This chapter examines the general biophysical considerations relevant to the crossing fiber problem and describes a number of algorithms that have recently been proposed to estimate fiber orientations. It introduces a classification of these algorithms based on their conceptual framework, along with a brief description of their distinctive features where relevant. DWI acquisition requirements are different for resolving crossing fibers than for diffusion tensor imaging, generally requiring higher b-values and a larger number of directions, depending on the algorithm used. Crossing fibers have a profound impact on scalar measures of white matter “integrity” (e.g.m anisotropy), and make it extremely difficult, if not impossible, to obtain scalar markers of white matter status that are truly independent of crossing fibers.
Purpose:
To estimate the spatially varying noise map using a redundant series of magnitude MR images.
Methods:
We exploit redundancy in non-Gaussian distributed multidirectional diffusion MRI data by identifying its noise-only principal components, based on the theory of noisy covariance matrices. The bulk of principal component analysis eigenvalues, arising due to noise, is described by the universal Marchenko-Pastur distribution, parameterized by the noise level. This allows us to estimate noise level in a local neighborhood based on the singular value decomposition of a matrix combining neighborhood voxels and diffusion directions.
Results:
We present a model-independent local noise mapping method capable of estimating the noise level down to about 1% error. In contrast to current state-of-the-art techniques, the resultant noise maps do not show artifactual anatomical features that often reflect physiological noise, the presence of sharp edges, or a lack of adequate a priori knowledge of the expected form of MR signal.
Conclusions:
Simulations and experiments show that typical diffusion MRI data exhibit sufficient redundancy that enables accurate, precise, and robust estimation of the local noise level by interpreting the principal component analysis eigenspectrum in terms of the Marchenko-Pastur distribution. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.
Diffusion MRI tractography provides a non-invasive modality to examine the human retinofugal projection, which consists of the optic nerves, optic chiasm, optic tracts, the lateral geniculate nuclei (LGN) and the optic radiations. However, the pathway has several anatomic features that make it particularly challenging to study with tractography, including its location near blood vessels and bone-air interface at the base of the cerebrum, crossing fibers at the chiasm, somewhat-tortuous course around the temporal horn via Meyer's Loop, and multiple closely neighboring fiber bundles. To date, these unique complexities of the visual pathway have impeded the development of a robust and automated reconstruction method using tractography. To overcome these challenges, we develop a novel, fully automated system to reconstruct the retinofugal visual pathway from high-resolution diffusion imaging data. Using multi-shell, high angular resolution diffusion imaging (HARDI) data, we reconstruct precise fiber orientation distributions (FODs) with high order spherical harmonics (SPHARM) to resolve fiber crossings, which allows the tractography algorithm to successfully navigate the complicated anatomy surrounding the retinofugal pathway. We also develop automated algorithms for the identification of ROIs used for fiber bundle reconstruction. In particular, we develop a novel approach to extract the LGN region of interest (ROI) based on intrinsic shape analysis of a fiber bundle computed from a seed region at the optic chiasm to a target at the primary visual cortex. By combining automatically identified ROIs and FOD-based tractography, we obtain a fully automated system to compute the main components of the retinofugal pathway, including the optic tract and the optic radiation. We apply our method to the multi-shell HARDI data of 215 subjects from the Human Connectome Project (HCP). Through comparisons with post-mortem dissection measurements, we demonstrate the retinotopic organization of the optic radiation including a successful reconstruction of Meyer's loop. Then, using the reconstructed optic radiation bundle from the HCP cohort, we construct a probabilistic atlas and demonstrate its consistency with a post-mortem atlas. Finally, we generate a shape-based representation of the optic radiation for morphometry analysis.
The effects of inner ear abnormality on audibility have been explored since the early 20th century when sound detection measures were first used to define and quantify 'hearing loss'. The development in the 1970s of objective measures of cochlear hair cell function (cochlear microphonics, otoacoustic emissions, summating potentials) and auditory nerve/brainstem activity (auditory brainstem responses) have made it possible to distinguish both synaptic and auditory nerve disorders from sensory receptor loss. This distinction is critically important when considering aetiology and management. In this review we address the clinical and pathophysiological features of auditory neuropathy that distinguish site(s) of dysfunction. We describe the diagnostic criteria for: (i) presynaptic disorders affecting inner hair cells and ribbon synapses; (ii) postsynaptic disorders affecting unmyelinated auditory nerve dendrites; (iii) postsynaptic disorders affecting auditory ganglion cells and their myelinated axons and dendrites; and (iv) central neural pathway disorders affecting the auditory brainstem. We review data and principles to identify treatment options for affected patients and explore their benefits as a function of site of lesion. © 2015 The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: [email protected]
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The recent advent of diffusion imaging tractography has opened a new window into the in vivo white-matter anatomy of the human brain. This is of particular importance for the connections of the auditory system, which may have undergone substantial development in humans in relation to language. However, tractography of the human auditory pathways has proved to be challenging due to current methodologic limitations and the intrinsic anatomic features of the subcortical connections that carry acoustic information in the brainstem. More reliable findings are forthcoming from tractography studies of corticocortical connections associated with language processing. In this chapter we introduce the reader to basic principles of diffusion imaging and tractography. A selected review of the tractography studies of the auditory pathways will be presented, with particular attention given to the cerebral association pathways of the temporal lobe. Finally, new diffusion methods based on advanced model for mapping fiber crossing will be discussed in the context of the auditory and language networks.
© 2015 Elsevier B.V. All rights reserved.
A cochlear implant (CI) can restore hearing in patients with profound sensorineural hearing loss by direct electrical stimulation of the auditory nerve. Therefore, the viability of the auditory nerve is vitally important in successful hearing recovery. However, the nerve typically degenerates following cochlear hair cell loss, and the amount of degeneration may considerably differ between the two ears, also in patients with bilateral deafness. A measure that reflects the nerve's condition would help to assess the best of both nerves and decide accordingly which ear should be implanted for optimal benefit from a CI. Diffusion tensor MRI (DTI) may provide such a measure, by allowing noninvasive investigations of the nerve's microstructure. In this pilot study, we show the first use of DTI to image the auditory nerve in five normal-hearing subjects and five patients with long-term profound single-sided sensorineural hearing loss. A specialized acquisition protocol was designed for a 3 T MRI scanner to image the small nerve bundle. The nerve was reconstructed using fiber tractography and DTI metrics – which reflect the nerve's microstructural properties – were computed per tract. Comparing DTI metrics from the deaf-sided with the healthy-sided nerves in patients showed no significant differences. There was a small but significant reduction in fractional anisotropy in both auditory nerves in patients compared with normal-hearing controls. These results are the first evidence of possible changes in the microstructure of the bilateral auditory nerves as a result of single-sided deafness. Our results also indicate that it is too early to assess the degenerative status of the auditory nerve of a subject-specific basis.
INTRODUCTION Self-navigated interleaved spirals (SNAILS) (1) have been used for high resolution diffusion weighted imaging (DWI). Although spiral trajectories have many advantages for fast image acquisition, they normally suffer from image blurring caused by off-resonant spins. Many techniques have been developed for off-resonance correction (2). However, few studies have been reported for off resonance correction for multi-shot DWI. One difficulty in this situation originates from the k-space data distortion caused by motion-induced phase errors. Here, we integrate multi-frequency off-resonance correction with SNAILS image reconstruction. Using the proposed technique, off-resonance correction and phase correction are achieved simultaneously for multi-shot DWI. METHOD Phase navigation is crucial for multi-shot DWI. In SNAILS, phase navigation is achieved by oversampling the center of k-space. For each interleaf of a variable-density (VD) spiral (3), a low resolution phase map is estimated and iteratively applied to correct for the phase error (2). To incorporate off-resonance correction, the phase correction iteration needs to be performed at different frequency bands. Given one interleaf of VD spiral, we first grid the raw data onto Cartesian grids. For each k-space sampling points, the corresponding time delay from the beginning of the acquisition is calculated. A Cartesian time map is generated through gridding. The field map is measured at the beginning using two calibration scans. Following the multifrequency reconstruction algorithm (2), a finite set of frequencies are selected to cover the whole range of off-resonant frequencies. For each frequency level, the gridded k-space data is demodulated using the precomputed time map. Following the demodulation step, a phase map is estimated using the center k-space data. This low resolution phase map is then used to correct for the motion-induced phase error in the image domain. The resultant images are then masked using a mask that corresponds to each particular frequency level. Finally, images reconstructed at different frequecy levels are summed together to form the final image. This process can be iterated several times to achieve better phase correction. However, the demodulation steps can be neglected if the field map is not updated. The flow chart is shown in Figure 1. The combined off-resonance and phase correction algorithm was tested using both phantom and in vivo data. The data were acquired on a healthy volunteer with a GE Signa 1.5T whole-body system using the SNAILS sequence (TR = 2.5s and TE = 68ms). The field map was measured in two separate calibration scans at the beginning of the study. RESULTS Figure 2 compares phantom images reconstructed with and without off-resonance correction. Figure 3 shows in vivo results. Fig 3a and b shows the measured field map and the corresponding time map associated with k-space trajectory. Fig 3b and c shows in vivo images both with and without diffusion weighting. Fig 3b shows images without off-resonance correction. Fig 3c shows images after correction. DISCUSSION We have proposed an algorithm for simultaneous off-resonance and phase correction in high resolution DWI. Successful off resonance correction has been demonstrated on both phantom and in vivo images. With successful off-resonance correction, this algorithm allows a reduction of the number of interleaves required (4). Reducing the total number interleaves is important for fast acquisition of high resolution diffusion tensor data, where multiple averages are usually needed for sufficient signal to noise ratio (SNR). Besides sharpening the image, off-resonance correction also enhances image intensity as shown in Fig 3b and c. In particular, great signal improvement appears in areas of strong off-resonance. This is because by demodulating the signal at the correct frequencies, signal cancellation is eliminated.
Constrained spherical deconvolution (CSD) has become one of the most widely used methods to extract white matter (WM) fibre orientation information from diffusion-weighted MRI (DW-MRI) data, overcoming the crossing fibre limitations inherent in the diffusion tensor model. It is routinely used to obtain high quality fibre orientation distribution function (fODF) estimates and fibre tractograms and is increasingly used to obtain apparent fibre density (AFD) measures. Unfortunately, CSD typically only supports data acquired on a single shell in q-space. With multi-shell data becoming more and more prevalent, there is a growing need for CSD to fully support such data. Furthermore, CSD can only provide high quality fODF estimates in voxels containing WM only. In voxels containing other tissue types such as grey matter (GM) and cerebrospinal fluid (CSF), the WM response function may no longer be appropriate and spherical deconvolution produces unreliable, noisy fODF estimates. The aim of this study is to incorporate support for multi-shell data into the CSD approach as well as to exploit the unique b-value dependencies of the different tissue types to estimate a multi-tissue ODF. The resulting approach is dubbed multi-shell, multi-tissue CSD (MSMT-CSD) and is compared to the state-of-the-art single-shell, single-tissue CSD (SSST-CSD) approach. Using both simulations and real data, we show that MSMT-CSD can produce reliable WM/GM/CSF volume fraction maps, directly from the DW data, whereas SSST-CSD has a tendency to overestimate the WM volume in voxels containing GM and/or CSF. In addition, compared to SSST-CSD, MSMT-CSD can substantially increase the precision of the fODF fibre orientations and reduce the presence ofspurious fODF peaks in voxels containing GM and/or CSF. Both effects translate into more reliable AFD measures and tractography results with MSMT-CSD compared to SSST-CSD.
Age-related hearing loss (presbycusis) is caused mainly by the hypofunction of the inner ear, but recent findings point also toward a central component of presbycusis. We used MR morphometry and diffusion tensor imaging (DTI) with a 3 T MR system with the aim to study the state of the central auditory system in a group of elderly subjects (> 65 years) with mild presbycusis, in a group of elderly subjects with expressed presbycusis and in young controls. Cortical reconstruction, volumetric segmentation and auditory pathway tractography were performed. Three parameters were evaluated by morphometry: the volume of the gray matter, the surface area of the gyrus and the thickness of the cortex. In all experimental groups the surface area and gray matter volume were larger on the left side in the Heschl's gyrus and planum temporale and slightly larger in the gyrus frontalis superior, whereas they were larger on the right side in the primary visual cortex. Almost all of the measured parameters were significantly smaller in the elderly subjects in the Heschl's gyrus, planum temporale and gyrus frontalis superior. Aging did not change the side asymmetry (laterality) of the gyri. In the central part of the auditory pathway above the inferior colliculus, a trend towards an effect of aging was present in the axial vector of the diffusion (L1) variable of DTI, with increased values observed in elderly subjects. A trend towards a decrease of L1 on the left side, which was more pronounced in the elderly groups, was observed. The effect of hearing loss was present in subjects with expressed presbycusis as a trend towards an increase of the radial vectors (L2L3) in the white matter under the Heschĺs gyrus. These results suggest that in addition to peripheral changes, changes in the central part of the auditory system in elderly subjects are also present; however, the extent of hearing loss does not play a significant role in the central changes.
High-angular-resolution diffusion-weighted imaging (HARDI) is one of the most common MRI acquisition schemes for use with higher order models of diffusion. However, the optimal b value and number of diffusion-weighted (DW) directions for HARDI are still undetermined, primarily as a result of the large number of available reconstruction methods and corresponding parameters, making it impossible to identify a single criterion by which to assess performance. In this study, we estimate the minimum number of DW directions and optimal b values required for HARDI by focusing on the angular frequency content of the DW signal itself. The spherical harmonic (SH) series provides the spherical analogue of the Fourier series, and can hence be used to examine the angular frequency content of the DW signal. Using high-quality data acquired along 500 directions over a range of b values, we estimate that SH terms above l = 8 are negligible in practice for b values up to 5000 s/mm(2) , implying that a minimum of 45 DW directions is sufficient to fully characterise the DW signal. l > 0 SH terms were found to increase as a function of b value, levelling off at b = 3000 s/mm(2) , suggesting that this value already provides the highest achievable angular resolution. In practice, it is recommended to acquire more than the minimum of 45 DW directions to avoid issues with imperfections in the uniformity of the DW gradient directions and to meet signal-to-noise requirements of the intended reconstruction method. Copyright © 2013 John Wiley & Sons, Ltd.
Object:
Diffusion-based MRI tractography is an imaging tool increasingly used in neurosurgical procedures to generate 3D maps of white matter pathways as an aid to identifying safe margins of resection. The majority of white matter fiber tractography software packages currently available to clinicians rely on a fundamentally flawed framework to generate fiber orientations from diffusion-weighted data, namely diffusion tensor imaging (DTI). This work provides the first extensive and systematic exploration of the practical limitations of DTI-based tractography and investigates whether the higher-order tractography model constrained spherical deconvolution provides a reasonable solution to these problems within a clinically feasible timeframe.
Methods:
Comparison of tractography methodologies in visualizing the corticospinal tracts was made using the diffusion-weighted data sets from 45 healthy controls and 10 patients undergoing presurgical imaging assessment. Tensor-based and constrained spherical deconvolution-based tractography methodologies were applied to both patients and controls.
Results:
Diffusion tensor imaging-based tractography methods (using both deterministic and probabilistic tractography algorithms) substantially underestimated the extent of tracks connecting to the sensorimotor cortex in all participants in the control group. In contrast, the constrained spherical deconvolution tractography method consistently produced the biologically expected fan-shaped configuration of tracks. In the clinical cases, in which tractography was performed to visualize the corticospinal pathways in patients with concomitant risk of neurological deficit following neurosurgical resection, the constrained spherical deconvolution-based and tensor-based tractography methodologies indicated very different apparent safe margins of resection; the constrained spherical deconvolution-based method identified corticospinal tracts extending to the entire sensorimotor cortex, while the tensor-based method only identified a narrow subset of tracts extending medially to the vertex.
Conclusions:
This comprehensive study shows that the most widely used clinical tractography method (diffusion tensor imaging-based tractography) results in systematically unreliable and clinically misleading information. The higher-order tractography model, using the same diffusion-weighted data, clearly demonstrates fiber tracts more accurately, providing improved estimates of safety margins that may be useful in neurosurgical procedures. We therefore need to move beyond the diffusion tensor framework if we are to begin to provide neurosurgeons with biologically reliable tractography information.
Background and purpose:
The auditory radiation crosses other white matter tracts and cannot reliably be delineated or quantitatively assessed with DTI fiber tracking. This study investigates whether HARDI fiber tracking can be used to robustly delineate the full extent of the tract.
Materials and methods:
HARDI (64-direction, b=3000 s/mm²) and DTI (30-direction, b=1000 s/mm²) were acquired from 25 control participants between 8 and 26 years old. Probabilistic HARDI and DTI fiber tracking of the auditory radiation was performed with starting and filter regions automatically generated from the FreeSurfer white matter parcellation. DTI fiber tracking was performed with both the 64-direction and the 30-direction datasets. Fiber-tracking trials demonstrating connectivity from the Heschl gyrus to the medial geniculate nucleus were considered successful.
Results:
The HARDI fiber tracking success rate was 98% and was significantly higher than the 64-direction DTI rate of 50% or the 30-direction DTI rate of 42% (P < .001). The success rates of HARDI fiber tracking for the left and right auditory radiations were not significantly different. In contrast, the left auditory radiation was successfully delineated with DTI fiber tracking at a higher rate than the right auditory radiation.
Conclusions:
HARDI can discriminate the complex white matter pathways at the junction of the auditory radiation and the ILF. HARDI fiber tracking can reliably delineate the auditory radiation.
The aim of the present work was to provide the topography of the main gray nuclei and white matter tracts of the human brainstem at 7 Tesla (7 T) high-field magnetic resonance imaging (MRI) using structural imaging (T1) and diffusion tensor imaging (DTI). Both imaging techniques represent a new field of increasing interest for its potential neuroanatomic and neuropathologic value. Brainstems were obtained postmortem from human donors, fixated by intracarotid perfusion of 10% neutral buffered formalin, and scanned in a Bruker BioSpec 7 T horizontal scanner. 3D-data sets were acquired using the modified driven equilibrium Fourier transform (MDEFT) sequence and Spin Echo-DTI (SE-DTI) sequence was used for DTI acquisition. High-resolution structural MRI and DTI of the human brainstem acquired postmortem reveals its basic cyto- and myeloar-chitectonic organization, only visualized to this moment by histological techniques and higher magnetic field strengths. Brainstem structures that are usually not observed with lower magnetic fields were now topographically identified at midbrain, pons, and medullar levels. The application of high-resolution structural MRI will contribute to precisely determine the extension and topography of brain lesions. Indeed, the current findings will be useful to interpret future high-resolution in vivo MRI studies in living humans. Anat Rec, 2011. © 2011 Wiley-Liss, Inc.
Single auditory-nerve fibers were injected with horseradish peroxidase after their tuning properties, characteristic frequencies, and spontaneous discharge rates were measured. From these functional properties virtually all other aspects of auditory-nerve response can be predicted. Labeled fibers were reconstructed from the point of peripheral termination on cochlear hair cells to the point at which they enter the cochlear nucleus. Several morphological properties were measured at the light-microscopic level, including axonal diameter, axonal length, internodal distances, cell-body area, and cell-body shape. All of these parameters were correlated, though some weakly, with characteristic frequency. However, only axonal diameter was correlated with spontaneous discharge rate.
Brain tissue movements were studied in axial, sagittal and coronal planes in 15 healthy volunteers, using a gated spin echo MRI sequence. All movements had characteristics different from those of perfusion and diffusion. The highest velocities occurred during systole in the basal ganglia (maximum 1.0 mm/s) and brain stem (maximum 1.5 mm/s). The movements were directed caudally, medially and posteriorly in the basal ganglia, and caudally-anteriorly in the pons. Caudad and anterior motion increased towards the foramen magnum and towards the midline. The resultant movement occurred in a funnelshaped fashion as if the brain were pulled by the spinal cord. This may be explained by venting of brain and cerebrospinal fluid (CSF) through the tentorial notch and foramen magnum. The intracranial volume is assumed to be always constant by the Monro-Kellie doctrine. The intracranial dynamics can be viewed as an interplay between the spatial requirements of four main components: arterial blood, capillary blood (brain volume), venous blood and CSF. These components could be characterized, and the expansion of the arteries and the brain differentiated, by applying the Monro-Kellie doctrine to every moment of the cardiac cycle. The arterial expansion causes a remoulding of the brain that enables its piston-like action. The arterial expansion creates the prerequisites for the expansion of the brain by venting CSF to the spinal canal. The expansion of the brain is, in turn, responsible for compression of the ventricular system and hence for the intraventricular flow of CSF.
It has long been recognized that the diffusion tensor model is inappropriate to characterize complex fiber architecture, causing tensor-derived measures such as the primary eigenvector and fractional anisotropy to be unreliable or misleading in these regions. There is however still debate about the impact of this problem in practice. A recent study using a Bayesian automatic relevance detection (ARD) multicompartment model suggested that a third of white matter (WM) voxels contain crossing fibers, a value that, whilst already significant, is likely to be an underestimate. The aim of this study is to provide more robust estimates of the proportion of affected voxels, the number of fiber orientations within each WM voxel, and the impact on tensor-derived analyses, using large, high-quality diffusion-weighted data sets, with reconstruction parameters optimized specifically for this task. Two reconstruction algorithms were used: constrained spherical deconvolution (CSD), and the ARD method used in the previous study. We estimate the proportion of WM voxels containing crossing fibers to be ∼90% (using CSD) and 63% (using ARD). Both these values are much higher than previously reported, strongly suggesting that the diffusion tensor model is inadequate in the vast majority of WM regions. This has serious implications for downstream processing applications that depend on this model, particularly tractography, and the interpretation of anisotropy and radial/axial diffusivity measures. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.
The peripheral manifestations of the inherited neuropathies are increasingly well characterized, but their effects upon cranial nerve function are not well understood. Hearing loss is recognized in a minority of children with this condition, but has not previously been systemically studied. A clear understanding of the prevalence and degree of auditory difficulties in this population is important as hearing impairment can impact upon speech/language development, social interaction ability and educational progress. The aim of this study was to investigate auditory pathway function, speech perception ability and everyday listening and communication in a group of school-aged children with inherited neuropathies. Twenty-six children with Charcot-Marie-Tooth disease confirmed by genetic testing and physical examination participated. Eighteen had demyelinating neuropathies (Charcot-Marie-Tooth type 1) and eight had the axonal form (Charcot-Marie-Tooth type 2). While each subject had normal or near-normal sound detection, individuals in both disease groups showed electrophysiological evidence of auditory neuropathy with delayed or low amplitude auditory brainstem responses. Auditory perception was also affected, with >60% of subjects with Charcot-Marie-Tooth type 1 and >85% of Charcot-Marie-Tooth type 2 suffering impaired processing of auditory temporal (timing) cues and/or abnormal speech understanding in everyday listening conditions.
At its simplest, voxel-based morphometry (VBM) involves a voxel-wise comparison of the local concentration of gray matter between two groups of subjects. The procedure is relatively straightforward and involves spatially normalizing high-resolution images from all the subjects in the study into the same stereotactic space. This is followed by segmenting the gray matter from the spatially normalized images and smoothing the gray-matter segments. Voxel-wise parametric statistical tests which compare the smoothed gray-matter images from the two groups are performed. Corrections for multiple comparisons are made using the theory of Gaussian random fields. This paper describes the steps involved in VBM, with particular emphasis on segmenting gray matter from MR images with nonuniformity artifact. We provide evaluations of the assumptions that underpin the method, including the accuracy of the segmentation and the assumptions made about the statistical distribution of the data.
The functional organization of the main human brainstem centers and circuits are described as revealed in post-mortem material with high-resolution structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) acquired at ultra-high magnetic field 7 T. The description is complemented with a conventional in vivo fiber tracking study of the descending motor pathways. This type of neuroanatomic depiction of nuclei and nerve tracts at very high spatial resolution opens new possibilities to analyze the fine structure and circuits of the human brainstem, at least in post-mortem material.