High Definition Fiber Tracking Research Articles

Examining The Effects Of Mild Traumatic Brain Injury On Brainstem Integrity

Concussion-related brainstem injuries have received little attention in research, yet concussion-related symptoms, e.g. headache and postural instability, share a common neurological origin within the brainstem. As advanced neuroimaging techniques evolve, so do opportunities to better examine the underlying damage in the brainstem and its related white matter (WM) circuitry following an mTBI. PURPOSE: To examine the brainstem integrity in mTBI patients using advanced neuroimaging techniques. METHODS: T1-weighted and diffiusion-weighted MRI scans were performed on 13 mTBI participants within 14 days of their injuries and 3 individuals without history of brain injury. Diffusion images were acquired using a multishell high-definition fiber tracking sequence. The data were reconstructed using generalized q-sampling imaging, then a deterministic fiber tracking algorithm was applied to generate WM tract profiles indicating the quantitative anisotropy (QA) for the bilateral frontal, parietal, and occipital corticopontine tracts (CPT), the corticospinal tracts (CST), the corticoreticular tracts (CRT), and the middle cerebellar peduncle (MCP). Volumes of the midbrain, pons, medulla oblongata, and superior cerebellar peduncle were determined using Freesurfer v6. A two-sample t-test was used to determine between-group differences in the segmented brainstem structures. One-dimensional statistical parametric mapping was performed to compare WM tracts, and Hedge’s g was calculated to determine between-group effect size.RESULTS: QA values for the first 5% (caudal end) of the left CPT-F was significantly lower in the mTBI group (p = .021). Large effect sizes were found when comparing mTBI to control groups for overall tract QA for the right CPT-O and CPT-F, left and right CPT-P, CST, CRT, and MCP (g > 0.8), with the largest effect for the left CPT-F tract (g = 1.64). There were no significant differences between groups in the segmented brainstem volumes. CONCLUSION: Lower QA values in the caudal portion of the CPT-F indicate that WM near the brainstem may be susceptible to mTBI-related change despite a lack of effect on brainstem volume. Further research should investigate the brainstem after mTBI. Supported by NIH Grant R21 12973518

The ansa peduncularis in the human brain: A tractography and fiber dissection study

IntroductionThe ansa peduncularis is a composite of white matter fiber bundles closely packed together that sweeps around the cerebral peduncle. The exact components of the ansa peduncularis and their anatomical trajectories are still not established firmly in the literature. ObjectiveThe aim of this study was to examine the topographical anatomy of the ansa peduncularis and its subcomponents using the fiber dissection and tractography techniques. MethodsTen formalin-fixed brains were prepared according to Klingler’s method and dissected by the fiber dissection technique from the lateral, medial and inferior surfaces. The ansa peduncularis was also traced using high definition fiber tracking (HDFT) from the MRI data of twenty healthy adults and a 1021-subject template from the Human Connectome Project. ResultsThe ventral amygdalofugal pathway system includes white matter fiber bundles with a topographically close relation as they sweep around the cerebral peduncle and contribute to form the ansa peduncularis: amygdaloseptal fibers connect the amygdala and anterior temporal cortex to the septal region and amygdalohypothalamic fibers project from the amygdala to the hypothalamus. Additionally, from the amygdala and anterior temporal cortex, amygdalothalamic fibers project to the medial thalamic region. The ansa lenticularis, which connects the globus pallidus to the thalamus, was not shown in our study. ConclusionThe study demonstrated the trajectory of the ansa peduncularis and its subcomponents, based on fiber dissection and tractography, improving our understanding of human brain anatomical connectivity.

Endoscopic endonasal approach for brainstem cavernous malformation.

This 25-year-old woman presented after a second hemorrhage from a mesencephalic cavernous malformation. High-definition fiber tracking demonstrated lateral displacement of the corticospinal tracts, making a midline approach ideal. The lesion appeared to present to the third ventricle, but a transcallosal approach was abandoned due to the posterior third ventricular location and after FIESTA imaging revealed a superior and medial rim of normal parenchyma that would have to be transgressed to access the malformation. An endoscopic endonasal approach with interdural pituitary hemitransposition was performed. The interpeduncular cistern was accessed and the thalamoperforating arteries dissected to access the cavernous malformation that was completely removed in a piecemeal fashion. The patient’s preexisting internuclear ocular palsies and hemiparesis were slightly worsened after surgery as predicted by a drop in anterior tibialis motor evoked potentials. Postoperative MRI showed no infarct, and the hemiparesis was back to baseline at 1-month follow-up.The video can be found here: https://youtu.be/e6203R9HHmk.

A Preliminary High-Definition Fiber Tracking Study of the Executive Control Network in Blast-Induced Traumatic Brain Injury.

Blast-induced traumatic brain injury (bTBI) is common in veterans of the Iraq- and Afghanistan-era conflicts. However, the typical subtlety of neural alterations and absence of definitive biomarkers impede clinical detection on conventional imaging. This preliminary study examined the structure and functional correlates of executive control network (ECN) white matter in veterans to investigate the clinical utility of using high-definition fiber tracking (HDFT) to detect chronic bTBI. Demographically similar male veterans (N = 38) with and without bTBI (ages 24 to 50 years) completed standardized neuropsychological testing and magnetic resonance imaging. Quantitative HDFT metrics of subcortical-dorsolateral prefrontal cortex (DLPFC) tracts were derived. Moderate-to-large group effects were observed on HDFT metrics. Relative to comparisons, bTBI demonstrated elevated quantitative anisotropy (QA) and reduced right hemisphere volume of all examined tracts, and reduced fiber count and increased generalized fractional anisotropy in the right DLPFC-putamen tract and DLPFC-thalamus, respectively. The Group × Age interaction effect on DLPFC-caudate tract volume was large; age negatively related to volume in the bTBI group, but not comparison group. Groups performed similarly on the response inhibition measure. Performance (reaction time and commission errors) robustly correlated with HDFT tract metrics (QA and tract volume) in the comparison group, but not bTBI group. Results support anomalous density and integrity of ECN connectivity, particularly of the right DLPFC-putamen pathway, in bTBI. Results also support exacerbated aging in veterans with bTBI. Similar ECN function despite anomalous microstructure could reflect functional compensation in bTBI, although alternate interpretations are explored.

Segmentation of the Cingulum Bundle in the Human Brain: A New Perspective Based on DSI Tractography and Fiber Dissection Study.

The cingulum bundle (CB) is a critical white matter fiber tract in the brain, which forms connections between the frontal lobe, parietal lobe and temporal lobe. In non-human primates, the CB is actually divided into distinct subcomponents on the basis of corticocortical connections. However, at present, no study has verified similar distinct subdivisions in the human brain. In this study, we reconstructed these distinct subdivisions in the human brain, and determined their exact cortical connections using high definition fiber tracking (HDFT) technique on 10 healthy adults and a 488-subject template from the Human Connectome Project (HCP-488). Fiber dissections were performed to verify tractography results. Five CB segments were identified. CB-I ran from the subrostral areas to the precuneus and splenium, encircling the corpus callosum (CC). CB-II arched around the splenium and extended anteriorly above the CC to the medial aspect of the superior frontal gyrus (SFG). CB-III connected the superior parietal lobule (SPL) and precuneus with the medial aspect of the SFG. CB-IV was a relatively minor subcomponent from the SPL and precuneus to the frontal region. CB-V, the para-hippocampal cingulum, stemmed from the medial temporal lobe and fanned out to the occipital lobes. Our findings not only provide a more accurate and detailed description on the associated architecture of the subcomponents within the CB, but also offer new insights into the functional role of the CB in the human brain.

What's New in Traumatic Brain Injury: Update on Tracking, Monitoring and Treatment.

Traumatic brain injury (TBI), defined as an alteration in brain functions caused by an external force, is responsible for high morbidity and mortality around the world. It is important to identify and treat TBI victims as early as possible. Tracking and monitoring TBI with neuroimaging technologies, including functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), positron emission tomography (PET), and high definition fiber tracking (HDFT) show increasing sensitivity and specificity. Classical electrophysiological monitoring, together with newly established brain-on-chip, cerebral microdialysis techniques, both benefit TBI. First generation molecular biomarkers, based on genomic and proteomic changes following TBI, have proven effective and economical. It is conceivable that TBI-specific biomarkers will be developed with the combination of systems biology and bioinformation strategies. Advances in treatment of TBI include stem cell-based and nanotechnology-based therapy, physical and pharmaceutical interventions and also new use in TBI for approved drugs which all present favorable promise in preventing and reversing TBI.

An exploratory analysis linking neuropsychological testing to quantification of tractography using High Definition Fiber Tracking (HDFT) in military TBI.

To realize the potential value of tractography in traumatic brain injury (TBI), we must identify metrics that provide meaningful information about functional outcomes. The current study explores quantitative metrics describing the spatial properties of tractography from advanced diffusion imaging (High Definition Fiber Tracking, HDFT). In a small number of right-handed males from military TBI (N = 7) and civilian control (N = 6) samples, both tract homologue symmetry and tract spread (proportion of brain mask voxels contacted) differed for several tracts among civilian controls and extreme groups in the TBI sample (high scorers and low scorers) for verbal recall, serial reaction time, processing speed index, and trail-making. Notably, proportion of voxels contacted in the arcuate fasciculus distinguished high and low performers on the CVLT-II and PSI, potentially reflecting linguistic task demands, and GFA in the left corticospinal tract distinguished high and low performers in PSI and Trail Making Test Part A, potentially reflecting right hand motor response demands. The results suggest that, for advanced diffusion imaging, spatial properties of tractography may add analytic value to measures of tract anisotropy.

Quantifying white matter structural integrity with high-definition fiber tracking in traumatic brain injury.

There is an urgent, unmet demand for definitive biological diagnosis of traumatic brain injury (TBI) to pinpoint the location and extent of damage. We have developed High-Definition Fiber Tracking, a 3 T magnetic resonance imaging-based diffusion spectrum imaging and tractography analysis protocol, to quantify axonal injury in military and civilian TBI patients. A novel analytical methodology quantified white matter integrity in patients with TBI and healthy controls. Forty-one subjects (23 TBI, 18 controls) were scanned with the High-Definition Fiber Tracking diffusion spectrum imaging protocol. After reconstruction, segmentation was used to isolate bilateral hemisphere homologues of eight major tracts. Integrity of segmented tracts was estimated by calculating homologue correlation and tract coverage. Both groups showed high correlations for all tracts. TBI patients showed reduced homologue correlation and tract spread and increased outlier count (correlations>2.32 SD below control mean). On average, 6.5% of tracts in the TBI group were outliers with substantial variability among patients. Number and summed deviation of outlying tracts correlated with initial Glasgow Coma Scale score and 6-month Glasgow Outcome Scale-Extended score. The correlation metric used here can detect heterogeneous damage affecting a low proportion of tracts, presenting a potential mechanism for advancing TBI diagnosis.

A high-definition fiber tracking report for patients with traumatic brain injury and their doctors.

We have developed a tablet-based application, the High-Definition Fiber Tracking Report App, to enable clinicians and patients in research studies to see and understand damage from Traumatic Brain Injury (TBI) by viewing 2-dimensional and 3-dimensional images of their brain, with a focus on white matter tracts with quantitative metrics. The goal is to visualize white matter fiber tract injury like bone fractures; that is, to make the "invisible wounds of TBI" understandable for patients. Using mobile computing technology (iPad), imaging data for individual patients can be downloaded remotely within hours of a magnetic resonance imaging brain scan. Clinicians and patients can view the data in the form of images of each tract, rotating animations of the tracts, 3-dimensional models, and graphics. A growing number of tracts can be examined for asymmetry, gaps in streamline coverage, reduced arborization (branching), streamline volume, and standard quantitative metrics (e.g., Fractional Anisotropy (FA)). Novice users can learn to effectively navigate and interact with the application (explain the figures and graphs representing normal and injured brain tracts) within 15 minutes of simple orientation with high accuracy (96%). The architecture supports extensive graphics, configurable reports, provides an easy-to-use, attractive interface with a smooth user experience, and allows for securely serving cases from a database. Patients and clinicians have described the application as providing dramatic benefits in understanding their TBI and improving their lives.

Detection of white matter injury in concussion using high-definition fiber tractography.

Over the last few decades, structural imaging techniques of the human brain have undergone significant strides. High resolution provided by recent developments in magnetic resonance imaging (MRI) allows improved detection of injured regions in patients with moderate-to-severe traumatic brain injury (TBI). In addition, diffusion imaging techniques such as diffusion tensor imaging (DTI) has gained much interest recently due to its possible utility in detecting structural integrity of white matter pathways in mild TBI (mTBI) cases. However, the results from recent DTI studies in mTBI patients remain equivocal. Also, there are important shortcomings for DTI such as limited resolution in areas of multiple crossings and false tract formation. The detection of white matter damage in concussion remains challenging, and development of imaging biomarkers for mTBI is still in great need. In this chapter, we discuss our experience with high-definition fiber tracking (HDFT), a diffusion spectrum imaging-based technique. We also discuss ongoing developments and specific advantages HDFT may offer concussion patients.

Editorial: Seizure surgery

For years, surgeons and neurologists have debated the value of standard temporal lobe resections (mostly performed before 1996) compared with selective amygdalohippocampectomy (performed after 1995) in the management of temporal lobe epilepsy. This debate has raged due to comparisons on seizure outcome; morbidity; language; and cognitive, visual, and behavioral results. In this report, the authors compare a well-matched, noncontemporaneous cohort of patients with mesial temporal sclerosis who underwent surgery.1 The average length of follow-up after standard temporal lobectomy was almost 10 years and for selective surgery, almost 7 years. When a favorable outcome was defined as Engel Class I or II, there was no difference in epilepsy control. In addition, the authors found no difference in cognitive or psychological outcomes for the two resection strategies. Selective surgery was associated with more seizures while patients were reducing medication; the authors raised the issue that this could affect quality of life. They also theorized that selective surgery might be a better choice in patients with more severe preexisting psychiatric illness. Whether or not the findings of increased paranoia after temporal lobectomy would be validated in a larger patient series remains to be seen. One limitation of the study is that psychiatric outcomes were only available in a subset of the population, which was related to differences in the treating neuropsychologist. Clearly this represents a limitation of retrospective reviews for which a specific protocol for patient evaluation was not in place. Indeed, in a noncontemporaneous study one can always question the importance of experience gained over time, both in terms of patient selection and surgical technique. There have been numerous articles that compared the value of standard temporal lobectomy to more selective resections. It seems that in skilled hands, one approach may not have clear advantages over the other but one may be more appropriate for individual patients. Important questions beyond the scope of this research remain. Why do not more patients undergo epilepsy surgery, given its proven value in properly selected candidates? Will new imaging techniques such as high-definition fiber tracking show that preserved or resected limbic pathways make a difference in outcome? Will selective surgery be redefined further based on that knowledge? (http://thejns.org/doi/abs/10.3171/2013.1.JNS121886) Disclosure

Evidence for dysregulation of axonal growth and guidance in the etiology of ASD

Current theories concerning the cause of autism spectrum disorders (ASDs) have converged on the concept of abnormal development of brain connectivity. This concept is supported by accumulating evidence from functional imaging, diffusion tensor imaging, and high definition fiber tracking studies which suggest altered microstructure in the axonal tracts connecting cortical areas may underly many of the cognitive manifestations of ASD. Additionally, large-scale genomic studies implicate numerous gene candidates known or suspected to mediate neuritic outgrowth and axonal guidance in fetal and perinatal life. Neuropathological observations in postmortem ASD brain samples further support this model and include subtle disturbances of cortical lamination and subcortical axonal morphology. Of note is the relatively common finding of poor differentiation of the gray–white junction associated with an excess superficial white matter or “interstitial” neurons (INs). INs are thought to be remnants of the fetal subplate, a transient structure which plays a key role in the guidance and morphogenesis of thalamocortical and cortico-cortical connections and the organization of cortical columnar architecture. While not discounting the importance of synaptic dysfunction in the etiology of ASD, this paper will briefly review the cortical abnormalities and genetic evidence supporting a model of dysregulated axonal growth and guidance as key developmental processes underlying the clinical manifestations of ASD.

High-Definition Fiber Tractography of the Human Brain

High-definition fiber tracking (HDFT) is a novel combination of processing, reconstruction, and tractography methods that can track white matter fibers from cortex, through complex fiber crossings, to cortical and subcortical targets with subvoxel resolution. To perform neuroanatomical validation of HDFT and to investigate its neurosurgical applications. Six neurologically healthy adults and 36 patients with brain lesions were studied. Diffusion spectrum imaging data were reconstructed with a Generalized Q-Ball Imaging approach. Fiber dissection studies were performed in 20 human brains, and selected dissection results were compared with tractography. HDFT provides accurate replication of known neuroanatomical features such as the gyral and sulcal folding patterns, the characteristic shape of the claustrum, the segmentation of the thalamic nuclei, the decussation of the superior cerebellar peduncle, the multiple fiber crossing at the centrum semiovale, the complex angulation of the optic radiations, the terminal arborization of the arcuate tract, and the cortical segmentation of the dorsal Broca area. From a clinical perspective, we show that HDFT provides accurate structural connectivity studies in patients with intracerebral lesions, allowing qualitative and quantitative white matter damage assessment, aiding in understanding lesional patterns of white matter structural injury, and facilitating innovative neurosurgical applications. High-grade gliomas produce significant disruption of fibers, and low-grade gliomas cause fiber displacement. Cavernomas cause both displacement and disruption of fibers. Our HDFT approach provides an accurate reconstruction of white matter fiber tracts with unprecedented detail in both the normal and pathological human brain. Further studies to validate the clinical findings are needed.

High-definition fiber tracking for assessment of neurological deficit in a case of traumatic brain injury: finding, visualizing, and interpreting small sites of damage

For patients with traumatic brain injury (TBI), current clinical imaging methods generally do not provide highly detailed information about the location of axonal injury, severity of injury, or expected recovery. In a case of severe TBI, the authors applied a novel high-definition fiber tracking (HDFT) to directly visualize and quantify the degree of axonal fiber damage and predict functional deficits due to traumatic axonal injury and loss of cortical projections. This 32-year-old man sustained a severe TBI. Computed tomography and MRI revealed an area of hemorrhage in the basal ganglia with mass effect, but no specific information on the location of axonal injury could be obtained from these studies. Examinations of the patient at Week 3 and Week 8 after TBI revealed motor weaknesses of the left extremities. Four months postinjury, 257-direction diffusion spectrum imaging and HDFT analysis was performed to evaluate the degree of axonal damage in the motor pathway and quantify asymmetries in the left and right axonal pathways. High-definition fiber tracking was used to follow corticospinal and corona radiata pathways from the cortical surface to the midbrain and quantify projections from motor areas. Axonal damage was then localized by assessing the number of descending fibers at the level of the cortex, internal capsule, and midbrain. The motor deficit apparent in the clinical examinations correlated with the axonal losses visualized using HDFT. Fiber loss estimates at 4 months postinjury accurately predicted the nature of the motor deficits (severe, focal left-hand weakness) when other standard clinical imaging modalities did not. A repeat scan at 10 months postinjury, when edema and hemorrhage had receded, replicated the fiber loss. Using HDFT, the authors accurately identified the presence and location of damage to the underlying white matter in this patient with TBI. Detailed information of injury provided by this novel technique holds future potential for precise neuroimaging assessment of TBI.

Structural connectivity of face selective cortical regions with high definition fiber tracking

Structural connectivity of face selective cortical regions with high definition fiber tracking

In Vivo Mapping of Microstructural Somatotopies in the Human Corticospinal Pathways

The human corticospinal pathway is organized in a body-centric (i.e., somatotopic) manner that begins in cortical cell bodies and is maintained in the axons as they project through the midbrain on their way to spinal motor neurons. The subcortical segment of this somatotopy has been described using histological methods on non-human primates but only coarsely validated from lesion studies in human patient populations. Using high definition fiber tracking (HDFT) techniques, we set out to provide the first in vivo quantitative description of the midbrain somatotopy of corticospinal fibers in humans. Multi-shell diffusion imaging and deterministic fiber tracking were used to map white matter bundles that originate in the neocortex, navigate complex fiber crossings, and project through the midbrain. These fiber bundles were segmented into premotor (dorsal premotor, ventral premotor, and supplementary motor area) and primary motor sections based on the cortical origin of each fiber streamline. With HDFT, we were able to reveal several unique corticospinal patterns, including the cortical origins of ventral premotor fibers and small (∼ 1-2 mm) shifts in the midbrain location of premotor versus primary motor cortex fibers. More importantly, within the relatively small diameter of the pyramidal tracts (∼ 5 mm), we were able to map and quantify the direction of the corticospinal somatotopy. These results show how an HDFT approach to white matter mapping provides the first in vivo, quantitative mapping of subcortical corticospinal topographies at resolutions previously only available with postmortem histological techniques.

High-definition fiber tracking guidance for intraparenchymal endoscopic port surgery

The authors have applied high-definition fiber tracking (HDFT) to the resection of an intraparenchymal dermoid cyst by using a minimally invasive endoscopic port. The lesion was located within the mesial frontal lobe, septal area, hypothalamus, and suprasellar recess. Using high-dimensional (256 directions) diffusion imaging, more than 250,000 fiber tracts were imaged before and after surgery. Trajectory planning using HDFT in a computer model was used to facilitate cannulation of the cyst with the endoscopic port. Analysis of the proposed initial surgical route was overlaid onto the fiber tracts and was predicted to produce substantial disruption to prefrontal projection fibers (anterior limb of the internal capsule) and the cingulum. Adjustment of the cannulation entry point 1 cm medially was predicted to cross the corpus callosum instead of the anterior limb of the internal capsule or the cingulum. Following cyst resection performed using endoscopic port surgery, postoperative imaging demonstrated accurate cannulation of the lesion, with improved quantitative signal from both the anterior limb of the internal capsule and the cingulum. The observed fiber preservation from the cingulum and the anterior limb of the internal capsule, with minor injury to the corpus callosum, was in close agreement with preoperative trajectory modeling. Comparison of pre- and postoperative HDFT data facilitated quantification of the benefits and costs of the surgical trajectory. Future studies will help to determine whether HDFT combined with endoscopic port surgery facilitates anatomical and functional preservation in such challenging cases.