Sudhir Pathak

High-definition fiber tractography of the human brain: neuroanatomical validation and neurosurgical applications.

BACKGROUND 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. OBJECTIVE To perform neuroanatomical validation of HDFT and to investigate its neurosurgical applications. METHODS 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. RESULTS 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. CONCLUSION 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.

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.

Asymmetry, connectivity, and segmentation of the arcuate fascicle in the human brain

The structure and function of the arcuate fascicle is still controversial. The goal of this study was to investigate the asymmetry, connectivity, and segmentation patterns of the arcuate fascicle. We employed diffusion spectrum imaging reconstructed by generalized q-sampling and we applied both a subject-specific approach (10 subjects) and a template approach (q-space diffeomorphic reconstruction of 30 subjects). We complemented our imaging investigation with fiber microdissection of five post-mortem human brains. Our results confirmed the highly leftward asymmetry of the arcuate fascicle. In the template, the left arcuate had a volume twice as large as the right one, and the left superior temporal gyrus provided five times more volume of fibers than its counterpart. We identified four cortical frontal areas of termination: pars opercularis, pars triangularis, ventral precentral gyrus, and caudal middle frontal gyrus. We found clear asymmetry of the frontal terminations at pars opercularis and ventral precentral gyrus. The analysis of patterns of connectivity revealed the existence of a strong structural segmentation in the left arcuate, but not in the right one. The left arcuate fascicle is formed by an inner or ventral pathway, which interconnects pars opercularis with superior and rostral middle temporal gyri; and an outer or dorsal pathway, which interconnects ventral precentral and caudal middle frontal gyri with caudal middle and inferior temporal gyri. The fiber microdissection results provided further support to our tractography studies. We propose the existence of primary and supplementary language pathways within the dominant arcuate fascicle with potentially distinct functional and lesional features.

Advanced diffusion MRI fiber tracking in neurosurgical and neurodegenerative disorders and neuroanatomical studies: A review

Diffusion MRI enabled in vivo microstructural imaging of the fiber tracts in the brain resulting in its application in a wide range of settings, including in neurological and neurosurgical disorders. Conventional approaches such as diffusion tensor imaging (DTI) have been shown to have limited applications due to the crossing fiber problem and the susceptibility of their quantitative indices to partial volume effects. To overcome these limitations, the recent focus has shifted to the advanced acquisition methods and their related analytical approaches. Advanced white matter imaging techniques provide superior qualitative data in terms of demonstration of multiple crossing fibers in their spatial orientation in a three dimensional manner in the brain. In this review paper, we discuss the advancements in diffusion MRI and introduce their roles. Using examples, we demonstrate the role of advanced diffusion MRI-based fiber tracking in neuroanatomical studies. Results from its preliminary application in the evaluation of intracranial space occupying lesions, including with respect to future directions for prognostication, are also presented. Building upon the previous DTI studies assessing white matter disease in Huntingtons disease and Amyotrophic lateral sclerosis; we also discuss approaches which have led to encouraging preliminary results towards developing an imaging biomarker for these conditions.

Subcomponents and connectivity of the superior longitudinal fasciculus in the human brain.

The subcomponents of the human superior longitudinal fasciculus (SLF) are disputed. The objective of this study was to investigate the segments, connectivity and asymmetry of the SLF. We performed high angular diffusion spectrum imaging (DSI) analysis on ten healthy adults. We also conducted fiber tracking on a 30-subject DSI template (CMU-30) and 488-subject template from the Human Connectome Project (HCP-488). In addition, five normal brains obtained at autopsy were microdissected. Based on tractography and microdissection results, we show that the human SLF differs significantly from that of monkey. The fibers corresponding to SLF-I found in 6 out of 20 hemispheres proved to be part of the cingulum fiber system in all cases and confirmed on both DSI and HCP-488 template. The most common patterns of connectivity bilaterally were as follows: from angular gyrus to caudal middle frontal gyrus and dorsal precentral gyrus representing SLF-II (or dorsal SLF), and from supramarginal gyrus to ventral precentral gyrus and pars opercularis to form SLF-III (or ventral SLF). Some connectivity features were, however, clearly asymmetric. Thus, we identified a strong asymmetry of the dorsal SLF (SLF-II), where the connectivity between the supramarginal gyrus with the dorsal precentral gyrus and the caudal middle frontal gyrus was only present in the left hemisphere. Contrarily, the ventral SLF (SLF-III) showed fairly constant connectivity with pars triangularis only in the right hemisphere. The results provide a novel neuroanatomy of the SLF that may help to better understand its functional role in the human brain.

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.

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.

Visualization of Cranial Nerves Using High-Definition Fiber Tractography.

BACKGROUND Recent studies have demonstrated diffusion tensor imaging tractography of cranial nerves (CNs). Spatial and angular resolution, however, is limited with this modality. A substantial improvement in image resolution can be achieved with high-angle diffusion magnetic resonance imaging and atlas-based fiber tracking to provide detailed trajectories of CNs. OBJECTIVE To use high-definition fiber tractography to identify CNs in healthy subjects and patients with brain tumors. METHODS Five neurologically healthy adults and 3 patients with brain tumors were scanned with diffusion spectrum imaging that allowed high-angular-resolution fiber tracking. In addition, a 488-subject diffusion magnetic resonance imaging template constructed from the Human Connectome Project data was used to conduct atlas space fiber tracking of CNs. RESULTS The cisternal portions of most CNs were tracked and visualized in each healthy subject and in atlas fiber tracking. The entire optic radiation, medial longitudinal fasciculus, spinal trigeminal nucleus/tract, petroclival portion of the abducens nerve, and intrabrainstem portion of the facial nerve from the root exit zone to the adjacent abducens nucleus were identified. This suggested that the high-angular-resolution fiber tracking was able to distinguish the facial nerve from the vestibulocochlear nerve complex. The tractography clearly visualized CNs displaced by brain tumors. These tractography findings were confirmed intraoperatively. CONCLUSION Using high-angular-resolution fiber tracking and atlas-based fiber tracking, we were able to identify all CNs in unprecedented detail. This implies its potential in localization of CNs during surgical planning. ABBREVIATIONS CN, cranial nerveDSI, diffusion spectrum imagingDTI, diffusion tensor imagingHCP, Human Connectome ProjectHDFT, high-definition fiber tractographyMLF, medial longitudinal fasciculusODF, orientation distribution functionROI, region of interest.

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.

Application of high-definition fiber tractography in the management of supratentorial cavernous malformations: a combined qualitative and quantitative approach.

BACKGROUND High-definition fiber tractography (HDFT), an advanced white matter (WM) imaging technique, was evaluated in the management of supratentorial cavernous malformations. OBJECTIVE To investigate the relationship of cavernous malformations to the relevant perilesional WM tracts with HDFT and to characterize associated changes first qualitatively and then quantitatively with our novel imaging measure, quantitative anisotropy (QA). METHODS Imaging analysis was carried out by researchers blinded to the clinical details. Contralateral WM tracts were used for comparison. Mean QA values were obtained for whole WM tracts. Qualitatively affected superior longitudinal fasciculus/arcuate fibers and corticospinal tracts were further analyzed with the use of mean QA values for the perilesional segments. RESULTS Of 10 patients, HDFT assisted with the decision-making process and the offer of surgical resection in 2 patients, lesion approach and removal in 7 patients, and conservative management in 1 patient. Of 17 analyzed WM tracts, HDFT demonstrated partial disruption in 2 tracts, complete disruption in 2 tracts, a combination of displacement and partial disruption in 1 tract, displacement only in 7 tracts, and no change in 5 tracts. Qualitative changes correlated with clinical symptoms. Mean QA values for the whole WM tracts were similar, with the exception of 1 case demonstrating complete disruption of 2 WM tracts. QA-based perilesional segment analysis was consistent with qualitative data in 5 assessed WM tracts. CONCLUSION HDFT illustrated the precise spatial relationship of cavernous malformations to multiple WM tracts in a 3-dimensional fashion, optimizing surgical planning, and demonstrated associated disruption and/or displacement, with both occurring perilesionally. These changes were supported by our quantitative marker, which needs further validation.