CONCEPTS, INNOVATIONS, AND TECHNIQUES TOPIC CONCEPTS, INNOVATIONS, AND TECHNIQUES High-Definition Fiber Tractography of the Human Brain: Neuroanatomical Validation and Neurosurgical Applications Juan C. Fernandez-Miranda, MD* BACKGROUND: High-definition fiber tracking (HDFT) is a novel combination of pro- Sudhir Pathak, MS, MSc‡ cessing, reconstruction, and tractography methods that can track white matter fibers Johnathan Engh, MD* from cortex, through complex fiber crossings, to cortical and subcortical targets with subvoxel resolution. Kevin Jarbo, BS‡ OBJECTIVE: To perform neuroanatomical validation of HDFT and to investigate its ‡ Timothy Verstynen, PhD neurosurgical applications. Fang-Cheng Yeh, MD, PhD§ METHODS: Six neurologically healthy adults and 36 patients with brain lesions were Yibao Wang, MD* studied. Diffusion spectrum imaging data were reconstructed with a Generalized Q-Ball Arlan Mintz, MD* Imaging approach. Fiber dissection studies were performed in 20 human brains, and Fernando Boada, MD, PhDk selected dissection results were compared with tractography. RESULTS: HDFT provides accurate replication of known neuroanatomical features such Walter Schneider, PhD*‡ as the gyral and sulcal folding patterns, the characteristic shape of the claustrum, the Robert Friedlander, MD* segmentation of the thalamic nuclei, the decussation of the superior cerebellar *Department of Neurological Surgery peduncle, the multiple fiber crossing at the centrum semiovale, the complex angulation and kMagnetic Resonance Research Cen- of the optic radiations, the terminal arborization of the arcuate tract, and the cortical ter, Department of Radiology, University segmentation of the dorsal Broca area. From a clinical perspective, we show that HDFT of Pittsburgh School of Medicine, Uni- versity of Pittsburgh Medical Center, provides accurate structural connectivity studies in patients with intracerebral lesions, Pittsburgh, Pennsylvania; ‡Learning and allowing qualitative and quantitative white matter damage assessment, aiding in Research Development Center, Depart- understanding lesional patterns of white matter structural injury, and facilitating ment of Psychology, University of Pitts- burgh, Pittsburgh, Pennsylvania; §Carnegie innovative neurosurgical applications. High-grade gliomas produce significant disrup- Mellon University, Department of Biomed- tion of fibers, and low-grade gliomas cause fiber displacement. Cavernomas cause both ical Engineering, Pittsburgh, Pennsylvania displacement and disruption of fibers. CONCLUSION: Our HDFT approach provides an accurate reconstruction of white Correspondence: Juan C. Fernandez-Miranda, MD, matter fiber tracts with unprecedented detail in both the normal and pathological Department of Neurological Surgery, human brain. Further studies to validate the clinical findings are needed. University of Pittsburgh School of Medicine, University of Pittsburgh KEY WORDS: Cavernoma, DTI, Fiber tracking, Glioma, Human connectome, White matter Medical Center, 200 Lothrop St, PUH B-400, Neurosurgery 71:430–453, 2012 DOI: 10.1227/NEU.0b013e3182592faa www.neurosurgery-online.com Pittsburgh PA 15213. E-mail: [email protected] early 2 decades ago, Crick and Jones1 noninvasively map fiber tracts in the living Received, August 20, 2011. wrote that “to interpret the activity of human brain facilitated numerous applications Accepted, March 7, 2012. N in the diagnosis and treatment of brain disorders. Published Online, April 17, 2012. living human brains, their neuroanat- omy must be known in detail. New techniques The National Institute of Health Blueprint for Copyright ª 2012 by the to do this are urgently needed, since most of the Neuroscience Research stated that the Human Congress of Neurological Surgeons methods now used on monkeys cannot be used Connectome Project is one of the great scientific on humans.” The introduction of diffusion challenges for the upcoming decade and has tensor imaging (DTI) a decade ago represented made a major investment in brain connection a major step toward this goal.2,3 The ability to mapping.4 Several authors have demonstrated that DTI tractography provides accurate reconstruction of ABBREVIATIONS: DSI, diffusion spectrum imaging; the major stem of white matter tracts, in DTI, diffusion tensor imaging; HDFT, high-definition fiber tractography agreement with classic and contemporary neuro- anatomical studies.5,6 Consequently, DTI has 430 | VOLUME 71 | NUMBER 2 | AUGUST 2012 www.neurosurgery-online.com Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited. HIGH-DEFINITION FIBER TRACTOGRAPHY and surrounding edema, significantly decreasing the accuracy of 6,20 TABLE 1. List of Neurosurgical Cases Studied With High-Definition the technique in the clinical setting. Fiber Tractography New fiber mapping techniques such as high-angular-resolution Type of Cases n (n = 36) diffusion imaging and diffusion spectrum imaging (DSI) have been developed to solve the limitations of DTI. High-angular- High-grade gliomas 16 resolution diffusion imaging has better angular resolution and Low-grade gliomas 7 21 Cavernomas 5 smaller voxels. DSI measures diffusion spectra, thus enabling Miscellaneous resolution of intravoxel heterogeneity of diffusion and resolves Metastasis 2 not the average direction, such as in DTI, but a set of directions Meningiomas 2 of multiple pathways within the voxel.22 These are important Dermoid cyst 2 improvements that partially solve previous limitations and show Colloid cyst 2 qualitative matches to a few expected neuroanatomy features in primates23 and humans.18 Schmahmann et al23 compared DSI with radiographic techniques and stated that the techniques were in good agreement, specifically, “By replicating the major features been incorporated into the diagnostic neurosurgical armamen- of these tracts identified by histological techniques in monkey, we tarium, allowing for the first time the study of the spatial show that DSI has the potential to cast new light on the relationship of intracerebral lesions within the white matter tracts. organization of the human brain in the normal state and in Several authors have reported the utility of this technique for clinical disorders.” preoperative and even intraoperative localization of the pyramidal For the last 3 years, we have been applying high-angular- tract,7-11 primary motor area,12 optic radiations,13 and language resolution diffusion imaging and DSI techniques to the study of pathways.14,15 DTI may improve preservation of eloquent structural brain connectivity in normal subjects and patients with regions during surgery by providing access to direct connectivity brain lesions. The strengths and limitations of these techniques information between functional regions of the brain, and it has were identified.24 In an attempt to more effectively solve the progressively been incorporated into strategic planning for crossing and termination problems, we have focused on resection of complex brain lesions.15 optimizing these methods to obtain what we refer to as high- DTI, however, is unable to solve the crossing of fibers (the definition fiber tracking (HDFT). HDFT is a novel combination crossing problem) and to determine with accuracy the origin and of processing, reconstruction, and tractography methods that destination of fibers (the termination problem), producing can track fibers from cortex, through complex fiber crossings, to multiple artifacts and false tracts.16,17 Diffusion-based determin- cortical and subcortical targets with at least millimeter resolution. istic MRI methods cannot at present reliably replicate many basic This is in contrast to low directional methods such as DTI in neuroanatomical features described more than a century ago by which such resolution is not accessible. HDFT relies on the unique means of fiber dissection and histological techniques.6,18,19 The combination of several factors: dense sampling of region of interest– crossing and termination problems are accentuated in the analysis based tractography data, generalized Q-ball imaging reconstruction of fiber tracts in the periphery of a brain lesion with mass effect algorithm, multiple intravoxel sampling, and a multidirectional TABLE 2. High-Definition Fiber Tractography in the Normal Brain: Replication of Known Neuroanatomical Features Neuroanatomical Feature Neuroanatomical Region Neuroanatomical Replication Figure Cortical termination Hemispheric surface Sulcal and gyral pattern 1 and 2 Subcortical termination Claustrocortical projection system Ovoid shape of claustrum 3 Subcortical termination and subcortical Thalamocortical projection system Somatotopy of thalamic radiations 4 fiber-based segmentation Double subcortical termination and Superior cerebellar peduncle Characteristic shape of dentate and red 5 decussation of fibers nuclei; partial decussation of fibers Triple crossing Centrum semiovale Multidirectional crossing of callosal, arcuate, 6 and corona radiata fibers Complex angulations Meyers loop Anterograde loop of optic radiations 7 Arborization of terminal fibers and Arcuate fascicle Branching pattern of the arcuate tract at the 8 multiple cortical terminations frontal and temporal regions Cortical connectivity and segmentation Broca area Segmentation of Broca area based on fiber 9 connectivity NEUROSURGERY VOLUME 71 | NUMBER 2 | AUGUST 2012 | 431 Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited. FERNANDEZ-MIRANDA