Fang-Cheng Yeh

University of Pittsburgh | Pitt · Department of Neurological Surgery

Here we introduce the concept of the local connectome: the degree of connectivity between adjacent voxels within a white matter fascicle defined by the density of the diffusing spins. While most human structural connectomic analyses can be summarized as finding global connectivity patterns at either end of anatomical pathways, the analysis of local...

A comprehensive map of the structural connectome in the human brain has been a coveted resource for understanding macroscopic brain networks. Here we report an expert-vetted, population-averaged atlas of the structural connectome derived from diffusion MRI data (N = 842). This was achieved by creating a high-resolution template of diffusion pattern...

Connectome maps region-to-region connectivities but does not inform which white matter pathways form the connections. Here we constructed a population-based tract-to-region connectome to fill this information gap. The constructed connectome quantifies the population probability of a white matter tract innervating a cortical region. The results show...

Shape analysis has been widely used in digital image processing and computer vision, but they have not been utilized to compare the structural characteristics of the human association pathways. Here we used shape analysis to derive length, area, volume, and shape metrics from diffusion MRI tractography and utilized them to study the human associati...

OBJECTIVE The aim of this study was to describe the role and long-term outcomes of high-definition fiber tractography (HDFT) in the surgical management of brainstem cavernomas. METHODS The authors performed a retrospective evaluation of their database at the HDFT laboratory in a single academic institution. RESULTS The authors identified 11 patie...

Objective Epilepsy is recognized increasingly as a network disease, with changes extending beyond the epileptogenic zone (EZ). However, more studies of structural connectivity are needed to better understand the behavior and nature of this condition. Methods In this study, we applied differential tractography, a novel technique that measures chang...

Objectives This study aimed to elucidate the influences of 1p/19q co-deletion on structural connectivity alterations in patients with dominant hemisphere insular diffuse gliomas. Methods We incorporated 32 cases of left insular gliomas and 20 healthy controls for this study. Using diffusion MRI, we applied correlational tractography, differential...

Neuroimaging studies have consistently demonstrated concurrent activation of the human precuneus and temporal pole (TP), both during resting‐state conditions and various higher‐order cognitive functions. However, the precise underlying structural connectivity between these brain regions remains uncertain despite significant advancements in neurosci...

Human cortical development follows a sensorimotor-to-association sequence during childhood and adolescence 1–6 . The brain’s capacity to enact this sequence over decades indicates that it relies on intrinsic mechanisms to regulate inter-regional differences in the timing of cortical maturation, yet regulators of human developmental chronology are n...

Comprehensive understanding of the neural circuits involving the ventral tegmental area is essential for elucidating the anatomofunctional mechanisms governing human behaviour, in addition to the therapeutic and adverse effects of deep brain stimulation for neuropsychiatric diseases. Although the ventral tegmental area has been targeted successfull...

Surgical neuromodulation has witnessed significant progress in recent decades. Notably, deep brain stimulation (DBS), delivered precisely within therapeutic targets, has revolutionized the treatment of medication-refractory movement disorders and is now expanding for refractory psychiatric disorders, refractory epilepsy, and post-stroke motor recov...

Neuroscience is advancing standardization and tool development to support rigor and transparency. Consequently, data pipeline complexity has increased, hindering FAIR (findable, accessible, interoperable and reusable) access. brainlife.io was developed to democratize neuroimaging research. The platform provides data standardization, management, vis...

INTRODUCTION We recently characterized the Ventral Mammillo-tegmental tract (VMTT) throug Klingler’s microdissections and fiber tractography using an averaged template generated from diffusion MRI (dMRI) data of 1065 human healthy subjects acquired from the Human Connectome Project (HCP) and the 50/200 μm cadaveric brainstem dMRI Duke database. The...

The transition to parenthood remains an understudied window of potential neuroplasticity in the adult brain. White matter microstructural (WMM) organization, which reflects structural connectivity in the brain, has shown plasticity across the lifespan. No studies have examined how WMM organization changes from the prenatal to postpartum period in m...

We have combined MR histology and light sheet microscopy (LSM) of five postmortem C57BL/6J mouse brains in a stereotaxic space based on micro-CT yielding a multimodal 3D atlas with the highest spatial and contrast resolution yet reported. Brains were imaged in situ with multi gradient echo (mGRE) and diffusion tensor imaging (DTI) at 15 um resoluti...

Mapping circuits for DBS. Within the enigmatic depths of an aquatic universe, divers use flashlights to reveal the hidden contours of an uncharted seabed that teems with wondrous vegetation. In an analogous exploration, Hollunder et al. describe how invasive brain stimulation delivered to deep-seated brain nuclei may act as a beacon. Using deep br...

Frontal circuits play a critical role in motor, cognitive and affective processing, and their dysfunction may result in a variety of brain disorders. However, exactly which frontal domains mediate which (dys)functions remains largely elusive. We studied 534 deep brain stimulation electrodes implanted to treat four different brain disorders. By anal...

The frontal aslant tract (FAT) is a crucial neural pathway of language and speech, but little is known about its connectivity and segmentation differences across populations. In this study, we investigate the probabilistic coverage of the FAT in a large sample of 1065 young adults. Our primary goal was to reveal individual variability and lateraliz...

Background Insular low‐grade gliomas (LGGs) are surgically challenging due to their proximity to critical structures like the corticospinal tract (CST). Purpose This study aims to determine if preoperative CST shape metrics correlate with postoperative motor complications in insular LGG patients. Study Type Retrospective. Population 42 patients...

Objectives This study aims to explore the relationship between the methylation levels of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter and the structural connectivity in insular gliomas across hemispheres. Methods We analyzed 32 left and 29 right insular glioma cases and 50 healthy controls, using differential tractography, correlati...

Objectives To investigate the correlation between methylation of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter levels and structural connectivity in insular gliomas across hemispheres. Methods We analyzed 61 left insular glioma cases and 50 healthy controls, using differential tractography, correlational tractography, and graph theor...

Cortical neurons of eutherian mammals project to the contralateral hemisphere, crossing the midline primarily via the corpus callosum and the anterior, posterior, and hippocampal commissures. We recently reported and named the thalamic commissures (TCs) as an additional interhemispheric axonal fiber pathway connecting the cortex to the contralatera...

The model of the four streams of the prefrontal cortex proposes 4 streams of information: motor through Brodmann area (BA) 8, emotion through BA 9, memory through BA 10, and emotional-related sensory through BA 11. Although there is a surge of functional data supporting these 4 streams within the PFC, the structural connectivity underlying these ne...

Objective Our study aimed to investigate the shape and diffusion properties of the corticospinal tract (CST) in patients with insular incidental and symptomatic low-grade gliomas (LGGs), especially those in the incidental group, and evaluate their association with post-surgical motor function. Methods We performed automatic fiber tracking on 41 LG...

Deep learning models usually require sufficient training data to achieve high accuracy, but obtaining labeled data can be time-consuming and labor-intensive. Here we introduce a template-based training method to train a 3D U-Net model from scratch using only one population-averaged brain MRI template and its associated segmentation label. The proce...

Deep learning models usually require sufficient training data to achieve high accuracy, but obtaining labeled data can be time-consuming and labor-intensive. Here we introduce a template-based training method to train a 3D U-Net model from scratch using only one population-averaged brain MRI template and its associated segmentation label. The proce...

We evaluated the fiber bundles in mild traumatic brain injury (mTBI) patients using differential and correlational tractography in a longitudinal analysis. Diffusion MRI data were acquired in 34 mTBI patients at 7 days (acute stage) and 3 months or longer (chronic stage) after mTBI. Trail Making Test A (TMT-A) and Digital Symbol Substitution Test c...

The frontal aslant tract (FAT) is a crucial neural pathway of language and speech, but little is known about its connectivity and segmentation differences across populations. In this study, we utilized diffusion MRI automatic tractography to investigate the probabilistic coverage of the FAT in a large sample of 1065 young adults. Our primary goal w...

We have developed workflows to align 3D magnetic resonance histology (MRH) of the mouse brain with light sheet microscopy (LSM) and 3D delineations of the same specimen. We start with MRH of the brain in the skull with gradient echo and diffusion tensor imaging (DTI) at 15 μm isotropic resolution which is ~ 1,000 times higher than that of most prec...

Nonlinear gradients impact diffusion weighted MRI by introducing spatial variation in estimated diffusion tensors. Recent studies have shown that increasing signal-to-noise ratios and the use of ultra-strong gradients may lead to clinically significant impacts on analyses due to these nonlinear gradients in microstructural measures. These effects c...

It is estimated that short association fibers running immediately beneath the cortex may make up as much as 60 % of the total white matter volume. However, these have been understudied relative to the long-range association, projection, and commissural fibers of the brain. This is largely because of limitations of diffusion MRI fiber tractography,...

Neuroimaging studies have consistently demonstrated concurrent activation of the human precuneus and temporal pole, both during resting-state conditions and various higher-order cognitive functions. However, the precise underlying structural connectivity between these brain regions remains uncertain despite significant advancements in neuroscience...

Background and Hypothesis: Cortical (e.g., Broca’s area and Wernicke’s area) and subcortical (e.g., putamen) language-related areas and executive control areas (e.g., inferior frontal gyrus (IFG), dorsolateral prefrontal cortex (DLPFC)) show functional and structural dysconnectivity in long-term psychosis. We examined whether resting-state basal pe...

Despite recent improvements in diffusion-weighted imaging, spinal cord tractography is not used in routine clinical practice because of difficulties in reconstructing tractograms, with a pertinent tri-dimensional-rendering, in a long post-processing time. We propose a new full tractography approach to the cervical spinal cord without extensive manu...

Limitations in the accuracy of brain pathways reconstructed by diffusion MRI (dMRI) tractography have received considerable attention. While the technical advances spearheaded by the Human Connectome Project (HCP) led to significant improvements in dMRI data quality, it remains unclear how these data should be analyzed to maximize tractography accu...

Quantifying the microstructural and macrostructural geometrical features of the human brain’s connections is necessary for understanding normal aging and disease. Here, we examine brain white matter diffusion magnetic resonance imaging data from one cross-sectional and two longitudinal data sets totaling in 1218 subjects and 2459 sessions of people...

Kynurenic acid (KynA) and quinolinic acid (QA) are neuroactive kynurenine pathway (KP) metabolites that have neuroprotective and neurotoxic properties, respectively. At least partly as a result of immune activation, the ratio of KynA to QA in the blood is reduced in major depressive disorder (MDD) and has been reported to be positively correlated w...

File formats that store the results of computational tractography were typically developed within specific software packages. This approach has facilitated a myriad of applications, but this development approach has generated insularity within software packages, and has limited standardization. Moreover, because tractography file formats were devel...

It is estimated that short association fibers, or 'U-shaped' fibers running immediately beneath the cortex, may make up as much as 60% of the total white matter volume. However, these have been understudied relative to the long-range association, projection, and commissural fibers of the brain. This is largely because of limitations of diffusion MR...

Huntington’s disease (HD) is a neurodegenerative disorder characterized by motor, psychiatric, and cognitive symptoms. Due to its diverse manifestations, the scientific community has long recognized the need for sensitive, objective, individualized, and dynamic disease assessment tools. We examined the feasibility of Differential Tractography as a...

Objectives: Epileptic patients suffer from seizure recurrence after surgery due to the challenging localization. Improvement of the noninvasive imaging-based approach for a better definition of the abnormalities would be helpful for a better outcome. Methods: The quantitative anisotropy (QA) of diffusion spectrum imaging (DSI) is a quantitative...

Quantifying the microstructural and macrostructural geometrical features of the human brain's connections is necessary for understanding normal aging and disease. Here, we examine brain white matter diffusion magnetic resonance imaging data from one cross-sectional and two longitudinal datasets totaling in 1184 subjects and 2236 sessions of people...

We have developed new imaging and computational workflows to produce accurately aligned multimodal 3D images of the mouse brain that exploit high resolution magnetic resonance histology (MRH) and light sheet microscopy (LSM) with fully rendered 3D reference delineations of brain structures. The suite of methods starts with the acquisition of geomet...

Differential tractography and correlation tractography are new tractography modalities to study neuronal changes in brain diseases, but their performances in detecting neuronal injuries are yet to be investigated in patients with mild traumatic brain injury (mTBI). Here we investigated the white matter injury in mTBI patients using differential and...

(1) Background: Growing evidence indicates that inflammation can induce neural circuit dysfunction and plays a vital role in the pathogenesis of major depressive disorder (MDD). Nevertheless, whether inflammation affects the integrity of white matter pathways is only beginning to be explored. (2) Methods: We computed quantitative anisotropy (QA) fr...

Objective: Graph theory applications are commonly used in connectomics research to better understand connectivity architecture and characterize its role in cognition, behavior and disease conditions. One of the numerous open questions in the field is how to represent inter-individual differences with graph theoretical methods to make inferences for...

OBJECTIVE Outcomes after focused ultrasound ablation (FUSA) for essential tremor remain heterogeneous, despite therapeutic promise. Clinical outcomes are directly related to the volume and location of the therapeutic lesions, consistent with CNS ablative therapies. Recent data demonstrate that postoperative diffusion MRI, specifically the quantific...

Connectome maps region-to-region connectivities but does not inform which white matter pathways form the connections. Here we constructed the first population-based tract-to-region connectome to fill this information gap. The constructed connectome quantifies the population probability of a white matter tract innervating a cortical region. The resu...

White matter bundle segmentation using diffusion MRI fiber tractography has become the method of choice to identify white matter fiber pathways in vivo in human brains. However, like other analyses of complex data, there is considerable variability in segmentation protocols and techniques. This can result in different reconstructions of the same in...

The ability to dissociate axonal density in vivo from other microstructural properties is important for the diagnosis and treatment of neurologic disease, and new methods to do so are being developed. We investigated one such method—restricted diffusion imaging (RDI)—to see whether it can more accurately replicate histological axonal density patter...

White matter bundle segmentation using diffusion MRI fiber tractography has become the method of choice to identify white matter fiber pathways in vivo in human brains. However, like other analyses of complex data, there is considerable variability in segmentation protocols and techniques. This can result in different reconstructions of the same in...

OBJECTIVE Globus pallidus (GP) lesioning improves motor symptoms of Parkinson’s disease (PD) and is occasionally associated with nonmotor side effects. Although these variable clinical effects were shown to be site-specific within the GP, the motor and nonmotor subregions have not been distinguished radiologically in patients with PD. The GP was re...

Paul Lauterbur closed his seminal paper on MRI with the statement that “zeugmatographic (imaging) techniques should find many useful applications in studies of the internal structures, states and composition of microscopic objects” [1]. Magnetic resonance microscopy was subsequently demonstrated in 1986 by three groups [2] [3] [4]. The application...

The aim of this study is to investigate the trajectory of medial longitudinal fasciculus (MLF) and explore its anatomical relationship with the oculomotor nerve using tractography technique. The MLF and oculomotor nerve were reconstructed at the same time with preset three region of interests (ROIs): one set at the area of rostral midbrain, one pla...

White matter fiber tracking using diffusion magnetic resonance imaging (dMRI) provides a noninvasive approach to map brain connections, but improving anatomical accuracy has been a significant challenge since the birth of tractography methods. Utilizing tractography in brain studies therefore requires understanding of its technical limitations to a...

Background: Magnetic resonance (MR) scans are routine clinical procedures for monitoring people with multiple sclerosis (PwMS). Patient discomfort, timely scheduling, and financial burden motivate the need to accelerate MR scan time. We examined the clinical application of a deep learning (DL) model in restoring the image quality of accelerated rou...

When investigating connectivity and microstructure of white matter pathways of the brain using diffusion tractography bundle segmentation, it is important to understand potential confounds and sources of variation in the process. While cross-scanner and cross-protocol effects on diffusion microstructure measures are well described (in particular fr...

Purpose Diffusion‐weighted imaging allows investigators to identify structural, microstructural, and connectivity‐based differences between subjects, but variability due to session and scanner biases is a challenge. Methods To investigate DWI variability, we present MASiVar, a multisite data set consisting of 319 diffusion scans acquired at 3 T fr...

Diffusion-weighted magnetic resonance imaging (dMRI) is the primary method for noninvasively studying the organization of white matter in the human brain. Here we introduce QSIPrep, an integrative software platform for the processing of diffusion images that is compatible with nearly all dMRI sampling schemes. Drawing on a diverse set of software s...

While stress may be a potential mechanism by which childhood threat and deprivation influence mental health, few studies have considered specific stress‐related white matter pathways, such as the stria terminalis (ST) and medial forebrain bundle (MFB). Our goal was to examine the relationships between childhood adversity and ST and MFB structural i...