Thiolated bone and tendon tissue particles covalently bound in hydrogels for in vivo calvarial bone regeneration.

Bone regeneration of large cranial defects, potentially including traumatic brain injury (TBI) treatment, presents a major problem with non-crosslinking, clinically available products due to material migration outside the defect. Commercial products such as bone cements are permanent and thus not conducive to bone regeneration, and typical commercial bioactive materials for bone regeneration do not crosslink. Our previous work demonstrated that non-crosslinking materials may be prone to material migration following surgical placement, and the current study attempted to address these problems by introducing a new hydrogel system where tissue particles are themselves the crosslinker. Specifically, a pentenoate-modified hyaluronic acid (PHA) polymer was covalently linked to thiolated tissue particles of demineralized bone matrix (TDBM) or devitalized tendon (TDVT), thereby forming an interconnected hydrogel matrix for calvarial bone regeneration. All hydrogel precursor solutions exhibited sufficient yield stress for surgical placement and an adequate compressive modulus post-crosslinking. Critical-size calvarial defects were filled with a 4% PHA hydrogel containing 10 or 20% TDBM or TDVT, with the clinical product DBXⓇ being employed as the standard of care control for the in vivo study. At 12 weeks, micro-computed tomography analysis demonstrated similar bone regeneration among the experimental groups, TDBM and TDVT, and the standard of care control DBXⓇ. The group with 10% TDBM was therefore identified as an attractive material for potential calvarial defect repair, as it additionally exhibited a sufficient initial recovery after shearing (i.e., > 80% recovery). Future studies will focus on applying a hydrogel in a rat model for treatment of TBI. STATEMENT OF SIGNIFICANCE: Non-crosslinking materials may be prone to material migration from a calvarial bone defect following surgical placement, which is problematic for materials intended for bone regeneration. Unfortunately, typical crosslinking materials such as bone cements are permanent and thus not conducive to bone regeneration, and typical bioactive materials for bone regeneration such as tissue matrix are not crosslinked in commercial products. The current study addressed these problems by introducing a new biomaterial where tissue particles are themselves the crosslinker in a hydrogel system. The current study successfully demonstrated a new material based on pentenoate-modified hyaluronic acid with thiolated demineralized bone matrix that is capable of rapid crosslinking, with desirable paste-like rheology of the precursor material for surgical placement, and with bone regeneration comparable to a commercially available standard-of-care product. Such a material may hold promise for a single-surgery treatment of severe traumatic brain injury (TBI) following hemicraniectomy.

Parcellation-based tractographic modeling of the ventral attention network.

INTRODUCTION: The ventral attention network (VAN) is an important mediator of stimulus-driven attention. Multiple cortical areas, such as the middle and inferior frontal gyri, anterior insula, inferior parietal lobule, and temporo-parietal junction have been linked in this processing. However, knowledge of network connectivity has been devoid of structural specificity. METHODS: Using relevant task-based fMRI studies, an activation likelihood estimation (ALE) of the VAN was generated Regions of interest corresponding to the HCP cortical parcellation scheme were co-registered onto this ALE in MNI coordinate space and visually assessed for inclusion in the network. DSI-based fiber tractography was performed to determine the structural connections between cortical areas comprising the VAN. RESULTS: Fourteen regions within the right cerebral hemisphere were found to overlap the ALE of the VAN: 6a, 6r, 7AM, 7PM, 8C, AVI, FOP4, MIP, p9-46v, PCV, PFm, PGi, TPOJ1, and TPOJ2. Regions demonstrated consistent U-shaped interconnections between adjacent parcellations, and the SLF was found to connect frontal and parietal areas of the network. CONCLUSIONS: We present a tractographic model of the VAN. This model comprises parcellations within the frontal and parietal cortices that are linked via the SLF. Future studies may refine this model with the ultimate goal of clinical application.

Parcellation-based tractographic modeling of the dorsal attention network.

INTRODUCTION: The dorsal attention network (DAN) is an important mediator of goal-directed attentional processing. Multiple cortical areas, such as the frontal eye fields, intraparietal sulcus, superior parietal lobule, and visual cortex, have been linked in this processing. However, knowledge of network connectivity has been devoid of structural specificity. METHODS: Using attention-related task-based fMRI studies, an anatomic likelihood estimation (ALE) of the DAN was generated. Regions of interest corresponding to the cortical parcellation scheme previously published under the Human Connectome Project were co-registered onto the ALE in MNI coordinate space and visually assessed for inclusion in the network. DSI-based fiber tractography was performed to determine the structural connections between relevant cortical areas comprising the network. RESULTS: Twelve cortical regions were found to be part of the DAN: 6a, 7AM, 7PC, AIP, FEF, LIPd, LIPv, MST, MT, PH, V4t, VIP. All regions demonstrated consistent u-shaped interconnections between adjacent parcellations. The superior longitudinal fasciculus connects the frontal, parietal, and occipital areas of the network. CONCLUSIONS: We present a tractographic model of the DAN. This model comprises parcellations within the frontal, parietal, and occipital cortices principally linked through the superior longitudinal fasciculus. Future studies may refine this model with the ultimate goal of clinical application.

A Connectomic Atlas of the Human Cerebrum-Chapter 10: Tractographic Description of the Superior Longitudinal Fasciculus.

The superior longitudinal fasciculus/arcuate white matter complex (SLF/AC) is the largest and most complex white matter tract of the human cerebrum with multiple inter-linked connections encompassing multiple cognitive functions such as language, attention, memory, emotion, and visuospatial function. However, little is known regarding the overall connectivity of this complex. Recently, the Human Connectome Project parcellated the human cortex into 180 distinct regions. Utilizing diffusion spectrum magnetic resonance imaging tractography coupled with the human cortex parcellation data presented earlier in this supplement, we aim to describe the macro-connectome of the SLF/AC in relation to the linked parcellations present within the human cortex. The purpose of this study is to present this information in an indexed, illustrated, and tractographically aided series of figures and tables for anatomic and clinical reference.

A Connectomic Atlas of the Human Cerebrum-Chapter 1: Introduction, Methods, and Significance.

BACKGROUND: As knowledge of the brain has increased, clinicians have learned that the cerebrum is composed of complex networks that interact to execute key functions. While neurosurgeons can typically predict and preserve primary cortical function through the primary visual and motor cortices, preservation of higher cognitive functions that are less well localized in regions previously deemed "silent" has proven more difficult. This suggests these silent cortical regions are more anatomically complex and redundant than our previous methods of inquiry can explain, and that progress in cerebral surgery will be made with an improved understanding of brain connectomics. Newly published parcellated cortex maps provide one avenue to study such connectomics in greater detail, and they provide a superior framework and nomenclature for studying cerebral function and anatomy. OBJECTIVE: To describe the structural and functional aspects of the 180 distinct areas that comprise the human cortex model previously published under the Human Connectome Project (HCP). METHODS: We divided the cerebrum into 8 macroregions: lateral frontal, motor/premotor, medial frontal, insular, temporal, lateral parietal, medial parietal, and occipital. These regions were further subdivided into their relevant parcellations based on the HCP cortical scheme. Connectome Workbench was used to localize parcellations anatomically and to demonstrate their functional connectivity. DSI studio was used to assess the structural connectivity for each parcellation. RESULTS: The anatomy, functional connectivity, and structural connectivity of all 180 cortical parcellations identified in the HCP are compiled into a single atlas. Within each section of the atlas, we integrate this information, along with what is known about parcellation function to summarize the implications of these data on network connectivity. CONCLUSION: This multipart supplement aims to build on the work of the HCP. We present this information in the hope that the complexity of cerebral connectomics will be conveyed in a more manageable format that will allow neurosurgeons and neuroscientists to accurately communicate and formulate hypotheses regarding cerebral anatomy and connectivity. We believe access to this information may provide a foundation for improving surgical outcomes by preserving lesser-known networks.

A Connectomic Atlas of the Human Cerebrum-Chapter 8: The Posterior Cingulate Cortex, Medial Parietal Lobe, and Parieto-Occipital Sulcus.

In this supplement, we build on work previously published under the Human Connectome Project. Specifically, we seek to show a comprehensive anatomic atlas of the human cerebrum demonstrating all 180 distinct regions comprising the cerebral cortex. The location, functional connectivity, and structural connectivity of these regions are outlined, and where possible a discussion is included of the functional significance of these areas. In part 8, we specifically address regions relevant to the posterior cingulate cortex, medial parietal lobe, and the parieto-occipital sulcus.

A Connectomic Atlas of the Human Cerebrum-Chapter 2: The Lateral Frontal Lobe.

In this supplement, we show a comprehensive anatomic atlas of the human cerebrum demonstrating all 180 distinct regions comprising the cerebral cortex. The location, functional connectivity, and structural connectivity of these regions are outlined, and where possible a discussion is included of the functional significance of these areas. In part 2, we specifically address regions relevant to the lateral frontal lobe.

A Connectomic Atlas of the Human Cerebrum-Chapter 16: Tractographic Description of the Vertical Occipital Fasciculus.

In this supplement, we show a comprehensive anatomic atlas of the human cerebrum demonstrating all 180 distinct regions comprising the cerebral cortex. The location, functional connectivity, and structural connectivity of these regions are outlined, and where possible a discussion is included of the functional significance of these areas. In this chapter, we specifically address regions integrating to form the vertical occipital fasciculus.

A Connectomic Atlas of the Human Cerebrum-Chapter 7: The Lateral Parietal Lobe.

In this supplement, we build on work previously published under the Human Connectome Project. Specifically, we seek to show a comprehensive anatomic atlas of the human cerebrum demonstrating all 180 distinct regions comprising the cerebral cortex. The location, functional connectivity, and structural connectivity of these regions are outlined, and where possible a discussion is included of the functional significance of these areas. In part 7, we specifically address regions relevant to the lateral parietal lobe.

A Connectomic Atlas of the Human Cerebrum-Chapter 17: Tractographic Description of the Cingulum.

In this supplement, we show a comprehensive anatomic atlas of the human cerebrum demonstrating all 180 distinct regions comprising the cerebral cortex. The location, functional connectivity, and structural connectivity of these regions are outlined, and where possible a discussion is included of the functional significance of these areas. In this chapter, we specifically address regions integrating to form the cingulum.

A Connectomic Atlas of the Human Cerebrum-Chapter 18: The Connectional Anatomy of Human Brain Networks.

BACKGROUND: It is widely understood that cortical functions are mediated by complex, interdependent brain networks. These networks have been identified and studied using novel technologies such as functional magnetic resonance imaging under both resting-state and task-based conditions. However, no one has attempted to describe these networks in terms of their cortical parcellations. OBJECTIVE: To describe our approach to network modeling and discuss its significance for the future of neuronavigation in brain surgery using the cortical parcellation scheme detailed within this supplement. METHODS: Using network models previously elucidated by our group using coordinate-based meta-analytic techniques, we show the anatomic position and underlying white matter tracts of the cortical regions comprising 8 functional networks of the human cerebrum. These network models are displayed using Synaptive's clinically available BrightMatter tractography software (Synaptive Medical, Toronto, Canada). RESULTS: The relevant cortical parcellations of 8 different cerebral networks have been identified. The fiber tracts between these regions were used to construct anatomically precise models of the networks. Models are described for the dorsal attention, ventral attention, semantic, auditory, supplementary motor, ventral premotor, default mode, and salience networks. CONCLUSION: Our goal is to move towards more precise, anatomically specific models of brain networks that can be constructed for individual patients and utilized in navigational platforms during brain surgery. We believe network modeling and future advances in navigation technology can provide a foundation for improving neurosurgical outcomes by allowing us to preserve complex brain networks.

A Connectomic Atlas of the Human Cerebrum-Chapter 11: Tractographic Description of the Inferior Longitudinal Fasciculus.

In this supplement, we seek to show a comprehensive anatomic atlas of the human cerebrum demonstrating all 180 distinct regions comprising the cerebral cortex. The location, functional connectivity, and structural connectivity of these regions are outlined, and where possible a discussion is included of the functional significance of these areas. In this chapter, we specifically address regions integrating to form the inferior longitudinal fasciculus.

A Connectomic Atlas of the Human Cerebrum-Chapter 9: The Occipital Lobe.

In this supplement, we build on work previously published under the Human Connectome Project. Specifically, we seek to show a comprehensive anatomic atlas of the human cerebrum demonstrating all 180 distinct regions comprising the cerebral cortex. The location, functional connectivity, and structural connectivity of these regions are outlined, and where possible a discussion is included of the functional significance of these areas. In part 9, we specifically address regions relevant to the occipital lobe and the visual system.

A Connectomic Atlas of the Human Cerebrum-Chapter 13: Tractographic Description of the Inferior Fronto-Occipital Fasciculus.

The inferior fronto-occipital fasciculus (IFOF) is a large white matter tract of the human cerebrum with functional connectivity associated with semantic language processing and goal-oriented behavior. However, little is known regarding the overall connectivity of this tract. Recently, the Human Connectome Project parcellated the human cortex into 180 distinct regions. In our other work, we have shown these various regions in relation to clinically applicable anatomy and function. Utilizing Diffusion Spectrum Magnetic Resonance Imaging tractography coupled with the human cortex parcellation data presented earlier in this supplement, we aim to describe the macro-connectome of the IFOF in relation to the linked parcellations present within the human cortex. The purpose of this study is to present this information in an indexed, illustrated, and tractographically aided series of figures and tables for anatomic and clinical reference.

A Connectomic Atlas of the Human Cerebrum-Chapter 15: Tractographic Description of the Uncinate Fasciculus.

In this supplement, we show a comprehensive anatomic atlas of the human cerebrum demonstrating all 180 distinct regions comprising the cerebral cortex. The location, functional connectivity, and structural connectivity of these regions are outlined, and where possible a discussion is included of the functional significance of these areas. In this chapter, we specifically address the regions integrating to form the uncinate fasciculus.

A Connectomic Atlas of the Human Cerebrum-Chapter 14: Tractographic Description of the Frontal Aslant Tract.

In this supplement, we show a comprehensive anatomic atlas of the human cerebrum demonstrating all 180 distinct regions comprising the cerebral cortex. The location, functional connectivity, and structural connectivity of these regions are outlined, and where possible a discussion is included of the functional significance of these areas. In this chapter, we specifically address the regions integrating to form the frontal aslant tract.

A Connectomic Atlas of the Human Cerebrum-Chapter 4: The Medial Frontal Lobe, Anterior Cingulate Gyrus, and Orbitofrontal Cortex.

In this supplement, we build on work previously published under the Human Connectome Project. Specifically, we show a comprehensive anatomic atlas of the human cerebrum demonstrating all 180 distinct regions comprising the cerebral cortex. The location, functional connectivity, and structural connectivity of these regions are outlined, and where possible a discussion is included of the functional significance of these areas. In part 4, we specifically address regions relevant to the medial frontal lobe, anterior cingulate gyrus, and orbitofrontal cortex.

A Connectomic Atlas of the Human Cerebrum-Chapter 3: The Motor, Premotor, and Sensory Cortices.

In this supplement, we build on work previously published under the Human Connectome Project. Specifically, we show a comprehensive anatomic atlas of the human cerebrum demonstrating all 180 distinct regions comprising the cerebral cortex. The location, functional connectivity, and structural connectivity of these regions are outlined, and where possible a discussion is included of the functional significance of these areas. In part 3, we specifically address regions relevant to the sensorimotor cortices.

A Connectomic Atlas of the Human Cerebrum-Chapter 6: The Temporal Lobe.

In this supplement, we build on work previously published under the Human Connectome Project. Specifically, we show a comprehensive anatomic atlas of the human cerebrum demonstrating all 180 distinct regions comprising the cerebral cortex. The location, functional connectivity, and structural connectivity of these regions are outlined, and where possible a discussion is included of the functional significance of these areas. In part 6, we specifically address regions relevant to the temporal lobe.

A Connectomic Atlas of the Human Cerebrum-Chapter 12: Tractographic Description of the Middle Longitudinal Fasciculus.

The middle longitudinal fasciculus (MdLF) is a small and somewhat controversial white matter tract of the human cerebrum, confined to the posterior superior temporal region from which it courses posteriorly to connect at the occipital-parietal interface. The tract appears to be involved in language processing as well as auditory organization and localization, while sub-serving other higher level cognitive functions that have yet to be fully elucidated. Little is known about the specific, interparcellation connections that integrate to form the MdLF. Utilizing diffusion spectrum magnetic resonance imaging tractography coupled with the human cortex parcellation data presented earlier in this supplement, we aim to describe the macro-connectome of the MdLF in relation to the linked parcellations present within the human cortex. The purpose of this study is to present this information in an indexed, illustrated, and tractographically aided series of figures and tables for anatomic and clinical reference.