VE-cadherin in arachnoid and pia mater cells serves as a suitable landmark for in vivo imaging of CNS immune surveillance and inflammation.

Meninges cover the surface of the brain and spinal cord and contribute to protection and immune surveillance of the central nervous system (CNS). How the meningeal layers establish CNS compartments with different accessibility to immune cells and immune mediators is, however, not well understood. Here, using 2-photon imaging in female transgenic reporter mice, we describe VE-cadherin at intercellular junctions of arachnoid and pia mater cells that form the leptomeninges and border the subarachnoid space (SAS) filled with cerebrospinal fluid (CSF). VE-cadherin expression also marked a layer of Prox1+ cells located within the arachnoid beneath and separate from E-cadherin+ arachnoid barrier cells. In vivo imaging of the spinal cord and brain in female VE-cadherin-GFP reporter mice allowed for direct observation of accessibility of CSF derived tracers and T cells into the SAS bordered by the arachnoid and pia mater during health and neuroinflammation, and detection of volume changes of the SAS during CNS pathology. Together, the findings identified VE-cadherin as an informative landmark for in vivo imaging of the leptomeninges that can be used to visualize the borders of the SAS and thus potential barrier properties of the leptomeninges in controlling access of immune mediators and immune cells into the CNS during health and neuroinflammation.

Intraoperative Ultrasound: Real-Time Surgical Adjunct for Complete Resection of Spinal Arachnoid Webs.

Spinal arachnoid webs are abnormal formations of arachnoid membranes that reside in the arachnoid space. Clinically, they may present as an incidental finding or in patients with progressively worsening myelopathy. Early detection and surgical intervention are recommended in patients with progressive symptoms. Several methods have been described for the surgical treatment of these web formations.1-4 The success of surgery and the ability to prevent recurrence is dependent on complete surgical resection of these lesions, which in some cases can appear complex and intricate in nature. A few reports have highlighted the use of intraoperative ultrasound to localize the lesion; however, none have highlighted its value in establishing successful web resection and restoration of normal cerebrospinal fluid flow.3,4 Herein, we demonstrate the use of intraoperative ultrasound as an effective adjunct to assessing and establishing complete resection of arachnoid webs. We illustrate how intraoperative ultrasound allows for real-time, direct visualization of arachnoid lysis with restoration of normal cerebrospinal fluid flow (Video 1). Our patient was symptomatic for 12 months with rapid progression of myelopathic symptoms in the 3 months before presentation. Following surgery, she remained asymptomatic at 4-year follow-up with no reoccurrence at 24-month magnetic resonance imaging. Intraoperative ultrasound is a useful adjunct to successfully performing dorsal arachnoid web surgery and ensuring improved surgical outcomes through complete web resection and decompression of the spinal cord.

Importance of Arachnoid Dissection in Arteriovenous Malformation Microsurgery: A Technical Note.

Intracranial arteriovenous malformations (AVMs) are congenital anomalies where arteries and veins connect without a capillary bed. AVMs are the leading cause of nontraumatic intracerebral hemorrhages in people younger than 35 years old.1 The leptomeninges (arachnoid and pia) form from the meninx primitiva.2,3 Endothelial channels produce a vascular plexus in the meninx connected by primitive arachnoid. Remodeling of the plexus in response to changing metabolic demands results in a recognizable pattern of arteries and veins.2,3 Defects at the level of capillaries during arteriovenous specification are most likely responsible for arteriovenous fistula formation.4-6 Interplay between the congenital dysfunction and flow-related maturation in adulthood, when vasculogenesis has stopped, produces the AVM.6,7 The relationship between the primitive arachnoid and aberrant AVM vessels is preserved and forms the basis of microsurgical disconnection discussed in Video 1. Several authors have described dissecting these natural planes to delineate the abnormal AVM vessels, relax the brain, and avoid morbidity during AVM surgery.8-10 We recommend sharp arachnoid dissection with a scalpel or microscissors, occasionally helped by blunt dissection with patties or bipolar forceps. We present a 2-dimensional video of the microsurgical resection of a right parietal AVM. The patient, a healthy 30-year-old female, presented with intermittent headaches and mild impairment of arithmetic and visuospatial ability. Magnetic resonance imaging and digital subtraction angiography showed a compact 3.5-cm supramarginal gyrus AVM supplied by the middle cerebral artery, with superficial drainage. Complete microsurgical resection was performed without morbidity. We demonstrate the principles of arachnoid dissection requisite to disentanglement of the nidus and safe resection of the AVM.

Microstructure and Reasonable Management of the Arachnoid Associated with the Infrafloccular Approach for Microvascular Decompression of the Facial Nerve.

AIM: To understand the arachnoid microstructure during infrafloccular approach for facial nerve microvascular decompression (MVD). MATERIAL AND METHODS: This study recruited 55 patients with hemifacial spasm who underwent MVD. Retrospective analyses of the MVD surgical videos were performed to reveal the arachnoid microstructure during the procedures. Cadaveric head specimens (n=8, on 16 sides) were dissected for observation of the microstructure of the arachnoid in the cerebellopontine angle. RESULTS: The arachnoid membrane surrounding the facio-cochleovestibular and lower cranial nerves forms two arachnoid sheaths. Both arachnoid sheaths contain two parts: the outer membranous and inner trabecular part. The membranous part is an intact and translucent membrane that wraps around nerves. The inner trabecular part is located beneath the membranous part and forms a trabecular network that connects the membranous arachnoid, nerves, and blood vessels to form a physical structure. CONCLUSION: The arachnoid connects the facio-cochleovestibular and lower cranial nerves, blood vessels, and cerebellum as a complex physical entity. Therefore, during MVD surgery, sharply dissecting the arachnoid before retracting the flocculus and relocating the offending vessels helps reduce nerve injury.

Evaluation of anterior and middle cranial fossa intraosseous arachnoid granulations with 3D T2-SPACE sequence.

OBJECTIVES: Arachnoid granulations (AG) can be located anywhere outside the dural sinuses. Their presence is thought to be associated with idiopathic intracranial hypertension (IIH) and cerebrospinal fluid (CSF) leaks. It was aimed to evaluate the intraosseous AGs located in the middle and anterior cranial fosses in detail with three-dimensional T2-SPACE (Sampling Perfection with Application optimized Contrasts using different flip angle Evolution-Siemens) imaging and to investigate their clinical significance. MATERIALS AND METHODS: Sixty-five intraosseous AG of 46 patients were included in this retrospective study. The highest diameter, bone indentation degree (in the inner tabula, diploe distance, reaching and exceeding the outer tabula), content (CSF/+parenchyma) of each AG were evaluated by 2 experienced radiologists. In addition, the presence of other MRI findings supporting IIH was examined. RESULTS: Additional signs of IIH were detected in 25 patients, and they were statistically significantly more common in the middle cranial fossa. Parenchymal herniation (in four patients) was more common in the young population. CONCLUSIONS: Intraosseous AGs can be evaluated in detail with T2-SPACE imaging. Determining intraosseous AG is very important both as an indicator of IIH and in terms of its content. T2-SPACE imaging is superior to CT and conventional sequences in this regard.

Lateral Suboccipital Infrafloccular Approach with Extensive Arachnoid Dissection for Vertebral Artery-Associated Hemifacial Spasm: Two-Dimensional Operative Video.

Hemifacial spasm (HFS) is generally caused by compression of the root exit zone (REZ) of the facial nerve by the anterior and posterior inferior cerebellar arteries and occasionally the vertebral artery (VA). Owing to its large caliber and high stiffness, microvascular decompression (MVD) for VA-associated HFS is considered more difficult, and the result is worse than for HFS not associated with the VA.1,2 Therefore, a safer, more reliable MVD is required for VA-associated HFS. In Video 1, we demonstrate our MVD technique in a 57-year-old woman who presented with left HFS owing to facial nerve compression by a dolichoectatic VA. A lateral suboccipital infrafloccular approach with extensive arachnoid dissection was performed. Arachnoid dissection was started from the cisterna magna and continued from the caudal to the rostral direction. This extensive arachnoid dissection provided access to the facial nerve REZ through the infrafloccular route with gentle retraction of the flocculus in the caudorostral direction, while avoiding strong retraction of cranial nerve VIII and the cerebellum. In addition, we were able avoid damaging the neurovascular structures in the operative field. This is mandatory to make the operative field bloodless and facilitate identifying the relationship between the facial nerve REZ and the offending vessels. MVD of the facial nerve REZ was achieved. The patient's postoperative course was uneventful, and her HFS resolved postoperatively. Patient consent was obtained to perform the surgery and to publish the surgical video.

Brain herniation (encephalocele) into arachnoid granulations: prevalence and association with pulsatile tinnitus and idiopathic intracranial hypertension.

PURPOSE: Brain herniation into arachnoid granulations (BHAG) of the dural venous sinuses is a recently described finding of uncertain etiology. The purpose of this study was to investigate the prevalence of BHAG in a cohort of patients with pulsatile tinnitus (PT) and to clarify the physiologic and clinical implications of these lesions. METHODS: The imaging and charts of consecutive PT patients were retrospectively reviewed. All patients were examined with MRI including pre- and post-contrast T1- and T2-weighted sequences. Images were reviewed separately by three blinded neuroradiologists to identify the presence of BHAG. Their location, signal intensity, size, presence of arachnoid granulation, and associated dural venous sinus stenosis were documented. Clinical records were further reviewed for idiopathic intracranial hypertension, history of prior lumbar puncture, and opening pressure. RESULTS: Two hundred sixty-two consecutive PT patients over a 4-year period met inclusion criteria. PT patients with BHAG were significantly more likely to have idiopathic intracranial hypertension than PT patients without BHAG (OR 4.2, CI 1.5-12, p = 0.006). Sixteen out of 262 (6%) patients were found to have 18 BHAG. Eleven out of 16 (69%) patients had unilateral temporal or occipital lobe herniations located in the transverse sinus or the transverse-sigmoid junction. Three out of 16 (19%) patients had unilateral cerebellar herniations and 2/16 (13%) patients had bilateral BHAG. CONCLUSION: In patients with PT, BHAG is a prevalent MRI finding that is strongly associated with the clinical diagnosis of IIH. The pathogenesis of BHAG remains uncertain, but recognition should prompt comprehensive evaluation for IIH.

Arachnoid Membranes: Crawling Back into Radiologic Consciousness.

The arachnoid membranes are projections of connective tissue in the subarachnoid space that connect the arachnoid mater to the pia mater. These are underappreciated and largely unrecognized by most neuroradiologists despite being found to be increasingly important in the pathogenesis, imaging, and treatment of communicating hydrocephalus. This review aims to provide neuroradiologists with an overview of the history, embryology, histology, anatomy, and normal imaging appearance of these membranes, as well as some examples of their clinical importance.

External Neurolysis in Microvascular Decompression for Magnetic Resonance Imaging-Negative Idiopathic Trigeminal Neuralgia.

OBJECTIVE: Internal neurolysis has been proposed as an alternative to microvascular decompression in patients with idiopathic trigeminal neuralgia (TN) in whom neurovascular compression is not confirmed by magnetic resonance imaging (MRI). External neurolysis, which straightens and realigns the trigeminal nerve root axis by dissecting the arachnoid membranes around the nerve, was reported 20 years ago in the context of so-called negative exploration when MRI did not confirm the absence of the offending vessel, but is not currently used. METHODS: External neurolysis was performed in 4 patients with idiopathic TN with typical evoked neuralgic pain despite the absence of suspected offending vessels on MRI. The surgical findings that caused TN were summarized and the outcomes were evaluated using the Barrow Neurological Institute Pain Intensity Scale (BNI-PS). RESULTS: Tethering and distortion of the nerve root by surrounding arachnoid membranes were commonly found. All 4 patients showed complete pain relief immediately after surgery. During the follow-up period of 26.5 ± 16.92 months (±standard deviation), 3 of 4 patients had no pain (score I, BNI-PS). One patient received a score of IIIa on the BNI-PS assessment. There was no instance of recurrence or side effects associated with the surgery. CONCLUSIONS: Idiopathic TN can be induced by individual variation of the surrounding inner arachnoid membranes supporting the trigeminal nerve root, and the condition cannot be identified by MRI. Intradural external neurolysis may be considered an effective treatment for MRI-negative idiopathic TN.

Changes of arachnoid granulations after subarachnoid hemorrhage in cynomolgus monkeys.

This research explores ultrastructural changes of arachnoid granulations associated with hydrocephalus after subarachnoid hemorrhage in cynomolgus monkeys. It provides a theoretical basis for further study of the etiology and prevention of hydrocephalus. Female cynomolgus monkeys about one-year-old were selected. The position range of arachnoid granulations in superior sagittal sinus and transverse sinus was determined in a randomly selected control monkey. The morphology of normal arachnoid granulations in cynomolgus monkeys was observed under a transmission electron microscope. A primate model of subarachnoid hemorrhage was established by injecting autologous blood into cisterna magna. Vomiting, movement disorder, and reduced level of consciousness were gradually observed in monkeys. Computed tomography and magnetic resonance imaging scan results confirmed subarachnoid hemorrhage and hydrocephalus, and the morphology of arachnoid granulations in hydrocephalus was observed under a transmission electron microscope. Extensive fibrosis of arachnoid granulations was observed under a transmission electron microscope in cynomolgus monkeys with hydrocephalus after subarachnoid hemorrhage.

Utility of True Fast Imaging with Steady-State Precession in Detecting Arachnoid Veils of the Posterior Fossa.

INTRODUCTION: Arachnoid membranes are well recognized as a cause of cerebrospinal fluid (CSF) flow impairment in disorders such as obstructive hydrocephalus and syringohydromyelia, but can be difficult to detect with standard noninvasive imaging techniques. True fast imaging with steady-state precession (TrueFISP) can exhibit brain pulsations and CSF dynamics with high spatiotemporal resolution. Here, we demonstrate the utility of this technique in the diagnosis and management of arachnoid membranes in the posterior fossa. CASE PRESENTATIONS: Three symptomatic children underwent cine TrueFISP imaging for suspicion of CSF membranous obstruction. Whereas standard imaging failed to or did not clearly visualize the site of an obstructive lesion, preoperative TrueFISP identified a membrane in all 3 cases. The membranes were confirmed intraoperatively, and postoperative TrueFISP helped verify adequate marsupialization and recommunication of CSF flow. Two out of the 3 cases showed a decrease in cerebellar tonsillar pulsatility following surgery. All children showed symptomatic improvement. CONCLUSION: TrueFISP is able to detect pulsatile arachnoid membranes responsible for CSF outflow obstruction that are otherwise difficult to visualize using standard imaging techniques. We advocate use of this technology in pre- and postsurgical decision-making as it provides a more representative image of posterior fossa pathology and contributes to our understanding of CSF flow dynamics. There is potential to use this technology to establish prognostic biomarkers for disorders of CSF hydrodynamics.

Arachnoid granulations bulging into the transverse sinus, sigmoid sinus, straight sinus, and confluens sinuum: a magnetic resonance imaging study.

PURPOSE: Few studies have explored arachnoid granulations (AGs) bulging into the cranial dural sinuses using contrast-enhanced magnetic resonance imaging (MRI). This study aimed to explore such AGs in the transverse (TS), sigmoid (SigS), and straight (StS) sinuses, and confluens sinuum (ConfS) using thin-sliced, contrast MRI. METHODS: A total of 102 patients with intact dural sinuses underwent thin-sliced, contrast MRI in the axial, coronal, and sagittal planes. RESULTS: In 88.2%, more than one AG was identified in the TS and SigS, StS, and ConfS. In the TS, AGs were identified in 40.2% on the right side and 37.3% on the left and were frequently located in the middle and lateral thirds. In the SigS, AGs were identified on the right in 17.6% and on the left in 18.6% in the distal region. In the StS, AGs were identified in 35.3% of cases, most frequently located in the proximal third, followed by the distal third. In the ConfS, AGs were identified in 20.6% of cases. Furthermore, in 23.5%, a collection of multiple AGs of varying sizes was found in the TS. A statistical difference was not shown between the mean age of 90 patients with AGs and that of 12 patients without identifiable AGs. CONCLUSIONS: Bulging AGs may more frequently found in the TS. Thin-sliced, contrast MRI is useful for delineating AGs.

Arachnoiditis Ossificans of the Lumbar Spine: A Rare Cause of Progressive Cauda Equina Syndrome.

Arachnoiditis ossificans of the spine is a rare entity defined as an ossification of the leptomeninges resulting in neurologic decline. We describe the case of a 42-year-old woman, without any obvious predisposing factor, who presented with a progressive cauda equina syndrome. The imaging findings on magnetic resonance imaging were confusing by showing an atypical intraspinal lesion extending from L1 to S1. The computed tomography scan was more specific by showing suggestive images of a huge arachnoiditis ossificans of the lumbar spine. The patient underwent a large lumbar laminectomy with an incomplete resection of the ossified arachnoid. The histologic study confirmed the bony nature of the lesion. This illustrative case highlights the importance of helical computed tomography scan with multiplanar reconstruction for the diagnosis of arachnoiditis ossificans.

Tissue damage in herniated brain parenchyma into giant arachnoid granulations: demonstration with high resolution MRI.

BACKGROUND: Brain herniation (BH) into arachnoid granulation has been remarkable in recent years. PURPOSE: To evaluate the damage in herniated parenchyma into the giant arachnoid granulation (GAG) and to investigate the clinical-demographic importance of this damage. MATERIAL AND METHODS: Patients with BH into GAG were retrospectively included in the study. Each of the patients had at least one high-resolution 3D magnetic resonance imaging (MRI) sequence. The arachnoid granulation dimensions, locations, and origin of herniated parenchyma were evaluated by two experienced radiologists. The demographic and symptomatic features of the patients were recorded from the hospital database. RESULTS: A total of 27 patients (21 females, 6 males; age range 6-71 years; mean age 41.3 years) were found to contain BH into GAG. It was most commonly seen in the transverse sinus (67%); the origin was most common in the cerebellar parenchyma (56%). Abnormal signal and morphology were detected in herniated parenchyma in 11 (47%) patients, atrophy in six, and atrophy and gliosis in five. The most common complaints were headache (47%), while other frequent symptoms were vertigo (15%) and blurred vision (11%). There was a statistically significant positive correlation between frequency of damage in herniated brain parenchyma and the maximal size of GAG (P<0.05). CONCLUSION: In patients with BH into GAG, parenchymal damage may be associated with various symptoms, such as headache and vertigo, although they have not been statistically proven. It is important to carefully evaluate hernia tissue, as the risk of tissue damage may increase in larger GAGs.

Extradural Remodeling in Empty Sella Syndrome: 3-Dimensional Operative Video.

Sellar arachnoidocele is a term used to define the herniation of the subarachnoid space to the sella.1 This is a rare radiologic finding that, in most cases, does not require treatment.2-5 When symptoms appear, the term empty sella syndrome is used. Two varieties exist: primary and secondary empty sella syndrome.2 The aim of this 3-dimensional operative video (Video 1) is to demonstrate the extradural microsurgical remodeling of the sellar fossa with autologous bone in 2 cases of primary empty sella syndrome. Both patients signed an informed consent for the procedures and agree with the use of their images for research purposes. In both cases, magnetic resonance imaging scans showed herniation of the subarachnoid space into the pituitary fossa and an anchor-like silhouette on coronal view. Patients evolved favorably, improving their visual deficit after the surgery, as can be observed in the postoperative visual field study. If surgery is indicated due to visual loss, the procedure is known as chiasmapexy. Recently, Guinto et al3 described a technique for chiasmapexy. Our team considers this procedure to be useful, technically simple, and low cost. Being autologous, rejection possibilities are almost null. This 3D video serves as a complement to illustrate the technique.

Protuberancia ósea con adelgazamiento cortical / Bone protuberance with cortical thinning

No disponible

Multi-modality imaging evaluation of the dorsal arachnoid web.

PURPOSE: Dorsal arachnoid web (DAW) is a rare intradural abnormality which is associated with progressive myelopathy. Our objective was to review multi-modality imaging techniques demonstrating the scalpel sign appearance in evaluation of DAW. METHODS: We retrospectively reviewed various imaging modalities of patients found to have DAW at our institution during January 2015 to February 2020. Five patients underwent surgical decompression with pathological correlation. The remaining patients were presumptively diagnosed based on the characteristic finding of scalpel sign. Clinical data were evaluated and correlated to imaging findings. All imaging modalities demonstrated the characteristic scalpel sign. RESULTS: Sixteen patients (10 females, and six males) with multi-imaging modalities were evaluated. Their mean age was 52 year (range 23-74 years). Fifteen patients underwent conventional spine MRI. Further high-resolution MR imaging techniques, e.g. 3D T2 myelographic sequence, were utilized with two patients. MRI spine CSF flow study was performed to evaluate the flow dynamic across the arachnoid web in one patient. Eight patients were evaluated with CT myelogram. Syrinx formation was discovered in seven (44%) patients; five (71%) of them underwent surgical resection and decompression. Two patients underwent successful catheter-directed fenestration of the web with clinical improvement. We found a statically significant positive correlation between the degree of cord displacement and compression with syrinx formation (r = 0.55 and 0.65 with p-value of 0.03 and 0.009, respectively). CONCLUSION: DAW has characteristic scalpel sign independent of imaging modality. Multi-modality imaging evaluation of DAW is helpful for evaluation and surgical planning.

Percutaneous Fenestration of a Spinal Arachnoid Web Using an Intrathecal Catheter: Effect on Cerebrospinal Fluid Flow and Clinical Status.

BACKGROUND: Spinal arachnoid webs are a rare anatomic entity manifesting as neuropathic back pain, compressive myelopathy, radiculopathy, and hydrocephalus. Typical treatments include hemilaminectomy or full laminectomy with durotomy and microsurgical resection, which can result in secondary scarring and recurrent blockage of cerebrospinal fluid (CSF) flow perpetuating the cycle. CASE DESCRIPTION: A 66-year-old woman presented with progressively worsening gait and memory. Magnetic resonance imaging demonstrated an arachnoid web in the high thoracic region, causing CSF flow obstruction and hydrocephalus. A standard lumbar drainage catheter was introduced percutaneously into the lumbar thecal sac and advanced in a cephalad direction, across the arachnoid web, to the high thoracic region. The patient underwent continuous CSF drainage through this catheter for a total of 3 days, displaying measurable clinical improvement that persisted at the 3-month follow-up visit. Phase-contrast magnetic resonance imaging demonstrated interval reconstitution of dorsal synchronous CSF flow at the second thoracic vertebral level, both on day 3 and at the 3-month control imaging study. CONCLUSIONS: This minimally invasive approach seems useful in achieving restoration of spinal fluid flow at the thoracic region when the underlying blockage results from an arachnoid web and leads to quantifiable clinical improvement.

The Role of Arachnoid Granulations and the Glymphatic System in the Pathophysiology of Idiopathic Intracranial Hypertension.

PURPOSE OF REVIEW: Idiopathic intracranial hypertension (IIH) is a disorder characterized by long-standing elevated intracranial pressure (ICP). As the name applies, no uniform cause has been identified. IIH is typically characterized by headaches, pulsatile tinnitus, and visual deterioration. RECENT FINDINGS: Anomalies in cerebrospinal fluid (CSF) absorption are implicated in the pathophysiology of IIH. Non-invasive imaging of the brain parenchyma and the cerebral venous sinus has improved, and research has gained a better understanding of the role of cerebral venous sinus stenosis. Both have led to a better delineation of the role of arachnoid granulations (AG) and the glymphatic system in the development of IIH. IIH may occur as a result of restrictions of CSF absorption from the venous system, and or the congestion and overflow of the glymphatic system. Elucidating these mechanisms will lead to greater understanding of its underlying pathophysiologic mechanisms.

Spatial distribution of human arachnoid trabeculae.

Traumatic brain injury (TBI) is a common injury modality affecting a diverse patient population. Axonal injury occurs when the brain experiences excessive deformation as a result of head impact. Previous studies have shown that the arachnoid trabeculae (AT) in the subarachnoid space significantly influence the magnitude and distribution of brain deformation during impact. However, the quantity and spatial distribution of cranial AT in humans is unknown. Quantification of these microstructural features will improve understanding of force transfer during TBI, and may be a valuable dataset for microneurosurgical procedures. In this study, we quantify the spatial distribution of cranial AT in seven post-mortem human subjects. Optical coherence tomography (OCT) was used to conduct in situ imaging of AT microstructure across the surface of the human brain. OCT images were segmented to quantify the relative amounts of trabecular structures through a volume fraction (VF) measurement. The average VF for each brain ranged from 22.0% to 29.2%. Across all brains, there was a positive spatial correlation, with VF significantly greater by 12% near the superior aspect of the brain (p < .005), and significantly greater by 5%-10% in the frontal lobes (p < .005). These findings suggest that the distribution of AT between the brain and skull is heterogeneous, region-dependent, and likely contributes to brain deformation patterns. This study is the first to image and quantify human AT across the cerebrum and identify region-dependencies. Incorporation of this spatial heterogeneity may improve the accuracy of computational models of human TBI and enhance understanding of brain dynamics.