ABSTRACT
The pial vasculature is the sole source of blood supply to the neocortex. The brain is contained within the skull, a vascularized bone marrow with a unique anatomical connection to the brain meninges. Recent developments in tissue clearing have enabled detailed mapping of the entire pial and calvarial vasculature. However, what are the absolute flow rate values of those vascular networks? This information cannot accurately be retrieved with the commonly used bioimaging methods. Here, we introduce Pia-FLOW, a unique approach based on large-scale transcranial fluorescence localization microscopy, to attain hemodynamic imaging of the whole murine pial and calvarial vasculature at frame rates up to 1,000 Hz and spatial resolution reaching 5.4 µm. Using Pia-FLOW, we provide detailed maps of flow velocity, direction, and vascular diameters which can serve as ground-truth data for further studies, advancing our understanding of brain fluid dynamics. Furthermore, Pia-FLOW revealed that the pial vascular network functions as one unit for robust allocation of blood after stroke.
Subject(s)
Connectome , Hemodynamics , Pia Mater , Animals , Mice , Hemodynamics/physiology , Pia Mater/blood supply , Cerebrovascular Circulation/physiology , Brain/blood supply , Brain/diagnostic imaging , Skull/diagnostic imaging , Skull/blood supply , Stroke/physiopathology , Stroke/diagnostic imaging , Male , Mice, Inbred C57BLABSTRACT
PURPOSE: The traditional imaging findings reported in Sturge-Weber syndrome (SWS) include endpoints of cortical injury-cortical atrophy and cortical calcifications-but also what has been termed a "leptomeningeal angiomatosis," the latter recognized and reported as a leptomeningeal enhancement on magnetic resonance imaging (MRI). The objective of this study is to demonstrate through neuropathological correlation that the "leptomeningeal angiomatosis" in patients with Sturge-Weber syndrome (SWS), represents a re-opened primitive venous network in the subarachnoid space that likely acts as an alternative venous drainage pathway, seen separately to abnormal pial enhancement. MATERIALS AND METHODS: Retrospective review of MR imaging and surgical pathology of patients that underwent surgery for epilepsy at a tertiary, children's hospital. A pediatric radiologist with more than 20 years of experience reviewed the MR imaging. Surgically resected brain specimens that had been sectioned and fixed in 10% paraformaldehyde for histologic processing, following processing and paraffin embedding, were cut into 5-µm unstained slides which were subsequently stained with hematoxylin and eosin (H&E). Slides were re-examined by a board-certified pediatric neuropathologist, and histologic features specifically relating to cerebral surface and vascularity were documented for correlation with MR imaging of the resected region performed prior to resection. RESULTS: Five patients were reviewed (3 boys and 2 girls; the median age at the onset of seizures was 12 months (IQR, 7 to 45 months); the median age at surgery was 33 months (IQR, 23.5 to 56.5 months)). Surgical procedures included the following: 4, hemispherotomy (right: 2, left: 2) and 1, hemispherectomy (right). A subarachnoid space varicose network was present on both MRI and histology in 4 patients. Calcifications were seen on both MRI and histology in 3 patients. Abnormal leptomeningeal enhancement was present in 5 patients and seen separately from the subarachnoid vascular network in 4 patients. CONCLUSION: Histopathology confirmed the MRI findings of a subarachnoid space varicose network seen separately from leptomeningeal enhancement and presumed to represent an alternative venous drainage pathway to compensate for maldevelopment of cortical veins, the primary abnormality in SWS. No pial-based angioma was identified.
Subject(s)
Magnetic Resonance Imaging , Sturge-Weber Syndrome , Humans , Sturge-Weber Syndrome/diagnostic imaging , Sturge-Weber Syndrome/surgery , Sturge-Weber Syndrome/pathology , Male , Female , Retrospective Studies , Child, Preschool , Magnetic Resonance Imaging/methods , Child , Infant , Pia Mater/diagnostic imaging , Pia Mater/pathology , Subarachnoid Space/diagnostic imaging , Subarachnoid Space/pathology , Subarachnoid Space/surgery , Adolescent , Angiomatosis/surgery , Angiomatosis/diagnostic imaging , Angiomatosis/pathology , Varicose Veins/diagnostic imaging , Varicose Veins/surgery , Varicose Veins/pathologySubject(s)
Cerebral Revascularization , Collateral Circulation , Magnetic Resonance Angiography , Moyamoya Disease , Humans , Moyamoya Disease/surgery , Moyamoya Disease/diagnostic imaging , Cerebral Revascularization/methods , Collateral Circulation/physiology , Cerebrovascular Circulation/physiology , Female , Male , Pia Mater/blood supply , Pia Mater/diagnostic imaging , Pia Mater/surgery , AdultSubject(s)
Cerebral Revascularization , Collateral Circulation , Magnetic Resonance Angiography , Moyamoya Disease , Moyamoya Disease/surgery , Moyamoya Disease/diagnostic imaging , Humans , Cerebral Revascularization/methods , Collateral Circulation/physiology , Cerebrovascular Circulation/physiology , Pia Mater/blood supply , Pia Mater/diagnostic imaging , Pia Mater/surgeryABSTRACT
BACKGROUND: Pial arteriovenous fistulas (pAVFs) are rare vascular malformations characterized by high-flow arteriovenous shunting involving a cortical arterial supply directly connecting to venous drainage without an intermediate nidus. Dural arteriovenous fistulas (dAVFs) can infrequently involve additional pial feeders which can introduce higher flow shunting and increase the associated treatment risk. In the posterior fossa, arteriovenous fistula (AVF) angioarchitecture tends to be particularly complex, involving either multiple arterial feeders-sometimes from both dural and pial origins-or small caliber vessels that are difficult to catheterize and tend to be intimately involved with functionally critical brainstem or upper cervical cord structures. Given their rarity, published experience on microsurgical or endovascular treatment strategies for posterior fossa pAVFs and dAVFs with pial supply remains limited. METHODS: Retrospective chart review from 2019-2023 at a high-volume center identified six adult patients with posterior fossa pAVFs that were unable to be fully treated endovascularly and required microsurgical disconnection. These cases are individually presented with a technical emphasis and supported by comprehensive angiographic and intraoperative images. RESULTS: One vermian (Case 1), three cerebellopontine angle (Cases 2-4) and two craniovertebral junction (Cases 5-6) posterior fossa pAVFs or dAVFs with pial supply are presented. Three cases involved mixed dural and pial arterial supply (Cases 1, 4, and 6), and one case involved a concomitant microAVM (Case 2). Endovascular embolization was attempted in four cases (Cases 1-4): The small caliber and tortuosity of the main arterial feeder prevented catheterization in two cases (Cases 1 and 3). Partial embolization was achieved in Cases 2 and 4. In Cases 5 and 6, involvement of the lateral spinal artery or anterior spinal artery created a prohibitive risk for endovascular embolization, and surgical clip ligation was pursued as primary management. In all cases, microsurgical disconnection resulted in complete fistula obliteration without evidence of recurrence on follow-up imaging (mean follow-up 27.1 months). Two patients experienced persistent post-treatment sensory deficits without significant functional limitation. CONCLUSIONS: This illustrative case series highlights the technical difficulties and anatomical limitations of endovascular management for posterior fossa pAVFs and dAVFs with pial supply and emphasizes the relative safety and utility of microsurgical disconnection in this context. A combined approach involving partial preoperative embolization-when the angioarchitecture is permissive-can potentially decrease surgical morbidity. Larger studies are warranted to better define the role for multimodal intervention and to assess associated long-term AVF obliteration rates in the setting of pial arterial involvement.
Subject(s)
Central Nervous System Vascular Malformations , Pia Mater , Humans , Male , Female , Middle Aged , Central Nervous System Vascular Malformations/surgery , Aged , Pia Mater/blood supply , Pia Mater/surgery , Retrospective Studies , Adult , Arteriovenous Fistula/surgery , Cranial Fossa, Posterior/surgery , Neurosurgical Procedures/methods , Embolization, Therapeutic/methods , Intracranial Arteriovenous Malformations/surgeryABSTRACT
BACKGROUND AND OBJECTIVES: Moyamoya disease (MMD) is a chronic steno-occlusive disease of the intracranial circulation that depends on neoangiogenesis of collateral vessels to maintain cerebral perfusion and is primarily managed with cerebral revascularization surgery. A quantitative assessment of preoperative and postoperative collateral flow using quantitative magnetic resonance angiography with noninvasive optimal vessel analysis (NOVA) was used to illustrate the impact of revascularization on cerebral flow distribution. METHODS: A retrospective review of patients with unilateral MMD who underwent direct, indirect, or combined direct/indirect cerebral revascularization surgery was conducted between 2011 and 2020. Using NOVA, flow was measured at the anterior cerebral artery (ACA), ACA distal to the anterior communicating artery (A2), middle cerebral artery (MCA), posterior cerebral artery (PCA), and PCA distal to the posterior communicating artery (P2). Pial flow (A2 + P2) and collateral flow (ipsilateral [A2 + P2])-(contralateral [A2 + P2]) were measured and compared before and after revascularization surgery. Total hemispheric flow (MCA + A2 + P2) with the addition of the bypass graft flow postoperatively was likewise measured. RESULTS: Thirty-four patients with unilateral MMD underwent cerebral revascularization. Median collateral flow significantly decreased from 68 to 39.5 mL/min ( P = .007) after bypass. Hemispheres with maintained measurable bypass signal on postoperative NOVA demonstrated significant reduction in median collateral flow after bypass ( P = .002). Median total hemispheric flow significantly increased from 227 mL/min to 247 mL/min ( P = .007) after bypass. Only one patient suffered an ipsilateral ischemic stroke, and no patients suffered a hemorrhage during follow-up. CONCLUSION: NOVA measurements demonstrate a reduction in pial collateral flow and an increase in total hemispheric flow after bypass for MMD, likely representing a decrease in leptomeningeal collateral stress on the distal ACA and PCA territories. Further studies with these measures in larger cohorts may elucidate a role for NOVA in predicting the risk of ischemic and hemorrhagic events in MMD.
Subject(s)
Cerebral Revascularization , Cerebrovascular Circulation , Collateral Circulation , Magnetic Resonance Angiography , Moyamoya Disease , Humans , Moyamoya Disease/surgery , Moyamoya Disease/diagnostic imaging , Moyamoya Disease/physiopathology , Cerebral Revascularization/methods , Female , Male , Collateral Circulation/physiology , Adult , Retrospective Studies , Middle Aged , Cerebrovascular Circulation/physiology , Young Adult , Adolescent , Child , Pia Mater/blood supply , Pia Mater/diagnostic imaging , Pia Mater/surgeryABSTRACT
INTRODUCTION: Pediatric non-galenic pial arteriovenous fistulas (pAVFs) are rare vascular malformations that are characterized by a pial arterial-venous connection without an intervening capillary bed. Outcomes and treatment strategies for pAVFs are highly individualized, owing to the rarity of the disease and lack of large-scale data guiding optimal treatment approaches. METHODS: We performed a systematic review of pediatric patients (< 18 years at diagnosis) diagnosed with a pAVF by digital subtraction angiogram (DSA). The demographics, treatment modalities, and outcomes were documented for each patient and clinical outcome data was collected. Descriptive information stratified by outcome scores were classified as follows: 1 = excellent (no deficit and full premorbid activity), 2 = good (mild deficit and full premorbid activity), 3 = fair (moderate deficit and impaired activity), 4 = poor (severe deficit and dependent on others), 5 = death. RESULTS: A total of 87 studies involving 231 patients were identified. Median age at diagnosis was 3 years (neonates to 18 years). There was slight male preponderance (55.4%), and 150 subjects (81.1%*) experienced excellent outcomes after treatment. Of the 189 patients treated using endovascular approaches, 80.3% experienced excellent outcomes and of the 15 patients surgically treated subjects 75% had an excellent outcome. The highest rate of excellent outcomes was achieved in patients treated with Onyx (95.2%) and other forms of EvOH (100%). High output heart failure and comorbid vascular lesions tended to result in worse outcomes, with only 54.2% and 68% of subjects experiencing an excellent outcome, respectively. *Outcomes were reported in only 185 patients. CONCLUSION: pAVFs are rare lesions, necessitating aggregation of patient data to inform natural history and optimal treatment strategies. This review summarizes the current literature on pAVF in children, where children presenting with heart failure as a result of high flow through the lesion were less likely to experience an excellent outcome. Prospective, large-scale studies would further characterize pediatric pAVFs and enable quantitative analysis of outcomes to inform best treatment practices.
Subject(s)
Arteriovenous Fistula , Pia Mater , Humans , Child , Arteriovenous Fistula/surgery , Arteriovenous Fistula/diagnostic imaging , Arteriovenous Fistula/therapy , Pia Mater/blood supply , Child, Preschool , Adolescent , Infant , Female , Infant, Newborn , Treatment Outcome , Male , Intracranial Arteriovenous Malformations/therapy , Intracranial Arteriovenous Malformations/diagnostic imaging , Intracranial Arteriovenous Malformations/surgerySubject(s)
Arteriovenous Fistula , Humans , Infant, Newborn , Arteriovenous Fistula/surgery , Arteriovenous Fistula/diagnostic imaging , Pia Mater/blood supply , Pia Mater/surgery , Pia Mater/diagnostic imaging , Cerebral Veins/surgery , Cerebral Veins/diagnostic imaging , Cerebral Veins/abnormalities , Male , FemaleABSTRACT
BACKGROUND: CSF has long been accepted to circulate throughout the subarachnoid space, which lies between the arachnoid and pia maters of the meninges. How the CSF interacts with the cellular components of the developing postnatal meninges including the dura, arachnoid, and pia of both the meninges at the surface of the brain and the intracranial meninges, prior to its eventual efflux from the cranium and spine, is less understood. Here, we characterize small and large CSF solute distribution patterns along the intracranial and surface meninges in neonatal rodents and compare our findings to meningeal CSF solute distribution in a rodent model of intraventricular hemorrhage-posthemorrhagic hydrocephalus. We also examine CSF solute interactions with the tela choroidea and its pial invaginations into the choroid plexuses of the lateral, third, and fourth ventricles. METHODS: 1.9-nm gold nanoparticles, 15-nm gold nanoparticles, or 3 kDa Red Dextran Tetramethylrhodamine constituted in aCSF were infused into the right lateral ventricle of P7 rats to track CSF circulation. 10 min post-1.9-nm gold nanoparticle and Red Dextran Tetramethylrhodamine injection and 4 h post-15-nm gold nanoparticle injection, animals were sacrificed and brains harvested for histologic analysis to identify CSF tracer localization in the cranial and spine meninges and choroid plexus. Spinal dura and leptomeninges (arachnoid and pia) wholemounts were also evaluated. RESULTS: There was significantly less CSF tracer distribution in the dura compared to the arachnoid and pia maters in neonatal rodents. Both small and large CSF tracers were transported intracranially to the arachnoid and pia mater of the perimesencephalic cisterns and tela choroidea, but not the falx cerebri. CSF tracers followed a similar distribution pattern in the spinal meninges. In the choroid plexus, there was large CSF tracer distribution in the apical surface of epithelial cells, and small CSF tracer along the basolateral surface. There were no significant differences in tracer intensity in the intracranial meninges of control vs. intraventricular hemorrhage-posthemorrhagic hydrocephalus (PHH) rodents, indicating preserved meningeal transport in the setting of PHH. CONCLUSIONS: Differential CSF tracer handling by the meninges suggests that there are distinct roles for CSF handling between the arachnoid-pia and dura maters in the developing brain. Similarly, differences in apical vs. luminal choroid plexus CSF handling may provide insight into particle-size dependent CSF transport at the CSF-choroid plexus border.
Subject(s)
Hydrocephalus , Metal Nanoparticles , Animals , Rats , Pia Mater , Gold , Meninges , Arachnoid , Cerebral HemorrhageABSTRACT
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.
Subject(s)
Neuroinflammatory Diseases , Pia Mater , Female , Animals , Mice , Central Nervous System/diagnostic imaging , Arachnoid/diagnostic imaging , Cadherins , Inflammation , Mice, TransgenicABSTRACT
Leptomeninges, consisting of the pia mater and arachnoid, form a connective tissue investment and barrier enclosure of the brain. The exact nature of leptomeningeal cells has long been debated. In this study, we identify five molecularly distinct fibroblast-like transcriptomes in cerebral leptomeninges; link them to anatomically distinct cell types of the pia, inner arachnoid, outer arachnoid barrier, and dural border layer; and contrast them to a sixth fibroblast-like transcriptome present in the choroid plexus and median eminence. Newly identified transcriptional markers enabled molecular characterization of cell types responsible for adherence of arachnoid layers to one another and for the arachnoid barrier. These markers also proved useful in identifying the molecular features of leptomeningeal development, injury, and repair that were preserved or changed after traumatic brain injury. Together, the findings highlight the value of identifying fibroblast transcriptional subsets and their cellular locations toward advancing the understanding of leptomeningeal physiology and pathology.
Subject(s)
Arachnoid , Meninges , Mice , Animals , Arachnoid/anatomy & histology , Pia Mater , Choroid Plexus , BrainABSTRACT
The spinal cord comprises the part of the central nervous system located within the vertebral canal, extending from the foramen magnum to approximately the second lumbar vertebra. The spinal cord is covered by 3 meninges: dura mater, arachnoid mater, and pia mater (arranged from the outermost layer inward). A cross-section of the spinal cord reveals gray and white matter. Ascending and descending pathways have defined locations in the matter of the spinal cord. This article aims to review the spinal cord anatomy and demonstrate the imaging aspects, which are essential for the interpretation and understanding of spinal cord injuries.
Subject(s)
Dura Mater , Meninges , Humans , Spinal Cord/diagnostic imaging , Arachnoid , Pia MaterABSTRACT
INTRODUCTION: Pial arteriovenous fistulas (pAVF) are rare vascular malformations, especially in children and newborns. In neonates, the most common symptom is congestive heart failure. CASE PRESENTATION: We report a case of an asymptomatic preterm newborn incidentally diagnosed with pAVF during a routine cranial ultrasound (cUS) on the third day of life. Cerebral magnetic resonance (MRI) confirmed the diagnosis. A wait-and-see approach was chosen by the multidisciplinary team. The cUS and the MRI on day 14 of life showed the spontaneous resolution of the lesion. CONCLUSIONS: This case underlines the challenges in identifying pAVF in the first weeks of life and demonstrates a possible positive outcome for affected neonates.
Subject(s)
Arteriovenous Fistula , Intracranial Arteriovenous Malformations , Thrombosis , Child , Humans , Infant, Newborn , Intracranial Arteriovenous Malformations/complications , Intracranial Arteriovenous Malformations/diagnostic imaging , Pia Mater/diagnostic imaging , Magnetic Resonance Imaging , Arteriovenous Fistula/complications , Arteriovenous Fistula/diagnostic imagingABSTRACT
Computational modelling of the brain requires accurate representation of the tissues concerned. Mechanical testing has numerous challenges, in particular for low strain rates, like neurosurgery, where redistribution of fluid is biomechanically important. A finite-element (FE) model was generated in FEBio, incorporating a spring element/fluid-structure interaction representation of the pia-arachnoid complex (PAC). The model was loaded to represent gravity in prone and supine positions. Material parameter identification and sensitivity analysis were performed using statistical software, comparing the FE results to human in vivo measurements. Results for the brain Ogden parameters µ, α and k yielded values of 670 Pa, -19 and 148 kPa, supporting values reported in the literature. Values of the order of 1.2 MPa and 7.7 kPa were obtained for stiffness of the pia mater and out-of-plane tensile stiffness of the PAC, respectively. Positional brain shift was found to be non-rigid and largely driven by redistribution of fluid within the tissue. To the best of our knowledge, this is the first study using in vivo human data and gravitational loading in order to estimate the material properties of intracranial tissues. This model could now be applied to reduce the impact of positional brain shift in stereotactic neurosurgery.
Subject(s)
Brain , Pia Mater , Humans , Computer Simulation , Finite Element Analysis , Stress, Mechanical , Biomechanical PhenomenaABSTRACT
Inflammation triggers secondary brain damage after stroke. The meninges and other CNS border compartments serve as invasion sites for leukocyte influx into the brain thus promoting tissue damage after stroke. However, the post-ischemic immune response of border compartments compared to brain parenchyma remains poorly characterized. Here, we deeply characterize tissue-resident leukocytes in meninges and brain parenchyma and discover that leukocytes respond differently to stroke depending on their site of residence. We thereby discover a unique phenotype of myeloid cells exclusive to the brain after stroke. These stroke-associated myeloid cells partially resemble neurodegenerative disease-associated microglia. They are mainly of resident microglial origin, partially conserved in humans and exhibit a lipid-phagocytosing phenotype. Blocking markers specific for these cells partially ameliorates stroke outcome thus providing a potential therapeutic target. The injury-response of myeloid cells in the CNS is thus compartmentalized, adjusted to the type of injury and may represent a therapeutic target.
Subject(s)
Infarction, Middle Cerebral Artery/complications , Myeloid Cells/immunology , Neuroinflammatory Diseases/immunology , Aged , Aged, 80 and over , Animals , Brain/cytology , Brain/immunology , Brain/pathology , Disease Models, Animal , Female , Gene Knock-In Techniques , Humans , Infarction, Middle Cerebral Artery/immunology , Infarction, Middle Cerebral Artery/pathology , Male , Mice , Microglia/cytology , Microglia/immunology , Middle Aged , Neuroinflammatory Diseases/pathology , Pia Mater/cytology , Pia Mater/immunology , Pia Mater/pathologySubject(s)
Osteoma , Spinal Cord Neoplasms , Dura Mater , Humans , Magnetic Resonance Imaging , Osteoma/diagnostic imaging , Osteoma/surgery , Pia Mater , Spinal Cord/diagnostic imaging , Spinal Cord/surgery , Spinal Cord Neoplasms/diagnostic imaging , Spinal Cord Neoplasms/surgery , Thoracic Vertebrae/diagnostic imaging , Thoracic Vertebrae/surgeryABSTRACT
BACKGROUND AND OBJECTIVE: Accurate finite element (FE) simulation of the optic nerve head (ONH) depends on accurate mechanical properties of the load-bearing tissues. The peripapillary sclera in the ONH exhibits a depth-dependent, anisotropic, heterogeneous collagen fiber distribution. This study proposes a novel cable-in-solid modeling approach that mimics heterogeneous anisotropic collagen fiber distribution, validates the approach against published experimental biaxial tensile tests of scleral patches, and demonstrates its effectiveness in a complex model of the posterior human eye and ONH. METHODS: A computational pipeline was developed that defines control points in the sclera and pia mater, distributes the depth-dependent circumferential, radial, and isotropic cable elements in the sclera and pia in a pattern that mimics collagen fiber orientation, and couples the cable elements and solid matrix using a mesh-free penalty-based cable-in-solid algorithm. A parameter study was performed on a model of a human scleral patch subjected to biaxial deformation, and computational results were matched to published experimental data. The new approach was incorporated into a previously published eye-specific model to test the method; results were then interpreted in relation to the collagen fibers' (cable elements) role in the resultant ONH deformations, stresses, and strains. RESULTS: Results show that the cable-in-solid approach can mimic the full range of scleral mechanical behavior measured experimentally. Disregarding the collagen fibers/cable elements in the posterior eye model resulted in â¼20-60% greater tensile and shear stresses and strains, and â¼30% larger posterior deformations in the lamina cribrosa and peripapillary sclera. CONCLUSIONS: The cable-in-solid approach can easily be implemented into commercial FE packages to simulate the heterogeneous and anisotropic mechanical properties of collagenous biological tissues.
Subject(s)
Pia Mater , Sclera , Biomechanical Phenomena , Finite Element Analysis , Humans , Models, BiologicalABSTRACT
Brain tissues are surrounded by two tightly adhering thin membranes known as the pia-arachnoid complex (PAC), which is pivotal in regulating brain mechanical response upon mechanical impact. Despite the crucial role of PAC as a structural damper protecting the brain, its mechanical contribution has received minimal attention. In this work, the mechanical contribution of PAC on brain tissues against mechanical loading is characterized by using a custom-built indentation apparatus. The indentation responses of the isolated and PAC-overlaid brains are quantitatively compared at different length scales and strain rates. Results show that PAC substantially affects the indentation response of brain tissues at micro- and macro-scales and provides better protection against mechanical impact at a relatively small (µm) length scale. The modulus of the PAC-overlaid brain shows a threefold stiffening at the microscale compared with that of the isolated brain (with instantaneous shear modulus distribution means of 0.85 ± 0.14 kPa versus 2.64 ± 0.43 kPa at the strain rate of 0.64 s-1 and 1.40 ± 0.31 kPa versus 4.02 ± 0.51 at 1.27 s-1). These findings indicate that PAC seriously affects the mechanical response of brain tissues, especially at the microscale, and may have important implications for the studies of brain injury.
Subject(s)
Arachnoid , Brain Injuries , Animals , Arachnoid/physiology , Brain , Elastic Modulus , Head , Pia Mater/physiology , Stress, Mechanical , SwineABSTRACT
Introduction This study aims at identifying mechanical characteristics under bi-axial loading conditions of extracted swine pia mater (PM) and dura and arachnoid complex (DAC). Methods 59 porcine spinal samples have been tested on a bi-axial experimental device with a pre-load of 0.01 N and a displacement rate of 0.05 mm·s-1. Post-processing analysis included an elastic modulus, as well as constitutive model identification for Ogden model, reduced Gasser Ogden Holzapfel (GOH) model, anisotropic GOH model, transverse isotropic and anisotropic Gasser models as well as a Mooney-Rivlin model including fiber strengthening for PM. Additionally, micro-structure of the tissue was investigated using a bi-photon microscopy. Results Linear elastic moduli of 108 ± 40 MPa were found for DAC longitudinal direction, 53 ± 32 MPa for DAC circumferential direction, with a significant difference between directions (p < 0.001). PM presented significantly higher longitudinal than circumferential elastic moduli (26 ± 13 MPa vs 13 ± 9 MPa, p < 0.001). Transversely isotropic and anisotropic Gasser models were the most suited models for DAC (r2 = 0.99 and RMSE:0.4 and 0.3 MPa) and PM (r2 = 1 and RMSE:0.06 and 0.07 MPa) modelling. Conclusion This work provides reference values for further quasi-static bi-axial studies, and is the first for PM. Collagen structures observed by two photon microscopy confirmed the use of anisotropic Gasser model for PM and the existence of fenestration. The results from anisotropic Gasser model analysis depicted the best fit to experimental data as per this protocol. Further investigations are required to allow the use of meningeal tissue mechanical behaviour in finite element modelling with respect to physiological applications. STATEMENT OF SIGNIFICANCE: This study is the first to present biaxial tensile test of pia mater as well as constitutive model comparisons for dura and arachnoid complex tissue based on such tests. Collagen structures observed by semi-quantitative analysis of two photon microscopy confirmed the use of anisotropic Gasser model for pia mater and existence of fenestration. While clear identification of fibre population was not possible in DAC, results from anisotropic Gasser model depicted better fitting on experimental data as per this protocol. Bi-axial mechanical testing allows quasi-static characterization under conditions closer to the physiological context and the results presented could be used for further simulations of physiology. Indeed, the inclusion of meningeal tissue in finite element models will allow more accurate and reliable numerical simulations.
Subject(s)
Arachnoid , Pia Mater , Animals , Anisotropy , Biomechanical Phenomena , Elastic Modulus , Stress, Mechanical , Swine , Tensile StrengthABSTRACT
Background Cerebrovascular autoregulation (CA) regulates cerebral vascular tone to maintain near-constant cerebral blood flow during fluctuations in cerebral perfusion pressure (CPP). Preclinical and clinical research has challenged the classic triphasic pressure-flow relationship, leaving the normal pressure-flow relationship unclear. Methods and Results We used in vivo imaging of the hemodynamic response in pial arterioles to study CA in a porcine closed cranial window model during nonpharmacological blood pressure manipulation. Red blood cell flux was determined in 52 pial arterioles during 10 hypotension and 10 hypertension experiments to describe the pressure-flow relationship. We found a quadriphasic pressure-flow relationship with 4 distinct physiological phases. Smaller arterioles demonstrated greater vasodilation during low CPP when compared with large arterioles (P<0.01), whereas vasoconstrictive capacity during high CPP was not significantly different between arterioles (P>0.9). The upper limit of CA was defined by 2 breakpoints. Increases in CPP lead to a point of maximal vasoconstriction of the smallest pial arterioles (upper limit of autoregulation [ULA] 1). Beyond ULA1, only larger arterioles maintain a limited additional vasoconstrictive capacity, extending the buffer for high CPP. Beyond ULA2, vasoconstrictive capacity is exhausted, and all pial arterioles passively dilate. There was substantial intersubject variability, with ranges of 29.2, 47.3, and 50.9 mm Hg for the lower limit, ULA1, and ULA2, respectively. Conclusions We provide new insights into the quadriphasic physiology of CA, differentiating between truly active CA and an extended capacity to buffer increased CPP with progressive failure of CA. In this experimental model, the limits of CA widely varied between subjects.