An MRI-derived head-neck finite element model.

Minor neck injuries in rear collision accidents have become a huge problem in many countries. Therefore, it is urgent to develop a suitable criterion for assessing neck injury risk. In this study, a detailed head-neck finite element (FE) model was developed. Skull and vertebrae models were created based on CT images of a typical Japanese male. Models of intervertebral discs, ligaments and muscles were also created according to literatures. Furthermore, material properties were taken from the published data. In order to evaluate intervertebral soft tissue strain due to translational rotational coupled motion of vertebrae, a 2D strain analysis method was also proposed. The method was applied to cervical vertebral motion data obtained from previous rear impact tests using human volunteers and from test reconstruction using the head-neck model. A potential correlation between intervertebral strain and neck injury was clarified from the comparison between the intervertebral strain level and existence of neck discomforts. The model’s response is also in good agreement with the volunteers’ response, indicating that the head-neck model is suitable for minor neck injury analysis and that it is possible to analyze the intervertebral strain with a head-neck model.KeywordsNeck injuryrear impactfinite element analysishead-neck modelintervertebral strain

Stress is the leading precipitating factor for migraine attacks but the underlying mechanism is currently unknown. Nitric oxide (NO) has been implicated in migraine pathogenesis based on the ability of NO donors to induce migraine attacks. In the present study, we investigated in Wistar rats the effect of air stress on nitric oxide synthase (NOS) mRNA and protein expression in dura and pia mater using real-time polymerase chain reaction and Western blotting, respectively. Endothelial (e)NOS protein expression was significantly increased in dura and pia mater after air stress. Significantly augmented neuronal (n)NOS protein expression was detected in pia mater after air stress but not in dura mater. Inducible NOS mRNA and protein expression levels in dura and pia mater were unaffected by stress. The increased expression of eNOS in dura mater and eNOS and nNOS in pia mater seen after stress could not be antagonized by treatment with the migraine drug sumatriptan. These findings point towards the involvement of increased NO concentrations in dura and pia mater in response to air stress. However, the role of these findings in relation to migraine pathophysiology remains unclear.

The aims of this study were to develop a three-dimensional patient-specific finite element (FE) brain model with detailed anatomical structures and appropriate material properties to predict intraoperative brain shift during neurosurgery and to update preoperative magnetic resonance (MR) images using FE modeling for presurgical planning. A template-based algorithm was developed to build a 3D patient-specific FE brain model. The template model is a 50th percentile male FE brain model with gray and white matter, ventricles, pia mater, dura mater, falx, tentorium, brainstem, and cerebellum. Gravity-induced brain shift after opening of the dura was simulated based on one clinical case of computer-assisted neurosurgery for model validation. Preoperative MR images were updated using an FE model and displayed as intraoperative MR images easily recognizable by surgeons. To demonstrate the potential of FE modeling in presurgical planning, intraoperative brain shift was predicted for two additional head orientations. Two patient-specific FE models were constructed. The mesh quality of the resulting models was as high as that of the template model. One of the two FE models was selected to validate model-predicted brain shift against data acquired on intraoperative MR imaging. The brain shift predicted using the model was greater than that observed intraoperatively but was considered surgically acceptable. A set of algorithms for developing 3D patient-specific FE brain models is presented. Gravity-induced brain shift can be predicted using this model and displayed on high-resolution MR images. This strategy can be used not only for updating intraoperative MR imaging, but also for presurgical planning.

This chapter aimed to study the biomechanical response and injury mechanisms of brain in passenger car-to-pedestrian collision event. The kinematics of head impact to a passenger car was reconstructed using multibody dynamics (MBD) models. The brain injury biomechanics was investigated by using an FE model of human body head (HBM-head). The HBM-head model was developed in accordance with human head anatomy. The model consists of scalp, skull, dura mater, cerebrospinal fluid, pia mater, cerebrum, cerebellum, ventricle, brain stem, falx, tentorium, etc. The existing data from cadaveric head impact tests were used to validate the head FE model. The kinematic and kinetic responses of the head were determined by using MBD model. The brain injury-related physical parameters and the distribution of the intracranial pressure were calculated from simulations of head impact to the windscreen and A-pillar by using the HBM-head model. It is proved that the head FE model has good biofidelity and can be used to study head–brain trauma and injury mechanisms in vehicle collisions.

Quantitative magnetic resonance imaging (MRI) provides useful information about intervertebral disc (IVD) biomechanical properties, especially those in relation to the fluid phase. These properties may improve IVD finite element (FE) models using data closer to physiological reality. The aim of this study is to investigate IVD degeneration-related properties using a coupling between MRI and FE modeling. To this end, proton density ()-weighted MRI sequences of a porcine lumbar IVD were carried out to develop two biphasic swelling models with hyperelastic extracellular matrix behavior. The first model is isotropic, and the second one is anisotropic and takes into account the role of collagen fibers in the mechanical behavior of the IVD. MRI sequences permitted to determine the geometry and the real porosity mapping within the disc. The differentiation between disc components (nucleus pulposus, annulus fibrosus and cartilaginous end plates) was taken into account using spatial continuous distributions of the mechanical properties. The validation of the FE models was performed through two steps: the identification of the model's mechanical properties using relaxation compressive test and the comparison between the MRI after load porosity distributions and those numerically obtained using the set of identified properties. The results confirmed that the two developed FE models were able to predict the mechanical response of uniaxial time-dependent compressive test and the redistribution of porosity after load. A slight difference between the measured and the numerical local bulges of the disc was found. This study suggests that from the coupling between MRI imaging in different state of load and finite element modeling we can deduce relevant information that can be used in the assessment of the early intervertebral disc degeneration changes.

Development and global validation of a 1-week-old piglet head finite element model for impact simulations

Development, verification, and validation of a parametric cervical spine injury prediction model

Spinal cord impacts can have devastating consequences. Computational models can investigate such impacts but require biofidelic numerical representations of the neural tissues and fluid-structure interaction with cerebrospinal fluid. Achieving this biofidelity is challenging, particularly for efficient implementation of the cerebrospinal fluid in full computational human body models. The goal of this study was to assess the biofidelity and computational efficiency of fluid-structure interaction methods representing the cerebrospinal fluid interacting with the spinal cord, dura, and pia mater using experimental pellet impact test data from bovine spinal cords. Building on an existing finite element model of the spinal cord and pia mater, an orthotropic hyperelastic constitutive model was proposed for the dura mater and fit to literature data. The dura mater and cerebrospinal fluid were integrated with the existing finite element model to assess four fluid-structure interaction methods under transverse impact: Lagrange, pressurized volume, smoothed particle hydrodynamics, and arbitrary Lagrangian-Eulerian. The Lagrange method resulted in an overly stiff mechanical response, whereas the pressurized volume method over-predicted compression of the neural tissues. Both the smoothed particle hydrodynamics and arbitrary Lagrangian-Eulerian methods were able to effectively model the impact response of the pellet on the dura mater, outflow of the cerebrospinal fluid, and compression of the spinal cord; however, the arbitrary Lagrangian-Eulerian compute time was approximately five times higher than smoothed particle hydrodynamics. Crucial to implementation in human body models, the smoothed particle hydrodynamics method provided a computationally efficient and representative approach to model spinal cord fluid-structure interaction during transverse impact.

Clinically, spinal cord injuries (SCIs) are radiographically evaluated and diagnosed from plain radiographs, computed tomography (CT), and magnetic resonance imaging. However, it is difficult to conclude that radiographic evaluation of SCI can directly explain the fundamental mechanism of spinal cord damage. The von-Mises stress and maximum principal strain are directly associated with neurological damage in the spinal cord from a biomechanical viewpoint. In this study, the von-Mises stress and maximum principal strain in the spinal cord as well as the cord cross-sectional area (CSA) were analyzed under various magnitudes for contusion, dislocation, and distraction SCI mechanisms, using a finite-element (FE) model of the cervical spine with spinal cord including white matter, gray matter, dura mater with nerve roots, and cerebrospinal fluid (CSF). A regression analysis was performed to find correlation between peak von-Mises stress/peak maximum principal strain at the cross section of the highest reduction in CSA and corresponding reduction in CSA of the cord. Dislocation and contusion showed greater peak stress and strain values in the cord than distraction. The substantial increases in von-Mises stress as well as CSA reduction similar to or more than 30% were produced at a 60% contusion and a 60% dislocation, while the maximum principal strain was gradually increased as injury severity elevated. In addition, the CSA reduction had a strong correlation with peak von-Mises stress/peak maximum principal strain for the three injury mechanisms, which might be fundamental information in elucidating the relationship between radiographic and mechanical parameters related to SCI.

Intraparenchymal pressure (IPP) measurements in an in vitro cadaveric model of CNS edema. To assess the contribution of pia mater to IPP and the effect of piotomy. Multicenter randomized control trials have shown that decompression with durotomy/duroplasty significantly decreases intracranial pressure (ICP). There is a paucity of evidence regarding the effectiveness of decompression of the spinal cord by piotomy. The supratentorial brain and spinal cord were removed from six fresh cadavers. Dura and arachnoid mater were removed. ICP monitors were placed bilaterally in the frontal and parietal lobes, and centrally in the cervical and thoracic spinal cord. To simulate edema, specimens were submerged in hypotonic solution. IPP was recorded for 5 days. A complete dorsal midline piotomy was performed on the spinal cord and resulting IPP was recorded. Brain and spinal cord both increased in weight. IPP significantly increased in both brain and spinal cord. The IPP increase within the spinal cord was substantially greater (averages: all four lobes = 4.0 mm Hg; cervical = 73.7 mm Hg; thoracic = 49.3 mm Hg). After piotomy, cervical and thoracic spinal cord IPP decreased immediately (avg. postpiotomy IPP = 9.7 and 10.3, respectively). There were differential effects on brain and spinal cord IPP. Brain IPP increased only slightly, possibly because of the absence of the cranium and dura mater. In contrast, spinal cord IPP increased substantially even in the absence of the laminae, dura, and arachnoid mater. Piotomy immediately and dramatically reduced spinal cord IPP. These data are consistent with the hypothesis that spinal cord IPP is primarily dependent on constraints imposed by the pia mater. Conversely, in the absence of the cranium and dura mater, the sulci may permit the pia-invested brain to better accommodate edema without significant increases in IPP. N/A.

Professional drivers are frequently exposed to multi-axis vibration environments. The effect of active control of neck muscles on injury risk of cervical spine in a sustained vibration environment remains unclear. This study aims to explore the effect of multi-axis vibration and muscles on driver's neck health. A head-neck finite element model with active muscles was developed. The injury of the cervical spine tissues was analyzed under different muscle activation levels and vibration conditions. The results showed that compared with the uniaxial vibration, the vibration amplitude of head increased by 70.65% (vertical) under the multi-axis vibration condition. This indicated that the vibration of the head-neck was more intense under the multi-axis vibration environment compared with the uniaxial vertical vibration. Compared with passive muscles, the active muscles (activation level was 0.05) could reduce the head vibration amplitude by 39.88% in the vertical direction, 12.59% in the fore-aft direction, respectively, and this vibration suppression was more pronounced in the fore-aft direction compared with the vertical direction. In the multi-axis vibration environment, neck muscles could suppress head movements induced by vibration, especially in the fore-aft direction, reducing the risk of disc injury. The level of muscle activation was positively correlated with the suppressive effect.

A 76-year-old male presented with acute renal failure and cast nephropathy was diagnosed with IgG kappa multiple myeloma (MM). His paraprotein was 40 g/L, kappa-free light chain level was 17,058 mg/L, kappa: lambda light chain ratio was 1445. An automated full blood count showed hemoglobin 90 g/L, white blood cells 2.96 × 109/L, neutrophil 1.7 × 109/L, and platelet 179 × 109/L. Bone marrow trephine sample was hypercellular with nearly 100% plasma cells, which were positive for CD138, CD56, and cyclin D1, and showed kappa light chain restriction. Fluorescence in situ hybridization analysis with dual color/dual probes for immunoglobulin heavy chain (IGH) and MYC genes (Cytocell) and whole genome screening using 8 × 60K oligonucleotide arrays (Agilent) performed on the CD138 enriched cells (CD138 microbeads Miltenyi Biotech) from the liquid bone marrow sample showed no evidence of IGH rearrangement, MYC rearrangement, 1q gain, 1p loss, 17p loss, or any clinically significant imbalance. He was treated with eight cycles of bortezomib, cyclophosphamide, and dexamethasone (VCD) to very good partial response. He relapsed 30 months after diagnosis with paraprotein of 36 g/L, kappa light chains of 10,000 mg/L, and creatinine of 498 μmol/L. He was treated with eight cycles of bortezomib, thalidomide, and dexamethasone (VTD) to paraprotein undetectable and kappa light chain 29 mg/L. Seven months post completion of VTD (4 years after myeloma diagnosis), he presented with abnormal gait, falls, and a left-sided facial droop. His paraprotein was 2 g/L and serum-free kappa light chain was 81 mg/L. Magnetic resonance imaging (MRI) head and whole spine showed multifocal diseases in spinal canal and intracranially, involving the cranial nerves most prominent the fifth, seventh, eighth, and hypoglossal nerve on the left, anterior surface of the inferior pons medulla (Figure 1A). There were multiple lesions in the cervical spine as well as in the thoracic spine (Figure 1B). Computerized tomography (CT) chest abdomen pelvis did not show the evidence of other new diseases. Plasma cells were detected in cerebral spinal fluid (CSF) (Figure 1C, May–Grünwald–Giemsa stain x100 objective). He was treated with pomalidomide and dexamethasone. Weekly cytarabine intrathecal (IT) treatment was given until the clearance of plasma cells from CSF samples for three times. Four months later, he achieved the complete remission on MRI head and whole spine with undetectable paraprotein and normal light chain ratio. Serial MRI scans confirmed ongoing remission. A year later, he relapsed again with worsening mobility and reappearance of myeloma cells in CSF. By flow cytometry, these cells were positive for CD138, CD38, CD56, CD117, and negative for CD19. MRI head showed leptomeningeal disease with a new 2.2 cm frontal lobe lesion. His paraprotein remained undetectable and kappa light chain remained at below 100 mg/L. He continued systemic pomalidomide and dexamethasone chemotherapy and received palliative whole brain radiotherapy 20 Gy in 5 fractions for symptom control. His disease continued progressing and he passed away 3 months later (5.5 years after myeloma diagnosis). Here, we reported a myeloma patient with isolated CNS relapse, who achieved 1 year of remission with combination of intrathecal chemotherapy and systemic pomalidomide and dexamethasone treatment, but sadly passed away 4 months after second CNS relapse. CNS MM is a rare form of extramedullary disease, but carries a very poor prognosis. The optimal approach to treatment of CNS MM is not currently known. The current approach includes systemic therapy with agents known to cross the blood brain barrier, intrathecal therapy, and CNS irradiation. Innovative approach to treatment is urgently needed. The authors received no specific funding for this work. Ke Xu and Lucy Kamuriwo wrote the manuscript. Ke Xu, Lucy Kamuriwo, Claire Anderson and Parag Jasani critically revised the final version of the manuscript. The authors declare they have no conflicts of interest. No written or verbal consent obtained from patient. Patient has passed away.

Chapter 13 - Meninges, cerebrospinal fluid and cerebral ventricles

ObjectivesTo investigate the optimal timing for post-chemoradiotherapy (CRT) reference magnetic resonance imaging (MRI) in head and neck cancer, so as to demonstrate a maximal treatment response. To assess whether this differs in human papillomavirus–related oropharyngeal cancer (HPV-OPC) and whether the MRI timing impacts on the ability to predict treatment success.MethodsFollowing ethical approval and informed consent, 45 patients (40 male, mean age 59.7 ± 7.9 years, 33 HPV-OPC) with stage 3 and 4 HNSCC underwent pre-treatment, 6- and 12-week post-CRT MRIs in this prospective cohort study. Primary tumour (n = 39) size, T2w morphology and diffusion weight imaging (DWI) scores, together with nodal (n = 42) size and necrotic/cystic change, were recorded. Interval imaging changes were analysed for all patients and according to HPV-OPC status. MRI descriptors and their interval changes were also compared with 2-year progression-free survival (PFS).ResultsAll MRI descriptors significantly changed between pre-treatment and 6-week post-treatment MRI studies (p < .001). Primary tumour and nodal volume decreased between 6- and 12-week studies; however, interval changes in linear dimensions were only evident for HPV-OPC lymph nodes. Nodal necrosis scores also evolved after 6 weeks but other descriptors were stable. The 6-week nodal necrosis score and the 6- and 12-week nodal volume were predictive of 2-year PFS.ConclusionApart from HPV-OPC patients with nodal disease, the 6-week post-CRT MRI demonstrates maximal reduction in the linear dimensions of head and neck cancer; however, a later reference study should be considered if volumetric analysis is applied.Key Points• This study provides guidance on when early post-treatment imaging should be performed in head and neck cancer following chemoradiotherapy, in order to aid subsequent detection of recurrent tumour.• Lymph nodes in HPV-related oropharyngeal cancer patients clearly reduced in size from 6 to 12 weeks post-treatment. However, other lymph node disease and all primary tumours showed only a minor reduction in size beyond 6 weeks, and this required a detailed volumetric analysis for demonstration.• Timing of the reference MRI following chemoradiotherapy for head and neck cancer depends on whether the patient has HPV-related oropharyngeal cancer and whether there is nodal disease. MRI as early as 6 weeks post-treatment may be performed unless volumetric analysis is routinely performed.

Objective To evaluate the elementary characteristics of electrical stimulation on the cortex transferred from dura mater in order to verify the feasibility of a visual neuroprosthetic strategy based on epidural electrical stimulation.Methods This was an experimental study.A single square current was selected to stimulate the visual cortex of the cat through dura mater.The stimulus class and parameters of the single square current were varied and the voltage signal of the visual cortex was recorded.The visual cortex signal was recorded on paper and analyzed to study the attenuation of the transmission passing through dura mater, cerebrospinal fluid and pia mater. Results The cortical recordings agreed with some published experimental results when the stimulus type was altered.When the single-square current stimulus pulse width increased, the recorded voltage of the Vp-p phase changed noticeably but the Vp-p amplitude only changed within a narrow range.When the stimulus amplitude of the single-square current increased, the recorded voltage of the cortical Vp-p amplitude also increased.When the distance between the stimulating electrode and recording electrode decreased, the recorded voltage of the Vp-p amplitude increased.When the depth of the recording electrode gradually increased from 0 μm, 200 μm, 400 μm, 600 μm, 800 μm, the cortical recording of the vohage's amplitude decreased.Conclusion Cortical stimulation is still an effective signal,which originates from the epidural electrical stimulus by passing through dura mater,cerebrospinal fluid and pia mater.The strategy that epidural electrical stimulation can affect the visual cortex is verified to be feasible. Key words: Visual cortex ; Mater,dura; Electrical stimulation ; Electrode-tissue interface