The "state of the art" of intraoperative neurophysiological monitoring: An Italian neurosurgical survey.

Introduction: Intraoperative Neurophysiological Monitoring (IOM) is widely used in neurosurgery but specific guidelines are lacking. Therefore, we can assume differences in IOM application between Neurosurgical centers. Research question: The section of Functional Neurosurgery of the Italian Society of Neurosurgery realized a survey aiming to obtain general data on the current practice of IOM in Italy. Materials and methods: A 22-item questionnaire was designed focusing on: volume procedures, indications, awake surgery, experience, organization and equipe. The questionnaire has been sent to Italian Neurosurgery centers. Results: A total of 54 centers completed the survey. The annual volume of surgeries range from 300 to 2000, and IOM is used in 10-20% of the procedures. In 46% of the cases is a neurologist or a neurophysiologist who performs IOM. For supra-tentorial pathology, almost all perform MEPs (94%) SSEPs (89%), direct cortical stimulation (85%). All centers perform IOM in spinal surgery and 95% in posterior fossa surgery. Among the 50% that perform peripheral nerve surgery, all use IOM. Awake surgery is performed by 70% of centers. The neurosurgeon is the only responsible for IOM in 35% of centers. In 83% of cases IOM implementation is adequate to the request. Discussion and conclusions: The Italian Neurosurgical centers perform IOM with high level of specialization, but differences exist in organization, techniques, and expertise. Our survey provides a snapshot of the state of the art in Italy and it could be a starting point to implement a consensus on the practice of IOM.

Persistent hemiplegia with normal intraoperative neurophysiological monitoring in supratentorial neurosurgery: a case report and review of literature.

Intraoperative neurophysiological monitoring (IONM) is needed for evaluating and demonstrating the integrity of the central and peripheral nervous system during surgical manoeuvres that take place in proximity to eloquent motor and somatosensory nervous structures. The integrity of the monitored motor pathways is not always followed by consistent clinical normality, particularly in the first hours/days following surgery, when surgical resection involves brain structures such as the supplementary motor areas (SMA). We report the case of a patient who underwent surgical excision of a right frontal glioblastoma with normal preoperative, intraoperative (IONM), and postoperative central motor conduction, but with persistent postoperative hemiplegia (> 6 months). The literature regarding SMA syndrome and its diagnosis and prognosis is reviewed.

Phase I clinical trial of intracerebroventricular transplantation of allogeneic neural stem cells in people with progressive multiple sclerosis.

We report the analysis of 1 year of data from the first cohort of 15 patients enrolled in an open-label, first-in-human, dose-escalation phase I study (ClinicalTrials.gov: NCT03282760, EudraCT2015-004855-37) to determine the feasibility, safety, and tolerability of the transplantation of allogeneic human neural stem/progenitor cells (hNSCs) for the treatment of secondary progressive multiple sclerosis. Participants were treated with hNSCs delivered via intracerebroventricular injection in combination with an immunosuppressive regimen. No treatment-related deaths nor serious adverse events (AEs) were observed. All participants displayed stability of clinical and laboratory outcomes, as well as lesion load and brain activity (MRI), compared with the study entry. Longitudinal metabolomics and lipidomics of biological fluids identified time- and dose-dependent responses with increased levels of acyl-carnitines and fatty acids in the cerebrospinal fluid (CSF). The absence of AEs and the stability of functional and structural outcomes are reassuring and represent a milestone for the safe translation of stem cells into regenerative medicines.

The role of the osteoplastic flap in the endoscopic era: a retrospective multicentre experience on revision surgery.

Objective: To retrospectively review the experience of five tertiary-care university hospitals on frontal sinus revision surgery with osteoplastic flap (OPF). Methods: Descriptive analysis of patients who underwent frontal sinus surgery with OPF after one or more endoscopic procedures for benign and inflammatory pathologies from 2000 to 2022. Clinical charts were reviewed for demographics, indications, clinical presentation, previous frontal procedures, OPF technique and outcomes. Results: Of the 124 patients who underwent an OPF procedure, 33 met inclusion criteria. With a mean of 2.1 previous endoscopic surgeries, Draf III was the most common former procedure. In 30 (91%) cases OPF was part of a combined procedure. The most common indications were inverted papilloma (61%), mucocele (9%) and chronic rhinosinusitis (6%). Frontal outflow stenosis (36%) and mucocele (9%) were the most frequent complications observed. Improvement of overall symptoms and patient satisfaction after the OPF procedure were recorded. Conclusions: Even in the endoscopic era, OPF still represents a paramount procedure that should be included in the rhino-surgeon's armamentarium, in particular in patients with challenging pathologies and anatomy when previous endoscopic endonasal attempts have failed.

Estimated EEG functional connectivity and aperiodic component induced by vagal nerve stimulation in patients with drug-resistant epilepsy.

Background: Vagal nerve stimulation (VNS) improves seizure frequency and quality of life in patients with drug-resistant epilepsy (DRE), although the exact mechanism is not fully understood. Previous studies have evaluated the effect of VNS on functional connectivity using the phase lag index (PLI), but none has analyzed its effect on EEG aperiodic parameters (offset and exponent), which are highly conserved and related to physiological functions. Objective: This study aimed to evaluate the effect of VNS on PLI and aperiodic parameters and infer whether these changes correlate with clinical responses in subjects with DRE. Materials and methods: PLI, exponent, and offset were derived for each epoch (and each frequency band for PLI), on scalp-derived 64-channel EEG traces of 10 subjects with DRE, recorded before and 1 year after VNS. PLI, exponent, and offset were compared before and after VNS for each patient on a global basis, individual scalp regions, and channels and separately in responders and non-responders. A correlation analysis was performed between global changes in PLI and aperiodic parameters and clinical response. Results: PLI (global and regional) decreased after VNS for gamma and delta bands and increased for an alpha band in responders, but it was not modified in non-responders. Aperiodic parameters after VNS showed an opposite trend in responders vs. non-responders: both were reduced in responders after VNS, but they were increased in non-responders. Changes in aperiodic parameters correlated with the clinical response. Conclusion: This study explored the action of VNS therapy from a new perspective and identified EEG aperiodic parameters as a new and promising method to analyze the efficacy of neuromodulation.

Deep brain stimulation for Parkinson's disease in practice: results of the survey by the Italian Neurosurgery Society.

BACKGROUND: Deep brain stimulation (DBS) is a safe and effective treatment for patients with advanced Parkinson's disease (PD) and many neurosurgical centers in Italy have a DBS program. Considering the prevalence of PD and criteria for DBS implantation, about 3200-10,350 PD patients may benefit from DBS in Italy. The global management of patients underwent DBS is complex and it can be supposed that many differences exist between centers in clinical practice. The Italian Neurosurgery Society (SINch) designed this survey to investigate the state of the art of DBS for PD in Italy. METHODS: A 26-item closed-ended question survey was designed and sanded by email at all Italian Neurosurgery centers. The main topic investigated was DBS teams, anatomical target selection, surgical procedure, neuroimaging, intraoperative target localization, DBS device and patients' follow-up. RESULTS: A total of 23 neurosurgery centers completed the survey. There are mainly low-to medium-volume centers (<20 annual DBS procedures) with dedicated DBS teams. The principal anatomical target used is subthalamic nucleus (STN) and, relative to the surgical technique, it emerges that in Italy DBS are bilaterally implanted in a single-step session with awake anesthesia and with frame-based technique. Final leads positioning is defined by microelectrode recordings (MER) and microstimulation (MS), with limited role of intraoperative neuroimaging (MRI and O-Arm). The stimulation is started at 15 or 30 days from procedure. CONCLUSIONS: Many centers of neurosurgery in Italy have a well-established DBS program for patients with advanced PD and some practical differences in technique between centers exist. Further investigation is needed to investigate specific criteria for selecting one technique over another.

Incidence and spatial distribution of adult-onset primary malignant and other central nervous system tumors in Southern Sardinia, Italy.

PURPOSE: To study for the first time the incidence of adult-onset CNS tumors in Southern Sardinia, Italy. METHODS: Clinical records of patients > 18 years old who were diagnosed with primary CNS tumors during 2016-2019 in the study area were reviewed. Meningiomas, cranial/paraspinal nerve tumors, lymphomas, and pituitary tumors were excluded. Cases were classified according to the 2016 WHO classification of CNS tumors and to the morphology codes from the International Classification of Diseases-Oncology, third edition. Age-adjusted incidence rates were calculated by the direct method to the 2011-2020 European standard population. Kulldorff's spatial scan statistic was used to identify geographic clusters of patients who shared increased/decreased tendency to develop CNS tumors. RESULTS: CNS tumors were diagnosed in 234 incident patients, but histological diagnosis was available in 222/234 patients (95%) aged 64.3 ± 13.5 years at diagnosis. Crude incidence rate was 7.1 per 100,000 persons-year (95% CI, 6.2-8.1), 6.2 per 100,000 persons-year (95% CI, 5.4-7.0) when age-adjusted. CNS tumors were more frequent in men and after age 40. Glioblastoma accounted for 76% of the total (adjusted rate, 4.7 per 100,000 persons-year; 95% CI, 4.0-5.4). Spatial analysis revealed geographic variations of glioblastoma incidence within the study area. CONCLUSION: Although the distribution of tumor diagnoses in Sardinia reflects expected age and gender-related patterns in western populations, our findings would indicate a slightly higher incidence of glial tumors, glioblastoma in particular, in Sardinia than in other European countries. The identification of spatial clusters of high/low risk will serve as a resource for etiological research.

A Combined One-Staged Robot-Assisted Sacral Chordoma Resection.

BACKGROUND: The robotic surgery is an advanced modern minimally invasive technology, widely used in urologic oncology, and it has become useful in particular conditions. Over time, different surgical specialties made use of the robotic properties to minimize complications for high-risk procedures. A combined 1-staged robot-assisted multidisciplinary surgery with intraoperative neurophysiological monitoring can be a safe procedure to remove a sacral chordoma with low morbidity rates. CASE DESCRIPTION: A 64-year-old woman complained of a few months of drug-resistant low back and abdominal pain. The subsequent development of constipation brought the patient to undergo an abdominal computed tomography scan and magnetic resonance imaging. Radiologic investigations revealed a large size sacral mass associated with a partial destruction of the sacrum and posterior compression of the rectum. The tumor was en bloc removed by a combined 1-staged anterior laparoscopic robot-assisted and posterior open lumbosacral approach with continue intraoperative neurophysiological monitoring of sacral and pudendal plexuses. The histological diagnosis was of chordoma. After surgery, the patient reported pain relief and the total recovery of bowel dysfunction with good 11-month follow-up outcome. CONCLUSIONS: This combined technique represents a promising treatment option in selected cases. The robotic technology combined with the experience of highly qualified staff can improve the surgical result by minimizing complications. However, longer follow-up is necessary to confirm the long-term effects in terms of recurrence and survival.

An interdisciplinary approach for laparoscopic removal of a large retroperitoneal pelvic schwannoma attached to vital vessels: A case report.

RATIONALE: Retroperitoneal schwannomas are very rare and may grow very close to major abdominal vessels. Since the surgical approach to the retroperitoneal space may be complex due to surrounding vital organs, including major vessels, laparoscopic surgery is challenging and has only been recently adopted. Here, we report a case of laparoscopic resection of a large retroperitoneal schwannoma attached to large vital vessels. PATIENT CONCERNS: A 62-year-old woman presented with a chief complaint of pain in the lower right limb with consequent claudication, which had lasted for approximately 1 year. DIAGNOSES: Magnetic resonance imaging revealed a solid oval mass measuring 45 × 32 × 39 mm, located medially to the right iliopsoas muscle at the level of the intersomatic space between the 5th lumbar vertebra and the 1st sacral vertebra. This mass was inhomogeneously hypointense in T2 due to the presence of cystic areas, with intense and inhomogeneous contrast enhancement, compatible with the diagnosis of a schwannoma. The mass compressed the inferior caval vein near its bifurcation and the right common iliac vein, anteriorly dislocating the ipsilateral iliac arterial axis. INTERVENTIONS: A multidisciplinary team skilled in vascular and pelvic laparoscopy was involved. The patient underwent laparoscopic surgery via an anterior transperitoneal approach with right adnexectomy and radical excision of the tumor. The surgery lasted 120 minutes without intraoperative complications. Blood loss was less than 100 mL. The histologic diagnosis was a benign Schwannoma; grade I according to World Health Organization classification. OUTCOMES: The postoperative course was uneventful. At the 10-month follow-up, the patient had no recurrences and was asymptomatic. LESSONS: Laparoscopic removal of large retroperitoneal schwannomas, even if attached to major vital vessels, is feasible and safe when performed by experienced surgeons.

Use of gelatin hemostatic matrices in patients with intraparenchymal hemorrhage and drug-induced coagulopathy.

In the routine practice of neurosurgery, the attainment of appropriate hemostasis during and after surgery is of the utmost importance. In the last few years, we have noticed that in several cases the standard coagulation methods (bipolar, Tabotamp, Spongostan) were not sufficient; in particular, patients with intraparenchymal hemorrhage under anticoagulant or antiplatelet therapy were observed to be the most difficult hemostasis cases, and thus those most frequently subjected to gelatin hemostatic matrices. We report our trial on 57 patients under anticoagulant or antiplatelet therapy and with intraparenchymal hemorrhage in which gelatin hemostatic matrices were used. The excellent results both in terms of outcome and decreased bleeding allow for regarding such a practice as safe and reproducible in these cases.

Incidence of thromboembolic events after use of gelatin-thrombin-based hemostatic matrix during intracranial tumor surgery.

Association between the use of hemostatic agents made from collagen/gelatin mixed with thrombin and thromboembolic events in patients undergoing tumor resection has been suggested. This study evaluates the relationship between flowable hemostatic matrix and deep vein thrombosis in a large cohort of patients treated for brain tumor removal. The authors conducted a retrospective, multicenter, clinical review of all craniotomies for tumor removal performed between 2013 and 2014. Patients were classified in three groups: group I (flowable gelatin hemostatic matrix with thrombin), group II (gelatin hemostatic without thrombin), and group III (classical hemostatic). A total of 932 patients were selected: tumor pathology included 441 gliomas, 296 meningiomas, and 195 metastases. Thromboembolic events were identified in 4.7% of patients in which gelatin matrix with thrombin was applied, in 8.4% of patients with gelatin matrix without thrombin, and in 3.6% of cases with classical methods of hemostasis. Patients with venous thromboembolism had an increased proportion of high-grade gliomas (7.2%). Patients receiving a greater dose than 10 ml gelatin hemostatic had a higher rate of thromboembolic events. Intracranial hematoma requiring reintervention occurred in 19 cases: 4.5% of cases of group III, while reoperation was performed in 1.3 and 1.6% of patients in which gelatin matrix with or without thrombin was applied. Gelatin matrix hemostat is an efficacious tool for neurosurgeons in cases of difficult intraoperative bleeding during cranial tumor surgery. This study may help to identify those patients at high risk for developing thromboembolism and to treat them accordingly.

Neural stem cells and glioblastoma.

Glioblastoma multiforme represents one of the most common brain cancers with a rather heterogeneous cellular composition, as indicated by the term "multiforme". Recent reports have described the isolation and identification of cancer neural stem cells from human adult glioblastoma multiforme, which possess the capacity to establish, sustain, and expand these tumours, even under the challenging settings posed by serial transplantation experiments. Our study focused on the distribution of neural cancer stem cells inside the tumour. The study is divided into three phases: removal of tumoral specimens in different areas of the tumour (centre, periphery, marginal zone) in an operative room equipped with a 1.5 T scanner; isolation and characterization of neural cancer stem cells from human adult glioblastoma multiforme; identification of neural cancer stem cell distribution inside the tumour.

Impact of modeling fluid-structure interaction in the computational analysis of aortic root biomechanics.

Numerical modeling can provide detailed and quantitative information on aortic root (AR) biomechanics, improving the understanding of AR complex pathophysiology and supporting the development of more effective clinical treatments. From this standpoint, fluid-structure interaction (FSI) models are currently the most exhaustive and potentially realistic computational tools. However, AR FSI modeling is extremely challenging and computationally expensive, due to the explicit simulation of coupled AR fluid dynamics and structural response, while accounting for complex morphological and mechanical features. We developed a novel FSI model of the physiological AR simulating its function throughout the entire cardiac cycle. The model includes an asymmetric MRI-based geometry, the description of aortic valve (AV) non-linear and anisotropic mechanical properties, and time-dependent blood pressures. By comparison to an equivalent finite element structural model, we quantified the balance between the extra information and the extra computational cost associated with the FSI approach. Tissue strains and stresses computed through the two approaches did not differ significantly. The FSI approach better captured the fast AV opening and closure, and its interplay with blood fluid dynamics within the Valsalva sinuses. It also reproduced the main features of in vivo AR fluid dynamics. However, the FSI simulation was ten times more computationally demanding than its structural counterpart. Hence, the FSI approach may be worth the extra computational cost when the tackled scenarios are strongly dependent on AV transient dynamics, Valsalva sinuses fluid dynamics in relation to coronary perfusion (e.g. sparing techniques), or AR fluid dynamic alterations (e.g. bicuspid AV).

Restricted cusp motion in right-left type of bicuspid aortic valves: a new risk marker for aortopathy.

OBJECTIVE: Bicuspid aortic valve disease is heterogeneous with respect to valve morphology and aortopathy risk. This study searched for early imaging predictors of aortopathy in patients with a bicuspid aortic valve with right-left coronary cusp fusion, the most common morphotype. METHODS: Time-resolved magnetic resonance imaging was performed in 36 subjects with nonstenotic, nonregurgitant bicuspid aortic valves and nondilated aortas and in 10 healthy controls with tricuspid aortic valves. Sinus dimensions (diameter, width, and height), ascending tract diameters, and wall strain were measured for each sinus/leaflet unit and corresponding ascending tract area to account for asymmetries. A novel parameter, "cusp opening angle," measured the degree of valve leaflet alignment to outflow axis in systole, quantifying cusp motility. Phase-contrast magnetic resonance imaging and computational fluid dynamic models assessed flow patterns. Aortic growth rate was estimated over a follow-up period ranging from 9 to 84 months. RESULTS: The expected restriction of bicuspid aortic valve opening (conjoint cusp opening angle, 62°±5° vs 76°±3° for nonfused leaflet and 75°±3° for tricuspid aortic valve cusps; P<.001) was confirmed, and the introduced parameter reproducibly quantified this phenomenon. Phase-contrast magnetic resonance imaging demonstrated systolic flow deflection toward the right, affecting the right anterolateral ascending wall. Computational models confirmed that restricted cusp motion alone is sufficient to cause the observed flow pattern. Ascending tract wall strain was not circumferentially homogeneous in bicuspid aortic valves. In multivariable analyses, the conjoint cusp opening angle independently predicted ascending aorta diameters and growth rate (P<.001). CONCLUSIONS: In the bicuspid aortic valve commonly defined as normofunctional by echocardiographic criteria, restricted systolic conjoint cusp motion causes flow deflection. The novel measurement introduced can quantify restricted cusp opening, possibly assuming prognostic importance.

Aortic valve repair via neo-chordae technique: mechanistic insight through numerical modelling.

Recently, the neo-chordae technique (NCT) was proposed to stabilize the surgical correction of isolated aortic valve (AV) prolapse. Neo-chordae are inserted into the corrected leaflet to drive its closure by minimal tensions and prevent relapses. In a previous in vitro study we analysed the NCT effects on healthy aortic roots (ARs). Here we extend that analysis via finite element models (FEMs). After successfully replicating the experimental conditions for validation purposes, we modified our AR FEM, obtaining a continent AV with minor isolated prolapse, thus representing a realistic clinical scenario. We then simulated the NCT, and systematically assessed the acute effects of changing neo-chordae length, opening angle, asymmetry and insertion on the aorta. In the baseline configuration the NCT restored physiological AV dynamics and coaptation, without inducing abnormal leaflet stresses. This outcome was notably sensitive only to neo-chordae length, suggesting that the NCT is a potentially easy-to-standardize technique. However, this parameter is crucial: major shortenings (6 mm) prevent coaptation and increase leaflet stresses by 359 kPa, beyond the yield limit. Minor shortenings (2-4 mm) only induce a negligible stress increase and mild leaflet tethering, which however may hamper the long-term surgical outcome.

Trends in biomedical engineering: focus on Patient Specific Modeling and Life Support Systems.

Over the last twenty years major advancements have taken place in the design of medical devices and personalized therapies. They have paralleled the impressive evolution of three-dimensional, non invasive, medical imaging techniques and have been continuously fuelled by increasing computing power and the emergence of novel and sophisticated software tools. This paper aims to showcase a number of major contributions to the advancements of modeling of surgical and interventional procedures and to the design of life support systems. The selected examples will span from pediatric cardiac surgery procedures to valve and ventricle repair techniques, from stent design and endovascular procedures to life support systems and innovative ventilation techniques.

An unusual growth of an intraventricular meningioma: a case report.

Intraventricular meningiomas are rare often histologically benign tumors arising most always from the trigonal region of the lateral ventricle. We report the first described case of a rapidly growing histologically benign intraventricular meningioma in a 68-year-old woman whose magnetic resonance imaging (MRI) executed 1 year before surgical operation was negative for intracranial mass lesion.

Brain interstitial nociceptin/orphanin FQ levels are elevated in Parkinson's disease.

Expression and release of nociceptin/orphanin FQ (N/OFQ) are elevated in the substantia nigra reticulata of 6-hydroxydopamine-hemilesioned rats, suggesting a pathogenic role for N/OFQ in Parkinson's disease. In this study, we investigated whether elevation of N/OFQ expression in 6-hydroxydopamine-hemilesioned rats selectively occurs in substantia nigra and whether hypomotility following acute haloperidol administration is accompanied by a rise in nigral N/OFQ levels. Moreover, to prove a link between N/OFQ and idiopathic Parkinson's disease in humans, we measured N/OFQ levels in the cerebrospinal fluid of parkinsonian patients undergoing surgery for deep brain stimulation. In situ hybridization demonstrated that dopamine depletion was associated with increase of N/OFQ expression in substantia nigra (compacta +160%, reticulata +105%) and subthalamic nucleus (+45%), as well as reduction in caudate putamen (-20%). No change was observed in globus pallidus, nucleus accumbens, thalamus, and motor cortex. Microdialysis coupled to the bar test allowed to demonstrate that acute administration of haloperidol (0.8 and 3 mg/kg) increased nigral N/OFQ levels (maximally of +47% and +53%, respectively) in parallel with akinesia. A correlation with preclinical studies was found by analyzing N/OFQ levels in humans. Indeed, N/OFQ levels were found to be approximately 3.5-fold elevated in the cerebrospinal fluid of parkinsonian patients (148 fmol/ml) compared with nonparkinsonian neurologic controls (41 fmol/ml). These data represent the first clinical evidence linking N/OFQ to idiopathic Parkinson's disease in humans. They strengthen the pathogenic role of N/OFQ in the modulation of parkinsonism across species and provide a rationale for developing N/OFQ receptor antagonists as antiparkinsonian drugs.

Biomechanical implications of the congenital bicuspid aortic valve: a finite element study of aortic root function from in vivo data.

OBJECTIVE: Congenital bicuspid aortic valves frequently cause aortic stenosis or regurgitation. Improved understanding of valve and root biomechanics is needed to achieve advancements in surgical repair techniques. By using imaging-derived data, finite element models were developed to quantify aortic valve and root biomechanical alterations associated with bicuspid geometry. METHODS: A dynamic 3-dimensional finite element model of the aortic root with a bicuspid aortic valve (type 1 right/left) was developed. The model's geometry was based on measurements from 2-dimensional magnetic resonance images acquired in 8 normotensive and otherwise healthy subjects with echocardiographically normal function of their bicuspid aortic valves. Numeric results were compared with those obtained from our previous model representing the normal root with a tricuspid aortic valve. The effects of raphe thickening on valve kinematics and stresses were also evaluated. RESULTS: During systole, the bicuspid valve opened asymmetrically compared with the normal valve, resulting in an elliptic shape of its orifice. During diastole, the conjoint cusp occluded a larger proportion of the valve orifice and leaflet bending was altered, although competence was preserved. The bicuspid model presented higher stresses compared with the tricuspid model, particularly in the central basal region of the conjoint cusp (+800%). The presence of a raphe partially reduced stress in this region but increased stress in the other cusp. CONCLUSIONS: Aortic valve function is altered in clinically normally functioning bicuspid aortic valves. Bicuspid geometry per se entails abnormal leaflet stress. The stress location suggests that leaflet stress may play a role in tissue remodeling at the raphe region and in early leaflet degeneration.

Dynamic finite element analysis of the aortic root from MRI-derived parameters.

An understanding of aortic root biomechanics is pivotal for the optimisation of surgical procedures aimed at restoring normal root function in pathological subjects. For this purpose, computational models can provide important information, as long as they realistically capture the main anatomical and functional features of the aortic root. Here we present a novel and realistic finite element (FE) model of the physiological aortic root, which simulates its function during the entire cardiac cycle. Its geometry is based on magnetic resonance imaging (MRI) data obtained from 10 healthy subjects and accounts for the geometrical differences between the leaflet-sinus units. Morphological realism is combined with the modelling of the leaflets' non-linear and anisotropic mechanical response, in conjunction with dynamic boundary conditions. The results show that anatomical differences between leaflet-sinus units cause differences in stress and strain patterns. These are notably higher for the leaflets and smaller for the sinuses. For the maximum transvalvular pressure value, maximum principal stresses on the leaflets are equal to 759, 613 and 603 kPa on the non-coronary, right and left leaflet, respectively. For the maximum aortic pressure, average maximum principal stresses values are equal to 118, 112 and 111 kPa on the right, non-coronary and left sinus, respectively. Although liable of further improvements, the model seems to reliably reproduce the behaviour of the real aortic root: the model's leaflet stretches, leaflet coaptation lengths and commissure motions, as well as the timings of aortic leaflet closures and openings, all matched with the experimental findings reported in the literature.