An adaptive semi-implicit finite element solver for brain cancer progression modeling.

Glioblastoma is the most aggressive and infiltrative glioma, classified as Grade IV, with the poorest survival rate among patients. Accurate and rigorously tested mechanistic in silico modeling offers great value to understand and quantify the progression of primary brain tumors. This paper presents a continuum-based finite element framework that is built on high performance computing, open-source libraries to simulate glioblastoma progression. We adopt the established proliferation invasion hypoxia necrosis angiogenesis model in our framework to realize scalable simulations of cancer, and has demonstrated to produce accurate and efficient solutions in both two- and three-dimensional brain models. The in silico solver can successfully implement arbitrary order discretization schemes and adaptive remeshing algorithms. A model sensitivity analysis is conducted to test the impact of vascular density, cancer cell invasiveness and aggressiveness, the phenotypic transition potential, including that of necrosis, and the effect of tumor-induced angiogenesis in the evolution of glioblastoma. Additionally, individualized simulations of brain cancer progression are carried out using pertinent magnetic resonance imaging data, where the in silico model is used to investigate the complex dynamics of the disease. We conclude by arguing how the proposed framework can deliver patient-specific simulations of cancer prognosis and how it could bridge clinical imaging with modeling.

Impact of turbulence modeling on the simulation of blood flow in aortic coarctation.

Numerical simulations of pulsatile blood flow in an aortic coarctation require the use of turbulence modeling. This paper considers three models from the class of large eddy simulation (LES) models (Smagorinsky, Vreman, σ -model) and one model from the class of variational multiscale models (residual-based) within a finite element framework. The influence of these models on the estimation of clinically relevant biomarkers used to assess the degree of severity of the pathological condition (pressure difference, secondary flow degree, normalized flow displacement, wall shear stress) is investigated in detail. The simulations show that most methods are consistent in terms of severity indicators such as pressure difference and stenotic velocity. Moreover, using second-order velocity finite elements, different turbulence models might lead to considerably different results concerning other clinically relevant quantities such as wall shear stresses. These differences may be attributed to differences in numerical dissipation introduced by the turbulence models.

Consensus Report by the Italian Academy of Osseointegration on the Use of Graft Materials in Postextraction Sites.

PURPOSE: After tooth extraction, a modeling and remodeling phase of bone and soft tissues occurs. It has been fully demonstrated that bone resorption as high as 50% can take place regarding ridge width and a variable amount concerning ridge height, making it difficult to perform implant surgery. MATERIALS AND METHODS: Active members of the Italian Academy of Osseointegration (IAO) participated in this Consensus Conference, and three systematic reviews were conducted before the meeting to provide guidelines on alveolar ridge preservation procedures. The systematic reviews covered the following topics: (1) What material best preserves the dimensions of the ridge horizontally and vertically?; (2) what material favors the formation of the highest quantity of new bone?; (3) which technique would best seal the socket?; and (4) what effect does alveolar ridge preservation have on soft tissues? RESULTS: The main conclusions reached by the assembly were that alveolar ridge preservation is advisable after dental extraction, particularly in esthetic areas, in proximity of anatomical structures (ie, maxillary sinus, inferior alveolar nerve, and mental foramen), whenever the treatment plan requires delayed placement, and whenever patients ask to postpone implant insertion for various reasons. Socket debridement is advised before the use of a "regenerative material," and xenograft is considered the gold standard material to maintain ridge dimensions. Another indication is antibiotic therapy, which is recommended in the case of alveolar ridge preservation (amoxicillin 2 g 1 hour before the intervention and 1 g every 12 hours for 6 days). A membrane or autologous soft tissue should be used to seal the socket and protect the regenerative material, and the indicated reentry time (implant insertion) is 4 to 6 months. CONCLUSION: This Consensus Conference agreed that the adoption of alveolar ridge preservation can effectively prevent physiologic bone loss, especially in esthetic areas. It is recommended to cover the xenograft material with a membrane or autologous soft tissue, and antibiotic therapy is advisable.

Multiscale Coupling of One-dimensional Vascular Models and Elastic Tissues.

We present a computational multiscale model for the efficient simulation of vascularized tissues, composed of an elastic three-dimensional matrix and a vascular network. The effect of blood vessel pressure on the elastic tissue is surrogated via hyper-singular forcing terms in the elasticity equations, which depend on the fluid pressure. In turn, the blood flow in vessels is treated as a one-dimensional network. Intravascular pressure and velocity are simulated using a high-order finite volume scheme, while the elasticity equations for the tissue are solved using a finite element method. This work addresses the feasibility and the potential of the proposed coupled multiscale model. In particular, we assess whether the multiscale model is able to reproduce the tissue response at the effective scale (of the order of millimeters) while modeling the vasculature at the microscale. We validate the multiscale method against a full scale (three-dimensional) model, where the fluid/tissue interface is fully discretized and treated as a Neumann boundary for the elasticity equation. Next, we present simulation results obtained with the proposed approach in a realistic scenario, demonstrating that the method can robustly and efficiently handle the one-way coupling between complex fluid microstructures and the elastic matrix.

Inversion-recovery MR elastography of the human brain for improved stiffness quantification near fluid-solid boundaries.

PURPOSE: In vivo MR elastography (MRE) holds promise as a neuroimaging marker. In cerebral MRE, shear waves are introduced into the brain, which also stimulate vibrations in adjacent CSF, resulting in blurring and biased stiffness values near brain surfaces. We here propose inversion-recovery MRE (IR-MRE) to suppress CSF signal and improve stiffness quantification in brain surface areas. METHODS: Inversion-recovery MRE was demonstrated in agar-based phantoms with solid-fluid interfaces and 11 healthy volunteers using 31.25-Hz harmonic vibrations. It was performed by standard single-shot, spin-echo EPI MRE following 2800-ms IR preparation. Wave fields were acquired in 10 axial slices and analyzed for shear wave speed (SWS) as a surrogate marker of tissue stiffness by wavenumber-based multicomponent inversion. RESULTS: Phantom SWS values near fluid interfaces were 7.5 ± 3.0% higher in IR-MRE than MRE (P = .01). In the brain, IR-MRE SNR was 17% lower than in MRE, without influencing parenchymal SWS (MRE: 1.38 ± 0.02 m/s; IR-MRE: 1.39 ± 0.03 m/s; P = .18). The IR-MRE tissue-CSF interfaces appeared sharper, showing 10% higher SWS near brain surfaces (MRE: 1.01 ± 0.03 m/s; IR-MRE: 1.11 ± 0.01 m/s; P < .001) and 39% smaller ventricle sizes than MRE (P < .001). CONCLUSIONS: Our results show that brain MRE is affected by fluid oscillations that can be suppressed by IR-MRE, which improves the depiction of anatomy in stiffness maps and the quantification of stiffness values in brain surface areas. Moreover, we measured similar stiffness values in brain parenchyma with and without fluid suppression, which indicates that shear wavelengths in solid and fluid compartments are identical, consistent with the theory of biphasic poroelastic media.

Three-dimensional digital planning of class III decompensation with clear aligners: Hard and soft tissue augmentation with concomitant corticotomy to stretch the limits of safe orthodontic treatment.

PURPOSE: Three-dimensional diagnosis has shown that orthodontic therapy could potentially move the roots of the teeth outside the original bone structure. The purpose of these case studies was to test the possibility of obtaining correct three-dimensional tooth positioning with clear aligners, thereby modifying the periodontal structure accordingly, at the same time. METHODS: Regenerative Corticotomy (RC) was performed with clear aligners on ten adult patients (40 anterior teeth) with skeletal Class III malocclusion, for dental decompensation, prior to the orthognathic surgery. The CBCT examinations were performed before treatment (T0) and 1 year after orthognathic surgery (T1). The vertical and the horizontal hard tissue changes, the width of keratinized gingiva, the incisors proclination (IMPA) and the percentage of inclination compared to the planning were analyzed. RESULTS: The distance between the Cemento-Enamel Junction (CEJ) and the Bone Marginal Level (BML) decreased in average from 5.5 â€‹± â€‹3.2 â€‹mm to 1.39 â€‹± â€‹0.53 â€‹mm. The horizontal changes were at the 3 â€‹mm level 1.42 â€‹± â€‹0.5 â€‹mm, at the 5 â€‹mm level 1.98 â€‹± â€‹0.66 â€‹mm and at the 7 â€‹mm level 2.70 â€‹± â€‹0.87 â€‹mm. The width of Keratinized gingiva changes were on average 1.42 â€‹± â€‹0.36 â€‹at T0 and 4.16 â€‹± â€‹2.25 â€‹at T1. All the changes were statistically significant with p â€‹< â€‹0,05. The mean proclination based on IMPA values was +9.16 +-1.19°. The mean difference of the incisor's proclination compared to the digitally planned was -1 +-0.6° (89.87 +- 6.46%). CONCLUSION: Clear Aligners with three-dimensional digital planning seems to be reliable in controlling teeth movements in the pre-orthognathic decompensation phase. Regenerative Corticotomy seems to have the ability to improve the periodontal tissues despite proclination.

Consensus Report by the Italian Academy of Osseointegration on the Use of Antibiotics and Antiseptic Agents in Implant Surgery.

PURPOSE: Beneficial aspects of short and ultrashort antibiotic administration protocols could be clinically correlated to the reduced side effects on the gastrointestinal microflora. The aim of this Consensus Conference was to establish the necessity of an antibiotic prophylaxis and its dosage to reduce the risk of early implant failure in healthy (ASA 1 or 2), periodontally healthy patients, undergoing basic dental implant surgery (straightforward cases). Additionally, the need for an antiseptic protocol, used before and after the implant surgery, was evaluated. MATERIALS AND METHODS: Active members of the Italian Academy of Osseointegration (IAO), together with several worldwide-recognized key opinion experts in the field of microbiology, implant dentistry, and infectious diseases, were participants at this Consensus Conference. Two systematic reviews were carried out, before the Consensus Conference, and their results discussed in order to give guidelines on the administration of an antibiotic/antiseptic prophylaxis in implant surgery. The systematic reviews covered the following topics: (1) the use of antibiotics to reduce both implant failure rate and peri-implant infections in healthy patients and (2) the use of chlorhexidine compositions capable of reducing complications in patients undergoing surgical interventions. RESULTS: The main statements reached by the assembly were as follows: (1) Rinsing with chlorhexidine is highly recommended before and after implant surgery to minimize the bacterial load. (2) A single dose of antibiotics in straightforward cases is recommended. (3) In complex cases (long surgical time, regeneration procedures), it is advisable to continue the antibiotic administration. CONCLUSION: This Consensus Conference advocates the administration of a unique dose of antibiotics in straightforward implant cases combined with the use of chlorhexidine.

Regenerative Orthodontics: GBR and Corticotomy to Stretch the Limits of Orthodontic Treatment.

Orthodontic therapy could lead to marginal bone resorption in cases where the teeth are moved outside the envelope of bone. The purpose of this case series was to test corticotomy with a guided bone regeneration (GBR) procedure to regenerate bone in the direction of movement outside the original bony housing. Ten adult patients (60 anterior teeth), all presenting with severe anterior crowding, were enrolled in the study. Orthodontic therapy in all investigated sites was associated with selective surgical corticotomies and a simultaneous GBR procedure. CBCT examinations were performed before starting orthodontic treatment (T0) and at the end of treatment (T1; mean: 7 months; range: 6 to 9 months). Pre- and postoperative CBCTs were superimposed with a DICOM viewer (3D Slicer) and studied with an image-processing software (ImageJ, National Institutes of Health) to measure the area of interest of the buccal plate. The average area was found to be 0.58 ± 0.22 mm2 at T0 and 1.76 ± 0.4 mm2 at T1, with a statistically significant difference (P < .05). The combination of corticotomy and a regenerative procedure seems to have the ability to augment the original osseous anatomy when the root is moved outside of the original bony envelope.

Tunnel Regenerative Corticotomy (TURC): A modified approach in surgically-assisted orthodontics.

We present a modified surgical technique which encompasses a combination of surgically-assisted accelerated orthodontics and guided bone regeneration for combined surgical and orthodontic management of dental crowding and maxillary transverse deficiency malocclusions with minimally invasive surgery, in a rapid manner, and without the use of general anesthesia.

The Use of Antibiotics in Implant Therapy: A Systematic Review and Meta-Analysis with Trial Sequential Analysis on Early Implant Failure.

PURPOSE: The aim of this systematic review was to estimate if an antibiotic prophylaxis regimen reduces implant failure and postoperative infection in healthy patients who are going to receive dental implants. MATERIALS AND METHODS: An electronic database search (MEDLINE/PubMed, Scopus, Web of Science, Cochrane Library) until June 30, 2019, for randomized controlled trials (RCTs) was performed. The Cochrane Handbook for Systematic Reviews of Interventions to assess the risk of bias in individual studies was used. Patient- and implant-level data were extracted for the analyzed outcomes. The risk ratio (RR) and the 95% confidence interval were calculated as meta-analytic effects. A fixed- or a random-effect model was employed on the basis of the presence/absence of heterogeneity (I2 > 50%). Differences between groups were analyzed using the inverse of variance test. The Higgins Index and chi-square test were used to assess the studies' heterogeneity. Additionally, in order to evaluate the power of evidence and to adjust the meta-analytic findings for type 1 and 2 errors, a trial sequential analysis (TSA) was performed. RESULTS: Nine studies including 1,984 patients and 3,588 implants were selected. Eight hundred eighty-five patients (1,617 implants) received no antibiotics or a placebo therapy before the implant surgery; 1,971 implants (1,099 patients) were treated with an antibiotic therapy. The meta-analysis at the patient level showed a statistically significant reduction in the rate of early implant failure associated with the use of antibiotics (I2 = 0%) (RR = 0.32 [0.20, 0.51], P > .001). Similar results were obtained after pooling the implant-level data with the fixed-effect model (RR = 0.33 [0.22, 0.51], P > .001). Such results were also confirmed by the TSA after adjusting for type 1 and 2 errors. CONCLUSION: The results of this systematic review with meta-analysis indicate that an antibiotic prophylaxis prevents early implant failures in the case of healthy patients. No information can be provided on peri-implant infections.

Standard vs customized healing abutments with simultaneous bone grafting for tissue changes around immediate implants. 1-year outcomes from a randomized clinical trial.

BACKGROUND: Immediate implants have shown risks of esthetic complications. The hypothesis was that a customized healing abutment could improve the peri-implant tissue healing. PURPOSE: To evaluate and compare the soft and hard tissue healing around immediate implants that received bone grafting and a customized vs a standard healing abutment. MATERIALS AND METHODS: Patients, who required tooth extraction and who received an immediate implant (with an alloplastic graft material) were randomly assigned to a customized or a standard healing abutment group. Clinical and radiographic examinations were taken at baseline, at 4 and 12 months. RESULTS: Twenty-five patients out of 61 were excluded from the study because unsuitable for immediate implantation. In total, 36 patients were randomized in the two groups. There were 17 females and 19 males (age range 23-77). No prosthetic or implant failure was registered during the study period. The Papilla Index was significantly higher in the customized than in the standard group at 4 and 12 months (P = .0002). The bone loss at mesial sites was significantly higher in the control than in the test group (P = .0014). CONCLUSION: The customized healing abutment group showed the most favorable outcomes (in terms of PI and MBL) in case of immediate implant that received a peri-implant bone grafting procedure.

Antibiotic prophylaxis habits in oral implant surgery among dentists in Italy: a cross-sectional survey.

BACKGROUND: The prescription of prophylactic antibiotics in conjunction with oral implant surgery remains inconsistent among different populations of dentists. The main objective of this study was to assess the current antibiotic prescribing habits of dentist in conjunction with oral implant surgery in Italy. The secondary objective was to assess the nature and amount (mg) of antibiotics prescriptions in order to evaluate whether any consensus has been reached and if the current recommendations are complied. METHODS: Observational cross-sectional study based on a web-survey reported according to the STROBE guidelines. A questionnaire was sent via email to each registered member of the Italian Academy of Osseointegration (n = 400). The email included a link to the anonym web questionnaire developed on www.encuestafacil.com. It contained close-ended and some open-ended questions concerning demographics, antibiotic type, prescription duration and dosage. Collected data were analyzed using STATA® 14 software. RESULTS: 160 participants responded the survey (response rate = 40%). Approximately 84% routinely prescribed prophylactic antibiotics in conjunction with oral implant surgery, 15.6% prescribed antibiotics in certain situations and only 1 did not prescribe antibiotics at all. Overall, 116 respondents prescribed both pre- and postoperative antibiotics, 29 prescribed antibiotics only preoperatively and 14 prescribed antibiotics exclusively after surgery. Italian dentists prescribed an average amount of 10,331 mg antibiotics before, during or after oral implant surgery. Approximately, only 17% (n = 27) of the participants who prescribed antibiotics before oral implant surgery complied with the recommendations proposed by the latest publications (no more than 3 g of preoperative amoxicillin before oral implant surgery). CONCLUSIONS: Dentists in Italy on a large scale prescribe antibiotic prophylaxis in conjunction with oral implant surgery among healthy patients. A high range of prophylactic regimens is prescribed and they are not adhering to the new science-based specifications. Guidelines focused on the indications for prophylactic antibiotics among healthy patients are required to prevent bacterial resistance, side effects and costs caused by overtreatment and the irrational use of antibiotics.

Multiscale modeling of vascularized tissues via nonmatching immersed methods.

We consider a multiscale approach based on immersed methods for the efficient computational modeling of tissues composed of an elastic matrix (in two or three dimensions) and a thin vascular structure (treated as a co-dimension two manifold) at a given pressure. We derive different variational formulations of the coupled problem, in which the effect of the vasculature can be surrogated in the elasticity equations via singular or hypersingular forcing terms. These terms only depend on information defined on co-dimension two manifolds (such as vessel center line, cross-sectional area, and mean pressure over cross section), thus drastically reducing the complexity of the computational model. We perform several numerical tests, ranging from simple cases with known exact solutions to the modeling of materials with random distributions of vessels. In the latter case, we use our immersed method to perform an in silico characterization of the mechanical properties of the effective biphasic material tissue via statistical simulations.

Reduced-Order Unscented Kalman Filter With Observations in the Frequency Domain: Application to Computational Hemodynamics.

OBJECTIVE: The aim of this paper is to assess the potential of the reduced-order unscented Kalman's filter (ROUKF) in the context of computational hemodynamics, in order to estimate cardiovascular model parameters when employing real patient-specific data. METHODS: The approach combines an efficient blood flow solver for one-dimensional networks (for the forward problem) with the parameter estimation problem cast in the frequency space. Namely, the ROUKF is used to correct model parameters after each cardiac cycle, depending on the discrepancies of model outputs with respect to available observations properly mapped into the frequency space. RESULTS: First we validate the filter in frequency domain applying it in the context of a set of experimental measurements for an in vitro model. Second, we perform different numerical experiments aiming at parameter estimation using patient-specific data. CONCLUSION: Our results demonstrate that the filter in frequency domain allows a faster and more robust parameter estimation, when compared to its time-domain counterpart. Moreover, the proposed approach allows to estimate parameters that are not directly related to the network, but are crucial for targeting inter-individual parameter variability (e.g., parameters that characterize the cardiac output). SIGNIFICANCE: The ROUKF in frequency domain provides a robust and flexible tool for estimating parameters related to cardiovascular mathematical models using in vivo data.

Buccal Plate Preservation with Immediate Implant Placement and Provisionalization: 5-Year Follow-Up Outcomes.

PURPOSE: Despite socket preservation and/or immediate implant placement, resorption of the buccal plate after dental extraction continues to pose esthetic challenges to clinicians. Buccal plate preservation (BPP) is a technique that has been recently proposed with an aim to reduce the incidence of such resorption. This study was conducted to assess the long-term efficacy of BPP in maintaining the thickness of the buccal cortical plate after immediate implant insertion and provisionalization. MATERIALS AND METHODS: Ten consecutive patients were included in this study. Each patient underwent extraction of a non-restorable tooth, BPPPBPP, single immediate implant placement and immediate provisionalization. Cone beam CT scans were taken 3 months after surgery (T1) and 5 years after surgery (T2) to evaluate the effectiveness and longevity of the BPPPBPP technique in maintaining the augmented bone width. Two distinct measurements were taken for bone evaluation: (a) R1: 1 mm apical to the implant platform and (b) R2: 5 mm apical to the implant platform. The long axis of the implant was used as a fixed reference. Statistical test analysis was conducted using the SPSS software. Student's t test was used to assess statistical significance, and a p value of < 0.05 was considered significant. RESULTS: There were six females and four males in the study. The mean age of the sample was 37.6 years (range 23-64 years). At T1, the mean bone thickness of the buccal plate was found to be 2.36 mm at R1 (range: 1.9-3.1), and 2.23 at R2 (range: 1.9-3). At the T2 interval, the mean thickness of the plate was 2.28 mm at R1 (range: 1.7-3) and 2.18 at R2 (range: 1.9-3). The differences in these mean values were not statistically significant. CONCLUSIONS: BPPPBPP is an effective means for augmentation and maintenance of the buccal cortical plate around an immediately placed and provisionalized dental implant. It is a viable alternative to socket preservation with the added benefit that it allows for immediate implant placement.

Can corticotomy (with or without bone grafting) expand the limits of safe orthodontic therapy?

PURPOSE: To assess whether concomitant particulate bone grafting makes a difference in the ability to safely orthodontically reposition teeth outside the bony envelope after corticotomy. MATERIAL AND METHODS: Retrospective analysis of patients who underwent corticotomy as part of their orthodontic therapy for treatment of severe crowding. Patients were divided as: a) Group 1: corticotomy with bone grafting, and, b) Group 2: corticotomy without bone grafting. CT scan examinations were performed before and at the end of the treatment. Measurements of bone and tooth positions were obtained and differences between pre- and post-treatment values were calculated. RESULTS: The study sample included 20 adult patients between the ages of 25 to 58 years. A total of 144 teeth were orthodontically repositioned outside their native bony envelope after corticotomy. Average follow-up was 9 months. Teeth that were repositioned after corticotomy and bone grafting maintained the alveolar bone volume around them while corticotomy without bone grafting was not successful in maintaining bone thickness around teeth that were moved outside the alveolar housing. CONCLUSIONS: Corticotomy in combination with guided bone regeneration has the potential to increase the scope of conventional orthodontic treatment by allowing for expansive movements beyond the traditional limits.

Benchmark problems for numerical treatment of backflow at open boundaries.

In computational fluid dynamics, incoming velocity at open boundaries, or backflow, often yields unphysical instabilities already for moderate Reynolds numbers. Several treatments to overcome these backflow instabilities have been proposed in the literature. However, these approaches have not yet been compared in detail in terms of accuracy in different physiological regimes, in particular because of the difficulty to generate stable reference solutions apart from analytical forms. In this work, we present a set of benchmark problems in order to compare different methods in different backflow regimes (with a full reversal flow and with propagating vortices after a stenosis). The examples are implemented in FreeFem++, and the source code is openly available, making them a solid basis for future method developments.

A Novel Gaussian Extrapolation Approach for 2-D Gel Electrophoresis Saturated Protein Spots.

Analysis of images obtained from two-dimensional gel electrophoresis (2-D GE) is a topic of utmost importance in bioinformatics research, since commercial and academic software currently available have proven to be neither completely effective nor fully automatic, often requiring manual revision and refinement of computer generated matches. In this chapter, we present an effective technique for the detection and the reconstruction of over-saturated protein spots. Firstly, the algorithm reveals overexposed areas, where spots may be truncated, and plateau regions caused by smeared and overlapping spots. Next, it reconstructs the correct distribution of pixel values in these overexposed areas and plateau regions, using a two-dimensional least-squares fitting based on a generalized Gaussian distribution. Pixel correction in saturated and smeared spots allows more accurate proteins quantification, providing more reliable image analysis results. The method is validated for processing highly exposed 2-D GE images, comparing reconstructed spots with the corresponding non-saturated image. The results demonstrate that the algorithm enables correct spot quantification.