Virtual and augmented reality for biomedical applications.

3D visualization technologies such as virtual reality (VR), augmented reality (AR), and mixed reality (MR) have gained popularity in the recent decade. Digital extended reality (XR) technologies have been adopted in various domains ranging from entertainment to education because of their accessibility and affordability. XR modalities create an immersive experience, enabling 3D visualization of the content without a conventional 2D display constraint. Here, we provide a perspective on XR in current biomedical applications and demonstrate case studies using cell biology concepts, multiplexed proteomics images, surgical data for heart operations, and cardiac 3D models. Emerging challenges associated with XR technologies in the context of adverse health effects and a cost comparison of distinct platforms are discussed. The presented XR platforms will be useful for biomedical education, medical training, surgical guidance, and molecular data visualization to enhance trainees' and students' learning, medical operation accuracy, and the comprehensibility of complex biological systems.

Corrigendum to "Structural alterations of the brainstem in migraine" (Neuroimage Clin. 2017; 13: 223-227).

[This corrects the article DOI: 10.1016/j.nicl.2016.10.023.].

Alternative methods for virtual heart transplant-Size matching for pediatric heart transplantation with and without donor medical images available.

BACKGROUND: Listed pediatric heart transplant patients have the highest solid-organ waitlist mortality rate. The donor-recipient body weight (DRBW) ratio is the clinical standard for allograft size matching but may unnecessarily limit a patient's donor pool. To overcome DRBW ratio limitations, two methods of performing virtual heart transplant fit assessments were developed that account for patient-specific nuances. Method 1 uses an allograft total cardiac volume (TCV) prediction model informed by patient data wherein a matched allograft 3-D reconstruction is selected from a virtual library for assessment. Method 2 uses donor images for a direct virtual transplant assessment. METHODS: Assessments were performed in medical image reconstruction software. The allograft model was developed using allometric/isometric scaling assumptions and cross-validation. RESULTS: The final predictive model included gender, height, and weight. The 25th-, 50th-, and 75th-percentiles for TCV percentage errors were -13% (over-prediction), -1%, and 8% (under-prediction), respectively. Two examples illustrating the potential of virtual assessments are presented. CONCLUSION: Transplant centers can apply these methods to perform their virtual assessments using existing technology. These techniques have potential to improve organ allocation. With additional experience and refinement, virtual transplants may become standard of care for determining suitability of donor organ size for an identified recipient.

The Effect of Stents in Cerebral Aneurysms: A Review.

The etiology of up to 95% of cerebral aneurysms may be accounted for by hemodynamically-induced factors that create vascular injury. The purpose of this review is to describe key physical properties that stents have and how they affect cerebral aneurysms. We performed a two-step screening process. First, a structured search was performed using the PubMed database. The following search terms and keywords were used: "Hemodynamics," "wall shear stress (WSS)," "velocity," "viscosity," "cerebral aneurysm," "intracranial aneurysm," "stent," "flow diverter," "stent porosity," "stent geometry," "stent configuration," and "stent design." Reports were considered if they included original data, discussed hemodynamic changes after stent-based treatment of cerebral aneurysms, examined the hemodynamic effects of stent deployment, and/or described the geometric characteristics of both stents and the aneurysms they were used to treat. The search strategy yielded a total of 122 articles, 61 were excluded after screening the titles and abstracts. Additional articles were then identified by cross-checking reference lists. The final collection of 97 articles demonstrates that the geometric characteristics and configurations of deployed stents influenced hemodynamic parameters such as aneurysmal WSS, inflow, and pressure. The geometric characteristics of the aneurysm and its position also had significant influences on intra-aneurysmal hemodynamics after treatment. In conclusion, changes in specific aneurysmal hemodynamic parameters that result from stenting relate to a number of factors including the geometric properties and configurations of deployed stents, the geometric properties of the aneurysm, and the pretreatment hemodynamics.

Computational Fluid Dynamics and Additive Manufacturing to Diagnose and Treat Cardiovascular Disease.

Noninvasive engineering models are now being used for diagnosing and planning the treatment of cardiovascular disease. Techniques in computational modeling and additive manufacturing have matured concurrently, and results from simulations can inform and enable the design and optimization of therapeutic devices and treatment strategies. The emerging synergy between large-scale simulations and 3D printing is having a two-fold benefit: first, 3D printing can be used to validate the complex simulations, and second, the flow models can be used to improve treatment planning for cardiovascular disease. In this review, we summarize and discuss recent methods and findings for leveraging advances in both additive manufacturing and patient-specific computational modeling, with an emphasis on new directions in these fields and remaining open questions.

Structural alterations of the brainstem in migraine.

Atypical brainstem modulation of pain might contribute to changes in sensory processing typical of migraine. The study objective was to investigate whether migraine is associated with brainstem structural alterations that correlate with this altered pain processing. MRI T1-weighted images of 55 migraine patients and 58 healthy controls were used to: (1) create deformable mesh models of the brainstem that allow for shape analyses; (2) calculate volumes of the midbrain, pons, medulla and the superior cerebellar peduncles; (3) interrogate correlations between regional brainstem volumes, cutaneous heat pain thresholds, and allodynia symptoms. Migraineurs had smaller midbrain volumes (healthy controls = 61.28 mm3, SD = 5.89; migraineurs = 58.80 mm3, SD = 6.64; p = 0.038), and significant (p < 0.05) inward deformations in the ventral midbrain and pons, and outward deformations in the lateral medulla and dorsolateral pons relative to healthy controls. Migraineurs had a negative correlation between ASC-12 allodynia symptom severity with midbrain volume (r = - 0.32; p = 0.019) and a positive correlation between cutaneous heat pain thresholds with medulla (r = 0.337; p = 0.012) and cerebellar peduncle volumes (r = 0.435; p = 0.001). Migraineurs with greater symptoms of allodynia have smaller midbrain volumes and migraineurs with lower heat pain thresholds have smaller medulla and cerebellar peduncles. The brainstem likely plays a role in altered sensory processing in migraine and brainstem structure might reflect severity of allodynia and hypersensitivity to pain in migraine.

A High Performance Pulsatile Pump for Aortic Flow Experiments in 3-Dimensional Models.

Aortic pathologies such as coarctation, dissection, and aneurysm represent a particularly emergent class of cardiovascular diseases. Computational simulations of aortic flows are growing increasingly important as tools for gaining understanding of these pathologies, as well as for planning their surgical repair. In vitro experiments are required to validate the simulations against real world data, and the experiments require a pulsatile flow pump system that can provide physiologic flow conditions characteristic of the aorta. We designed a newly capable piston-based pulsatile flow pump system that can generate high volume flow rates (850 mL/s), replicate physiologic waveforms, and pump high viscosity fluids against large impedances. The system is also compatible with a broad range of fluid types, and is operable in magnetic resonance imaging environments. Performance of the system was validated using image processing-based analysis of piston motion as well as particle image velocimetry. The new system represents a more capable pumping solution for aortic flow experiments than other available designs, and can be manufactured at a relatively low cost.

Cerebral Aneurysm Clipping Surgery Simulation Using Patient-Specific 3D Printing and Silicone Casting.

BACKGROUND: Neurosurgery simulator development is growing as practitioners recognize the need for improved instructional and rehearsal platforms to improve procedural skills and patient care. In addition, changes in practice patterns have decreased the volume of specific cases, such as aneurysm clippings, which reduces the opportunity for operating room experience. OBJECTIVE: The authors developed a hands-on, dimensionally accurate model for aneurysm clipping using patient-derived anatomic data and three-dimensional (3D) printing. Design of the model focused on reproducibility as well as adaptability to new patient geometry. METHODS: A modular, reproducible, and patient-derived medical simulacrum was developed for medical learners to practice aneurysmal clipping procedures. Various forms of 3D printing were used to develop a geometrically accurate cranium and vascular tree featuring 9 patient-derived aneurysms. 3D printing in conjunction with elastomeric casting was leveraged to achieve a patient-derived brain model with tactile properties not yet available from commercial 3D printing technology. An educational pilot study was performed to gauge simulation efficacy. RESULTS: Through the novel manufacturing process, a patient-derived simulacrum was developed for neurovascular surgical simulation. A follow-up qualitative study suggests potential to enhance current educational programs; assessments support the efficacy of the simulacrum. CONCLUSIONS: The proposed aneurysm clipping simulator has the potential to improve learning experiences in surgical environment. 3D printing and elastomeric casting can produce patient-derived models for a dynamic learning environment that add value to surgical training and preparation.

Ventriculostomy Simulation Using Patient-Specific Ventricular Anatomy, 3D Printing, and Hydrogel Casting.

BACKGROUND: Educational simulators provide a means for students and experts to learn and refine surgical skills. Educators can leverage the strengths of medical simulators to effectively teach complex and high-risk surgical procedures, such as placement of an external ventricular drain. OBJECTIVE: Our objective was to develop a cost-effective, patient-derived medical simulacrum for cerebral lateral ventriculostomy. METHODS: A cost-effective, patient-derived medical simulacrum was developed for placement of an external lateral ventriculostomy. Elastomeric and gel casting techniques were used to achieve realistic brain geometry and material properties. 3D printing technology was leveraged to develop accurate cranial properties and dimensions. An economical, gravity-driven pump was developed to provide normal and abnormal ventricular pressures. A small pilot study was performed to gauge simulation efficacy using a technology acceptance model. RESULTS: An accurate geometric representation of the brain was developed with independent lateral cerebral ventricular chambers. A gravity-driven pump pressurized the ventricular cavities to physiologic values. A qualitative study illustrated that the simulation has potential as an educational tool to train medical professionals in the ventriculostomy procedure. CONCLUSION: The ventricular simulacrum can improve learning in a medical education environment. Rapid prototyping and multi-material casting techniques can produce patient-derived models for cost-effective and realistic surgical training scenarios.

Finite element modeling of embolic coil deployment: multifactor characterization of treatment effects on cerebral aneurysm hemodynamics.

Endovascular coiling is the most common treatment for cerebral aneurysms. During the treatment, a sequence of embolic coils with different stiffness, shapes, sizes, and lengths is deployed to fill the aneurysmal sac. Although coil packing density has been clinically correlated with treatment success, many studies have also reported success at low packing densities, as well as recurrence at high packing densities. Such reports indicate that other factors may influence treatment success. In this study, we used a novel finite element approach and computational fluid dynamics (CFD) to investigate the effects of packing density, coil shape, aneurysmal neck size, and parent vessel flow rate on aneurysmal hemodynamics. The study examines a testbed of 80 unique CFD simulations of post-treatment flows in idealized basilar tip aneurysm models. Simulated coil deployments were validated against in vitro and in vivo deployments. Among the investigated factors, packing density had the largest effect on intra-aneurysmal velocities. However, multifactor analysis of variance showed that coil shape can also have considerable effects, depending on packing density and neck size. Further, linear regression analysis showed an inverse relationship between mean void diameter in the aneurysm and mean intra-aneurysmal velocities, which underscores the importance of coil distribution and thus coil shape. Our study suggests that while packing density plays a key role in determining post-treatment hemodynamics, other factors such as coil shape, aneurysmal geometry, and parent vessel flow may also be very important.

Flow diverter effect on cerebral aneurysm hemodynamics: an in vitro comparison of telescoping stents and the Pipeline.

INTRODUCTION: Flow diverting devices and stents can be used to treat cerebral aneurysms too difficult to treat with coiling or craniotomy and clipping. However, the hemodynamic effects of these devices have not been studied in depth. The objective of this study was to quantify and understand the fluid dynamic changes that occur within bifurcating aneurysms when treated with different devices and configurations. METHODS: Two physical models of bifurcating cerebral aneurysms were constructed: an idealized model and a patient-specific model. The models were treated with four device configurations: a single low-porosity Pipeline embolization device (PED) and one, two, and three high-porosity Enterprise stents deployed in a telescoping fashion. Particle image velocimetry was used to measure the fluid dynamics within the aneurysms; pressure was measured within the patient-specific model. RESULTS: The PED resulted in the greatest reductions in fluid dynamic activity within the aneurysm for both models. However, a configuration of three telescoping stents reduced the fluid dynamic activity within the aneurysm similarly to the PED treatment. Pressure within the patient-specific aneurysm did not show significant changes among the treatment configurations; however, the pressure difference across the untreated vessel side of the model was greatest with the PED. CONCLUSION: Treatment with stents and a flow diverter led to reductions in aneurysmal fluid dynamic activity for both idealized and patient-specific models. While the PED resulted in the greatest flow reductions, telescoping high-porosity stents performed similarly and may represent a viable treatment alternative in situations where the use of a PED is not an option.

In vitro and in silico study of intracranial stent treatments for cerebral aneurysms: effects on perforating vessel flows.

BACKGROUND: Many cerebral aneurysms can be treated effectively with intracranial stents. Unfortunately, stents can occlude perforating vessels near the treatment site which can decrease cerebral perfusion and increase the risk of stroke. METHODS: Particle image velocimetry was used to investigate the effects of intracranial stents on flows in perforators near a treated aneurysm. In Phase 1 of the study, different stent configurations were deployed into an idealized physical model of a sidewall aneurysm with perforating vessels. The configurations investigated were the Pipeline embolization device (PED) and one, two and three telescoping Neuroform stents. In Phase 2 of the study a single Neuroform stent was deployed so that the stent struts directly occluded the perforating vessel. RESULTS: In Phase 1 of the study it was found that even three telescoping stents affected perforating vessel flow less than a single PED under pulsatile conditions (average reduction 32.7% vs 46.5%). Results from Phase 2 indicated that the location of the occluding strut across the perforating vessel orifice had a greater impact on perforating vessel flow than the percentage occlusion. CONCLUSION: The findings of this study show that the use, configuration and positioning of intracranial stents can all have considerable influence on flow in affected perforating vessels near treated cerebral aneurysms.

An in vitro study of pulsatile fluid dynamics in intracranial aneurysm models treated with embolic coils and flow diverters.

Although coil embolization is one of the most effective treatments for intracranial aneurysms (ICAs), the procedure is often unsuccessful. For example, an ICA may persist after coil embolization if deployed coils fail to block the flow of blood into the aneurysm. Unfortunately, the specific flow changes that are effected by embolic coiling (and other endovascular therapies) are poorly understood, which creates a barrier to the design and execution of optimal treatments in the clinic. We present an in vitro pulsatile flow study of treated basilar tip aneurysm models that elucidates relationships between controllable treatment parameters and clinically important post-treatment fluid dynamics. We also compare fluid dynamic performance across embolic coils and more recently proposed devices (e.g., the Pipeline Embolization Device) that focus on treating ICAs by diverting rather than blocking blood flow. In agreement with previous steady flow studies, coil embolization-reduced velocity magnitude at the aneurysmal neck by greater percentages for a narrow-neck aneurysm, and reduced flow into aneurysms by greater percentages at lower parent vessel flow rates. However, flow diversion reduced flow into a wide-neck aneurysm more so than coil embolization, regardless of flow conditions. Finally, results also showed that for the endovascular devices we examined, treatment effects were generally less dramatic under physiologic pulsatile flow conditions as compared to steady flow conditions. The fluid dynamic performance data presented in this study represent the first direct in vitro comparison of coils and flow diverters in aneurysm models, and provide a novel, quantitative basis to aid in designing endovascular treatments toward specific fluid dynamic outcomes.

Segment adaptive gradient angle interpolation.

We introduce a new edge-directed interpolator based on locally defined, straight line approximations of image isophotes. Spatial derivatives of image intensity are used to describe the principal behavior of pixel-intersecting isophotes in terms of their slopes. The slopes are determined by inverting a tridiagonal matrix and are forced to vary linearly from pixel-to-pixel within segments. Image resizing is performed by interpolating along the approximated isophotes. The proposed method can accommodate arbitrary scaling factors, provides state-of-the-art results in terms of PSNR as well as other quantitative visual quality metrics, and has the advantage of reduced computational complexity that is directly proportional to the number of pixels.

Influence of stent configuration on cerebral aneurysm fluid dynamics.

Embolic coiling is the most popular endovascular treatment available for cerebral aneurysms. Nevertheless, the embolic coiling of wide-neck aneurysms is challenging and, in many cases, ineffective. Use of highly porous stents to support coiling of wide-neck aneurysms has become a common procedure in recent years. Several studies have also demonstrated that high porosity stents alone can significantly alter aneurysmal hemodynamics, but differences among different stent configurations have not been fully characterized. As a result, it is usually unclear which stent configuration is optimal for treatment. In this paper, we present a flow study that elucidates the influence of stent configuration on cerebral aneurysm fluid dynamics in an idealized wide-neck basilar tip aneurysm model. Aneurysmal fluid dynamics for three different stent configurations (half-Y, Y and, cross-bar) were first quantified using particle image velocimetry and then compared. Computational fluid dynamics (CFD) simulations were also conducted for selected stent configurations to facilitate validation and provide more detailed characterizations of the fluid dynamics promoted by different stent configurations. In vitro results showed that the Y stent configuration reduced cross-neck flow most significantly, while the cross-bar configuration reduced velocity magnitudes within the aneurysmal sac most significantly. The half-Y configuration led to increased velocity magnitudes within the aneurysmal sac at high parent-vessel flow rates. Experimental results were in strong agreement with CFD simulations. Simulated results indicated that differences in fluid dynamic performance among the different stent configurations can be attributed primarily to protruding struts within the bifurcation region.

Visualization of flow structures in Fontan patients using 3-dimensional phase contrast magnetic resonance imaging.

OBJECTIVE: Our objective was to analyze 3-dimensional (3D) blood flow patterns within the total cavopulmonary connection (TCPC) using in vivo phase contrast magnetic resonance imaging (PC MRI). METHODS: Sixteen single-ventricle patients were prospectively recruited at 2 leading pediatric institutions for PC MRI evaluation of their Fontan pathway. Patients were divided into 2 groups. Group 1 comprised 8 patients with an extracardiac (EC) TCPC, and group 2 comprised 8 patients with a lateral tunnel (LT) TCPC. A coronal stack of 5 to 10 contiguous PC MRI slices with 3D velocity encoding (5-9 ms resolution) was acquired and a volumetric flow field was reconstructed. RESULTS: Analysis revealed large vortices in LT TCPCs and helical flow structures in EC TCPCs. On average, there was no difference between LT and EC TCPCs in the proportion of inferior vena cava flow going to the left pulmonary artery (43% ± 7% vs 46% ± 5%; P = .34). However, for EC TCPCs, the presence of a caval offset was a primary determinant of inferior vena caval flow distribution to the pulmonary arteries with a significant bias to the offset side. CONCLUSIONS: 3D flow structures within LT and EC TCPCs were reconstructed and analyzed for the first time using PC MRI. TCPC flow patterns were shown to be different, not only on the basis of LT or EC considerations, but with significant influence from the superior vena cava connection as well. This work adds to the ongoing body of research demonstrating the impact of TCPC geometry on the overall hemodynamic profile.

Measuring glomerular number and size in perfused kidneys using MRI.

The goal of this work was to nondestructively measure glomerular (and thereby nephron) number in the whole kidney. Variations in the number and size of glomeruli have been linked to many renal and systemic diseases. Here, we develop a robust magnetic resonance imaging (MRI) technique based on injection of cationic ferritin (CF) to produce an accurate measurement of number and size of individual glomeruli. High-field (19 Tesla) gradient-echo MR images of perfused rat kidneys after in vivo intravenous injection of CF showed specific labeling of individual glomeruli with CF throughout the kidney. We developed a three-dimensional image-processing algorithm to count every labeled glomerulus. MRI-based counts yielded 33,786 ± 3,753 labeled glomeruli (n = 5 kidneys). Acid maceration counting of contralateral kidneys yielded an estimate of 30,585 ± 2,053 glomeruli (n = 6 kidneys). Disector/fractionator stereology counting yielded an estimate of 34,963 glomeruli (n = 2). MRI-based measurement of apparent glomerular volume of labeled glomeruli was 4.89 × 10(-4) mm(3) (n = 5) compared with the average stereological measurement of 4.99 × 10(-4) mm(3) (n = 2). The MRI-based technique also yielded the intrarenal distribution of apparent glomerular volume, a measurement previously unobtainable in histology. This work makes it possible to nondestructively measure whole-kidney glomerular number and apparent glomerular volumes to study susceptibility to renal diseases and opens the door to similar in vivo measurements in animals and humans.

Renal arterial blood flow measurement by breath-held MRI: Accuracy in phantom scans and reproducibility in healthy subjects.

This study evaluates reliability of current technology for measurement of renal arterial blood flow by breath-held velocity-encoded MRI. Overall accuracy was determined by comparing MRI measurements with known flow in controlled-flow-loop phantom studies. Measurements using prospective and retrospective gating methods were compared in phantom studies with pulsatile flow, not revealing significant differences. Phantom study results showed good accuracy, with deviations from true flow consistently below 13% for vessel diameters 3mm and above. Reproducibility in human subjects was evaluated by repeated studies in six healthy control subjects, comparing immediate repetition of the scan, repetition of the scan plane scouting, and week-to-week variation in repeated studies. The standard deviation in the 4-week protocol of repeated in vivo measurements of single-kidney renal flow in normal subjects was 59.7 mL/min, corresponding with an average coefficient of variation of 10.55%. Comparison of renal arterial blood flow reproducibility with and without gadolinium contrast showed no significant differences in mean or standard deviation. A breakdown among error components showed corresponding marginal standard deviations (coefficients of variation) 23.8 mL/min (4.21%) for immediate repetition of the breath-held flow scan, 39.13 mL/min (6.90%) for repeated plane scouting, and 40.76 mL/min (7.20%) for weekly fluctuations in renal blood flow.