Use of the HoloLens2 Mixed Reality Headset for Protecting Health Care Workers During the COVID-19 Pandemic: Prospective, Observational Evaluation.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has led to rapid acceleration in the deployment of new digital technologies to improve both accessibility to and quality of care, and to protect staff. Mixed-reality (MR) technology is the latest iteration of telemedicine innovation; it is a logical next step in the move toward the provision of digitally supported clinical care and medical education. This technology has the potential to revolutionize care both during and after the COVID-19 pandemic. OBJECTIVE: This pilot project sought to deploy the HoloLens2 MR device to support the delivery of remote care in COVID-19 hospital environments. METHODS: A prospective, observational, nested cohort evaluation of the HoloLens2 was undertaken across three distinct clinical clusters in a teaching hospital in the United Kingdom. Data pertaining to staff exposure to high-risk COVID-19 environments and personal protective equipment (PPE) use by clinical staff (N=28) were collected, and assessments of acceptability and feasibility were conducted. RESULTS: The deployment of the HoloLens2 led to a 51.5% reduction in time exposed to harm for staff looking after COVID-19 patients (3.32 vs 1.63 hours/day/staff member; P=.002), and an 83.1% reduction in the amount of PPE used (178 vs 30 items/round/day; P=.02). This represents 222.98 hours of reduced staff exposure to COVID-19, and 3100 fewer PPE items used each week across the three clusters evaluated. The majority of staff using the device agreed it was easy to set up and comfortable to wear, improved the quality of care and decision making, and led to better teamwork and communication. In total, 89.3% (25/28) of users felt that their clinical team was safer when using the HoloLens2. CONCLUSIONS: New technologies have a role in minimizing exposure to nosocomial infection, optimizing the use of PPE, and enhancing aspects of care. Deploying such technologies at pace requires context-specific information security, infection control, user experience, and workflow integration to be addressed at the outset and led by clinical end-users. The deployment of new telemedicine technology must be supported with objective evidence for its safety and effectiveness to ensure maximum impact.

Perfect Registration Leads to Imperfect Performance: A Randomized Trial of Multimodal Intraoperative Image Guidance.

OBJECTIVE: To compare surgical safety and efficiency of 2 image guidance modalities, perfect augmented reality (AR) and side-by-side unregistered image guidance (IG), against a no guidance control (NG), when performing a simulated laparoscopic cholecystectomy (LC). BACKGROUND: Image guidance using AR offers the potential to improve understanding of subsurface anatomy, with positive ramifications for surgical safety and efficiency. No intra-abdominal study has demonstrated any advantage for the technology. Perfect AR cannot be provided in the operative setting in a patient; however, it can be generated in the simulated setting. METHODS: Thirty-six experienced surgeons performed a baseline LC using the LapMentor simulator before randomization to 1 of 3 study arms: AR, IG, or NG. Each performed 3 further LC. Safety and efficiency-related simulator metrics, and task workload (SURG-TLX) were collected. RESULTS: The IG group had a shorter total instrument path length and fewer movements than NG and AR groups. Both IG and NG took a significantly shorter time than AR to complete dissection of Calot triangle. Use of IG and AR resulted in significantly fewer perforations and serious complications than the NG group. IG had significantly fewer perforations and serious complications than the AR group. Compared with IG, AR guidance was found to be significantly more distracting. CONCLUSION: Side-by-side unregistered image guidance (IG) improved safety and surgical efficiency in a simulated setting when compared with AR or NG. IG provides a more tangible opportunity for integrating image guidance into existing surgical workflow as well as delivering the safety and efficiency benefits desired.

Evaluating the impact of image guidance in the surgical setting: a systematic review.

BACKGROUND: Image guidance has been clinically available for over a period of 20 years. Although research increasingly has a translational emphasis, overall the clinical uptake of image guidance systems in surgery remains low. The objective of this review was to establish the metrics used to report on the impact of surgical image guidance systems used in a clinical setting. METHODS: A systematic review of the literature was carried out on all relevant publications between January 2000 and April 2016. Ovid MEDLINE and Embase databases were searched using a title strategy. Reported outcome metrics were grouped into clinically relevant domains and subsequent sub-categories for analysis. RESULTS: In total, 232 publications were eligible for inclusion. Analysis showed that clinical outcomes and system interaction were consistently reported. However, metrics focusing on surgeon, patient and economic impact were reported less often. No increase in the quality of reporting was observed during the study time period, associated with study design, or when the clinical setting involved a surgical specialty that had been using image guidance for longer. CONCLUSIONS: Publications reporting on the clinical use of image guidance systems are evaluating traditional surgical outcomes and neglecting important human and economic factors, which are pertinent to the uptake, diffusion and sustainability of image-guided surgery. A framework is proposed to assist researchers in providing comprehensive evaluation metrics, which should also be considered in the design phase. Use of these would help demonstrate the impact in the clinical setting leading to increased clinical integration of image guidance systems.

Patient-Specific Simulation of Pneumoperitoneum for Laparoscopic Surgical Planning.

Gas insufflation in laparoscopy deforms the abdomen and stretches the overlying skin. This limits the use of surgical image-guidance technologies and challenges the appropriate placement of trocars, which influences the operative ease and potential quality of laparoscopic surgery. This work describes the development of a platform that simulates pneumoperitoneum in a patient-specific manner, using preoperative CT scans as input data. This aims to provide a more realistic representation of the intraoperative scenario and guide trocar positioning to optimize the ergonomics of laparoscopic instrumentation. The simulation was developed by generating 3D reconstructions of insufflated and deflated porcine CT scans and simulating an artificial pneumoperitoneum on the deflated model. Simulation parameters were optimized by minimizing the discrepancy between the simulated pneumoperitoneum and the ground truth model extracted from insufflated porcine scans. Insufflation modeling in humans was investigated by correlating the simulation's output to real post-insufflation measurements obtained from patients in theatre. The simulation returned an average error of 7.26 mm and 10.5 mm in the most and least accurate datasets respectively. In context of the initial discrepancy without simulation (23.8 mm and 19.6 mm), the methods proposed here provide a significantly improved picture of the intraoperative scenario. The framework was also demonstrated capable of simulating pneumoperitoneum in humans. This study proposes a method for realistically simulating pneumoperitoneum to achieve optimal ergonomics during laparoscopy. Although further studies to validate the simulation in humans are needed, there is the opportunity to provide a more realistic, interactive simulation platform for future image-guided minimally invasive surgery.

Transoral Robotic Surgery: Image Guidance and Augmented Reality.

Transoral robotic surgery (TORS) is being used increasingly as an alternative to conventional open procedures, as its minimally invasive approach results in significant benefits for the patient. This includes faster recovery times and better functional outcomes, less postoperative pain and morbidity associated with open access, shorter operative times, and a reduction in the risk of infection. However, the confined working spaces and sensory deficit, due to a lack of haptic sensation, and proximity to critical vasculature and other vitally important anatomical structures bestow significant challenges on the surgeon. Recent advances in the field of surgical image guidance show promise in helping address these issues. This overview considers a number of important recent developments, all of which exploit imaging technologies that, to a lesser or greater extent, are integrated with the surgical robot platform. In its most advanced form, this combination of technologies results in a fusion of visual information such that the operative field is combined with navigational cues and representations of key anatomical structures through augmented reality registration and overlay. In terms of registration accuracy, image guidance as applied to TORS procedures is an exciting proposition, since the regions of interest (e.g., the tongue base, oropharynx) are typically adjacent to and enclosed by rigid anatomy. Clinical indications and overall effectiveness are discussed together with the limitations of the current technologies. Where appropriate, directions for future work are identified.

Evaluating a Novel 3D Stereoscopic Visual Display for Transanal Endoscopic Surgery: A Randomized Controlled Crossover Study.

OBJECTIVE: To compare surgical performance with transanal endoscopic surgery (TES) using a novel 3-dimensional (3D) stereoscopic viewer against the current modalities of a 3D stereoendoscope, 3D, and 2-dimensional (2D) high-definition monitors. BACKGROUND: TES is accepted as the primary treatment for selected rectal tumors. Current TES systems offer a 2D monitor, or 3D image, viewed directly via a stereoendoscope, necessitating an uncomfortable operating position. To address this and provide a platform for future image augmentation, a 3D stereoscopic display was created. METHODS: Forty participants, of mixed experience level, completed a simulated TES task using 4 visual displays (novel stereoscopic viewer and currently utilized stereoendoscope, 3D, and 2D high-definition monitors) in a randomly allocated order. Primary outcome measures were: time taken, path length, and accuracy. Secondary outcomes were: task workload and participant questionnaire results. RESULTS: Median time taken and path length were significantly shorter for the novel viewer versus 2D and 3D, and not significantly different to the traditional stereoendoscope. Significant differences were found in accuracy, task workload, and questionnaire assessment in favor of the novel viewer, as compared to all 3 modalities. CONCLUSIONS: This novel 3D stereoscopic viewer allows surgical performance in TES equivalent to that achieved using the current stereoendoscope and superior to standard 2D and 3D displays, but with lower physical and mental demands for the surgeon. Participants expressed a preference for this system, ranking it more highly on a questionnaire. Clinical translation of this work has begun with the novel viewer being used in 5 TES patients.

Comparative effectiveness and safety of image guidance systems in surgery: a preclinical randomised study.

BACKGROUND: Over the past decade image guidance systems have been widely adopted in specialties such as neurosurgery and otorhinolaryngology. Nonetheless, the evidence supporting the use of image guidance systems in surgery remains limited. New augmented reality systems offer the possibility of enhanced operating room workflow compared with existing triplanar image displays, but recent studies have highlighted several concerns, particularly the risk of inattentional blindness and impaired depth perception. The aim of this study was to compare simultaneously the effectiveness and safety of various image guidance systems against standard surgery. METHODS: In this preclinical randomised study design 50 novice surgeons were allocated to no image guidance, triplanar display, always-on solid overlay, always-on wire mesh overlay, or on-demand inverse realism overlay. Each participant was asked to identify a basilar tip aneurysm in a validated model head. The primary outcomes were time to task completion, and tool path length. The secondary outcomes were recognition of an unexpected finding (a surgical clip) and subjective depth perception (using a Likert scale). FINDINGS: Surgeons' time to task completion and tool path length were significantly lower in groups using any form of image guidance than in groups with no image guidance (p<0·001 and p=0·003, respectively). The tool path distance was also lower in groups using augmented reality than in those using triplanar display (p=0·010). Always-on solid overlay resulted in the greatest inattentional blindness (20% recognition of unexpected finding by all surgeons). Wire mesh and on-demand overlays mitigated but did not negate inattentional blindness, and were comparable with triplanar display (40% recognition of unexpected finding in all groups). Wire mesh and inverse realism overlays also resulted in better subjective depth perception than always-on solid overlay (p=0·031 and p=0·008, respectively). INTERPRETATION: This study suggests that new augmented reality platforms incorporating always-on wire mesh and on-demand inverse realism might improve surgical performance, at least in novice surgeons. All image display modalities, including existing triplanar display, carry a risk of inattentional blindness. FUNDING: Wellcome Trust.

Inattention blindness in surgery.

BACKGROUND: Inattention blindness (IB) can be defined as the failure to perceive an unexpected object when attention is focussed on another object or task. The principal aim of this study was to determine the effect of cognitive load and surgical image guidance on operative IB. METHODS: Using a randomised control study design, participants were allocated to a high or low cognitive load group and subsequently to one of three augmented reality (AR) image guidance groups (no guidance, wireframe overlay and solid overlay). Randomised participants watched a segment of video from a robotic partial nephrectomy. Those in the high cognitive load groups were asked to keep a count of instrument movements, while those in the low cognitive load groups were only asked to watch the video. Two foreign bodies were visible within the operative scene: a swab, within the periphery of vision; and a suture, in the centre of the operative scene. Once the participants had finished watching the video, they were asked to report whether they had observed a swab or suture. RESULTS: The overall level of prompted inattention blindness was 74 and 10 % for the swab and suture, respectively. Significantly higher levels of IB for the swab were seen in the high versus the low cognitive load groups, but not for the suture (8 vs. 47 %, p < 0.001 and 90 vs. 91 %, p = 1.000, for swab and suture, respectively). No significant difference was seen between image guidance groups for attention of the swab or suture (29 vs. 20 %, p = 0.520 and 22 vs. 22 %, p = 1.000, respectively). CONCLUSIONS: The overall effect of IB on operative practice appeared to be significant, within the context of this study. When examining for the effects of AR image guidance and cognitive load on IB, only the latter was found to have significance.

Quantifying innovation in surgery.

OBJECTIVES: The objectives of this study were to assess the applicability of patents and publications as metrics of surgical technology and innovation; evaluate the historical relationship between patents and publications; develop a methodology that can be used to determine the rate of innovation growth in any given health care technology. BACKGROUND: The study of health care innovation represents an emerging academic field, yet it is limited by a lack of valid scientific methods for quantitative analysis. This article explores and cross-validates 2 innovation metrics using surgical technology as an exemplar. METHODS: Electronic patenting databases and the MEDLINE database were searched between 1980 and 2010 for "surgeon" OR "surgical" OR "surgery." Resulting patent codes were grouped into technology clusters. Growth curves were plotted for these technology clusters to establish the rate and characteristics of growth. RESULTS: The initial search retrieved 52,046 patents and 1,801,075 publications. The top performing technology cluster of the last 30 years was minimally invasive surgery. Robotic surgery, surgical staplers, and image guidance were the most emergent technology clusters. When examining the growth curves for these clusters they were found to follow an S-shaped pattern of growth, with the emergent technologies lying on the exponential phases of their respective growth curves. In addition, publication and patent counts were closely correlated in areas of technology expansion. CONCLUSIONS: This article demonstrates the utility of publically available patent and publication data to quantify innovations within surgical technology and proposes a novel methodology for assessing and forecasting areas of technological innovation.

Specificity and detection of insulin-reactive CD4+ T cells in type 1 diabetes in the nonobese diabetic (NOD) mouse.

In the nonobese diabetic (NOD) mouse model of type 1 diabetes (T1D), an insulin peptide (B:9-23) is a major target for pathogenic CD4(+) T cells. However, there is no consensus on the relative importance of the various positions or "registers" this peptide can take when bound in the groove of the NOD MHCII molecule, IA(g7). This has hindered structural studies and the tracking of the relevant T cells in vivo with fluorescent peptide-MHCII tetramers. Using mutated B:9-23 peptides and methods for trapping the peptide in particular registers, we show that most, if not all, NOD CD4(+) T cells react to B:9-23 bound in low-affinity register 3. However, these T cells can be divided into two types depending on whether their response is improved or inhibited by substituting a glycine for the B:21 glutamic acid at the p8 position of the peptide. On the basis of these findings, we constructed a set of fluorescent insulin-IA(g7) tetramers that bind to most insulin-specific T-cell clones tested. A mixture of these tetramers detected a high frequency of B:9-23-reactive CD4(+) T cells in the pancreases of prediabetic NOD mice. Our data are consistent with the idea that, within the pancreas, unique processing of insulin generates truncated peptides that lack or contain the B:21 glutamic acid. In the thymus, the absence of this type of processing combined with the low affinity of B:9-23 binding to IA(g7) in register 3 may explain the escape of insulin-specific CD4(+) T cells from the mechanisms that usually eliminate self-reactive T cells.

HoloLens in Breast Reconstruction: What Is the Future?

SUMMARY: Autologous breast reconstruction using the deep inferior epigastric perforator flap has been established as the standard for perforator-based free-flap breast reconstruction. This technique relies on the surgeon's ability to identify the patient's relevant abdominal vasculature to facilitate accurate dissection, optimize surgical outcomes, and minimize morbidity. A technique is described in which the authors incorporate augmented reality using HoloLens technology in their surgical planning to identify epigastric arteries and perforators. This technology allows the surgeon to superimpose computed tomography angiography images directly onto the patient, facilitating an in vivo appreciation of underlying anatomy before incision and dissection. This allows real-time surgical planning, increasing the value and tangibility of preoperative computed tomography angiography with the potential to enhance the accuracy and efficiency of the operative technique. Although the authors did not use the HoloLens technology to make clinical decisions, they provide evidence of its accuracy and ease of use, offering a proof of concept. The potential of this technology is demonstrated, and the authors encourage future application in free-flap breast reconstruction and beyond.

Using Mixed Reality Headsets to Deliver Remote Bedside Teaching During the COVID-19 Pandemic: Feasibility Trial of HoloLens 2.

BACKGROUND: COVID-19 has had a catastrophic impact in terms of human lives lost. Medical education has also been impacted as appropriately stringent infection control policies precluded medical trainees from attending clinical teaching. Lecture-based education has been easily transferred to a digital platform, but bedside teaching has not. OBJECTIVE: This study aims to assess the feasibility of using a mixed reality (MR) headset to deliver remote bedside teaching. METHODS: Two MR sessions were led by senior doctors wearing the HoloLens headset. The trainers selected patients requiring their specialist input. The headset allowed bidirectional audiovisual communication between the trainer and trainee doctors. Trainee doctor conceptions of bedside teaching, impact of the COVID-19 pandemic on bedside teaching, and the MR sessions were evaluated using pre- and postround questionnaires, using Likert scales. Data related to clinician exposure to at-risk patients and use of personal protective equipment (PPE) were collected. RESULTS: Prequestionnaire respondents (n=24) strongly agreed that bedside teaching is key to educating clinicians (median 7, IQR 6-7). Postsession questionnaires showed that, overall, users subjectively agreed the MR session was helpful to their learning (median 6, IQR 5.25-7) and that it was worthwhile (median 6, IQR 5.25-7). Mixed reality versus in-person teaching led to a 79.5% reduction in cumulative clinician exposure time and 83.3% reduction in PPE use. CONCLUSIONS: This study is proof of principle that HoloLens can be used effectively to deliver clinical bedside teaching. This novel format confers significant advantages in terms of minimizing exposure of trainees to COVID-19, reducing PPE use, enabling larger attendance, and delivering convenient and accessible real-time clinical training.

Isoflurane differentially modulates mitochondrial reactive oxygen species production via forward versus reverse electron transport flow: implications for preconditioning.

BACKGROUND: Reactive oxygen species (ROS) mediate the effects of anesthetic precondition to protect against ischemia and reperfusion injury, but the mechanisms of ROS generation remain unclear. In this study, the authors investigated if mitochondria-targeted antioxidant (mitotempol) abolishes the cardioprotective effects of anesthetic preconditioning. Further, the authors investigated the mechanism by which isoflurane alters ROS generation in isolated mitochondria and submitochondrial particles. METHODS: Rats were pretreated with 0.9% saline, 3.0 mg/kg mitotempol in the absence or presence of 30 min exposure to isoflurane. Myocardial infarction was induced by left anterior descending artery occlusion for 30 min followed by reperfusion for 2 h and infarct size measurements. Mitochondrial ROS production was determined spectrofluorometrically. The effect of isoflurane on enzymatic activity of mitochondrial respiratory complexes was also determined. RESULTS: Isoflurane reduced myocardial infarct size (40 ± 9% = mean ± SD) compared with control experiments (60 ± 4%). Mitotempol abolished the cardioprotective effects of anesthetic preconditioning (60 ± 9%). Isoflurane enhanced ROS generation in submitochondrial particles with nicotinamide adenine dinucleotide (reduced form), but not with succinate, as substrate. In intact mitochondria, isoflurane enhanced ROS production in the presence of rotenone, antimycin A, or ubiquinone when pyruvate and malate were substrates, but isoflurane attenuated ROS production when succinate was substrate. Mitochondrial respiratory experiments and electron transport chain complex assays revealed that isoflurane inhibited only complex I activity. CONCLUSIONS: The results demonstrated that isoflurane produces ROS at complex I and III of the respiratory chain via the attenuation of complex I activity. The action on complex I decreases unfavorable reverse electron flow and ROS release in myocardium during reperfusion.

A remote access mixed reality teaching ward round.

BACKGROUND: Heterogeneous access to clinical learning opportunities and inconsistency in teaching is a common source of dissatisfaction among medical students. This was exacerbated during the COVID-19 pandemic, with limited exposure to patients for clinical teaching. METHODS: We conducted a proof-of-concept study at a London teaching hospital using mixed reality (MR) technology (HoloLens2™) to deliver a remote access teaching ward round. RESULTS: Students unanimously agreed that use of this technology was enjoyable and provided teaching that was otherwise inaccessible. The majority of participants gave positive feedback on the MR (holographic) content used (n = 8 out of 11) and agreed they could interact with and have their questions answered by the clinician leading the ward round (n = 9). Quantitative and free text feedback from students, patients and faculty members demonstrated that this is a feasible, acceptable and effective method for delivery of clinical education. DISCUSSION: We have used this technology in a novel way to transform the delivery of medical education and enable consistent access to high-quality teaching. This can now be integrated across the curriculum and will include remote access to specialist clinics and surgery. A library of bespoke MR educational resources will be created for future generations of medical students and doctors to use on an international scale.

Visual behaviour in robotic surgery-Demonstrating the validity of the simulated environment.

BACKGROUND: Eye metrics provide insight into surgical behaviour allowing differentiation of performance, however have not been used in robotic surgery. This study explores eye metrics of robotic surgeons in training in simulated and real tissue environments. METHODS: Following the Fundamentals of Robotic Surgery (FRS), training curriculum novice robotic surgeons were trained to expert-derived benchmark proficiency using real tissue on the da Vinci Si and the da Vinci skills simulator (dVSS) simulator. Surgeons eye metrics were recorded using eye-tracking glasses when both "novice" and "proficient" in both environments. Performance was assessed using Global Evaluative Assessment of Robotic skills (GEARS) and numeric psychomotor test score (NPMTS) scores. RESULTS: Significant (P ≤ .05) correlations were seen between pupil size, rate of change and entropy, and associated GEARS/NPMTS in "novice" and "proficient" surgeons. Only number of blinks per minute was significantly different between pupilometrics in the simulated and real tissue environments. CONCLUSIONS: This study illustrates the value of eye tracking as an objective physiological tool in the robotic setting. Pupilometrics significantly correlate with established assessment methods and could be incorporated into robotic surgery assessments.

Near infrared light protects cardiomyocytes from hypoxia and reoxygenation injury by a nitric oxide dependent mechanism.

Photobiomodulation with near infrared light (NIR) provides cellular protection in various disease models. Previously, infrared light emitted by a low-energy laser has been shown to significantly improve recovery from ischemic injury of the canine heart. The goal of this investigation was to test the hypothesis that NIR (670 nm) from light emitting diodes produces cellular protection against hypoxia and reoxygenation-induced cardiomyocyte injury. Additionally, nitric oxide (NO) was investigated as a potential cellular mediator of NIR. Our results demonstrate that exposure to NIR at the time of reoxygenation protects neonatal rat cardiomyocytes and HL-1 cells from injury, as assessed by lactate dehydrogenase release and MTT assay. Similarly, indices of apoptosis, including caspase 3 activity, annexin binding and the release of cytochrome c from mitochondria into the cytosol, were decreased after NIR treatment. NIR increased NO in cardiomyocytes, and the protective effect of NIR was completely reversed by the NO scavengers carboxy-PTIO and oxyhemoglobin, but only partially blocked by the NO synthase (NOS) inhibitor L-NMMA. Mitochondrial metabolism, measured by ATP synthase activity, was increased by NIR, and NO-induced inhibition of oxygen consumption with substrates for complex I or complex IV was reversed by exposure to NIR. Taken together these data provide evidence for protection against hypoxia and reoxygenation injury in cardiomyocytes by NIR in a manner that is dependent upon NO derived from NOS and non-NOS sources.

Role of heat shock protein 90 and endothelial nitric oxide synthase during early anesthetic and ischemic preconditioning.

BACKGROUND: Nitric oxide is known to be essential for early anesthetic preconditioning (APC) and ischemic preconditioning (IPC) of myocardium. Heat shock protein 90 (Hsp90) regulates endothelial nitric oxide synthase (eNOS) activity. In this study, the authors tested the hypothesis that Hsp90-eNOS interactions modulate APC and IPC. METHODS: Myocardial infarct size was measured in rabbits after coronary occlusion and reperfusion in the absence or presence of preconditioning within 30 min of isoflurane (APC) or 5 min of coronary artery occlusion (IPC), and with or without pretreatment with geldanamycin or radicicol, two chemically distinct Hsp90 inhibitors, or N-nitro-L-arginine methyl ester, a nonspecific nitric oxide synthase NOS inhibitor. Isoflurane-dependent nitric oxide production was measured (ozone chemiluminescence) in human coronary artery endothelial cells or mouse cardiomyocytes, in the absence or presence of Hsp90 inhibitors or N-nitro-L-arginine methyl ester. Interactions between Hsp90 and eNOS, and eNOS activation, were assessed with immunoprecipitation, immunoblotting, and confocal microscopy. RESULTS: APC and IPC decreased infarct size (by 50% and 59%, respectively), and this action was abolished by Hsp90 inhibitors. N-nitro-L-arginine methyl ester blocked APC but not IPC. Isoflurane increased nitric oxide production in human coronary artery endothelial cells concomitantly with an increase in Hsp90-eNOS interaction (immunoprecipitation, immunoblotting, and immunohistochemistry). Pretreatment with Hsp90 inhibitors abolished isoflurane-dependent nitric oxide production and decreased Hsp90-eNOS interactions. Isoflurane did not increase nitric oxide production in mouse cardiomyocytes, and eNOS was below the level of detection. CONCLUSION: The results indicate that Hsp90 plays a critical role in mediating APC and IPC through protein-protein interactions, and suggest that endothelial cells are important contributors to nitric oxide-mediated signaling during APC.

Intraoperative ultrasound for improved 3D tumour reconstruction in robot-assisted surgery: An evaluation of feedback modalities.

BACKGROUND: Intraoperative ultrasound scanning induces deformation on the tissue in the absence of a feedback modality, which results in a 3D tumour reconstruction that is not directly representative of real anatomy. METHODS: A biomechanical model with different feedback modalities (haptic, visual, or auditory) was implemented in a simulation environment. A user study with 20 clinicians was performed to assess which modality resulted in the 3D tumour volume reconstruction that most resembled the reference configuration from the respective computed tomography (CT) scans. RESULTS: Integrating a feedback modality significantly improved the scanning performance across all participants and data sets. The optimal feedback modality to adopt varied depending on the evaluation. Nonetheless, using guidance with feedback is always preferred compared with none. CONCLUSIONS: The results demonstrated the urgency to integrate a feedback modality framework into clinical practice, to ensure an improved scanning performance. Furthermore, this framework enabled an evaluation that cannot be performed in vivo.

Subject-specific modelling of pneumoperitoneum: model implementation, validation and human feasibility assessment.

PURPOSE: The aim of this study is to propose a model that simulates patient-specific anatomical changes resulting from pneumoperitoneum, using preoperative data as input. The framework can assist the surgeon through a real-time visualisation and interaction with the model. Such could further facilitate surgical planning preoperatively, by defining a surgical strategy, and intraoperatively to estimate port positions. METHODS: The biomechanical model that simulates pneumoperitoneum was implemented within the GPU-accelerated NVIDIA FleX position-based dynamics framework. Datasets of multiple porcine subjects before and after abdominal insufflation were used to generate, calibrate and validate the model. The feasibility of modelling pneumoperitoneum in human subjects was assessed by comparing distances between specific landmarks from a patient abdominal wall, to the same landmark measurements on the simulated model. RESULTS: The calibration of simulation parameters resulted in a successful estimation of an optimal set parameters. A correspondence between the simulation pressure parameter and the experimental insufflation pressure was determined. The simulation of pneumoperitoneum in a porcine subject resulted in a mean Hausdorff distance error of 5-6 mm. Feasibility of modelling pneumoperitoneum in humans was successfully demonstrated. CONCLUSION: Simulation of pneumoperitoneum provides an accurate subject-specific 3D model of the inflated abdomen, which is a more realistic representation of the intraoperative scenario when compared to preoperative imaging alone. The simulation results in a stable and interactive framework that performs in real time, and supports patient-specific data, which can assist in surgical planning.

Interactive finite element simulation of the beating heart for image-guided robotic cardiac surgery.

An interactive finite element simulation of the beating heart is described in which the intrinsic motion is implied from preoperative 4D tomographic scan data. The equations of motion are reversed such that, given changes in node displacements over time, the node forces that produce those changes are recovered. Subsequently, these forces are resolved from the global coordinate system into systems local to each mesh element such that, at each simulation time step, the collection of node forces can be expressed as simple weighted sums of current node positions. This facilitates the combination of extrinsic forces like those due to tool-tissue interactions, gravity, insufflation of the thoracic cavity and left lung deflation. The method has been applied initially to volumetric images of a pneumatically-operated beating heart phantom.