Serious game for radiotherapy training.

BACKGROUND: Cancer patients are often treated with radiation, therefore increasing their exposure to high energy emissions. In such cases, medical errors may be threatening or fatal, inducing the need to innovate new methods for maximum reduction of irreversible events. Training is an efficient and methodical tool to subject professionals to the real world and heavily educate them on how to perform with minimal errors. An evolving technique for this is Serious Gaming that can fulfill this purpose, especially with the rise of COVID-19 and the shift to the online world, by realistic and visual simulations built to present engaging scenarios. This paper presents the first Serious Game for Lung Cancer Radiotherapy training that embodies Biomedical Engineering principles and clinical experience to create a realistic and precise platform for coherent training. METHODS: To develop the game, thorough 3D modeling, animation, and gaming fundamentals were utilized to represent the whole clinical process of treatment, along with the scores and progress of every player. The model's goal is to output coherency and organization for students' ease of use and progress tracking, and to provide a beneficial educational experience supplementary to the users' training. It aims to also expand their knowledge and use of skills in critical cases where they must perform crucial decision-making and procedures on patients of different cases. RESULTS: At the end of this research, one of the accomplished goals consists of building a realistic model of the different equipment and tools accompanied with the radiotherapy process received by the patient on Maya 2018, including the true beam table, gantry, X-ray tube, CT Scanner, and so on. The serious game itself was then implemented on Unity Scenes with the built models to create a gamified authentic environment that incorporates the 5 main series of steps; Screening, Contouring, External Beam Planning, Plan Evaluation, Treatment, to simulate the practical workflow of an actual Oncology treatment delivery for lung cancer patients. CONCLUSION: This serious game provides an educational and empirical space for training and practice that can be used by students, trainees, and professionals to expand their knowledge and skills in the aim of reducing potential errors.

Lymph transport in rat mesenteric lymphatics experiencing edemagenic stress.

OBJECTIVE: To assess lymphatic flow adaptations to edema, we evaluated lymph transport function in rat mesenteric lymphatics under normal and increased fluid volume (edemagenic) conditions in situ. METHODS: Twelve rats were infused with saline (intravenous infusion, 0.2 mL/min/100 g body weight) to induce edema. We intravitally measured mesenteric lymphatic diameter and contraction frequency, as well as lymphocyte velocity and density before, during, and after infusion. RESULTS: A 10-fold increase in lymphocyte velocity (0.1-1 mm/s) and a sixfold increase in flow rate (0.1-0.6 µL/min), were observed post infusion, respectively. There were also increases in contraction frequency and fractional pump flow one minute post infusion. Time-averaged wall shear stress increased 10 fold post infusion to nearly 1.5 dynes/cm(2) . Similarly, maximum shear stress rose from 5 to 40 dynes/cm(2) . CONCLUSIONS: Lymphatic vessels adapted to edemagenic stress by increasing lymph transport. Specifically, the increases in lymphatic contraction frequency, lymphocyte velocity, and shear stress were significant. Lymph pumping increased post infusion, though changes in lymphatic diameter were not statistically significant. These results indicate that edemagenic conditions stimulate lymph transport via increases in lymphatic contraction frequency, lymphocyte velocity, and flow. These changes, consequently, resulted in large increases in wall shear stress, which could then activate NO pathways and modulate lymphatic transport function.

Measuring congestion with a non-invasive monitoring device in heart failure and haemodialysis: CONGEST-HF.

AIMS: We examined the effectiveness of a novel cardiopulmonary management wearable sensor (worn for less than 5 mins) at measuring congestion and correlated the device findings with established clinical measures of congestion. METHODS AND RESULTS: We enrolled three cohorts of patients: (1) patients with heart failure (HF) receiving intravenous diuretics in hospital; (2) patients established on haemodialysis, and (3) HF patients undergoing right heart catheterization (RHC). The primary outcomes in the respective cohorts were a Spearman correlation between (1) change in weight and change in thoracic impedance (TI) (from enrolment, 24 h after admission to discharge) in patients hospitalized for HF; (2) lung ultrasound B-lines and volume removed during dialysis with device measured TI, and (3) pulmonary capillary wedge pressure (PCWP) and sub-acoustic diastolic, third heart sound (S3) in the patients undergoing RHC. A total of 66 patients were enrolled. In HF patients (n = 25), change in weight was correlated with both change in device TI (Spearman correlation [rsp] = -0.64, p = 0.002) and change in device S3 (rsp = -0.53, p = 0.014). In the haemodialysis cohort (n = 21), B-lines and TI were strongly correlated before (rsp = -0.71, p < 0.001) and after (rsp = -0.77, p < 0.001) dialysis. Volume of fluid removed by dialysis was correlated with change in device TI (rsp = 0.49, p = 0.024). In the RHC cohort (n = 20), PCWP measured at one time point and device S3 were not significantly correlated (rsp = 0.230, p = 0.204). There were no device-related adverse events. CONCLUSIONS: A non-invasive device was able to detect changes in congestion in patients with HF receiving decongestion therapy and patients having fluid removed at haemodialysis. The cardiopulmonary management device, which measures multiple parameters, is a potentially useful tool to monitor patients with HF to prevent hospitalizations.

Mesenteric lymph flow in adult and aged rats.

The objective of study was to evaluate the aging-associated changes, contractile characteristics of mesenteric lymphatic vessels (MLV), and lymph flow in vivo in male 9- and 24-mo-old Fischer-344 rats. Lymphatic diameter, contraction amplitude, contraction frequency, and fractional pump flow, lymph flow velocity, wall shear stress, and minute active wall shear stress load were determined in MLV in vivo before and after N(ω)-nitro-L-arginine methyl ester hydrochloride (L-NAME) application at 100 µM. The active pumping of the aged rat MLV in vivo was found to be severely depleted, predominantly through the aging-associated decrease in lymphatic contractile frequency. Such changes correlate with enlargement of aged MLV, which experienced much lower minute active shear stress load than adult vessels. At the same time, pumping in aged MLV in vivo may be rapidly increased back to levels of adult vessels predominantly through the increase in contraction frequency induced by nitric oxide (NO) elimination. Findings support the idea that in aged tissues surrounding the aged MLV, the additional source of some yet unlinked lymphatic contraction-stimulatory metabolites is counterbalanced or blocked by NO release. The comparative analysis of the control data obtained from experiments with both adult and aged MLV in vivo and from isolated vessel-based studies clearly demonstrated that ex vivo isolated lymphatic vessels exhibit identical contractile characteristics to lymphatic vessels in vivo.

Electrodermal Activity Based Pre-surgery Stress Detection Using a Wrist Wearable.

Surgery is a particularly potent stressor and the detrimental effects of stress on people undergoing any surgery is indisputable. When left unchecked, the pre-surgery stress adversely impacts people's physical and psychological well-being, and may even evolve into severe pathological states. Therefore, it is essential to identify levels of preoperative stress in surgical patients. This paper focuses on developing an automatic pre-surgery stress detection scheme based on electrodermal activity (EDA). The measurement set up involves a wrist wearable that monitors EDA of a subject continuously in the most non-invasive and unobtrusive manner. Data were collected from 41 subjects [17 females and 24 males, age: 54.8 ± 16.8 years (mean ± SD)], who subsequently underwent different surgical procedures at the Sri Ramakrishna Hospital, Coimbatore, India. A supervised machine learning algorithm that detects motion artifacts in the recorded EDA data was developed. It yielded an accuracy of 97.83% on a new user dataset. The clean EDA data were further analyzed to determine low, moderate, and high levels of stress. A novel localized supervised learning scheme based on the adaptive partitioning of the dataset was adopted for stress detection. Consequently, the interindividual variability in the EDA due to person-specific factors such as the sweat gland density and skin thickness, which may lead to erroneous classification, could be eliminated. The scheme yielded a classification accuracy of 85.06% on a new user dataset and proved to be more effective than the general supervised classification model.

Aging-related anatomical and biochemical changes in lymphatic collectors impair lymph transport, fluid homeostasis, and pathogen clearance.

The role of lymphatic vessels is to transport fluid, soluble molecules, and immune cells to the draining lymph nodes. Here, we analyze how the aging process affects the functionality of the lymphatic collectors and the dynamics of lymph flow. Ultrastructural, biochemical, and proteomic analysis indicates a loss of matrix proteins, and smooth muscle cells in aged collectors resulting in a decrease in contraction frequency, systolic lymph flow velocity, and pumping activity, as measured in vivo in lymphatic collectors. Functionally, this impairment also translated into a reduced ability for in vivo bacterial transport as determined by time-lapse microscopy. Ultrastructural and proteomic analysis also indicates a decrease in the thickness of the endothelial cell glycocalyx and loss of gap junction proteins in aged lymph collectors. Redox proteomic analysis mapped an aging-related increase in the glycation and carboxylation of lymphatic's endothelial cell and matrix proteins. Functionally, these modifications translate into apparent hyperpermeability of the lymphatics with pathogen escaping from the collectors into the surrounding tissue and a decreased ability to control tissue fluid homeostasis. Altogether, our data provide a mechanistic analysis of how the anatomical and biochemical changes, occurring in aged lymphatic vessels, compromise lymph flow, tissue fluid homeostasis, and pathogen transport.

Wireless monitoring of liver hemodynamics in vivo.

Liver transplants have their highest technical failure rate in the first two weeks following surgery. Currently, there are limited devices for continuous, real-time monitoring of the graft. In this work, a three wavelengths system is presented that combines near-infrared spectroscopy and photoplethysmography with a processing method that can uniquely measure and separate the venous and arterial oxygen contributions. This strategy allows for the quantification of tissue oxygen consumption used to study hepatic metabolic activity and to relate it to tissue stress. The sensor is battery operated and communicates wirelessly with a data acquisition computer which provides the possibility of implantation provided sufficient miniaturization. In two in vivo porcine studies, the sensor tracked perfusion changes in hepatic tissue during vascular occlusions with a root mean square error (RMSE) of 0.135 mL/min/g of tissue. We show the possibility of using the pulsatile wave to measure the arterial oxygen saturation similar to pulse oximetry. The signal is also used to extract the venous oxygen saturation from the direct current (DC) levels. Arterial and venous oxygen saturation changes were measured with an RMSE of 2.19% and 1.39% respectively when no vascular occlusions were induced. This error increased to 2.82% and 3.83% when vascular occlusions were induced during hypoxia. These errors are similar to the resolution of a commercial oximetry catheter used as a reference. This work is the first realization of a wireless optical sensor for continuous monitoring of hepatic hemodynamics.

Quantifying tissue mechanical properties using photoplethysmography.

Photoplethysmography (PPG) is a non-invasive optical method that can be used to detect blood volume changes in the microvascular bed of tissue. The PPG signal comprises two components; a pulsatile waveform (AC) attributed to changes in the interrogated blood volume with each heartbeat, and a slowly varying baseline (DC) combining low frequency fluctuations mainly due to respiration and sympathetic nervous system activity. In this report, we investigate the AC pulsatile waveform of the PPG pulse for ultimate use in extracting information regarding the biomechanical properties of tissue and vasculature. By analyzing the rise time of the pulse in the diastole period, we show that PPG is capable of measuring changes in the Young's Modulus of tissue mimicking phantoms with a resolution of 4 KPa in the range of 12 to 61 KPa. In addition, the shape of the pulse can potentially be used to diagnose vascular complications by differentiating upstream from downstream complications. A Windkessel model was used to model changes in the biomechanical properties of the circulation and to test the proposed concept. The modeling data confirmed the response seen in vitro and showed the same trends in the PPG rise and fall times with changes in compliance and vascular resistance.

Intestinal perfusion monitoring using photoplethysmography.

In abdominal trauma patients, monitoring intestinal perfusion and oxygen consumption is essential during the resuscitation period. Photoplethysmography is an optical technique potentially capable of monitoring these changes in real time to provide the medical staff with a timely and quantitative measure of the adequacy of resuscitation. The challenges for using optical techniques in monitoring hemodynamics in intestinal tissue are discussed, and the solutions to these challenges are presented using a combination of Monte Carlo modeling and theoretical analysis of light propagation in tissue. In particular, it is shown that by using visible wavelengths (i.e., 470 and 525 nm), the perfusion signal is enhanced and the background contribution is decreased compared with using traditional near-infrared wavelengths leading to an order of magnitude enhancement in the signal-to-background ratio. It was further shown that, using the visible wavelengths, similar sensitivity to oxygenation changes could be obtained (over 50% compared with that of near-infrared wavelengths). This is mainly due to the increased contrast between tissue and blood in that spectral region and the confinement of the photons to the thickness of the small intestine. Moreover, the modeling results show that the source to detector separation should be limited to roughly 6 mm while using traditional near-infrared light, with a few centimeters source to detector separation leads to poor signal-to-background ratio. Finally, a visible wavelength system is tested in an in vivo porcine study, and the possibility of monitoring intestinal perfusion changes is showed.

Performance assessment of an opto-fluidic phantom mimicking porcine liver parenchyma.

An implantable, optical oxygenation and perfusion sensor to monitor liver transplants during the two-week period following the transplant procedure is currently being developed. In order to minimize the number of animal experiments required for this research, a phantom that mimics the optical, anatomical, and physiologic flow properties of liver parenchyma is being developed as well. In this work, the suitability of this phantom for liver parenchyma perfusion research was evaluated by direct comparison of phantom perfusion data with data collected from in vivo porcine studies, both using the same prototype perfusion sensor. In vitro perfusion and occlusion experiments were performed on a single-layer and on a three-layer phantom perfused with a dye solution possessing the absorption properties of oxygenated hemoglobin. While both phantoms exhibited response patterns similar to the liver parenchyma, the signal measured from the multilayer phantom was three times higher than the single layer phantom and approximately 21 percent more sensitive to in vitro changes in perfusion. Although the multilayer phantom replicated the in vivo flow patterns more closely, the data suggests that both phantoms can be used in vitro to facilitate sensor design.

Measuring contraction propagation and localizing pacemaker cells using high speed video microscopy.

Previous studies have shown the ability of many lymphatic vessels to contract phasically to pump lymph. Every lymphangion can act like a heart with pacemaker sites that initiate the phasic contractions. The contractile wave propagates along the vessel to synchronize the contraction. However, determining the location of the pacemaker sites within these vessels has proven to be very difficult. A high speed video microscopy system with an automated algorithm to detect pacemaker location and calculate the propagation velocity, speed, duration, and frequency of the contractions is presented in this paper. Previous methods for determining the contractile wave propagation velocity manually were time consuming and subject to errors and potential bias. The presented algorithm is semiautomated giving objective results based on predefined criteria with the option of user intervention. The system was first tested on simulation images and then on images acquired from isolated microlymphatic mesenteric vessels. We recorded contraction propagation velocities around 10 mm/s with a shortening speed of 20.4 to 27.1 µm/s on average and a contraction frequency of 7.4 to 21.6 contractions/min. The simulation results showed that the algorithm has no systematic error when compared to manual tracking. The system was used to determine the pacemaker location with a precision of 28 µm when using a frame rate of 300 frames per second.

Optofluidic phantom mimicking optical properties of porcine livers.

One strategy for assessing efficacy of a liver transplant is to monitor perfusion and oxygenation after transplantation. An implantable optical sensor is being developed to overcome inadequacies of current monitoring approaches. To facilitate sensor design while minimizing animal use, a polydimethylsiloxane (PDMS)-based liver phantom was developed to mimic the optical properties of porcine liver in the 630-1000 nm wavelength range and the anatomical geometry of liver parenchyma. Using soft lithography to construct microfluidic channels in pigmented elastomer enabled the 2D approximation of hexagonal liver lobules with 15mm sinusoidal channels, which will allow perfusion with blood-mimicking fluids to facilitate the development of the liver perfusion and oxygenation monitoring system.

Optimizing probe design for an implantable perfusion and oxygenation sensor.

In an effort to develop an implantable optical perfusion and oxygenation sensor, based on multiwavelength reflectance pulse oximetry, we investigate the effect of source-detector separation and other source-detector characteristics to optimize the sensor's signal to background ratio using Monte Carlo (MC) based simulations and in vitro phantom studies. Separations in the range 0.45 to 1.25 mm were found to be optimal in the case of a point source. The numerical aperture (NA) of the source had no effect on the collected signal while the widening of the source spatial profile caused a shift in the optimal source-detector separation. Specifically, for a 4.5 mm flat beam and a 2.4 mm × 2.5 mm photodetector, the optimal performance was found to be when the source and detector are adjacent to each other. These modeling results were confirmed by data collected from in vitro experiments on a liver phantom perfused with dye solutions mimicking the absorption properties of hemoglobin for different oxygenation states.