Modeling Realistic Geometries in Human Intrathoracic Airways.

Geometrical models of the airways offer a comprehensive perspective on the complex interplay between lung structure and function. Originating from mathematical frameworks, these models have evolved to include detailed lung imagery, a crucial enhancement that aids in the early detection of morphological changes in the airways, which are often the first indicators of diseases. The accurate representation of airway geometry is crucial in research areas such as biomechanical modeling, acoustics, and particle deposition prediction. This review chronicles the evolution of these models, from their inception in the 1960s based on ideal mathematical constructs, to the introduction of advanced imaging techniques like computerized tomography (CT) and, to a lesser degree, magnetic resonance imaging (MRI). The advent of these techniques, coupled with the surge in data processing capabilities, has revolutionized the anatomical modeling of the bronchial tree. The limitations and challenges in both mathematical and image-based modeling are discussed, along with their applications. The foundation of image-based modeling is discussed, and recent segmentation strategies from CT and MRI scans and their clinical implications are also examined. By providing a chronological review of these models, this work offers insights into the evolution and potential future of airway geometry modeling, setting the stage for advancements in diagnosing and treating lung diseases. This review offers a novel perspective by highlighting how advancements in imaging techniques and data processing capabilities have significantly enhanced the accuracy and applicability of airway geometry models in both clinical and research settings. These advancements provide unique opportunities for developing patient-specific models.

Three-dimensional geometric morphometric shape analysis of chest wall kinematics in different breathing conditions.

Breathing motion is based on the differential activity of the thoracic, diaphragmatic and abdominal muscles. Muscle contributions differ between rest and exercise conditions and depend on posture and other factors. Traditionally, these changes are investigated on volumetric data using optoelectronic plethysmography (OEP). OEP offers insight into size variations of different chest wall (CW) compartments but does not provide three-dimensional visualization methods of CW breathing kinematics. Here we explore the use of three-dimensional geometric morphometrics to analyse size and shape changes caused by spontaneous breathing motion during quiet (QB), and recovery breathing (REC, immediately after heavy exercise) in two different postures (SIT, sitting on cycle ergometer; STA, standing position). Our findings show that size and shape differ significantly between inspiration and expiration and that differences are greater in REC than in QB. However, this is achieved by stronger expiration in SIT but by greater expiratory and inspiratory movements in STA. Shape analysis suggests that these differences may be attributed to constrained mobility of the shoulder girdle and a minor thoracic spine extension during inspiration owing to position on the ergometer. Breathing motion in STA seems biomechanically less constrained. Geometric morphometrics analyses can provide additional insights into data obtained by OEP.

Micro-CT-assisted identification of the optimal time-window for antifibrotic treatment in a bleomycin mouse model of long-lasting pulmonary fibrosis.

Idiopathic Pulmonary Fibrosis (IPF) is a debilitating and fatal lung disease characterized by the excessive formation of scar tissue and decline of lung function. Despite extensive research, only two FDA-approved drugs exist for IPF, with limited efficacy and relevant side effects. Thus, there is an urgent need for new effective therapies, whose discovery strongly relies on IPF animal models. Despite some limitations, the Bleomycin (BLM)-induced lung fibrosis mouse model is widely used for antifibrotic drug discovery and for investigating disease pathogenesis. The initial acute inflammation triggered by BLM instillation and the spontaneous fibrosis resolution that occurs after 3 weeks are the major drawbacks of this system. In the present study, we applied micro-CT technology to a longer-lasting, triple BLM administration fibrosis mouse model to define the best time-window for Nintedanib (NINT) treatment. Two different treatment regimens were examined, with a daily NINT administration from day 7 to 28 (NINT 7-28), and from day 14 to 28 (NINT 14-28). For the first time, we automatically derived both morphological and functional readouts from longitudinal micro-CT. NINT 14-28 showed significant effects on morphological parameters after just 1 week of treatment, while no modulations of these biomarkers were observed during the preceding 7-14-days period, likely due to persistent inflammation. Micro-CT morphological data evaluated on day 28 were confirmed by lung histology and bronchoalveolar lavage fluid (BALF) cells; Once again, the NINT 7-21 regimen did not provide substantial benefits over the NINT 14-28. Interestingly, both NINT treatments failed to improve micro-CT-derived functional parameters. Altogether, our findings support the need for optimized protocols in preclinical studies to expedite the drug discovery process for antifibrotic agents. This study represents a significant advancement in pulmonary fibrosis animal modeling and antifibrotic treatment understanding, with the potential for improved translatability through the concurrent structural-functional analysis offered by longitudinal micro-CT.

A Review of AIoT-based Human Activity Recognition: From Application to Technique.

This scoping review paper redefines the Artificial Intelligence-based Internet of Things (AIoT) driven Human Activity Recognition (HAR) field by systematically extrapolating from various application domains to deduce potential techniques and algorithms. We distill a general model with adaptive learning and optimization mechanisms by conducting a detailed analysis of human activity types and utilizing contact or non-contact devices. It presents various system integration mathematical paradigms driven by multimodal data fusion, covering predictions of complex behaviors and redefining valuable methods, devices, and systems for HAR. Additionally, this paper establishes benchmarks for behavior recognition across different application requirements, from simple localized actions to group activities. It summarizes open research directions, including data diversity and volume, computational limitations, interoperability, real-time recognition, data security, and privacy concerns. Finally, we aim to serve as a comprehensive and foundational resource for researchers delving into the complex and burgeoning realm of AIoT-enhanced HAR, providing insights and guidance for future innovations and developments.

Performance Assessment for the Validation of Wireless Communication Engines in an Innovative Wearable Monitoring Platform.

In today's health-monitoring applications, there is a growing demand for wireless and wearable acquisition platforms capable of simultaneously gathering multiple bio-signals from multiple body areas. These systems require well-structured software architectures, both to keep different wireless sensing nodes synchronized each other and to flush collected data towards an external gateway. This paper presents a quantitative analysis aimed at validating both the wireless synchronization task (implemented with a custom protocol) and the data transmission task (implemented with the BLE protocol) in a prototype wearable monitoring platform. We evaluated seven frequencies for exchanging synchronization packets (10 Hz, 20 Hz, 30 Hz, 40 Hz, 50 Hz, 60 Hz, 70 Hz) as well as two different BLE configurations (with and without the implementation of a dynamic adaptation of the BLE Connection Interval parameter). Additionally, we tested BLE data transmission performance in five different use case scenarios. As a result, we achieved the optimal performance in the synchronization task (1.18 ticks as median synchronization delay with a Min-Max range of 1.60 ticks and an Interquartile range (IQR) of 0.42 ticks) when exploiting a synchronization frequency of 40 Hz and the dynamic adaptation of the Connection Interval. Moreover, BLE data transmission proved to be significantly more efficient with shorter distances between the communicating nodes, growing worse by 30.5% beyond 8 m. In summary, this study suggests the best-performing network configurations to enhance the synchronization task of the prototype platform under analysis, as well as quantitative details on the best placement of data collectors.

Spinal Postures and Mobility in Children with Achondroplasia vs. Age- and Sex-Matched Healthy Individuals: A Preliminary Report.

Background: Achondroplasia is a rare genetic disease, yet the most common form of dwarfism, characterized by limb shortening and disproportionate short stature along with musculoskeletal changes, such as postural deviations. Although postural changes in the spine in children with achondroplasia have been well investigated, little is known about the association of achondroplasia with spinal movements/mobility. Methods: This preliminary study aims to explore the association of achondroplasia with spinal mobility in children with achondroplasia compared to age- and sex-matched healthy individuals. Spinal posture and mobility were assessed using a radiation-free back scan, the Idiag M360 (Idiag, Fehraltorf, Switzerland). Between-group differences were determined using a two-way analysis of variance. Results: Children with achondroplasia had smaller thoracic lateral flexion [difference between groups (Δ) = 20.4°, 95% CI 0.1°-40.6°, p = 0.04], lumbar flexion (Δ = 17.4°, 95% CI 5.5°-29.4°, p = 0.006), lumbar extension (Δ = 14.2°, 95% CI 5.7°-22.8°, p = 0.002) and lumbar lateral flexion (Δ = 19.6°, 95% CI 10.7°-28.4°, p < 0.001) than age- and sex-matched healthy individuals, except for thoracic extension (Δ = 16.5°, 95% CI 4.4°-28.7°, p = 0.009) which was greater in children with achondroplasia. No differences were observed in global spinal postures between the two groups. Conclusions: Spinal mobility appears to be more influenced by achondroplasia than global spinal postures in childhood. These results also highlight the importance of considering the musculoskeletal assessment of segmental spinal postures and rehabilitative interventions aimed at promoting spinal flexibility in children with achondroplasia.

Limb Volume Measurements: A Comparison of Circumferential Techniques and Optoelectronic Systems against Water Displacement.

BACKGROUND: Accurate measurements of limb volumes are important for clinical reasons. We aimed to assess the reliability and validity of two centimetric and two optoelectronic techniques for limb volume measurements against water volumetry, defined as the gold standard. METHODS: Five different measurement methods were executed on the same day for each participant, namely water displacement, fixed-height (circumferences measured every 5 (10) cm for the upper (lower limb) centimetric technique, segmental centimetric technique (circumferences measured according to proportional height), optoelectronic plethysmography (OEP, based on a motion analysis system), and IGOODI Gate body scanner technology (which creates an accurate 3D avatar). RESULTS: A population of 22 (15 lower limbs, 11 upper limbs, 8 unilateral upper limb lymphoedema, and 6 unilateral lower limb lymphoedema) participants was selected. Compared to water displacement, the fixed-height centimetric method, the segmental centimetric method, the OEP, and the IGOODI technique resulted in mean errors of 1.2, 0.86, -16.0, and 0.71%, respectively. The corresponding slopes (and regression coefficients) of the linear regression lines were 1.0002 (0.98), 1.0047 (0.99), 0.874 (0.94) and 0.9966 (0.99). CONCLUSION: The centimetric methods and the IGOODI system are accurate in measuring limb volume with an error of <2%. It is important to evaluate new objective and reliable techniques to improve diagnostic and follow-up possibilities.

Recent Technologies for Transcutaneous Oxygen and Carbon Dioxide Monitoring.

The measurement of partial pressures of oxygen (O2) and carbon dioxide (CO2) is fundamental for evaluating a patient's conditions in clinical practice. There are many ways to retrieve O2/CO2 partial pressures and concentrations. Arterial blood gas (ABG) analysis is the gold standard technique for such a purpose, but it is invasive, intermittent, and potentially painful. Among all the alternative methods for gas monitoring, non-invasive transcutaneous O2 and CO2 monitoring has been emerging since the 1970s, being able to overcome the main drawbacks of ABG analysis. Clark and Severinghaus electrodes enabled the breakthrough for transcutaneous O2 and CO2 monitoring, respectively, and in the last twenty years, many innovations have been introduced as alternatives to overcome their limitations. This review reports the most recent solutions for transcutaneous O2 and CO2 monitoring, with a particular consideration for wearable measurement systems. Luminescence-based electronic paramagnetic resonance and photoacoustic sensors are investigated. Optical sensors appear to be the most promising, giving fast and accurate measurements without the need for frequent calibrations and being suitable for integration into wearable measurement systems.

Effect of decreasing PEEP on hyperinflation and collapse in COVID-19: A computed tomography study.

BACKGROUND: High positive end-expiratory pressure (PEEP>10 cmH2O) is commonly used in mechanically ventilated hypoxemic patients with COVID-19. However, some epidemiological and physiological studies indirectly suggest that using a lower PEEP may primarily and beneficially decrease lung hyperinflation in this population. Herein we directly quantified the effect of decreasing PEEP from 15 to 10 cmH2O on lung hyperinflation and collapse in mechanically ventilated patients with COVID-19. METHODS: Twenty mechanically ventilated patients with COVID-19 underwent a lung computed tomography (CT) at PEEP of 15 and 10 cmH2O. The effect of decreasing PEEP on lung hyperinflation and collapse was directly quantified as the change in the over-aerated (density below -900 HU) and non-aerated (density above -100 HU) lung volumes. The net response to decreasing PEEP was computed as the sum of the change in those two compartments and expressed as the change in the "pathologic" lung volume. If the pathologic lung volume decreased (i.e., hyperinflation decreased more than collapse increased) when PEEP was decreased, the net response was considered positive; otherwise, it was considered negative. RESULTS: On average, the ratio of arterial tension to inspiratory fraction of oxygen (PaO2:FiO2) in the overall study population was 137 (119-162) mmHg. In 11 (55%) patients, the net response to decreasing PEEP was positive. Their over-aerated lung volume decreased by 159 (98-186) mL, while the non-aerated lung volume increased by only 58 (31-91) mL. In nine (45%) patients, the net response was negative. Their over-aerated lung volume decreased by 46 (18-72) mL, but their non-aerated lung volume increased by 107 (44-121) mL. CONCLUSION: In 20 patients with COVID-19 the net response to decreasing PEEP, as assessed with lung CT, was variable. In approximately half of them it was positive (and possibly beneficial), with a decrease in hyperinflation larger than the increase in collapse.

Multiphase micro-computed tomography reconstructions provide dynamic respiratory function in a mouse lung fibrosis model.

Micro-computed tomography derived functional biomarkers used in lung disease research can significantly complement end-stage histomorphometric measures while also allowing for longitudinal studies. However, no approach for visualizing lung dynamics across a full respiratory cycle has yet been described. Using bleomycin-induced lung fibrosis and the antifibrotic drug nintedanib as a test model, we implemented a four-dimensional (4D) micro-CT imaging approach consisting of 30 reconstructed volumes per respiratory cycle, coupled with deep-learning-assisted segmentation of lung volumes. 4D micro-CT provided an accurate description of inhalatory and exhalatory lung dynamics under resting conditions and revealed an inflammation-related obstructive pattern at day 7, followed by a restrictive pattern associated with fibrosis development at day 21. A milder restriction and fibrotic pathology resulted from nintedanib treatment. The similarity of 4D micro-CT data with those produced by diagnostic measurements, also points to its great potential as an exploratory tool for the discovery of clinically relevant therapeutic compounds.

Path tracking control of a steerable catheter in transcatheter cardiology interventions.

PURPOSE: Intracardiac transcatheter interventions allow for reducing trauma and hospitalization stays as compared to standard surgery. In the treatment of mitral regurgitation, the most widely adopted transcatheter approach consists in deploying a clip on the mitral valve leaflets by means of a catheter that is run through veins from a peripheral access to the left atrium. However, precise manipulation of the catheter from outside the body while copying with the path constraints imposed by the vessels remains challenging. METHODS: We proposed a path tracking control framework that provides adequate motion commands to the robotic steerable catheter for autonomous navigation through vascular lumens. The proposed work implements a catheter kinematic model featuring nonholonomic constraints. Relying on the real-time measurements from an electromagnetic sensor and a fiber Bragg grating sensor, a two-level feedback controller was designed to control the catheter. RESULTS: The proposed method was tested in a patient-specific vessel phantom. A median position error between the center line of the vessel and the catheter tip trajectory was found to be below 2 mm, with a maximum error below 3 mm. Statistical testing confirmed that the performance of the proposed method exhibited no significant difference in both free space and the contact region. CONCLUSION: The preliminary in vitro studies presented in this paper showed promising accuracy in navigating the catheter within the vessel. The proposed approach enables autonomous control of a steerable catheter for transcatheter cardiology interventions without the request of calibrating the intuitive parameters or acquiring a training dataset.

Integration of a body sensor network of wearable devices for cardio-respiratory monitoring.

Wearable devices represent a non-invasive tool to monitor cardio-respiratory parameters. This paper presents a telemedicine platform constituted of four wireless units. Three wearable inertial measurement units monitor the respiratory-related excursions of the thorax and of the abdomen with respect to a reference unit (positioned on the lower back), through which respiratory rate and normalized tidal volume are extracted. The fourth unit is a reflectance wrist-worn pulse oximeter. To validate the system, 20 healthy volunteers (12 men) participated in a protocol designed to induce desaturation conditions and subsequent changes in the respiratory pattern by means of rebreathing. The results were evaluated against two different gold standards (SenTec for pulse oximetry and Cardiopulmonary Exercise Testing machine for all units) with Bland-Altman analyses. The resulting biases for the oxygen saturation comparison between the device to be validated and the SenTec and CPET systems are -0.90% and -2.68% respectively, with agreement intervals equal to [-6.37, 4.57] and [-9.00, 3.63]. Regarding the respiratory rate comparison with respect to the CPET system, the bias is -0.01 bpm with a [-11.36, 11.35] agreement interval.Clinical Relevance-This paper provides a validation of an integrated non-invasive wearable system for cardio-respiratory monitoring to be used outside of clinical settings and during the daily life of patients.

Analysis of Fluency of Movement in Parkour Using a Video and Inertial Measurement Unit Technology.

Fluency is a movement parameter combining smoothness and hesitation, and its objective measurement may be used to determine the effects of practice on sports performance. This study aimed to measure fluency in parkour, an acrobatic discipline comprising complex non-cyclical movements, which involves fluency as a critical aspect of performance. Inter-individual fluidity differences between advanced and novice athletes as well as intra-individual variations of fluency between different parts and subsequent repetitions of a path were addressed. Seventeen parkour participants were enrolled and divided into two groups based on their experience. We analysed signals captured from an inertial measurement unit fixed on the back of the pelvis of each participant during three consecutive repetitions of a specifically designed parkour routine under the guidance of video analysis. Two fluency parameters, namely smoothness and hesitation, were measured. Smoothness was calculated as the number of inflexions on the so-called jerk graph; hesitation was the percentage of the drop in the centre of mass velocity. Smoothness resulted in significantly lower values in advanced athletes (mean: 126.4; range: 36-192) than in beginners (mean: 179.37; range: 98-272) during one of the three motor activities (p = 0.02). A qualitative analysis of hesitation showed that beginner athletes tended to experience more prominent velocity drops and negative deflection than more advanced athletes. In conclusion, a system based on a video and an inertial measurement unit is a promising approach for quantification and the assessment of variability of fluency, and it is potentially beneficial to guide and evaluate the training process.

A participatory process to design an app to improve adherence to anti-osteoporotic therapies: A development and usability study.

Objective: The aim of the study was to develop an app to improve patients' adherence to therapy for osteoporosis and to test its usability. Methods: In Phase I, the app functions needed to improve medication adherence were identified through a focus group with six patients with osteoporosis and a joint interview with two bone specialists. The app prototype was then developed (Phase II) and refined after its feasibility testing (Phase III) for 13-25 days by eight patients. Finally, the app underwent usability testing (Phase IV) for 6 months by nine other patients. The mHealth App Usability Questionnaire (MAUQ) was used to collect the assessment of the app by the 17 patients. Results: The final version of the app provided information on osteoporosis, allowed patients to contact the bone specialist for an additional consultation, and generated a reminder for taking medications accompanied by feedback on adherence. The assessment of the app was positive but evaluations differed between the feasibility and usability testing, with the former displaying a significantly (p ≤ .05) better assessment across all MAUQ items. Conclusions: In this study, we tested an app for improving adherence to medical therapies in patients with osteoporosis. The usability testing revealed a lower "patient-centered" performance of the app as compared to that observed during the feasibility phase. Future developments of the study include increasing the testing cohort and adding a technical support during the usability testing.

Digital technologies for step counting: between promises of reliability and risks of reductionism.

Step counting is among the fundamental features of wearable technology, as it grounds several uses of wearables in biomedical research and clinical care, is at the center of emerging public health interventions and recommendations, and is gaining increasing scientific and political importance. This paper provides a perspective of step counting in wearable technology, identifying some limitations to the ways in which wearable technology measures steps and indicating caution in current uses of step counting as a proxy for physical activity. Based on an overview of the current state of the art of technologies and approaches to step counting in digital wearable technologies, we discuss limitations that are methodological as well as epistemic and ethical-limitations to the use of step counting as a basis to build scientific knowledge on physical activity (epistemic limitations) as well as limitations to the accessibility and representativity of these tools (ethical limitations). As such, using step counting as a proxy for physical activity should be considered a form of reductionism. This is not per se problematic, but there is a need for critical appreciation and awareness of the limitations of reductionistic approaches. Perspective research should focus on holistic approaches for better representation of physical activity levels and inclusivity of different user populations.

Pulmonary and chest wall function in obese adults.

Obesity is frequently associated with breathing disorders. To investigate if and how the highest levels of obesity impact respiratory function, 17 subjects with obesity (median age: 49 years; BMI: 39.7 kg/m2, 8 females) and 10 normal-weighted subjects (49 years; 23.9 kg/m2, 5 females) were studied. The abdominal volume occupied 41% in the obese group, being higher (p < 0.001) than the normal-weighted group (31%), indicating accumulation of abdominal fat. Restrictive lung defect was present in 17% of subjects with obesity. At rest in the supine position, subjects with obesity breathed with higher minute ventilation (11.9 L/min) and lower ribcage contribution (5.7%) than normal weighted subjects (7.5 L/min, p = 0.001 and 31.1%, p = 0.003, respectively), thus indicating thoracic restriction. Otherwise healthy obesity might not be characterized by a systematic restrictive lung pattern. Despite this, another sign of restriction could be poor thoracic expansion at rest in the supine position, resulting in increased ventilation. Class 3 obesity made respiratory rate further increased. Opto-electronic plethysmography and its thoraco-abdominal analysis of awake breathing add viable and interesting information in subjects with obesity that were complementary to pulmonary function tests. In addition, OEP is able to localize the restrictive effect of obesity.

Dysregulation of ventilation at day and night time in heart failure.

Heart failure (HF) is characterized by an increase in ventilatory response to exercise of multifactorial aetiology and by a dysregulation in the ventilatory control during sleep with the occurrence of both central and obstructive apnoeas. In this setting, the study of the ventilatory behaviour during exercise, by cardiopulmonary exercise testing, or during sleep, by complete polysomnography or simplified nocturnal cardiorespiratory monitoring, is of paramount importance because of its prognostic value and of the possible effects of sleep-disordered breathing on the progression of the disease. Moreover, several therapeutic interventions can significantly influence ventilatory control in HF. Also, rest daytime monitoring of cardiac, metabolic, and respiratory activities through specific wearable devices could provide useful information for HF management. The aim of the review is to summarize the main studies conducted at Centro Cardiologico Monzino on these topics.

Pathophysiology of hypoxemia in mechanically-ventilated patients with COVID-19: A computed tomography study.

The pathogenesis of hypoxemia during acute respiratory distress syndrome caused by SARS-CoV-2 infection (C-ARDS) is debated. Some observations led to hypothesize ventilation to perfusion mismatch, rather than anatomical shunt, as the main determinant of hypoxemia. In this observational study 24 C-ARDS patients were studied 1 (0-1) days after intubation. Patients underwent a CT scan analysis to estimate anatomical shunt and a clinical test to measure venous admixture at two fractions of inspired oxygen (FiO2), to eliminate oxygen-responsive mechanisms of hypoxemia (ventilation to perfusion mismatch and diffusion limitation). In 10 out of 24 patients venous admixture was higher than anatomical shunt both at clinical (≈50 %) and 100 % FiO2. These patients were ventilated with a higher PEEP and had lower amount of anatomical shunt compared with patients with venous admixture equal/lower than anatomical shunt. In a subset of C-ARDS patients early after endotracheal intubation, hypoxemia might be explained by an abnormally high perfusion of a relatively low anatomical shunt.

Wearable Technologies and Stress: Toward an Ethically Grounded Approach.

The widespread use of digital technologies that can be worn on our bodies-wearables-is presented as a turning point for various areas of biomedical research and healthcare, such as stress. The ability to constantly measure these parameters, the perceived quality of measurement, and their individual and personal level frame wearable technology as a possibly crucial step in the direction of a more accurate and objective definition and measurement of stress for clinical, research, and personal purposes. In this paper, we discuss the hypothesis that the use of wearables for stress is also beneficial from an ethical viewpoint. We start by situating wearables in the context of existing methods and limitations of stress research. On this basis, we discuss the ethics of wearables for stress by applying ethical principles from bioethics (beneficence, non-maleficence, autonomy, justice), which allows us to identify ethical benefits as well as challenges in this context. As a result, we develop a more balanced view of the ethics of wearables for stress, which we use to present recommendations and indications with a focus on certification, accessibility, and inclusion. This article is, thus, a contribution towards ethically grounded wearable and digital health technology for stress.

ERS International Congress 2022: highlights from the Respiratory Clinical Care and Physiology Assembly.

It is a challenge to keep abreast of all the clinical and scientific advances in the field of respiratory medicine. This article contains an overview of the laboratory-based science, clinical trials and qualitative research that were presented during the 2022 European Respiratory Society International Congress within the sessions from the five groups of Assembly 1 (Respiratory Clinical Care and Physiology). Selected presentations are summarised from a wide range of topics: clinical problems, rehabilitation and chronic care, general practice and primary care, mobile/electronic health (m-health/e-health), clinical respiratory physiology, exercise and functional imaging.