Methods for medical applications

Purpose: Planar cardiac scintigraphy with [123I]I-mIBG is widely used to image myocardial sympathetic activity. In multicentre studies, different γ-cameras can cause variability in quantitative parameters. This study aimed to harmonise multicentre [123I]I-mIBG data using a custom-designed phantom and to assess its feasibility and acceptability. Methods: A ‘tube and bottle' phantom was designed to standardise the heart-to-mediastinum (H/M) ratio across 15 centres. Each centre prepared three versions of the phantom (A, B, and C) with varying pertechnetate ([99mTc]Tc-O4-) activities, acquired static images using their own γ-camera, and uploaded DICOM data to a shared platform. In the phantom, the tube and bottle represent the heart and mediastinum, respectively, with the tube-to-bottle (T/B) ratio simulating the H/M ratio. The reference centre analysed the images and calculated the T/B ratios, applying linear regression for data harmonisation. A survey was conducted to assess the phantom's usability. Results: The harmonised T/B ratios for versions A and B were 20.46 ± 0.78 and 6.19 ± 0.39, respectively. The average slope and intercept of the regression line across the participating centres resulted in 1.07 ± 0.38 and − 0.82 ± 4.95. Survey feedback indicated high feasibility and acceptability, with all centres recommending the phantom for multicentre harmonisation.

Keywords: Artificial intelligence , Heart-to-mediastinum ratio , Multicentre studies , Radiomics , [¹²³I]I-mIBG , Γ-camera

Several studies suggest that changes in nuclear morphology due to forces and deformations as result of cell adhesion on biological substrates can induce molecular streaming through nuclear pore openings and alter chromatin structure. The condensed state of chromatin hinders transcription and replication, while its decompaction, induced by adhesion, plays a key role in differentiation. However, assessing nuclear stress/strain in vivo remains challenging, and the impact of substrate curvature on nuclear mechanics and chromatin structures is still unclear. In this study, we developed an axisymmetric finite element model of a mesenchymal stem cell adhering to substrates with different curvatures to analyze nuclear stress distribution and identify locations where adhesion-induced gene expression may occur. Results reveal a nuclear stress field with principal stresses in radial and circumferential directions, leading to chromatin decondensation and nuclear pore opening. The predicted forces acting on chromatin fibers, estimated and compared with experimental data, remain slightly below 5 pN—the threshold at which internucleosomal attraction is disrupted, triggering chromatin condensation-decondensation transition—. During early spreading, nuclear forces achieved through adhesion on convex substrates approach this threshold more closely than in concave or flat cases. These findings provide insights for tissue engineering and regenerative medicine, where early control of stem cell fate through substrate design is crucial. Understanding how mesenchymal stem cells respond to substrate curvature could lead to improved biomaterial surface topographies for guiding cell behavior.

Keywords: Cell adhesion , Chromatin decondensation , Chromatin stretching , Nuclear pore opening , Nuclear stress-strain , Substrate curvature

Regenerative medicine is an emerging discipline that investigates the possibilities of restoring portions of damaged biological tissues in a controlled way. An interesting practice in this field consists in the implantation of biomimetic scaffolds colonized by mesenchymal stem cells taken from the patient. In this work, a set of design guidelines for customized biomimetic scaffolds was analyzed, and a full procedure aimed at implementing them for the treatment of a real clinical case was outlined. In detail, a highly sustainable and biocompatible material obtained from chemical processing of fish industry by-products was selected. The primary phases of the proposed design procedure consisted in biomedical data acquisition, parametric modelling of the damaged region to regenerate, structural design of the scaffold based on the avoidance of stress shielding effects, and evaluation of the physiological pressure to apply on the implanted porous construct to maximize mature bone formation.

Keywords: CAD Modelling , Mechanical Design , Tissue Engineering

The primary procedures performed in maxillofacial surgery are osteotomy and repositioning. Surgeons usually exploit 3D printed guides and splints which entail considerable production time and high costs. To address these issues, innovative technologies such as mixed reality (MR) are emerging, but accuracy must still be assessed. Head-mounted displays (HMDs) are categorised into two main types: optical and video see-through. Recognisable comparisons between HoloLoens 2 (optical see-through) and Varjo XR3 (video see-through) are still not available in the scientific literature. This paper compares the accuracy of simulating maxillofacial surgery through these two different headsets. For the evaluation, a 3D model of a skull was 3D printed using Color Material Jetting 3D printing technology. Six people tested the MR application by i) tracing lines and holes with a pen following the holograms displayed on the phantom's anatomy for osteotomies, ii) moving the maxillary fragmented bone according to the projected hologram for repositioning. Times were recorded during the trial. The tested geometries were then 3D scanned to reconstruct the traced cutting lines and holes, and quantitative results were extracted in CloudCompare by comparing the drawn and nominal lines. For the repositioning, deviations have been computed to calculate the mean deviation from the planned displacement.

Keywords: Healthcare Design , Maxillofacial Surgery , Mixed Reality , Optical See-Through , Video See-Through

Stroke survivors often experience debilitating upper limb conditions, requiring therapy and rehabilitation exercises to regain limb function. However, frequent visits to medical centers for treatment sessions pose challenges. This paper presents GripDome, a prototype designed to measure grip strength in a user-friendly and highly tailorable manner, enabling strength recovery for patients in domestic environments without the need for medical assistance. GripDome consists of an elastic, inflatable silicone dome connected to a plastic base. Patients exert pressure inside the device by squeezing the dome with varying forces, which is measured using an external pressure transducer and a microcontroller. The prototype offers adjustable resistance levels, facilitating quantitative assessment of grip strength and personalized rehabilitation progress tracking.3D printing is employed for plastic components, enhancing affordability and customization. Experimental tests demonstrate GripDome's ability to distinguish forces of different intensities and repeatability of measurements.

Keywords: 3D printing , Grip Strength , Pneumatic , Rehabilitation , Soft Material

With approximately 431,000 cases, kidney cancer ranks 14th in terms of diagnostic frequency and accounts for 2.2% of all new cancer cases worldwide.12. For malignant clear cell renal cell carcinoma (ccRCC), which necessitates WHO/ISUP grading based on tissue microscopic analysis, early diagnosis is critical for targeted treatment. With the use of a convolutional neural network with three blocks, this study presents a machine learning-based system to grade kidney tumors using CT scans. The system divides tumours into low-grade (grades 1 and 2) and high-grade (grades 3 and 4), which corresponds to the tumour's aggressiveness and helps determine the prognosis. The challenge kits21 database's 237 preoperative CT scans were used to train the model, which yielded an accuracy of 93.67% and an f-score of 91.80%. For reliable performance validation, the approach consists of data preprocessing, augmentation, and a binary classifier with a majority voting ensemble model. The objective of this non-invasive method is to improve diagnostic accuracy in clinical settings by decreasing inter-observer variability. The dataset will be enlarged in future work to enable wider application. Although there is hope for the system's clinical support, more validation is necessary before generalization can occur.

Keywords: AI , ccRCC , Deep learning , grading , image processing , kidney cancer

More than 90% of atrial thrombi in patients with non-valvular atrial fibrillation originate in the Left Atrial Appendage (LAA), a diverticulum of the left atrium of the human heart, whose morphology predisposes the stasis of blood within it. The Left Atrial Appendage Occlusion procedure shows promise for reducing the risk of stroke due to blood clots in the body circulation after forming in the LAA; however, it must be performed by experienced operators due to the numerous associated risks. The objective is to develop a simulator for training novice operators in the procedure to plan the optimal occlusion path on representative models. Starting from a dataset of 20 diagnostic images provided by the Azienda Ospedaliero Universitaria of Careggi, a three-dimensional reconstruction of the anatomical areas involved in the surgical procedure and their spatial identification are performed. These results are used to design a device for the adjustment of a 3D printed model of the LAA with correct orientation and spatial coordinates. The simulator is a highly customizable and patient-specific prototype system; the ease of use and small size help its acceptability and reduce the time required for practice in use.

Keywords: 3D Printing , LAA , Simulator , Surgical training

In bone tumor resection surgery, patient-specific cutting guides aid the surgeon in the resection of a precise part of the bone. Despite the use of automation methodologies in surgical guide modeling, to date, the placement of cutting planes is a manual task. This work presents an algorithm for the automatic positioning of cutting planes to reduce healthy bone resected and thus improve post-operative outcomes. The algorithm uses particle swarm optimization to search for the optimal positioning of points defining a cutting surface composed of planes parallel to a surgical approach direction. The quality of a cutting surface is evaluated by an objective function that considers two key variables: the volumes of healthy bone resected and tumor removed. The algorithm was tested on three tumor cases in long bone epiphyses (two tibial, one humeral) with varying plane numbers. Optimal optimization parameters were determined, with varying parameters through iterations providing lower mean and standard deviation of the objective function. Initializing particle swarm optimization with a plausible cutting surface configuration further improved stability and minimized healthy bone resection. Future work is required to reach 3D optimization of the planes positioning, further improving the solution.

Keywords: Computer-aided surgery , Optimization , Orthopedic surgery , Surgical planning , Tumor resection

Parkinsons disease (PD) is the second most common progressive degenerative disease after Alzheimers disease, and occurs mainly in the population over 65 years of age. This disease, which is usually detected at an advanced stage, depends on a dysfunction of neuronal circuits comprising the motor cortical areas and the basal ganglia, resulting in movement abnormalities. This has a substantial impact on quality of life and requires various strategic treatments, including drug therapy, surgery and rehabilitation. This research work proposes a parametric multibody digital-twin model, developed in the Simulink-Simscape environment, capable of reproducing the posture and movements of PD patients. The model allows an accurate and non-invasive real-time or delayed assessment of patients' movements, with the aim of identifying the main signs of disease progression at an early stage in order to prevent possible related risk factors and delay disease progression.

Keywords: Disease rating scale , Impaired motor control , Multibody digital-twin model , Neurodegenerative disease , Parkinsons disease

Accurate evaluation of the cerebral aneurysm rupture risk is currently a challenge. Indeed, an accurate prediction is crucial for optimising clinical surveillance and treatment decisions. This study aims to evaluate rupture risk by analysing hemodynamic and morphological factors that would influence aneurysm growth and rupture. A computational fluid dynamics approach was employed to simulate blood flow dynamics with aneurysm geometry obtained through angiography. The blood was modelled as a non-Newtonian, incompressible, turbulent fluid, using velocity profiles derived from transcranial Doppler ultrasound as the inflow condition. The outcomes of this investigation yield significant insights into the interior of the aneurysm, specifically regarding pressure distributions and wall shear stress. These were evaluated in conjunction with the characteristics of the aneurysm shape.

Keywords: Cerebral aneurysm , CFD , rupture

In the Medical Reverse Engineering (MRE) field, the manipulation of computed tomography (CT) scans from patients is complex, especially regarding the development of 3D anatomical models of patients' anatomy. This complexity depends on the variability of human anatomy, thus involving several challenges in the fabrication of custom biomedical devices. Low back pain is a worldwide widespread disease, whose cause is still unknown today. Indeed, a comprehensive understanding of spinal biomechanics is the goal that needs to be achieved for the evolution of surgical therapies and the design of useful devices for pathologies. Hence, Finite Element (FE) modelling of the lumbar spine is an important tool, useful for understanding the spinal physiological and pathological conditions. However, the obstacle of complex geometries is of extreme relevance. The aim of this paper is to support the existing literature to provide new models that can be used in FE modelling of the spine. Therefore, a novel model of the lumbar spine L4-5 with simplified intervertebral disc geometry was created and then the following model was validated using experimental data obtained from the literature about the long-term loading.

Keywords: Biomechanics , Intervertebral disc , Lumbar spine , Medical Reverse Engineering

The use of osseointegrated implants as a solution for amputation treatment, providing a stable connection between the stump and prosthetic limb, is expanding its application to different anatomical districts. A particular focus is put on upper limb amputations, where socket-suspended systems often lead to high abandonment rates of prostheses and osseointegrated implants can enhance prosthetic-limb use, and improve bone perception and range of motion, leading to a better quality of life. This study aims to evaluate the effect of bone-implant interference and implant length of a straight implant, on the primary stability of a humerus CAD model through finite element analysis. The results suggest that a compromise can be made between interference and length to accommodate varying bone morphology and stump length. Additionally, the study results may suggest re-evaluating the prescribed weight limits for transhumeral implants based on their actual load-bearing capacity.

Keywords: <h3 class="h4">Author keywords</h3> , finite element method , osseointegration , primary stability

Total ankle arthroplasty (TAA) is a common surgical intervention for end-stage ankle arthritis. This study investigates the impact of polyethylene insert size on TAA stability. Dynamic finite element modeling incorporating anatomically accurate talus and tibia components, along with varying insert sizes, was utilized. Kinematic data acquired through dynamic radiostereometric analysis have been used as input in the FE model. Results showed that a congruent ankle prosthetic implant (all components of size 2) involves in a greater stability but also in concentrate contact pressures. This aspects could lead to a better proprioception of the patient but also to a faster insert wear over time. This underscores the importance of personalized insert sizing in TAA surgery, guided by patient-specific factors. Advanced imaging and computational tools facilitate precise preoperative planning and intraoperative decision-making. Optimal insert selection is crucial for improving long-term TAA outcomes.

Keywords: Contact pressure , FE model , RSA dynamic , TAA stability , Total ankle arthroplasty

In today's advanced era of medical science and techniques, acquiring comprehensive knowledge for conducting medical examinations has become increasingly challenging. While theoretical learning remains essential in the medical field, such as when performing ultrasound scans, the demand for practical learning opportunities prior to working with real patients has grown significantly. By leveraging on VR technology, we propose a solution that provide learners with an immersive and realistic environment where they can undergo training in ultrasound scans. This approach aims to simulate the experience of conducting actual scans, enabling learners to develop their skills effectively. In this paper, we describe our solution focusing on the technique we developed to transform any set of DICOM images into visually realistic ultrasound images to be used inside our real-time VR-based training simulation. The use of VR can overcome the financial obstacles associated with procuring expensive equipment for training purposes, while the flexibility of our approach enhances the learning experience by adapting to various scenarios and accommodating different skill levels. Learners can navigate through a range of simulated cases, reinforcing their knowledge and competence in ultrasound techniques.

Keywords: Practical Learning , Ultrasound Simulation , Virtual Reality

This study validates an innovative method using 3D facial scanning technology to analyze the depth of wrinkles and their potential correlation with cardiovascular risk factors. The research quantitatively assessed the severity of wrinkles in the forehead (HF), glabellar (GF), and periorbital (PO) regions, establishing a link between visible signs of aging and cardiovascular health risks. A trend was observed where greater wrinkle volume corresponds to higher cardiovascular risk scores, although the relationship was not uniformly linear, suggesting a complex interplay of factors influencing both cardiovascular health and aging.

Keywords: 3D Facial Scanning , 3D Model , Cardiovascular Risk , Deviation Analysis , Wrinkles

Conventional ground-based transport systems often experience delays due to congested traffic. This is unacceptable in the case of transporting organs, blood, medicines and emergency supplies, when time is critical. Urban Air Mobility (UAM) offers a solution to overcome transportation inefficiencies. In fact, Unmanned Aerial Systems (UAS) can quickly reach remote locations providing critical care in a timely manner. However, ensuring efficiency, safety and compliance with regulations is essential. This paper presents the mission-oriented design approach of a UAS, focusing on two subsystems, namely the Unmanned Aircraft (UA) and the Functional Container (FC). The design of the UA involves choices for configuring its layout. The FC design focuses on the preservation of the transported material. Lightweight and reliable dedicated solutions are designed for FC leveraging Additive Manufacturing (AM) technology. The design is mission-oriented, but allows systems to be reconfigured for additional missions.

Keywords: Advanced air mobility , Drone , medical , mission-oriented design , Unmanned air vehicle

Industry 5.0 emphasizes human-centric approaches in technological advancement, particularly crucial in healthcare applications such as prosthetics development. While individual technologies like additive manufacturing, machine learning, digital twins, and tissue engineering have shown promise in prosthetics innovation, their integration remains a significant challenge. This paper presents a novel multidisciplinary framework developed through the National Centre for High-Performance Computing (CN-HPC) project, which addresses the gap between individual technological capabilities and their coordinated application in personalized prosthetics development. The framework, implemented through collaboration between six research groups from two universities, employs the House of Quality methodology to align technological integration with patient needs. Our approach encompasses a comprehensive seven-step process, from initial patient requirements definition through virtual modeling, production process optimization, virtual sensing, machine learning enhancement, digital twin simulation, to advanced tissue engineering. A data model facilitates seamless information exchange between different technological domains and research groups. This research contributes to the field by providing a scalable, human-centered framework for technology integration in medical device development, potentially extending beyond prosthetics to other healthcare applications. The proposed framework represents a significant step toward realizing the full potential of Industry 5.

Keywords: Healthcare , House of Quality , Human-Centricity , Industry 5.0 , Prosthesis

In orthopedic surgery, bone tissues aid in the reconstruction of damaged or missing bone and ligaments, allowing patients to achieve optimal motor function recovery. A musculoskeletal tissue bank collects and certifies donated tissue for transplantation. However, sometimes suitable bone tissue is unavailable or incompatible geometrically with the required implant. Custom-made, biocompatible artificial bone tissue development could mitigate such challenges. Scaffolds, either biological or synthetic, promote bone regeneration within the body. Despite research on their chemical compositions and mechanical properties, limited attention is given to their geometric design and personalized shape. This study presents a method for designing bone scaffold geometry using additive manufacturing in a biocompatible material. The aim is to create a scaffold with variable density, from denser cortical to less dense medullary zones. CT images determine bone tissue density, compared to the density imposed on the scaffold. Additionally, the printability of the PEEK, the chosen material, is investigated.

Keywords: 3D Printing , Biomaterials , CAD , Lattice structures , PEEK

The development of prototypes prior to the market launch of final products requires adapting production components to reduce costs and increase flexibility for potential modifications. While the manufacturing of rigid or structural components is well-established and widely practiced, the production of expanded materials presents significantly greater challenges due to the final product's reliance on the specific process employed. Changing the process to lower costs necessitates reproducing the same mechanical behaviour and appearance to ensure validation in terms of both style and function. This study focuses on replicating the behaviour of expanded polyurethane foam, commonly used in motorcycle seat padding, using thermoplastic polyurethane (TPU). The aim is to create a prototype or a customised version of the foam. The internal stochastic closed-cell structure is designed using slicing software, and test specimens are subsequently fabricated through Material Extrusion (MEX) additive manufacturing and subjected to compression testing. The results emphasise the critical influence of material hardness and infill density on the force-displacement curves. An experimental map, derived from three parameters (material hardness, elastic modulus, and foam density) illustrates the behaviour of the specimens, with iso-lines representing constant density.

Keywords: Additive manufacturing , Material extrusion (MEX) , Motorcycle saddle , Polymeric foams , Rapid prototyping , Stochastic infill