Methods for medical applications

Background/Aim: Proliferation biomarkers such as MIB-1 are strong predictors of clinical outcome and response to therapy in patients with non-small-cell lung cancer, but they require histological examination. In this work, we present a classification model to predict MIB-1 expression based on clinical parameters from positron emission tomography. Patients and Methods: We retrospectively evaluated 78 patients with histology-proven non-small-cell lung cancer (NSCLC) who underwent 18F-FDG-PET/CT for clinical examination. We stratified the population into a low and high proliferation group using MIB-1=25% as cut-off value. We built a predictive model based on binary classification trees to estimate the group label from the maximum standardized uptake value (SUVmax) and lesion diameter. Results: The proposed model showed ability to predict the correct proliferation group with overall accuracy >82% (78% and 86% for the low- and high-proliferation group, respectively). Conclusion: Our results indicate that radiotracer activity evaluated via SUVmax and lesion diameter are correlated with tumour proliferation index MIB-1.

Keywords: 18 F-FDG PET/CT , Artificial intelligence , MIB-1 , Non-small-cell lung cancer

Purpose: To provide reliable and reproducible heart/mediastinum (H/M) ratio cut-off values for parkinsonian disorders using two machine learning techniques, Support Vector Machines (SVM) and Random Forest (RF) classifier, applied to [123I]MIBG cardiac scintigraphy. Procedures: We studied 85 subjects, 50 with idiopathic Parkinson's disease, 26 with atypical Parkinsonian syndromes (P), and 9 with essential tremor (ET). All patients underwent planar early and delayed cardiac scintigraphy after [123I]MIBG (111 MBq) intravenous injection. Images were evaluated both qualitatively and quantitatively; the latter by the early and delayed H/M ratio obtained from regions of interest (ROIt1 and ROIt2) drawn on planar images. SVM and RF classifiers were finally used to obtain the correct cut-off value. Results: SVM and RF produced excellent classification performances: SVM classifier achieved perfect classification and RF also attained very good accuracy. The better cut-off for H/M value was 1.55 since it remains the same for both ROIt1 and ROIt2. This value allowed to correctly classify PD from P and ET: patients with H/M ratio less than 1.55 were classified as PD while those with values higher than 1.55 were considered as affected by parkinsonism and/or ET. No difference was found when early or late H/M ratio were considered separately thus suggesting that a single early evaluation could be sufficient to obtain the final diagnosis. Conclusions: Our results evidenced that the use of SVM and CT permitted to define the better cut-off value for H/M ratios both in early and in delayed phase thus underlining the role of [123I]MIBG cardiac scintigraphy and the effectiveness of H/M ratio in differentiating PD from other parkinsonism or ET. Moreover, early scans alone could be used for a reliable diagnosis since no difference was found between early and late. Definitely, a larger series of cases is needed to confirm this data.

Keywords: Automated classification techniques , Heart/mediastinum ratio cut-off value , Parkinson disease , Parkinsonism , Random Forest classifier , Support vector machines , [ I]MIBG cardiac scintigraphy 123

Quantitative extraction of imaging features from medical scans ('radiomics') has attracted a lot of research attention in the last few years. The literature has consistently emphasized the potential use of radiomics for computer-assisted diagnosis, as well as for predicting survival and response to treatment. Radiomics is appealing in that it enables full-field analysis of the lesion, provides nearly real-time results, and is non-invasive. Still, a lot of studies suffer from a series of drawbacks such as lack of standardization and repeatability. Such limitations, along with the unmet demand for large enough image datasets for training the algorithms, are major hurdles that still limit the application of radiomics on a large scale. In this paper, we review the current developments, potential applications, limitations, and perspectives of PET/CT radiomics with specific focus on the management of patients with lung cancer.

Keywords: CT , Lung cancer , PET , Radiomics

There is increasing evidence that shape and texture descriptors from imaging data could be used as image biomarkers for computer-assisted diagnosis and prognostication in a number of clinical conditions. It is believed that such quantitative features may help uncover patterns that would otherwise go unnoticed to the human eye, this way offering significant advantages against traditional visual interpretation. The objective of this paper is to provide an overview of the steps involved in the process – from image acquisition to feature extraction and classification. A significant part of the work deals with the description of the most common texture and shape features used in the literature; overall issues, perspectives and directions for future research are also discussed.

Keywords: Computer-assisted medicine , Radiomics , Shape , Texture

The use of continuum mechanics, especially Finite Element Analysis (FEA) has gained an extensive application in the medical field, in order to simulate soft tissues. In particular, colorectal simulations can be used to understand the interaction between colon and the surrounding tissues, and also, between colon and surgical instruments. Although several works have been introduced considering small displacements, FEA applied to colorectal surgical scenarios with large displacements is still a challenge. This work aims to investigate how FEA can describe non-linear effects induced by material properties and different approximating geometries for colon. More in detail, it shows a comparison between simulations that are performed using well-known hyperelastic models (principally Mooney-Rivlin and, in one case, Yeoh) and the linear one. These different mechanical behaviours are applied on different geometrical models (planar, cylindrical and a 3D-shape from digital acquisitions) with the aim of evaluating also the effects of geometric non-linearity. Increasing the displacements imposed by the surgical instruments, the adoption of a hyperelastic model shows lower stresses than the linear elastic one that seems to overestimate the averaged stress. Moreover, the details of the geometrical models affect the results in terms of stress-strain distribution, since it provides a better localisation of the effects related to the hypothesis of large strains.

Keywords: computer assisted surgical planning , Finite element analysis , segmentation of medical images , soft tissues simulation , surface modelling

Despite the wide use of scaffolds with spherical pores in the clinical context, no studies are reported in the literature that optimize the micro-architecture dimensions of such scaffolds to maximize the amounts of neo-formed bone. In this study, a mechanobiology-based optimization algorithm was implemented to determine the optimal geometry of scaffolds with spherical pores subjected to both compression and shear loading. We found that these scaffolds are particularly suited to bear shear loads; the amounts of bone predicted to form for this load type are, in fact, larger than those predicted in other scaffold geometries. Knowing the anthropometric characteristics of the patient, one can hypothesize the possible value of load acting on the scaffold that will be implanted and, through the proposed algorithm, determine the optimal dimensions of the scaffold that favor the formation of the largest amounts of bone. The proposed algorithm can guide and support the surgeon in the choice of a "personalized" scaffold that better suits the anthropometric characteristics of the patient, thus allowing to achieve a successful follow-up in the shortest possible time.

Keywords: Bone tissue engineering , Computational mechanobiology , Geometry optimization , Parametric CAD (Computer aided design) model , Python code

In spite of the rather large use of the fused deposition modeling (FDM) technique for the fabrication of scaffolds, no studies are reported in the literature that optimize the geometry of such scaffold types based on mechanobiological criteria. We implemented a mechanobiology-based optimization algorithm to determine the optimal distance between the strands in cylindrical scaffolds subjected to compression. The optimized scaffolds were then 3D printed with the FDM technique and successively measured. We found that the difference between the optimized distances and the average measured ones never exceeded 8.27% of the optimized distance. However, we found that large fabrication errors are made on the filament diameter when the filament diameter to be realized differs significantly with respect to the diameter of the nozzle utilized for the extrusion. This feasibility study demonstrated that the FDM technique is suitable to build accurate scaffold samples only in the cases where the strand diameter is close to the nozzle diameter. Conversely, when a large difference exists, large fabrication errors can be committed on the diameter of the filaments. In general, the scaffolds realized with the FDM technique were predicted to stimulate the formation of amounts of bone smaller than those that can be obtained with other regular beam-based scaffolds.

Keywords: Biomaterials , Geometry optimization , Mechanobiology , Scaffold design , Tissue engineering

The present work illustrates the dynamization of an orthopaedic plate for internal fracture fixation which is thought to shorten healing times and enhance the quality of the new formed bone. The dynamization is performed wirelessly thanks to a magnetic coupling. The paper shows the peculiarities of the design and manufacturing of this system: it involves two components, sliding with respect to each other with an uncertain coefficient of friction, and with a specific compounded geometry; there are stringent limits on component size, and on the required activation energy. Finally, the device belongs to medical devices and, as such, it must comply with the respective regulation (EU 2017/745, ASTM F382). The design of the dynamizable fracture fixation plate has required verifying the dynamic of the unlocking mechanism through the development of a parametric multibody model which has allowed us to fix the main design variables. As a second step, the fatigue strength of the device and the static strength of the whole bone-plate system was evaluated by finite element analysis. Both analyses have contributed to defining the final optimized geometry and the constitutive materials of the plate; finally, the respective working process was set up and its performance was tested experimentally on a reference fractured femur. As a result of these tests, the flexural stiffness of the bone-plate system resulted equal to 370 N/mm, while a maximum bending moment equal to 75.3 kNmm can be withstood without plate failure. On the whole, the performance of this dynamic plate was proved to be equal or superior to those measured for static plates already on the market, with excellent clinical results. At the same time, pre-clinical tests will be an interesting step of the future research, for which more prototypes are now being produced.

Keywords: Dynamizable plate , Fracture synthesis , Internal fixation , Mechanical tests , Medical device manufacturing , Stress analysis

This paper discusses an approach developed for exploiting the local elementary movements of evolution to study complex networks in terms of shared common embedding and, consequently, shared fractal properties. This approach can be useful for the analysis of lung cancer DNA sequences and their properties by using the concepts of graph theory and fractal geometry. The proposed method advances a renewed consideration of network complexity both on local and global scales. Several researchers have illustrated the advantages of fractal mathematics, as well as its applicability to lung cancer research. Nevertheless, many researchers and clinicians continue to be unaware of its potential. Therefore, this paper aims to examine the underlying assumptions of fractals and analyze the fractal dimension and related measurements for possible application to complex networks and, especially, to the lung cancer network. The strict relationship between the lung cancer network properties and the fractal dimension is proved. Results show that the fractal dimension decreases in the lung cancer network while the topological properties of the network increase in the lung cancer network. Finally, statistical and topological significance between the complexity of the network and lung cancer network is shown.

Keywords: Bioengineering , Complex networks , DNA geometry , Fractal dimension , Topological properties

The aim of this research is to develop patient-specific 3D mandible models, based on a limited number of measurements taken on the patient. Twenty Computed Tomography scans were used to build the respective 3D cad models of the mandible. Fifteen of these models were given as an input to a Principal Component Analysis software, and eight ‘principal' mandible morphologies were produced. The following step was to identify the most efficient landmarks to ‘weight' these morphologies when building a patient-specific model. Two further mandible computed tomography scans (a ‘normal' mandible and a ‘severely resorbed' one) were used to test the full procedure and to assess its accuracy. The accuracy of the 3D morphed surface resulted to range between 0.025 and 3.235 mm for the ‘normal' mandible and between 0.012 and 1.149 mm for the ‘severely resorbed' one having used eight landmarks to morph a ‘standard' mandible. This work demonstrates how patient-specific models can be obtained registering the position of a limited number of points (on panoramic x-ray or on the physical model), reaching a good accuracy. This allows performing patient-specific planning and numerical simulations even for those cases where a computed tomography scan would not be available. In fact, this procedure can be interfaced with mesh morphing algorithms to automatically build finite element models. The accuracy of the procedure can be further improved, widening the mandibles computed tomography scans database and optimizing landmarks position.

Keywords: Morphing , Patient-specific models , Principal Component Analysis

This paper presents a methodological procedure, based on the anatomical reconstruction and constrained deformation, to design custom-made implants for forehead augmentation in people affected by Apert syndrome, experiencing a frontal bone deficiency. According to the anthropometric theory, a cranial landmarks identification procedure was applied to retrieve, from a repository, a healthy skull, used as reference geometry for implant modelling. Then, using constrained deformation and free-form modelling techniques, it was possible to design a patient-specific implant. At last, the implant was realised using a custom mould, specially designed according to the patient's needs to provide an accurate fit of the defect site. The design procedure was tested on a patient suffering from Apert syndrome. Three implants were virtually modelled and 3D-printed for pre-surgical evaluation. Their shapes were 3D compared with a reference one (handcrafted by a surgeon) to test the accuracy. Deviations are negligible, and the customised implant fulfilled the surgeon's requirements.

Keywords: Computer-aided design , Craniomaxillofacial surgery , Implant design , Medical devices , Rapid prototyping

Impaired hand function is a major contributor to overall disability and reduced health-related quality of life in scleroderma patients. A relevant issue concerns interaction of scleroderma subjects with touchscreen interfaces. This study aims at investigating this problem assessing scleroderma patients' performance with a novel, aptly designed, touchscreen application in order to identify critical items of touchscreen technology which may impair or facilitate the use by scleroderma subjects. Eighty scleroderma patients performed this novel application including three games, each of which tested a different gesture: tapping, dragging/dropping, and pinching-to-zoom. Eighty healthy subjects without hand impairments were recruited as controls. Scleroderma patients performed worse than healthy users in each game, and statistically significant negatively impacting items were identified. In the second phase of the study, the 10 worst touchscreen performers within the scleroderma cohort were recruited for a physio-rehabilitation trial based on the daily use at home of a modified version of the software application downloaded into the personal devices of patients. The results of this study allow introduction of guidelines to design accessible touchscreen interfaces for subjects with scleroderma and suggest that touchscreen technology may be included in self-administered physio-rehabilitation programs for scleroderma hand.

Keywords: hand , hand disability , hand rehabilitation , Scleroderma , SSc , systemic sclerosis , touchscreen , touchscreen application , touchscreen device , touchscreen interface

The availability of advanced tools able to model complex geometries along with the relaxing of the constraints related to the manufacturing technologies are heavily transforming the design approach in many fields, including healthcare. The focus of this paper is on the optimization of porous lightweight cellular geometries in the orthopedic implants design: lattice structures have proven to fulfill the biological, mechanical, and technological constraints required in designing load bearing devices. The aim is to collect the information provided by the related literature to describe the effects induced by the selection of parameters designing lattice gyroid structures for orthopedic implants.

Keywords: custom metal implant , design for additive manufacturing , gyroid , metallic lattice structures , triply periodic minimal surface

In recent years, breakthroughs in the fields of reverse engineering and additive manufacturing techniques have led to the development of innovative solutions for personalized medicine. 3D technologies are quickly becoming a new treatment concept that hinges on the ability to shape patient-specific devices.Among the wide spectrum of medical applications, the orthopaedic sector is experiencing the most benefits. Several studies proposed modelling procedures for patient-specific 3D-printed casts for wrist orthoses, for example. Unfortunately, the proposed approaches are not ready to be used directly in clinical practice since the design of these devices requires significant interaction among medical staff, reverse engineering experts, additive manufacturing specialists and CAD designers. This paper proposes a new practical methodology to produce 3D printable casts for wrist immobilization with the aim of overcoming these drawbacks. In particular, the idea is to realize an exhaustive system that can be used within a paediatric environment. It should provide both a fast and accurate dedicated scanning of the hand-wrist-arm district, along with a series of easy-to-use semi-automatic tools for the modelling of the medical device. The system was designed to be used directly by the clinical staff after a brief training. It was tested on a set of five case studies with the aim of proving its general reliability and identifying possible major flaws. Casts obtained using the proposed system were manufactured using a commercial 3D printer, and the device's compliance with medical requirements was tested. Results showed that the designed casts were correctly generated by the medical staff without the need of involving engineers. Moreover, positive feedback was provided by the users involved in the experiment.

Keywords: CAD , Cast modelling , Orthosis modelling , Personalized medicine , Reverse engineering

Bone tumor resections have to be carefully planned in order to avoid intralesional cuts and thus lower the recurrence rate. Until the present-day bone resections have been performed freehand, using anatomical landmarks as reference points to retrieve planned resection planes over the very patient. Such method is highly prone to failure to the detriment of the patient's health, in fact survival rate for osteosarcomas is very low, ranging between 20% and 47%. The clinical outcome is highly dependent on the resections' accuracy; several emerging techniques proved to dramatically increase cutting accuracy, as well as survival rate, in particular Patient Specific Instruments (PSIs) and custom 3D printed metal prosthesis. The main limitation to a massive spread of this method is the large manufacturing time due to a lack of communication between surgeons and engineers about the surgical approach and the design constraints. This paper aims to compare several general-purpose low-cost software and to provide surgeons with an effective and easy to use platform to visually share information in a natural manner with engineers thus providing as many design constraints as possible, speed up the design process and avoid unfeasible results. Two surgeons from Azienda Ospedaliera Universitaria Careggi tested and evaluated a series of software. From this preliminary investigation Forger, a digital sculpting and texture painting application for iOS, resulted as the most user friendly and intuitive application among the test group.

Keywords: Computer aided surgery , Concurrent design , Digital surgical planning , Human computer interaction

The introduction of the vacuum bell (VB) for the conservative treatment of Pectus Excavatum (PE) has led to a new non-invasive alternative to thoracic surgery. The VB works by elevating the chest as long as a negative differential pressure is internally assured. In recent years studies have been conducted to validate this type of treatment and to outline its correct use; results show a short-term PE improvement when the device is worn for a minimum of 30 min (twice a day) up to a maximum of several hours a day for 12–15 months. Although the worldwide diffusion of VB devices increases year after year, its ability to lift the chest during treatment with respect to the applied pressure has begun to be evaluated only recently. In this paper, a new instrument for measuring chest elevation during treatment is presented and validated. The proposed system consists of two measurement devices: a commercial instrument for the detection of the negative pressure inside the VB, and a specifically developed optical system for the detection of chest movement. The effectiveness of the proposed system, tested on five paediatric patients, paves the way to the objective definition of an optimised patient specific VB scheme of use.

Keywords: Image processing , Optical measurement , Pectus Excavatum , Vacuum bell

This paper presents IART, a novel inertial wearable system for automatic detection of infringements and analysis of sports performance in race walking. IART algorithms are developed from raw inertial measurements collected by a single sensor located at the bottom of the vertebral column (L5–S1). Two novel parameters are developed to estimate infringements: loss of ground contact time and loss of ground contact step classification; three classic parameters are indeed used to estimate performance: step length ratio, step cadence, and smoothness. From these parameters, five biomechanical indices customized for elite athletes are derived. The experimental protocol consists of four repetitions of a straight path of 300 m on a long-paved road, performed by nine elite athletes. Over a total of 1620 steps (54 sequences of 30 steps each), the average accuracy of correct detection of loss of ground contact events is equal to 99%, whereas the correct classification of the infringement is equal to 87% for each step sequence, with a 92% of acceptable classifications. A great emphasis is dedicated on the user-centered development of IART: an intuitive radar chart representation is indeed developed to provide practical usability and interpretation of IART indices from the athletes, coaches, and referees perspectives. The results of IART, in terms of accuracy of its indices and usability from end-users, are encouraging for its usage as tool to support athletes and coaches in training and referees in real competitions.

Keywords: Biomechanics , Inertial sensor , Judgment , Race walking , Step classification , Training improvement , User-centered design

The most common type of spine instrumentation is the pedicle screw fixation. The recent literature shows how customized drilling templates help surgeons to perform the surgery better. This work aims to validate the design of a customized template for inserting lumbar pedicle screw via a procedure based on rapid prototyping and reverse engineering techniques and to show the benefits. The novelties of this template are its low-invasive sizes, its design based on a patented algorithm, which calculates the sizes of the screws and the optimal insertion direction, the engage/disengage system, and the adaptability to every kind of surgeon's kit. Accuracy of pedicle screw location, surgery duration, and X-ray exposition have been used to evaluate the performances of the template. Mono-centric in vivo trial was performed. Twenty patients (8 women and 12 men) were enrolled randomly corresponding to sixty vertebrae treated with spinal arthrodesis (30 with and 30 without templates). Accuracy of the screw positioning and reduction in both surgery duration and patients' exposure to X-rays achieved excellent results because the time spent on the insertion of pedicle screws via the surgical template was cut down by about 63%, while the number of X-ray shots was reduced by about 92%. The proposed template performed better than the standard approach and could be helpful both for skilled and novice surgeons.

Keywords: Lumbar spinal arthrodesis , Screw location optimisation , Spine surgery , Surgical template , X-ray minimisation

Virtual and Augmented Reality systems have been increasingly studied, becoming an important complement to traditional therapy as they can provide high-intensity, repetitive and interactive treatments. Several systems have been developed in research projects and some of these have become products mainly for being used at hospitals and care centers. After the initial cognitive rehabilitation performed at rehabilitation centers, patients are obliged to go to the centers, with many consequences, as costs, loss of time, discomfort and demotivation. However, it has been demonstrated that patients recovering at home heal faster because surrounded by the love of their relatives and with the community support.

Keywords: Cognitive rehabilitation , Gaming , LeapMotion , Oculus rift , VR/AR

Total Knee Arthroplasty is one of the most commonly performed orthopedic procedures and it is expected to grow in the next future . In the last past years, computer-assisted procedures represent one of the trends that are transforming the way of practicing medicine. Cornering the Total Knee Arthroplasty, digital models of the joints have been used to carry out simulation of their kinematics and mechanical performance. Whilst for the 3D digital reconstruction of the patient geometry several studies have been conducted, an approximated geometry of the prosthesis has been several times employed, with undeniable consequences on the final results. This paper aims at comparing two non-contact reverse engineering technologies to acquire the shape of femoral components employed for total knee arthroplasty. A high-level device (Konika Minolta Vivid 9i) and a mid-low cost laser (NextEngine) has been compared. For the comparison, a systematic procedure of acquisition and elaboration of the results has been adopted in order to have as unbiased as possible results. The procedure involves the use of the proprietary software of the scanners for the elaboration of the raw data and the meshing procedure has been kept the same for all the models. Since the as-is acquired mesh is of high-resolution, a decimation procedure has been carried out in order to make the 3D models lighter and easier to be handled. Once the decimation procedure has been evaluated comparing the original and the simplified models to one another, the digitalized models have been compared with the measurements taken from a coordinate measuring machines. As a preliminary result, the two lasers seem to be adequate to accomplish the reverse engineering process as required by this application. Of course, the mid-low cost laser would be preferable whether the performance will be confirmed to be (statistically) equal.