Methods for medical applications

Medical simulation tools have become increasingly popular in recent years for planning complex and non-routine surgeries. This applies also to autologous ear reconstruction, a procedure that is performed when patients have a complete or partial lack of the outer ear. On the basis of the contralateral ear, the physician sculpts a portion of costal cartilage that is then placed subcutaneously in the auricular region. Simulation tools can help the physician to familiarize with the specific geometries and shapes of the ear to be reconstructed. Making simulation tools requires the 3D acquisition of the ear, which can be done through optical scanners or diagnostic images (CT scan). This work focused on the development of a non-invasive, low-cost scanner for the acquisition of the outer ear. To this end, Intel RealSense D405 cameras were chosen, and a dedicated structure for the acquisition of ear anatomy was designed and manufactured, coupled with management software. The design of the scanner leveraged tests made with the Blender software for the optimization of the position and number of devices, while ensuring complete ear acquisition. Tests allowed the validation of the instrument both qualitatively, indicating the satisfaction of the medical staff in using the scanner, and quantitatively, measuring the deviation of the acquisition from a reference model obtained with professional scanners.

Keywords: 3D Ear Acquisition , CAD Modelling , Optical Scanner , Reverse Engineering

The 3D reconstruction of upper limb anatomy plays a significant role in many biomedical fields such as ergonomics, motion rehabilitation, and prosthesis design. In the last few years, the technical advancement of consumer-grade depth cameras has supported the development of portable and low-cost optical 3D body scanners for healthcare applications. The real-time scanning of human body parts, however, still represents a complex task due to the non-stationary nature of the scanning target. This issue imposes that the scanning time must be reduced as much as possible to minimize scanning artifacts. In this regard, depth cameras can capture geometrical information at video frame rates, thus guaranteeing fast acquisition times. Furthermore, the simultaneous use of multiple sensors would minimize undercut geometries, which impair the 3D reconstruction's completeness. In this work, a portable 3D optical scanner has been developed by rigidly assembling three Intel® RealSense™ D415 depth cameras on a lightweight circular frame. The three sensors are mutually calibrated, by using a 3D printed calibration specimen, to simultaneously align acquisitions from the three different camera viewpoints for each scanner pose. The system's effectiveness has been assessed by acquiring the geometry of both a plaster hand and a human hand and comparing the results with those obtained by a high-end stationary structured light scanner. The developed system represents a low-cost handheld alternative to existing body scanners for collecting and storing 3D anatomical data, which can be used in the design process of bespoke medical devices.

Keywords: 3D optical scanning , D415 Intel® RealSense™ , Depth-camera , Upper Limb Reconstruction

Introduction: In the last decade, two new radionuclide-based therapies, 223Radichloride and radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA), have been approved by the regulatory authorities for the management of castrate-resistant prostate cancer (PCa). Areas covered: The basic principles of PCa molecular imaging are illustrated, with a particular attention to the combined use of diagnosis and therapy in a unique approach (the so-called theranostics) for response prediction and assessment in patients submitted to 223Radichloride or PSMA targeted therapies. In this perspective, the potential of radiomics, an emerging discipline based on the extraction of quantitative features from medical images, is covered. Expert opinion: Theranostic metabolic and molecular probes have been successfully applied to predict and monitor response to radionuclide-based therapies. In particular, both 99mTc-MDP and 18F-NaF resulted useful tools for personalized dosimetry and prognostic stratification before 223Ra-therapy, while PSMA-ligands, alone or in combination with 18F-FDG, provided valuable information to select patients who are more likely to benefit from RLT and getting information on PCa grade of differentiation and aggressiveness. In spite of its high potential, PET-radiomics for PCa is still at an embryonic phase and needs further validation.

Keywords: artificial intelligence , positron emission computed tomography , precision medicine , Prostate cancer , radiomics , single photon emission tomography , targeted therapy , theranostics

A growing interest in creating advanced biomaterials with specific physical and chemical properties is currently being observed. These high-standard materials must be capable to integrate into biological environments such as the oral cavity or other anatomical regions in the human body. Given these requirements, ceramic biomaterials offer a feasible solution in terms of mechanical strength, biological functionality, and biocompatibility. In this review, the fundamental physical, chemical, and mechanical properties of the main ceramic biomaterials and ceramic nanocomposites are drawn, along with some primary related applications in biomedical fields, such as orthopedics, dentistry, and regenerative medicine. Furthermore, an in-depth focus on bone-tissue engineering and biomimetic ceramic scaffold design and fabrication is presented.

Keywords: bioceramics , biomaterials , bone tissue engineering , dentistry

In response to rapid population ageing, digital technology represents the greatest resource in supporting the implementation of active and healthy ageing principles at clinical and service levels. However, digital information platforms that deliver coordinated health and social care services for older people to cover their needs comprehensively and adequately are still not widespread. The present work is part of a project that focuses on creating a new personalised healthcare and social assistance model to enhance older people's quality of life. This model aims to prevent acute events to favour the elderly staying healthy in their own home while reducing hospitalisations. In this context, the prompt identification of criticalities and vulnerabilities through ICT devices and services is crucial. According to the human-centred care vision, this paper proposes a decision-support algorithm for the automatic and patient-specific assignment of tailored sets of devices and local services based on adults' health and social needs. This decision-support tool, which uses a tree-like model, contains conditional control statements. Using sequences of binary divisions drives the assignation of products and services to each user. Based on many predictive factors of frailty, the algorithm aims to be efficient and time-effective. This goal is achieved by adequately combining specific features, thresholds, and constraints related to the ICT devices and patients' characteristics. The validation was carried out on 50 participants. To test the algorithm, its output was compared to clinicians' decisions during the multidimensional evaluation. The algorithm reported a high sensitivity (96% for fall monitoring and 93% for cardiac tracking) and a lower specificity (60% for fall monitoring and 27% for cardiac monitoring). Results highlight the preventive and protective behaviour of the algorithm.

Keywords: decision-support algorithm , digital health , elderly , healthy ageing , personalised care , wearable sensors

Artificial limbs can help people missing body parts to restore some of their daily-life activities. However, the user should spend up to a few months to intuitively control the new device. During this period, she/he may suffer pain due to wearing or using the prosthesis inappropriately. This research presents a virtual simulator that allows the user to carry out training sessions for controlling the prosthesis. A set of Surface Electromyographic (sEMG) sensors are used to acquire the signals from user's muscles and send them to a recognition algorithm that interprets the patient's intentions. Simultaneously, the patient observes the response of her/his device on the simulator. Two studies are presented: the first study evaluate the performance of three different recognition algorithms i.e., Linear Discriminant Analysis (LDA), Support Vector Machine (SVM), and Multi-Layer Perceptron (MLP), based on the successful recognition of the patient's intentions. The second study investigates the least number of sEMG sensors to be used, as having less components improves the patient's wearability and decreases the processing time. The developed simulator represents a real prosthetic device, PRISMA hand II. The results showed the superiority of the MLP with 80% of successful recognition when 6-sEMG sensors are used. If a reduced set of gestures is considered (frequently needed by the patient), 90% of successful recognition could be achieved. Less sEMG sensors significantly degraded the performance of the recognition algorithm as only 53.8% of successful recognition could be achieved. All experiments were conducted with the help of a patient with below-elbow amputation.

Keywords: Active prosthetic hand , Biomechatronic application , Multi-Layer Perceptron (MLP) , Pattern recognition , Rehabilitation robotics , sEMG signal processing

PURPOSE. Digital technology has enabled improvements in the fitting accuracy of denture bases via milling techniques. The aim of this study was to evaluate the trueness and precision of digital and analog techniques for manufacturing complete dentures (CDs). MATERIALS AND METHODS. Sixty identical CDs were manufactured using different production protocols. Digital and analog technologies were compared using the reference geometric approach, and the Δ-error values of eight areas of interest (AOI) were calculated. For each AOI, a precise number of measurement points was selected according to sensitivity analyses to compare the Δ-error of trueness and precision between the original model and manufactured prosthesis. Three types of statistical analysis were performed: to calculate the intergroup cumulative difference among the three protocols, the intergroup among the AOIs, and the intragroup difference among AOIs. RESULTS. There was a statistically significant difference between the dentures made using the oversize process and injection molding process (P <.001), but no significant difference between the other two manufacturing methods (P =.1227). There was also a statistically significant difference between the dentures made using the monolithic process and the other two processes for all AOIs (P =.0061), but there was no significant difference between the other two processes (P = 1). Within each group, significant differences among the AOIs were observed. CONCLUSION. The monolithic process yielded better results, in terms of accuracy (trueness and precision), than the other groups, although all three processes led to dentures with Δ-error values well within the clinical tolerance limit.

Keywords: CAD-CAM , Complete denture , Digital denture , Digital workflow , Reference geometry measurement

Internal prosthesis and grafts are currently made of Ti alloys, stainless steels and Co–Cr alloys. In spite of excellent biocompatibility, they show some drawbacks that concern their mechanical properties (e.g. elastic modulus) and the need of secondary surgery for removing the implant. For this reason, a growing attention has been focused on biodegradable materials that can be absorbed into the body after tissue remodelling. In particular, Mg alloys are promising candidates for temporary implants thanks to their high biocompatibility, biodegradability and good mechanical properties that match those of human bone. In this work, the surface modifications of biodegradable AZ31 alloy were analysed after immersion for 15 days in a physiological solution (NaCl 0.09%) by using X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and scanning electron microscopy (SEM) techniques. XPS analysis of the surface of as-supplied AZ31 alloy showed the presence of MgO, whereas after immersion in the physiological solution, only Mg (OH)2 was detected. The result has been discussed with reference to literature data. From the photoemission spectra and quantitative analysis, a small amount of Ca (about 2 wt%) was also detected.

Keywords: AZ31 , biodegradable alloys , corrosion , magnesium alloys , SEM , XPS , XRD

The analysis of human gait is of fundamental importance for the monitoring and enhancement of athletes' performances. The kinematics and kinetics of human gait are mostly investigated with optical motion capture systems and force plates that require specialised laboratories and limit the possible test conditions. On the contrary, body-attached sensor networks provide an opportunity for long-term acquisitions in unsupervised, naturalistic scenarios. In this study, a wearable sensor network consisting of two wireless dataloggers and two instrumented insoles with eight pressure sensors each is used. Custom algorithms for the automatic detection of hike events and the estimation of the related temporal parameters based on sensors data are presented. The proposed algorithms were tested against laboratory measurements performed on an instrumented treadmill and showed relative errors of less than 2.5% in the estimation of stride time, step time and cadence. Higher relative errors were found in the estimation of stance and swing phases. The developed algorithms were also applied in a field study. In this paper data from one subject are considered. The aim of this research work is to provide an effective sensor-based methodology for the evaluation of gait parameters in naturalistic settings.

Keywords: Gait analysis , Hike events , Pressure insoles , Temporal parameters , Wearables

The Heavy Ion Therapy Research Integration plus (HITRIplus) is an European project that aims to integrate and propel research and technologies related to cancer treatment with heavy ion beams. Among the ambitious goals of the project, a specific work package includes the design of a gantry for carbon ions, based on superconducting magnets. The first milestone to achieve is the choice of the fundamental gantry parameters, namely the beam optics layout, the superconducting magnet technology, and the main user requirements. Starting from a reference 3 T design, the collaboration widely explored dozens of possible gantry configurations at 4 T, aiming to find the best compromise in terms of footprint, capital cost, and required R&D. We present here a summary of these configurations, underlying the initial correlation between the beam optics, the mechanics and the main superconducting dipoles design: the bending field (up to 4 T), combined function features (integrated quadrupoles), magnet aperture (up to 90 mm), and angular length (30° – 45°). The resulting main parameters are then listed, compared, and used to drive the choice of the best gantry layout to be developed in HITRIplus.

Keywords: Heavy ions , Ion beams

Despite an increase in the use of exoskeletons, particularly for medical and occupational applications, few studies have focused on the wrist, even though it is the fourth most common site of musculoskeletal pain in the upper limb. The first part of this paper will present the key challenges to be addressed to implement wrist exoskeletons as wearable devices for novel rehabilitation practices and tools in the occupational/industrial sector. Since the wrist is one of the most complex joints in the body, an understanding of the bio-mechanics and musculo-skeletal disorders of the wrist is essential to extracting design requirements. Depending on the application, each wrist exoskeleton has certain specific design requirements. These requirements have been categorized into six sections: purpose, kinematics, dynamics, rigidity, ergonomics, and safety. These form the driving factors behind the choice of a design depending on the objectives. Different design architectures are explored, forming the basis for the various technical challenges that relate to: actuation type, power source, power transmission, sensing, and control architecture. This paper summarizes, in a systematic approach, all the current technologies adopted, analyzes their benefits and limitations, and finally proposes future perspectives.

Keywords: design architectures , exoskeletons requirements , wearable devices , wrist exoskeletons

Indeterminate lung nodules detected on CT are common findings in the clinical practice, and the correct assessment of their size is critical for patient evaluation and management. We compared the stability of three definitions of nodule diameter (Feret's mean diameter, Martin's mean diameter and area-equivalent diameter) to inter-observer variability on a population of 336 solid nodules from 207 subjects. We found that inter-observer agreement was highest with Martin's mean diameter (intra-class correlation coefficient = 0.977, 95% Confidence interval = 0.977–0.978), followed by area-equivalent diameter (0.972, 0.971–0.973) and Feret's mean diameter (0.965, 0.964–0.966). The differences were statistically significant. In conclusion, although all the three diameter definitions achieved very good inter-observer agreement (ICC > 0.96), Martin's mean diameter was significantly better than the others. Future guidelines may consider adopting Martin's mean diameter as an alternative to the currently used Feret's (caliper) diameter for assessing the size of lung nodules on CT.

Keywords: Computed tomography , Inter-observer variability , Lung nodules , Size assessment

(1) Background: The application of computer-aided planning in the surgical treatment of post-traumatic forearm deformities has been increasingly widening the range of techniques over the last two decades. We present the “flipping-wedge osteotomy”, a promising geometrical approach to correct uniapical deformities defined during our experience with virtual surgical planning (VSP); (2) Methods: a case of post-traumatic distal radius deformity (magnitude 43°) treated with a flipping-wedge osteotomy in an 11-year-old girl is reported, presenting the planning rationale, its geometrical demonstration, and the outcome of the procedure; (3) Results: surgery achieved correction of both the angular and rotational deformities with a neutral ulnar variance; (4) Conclusions: flipping-wedge osteotomy may be a viable option to achieve correction in forearm deformities, and it deserves further clinical investigation.

Keywords: computer-aided surgery , forearm deformity , malunion , osteotomy , pediatric , post-traumatic , VSP

This paper presents a collaborative platform developed to allow the communication between surgeons and engineers in the process of designing patient-specific surgical instruments. To date, only a few applications are available to collaboratively create surgical instruments from medical 3D models, mostly dedicated to expert CAD modelers. This makes the preoperative planning process time-consuming and inefficient limiting the usability of applications and making planning difficult and inaccurate. Accordingly, we propose a solution in the form of a web-based, interactive, extendable, 3D navigation and manipulation application, called Precise, which does not require client installation. Precise is a lightweight, high-performance application built to provide easy-to-use, powerful, on-demand visualization and manipulation of 3D images, implemented using open-source libraries.

Keywords: 3D manipulation , Medical application , Rapid prototyping , Surgical planning

Background and objective: The ability to accomplish a consistent restoration of a missing or deformed anatomical area is a fundamental step for defining a custom implant, especially in the maxillofacial and cranial reconstruction where the aesthetical aspect is crucial for a successful surgical outcome. At the same time, this task is also the most difficult, time-consuming, and complicated across the whole reconstruction process. This is mostly due to the high geometric complexity of the anatomical structures, insufficient references, and significant interindividual anatomical heterogeneity. Numerous solutions, specifically for the neurocranium, have been put forward in the scientific literature to address the reconstruction issue, but none of them has yet been persuasive enough to guarantee an easily automatable approach with a consistent shape reconstruction. Methods: This work aims to present a novel reconstruction method (named HyM3D) for the automatic restoration of the exocranial surface by ensuring both the symmetry of the resulting skull and the continuity between the reconstructive patch and the surrounding bone. To achieve this goal, the strengths of the Template-based methods are exploited to provide knowledge of the missing or deformed region and to guide a subsequent Surface Interpolation-based algorithm. HyM3D is an improved version of a methodology presented by the authors in a previous publication for the restoration of unilateral defects. Differently from the first version, the novel procedure applies to all kinds of cranial defects, whether they are unilateral or not. Results: The presented method has been tested on several test cases, both synthetic and real, and the results show that it is reliable and trustworthy, providing a consistent outcome with no user intervention even when dealing with complex defects. Conclusions: HyM3D method proved to be a valid alternative to the existing approaches for the digital reconstruction of a defective cranial vault; furthermore, with respect to the current alternatives, it demands less user interaction since the method is landmarks-independent and does not require any patch adaptation.

Keywords: Bioinformatics , Computed aided design , Cranioplasty , Statistical shape model , Surface Interpolation

Background: The functional results of total elbow arthroplasty (TEA) are controversial and the medium- to long-term revision rates are relatively high. The aim of the present study was to analyze the stresses of TEA in its classic configuration, identify the areas of greatest stress in the prosthesis–bone–cement interface, and evaluate the most wearing working conditions. Materials and methods: By means of a reverse engineering process and using a 3D laser scanner, CAD (computer-aided drafting) models of a constrained elbow prosthesis were acquired. These CAD models were developed and their elastic properties, resistance, and stresses were studied through finite element analysis (finite element method—FEM). The obtained 3D elbow-prosthesis model was then evaluated in cyclic flexion–extension movements (> 10 million cycles). We highlighted the configuration of the angle at which the highest stresses and the areas most at risk of implant mobilization develop. Finally, we performed a quantitative study of the stress state after varying the positioning of the stem of the ulnar component in the sagittal plane by ± 3°. Results: The greatest von Mises stress state in the bone component for the 90° working configuration was 3.1635 MPa, which occurred in the most proximal portion of the humeral blade and in the proximal middle third of the shaft. At the ulnar level, peaks of 4.1763 MPa were recorded at the proximal coronoid/metaepiphysis level. The minimum elastic resistance and therefore the greatest stress states were recorded in the bone region at the apex of the ulnar stem (0.001967 MPa). The results of the analysis for the working configurations at 0° and 145° showed significant reductions in the stress states for both prosthetic components; similarly, varying the positioning of the ulnar component at 90° (− 3° in the sagittal plane, 0° in the frontal plane) resulted in better working conditions with a greater resulting developed force and a lower stress peak in the ulnar cement. Conclusion: The areas of greatest stress occur in specific regions of the ulnar and humeral components at the bone–cement–prosthesis interface. The heaviest configuration in terms of stresses was when the elbow was flexed at 90°. Variations in the positioning in the sagittal plane can mechanically affect the movement, possibly resulting in longer survival of the implant. Level of evidence: 5

Keywords: Biomechanics , Elbow finite element , Elbow replacement , Prosthetic posizioning , Totel elbow arthroplasty

PURPOSE. The aim of this study is to evaluate the accuracy of removable partial denture (RPD) frameworks produced using different digital protocols. MATERIALS AND METHODS. 80 frameworks for RPDs were produced using CAD-CAM technology and divided into four groups of twenty (n = 20): Group 1, Titanium frameworks manufactured by digital metal laser sintering (DMLS); Group 2, Co-Cr frameworks manufactured by DMLS; Group 3, Polyamide PA12 castable resin manufactured by multi-jet fusion (MJF); and Group 4, Metal (Co-Cr) casting by using lost-wax technique. After the digital acquisition, eight specific areas were selected in order to measure the Δ-error value at the intaglio surface of RPD. The minimum value required for point sampling density (0.4 mm) was derived from the sensitivity analysis. The obtained Δ-error mean value was used for comparisons: 1. between different manufacturing processes; 2. between different manufacturing techniques in the same area of interest (AOI); and 3. between different AOI of the same group. RESULTS. The Δ-error mean value of each group ranged between -0.002 (Ti) and 0.041 (Co-Cr) mm. The Pearson's Chi-squared test revealed significant differences considering all groups paired two by two, except for group 3 and 4. The multiple comparison test documented a significant difference for each AOI among group 1, 3, and 4. The multiple comparison test showed significant differences among almost all different AOIs of each group. CONCLUSION. All Δ-mean error values of all digital protocols for manufacturing RPD frameworks optimally fit within the clinical tolerance limit of trueness and precision.

Keywords: Accuracy , CAD-CAM , Digital framework , Metrological measurements , Removable partial denture

Background: The COVID-19 outbreak led to the diffusion of several telemedicine solutions. The choice of the correct platform is crucial for ensuring the release of effective assistance. However, there is a lack of an objective method for the assessment of technical features. Objective: This study proposes a methodology for the evaluation of functional requirements of telemedicine platforms. This approach also permits the comparison of solutions in the Italian market by means of defined parameters, thus directing the choice of health care professionals. Methods: The study is divided into three phases. First, a mapping of the telemedicine platforms operating in Italy is performed. Then, the available platforms are selected based on the offered telemedicine activity. Finally, a method for evaluating the investigated platforms is defined. Results: Thirty-three (n = 33) technological systems were identified through an accurate investigation on the web and interviews with IT companies. Fifteen parameters were defined and organized into three categories: (1) usability of the telemedicine platform, (2) security, and (3) technological and organizational aspects. A score between 1 and 4 was assigned to each parameter, proportionally to the completeness of the platform. In particular, 62.96% of platforms reached an average score between 3.01 and 4 points; 33.33% of them had scores between 2.01 and 3, while the remaining 3.70% of solutions obtained a result between 1.01 and 2. Conclusions: The study provides an evaluation approach that is easily usable by health professionals to select the most suitable platform. The number of solutions and quality of information could be updated to obtain a complete tool.

Keywords: technological assessment , telemedicine platforms , telemedicine solutions

The current study presents a multi-task end-to-end deep learning model for real-time blood accumulation detection and tools semantic segmentation from a laparoscopic surgery video. Intraoperative bleeding is one of the most problematic aspects of laparoscopic surgery. It is challenging to control and limits the visibility of the surgical site. Consequently, prompt treatment is required to avoid undesirable outcomes. This system exploits a shared backbone based on the encoder of the U-Net architecture and two separate branches to classify the blood accumulation event and output the segmentation map, respectively. Our main contribution is an efficient multi-task approach that achieved satisfactory results during the test on surgical videos, although trained with only RGB images and no other additional information. The proposed multi-tasking convolutional neural network did not employ any pre- or postprocessing step. It achieved a Dice Score equal to 81.89% for the semantic segmentation task and an accuracy of 90.63% for the event detection task. The results demonstrated that the concurrent tasks were properly combined since the common backbone extracted features proved beneficial for tool segmentation and event detection. Indeed, active bleeding usually happens when one of the instruments closes or interacts with anatomical tissues, and it decreases when the aspirator begins to remove the accumulated blood. Even if different aspects of the presented methodology could be improved, this work represents a preliminary attempt toward an end-to-end multi-task deep learning model for real-time video understanding.

Keywords: bleeding detection , CNN , laparoscopic surgery , multi-task convolutional neural network , semantic segmentation

Radio Pharmaceutical Therapy (RPT) comes forth as a promising technique to treat a wide range of tumors while ensuring low collateral damage to nearby healthy tissues. This kind of cancer therapy exploits the radiation following the decay of a specific radionuclide to deliver a lethal dose to tumor tissues. In the framework of the ISOLPHARM project of INFN, 111Ag was recently proposed as a promising core of a therapeutic radiopharmaceutical. In this paper, the production of 111Ag via neutron activation of 110Pd-enriched samples inside a TRIGA Mark II nuclear research reactor is studied. The radioisotope production is modeled using two different Monte Carlo codes (MCNPX and PHITS) and a stand-alone inventory calculation code FISPACT-II, with different cross section data libraries. The whole process is simulated starting from an MCNP6-based reactor model producing the neutron spectrum and flux in the selected irradiation facility. Moreover, a cost-effective, robust and easy-to-use spectroscopic system, based on a Lanthanum Bromo-Chloride (LBC) inorganic scintillator, is designed and characterized, with the aim of using it, in the future, for the quality control of the ISOLPHARM irradiated targets at the SPES facility of the Legnaro National Laboratories of INFN. natPd and 110Pd-enriched samples are irradiated in the reactor main irradiation facility and spectroscopically characterized using the LBC-based setup and a multiple-fit analysis procedure. Experimental results are compared with theoretical predictions of the developed models, showing that inaccuracies in the available cross section libraries prevent an accurate reproduction of the generated radioisotope activities. Nevertheless, models are normalized to our experimental data allowing for a reliable planning of the 111Ag production in a TRIGA Mark II reactor.

Keywords: 111Ag , ISOLPHARM project , Nuclear reactor , Radiopharmaceuticals , γ-spectroscopy