Statistical Properties of a Virtual Cohort for In Silico Trials Generated with a Statistical Anatomy Atlas

Osteoporosis-related hip fragility fractures are a catastrophic event for patient lives but are not frequently observed in prospective studies, and therefore phase III clinical trials using fractures as primary clinical endpoint require thousands of patients enrolled for several years to reach statistical significance. A novel answer to the large number of subjects needed to reach the desired evidence level is offered by In Silico Trials, that is, the simulation of a clinical trial on a large cohort of virtual patients, monitoring the biomarkers of interest. In this work we investigated if statistical aliasing from a custom anatomy atlas could be used to expand the patient cohort while retaining the original biomechanical characteristics. We used a pair-matched cohort of 94 post-menopausal women (at the time of the CT scan, 47 fractured and 47 not fractured) to create a statistical anatomy atlas through principal component analysis, and up-sampled the atlas in order to obtain over 1000 synthetic patient models. We applied the biomechanical computed tomography pipeline to the resulting virtual cohort and compared its fracture risk distribution with that of the original physical cohort. While the distribution of femoral strength values in the non-fractured sub-group was nearly identical to that of the original physical cohort, that of the fractured sub-group was lower than in the physical cohort. Nonetheless, by using the classification threshold used for the original population, the synthetic population was still divided into two parts of approximatively equal number

Computational dosimetry in MRI in presence of hip, knee or shoulder implants: do we need accurate surgery models?

Objective. To quantify the effects of different levels of realism in the description of the anatomy around hip, knee or shoulder implants when simulating, numerically, radiofrequency and gradient-induced heating in magnetic resonance imaging. This quantification is needed to define how precise the digital human model modified with the implant should be to get realistic dosimetric assessments. Approach. The analysis is based on a large number of numerical simulations where four 'levels of realism' have been adopted in modelling human bodies carrying orthopaedic implants. Main results. Results show that the quantification of the heating due to switched gradient fields does not strictly require a detailed local anatomical description when preparing the digital human model carrying an implant. In this case, a simple overlapping of the implant CAD with the body anatomy is sufficient to provide a quite good and conservative estimation of the heating. On the contrary, the evaluation of the electromagnetic field distribution and heating caused by the radiofrequency field requires an accurate description of the tissues around the prosthesis. Significance. The results of this paper provide hints for selecting the 'level of realism' in the definition of the anatomical models with embedded passive implants when performing simulations that should reproduce, as closely as possible, the in vivo scenarios of patients carrying orthopaedic implants

Intra-operator Repeatability of Manual Segmentations of the Hip Muscles on Clinical Magnetic Resonance Images

The manual segmentation of muscles on magnetic resonance images is the gold standard procedure to reconstruct muscle volumes from medical imaging data and extract critical information for clinical and research purposes. (Semi)automatic methods have been proposed to expedite the otherwise lengthy process. These, however, rely on manual segmentations. Nonetheless, the repeatability of manual muscle volume segmentations performed on clinical MRI data has not been thoroughly assessed. When conducted, volumetric assessments often disregard the hip muscles. Therefore, one trained operator performed repeated manual segmentations (n = 3) of the iliopsoas (n = 34) and gluteus medius (n = 40) muscles on coronal T1-weighted MRI scans, acquired on 1.5 T scanners on a clinical population of patients elected for hip replacement surgery. Reconstructed muscle volumes were divided in sub-volumes and compared in terms of volume variance (normalized variance of volumes - nVV), shape (Jaccard Index-JI) and surface similarity (maximal Hausdorff distance-HD), to quantify intra-operator repeatability. One-way repeated measures ANOVA (or equivalent) tests with Bonferroni corrections for multiple comparisons were conducted to assess statistical significance. For both muscles, repeated manual segmentations were highly similar to one another (nVV: 2-6%, JI > 0.78, HD < 15 mm). However, shape and surface similarity were significantly lower when muscle extremities were included in the segmentations (e.g., iliopsoas: HD -12.06 to 14.42 mm, P < 0.05). Our findings show that the manual segmentation of hip muscle volumes on clinical MRI scans provides repeatable results over time. Nonetheless, extreme care should be taken in the segmentation of muscle extremities

Classification Scheme of Heating Risk during MRI Scans on Patients with Orthopaedic Prostheses

Due to the large variety of possible clinical scenarios, a reliable heating-risk assessment is not straightforward when patients with arthroplasty undergo MRI scans. This paper proposes a simple procedure to estimate the thermal effects induced in patients with hip, knee, or shoulder arthroplasty during MRI exams. The most representative clinical scenarios were identified by a preliminary frequency analysis, based on clinical service databases, collecting MRI exams of 11,658 implant carrier patients. The thermal effects produced by radiofrequency and switching gradient fields were investigated through 588 numerical simulations performed on an ASTM-like phantom, considering four prostheses, two static field values, seven MR sequences, and seven regions of imaging. The risk assessment was inspired by standards for radiofrequency fields and by scientific studies for gradient fields. Three risk tiers were defined for the radiofrequency, in terms of whole-body and local SAR averages, and for GC fields, in terms of temperature elevation. Only 50 out of 588 scenarios require some caution to be managed. Results showed that the whole-body SAR is not a self-reliant safety parameter for patients with metallic implants. The proposed numerical procedure can be easily extended to any other scenario, including the use of detailed anatomical models

Orthopedic implants affect the electric field induced by switching gradients in MRI

PurposeTo investigate whether the risk of peripheral nerve stimulation increases in the presence of bulky metallic prostheses implanted in a patient's body.MethodsA computational tool was used to calculate the electric field (E-field) induced in a realistic human model due to the action of gradient fields. The calculations were performed both on the original version of the anatomical model and on a version modified through "virtual surgery" to incorporate knee, hip, and shoulder prostheses. Five exam positions within a body gradient coil and one position using a head gradient coil were simulated, subjecting the human model to the readout gradient from an EPI sequence. The induced E-field in models with and without prostheses was compared, focusing on the nerves and all other tissues (both including and excluding the bones from the analysis).ResultsIn the nerves, the most pronounced increase in the E-field (+24%) was observed around the knee implant during an abdominal MRI (Y axis readout). When extending the analysis to encompass all tissues (excluding bones), the greatest amplification (+360%) occurred around the knee implant during pelvic MRI (Z axis readout). Notable increases in E-field peaks were also identified around the shoulder and hip implants in multiple scenarios.ConclusionBased on the presented results, further investigations aimed at quantifying the threshold of nerve stimulation in the presence of bulky implants are desirable

HFValid collection: Hip-Fracture validation collection

The HFValid dataset is composed of 101 calibrated CT scans of whole femurs, the corresponding segmentations, and selected anatomical landmarks. The CT scans were collected at Rizzoli Orthopaedic Institute (IOR) from 1999 to 2016 for surgical planning of hip arthroplasty at the contralateral femur. In this version the image calibrations have been updated based a shrinked segmentation of the phantom so as to prevent partial volume effects

A Cationic Contrast Agent in X-ray Imaging of Articular Cartilage: Pre-Clinical Evaluation of Diffusion and Attenuation Properties

The aim of this study was the preliminary assessment of a new cationic contrast agent, the CA4+, via the analysis of spatial distribution in cartilage of ex vivo bovine samples, at micrometer and millimeter scale. Osteochondral plugs (n = 18) extracted from bovine stifle joints (n = 2) were immersed in CA4+ solution up to 26 h. Planar images were acquired at different time points, using a microCT apparatus. The CA4+ distribution in cartilage and saturation time were evaluated. Tibial plates from bovine stifle joints (n = 3) were imaged with CT, before and after 24 h-CA4+ bath immersion, at different concentrations. Afterward, potential CA4+ washout from cartilage was investigated. From microCT acquisitions, the CA4+ distribution differentiated into three distinct layers inside the cartilage, reflecting the spatial distribution of proteoglycans. After 24 h of diffusion, the iodine concentration reached in cartilage was approximately seven times that of the CA4+ bath. The resulting saturation time was 1.9 ± 0.9 h and 2.6 ± 2.9 h for femoral and tibial samples, respectively. Analysis of clinical CT acquisitions confirmed overall contrast enhancement of cartilage after 24 h immersion, observed for each CA4+ concentration. Distinct contrast enhancement was reached in different cartilage regions, depending on tissue's local features. Incomplete but remarkable washout of cartilage was observed. CA4+ significantly improved cartilage visualization and its qualitative analysis

Human talar ontogeny: Insights from morphological and trabecular changes during postnatal growth

The study of the development of human bipedalism can provide a unique perspective on the evolution of morphology and behavior across species. To generate new knowledge of these mechanisms, we analyze changes in both internal and external morphology of the growing human talus in a sample of modern human juveniles using an innovative approach. The sample consists of high‐resolution microCT scans of 70 modern juvenile tali, aged between 8 postnatal weeks and 10 years old, from a broad chronological range from Middle/Late Neolithic, that is, between 4800 and 4500 BCE, to the 20th century. We applied geometric morphometric and whole‐bone trabecular analysis (bone volume fraction, degree of anisotropy, trabecular number, thickness, and spacing) to all specimens to identify changes in the external and internal morphology during growth. Morphometric maps were also generated. During the first year of life, the talus has an immature and globular shape, with a dense, compact, and rather isotropic trabecular architecture, with numerous trabeculae packed closely together. This pattern changes while children acquire a more mature gait, and the talus tends to have a lower bone volume fraction, a higher anisotropy, and a more mature shape. The changes in talar internal and external morphologies reflect the different loading patterns experienced during growth, gradually shifting from an “unspecialized” morphology to a more complex one, following the development of bipedal gait. Our research shows that talar plasticity, even though genetically driven, may show mechanical influences and contribute to tracking the main locomotor milestones

Life history and ancestry of the late Upper Palaeolithic infant from Grotta delle Mura, Italy

The biological aspects of infancy within late Upper Palaeolithic populations and the role of southern refugia at the end of the Last Glacial Maximum are not yet fully understood. This study presents a multidisciplinary, high temporal resolution investigation of an Upper Palaeolithic infant from Grotta delle Mura (Apulia, southern Italy) combining palaeogenomics, dental palaeohistology, spatially-resolved geochemical analyses, direct radiocarbon dating, and traditional anthropological studies. The skeletal remains of the infant – Le Mura 1 – were directly dated to 17,320-16,910 cal BP. The results portray a biological history of the infant’s development, early life, health and death (estimated at ~72 weeks). They identify, several phenotypic traits and a potential congenital disease in the infant, the mother’s low mobility during gestation, and a high level of endogamy. Furthermore, the genomic data indicates an early spread of the Villabruna-like components along the Italian peninsula, confirming a population turnover around the time of the Last Glacial Maximum, and highlighting a general reduction in genetic variability from northern to southern Italy. Overall, Le Mura 1 contributes to our better understanding of the early stages of life and the genetic puzzle in the Italian peninsula at the end of the Last Glacial Maximum. © The Author(s) 2024

An infant burial from Arma Veirana in northwestern Italy provides insights into funerary practices and female personhood in early Mesolithic Europe

The evolution and development of human mortuary behaviors is of enormous cultural significance. Here we report a richly-decorated young infant burial (AVH-1) from Arma Veirana (Liguria, northwestern Italy) that is directly dated to 10,211–9910 cal BP (95.4% probability), placing it within the early Holocene and therefore attributable to the early Mesolithic, a cultural period from which well-documented burials are exceedingly rare. Virtual dental histology, proteomics, and aDNA indicate that the infant was a 40–50 days old female. Associated artifacts indicate significant material and emotional investment in the child’s interment. The detailed biological profile of AVH-1 establishes the child as the earliest European near-neonate documented to be female. The Arma Veirana burial thus provides insight into sex/gender-based social status, funerary treatment, and the attribution of personhood to the youngest individuals among prehistoric hunter-gatherer groups and adds substantially to the scant data on mortuary practices from an important period in prehistory shortly following the end of the last Ice Age