Impact of skull sutures, spongiform bone distribution, and aging skull conductivities on the EEG forward and inverse problems

Source imaging is a principal objective for electroencephalography (EEG), the solutions of which require forward problem (FP) computations characterising the electric potential distribution on the scalp due to known sources. Additionally, the EEG-FP is dependent upon realistic, anatomically correct volume conductors and accurate tissue conductivities, where the skull is particularly important. Skull conductivity, however, deviates according to bone composition and the presence of adult sutures. The presented study therefore analyses the effect the presence of adult sutures and differing bone composition have on the EEG-FP and inverse problem (IP) solutions. Utilising a well-established head atlas, detailed head models were generated including compact and spongiform bone and adult sutures. The true skull conductivity was considered as inhomogeneous according to spongiform bone proportion and sutures. The EEG-FP and EEG-IP were solved and compared to results employing homogeneous skull models, with varying conductivities and omitting sutures, as well as using a hypothesised aging skull conductivity model. Significant localised FP errors, with relative error up to 85%, were revealed, particularly evident along suture lines and directly related to the proportion of spongiform bone. This remained evident at various ages. Similar EEG-IP inaccuracies were found, with the largest (maximum 4.14 cm) across suture lines. It is concluded that modelling the skull as an inhomogeneous layer that varies according to spongiform bone proportion and includes differing suture conductivity is imperative for accurate EEG-FP and source localisation calculations. Their omission can result in significant errors, relevant for EEG research and clinical diagnosis.

EXPRESS: Infrared Spectroscopy-Determined Bone Compositional Changes Associated with Anti-Resorptive Treatment of the Oim/Oim Mouse Model of Osteogenesis Imperfecta

Applications of vibrational spectroscopy to assess bone disease and therapeutic interventions are continually advancing, with tissue mineral and protein composition frequently investigated. Here, we used two spectroscopic approaches for determining bone composition in a mouse model of the brittle bone disease osteogenesis imperfecta (OIM) with and without antiresorptive agent treatment (alendronate (ALN) and RANK-Fc). Near infrared (NIR) spectral analysis via a fiber optic probe and Fourier transform infrared spectroscopy using attenuated total reflection (FTIR-ATR) mode were applied to investigate bone composition, including water, mineral and protein content. Spectral parameters revealed differences among the control wildtype (WT) and OIM groups. NIR spectral analysis of protein and water showed that OIM mouse humerii had ~ 50% lower protein and ~ 50% higher overall water content compared to WT bone. Moreover, some OIM treated groups showed a reduction in bone water compared to OIM controls, approximating values observed in WT bone. Differences in bone quality based on increased mineral content and reduced carbonate content were also found between some groups of treated OIM and WT bone, but crystallinity did not differ among all groups. The spectroscopically-determined parameters were evaluated for correlations with gold-standard mechanical testing values to gain insight into how composition influenced bone strength. As expected, bone mechanical strength parameters were consistently up to three-fold greater in WT mice compared to OIM groups, except for stiffness in the ALN-treated OIM groups. Further, bone stiffness, maximum load and post-yield displacement showed the strongest correlations with NIR-determined protein content (positive correlations) and bound-water content (negative correlations). These results demonstrate that in this study, NIR spectral parameters were more sensitive to bone composition differences than ATR parameters, highlighting the potential of this nondestructive approach for screening of bone diseases and therapeutic efficacy in pre-clinical models.

Recombinant IGF-1 Induces Sex-Specific Changes in Bone Composition and Remodeling in Adult Mice with Pappa2 Deficiency

Deficiency of pregnancy-associated plasma protein-A2 (PAPP-A2), an IGF-1 availability regulator, causes postnatal growth failure and dysregulation of bone size and density. The present study aimed to determine the effects of recombinant murine IGF-1 (rmIGF-1) on bone composition and remodeling in constitutive Pappa2 knock-out (ko/ko) mice. To address this challenge, X-ray diffraction (XRD), attenuated total reflection-fourier transform infra-red (ATR-FTIR) spectroscopy and gene expression analysis of members of the IGF-1 system and bone resorption/formation were performed. Pappa2ko/ko mice (both sexes) had reduced body and bone length. Male Pappa2ko/ko mice had specific alterations in bone composition (mineral-to-matrix ratio, carbonate substitution and mineral crystallinity), but not in bone remodeling. In contrast, decreases in collagen maturity and increases in Igfbp3, osteopontin (resorption) and osteocalcin (formation) characterized the bone of Pappa2ko/ko females. A single rmIGF-1 administration (0.3 mg/kg) induced short-term changes in bone composition in Pappa2ko/ko mice (both sexes). rmIGF-1 treatment in Pappa2ko/ko females also increased collagen maturity, and Igfbp3, Igfbp5, Col1a1 and osteopontin expression. In summary, acute IGF-1 treatment modifies bone composition and local IGF-1 response to bone remodeling in mice with Pappa2 deficiency. These effects depend on sex and provide important insights into potential IGF-1 therapy for growth failure and bone loss and repair.

Title Changes in the Mineral Composition of Rat Femoral Bones Induced by Implantation of LNCaP Prostate Cancer Cells and Dietary Supplementation

Prostate cancer (PCa) is the second most frequent cancer in men and the fifth most common cause of death worldwide, with an estimated 378,553 deaths in 2020. Prostate cancer shows a strong tendency to form metastatic foci in the bones. A number of interactions between cancer cells attacking bones and cells of the bone matrix lead to destruction of the bone and growth of the tumour. The last few decades have seen increased interest in the precise role of minerals in human health and disease. Tumour cells accumulate various minerals that promote their intensive growth. Bone, as a storehouse of elements, can be a valuable source of them for the growing tumour. There are also reports suggesting that the presence of some tumours, e.g., of the breast, can adversely affect bone structure even in the absence of metastasis to this organ. This paper presents the effect of chronic dietary intake of calcium, iron and zinc, administered in doses corresponding maximally to twice their level in a standard diet, on homeostasis of selected elements (Ca, K, Zn, Fe, Cu, Sr, Ni, Co, Mn and Mo) in the femoral bones of healthy rats and rats with implanted cancer cells of the LNCaP line. The experiment was conducted over 90 days. After the adaptation period, the animals were randomly divided into four dietary groups: standard diet and supplementation with Zn, Fe and Ca. Every dietary group was divided into experimental group (with implanted cancer cells) and control group (without implanted cancer cells). The cancer cells (LnCaP) were implanted intraperitoneally in the amount 1 × 106 to the rats at day 90 of their lifetime. Bone tissue was dried and treated with microwave-assisted mineral digestation. Total elemental content was quantified by ICP-MS. Student’s t-test and Anova or Kruskal–Wallis tests were applied in order to compare treatment and dietary groups. In the case of most of the diets, especially the standard diet, the femoral bones of rats with implanted LNCaP cells showed a clear downward trend in the content of the elements tested, which may be indicative of slow osteolysis taking place in the bone tissue. In the group of rats receiving the standard diet, there were significant reductions in the content of Mo (by 83%), Ca (25%), Co (22%), Mn (13%), K (13%) and Sr (9%) in the bone tissue of rats with implanted LNCaP cells in comparison with the control group receiving the same diet but without LNCaP implantation. Supplementation of the rat diet with calcium, zinc and iron decreased the frequency of these changes relative to the standard diet, which may indicate that the diet had an inhibitory effect on bone resorption in conditions of LNCaP implantation. The principal component analysis (PCA) score plot confirms the pronounced effect of implanted LNCaP cells and the standard diet on bone composition. At the same time, supplementation with calcium, zinc and iron seems to improve bone composition. The microelements that most often underwent quantitative changes in the experimental conditions were cobalt, manganese and molybdenum.