Pathological Heart Rate Regulation in Apparently Healthy Individuals.

Cardiovascular diseases are the leading cause of morbidity and mortality in adults worldwide. There is one common pathophysiological aspect present in all cardiovascular diseases-dysfunctional heart rhythm regulation. Taking this aspect into consideration for cardiovascular risk predictions opens important research perspectives, allowing for the development of preventive treatment techniques. The aim of this study was to find out whether certain pathologically appearing signs in the heart rate variability (HRV) of an apparently healthy person, even with high HRV, can be defined as biomarkers for a disturbed cardiac regulation and whether this can be treated preventively by a drug-free method. This multi-phase study included 218 healthy subjects of either sex, who consecutively visited the physician at Gesundheit clinic because of arterial hypertension, depression, headache, psycho-emotional stress, extreme weakness, disturbed night sleep, heart palpitations, or chest pain. In study phase A, baseline measurement to identify individuals with cardiovascular risks was done. Therefore, standard HRV, as well as the new cardiorhythmogram (CRG) method, were applied to all subjects. The new CRG analysis used here is based on the recently introduced LF drops and HF counter-regulation. Regarding the mechanisms of why these appear in a steady-state cardiorhythmmogram, they represent non-linear event-based dynamical HRV biomarkers. The next phase of the study, phase B, tested whether the pathologically appearing signs identified via CRG in phase A could be clinically influenced by drug-free treatment. In order to validate the new CRG method, it was supported by non-linear HRV analysis in both phase A and in phase B. Out of 218 subjects, the pathologically appearing signs could be detected in 130 cases (60%), p < 0.01, by the new CRG method, and by the standard HRV analysis in 40 cases (18%), p < 0.05. Thus, the CRG method was able to detect 42% more cases with pathologically appearing cardiac regulation. In addition, the comparative CRG analysis before and after treatment showed that the pathologically appearing signs could be clinically influenced without the use of medication. After treatment, the risk group decreased eight-fold-from 130 people to 16 (p < 0.01). Therefore, progression of the detected pathological signs to structural cardiac pathology or arrhythmia could be prevented in most of the cases. However, in the remaining risk group of 16 apparently healthy subjects, 8 people died due to all-cause mortality. In contrast, no other subject in this study has died so far. The non-linear parameter which is able to quantify the changes in CRGs before versus after treatment is FWRENYI4 (symbolic dynamic feature); it decreased from 2.85 to 2.53 (p < 0.001). In summary, signs of pathological cardiac regulation can be identified by the CRG analysis of apparently healthy subjects in the early stages of development of cardiac pathology. Thus, our method offers a sensitive biomarker for cardiovascular risks. The latter can be influenced by non-drug treatments (acupuncture) to stop the progression into structural cardiac pathologies or arrhythmias in most but not all of the patients. Therefore, this could be a real and easy-to-use supplemental method, contributing to primary prevention in cardiology.

Glycocalyx Sensing with a Mathematical Model of Acoustic Shear Wave Biosensor.

The article deals with an idea of exploiting an acoustic shear wave biosensor for investigating the glycocalyx, a polysaccharide polymer molecule layer on the endothelium of blood vessels that, according to recent studies, plays an important role in protecting against diseases. To test this idea, a mathematical model of an acoustic shear wave sensor and corresponding software developed earlier for proteomic applications are used. In this case, the glycocalyx is treated as a layer homogenized over the thin polymer "villi". Its material characteristics depend on the density, thickness, and length of the villi and on the viscous properties of the surrounding liquid (blood plasma). It is proved that the model used has a good sensitivity to the above parameters of the villi and blood plasma. Numerical experiments performed using real data collected retrospectively from premature infants show that the use of acoustic shear wave sensors may be a promising approach to investigate properties of glycocalyx-like structures and their role in prematurity.

Modeling of the cerebral blood circulation in a capillary network accounting for the influence of the endothelial surface layer.

BACKGROUND AND OBJECTIVE: The paper describes a mathematical model of blood flow in capillaries with accounting for the endothelial surface layer (ESL). METHOD: The influence of ESL is modeled by a boundary layer with zero flow velocity. Finite element modeling and an analytical approach based on the homogenization of the core region of blood flow occupied by erythrocytes are developed to describe the resistance of a capillary. The reliability of the results obtained is verified for different values of the discharge hematocrit and vessel diameter using known in vivo data. RESULTS: The proposed approach is applied to the numerical simulation of blood circulation in a capillary network of the germinal matrix of infants born at 25 gestational weeks. The influence of the hematocrit level and effective thickness of ESL on the resistance of the capillary network of the germinal matrix of preterm infants is studied. It was found that a decrease in the effective thickness of ESL in the capillary network (and/or a decrease in the hematocrit) leads to reducing the resistance of the capillary network. CONCLUSION: A decrease in the effective thickness of ESL in the capillary network leads to an increase in the pressure drop in arterioles, which may be considered as an additional risk factor for hemorrhages in fragile blood vessels within the germinal matrix.

Accounting for arterial and capillary blood gases for calculation of cerebral blood flow in preterm infants.

One of the most feared neurological complications of premature birth is intraventricular hemorrhage, frequently triggered by fluctuations in cerebral blood flow (CBF). Although several techniques for CBF measurement have been developed, they are not part of clinical routine in neonatal intensive care. A promising tool for monitoring of CBF is its numerical assessment using standard clinical parameters such as mean arterial pressure, carbon dioxide partial pressure (pCO2) and oxygen partial pressure (pO2). A standard blood gas analysis is performed on arterial blood. In neonates, capillary blood is widely used for analysis of blood gas parameters. The purpose of this study was the assessment of differences between arterial and capillary analysis of blood gases and adjustment of the mathematical model for CBF calculation to capillary values. The statistical analysis of pCO2 and pO2 values collected from 254 preterm infants with a gestational age of 23-30 weeks revealed no significant differences between arterial and capillary pCO2 and significantly lower values for capillary pO2. The estimated mean differences between arterial and capillary pO2 of 15.15 mmHg (2.02 kPa) resulted in a significantly higher CBF calculated for capillary pO2 compared to CBF calculated for arterial pO2. Two methods for correction of capillary pO2 were proposed and compared, one based on the mean difference and another one based on a regression model. CONCLUSION: Capillary blood gas analysis with correction for pO2 as proposed in the present work is an acceptable alternative to arterial sampling for the assessment of CBF. WHAT IS KNOWN: • Arterial blood analysis is the gold standard in clinical practice. However, capillary blood is widely used for estimating blood gas parameters. • There is no significant difference between the arterial and capillary pCO2 values, but the capillary pO2 differs significantly from the arterial one. WHAT IS NEW: • The lower capillary pO2 values yield significantly higher values of calculated CBF compared to CBF computed from arterial pO2 measurements. • Two correction methods for the adjustment of capillary pO2 to arterial pO2 that made the difference in the calculated CBF insignificant have been proposed.

A randomized trial assessing the efficacy, immunogenicity, and safety of vaccination with live attenuated varicella zoster virus-containing vaccines: ten-year follow-up in Russian children.

In Russia, a universal varicella vaccination (UVV) program has not been implemented, and varicella vaccination coverage is low. We assessed the efficacy, antibody persistence, and safety of one- and two-dose varicella vaccination schedules in Russian children with a ten-year follow-up period, as part of an international phase IIIB, observer-blind, randomized, controlled trial (NCT00226499). Children aged 12-22 months were randomized (3:3:1) to receive two doses of tetravalent measles-mumps-rubella-varicella vaccine (V2 group), one dose trivalent measles-mumps-rubella (MMR) vaccine and one dose of varicella vaccine (V1 group), or two doses of MMR vaccine (V0 [control] group), 42 days apart. Main study outcomes were: vaccine efficacy (VE) against confirmed varicella cases, anti-varicella zoster virus (VZV) seropositivity rates and geometric mean concentrations, and reporting of (serious) adverse events ([S]AEs). The total vaccinated cohort in Russia comprised 1000 children; 900 were followed up until study end (year [Y] 10). VE estimates against confirmed varicella (Y10) were 92.4% in the V2 group and 74.7% in the V1 group. Anti-VZV seropositivity rates remained ≥99.4% in the V2 group and ≥89.7% in the V1 group from day 42 post-vaccination 2 until Y10. Occurrence of (un)solicited AEs and SAEs was similar across groups and confirmed the safety profile of the vaccines. No vaccination-related SAEs or deaths were reported. These results are consistent with the global trial results, i.e., the highest VE estimates observed following the two-dose schedule compared to the one-dose schedule. These data may inform decision-making related to potential implementation of a UVV program.

What is the context?Varicella is a common childhood disease caused by the highly contagious varicella zoster virus.Varicella vaccines have been used for more than three decades.A large clinical trial conducted in ten countries assessed the efficacy and safety of one dose of monovalent varicella vaccine or two doses of combined varicella vaccine (MMRV). The enrolled children were also followed up for a ten-year period to evaluate the persistence of the immune response and the long-term efficacy of the vaccine.What is new?Here, we present the long-term efficacy, immunogenicity, and safety results in the cohort of children enrolled in Russia, as part of the global ten-year follow-up study. We found that:The monovalent and combined vaccines reduced the number of varicella cases.The MMRV two-dose regimen displayed higher efficacy in preventing varicella of all severities compared to the one-dose regimen.The immune response conferred by the vaccine persisted up to ten years post-vaccination.No vaccination-related deaths occurred, and no safety concerns were raised.What is the impact?Vaccination against varicella resulted in long-term protective efficacy and antibody persistence over ten years post-vaccination in Russian children.Although one-dose varicella vaccination was effective at protecting against varicella, a two-dose schedule provided a more complete protection. This could inform health policy decisions regarding the implementation of varicella vaccination in routine immunization program in Russia.

Mathematical modeling of the hematocrit influence on cerebral blood flow in preterm infants.

Premature birth is one of the most important factors increasing the risk for brain damage in newborns. Development of an intraventricular hemorrhage in the immature brain is often triggered by fluctuations of cerebral blood flow (CBF). Therefore, monitoring of CBF becomes an important task in clinical care of preterm infants. Mathematical modeling of CBF can be a complementary tool in addition to diagnostic tools in clinical practice and research. The purpose of the present study is an enhancement of the previously developed mathematical model for CBF by a detailed description of apparent blood viscosity and vessel resistance, accounting for inhomogeneous hematocrit distribution in multiscale blood vessel architectures. The enhanced model is applied to our medical database retrospectively collected from the 254 preterm infants with a gestational age of 23-30 weeks. It is shown that by including clinically measured hematocrit in the mathematical model, apparent blood viscosity, vessel resistance, and hence the CBF are strongly affected. Thus, a statistically significant decrease in hematocrit values observed in the group of preterm infants with intraventricular hemorrhage resulted in a statistically significant increase in calculated CBF values.

Assessing haemorrhage-critical values of cerebral blood flow by modelling biomechanical stresses on capillaries in the immature brain.

The development of intraventricular haemorrhages (IVH) in preterm newborns is triggered by a disruption of the vessels responsible for cerebral microcirculation. Analysis of the stresses exerted on vessel walls enables the identification of the critical values of cerebral blood flow (CBF) associated with the development of IVH in preterm infants. The purpose of the present study is the estimation of these critical CBF values using the biomechanical stresses obtained by the finite element modelling of immature brain capillaries. The properties of the endothelial cells and basement membranes employed were selected on the basis of published nanoindentation measurements using atomic force microscopes. The forces acting on individual capillaries were derived with a mathematical model that accounts for the peculiarities of microvascularity in the immature brain. Calculations were based on clinical measurements obtained from 254 preterm infants with the gestational age ranging from 23 to 30 weeks, with and without diagnosis of IVH. No distinction between the affected and control groups with the gestational age of 23 to 26 weeks was possible. For infants with the gestational age of 27 to 30 weeks, the CBF value of 17.03 ml/100 g/min was determined as the critical upper value, above which the likelihood of IVH increases.

Nonstationary Model of Oxygen Transport in Brain Tissue.

The paper addresses the mathematical study of a nonstationary continuum model describing oxygen propagation in cerebral substance. The model allows to estimate the rate of oxygen saturation and stabilization of oxygen concentration in relatively large parts of cerebral tissue. A theoretical and numerical analysis of the model is performed. The unique solvability of the underlying initial-boundary value problem for a system of coupled nonlinear parabolic equations is proved. In the numerical experiment, the tissue oxygen saturation after hypoxia is analyzed for the case when a sufficient amount of oxygen begins to flow into the capillary network. A fast stabilization of the tissue oxygen concentration is demonstrated. The reliability of the results of the numerical simulation is discussed.

Assessing key clinical parameters before and after intraventricular hemorrhage in very preterm infants.

Intraventricular cerebral hemorrhage (IVH) is one of the most severe complications of premature birth, potentially leading to lifelong disability. The purpose of this paper is the assessment of the evolution of three of the most relevant parameters, before and after IVH: mean arterial pressure (MAP), arterial carbon dioxide pressure (pCO2), and cerebral blood flow (CBF). Clinical records of 254 preterm infants with a gestational age of 23-30 weeks, with and without a diagnosis of IVH, were reviewed for MAP and arterial pCO2 in the period up to 7 days before and 3 days after IVH or during the first 10 days of life in cases without IVH.Conclusion: A statistically significant increase in pCO2 and decrease in MAP in patients with IVH compared with those without were detected. Both the mean values and the mean absolute deviations of CBF were computed in this study, and the latter was significantly higher than in control group. High deviations of CBF, as well as hypercapnia and hypotension, are likely to contribute to the rupture of cerebral blood vessels in preterm infants, and consequently, to the development of IVH.What is Known:• The origin of IVH is multifactorial, but mean arterial pressure, carbon dioxide partial pressure, and cerebral blood flow are recognized as the most important parameters.• In premature infants, the autoregulation mechanisms are still underdeveloped and cannot compensate for cerebral blood flow fluctuations.What is New:• The numerical simulation of CBF is shown to be a promising approach that may be useful in the care of preterm infants.• The mean values of CBF before and after IVH in the affected group were similar to those in the control group, but the mean absolute deviations of CBF in the affected group before and after IVH were significantly higher than that in the control group.

Machine learning models for identifying preterm infants at risk of cerebral hemorrhage.

Intracerebral hemorrhage in preterm infants is a major cause of brain damage and cerebral palsy. The pathogenesis of cerebral hemorrhage is multifactorial. Among the risk factors are impaired cerebral autoregulation, infections, and coagulation disorders. Machine learning methods allow the identification of combinations of clinical factors to best differentiate preterm infants with intra-cerebral bleeding and the development of models for patients at risk of cerebral hemorrhage. In the current study, a Random Forest approach is applied to develop such models for extremely and very preterm infants (23-30 weeks gestation) based on data collected from a cohort of 229 individuals. The constructed models exhibit good prediction accuracy and might be used in clinical practice to reduce the risk of cerebral bleeding in prematurity.

Accounting for Tube Hematocrit in Modeling of Blood Flow in Cerebral Capillary Networks.

The aim of this paper consists in the derivation of an analytic formula for the hydraulic resistance of capillaries, taking into account the tube hematocrit level. The consistency of the derived formula is verified using Finite Element simulations. Such an effective formula allows for assigning resistances, depending on the hematocrit level, to the edges of networks modeling biological capillary systems, which extends our earlier models of blood flow through large capillary networks. Numerical simulations conducted for large capillary networks with random topologies demonstrate the importance of accounting for the hematocrit level for obtaining consistent results.

Extended model of impaired cerebral autoregulation in preterm infants: Heuristic feedback control.

Cerebral autoregulation is the ability to keep almost constant cerebral blood flow (CBF) for some range of changing the mean arterial pressure (MAP). In preterm infants, this range is usually very small, even absent, and a passive (linear) dependence of CBF on MAP is observed. Also, variations of the partial CO2 pressure and intracranial/venous pressure result in fluctuations of CBF. The absence of cerebral autoregulation may be a cause of intracranial hemorrhages due to instability of cerebral blood vessels, especially in the so-called germinal matrix which exists in a developing brain from 22 to 32 weeks of gestation. In the current paper, a mathematical model of impaired cerebral autoregulation is extended compared with previous works of the authors, and a heuristic feedback control that is able to keep deviations from a nominal CBF within a reasonable range is proposed. Viability theory is used to prove that this control can successfully work against a wide range of disturbances.

Postnatal Paraclinical Parameters Associated to Occurrence of Intracerebral Hemorrhage in Preterm Infants.

Intracerebral hemorrhage (ICH) is the most frequent complication in postnatal development of preterm infants. The purpose of the present work is the statistical evaluation of seven standard paraclinical parameters and their association to the development of ICH. Clinical records of 265 preterm infants with gestational age (GA) 23 to 30 weeks were analyzed. According to ICH status, patients were divided into control (without ICH) and affected (with ICH) groups. Mean values of paraclinical parameters at each week of gestation were compared. Different ICH grades, periods before and after ICH were considered separately. Lower hematocrit, SaO2, and pH were statistically significant for preterm infants with 23 to 30 weeks GA and diagnosis of ICH relative to infants without ICH. Additionally, for preterm infants with 27 to 30 weeks GA, higher C-reactive protein, as well as lower values of thrombocytes were associated with the occurrence of ICH. Preterm infants with 23 to 26 weeks GA showed C-reactive protein values similar to those in the group without ICH and lower levels of thrombocytes after bleeding. Significant differences in paraclinical parameters between preterm infants with and without ICH may constitute useful indicators for closer clinical observation of preterm infants at risk of ICH.

Efficacy of a Novel Intranasal Formulation of Azelastine Hydrochloride and Fluticasone Propionate, Delivered in a Single Spray, for the Treatment of Seasonal Allergic Rhinitis: Results from Russia.

BACKGROUND: The novel intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP) in a single spray (MP-AzeFlu) was compared with a first-line intranasal antihistamine spray (AZE) in Russian seasonal allergic rhinitis (SAR) patients. METHODS: Moderate-to-severe SAR/rhinoconjunctivitis patients (n = 149; aged 18-65 years) were randomized to receive MP-AzeFlu (137/50 µg AZE/FP per spray) or AZE (137 µg/spray), both as 1 spray/nostril twice daily, in a multicenter, open-label, 14-day, parallel-group trial. The primary outcome was change from baseline in morning and evening reflective total nasal symptom score (rTNSS). Secondary end points included: change from baseline in reflective total ocular symptom score (rTOSS), reflective total of 7 symptom scores (rT7SS), 28-item Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) overall score, and EuroQol-5D (EQ-5D) questionnaire score. RESULTS: When compared with AZE-treated patients, those treated with MP-AzeFlu experienced significantly greater reductions in rTNSS (difference: -2.47; 95% confidence interval [CI] -3.65 to -1.30; p < 0.001), rTOSS (difference: -1.62; 95% CI -2.32 to -0.92; p < 0.001), and rT7SS (difference: -4.34; 95% CI -5.98 to -2.70; p < 0.001). Superior relief observed on day 2 with MP-AzeFlu versus AZE was sustained throughout the study. MP-AzeFlu-treated patients experienced a greater improvement in QoL than AZE-treated patients as measured by overall RQLQ score (mean ± SD 2.91 ± 1.08 vs. 2.05 ± 1.15) and EQ-5D score (mean ± SD 87.4 ± 10.3 vs. 83.0 ± 12.8). MP-AzeFlu was well tolerated. CONCLUSIONS: MP-AzeFlu was superior to AZE in reducing moderate-to-severe SAR symptoms, providing earlier and more complete symptom relief.

Modeling Cerebral Blood Flow Dependence on Carbon Dioxide and Mean Arterial Blood Pressure in the Immature Brain With Accounting for the Germinal Matrix.

Intraventricular hemorrhage (IVH) is one of the most critical complications in the development of preterm infants. The likelihood of IVH is strongly associated with disturbances in cerebral blood flow (CBF) and with microvascular fragility in the germinal matrix (GM). The CBF value and its reactivity to changes in arterial carbon dioxide pressure (pCO 2 ) and mean arterial blood pressure (MABP) are relevant indicators in the clinical assessment of preterm infants. The objective of the present study is mathematical modeling of the influence of pCO 2 and MABP on CBF in immature brain, based on clinical data collected from 265 preterm infants with 23-30 gestational weeks. The model was adapted to the peculiarities of immature brain by taking into account the morphological characteristics of the GM capillary network and vascular reactivity, according to gestational and postnatal age. An analysis of model based values of CBF and its reactivity to changes in MABP and pCO 2 was performed separately for each gestational week and for the first two days of life both for preterm infants with and without IVH. The developed model for the estimation of CBF was validated against equivalent experimental measurements taken from the literature. A good agreement between the estimated values of CBF, as well as its reaction on changes in MABP and pCO 2 and the equivalent values obtained in experimental studies was shown.

Direct modeling of blood flow through the vascular network of the germinal matrix.

A premature birth, before completion of the 32nd pregnancy week, increases the risk of cerebral hemorrhage. The cause of brain bleeding is very often the germinal matrix of the immature brain. The germinal matrix consists of richly vascularized neuroepithelial cells and is located over the lower part of the head of the caudate nucleus. By 32-36 gestation weeks, the germinal matrix essentially disappears so that its hemorrhage is a disease of premature infants. The aim of this paper consists in developing a model of the brain vascular network and computing the pressure distribution in the germinal matrix, particularly near arterioles and venules, where cerebral hemorrhage may occur. Capillary networks consisting of several millions of vessels are directly simulated in the present study.

Application of the PAMONO-Sensor for Quantification of Microvesicles and Determination of Nano-Particle Size Distribution.

The PAMONO-sensor (plasmon assisted microscopy of nano-objects) demonstrated an ability to detect and quantify individual viruses and virus-like particles. However, another group of biological vesicles-microvesicles (100-1000 nm)-also attracts growing interest as biomarkers of different pathologies and needs development of novel techniques for characterization. This work shows the applicability of a PAMONO-sensor for selective detection of microvesicles in aquatic samples. The sensor permits comparison of relative concentrations of microvesicles between samples. We also study a possibility of repeated use of a sensor chip after elution of the microvesicle capturing layer. Moreover, we improve the detection features of the PAMONO-sensor. The detection process utilizes novel machine learning techniques on the sensor image data to estimate particle size distributions of nano-particles in polydisperse samples. Altogether, our findings expand analytical features and the application field of the PAMONO-sensor. They can also serve for a maturation of diagnostic tools based on the PAMONO-sensor platform.

Prediction of bone strength by µCT and MDCT-based finite-element-models: how much spatial resolution is needed?

OBJECTIVES: Finite-element-models (FEM) are a promising technology to predict bone strength and fracture risk. Usually, the highest spatial resolution technically available is used, but this requires excessive computation time and memory in numerical simulations of large volumes. Thus, FEM were compared at decreasing resolutions with respect to local strain distribution and prediction of failure load to (1) validate MDCT-based FEM and to (2) optimize spatial resolution to save computation time. MATERIALS AND METHODS: 20 cylindrical trabecular bone specimens (diameter 12 mm, length 15-20mm) were harvested from elderly formalin-fixed human thoracic spines. All specimens were examined by micro-CT (isotropic resolution 30 µm) and whole-body multi-row-detector computed tomography (MDCT, 250 µm × 250 µm × 500 µm). The resolution of all datasets was lowered in eight steps to ~ 2,000 µm × 2000 µm × 500 µm and FEM were calculated at all resolutions. Failure load was determined by biomechanical testing. Probability density functions of local micro-strains were compared in all datasets and correlations between FEM-based and biomechanically measured failure loads were determined. RESULTS: The distribution of local micro-strains was similar for micro-CT and MDCT at comparable resolutions and showed a shift toward higher average values with decreasing resolution, corresponding to the increasing apparent trabecular thickness. Small micro-strains (εeff<0.005) could be calculated down to 250 µm × 250 µm × 500 µm. Biomechanically determined failure load showed significant correlations with all FEM, up to r=0.85 and did not significantly change with lower resolution but decreased with high thresholds, due to loss of trabecular connectivity. CONCLUSION: When choosing connectivity-preserving thresholds, both micro-CT- and MDCT-based finite-element-models well predicted failure load and still accurately revealed the distribution of local micro-strains in spatial resolutions, available in vivo (250 µm × 250 µm × 500 µm), that thus seemed to be the optimal compromise between high accuracy and low computation time.

LMNA-related dilated cardiomyopathy.

A case of idiopathic dilated cardiomyopathy (DCM) that is likely to be associated with LMNA mutation Arg190Pro in a heterozygote is described. The features of DCM in the patient were conduction disorders, cardiac arrhythmias, progressive heart failure and minor musculoskeletal disturbances. We consider that the mutation Arg190Pro contributes to the formation of a weak nuclear lamina and diminishes muscle mechanical stability which is critical during cardiac contraction. The case report illustrates in detail the phenotypic manifestations of the novel LMNA mutation and difficulties in management related to it.

Scaling relations between trabecular bone volume fraction and microstructure at different skeletal sites.

In this study, we investigated the scaling relations between trabecular bone volume fraction (BV/TV) and parameters of the trabecular microstructure at different skeletal sites. Cylindrical bone samples with a diameter of 8mm were harvested from different skeletal sites of 154 human donors in vitro: 87 from the distal radius, 59/69 from the thoracic/lumbar spine, 51 from the femoral neck, and 83 from the greater trochanter. µCT images were obtained with an isotropic spatial resolution of 26µm. BV/TV and trabecular microstructure parameters (TbN, TbTh, TbSp, scaling indices (< > and σ of α and αz), and Minkowski Functionals (Surface, Curvature, Euler)) were computed for each sample. The regression coefficient ß was determined for each skeletal site as the slope of a linear fit in the double-logarithmic representations of the correlations of BV/TV versus the respective microstructure parameter. Statistically significant correlation coefficients ranging from r=0.36 to r=0.97 were observed for BV/TV versus microstructure parameters, except for Curvature and Euler. The regression coefficients ß were 0.19 to 0.23 (TbN), 0.21 to 0.30 (TbTh), -0.28 to -0.24 (TbSp), 0.58 to 0.71 (Surface) and 0.12 to 0.16 (<α>), 0.07 to 0.11 (<αz>), -0.44 to -0.30 (σ(α)), and -0.39 to -0.14 (σ(αz)) at the different skeletal sites. The 95% confidence intervals of ß overlapped for almost all microstructure parameters at the different skeletal sites. The scaling relations were independent of vertebral fracture status and similar for subjects aged 60-69, 70-79, and >79years. In conclusion, the bone volume fraction-microstructure scaling relations showed a rather universal character.