The relationship between bone strain index, bone mass, microarchitecture and mechanical behavior in human vertebrae: an ex vivo study.

The aim of this study was to determine whether the Bone Strain Index (BSI), a recent DXA-based bone index, is related to bone mechanical behavior, microarchitecture and finally, to determine whether BSI improves the prediction of bone strength and the predictive role of BMD in clinical practice. PURPOSE: Bone Strain Index (BSI) is a new DXA-based bone index that represents the finite element analysis of the bone deformation under load. The current study aimed to assess whether the BSI is associated with 3D microarchitecture and the mechanical behavior of human lumbar vertebrae. METHODS: Lumbar vertebrae (L3) were harvested fresh from 31 human donors. The anteroposterior BMC (g) and aBMD (g/cm2) of the vertebral body were measured using DXA, and then the BSI was automatically derived. The trabecular bone volume (Tb.BV/TV), trabecular thickness (Tb.Th), degree of anisotropy (DA), and structure model index (SMI) were measured using µCT with a 35-µm isotropic voxel size. Quasi-static uniaxial compressive testing was performed on L3 vertebral bodies under displacement control to assess failure load and stiffness. RESULTS: The BSI was significantly correlated with failure load and stiffness (r = -0.60 and -0.59; p < 0.0001), aBMD and BMC (r = -0.93 and -0.86; p < 0.0001); Tb.BV/TV and SMI (r = -0.58 and 0.51; p = 0.001 and 0.004 respectively). After adjustment for aBMD, the association between BSI and stiffness, BSI and SMI remained significant (r = -0.51; p = 0.004 and r = -0.39; p = 0.03 respectively, partial correlations) and the relation between BSI and failure load was close to significance (r = -0.35; p = 0.06). CONCLUSION: The BSI was significantly correlated with the microarchitecture and mechanical behavior of L3 vertebrae, and these associations remained statistically significant regardless of aBMD.

Inhibition of alkaline phosphatase impairs dyslipidemia and protects mice from atherosclerosis.

Calcium accumulation in atherosclerotic plaques predicts cardiovascular mortality, but the mechanisms responsible for plaque calcification and how calcification impacts plaque stability remain debated. Tissue-nonspecific alkaline phosphatase (TNAP) recently emerged as a promising therapeutic target to block cardiovascular calcification. In this study, we sought to investigate the effect of the recently developed TNAP inhibitor SBI-425 on atherosclerosis plaque calcification and progression. TNAP levels were investigated in ApoE-deficient mice fed a high-fat diet from 10 weeks of age and in plaques from the human ECLAGEN biocollection (101 calcified and 14 non-calcified carotid plaques). TNAP was inhibited in mice using SBI-425 administered from 10 to 25 weeks of age, and in human vascular smooth muscle cells (VSMCs) with MLS-0038949. Plaque calcification was imaged in vivo with 18F-NaF-PET/CT, ex vivo with osteosense, and in vitro with alizarin red. Bone architecture was determined with µCT. TNAP activation preceded and predicted calcification in human and mouse plaques, and TNAP inhibition prevented calcification in human VSMCs and in ApoE-deficient mice. More unexpectedly, TNAP inhibition reduced the blood levels of cholesterol and triglycerides, and protected mice from atherosclerosis, without impacting the skeletal architecture. Metabolomics analysis of liver extracts identified phosphocholine as a substrate of liver TNAP, who's decreased dephosphorylation upon TNAP inhibition likely reduced the release of cholesterol and triglycerides into the blood. Systemic inhibition of TNAP protects from atherosclerosis, by ameliorating dyslipidemia, and preventing plaque calcification.

The bone strain index predicts fragility fractures. The OFELY study.

Recently, the bone strain index (BSI), a new index of bone strength based on a finite element model (FEA) from dual X-ray absorptiometry (DXA), has been developed. BSI represents the average equivalent strain inside the bone, assuming that a higher strain level (high BSI) indicates a condition of higher risk. Our study aimed to analyze the relationship between BSI and age, BMI and areal BMD in pre- and postmenopausal women and to prospectively investigate fracture prediction (Fx) by BSI in postmenopausal women. Methods. At the 14th annual follow-up of the OFELY study, BSI was measured at spine (Spine BSI) and femoral scans (Neck and Total Hip BSI), in addition to areal BMD with DXA (Hologic QDR 4500) in 846 women, mean (SD) age 60 yr (15). The FRAX® (fracture risk assessment tool) for major osteoporotic fractures (MOF) was calculated with FN areal BMD (aBMD) at baseline; incident fragility fractures were annually registered until January 2016. Results. In premenopausal women (n = 261), Neck and Total Hip BSI were slightly negatively correlated with age (Spearman r = -0.13 and -0.15 respectively, p = 0.03), whereas all BSIs were positively correlated with BMI (r = +0.20 to 0.37, p < 0.01) and negatively with BMD (r = -0.69 to -0.37, p < 0.0001). In postmenopausal women (n = 585), Neck and Total Hip BSI were positively correlated with age (Spearman r = +0.26 and +0.31 respectively, p < 0.0001), whereas Spine BSI was positively correlated with BMI (r = +0.22, p < 0.0001) and all BSIs were negatively correlated with BMD (r = -0.81 to -0.60, p < 0.0001). During a median [IQ] 9.3 [1.0] years of follow-up, 133 postmenopausal women reported an incident fragility Fx, including 80 women with a major osteoporotic Fx (MOF) and 26 women with clinical vertebral Fx (VFx). Each SD increase of BSI value was associated with a significant increase of the risk of all fragility Fx with an age-adjusted HR of 1.23 for Neck BSI (p = 0.02); 1.27 for Total Hip BSI (p = 0.004) and 1.35 for Spine BSI (p < 0.0001). After adjustment for FRAX®, the association remained statistically significant for Total Hip BSI (HR 1.24, p = 0.02 for all fragility Fx; 1.31, p = 0.01 for MOF) and Spine BSI (HR 1.33, p < 0.0001 for all fragility Fx; 1.33, p = 0.005 for MOF; 1.67, p = 0.002 for clinical VFx). In conclusion, spine and femur BSI, an FEA DXA derived index, predict incident fragility fracture in postmenopausal women, regardless of FRAX®.

Dual-energy CT hybridation and kernel processing effects on the estimation of bone mineral mass and density: a calcination study on ex vivo human femur.

INTRODUCTION: Recent technological advances with dual-energy quantitative computed tomography (DEQCT) allow to combine two images of different level of energy to obtain simulated mono-energetic images at 60 keV (SIM60KeV-QCT) with improved image contrast in clinical practice. This study includes three topics: (1) compare bone mineral content (BMC), areal and volumetric bone mineral density (aBMD, vBMD) obtained with SIM60KeV-QCT, single-energy QCT (SEQCT), and dual X-ray absorptiometry (DXA); (2) compare ash density and weight with respective vBMD and BMC assessed on SIM60KeV-QCT, SEQCT, and DXA; and (3) compare the influence of reconstruction kernels on the accuracy of vBMD and BMC using ash density and ash weight as the reference values. METHODS: DXA, SEQCT, and DEQCT acquisitions were performed ex vivo on 42 human femurs. Standard kernel (SK) and bone kernel (BK) were applied to each stack of images. Ten diaphyses and 10 femoral necks were cut, scanned, and reconstructed using the techniques described above. Finally, the bone specimens were calcined to obtain the ash weight. RESULTS: QCT analysis (SEQCT, SIM60KeV-QCT) underestimated BMC value compared to DXA. For femoral necks, all QCT analyses provided an unbiased estimate of ash weight but underestimated ash density regardless of the kernel used. For femoral diaphysis, SEQCT BK, SIM60KeV-QCT BK, and SK underestimated ash weight but not ash density. CONCLUSION: BMC and vBMD quantifications with the SIM60KeV-QCT gave similar results as the SEQCT. Further studies are needed to optimize the use of SIM60KeV-QCT in clinical situations. SK should be used given the effect of kernels on QCT assessment.

Tamoxifen Treatment in the Neonatal Period Affects Glucose Homeostasis in Adult Mice in a Sex-Dependent Manner.

Tamoxifen is a selective estrogen receptor modulator used to activate the CREERT2 recombinase, allowing tissue-specific and temporal control of the somatic mutagenesis to generate transgenic mice. Studies integrating development and metabolism require a genetic modification induced by a neonatal tamoxifen administration. Here, we investigate the effects of a neonatal tamoxifen administration on energy homeostasis in adult male and female C57BL/6J mice. C57BL/6J male and female mouse pups received a single injection of tamoxifen 1 day after birth (NTT) and were fed a high-fat/high-sucrose diet at 6 weeks of age. We measured weight, body composition, glucose and insulin tolerance, basal metabolism, and tibia length and weight in adult mice. The neonatal tamoxifen administration exerted long-term, sex-dependent effects on energy homeostasis. NTT female mice became overweight and developed impaired glucose control in comparison to vehicle-treated littermates. NTT females exhibited 60% increased fat mass, increased food intake, decreased physical activity and energy expenditure, impaired glucose and insulin tolerance, and fasting hyperglycemia and hyperinsulinemia. In contrast, NTT male mice exhibited a modest amelioration of glucose and insulin tolerance and long-term decreased lean mass linked to decreased bone weight. These results suggest that the neonatal tamoxifen administration exerted a marked and sex-dependent influence on adult energy homeostasis and bone weight and must therefore be used with caution for the development of transgenic mouse models regarding studies on energy homeostasis and bone biology.

DXA body composition corrective factors between Hologic Discovery models to conduct multicenter studies.

BACKGROUND: Dual X-ray absorptiometry body composition measurements are widely used for clinical and research settings. It is well known that measurements vary across instruments, needing caution for longitudinal monitoring or multicentric studies. This study was to quantify intra- and inter-center variability of bone mineral content, bone mineral density, fat and lean body composition measurements between Hologic Discovery models in order to calculate the corrective factors to be applied for multicenter research projects. MATERIALS AND METHODS: A whole body phantom composed of materials representing the thickness and percentage of bone, lean and fat mass in the human physiological range was analyzed ten times in three different centers using dual energy X-ray absorptiometry scanners (Two Hologic Discovery QDR A and one QDR W). In addition, we used a morphometric vertebral phantom to monitor stability and a three steps block phantom to check accuracy. RESULTS: We found a good long-term stability and accuracy for the three devices. Intra-center coefficients of variation were within the range of the manufacturer acceptable values (bone mineral density: 1.40%, bone mineral content: 1%, area: 1.50%, fat mass: 0.89%, lean mass: 0.76%, total mass: 0.12%). Whereas the inter-center coefficient of variation exceeded 8% (bone mineral density: 8.18%, bone mineral content: 3.03%, area: 8.63%: fat mass: 3,92%, lean mass: 7.89%, total mass: 2.85%). CONCLUSION: Our study showed that the discrepancies across centers remain a major concern, particularly with regard to body composition results. Our study highlight the need of cross calibration between densitometers and proposes corrective factors evaluated from a whole body phantom to lead multicentric studies adjustment.

Expression of the type 1 lysophosphatidic acid receptor in osteoblastic cell lineage controls both bone mineralization and osteocyte specification.

Lysphosphatidic acid (LPA) is a major natural bioactive lipid mediator whose biological functions affect multiple organs. These include bone as demonstrated by global Lpar1-knockout mice (Lpar1-/-) which present a bone growth defect. LPA acts on all bone cells including osteoblasts, that are responsible for bone formation, and osteoclasts, which are specialized cells that resorb bone. LPA appears as a potential new coupling molecule during bone remodeling. LPA1 is the most ubiquitous LPA receptor among the six LPA receptor family members (LPA1-6). To better understand the specific role of LPA via its receptor LPA1 in osteoblastic cell lineage we generated osteoblast-specific Lpar1 knockout mice (Lpar1-∆Ob) by crossing Lpar1flox/flox and Osx:Cre+ mouse lines. Lpar1-∆Ob mice do not recapitulate the bone defects of Lpar1-/- mice but revealed reduced bone mineralization and decreased cortical thickness, as well as increased bone porosity associated with an augmentation in the lacunae areas of osteocyte and their apoptotic yield. In vitro, primary Lpar1-∆Ob and immortalized cl1-Ob-Lpar1-/- osteoblasts revealed a remarkable premature expression of alkaline phosphatase, reduced cell proliferation associated with decreased YAP-P nuclear accumulation, and reduced mineralization activity. Osteocyte specification is markedly impaired as demonstrated by reduced expression of early (E11) and late (DMP1, DKK1, SOST) osteocyte markers ex vivo in enriched osteocytic fractions of Lpar1-∆Ob mouse bone explants. In addition, E11 expression and dendrite formation induced by FGF2 are markedly impaired in both primary Lpar1-∆Ob and immortalized cl1-Ob-Lpar1-/- osteoblasts. Taken together these results suggest a new role for LPA in bone mass control via bone mineralization and osteocyte function.

Osteoclast-Derived Autotaxin, a Distinguishing Factor for Inflammatory Bone Loss.

OBJECTIVE: The severity of rheumatoid arthritis (RA) correlates directly with bone erosions arising from osteoclast (OC) hyperactivity. Despite the fact that inflammation may be controlled in patients with RA, those in a state of sustained clinical remission or low disease activity may continue to accrue erosions, which supports the need for treatments that would be suitable for long-lasting inhibition of OC activity without altering the physiologic function of OCs in bone remodeling. Autotaxin (ATX) contributes to inflammation, but its role in bone erosion is unknown. METHODS: ATX was targeted by inhibitory treatment with pharmacologic drugs and also by conditional inactivation of the ATX gene Ennp2 in murine OCs (ΔATXC tsk ). Arthritic and erosive diseases were studied in human tumor necrosis factor-transgenic (hTNF+/- ) mice and mice with K/BxN serum transfer-induced arthritis. Systemic bone loss was also analyzed in mice with lipopolysaccharide (LPS)-induced inflammation and estrogen deprivation. Joint inflammation and bone erosion were assessed by histology and micro-computed tomography. The role of ATX in RA was also examined in OC differentiation and activity assays. RESULTS: OCs present at sites of inflammation overexpressed ATX. Pharmacologic inhibition of ATX in hTNF+/- mice, as compared to vehicle-treated controls, significantly mitigated focal bone erosion (36% decrease; P < 0.05) and systemic bone loss (43% decrease; P < 0.05), without affecting synovial inflammation. OC-derived ATX was revealed to be instrumental in OC bone resorptive activity and was up-regulated by the inflammation elicited in the presence of TNF or LPS. Specific loss of ATX in OCs from mice subjected to ovariectomy significantly protected against the systemic bone loss and erosion that had been induced with LPS and K/BxN serum treatments (30% reversal of systemic bone loss [P < 0.01]; 55% reversal of erosion [P < 0.001]), without conferring bone-protective properties. CONCLUSION: Our results identify ATX as a novel OC factor that specifically controls inflammation-induced bone erosions and systemic bone loss. Therefore, ATX inhibition offers a novel therapeutic approach for potentially preventing bone erosion in patients with RA.

Bone, muscle, and metabolic parameters predict survival in patients with synchronous bone metastases from lung cancers.

BACKGROUND: Lung adenocarcinoma regularly induces bone metastases that are responsible for impaired quality of life as well as significant morbidity, including bone pain and fractures. We aimed at identifying whether bone and metabolic biomarkers were associated with the prognosis of lung adenocarcinoma patients with synchronous bone metastases. PATIENTS AND METHODS: POUMOS is a prospective cohort of patients diagnosed with lung adenocarcinoma and synchronous bone metastases. All patients underwent biopsy of bone metastases to confirm diagnosis, including genotyping of oncogenic drivers such as EGFR and KRAS. Whole-body composition was assessed using DEXA scan. Serum levels of C-reactive protein, HbA1C, calcaemia, sCTX, and DKK1 were also measured. RESULTS: Sixty four patients, aged (mean ±â€¯SD) 65 ±â€¯11 years, were included. Thirty-nine (61%) patients had a good performance status (PS 0-1); 56% had >5 bone lesions, and 41% a weight-bearing bone (femour or tibia) involvement. Median overall survival was 7 months. In multivariate analysis, HbA1c (HR = 1.69 [1.10-2.63] per 0.5% decrease; p = .02), DKK1 (HR = 1.28 [1.01-1.61] per 10 ng/mL increase; p = .04), and hypercalcaemia (HR = 2.83 [1.10-7.30]; p = .03) were independently associated with poorer survival. In the subgroup of patients with DEXA, sarcopenia was also associated with poorer survival (HR = 2.96, 95%CI [1.40-6.27]; p = .005). CONCLUSIONS: In patients with lung adenocarcinoma and synchronous bone metastases, bone, sarcopenia, and metabolic parameters were predictors of poor overall survival independently of common prognostic factors. We suggest that, in addition to oncological therapy, supportive treatment dedicated to bone metastases, muscle wasting, and energy metabolism are essential to improve prognosis.

Bone Microarchitecture Assessed by HR-pQCT as Predictor of Fracture Risk in Postmenopausal Women: The OFELY Study.

Several cross-sectional studies have shown that impairment of bone microarchitecture contributes to skeletal fragility. The aim of this study was to prospectively investigate the prediction of fracture (Fx) by bone microarchitecture assessed by high-resolution peripheral computed tomography (HR- pQCT) in postmenopausal women. We measured microarchitecture at the distal radius and tibia with HR-pQCT in the OFELY study, in addition to areal BMD with dual-energy X-ray absorptiometry (DXA) in 589 women, mean ± SD age 68 ± 9 years. During a median [IQ] 9.4 [1.0] years of follow-up, 135 women sustained an incident fragility Fx, including 81 women with a major osteoporotic Fx (MOP Fx). After adjustment for age, women who sustained Fx had significantly lower total and trabecular volumetric densities (vBMD) at both sites, cortical parameters (area and thickness at the radius, vBMD at the tibia), trabecular number (Tb.N), connectivity density (Conn.D), stiffness, and estimated failure load at both sites, compared with control women. After adjustment for age, current smoking, falls, prior Fx, use of osteoporosis-related drugs, and total hip BMD, each quartile decrease of several baseline values of bone microarchitecture at the radius was associated with significant change of the risk of Fx (HR of 1.39 for Tb.BMD [p = 0.001], 1.32 for Tb.N [p = 0.01], 0.76 for Tb.Sp.SD [p = 0.01], 1.49 [p = 0.01] for Conn.D, and 1.27 for stiffness [p = 0.02]). At the tibia, the association remained significant for stiffness and failure load in the multivariate model for all fragility Fx and for Tt.BMD, stiffness, and failure load for MOP Fx. We conclude that impairment of bone microarchitecture-essentially in the trabecular compartment of the radius-predict the occurrence of incident fracture in postmenopausal women. This assessment may play an important role in identifying women at high risk of fracture who could not be adequately detected by BMD measurement alone, to benefit from a therapeutic intervention. © 2017 American Society for Bone and Mineral Research.

Age-Related Changes in Fat Mass and Distribution in Men-the Cross-Sectional STRAMBO Study.

Data on age-related differences in fat mass and distribution in men are scarce. We performed a cross-sectional analysis of age-related differences in fat distribution in men. In a cohort of 1133 men aged 20-87 yr, body composition was assessed using a Hologic Discovery A device. We assessed fat mass (FM) and FM indices adjusted for height. Interindividual variability was calculated as standard deviation, interquartile range, and difference between the 95th and 5th percentiles in 5-yr age groups. After adjustment for lifestyle factors, the FM and FM index of appendicular, gynoid, central, android, and subcutaneous abdominal compartments increased with age. Their variability did not vary with age. Visceral FM was 181% higher in men aged >80 yr compared to men aged 20-30 yr, and the variability increased with age. FM in the central, android, subcutaneous abdominal, and visceral compartments correlated with age significantly more strongly before the age of 70 than after this age. The relative differences between the elderly and younger men were greater for visceral FM than for subcutaneous (abdominal and appendicular) fat. The interindividual variability in visceral FM is higher in elderly men. The association between visceral FM and age is stronger before the age of 70.

Reproducibility of Vertebral Fracture Assessment Readings From Dual-energy X-ray Absorptiometry in Both a Population-based and Clinical Cohort: Cohen's and Uniform Kappa.

Vertebral fracture assessments (VFAs) using dual-energy X-ray absorptiometry increase vertebral fracture detection in clinical practice and are highly reproducible. Measures of reproducibility are dependent on the frequency and distribution of the event. The aim of this study was to compare 2 reproducibility measures, reliability and agreement, in VFA readings in both a population-based and a clinical cohort. We measured agreement and reliability by uniform kappa and Cohen's kappa for vertebral reading and fracture identification: 360 VFAs from a population-based cohort and 85 from a clinical cohort. In the population-based cohort, 12% of vertebrae were unreadable. Vertebral fracture prevalence ranged from 3% to 4%. Inter-reader and intrareader reliability with Cohen's kappa was fair to good (0.35-0.71 and 0.36-0.74, respectively), with good inter-reader and intrareader agreement by uniform kappa (0.74-0.98 and 0.76-0.99, respectively). In the clinical cohort, 15% of vertebrae were unreadable, and vertebral fracture prevalence ranged from 7.6% to 8.1%. Inter-reader reliability was moderate to good (0.43-0.71), and the agreement was good (0.68-0.91). In clinical situations, the levels of reproducibility measured by the 2 kappa statistics are concordant, so that either could be used to measure agreement and reliability. However, if events are rare, as in a population-based cohort, we recommend evaluating reproducibility using the uniform kappa, as Cohen's kappa may be less accurate.

Bone quality and biomechanical function: a lesson from human ossicles.

In humans, the middle ear contains a chain of three ossicles with a major highly specific mechanical property (transmission of vibrations) and modeling that stops rapidly after birth. Their bone quality has been rarely studied either in noninflammatory ossicles or in those from ears with chronic inflammation. Our primary goal was to assess bone microarchitecture, morphology and variables reflecting bone quality from incuses, in comparison with those from human femoral cortical bone as controls. Secondly, the impact of chronic inflammation on quality of ossicles was documented. The study was performed on 15 noninflammatory incuses from 15 patients (35±32 years, range: 2-91). Comparisons were performed with 13 inflammatory incuses from 13 patients (55±20 years, range: 1-79) with chronic inflammation of the middle ear, essentially cholesteatoma. Microarchitecture and bone mineral density (BMD) were assessed by microcomputed tomography. Microhardness was measured by microindentation. Mineral and organic characteristics were investigated by Fourier transform infrared microspectroscopy. Noninflammatory incuses were composed of a compact, well mineralized bone without bone marrow and with sparse vessels. Remodeling activity was rarely observed. Woven or lamellar textures and numerous osteocytes were observed. In inflammatory incuses, architecture was degraded, organic tissue was abundant and bone cavities contained fibrocellular tissue and adipocytes. BMD of noninflammatory incuses was significantly higher than BMD from both control bones (4 embedded cortical femoral bone samples; age: 72±15 years, range: 50-85) and inflammatory incuses. Noninflammatory incuses were less hard than both control bone (8 cortical femoral bone samples; age: 49±18 years, range: 24-74) and inflammatory incuses. All incuses were more mineralized and less mature than controls. In conclusion, bone quality of incuses (dense, well mineralized, hard) is well adapted to their function of sound transmission. In inflammatory condition, incuses were degraded, thus explaining the decline of hearing. Moreover, microhardness was found higher than in noninflammatory incuses. Compared to bone with remodeling, the mineralization index in incuses does not explain variation of microhardness. Interestingly, a linear multiple regression model indicated that a combination of two variables, i.e., crystallinity index (crystal size/perfection) and carbonation (incorporation of carbonate ions in apatite) explains 26% of the increase in microhardness variability. Because the low remodeling level of ossicles could not prevent the reversibility of their degradation which impacts audition quality, an early management of ear inflammation in chronic otitis is recommended.

Hyperpolarized 3He MR for sensitive imaging of ventilation function and treatment efficiency in young cystic fibrosis patients with normal lung function.

PURPOSE: To assess the sensitivity of hyperpolarized helium 3 ((3)He) magnetic resonance (MR) imaging for the detection of peripheral airway obstruction in younger cystic fibrosis (CF) patients showing normal spirometric results (mean forced expiratory volume in 1 second [FEV(1)], 112% +/- 14.5 [standard deviation]) and to observe the immediate effects of a single chest physical therapy (CPT) session, thereby comparing two image quantification techniques. MATERIALS AND METHODS: Ten pediatric CF patients (age range, 8-16 years) with normal spirometric results were included in this study after approval from the local research ethics committee. Spirometry followed by proton and hyperpolarized (3)He three-dimensional lung imaging were performed with a 1.5-T MR unit before and after 20 minutes of CPT. The number of ventilation defects per image (VDI) and the ventilated lung fraction (VF), defined as the ratio of ventilated lung volume divided by total lung volume, were quantified. RESULTS: Ventilation defects were found in all patients (mean VDI, 5.1 +/- 1.9; mean global VF, 78.5% +/- 12.3; and mean peripheral VF, 75.5% +/- 17.1) despite normal spirometric results. After CPT, disparate changes in the distribution of ventilation defects were observed but the average VDI and VF did not change significantly (mean VDI, 5.1 +/- 1.1; mean global VF, 83.5% +/- 12.2; and mean peripheral VF, 80.3% +/- 12.2). There was no correlation between FEV(1) and VDI (rho = -0.041, P = .863) or global VF (rho = -0.196, P = .408) values but peripheral VF and VDI were correlated (rho = -0.563, P = .011). CONCLUSION: Although spirometric results indicate normal lung function, the mean VDI in patients (5.1) found in this study is well above the VDI in healthy subjects (1.6) reported in the literature. A single CPT session induces disparate changes in the distribution and extent of ventilation defects.

Investigation of PVA cryogel Young's modulus stability with time, controlled by a simple reliable technique.

We describe a quasistatic method for mechanical characterization of tissue-mimicking material used in elastography. We demonstrate that it is possible to assess the elasticity modulus with a reasonable reproducibility using simple and easy tools and methods. Possessing a simple relevant technique with evaluated relative error to assess Young's modulus of these phantoms could deeply improve the quality of the research in the field of elastography. The method was tested and validated with four samples of polyvinyl alcohol (PVA) cryogel with different elasticity values corresponding to those of stiffer soft biological tissues. Young's moduli, varying from 70 to 180 kPa depending on the number of freeze-thaw cycles (two to five), were measured within strict measurement conditions and found to have a reproducibility varying from 4% to 8%. Relative error, estimated as the ratio between observed and reference values, varied from 16% to 32%. Besides, measurement stability over 4 months was evaluated. The method demonstrated good feasibility and acceptable reproducibility for mechanically characterizing and controlled over time phantoms used for validating new potential ultrasound imaging techniques in the field of elastography. Nevertheless, in this study, investigation was performed on gel possessing young's modulus values ranging from 80 to 215 kPa. Some tissue values of Young'modulus were reported to be lower, ranging from 0.6 to 28 kPa as liver or glandular values. Consequently, further validation of this static method for mechanical characterization of phantom gels should be performed using softer PVA cryogel.

Bimodal ultrasound and fluorescence approach for prostate cancer diagnosis.

Finding a way to combine ultrasound and fluorescence optical imaging on an endorectal probe may improve early detection of prostate cancer. The ultrasound provides morphological information about the prostate, while the optical system detects and locates fluorophore-marked tumors. A tissue-mimicking phantom, which is representative of prostate tissues both on its optical (absorption mu(a) and diffusion mu(s) (')) and its ultrasound properties, has been made by our team. A transrectal probe adapted to fluorescence diffuse optical tomography measurements was also developed. Measurements were taken on the prostate phantom with this probe based on a pulsed laser and a time-resolved detection system. A reconstruction algorithm was then used to help locate and quantify fluorescent inclusions of different concentrations at fixed depths.

Characterization of hepatocellular carcinoma and colorectal liver metastasis by means of perfusion MRI.

PURPOSE: To characterize and compare hepatocellular carcinoma and liver metastases of colorectal metastatic cancer (CMC) by means of quantitative liver perfusion MRI. MATERIALS AND METHODS: Liver perfusion was assessed in 26 HCC and CMC patients (50 nodules) by means of contrast-enhanced MRI. Six perfusion parameters-hepatic perfusion index (HPI), mean transit time (MTT), distribution volume (DV), total blood flow (F(T)), arterial blood flow (F(A)), and portal blood flow (F(P))-were calculated in tumor nodules and the adjacent hepatic parenchyma. RESULTS: The values of F(T), F(A), F(P), and DV were significantly higher in the HCC than in the CMC group, whereas MTT was significantly higher in the CMC group. There was no significant difference in HPI. Arterial blood flow was higher than portal blood flow in the CMC group, while portal blood flow was slightly higher than arterial blood flow in the HCC group. CONCLUSION: The present work describes the use of dynamic MRI to quantitatively assess liver perfusion, which in the future may help studying liver cancers on the basis of their microvascular characteristics.

Bone sialoprotein plays a functional role in bone formation and osteoclastogenesis.

Bone sialoprotein (BSP) and osteopontin (OPN) are both highly expressed in bone, but their functional specificities are unknown. OPN knockout (-/-) mice do not lose bone in a model of hindlimb disuse (tail suspension), showing the importance of OPN in bone remodeling. We report that BSP(-/-) mice are viable and breed normally, but their weight and size are lower than wild-type (WT) mice. Bone is undermineralized in fetuses and young adults, but not in older (> or =12 mo) BSP(-/-) mice. At 4 mo, BSP(-/-) mice display thinner cortical bones than WT, but greater trabecular bone volume with very low bone formation rate, which indicates reduced resorption, as confirmed by lower osteoclast surfaces. Although the frequency of total colonies and committed osteoblast colonies is the same, fewer mineralized colonies expressing decreased levels of osteoblast markers form in BSP(-/-) versus WT bone marrow stromal cultures. BSP(-/-) hematopoietic progenitors form fewer osteoclasts, but their resorptive activity on dentin is normal. Tail-suspended BSP(-/-) mice lose bone in hindlimbs, as expected. In conclusion, BSP deficiency impairs bone growth and mineralization, concomitant with dramatically reduced bone formation. It does not, however, prevent the bone loss resulting from loss of mechanical stimulation, a phenotype that is clearly different from OPN(-/-) mice.

Locally regularized strain field estimation for freehand elastography.

This paper focuses on strain estimation methods in ultrasound elastography. We recently developed a 2D locally regularized strain estimation algorithm, whose performance was assessed with simulations and experimental data, but in the case of a well controlled medium deformation. In this study, we investigate the robustness of our algorithm to image tissue deformation during freehand scanning. Results on an elastography dedicated phantom and biological tissue ex vivo demonstrate the ability of our algorithm to provide good-quality strain maps, even in more complex loading conditions.