A meta-analysis of trabecular bone score in fracture risk prediction and its relationship to FRAX

Trabecular bone score (TBS) is a grey-level textural index of bone microarchitecture derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images. TBS is a BMD-independent predictor of fracture risk. The objective of this meta-analysis was to determine whether TBS predicted fracture risk independently of FRAX probability and to examine their combined performance by adjusting the FRAX probability for TBS. We utilized individual level data from 17,809 men and women in 14 prospective population-based cohorts. Baseline evaluation included TBS and the FRAX risk variables and outcomes during follow up (mean 6.7 years) comprised major osteoporotic fractures. The association between TBS, FRAX probabilities and the risk of fracture was examined using an extension of the Poisson regression model in each cohort and for each sex and expressed as the gradient of risk (GR; hazard ratio per 1SD change in risk variable in direction of increased risk). FRAX probabilities were adjusted for TBS using an adjustment factor derived from an independent cohort (the Manitoba Bone Density Cohort). Overall, the GR of TBS for major osteoporotic fracture was 1.44 (95% CI: 1.35-1.53) when adjusted for age and time since baseline and was similar in men and women (p > 0.10). When additionally adjusted for FRAX 10-year probability of major osteoporotic fracture, TBS remained a significant, independent predictor for fracture (GR 1.32, 95%CI: 1.24-1.41). The adjustment of FRAX probability for TBS resulted in a small increase in the GR (1.76, 95%CI: 1.65, 1.87 vs. 1.70, 95%CI: 1.60-1.81). A smaller change in GR for hip fracture was observed (FRAX hip fracture probability GR 2.25 vs. 2.22). TBS is a significant predictor of fracture risk independently of FRAX. The findings support the use of TBS as a potential adjustment for FRAX probability, though the impact of the adjustment remains to be determined in the context of clinical assessment guidelines. This article is protected by copyright. All rights reserved.

Biomechanical comparison between bicortical pin and monocortical screw/polymethylmethacrylate constructs in the cadaveric canine cervical vertebral column.

OBJECTIVE To compare biomechanical stiffness of cadaveric canine cervical spine constructs stabilized with bicortical stainless steel pins and polymethylmethacrylate (PMMA), monocortical stainless steel screws with PMMA, or monocortical titanium screws with PMMA. STUDY DESIGN Biomechanical cadaver study. ANIMALS Eighteen canine cervical vertebral columns (C2-C7) were collected from skeletally mature dogs (weighing 22-32 kg). METHODS Specimens were radiographed and examined by dual energy X-ray absorptiometry. Stiffness of the unaltered C4-C5 intervertebral motion unit was measured in extension, flexion and lateral bending using non-destructive 4-point bend testing. Specimens were then stabilized by (1) bicortical stainless steel pins/PMMA, (2) monocortical stainless steel screws/PMMA, or (3) monocortical titanium screws/PMMA. Mechanical testing was repeated and stiffness data from unaltered specimens and the 3 treatment groups were compared. RESULTS All 3 surgical methods significantly increased stiffness of the C4-C5 motion unit compared with the unaltered specimen (P < .001 for all treatments), but stiffness was not significantly different among the 3 fixation groups (P = .578). CONCLUSIONS In this model, monocortical screw fixation (with stainless steel or titanium screws) was biomechanically equivalent to bicortical fixation.

Bone mineral density and circulating biomarkers in the BIG 1-98 trial comparing adjuvant letrozole, tamoxifen and their sequences.

The purpose of the study is to determine the effects of the BIG 1-98 treatments on bone mineral density. BIG 1-98 compared 5-year adjuvant hormone therapy in postmenopausal women allocated to four groups: tamoxifen (T); letrozole (L); 2-years T, 3-years L (TL); and 2-years L, 3-years T (LT). Bone mineral density T-score was measured prospectively annually by dual energy X-ray absorption in 424 patients enrolled in a sub-study after 3 (n = 150), 4 (n = 200), and 5 years (n = 74) from randomization, and 1 year after treatment cessation. Prevalence of osteoporosis and the association of C-telopeptide, osteocalcin, and bone alkaline phosphatase with T-scores were assessed. At 3 years, T had the highest and TL the lowest T-score. All arms except for LT showed a decline up to 5 years, with TL exhibiting the greatest. At 5 years, there were significant differences on lumbar T-score only between T and TL, whereas for femur T-score, differences were significant for T versus L or TL, and L versus LT. The 5-year prevalence of spine and femur osteoporosis was the highest on TL (14.5 %, 7.1 %) then L (4.3 %, 5.1 %), LT (4.2 %, 1.4 %) and T (4 %, 0). C-telopeptide and osteocalcin were significantly associated with T-scores. While adjuvant L increases bone mineral density loss compared with T, the sequence LT has an acceptable bone safety profile. C-telopeptide and osteocalcin are useful markers of bone density that may be used to monitor bone health during treatment. The sequence LT may be a valid treatment option in patients with low and intermediate risk of recurrence.

DXA predictions of human femoral mechanical properties depend on the load configuration

The aim of this study was to evaluate the ability of dual energy X-rays absorptiometry (DXA) areal bone mineral density (aBMD) measured in different regions of the proximal part of the human femur for predicting the mechanical properties of matched proximal femora tested in two different loading configurations. 36 pairs of fresh frozen femora were DXA scanned and tested until failure in two loading configurations: a fall on the side or a one-legged standing. The ability of the DXA output from four different regions of the proximal femur in predicting the femoral mechanical properties was measured and compared for the two loading scenarios. The femoral neck DXA BMD was best correlated to the femoral ultimate force for both configurations and predicted significantly better femoral failure load (R2=0.80 vs. R2=0.66, P<0.05) when simulating a side than when simulating a standing configuration. Conversely, the work to failure was predicted similarly for both loading configurations (R2=0.54 vs. R2=0.53, P>0.05). Therefore, neck BMD should be considered as one of the key factors for discriminating femoral fracture risk in vivo. Moreover, the better predictive ability of neck BMD for femoral strength if tested in a fall compared to a one-legged stance configuration suggests that DXA's clinical relevance may not be as high for spontaneous femoral fractures than for fractures associated to a fall.

Proteomic changes in the rat brain induced by homogenous irradiation and by the bystander effect resulting from high energy synchrotron X-ray microbeams

Abstract Purpose: To further evaluate the use of microbeam irradiation (MBI) as a potential means of non-invasive brain tumor treatment by investigating the induction of a bystander effect in non-irradiated tissue. Methods: Adult rats were irradiated with 35 or 350 Gy at the European Synchotron Research Facility (ESRF), using homogenous (broad beam) irradiation (HI) or a high energy microbeam delivered to the right brain hemisphere only. The proteome of the frontal lobes were then analyzed using two-dimensional electrophoresis (2-DE) and mass spectrometry. Results: HI resulted in proteomic responses indicative of tumourigenesis; increased albumin, aconitase and triosphosphate isomerase (TPI), and decreased dihydrolipoyldehydrogenase (DLD). The MBI bystander effect proteomic changes were indicative of reactive oxygen species mediated apoptosis; reduced TPI, prohibitin and tubulin and increased glial fibrillary acidic protein (GFAP). These potentially anti-tumourigenic apoptotic proteomic changes are also associated with neurodegeneration. However the bystander effect also increased heat shock protein (HSP) 71 turnover. HSP 71 is known to protect against all of the neurological disorders characterized by the bystander effect proteome changes. Conclusions: These results indicate that the collective interaction of these MBI-induced bystander effect proteins and their mediation by HSP 71, may confer a protective effect which now warrants additional experimental attention.

Unifying energy minimization and mutual information maximization for robust 2D/3D registration of X-ray and CT images

Similarity measure is one of the main factors that affect the accuracy of intensity-based 2D/3D registration of X-ray fluoroscopy to CT images. Information theory has been used to derive similarity measure for image registration leading to the introduction of mutual information, an accurate similarity measure for multi-modal and mono-modal image registration tasks. However, it is known that the standard mutual information measure only takes intensity values into account without considering spatial information and its robustness is questionable. Previous attempt to incorporate spatial information into mutual information either requires computing the entropy of higher dimensional probability distributions, or is not robust to outliers. In this paper, we show how to incorporate spatial information into mutual information without suffering from these problems. Using a variational approximation derived from the Kullback-Leibler bound, spatial information can be effectively incorporated into mutual information via energy minimization. The resulting similarity measure has a least-squares form and can be effectively minimized by a multi-resolution Levenberg-Marquardt optimizer. Experimental results are presented on datasets of two applications: (a) intra-operative patient pose estimation from a few (e.g. 2) calibrated fluoroscopic images, and (b) post-operative cup alignment estimation from single X-ray radiograph with gonadal shielding.

Advances of dual source, dual-energy imaging in postmortem CT

This paper focuses on the use of multi-detector row dual-energy computed tomography (DECT) in the evaluation of postmortal examinations. The use of dual energy moves postmortem CT to an entirely new dimension of diagnostic sensitivity where contrast in the image is not merely limited to X-ray attenuation differences, but may include elements of functional and tissue characterization. This additional information may be used to improve the benefit postmortem imaging can provide to supplement and simplify the conventional autopsy.

Personalized X-Ray Reconstruction of the Proximal Femur via Intensity-Based Non-rigid 2D-3D Registration

This paper presents a new approach for reconstructing a patient-specific shape model and internal relative intensity distribution of the proximal femur from a limited number (e.g., 2) of calibrated C-arm images or X-ray radiographs. Our approach uses independent shape and appearance models that are learned from a set of training data to encode the a priori information about the proximal femur. An intensity-based non-rigid 2D-3D registration algorithm is then proposed to deformably fit the learned models to the input images. The fitting is conducted iteratively by minimizing the dissimilarity between the input images and the associated digitally reconstructed radiographs of the learned models together with regularization terms encoding the strain energy of the forward deformation and the smoothness of the inverse deformation. Comprehensive experiments conducted on images of cadaveric femurs and on clinical datasets demonstrate the efficacy of the present approach.

Comparison of dual-energy subtraction and electronic bone suppression combined with computer-aided detection on chest radiographs: effect on human observers' performance in nodule detection

The objective of our study was to compare the effect of dual-energy subtraction and bone suppression software alone and in combination with computer-aided detection (CAD) on the performance of human observers in lung nodule detection.

Effect of X-ray tube parameters, iodine concentration, and patient size on image quality in pulmonary computed tomography angiography: a chest-phantom-study

OBJECTIVES: The aim of this phantom study was to evaluate the contrast-to-noise ratio (CNR) in pulmonary computed tomography (CT)-angiography for 300 and 400 mg iodine/mL contrast media using variable x-ray tube parameters and patient sizes. We also analyzed the possible strategies of dose reduction in patients with different sizes. MATERIALS AND METHODS: The segmental pulmonary arteries were simulated by plastic tubes filled with 1:30 diluted solutions of 300 and 400 mg iodine/mL contrast media in a chest phantom mimicking thick, intermediate, and thin patients. Volume scanning was done with a CT scanner at 80, 100, 120, and 140 kVp. Tube current-time products (mAs) varied between 50 and 120% of the optimal value given by the built-in automatic dose optimization protocol. Attenuation values and CNR for both contrast media were evaluated and compared with the volume CT dose index (CTDI(vol)). Figure of merit, calculated as CNR/CTDIvol, was used to quantify image quality improvement per exposure risk to the patient. RESULTS: Attenuation of iodinated contrast media increased both with decreasing tube voltage and patient size. A CTDIvol reduction by 44% was achieved in the thin phantom with the use of 80 instead of 140 kVp without deterioration of CNR. Figure of merit correlated with kVp in the thin phantom (r = -0.897 to -0.999; P < 0.05) but not in the intermediate and thick phantoms (P = 0.09-0.71), reflecting a decreasing benefit of tube voltage reduction on image quality as the thickness of the phantom increased. Compared with the 300 mg iodine/mL concentration, the same CNR for 400 mg iodine/mL contrast medium was achieved at a lower CTDIvol by 18 to 40%, depending on phantom size and applied tube voltage. CONCLUSIONS: Low kVp protocols for pulmonary embolism are potentially advantageous especially in thin and, to a lesser extent, in intermediate patients. Thin patients profit from low voltage protocols preserving a good CNR at a lower exposure. The use of 80 kVp in obese patients may be problematic because of the limitation of the tube current available, reduced CNR, and high skin dose. The high CNR of the 400 mg iodine/mL contrast medium together with lower tube energy and/or current can be used for exposure reduction.

Mössbauer, X-ray and Magnetic Studies of Black Sand from the Italian Mediterranean Sea

The study of natural magnetic sands is instrumental to investigate the geological aspects of their formation and of the origin of their territory. In particular, Mössbauer spectroscopy provides unique information on their iron content and on the oxidation state of iron in their mineral composition. The Italian coast on the Mediterranean Sea near Rome is known for the presence of highly magnetic black sands of volcanic origin. A study of the room temperature Mössbauer spec- trum, powder X-ray diffraction, energy dispersive X-ray spectroscopy, and magnetic measurements of a sample of black magnetic sand collected on the seashore of the town of Ladispoli is performed. This study reveals magnetite as main constituent with iron in both tetrahedral and octahedral sites. Minor constituents are the iron minerals hematite and ilmenite, the iron containing minerals diopsite, gossular, and allanite, as well as ubiquitous sanidine, quartz, and calcite.

Hohlraum Target for Overcoming Refractive Losses in Plasma X-ray Lasers

Refractive losses in laser-produced plasmas used as gain media are caused by electron density gradients, and limit the energy transport range. The pump pulse is thus deflected from the high-gain region and the short wavelength laser signal also steers away, causing loss of collimation. A Hohlraum used as a target makes the plasma homogeneous and can mitigate refractive losses by means of wave-guiding. A computational study combining a hydrodynamics code and an atomic physics code is presented, which includes a ray-tracing modeling based on the eikonal theory of the trajectory equation. This study presents gain calculations based on population inversion produced by free-electron collisions exciting bound electrons into metastable levels in the 3d94d1(J = 0) → 3d94p1(J = 1) transition of Ni-like Sn. Further, the Hohlraum suggests a dramatic enhancement of the conversion efficiency of collisionally excited x-ray lasing for Ni-like Sn.

Lung Nodule Detection by Microdose CT Versus Chest Radiography (Standard and Dual-Energy Subtracted).

OBJECTIVE The purpose of this study was to investigate the feasibility of microdose CT using a comparable dose as for conventional chest radiographs in two planes including dual-energy subtraction for lung nodule assessment. MATERIALS AND METHODS We investigated 65 chest phantoms with 141 lung nodules, using an anthropomorphic chest phantom with artificial lung nodules. Microdose CT parameters were 80 kV and 6 mAs, with pitch of 2.2. Iterative reconstruction algorithms and an integrated circuit detector system (Stellar, Siemens Healthcare) were applied for maximum dose reduction. Maximum intensity projections (MIPs) were reconstructed. Chest radiographs were acquired in two projections with bone suppression. Four blinded radiologists interpreted the images in random order. RESULTS A soft-tissue CT kernel (I30f) delivered better sensitivities in a pilot study than a hard kernel (I70f), with respective mean (SD) sensitivities of 91.1% ± 2.2% versus 85.6% ± 5.6% (p = 0.041). Nodule size was measured accurately for all kernels. Mean clustered nodule sensitivity with chest radiography was 45.7% ± 8.1% (with bone suppression, 46.1% ± 8%; p = 0.94); for microdose CT, nodule sensitivity was 83.6% ± 9% without MIP (with additional MIP, 92.5% ± 6%; p < 10(-3)). Individual sensitivities of microdose CT for readers 1, 2, 3, and 4 were 84.3%, 90.7%, 68.6%, and 45.0%, respectively. Sensitivities with chest radiography for readers 1, 2, 3, and 4 were 42.9%, 58.6%, 36.4%, and 90.7%, respectively. In the per-phantom analysis, respective sensitivities of microdose CT versus chest radiography were 96.2% and 75% (p < 10(-6)). The effective dose for chest radiography including dual-energy subtraction was 0.242 mSv; for microdose CT, the applied dose was 0.1323 mSv. CONCLUSION Microdose CT is better than the combination of chest radiography and dual-energy subtraction for the detection of solid nodules between 5 and 12 mm at a lower dose level of 0.13 mSv. Soft-tissue kernels allow better sensitivities. These preliminary results indicate that microdose CT has the potential to replace conventional chest radiography for lung nodule detection.