Improving ultrasound-based bone registration using the iterative closest point algorithm paired with a complex optimization solver.

The Iterative Close Point (ICP) algorithm is used for bone registrations based on ultrasound measurements. However, the ICP has been shown to suffer from local minima. The Complex optimization, as a more robust routine compared to the commonly used gradient-based algorithms, could be an alternative for solving the ICP problem. In this study, we investigated the effect of the initial estimate and the number of registration points on bone registrations achieved using the ICP and a Complex optimization routine and we compared it against using Quadratic Sequential Programming (SQP). Ultrasound measurements were performed with an A-mode probe on a bovine humerus and an ovine femur embedded into ballistic gel. Simultaneously, the bones and the probe were tracked in 3D space using retroreflective markers. Kinematic, ultrasound and geometrical data obtained from scans of the specimens and the probe served as input to a bone registrations routine. Registrations were performed using two ICP solvers for different initial estimates and number of registration points. On average, 68 % of the Complex optimization registrations had less than 1 mm translation error and less than 1° rotational error for perturbations of the initial estimate from the reference measurements compared to the 35 % of the SQP ones. Similar medians of registration errors were observed between the two methods for variations of the number of the employed registration points. Although the Complex optimization provided accurate bone registrations for all cases, the objective function could not always determine the registrations with the smallest registration error. Future research should explore methodologies to overcome this challenge.

Backscatter measurement of cancellous bone using the ultrasound transit time spectroscopy.

Recently, ultrasound transit time spectroscopy (UTTS) was proposed as a promising method for bone quantitative ultrasound measurement. Studies have showed that UTTS could estimate the bone volume fraction and other trabecular bone structure in ultrasonic through-transmission measurements. The goal of this study was to explore the feasibility of UTTS to be adapted in ultrasonic backscatter measurement and further evaluate the performance of backscattered ultrasound transit time spectrum (BS-UTTS) in the measurement of cancellous bone density and structure. First, taking ultrasonic attenuation into account, the concept of BS-UTTS was verified on ultrasonic backscatter signals simulated from a set of scatterers with different positions and intensities. Then, in vitro backscatter measurements were performed on 26 bovine cancellous bone specimens. After a logarithmic compression of the BS-UTTS, a linear fitting of the log-compressed BS-UTTS versus ultrasonic propagated distance was performed and the slope and intercept of the fitted line for BS-UTTS were determined. The associations between BS-UTTS parameters and cancellous bone features were analyzed using simple linear regression. The results showed that the BS-UTTS could make an accurate deconvolution of the backscatter signal and predict the position and intensity of the simulated scatterers eliminating phase interference, even the simulated backscatter signal was with a relatively low signal-to-noise ratio. With varied positions and intensities of the scatterers, the slope of the fitted line for the log-compressed BS-UTTS versus ultrasonic propagated distance (i.e., slope of BS-UTTS for short) yield a high agreement (r2 = 99.84%-99.96%) with ultrasonic attenuation in simulated backscatter signal. Compared with the high-density cancellous bone, the low-density specimen showed more abundant backscatter impulse response in the BS-UTTS. The slope of BS-UTTS yield a significant correlation with bone mineral density (r = 0.87; p < 0.001), BV/TV (r = 0.87; p < 0.001), and cancellous bone microstructures (r up to 0.87; p < 0.05). The intercept of BS-UTTS was also significantly correlated with bone densities (r = -0.87; p < 0.001) and trabecular structures (|r|=0.43-0.80; p < 0.05). However, the slope of the BS-UTTS underestimated attenuation when measurements were performed experimentally. In addition, a significant non-linear relationship was observed between the measured attenuation and the attenuation estimated by the slope of the BS-UTTS. This study demonstrated that the UTTS method could be adapted to ultrasonic backscatter measurement of cancellous bone. The derived slope and intercept of BS-UTTS could be used in the measurement of bone density and microstructure. The backscattered ultrasound transit time spectroscopy might have potential in the diagnosis of osteoporosis in the clinic.

Evaluation of 188Re- IBA as a novel radiopharmaceutical for bone marrow ablation.

In this study, Ibandronate as a third generation of bisphosphonates was labeled with rhenium-188 radionuclide. Production and quality control of 188Re-IBA radiopharmaceutical was investigated. The radiation absorbed dose of this radiopharmaceutical was evaluated for adult male based on biodistribution data in mice using the RADAR and Sparks and Aydogan methodologies. The 188Re-IBA was produced with more than 96% radiochemical purity. The highest value of %ID/g was related to bone with 7.11% at 12 h post-injection. About 48% of injected activity was cumulated on the surface of bone tissue 48 h post-injection. The imaging studies confirmed the biodistribution pattern. Radiation absorbed doses of red bone marrow and osteogenic cells were estimated to about 0.39 and 0.71 mGy MBq-1, respectively. The maximum administrated activity was obtained 73.1 MBq kg-1 (2.0 mCi kg-1) of body weight. Effective dose was evaluated about 0.09 mSv MBq-1. The results were compared with other clinically used bone pain palliation radiopharmaceuticals. It was concluded that the 188Re-IBA radiopharmaceutical has a great tendency to be absorbed in bone tissue and it can provide sufficient care for bone marrow ablation with low undesired dose to other normal organs.

Theoretical and experimental study of attenuation in cancellous bone.

Significance: Photoacoustic (PA) technology shows great potential for bone assessment. However, the PA signals in cancellous bone are complex due to its complex composition and porous structure, making such signals challenging to apply directly in bone analysis. Aim: We introduce a photoacoustic differential attenuation spectrum (PA-DAS) method to separate the contribution of the acoustic propagation path to the PA signal from that of the source, and theoretically and experimentally investigate the propagation attenuation characteristics of cancellous bone. Approach: We modified Biot's theory by accounting for the high frequency and viscosity. In parallel with the rabbit osteoporosis model, we build an experimental PA-DAS system featuring an eccentric excitation differential detection mechanism. Moreover, we extract a PA-DAS quantization parameter-slope-to quantify the attenuation of high- and low-frequency components. Results: The results show that the porosity of cancellous bone can be evaluated by fast longitude wave attenuation at different frequencies and the PA-DAS slope of the osteoporotic group is significantly lower compared with the normal group (**p<0.01). Conclusions: Findings demonstrate that PA-DAS effectively differentiates osteoporotic bone from healthy bone, facilitating quantitative assessment of bone mineral density, and osteoporosis diagnosis.

Region fine-grained attention network for accurate bone age assessment.

Bone age assessment plays a vital role in monitoring the growth and development of adolescents. However, it is still challenging to obtain precise bone age from hand radiography due to these problems: 1) Hand bone varies greatly and is always masked by the background; 2) the hand bone radiographs with successive ages offer high similarity. To solve such issues, a region fine-grained attention network (RFGA-Net) was proposed for bone age assessment, where the region aware attention (RAA) module was developed to distinguish the skeletal regions from the background by modeling global spatial dependency; then the fine-grained feature attention (FFA) module was devised to identify similar bone radiographs by recognizing critical fine-grained feature regions. The experimental results demonstrate that the proposed RFGA-Net shows the best performance on the Radiological Society of North America (RSNA) pediatric bone dataset, achieving the mean absolute error (MAE) of 3.34 and the root mean square error (RMSE) of 4.02, respectively.

Quantitative and qualitative evaluation of three MSCT for high resolution bone imaging.

INTRODUCTION: Strategies for achieving high resolution varies between manufacturers. In CT, the helical mode with narrow collimation has long been considered as the gold standard for high-resolution imaging. More recently, incremental modes with small dexels and focal spot, have been developed but have not been compared with helical acquisitions under optimal conditions. The aim of this work is to compare the high-resolution acquisition strategies currently proposed by recent MSCT. METHODS: Three CT systems were compared. A phantom was used to evaluate geometric accuracy, uniformity, scan slice geometry, and spatial resolution. Human dry bones were used to test different protocols on real bone architecture. A blind visual analysis was conducted by trained CT users for classifying the different acquisitions (p-values). RESULTS: All systems give satisfactory results in terms of geometric accuracy and uniformity. The in-plane MTF at 5% were respectively 13.4, 15.9 and 18.1 lp/cm. Dry-bones evaluation confirms that acquisition#3 is considered as the best. CONCLUSIONS: The incremental acquisition coupled with à small focal spot, and a high-sampling detector, overpasses the reference of low-pitch helical acquisitions for high-resolution imaging. Cortical bone, bony vessels, and tumoral matrix analysis are the very next challenges that will have to be managed to improve normal and pathologic bone imaging thanks to the availability UHR-CT systems.

Bone microarchitecture and strength assessment in adults with osteogenesis imperfecta using HR-pQCT: normative comparison and challenges.

Data on bone microarchitecture in osteogenesis imperfecta (OI) are scarce. The aim of this cross-sectional study was to assess bone microarchitecture and strength in a large cohort of adults with OI using high-resolution peripheral quantitative computed tomography (HR-pQCT) and to evaluate challenges of using HR-pQCT in this cohort. Second-generation HR-pQCT scans were obtained at the distal radius and tibia in 118 men and women with Sillence OI type I, III, or IV using an extremity-length-dependent scan protocol. In total, 102 radius and 105 tibia scans of sufficient quality could be obtained, of which 11 radius scans (11%) and 14 tibia scans (13%) had a deviated axial scan angle as compared with axial angle data of 13 young women. In the scans without a deviated axial angle and compared with normative HR-pQCT data, Z-scores at the radius for trabecular bone mineral density (BMD), number, and separation were -1.6 ± 1.3, -2.5 ± 1.4, and -2.7 (IQR: 2.7), respectively. They were -1.4 ± 1.5 and -1.1 ± 1.2 for stiffness and failure load and between ±1 for trabecular thickness and cortical bone parameters. Z-scores were significantly lower for total and trabecular BMD, stiffness, failure load, and cortical area and thickness at the tibia. Additionally, local microarchitectural inhomogeneities were observed, most pronounced being trabecular void volumes. In the scans with a deviated axial angle, the proportion of Z-scores <-4 or >4 was significantly higher for trabecular BMD and separation (radius) or most total and trabecular bone parameters (tibia). To conclude, especially trabecular bone microarchitecture and bone strength were impaired in adults with OI. HR-pQCT may be used without challenges in most adults with OI, but approximately 12% of the scans may have a deviated axial angle in OI due to bone deformities or scan positioning limitations. Furthermore, standard HR-pQCT parameters may not always be reliable due to microarchitectural inhomogeneities nor fully reflect all inhomogeneities.

OI is a rare condition with large clinical heterogeneity. One of the major characteristics associated with OI is the increased fracture risk due to defects in bone structure and material. Data on the defects in bone structure at the micrometer level (i.e. bone microarchitecture) are scarce. Bone microarchitecture can be assessed noninvasively using HR-pQCT, but its use in OI has not extensively been described. Yet, potential challenges may arise related to among others the occurrence of short extremities and skeletal deformities in OI. We assessed bone microarchitecture and strength in 118 adults with OI types I, III, or IV using HR-pQCT with an extremity-length-dependent scan protocol. Additionally, we evaluated potential challenges of using HR-pQCT in this cohort. Our results demonstrated that predominantly trabecular microarchitecture­especially trabecular number and separation­and overall bone strength were impaired in adults with OI as compared with normative data. Furthermore, we observed various microarchitectural inhomogeneities, most pronounced being trabecular void volumes. Regarding applicability, HR-pQCT could be used without challenges in most adults with OI. However, deviations in scan region may potentially influence HR-pQCT parameters, and standard HR-pQCT analyses may not always give accurate results due to microarchitectural inhomogeneities nor fully reflect all microarchitectural inhomogeneities.

Estimation of the in-plane ultimate stress of lamellar tissue as a function of bone mineral density and osteocyte lacunae porosity.

BACKGROUND AND OBJECTIVE: Detailed finite element models based on medical images (µ-CT) are commonly used to analyze the mechanical behavior of bone at microscale. In order to simulate the tissue failure onset, isotropic failure criteria of lamellar tissue are often used, despite its non-isotropic and heterogeneous nature. The main goal of the present work is to estimate the in-plane ultimate stress of lamellar bone, considering the influence of mineral content and the porosity due to the osteocyte lacunae concentration. METHODS: To this aim, a representative volume cell of lamellar tissue is modeled numerically, including: (1) non-isotropic elastic properties of tissue as a function of the bone mineral density and (2) explicit modeling of the osteocyte lacunae, considering the range of porosity content, size and orientation of ellipsoid-shaped lacunae. Firstly, the element size for the finite element models have been defined from a preliminary convergence analysis. Bounds on the ultimate stress of non-porous lamellar tissue are estimated for two values of bone mineral density, considering the results of tensile and compressive tests of wet osteons from the literature. Subsequently, the ultimate stress of lamellar tissue considering several values of micro-porosity is addressed. RESULTS: Results obtained in this work show that the strength of lamellar bone decreases exponentially with the increase of lacunae porosity concentration. Ultimate stress of non-porous tissue (p=0%) increases with high mineral content, reaching a value of S¯transc=355.40±39.80 MPa for compression in the transversal direction of the fiber bundles, being BMD=1.246g/cm3. The mean value for the longitudinal to transverse strength ratio evaluated for porosity p=0%,1% and 5% and a mineral content BMD=1.2g/cm3, is 2.47:1 for tension and 1.55:1 for compression. These values are in agreement with literature. CONCLUSIONS: Osteocyte lacunae act as stress concentrators, acting as potential stimulus for the bone regeneration process. A novel micromechanical model for the in-plane ultimate stress of lamellar tissue as a function of mineral content and lacunae concentration is presented. Additional considerations about the intralamellar shear stress evolution are also given.

Injectable ultrasound-powered bone-adhesive nanocomposite hydrogel for electrically accelerated irregular bone defect healing.

The treatment of critical-size bone defects with irregular shapes remains a major challenge in the field of orthopedics. Bone implants with adaptability to complex morphological bone defects, bone-adhesive properties, and potent osteogenic capacity are necessary. Here, a shape-adaptive, highly bone-adhesive, and ultrasound-powered injectable nanocomposite hydrogel is developed via dynamic covalent crosslinking of amine-modified piezoelectric nanoparticles and biopolymer hydrogel networks for electrically accelerated bone healing. Depending on the inorganic-organic interaction between the amino-modified piezoelectric nanoparticles and the bio-adhesive hydrogel network, the bone adhesive strength of the prepared hydrogel exhibited an approximately 3-fold increase. In response to ultrasound radiation, the nanocomposite hydrogel could generate a controllable electrical output (-41.16 to 61.82 mV) to enhance the osteogenic effect in vitro and in vivo significantly. Rat critical-size calvarial defect repair validates accelerated bone healing. In addition, bioinformatics analysis reveals that the ultrasound-responsive nanocomposite hydrogel enhanced the osteogenic differentiation of bone mesenchymal stem cells by increasing calcium ion influx and up-regulating the PI3K/AKT and MEK/ERK signaling pathways. Overall, the present work reveals a novel wireless ultrasound-powered bone-adhesive nanocomposite hydrogel that broadens the therapeutic horizons for irregular bone defects.

Evaluation of cortical bone strength using a quantitative ultrasound measurement device in dogs.

This study was performed to evaluate cortical bone strength in dogs using a quantitative ultrasound measurement device. In this study, 16 clinically healthy dogs with no lameness underwent measurement of the ultrasound propagation velocity of cortical bone (namely, speed of sound [SOS]) at the radius and tibia. Additionally, computed tomography examination with a calibration phantom was performed in 10 dogs. We calculated the bone mineral density (BMD) and Young's modulus from the computed tomography data using bone strength evaluation software. SOS, BMD, and Young's modulus were statistically compared between the radius and tibia. In addition, we examined the correlation between SOS and BMD and between SOS and Young's modulus. We also examined the correlation between SOS and age in the 13 dogs whose age was known. BMD and Young's modulus were not significantly different between the radius and tibia, but SOS was significantly different (P<0.05). Moreover, SOS and BMD showed a positive correlation in both radius and tibia. Similarly, SOS and Young's modulus showed a positive correlation. In addition, SOS and age showed a strong positive correlation (radius: r=0.77, P<0.05, tibia: r=0.83, P<0.05). Our finding that SOS of the radius and tibia cortical bone was correlated with BMD and Young's modulus indicates that quantitative ultrasound can be useful for evaluating cortical bone strength in dogs.

Histologic Heterogeneity of Chondrosarcoma Reflected on Bone SPECT/CT.

ABSTRACT: Chondrosarcomas are a heterogeneous group of cartilage-forming tumors. The tumor is graded on areas demonstrating the highest grade. A 71-year-old man underwent bone SPECT/CT to investigate a tumorous lesion on his right femur. Correlating with the pathological findings, the high-grade area showed higher uptake in bone SPECT/CT. This case suggests that bone SPECT/CT could aid in selecting an optimal biopsy site for diagnosis, and determining the proper treatment of patients with suspected chondroid tumors.

From breast cancer cell homing to the onset of early bone metastasis: The role of bone (re)modeling in early lesion formation.

Breast cancer often metastasizes to bone, causing osteolytic lesions. Structural and biophysical changes are rarely studied yet are hypothesized to influence metastasis. We developed a mouse model of early bone metastasis and multimodal imaging to quantify cancer cell homing, bone (re)modeling, and onset of metastasis. Using tissue clearing and three-dimensional (3D) light sheet fluorescence microscopy, we located enhanced green fluorescent protein-positive cancer cells and small clusters in intact bones and quantified their size and spatial distribution. We detected early bone lesions using in vivo microcomputed tomography (microCT)-based time-lapse morphometry and revealed altered bone (re)modeling in the absence of detectable lesions. With a new microCT image analysis tool, we tracked the growth of early lesions over time. We showed that cancer cells home in all bone compartments, while osteolytic lesions are only detected in the metaphysis, a region of high (re)modeling. Our study suggests that higher rates of (re)modeling act as a driver of lesion formation during early metastasis.

Establishing error bounds for internal calibration of quantitative computed tomography.

Opportunistic computed tomography (CT) scans, which can assess relevant osteoporotic bones of interest, offer a potential solution for identifying osteoporotic individuals. CT scans usually do not contain calibration phantoms, so internal calibration methods have been developed to create a voxel-specific density calibration that can be used in opportunistic CT. It remains a challenge, however, to account for potential sources of error in internal calibration, such as beam hardening or heterogeneous internal reference tissues. The purpose of this work was to introduce our internal calibration method that accounts for these variations and to estimate error bounds for the bone mineral density (BMD) measurements taken from internally calibrated scans. The error bounds are derived by incorporating a combination of a Monte Carlo simulation and standard error propagation into our previously established internal calibration method. A cohort of 138 clinical abdominal CT scans were calibrated for BMD assessment with a phantom placed in the field of view and used as the ground truth. Our modified internal calibration method provided error bounds on the same images and was tested to contain the ground truth phantom-calibrated BMD. This was repeated using 10 different internal reference tissue combinations to explore how error bounds are affected by the choice of internal tissue referents. We found that the tissue combination of air, skeletal muscle, and cortical bone yielded the most accurate BMD estimates while maintaining error bounds that were sufficiently conservative to account for sources of error such as beam hardening and heterogeneous tissue samples. The mean difference between the phantom BMD and the BMD resulting from the tissue combination of air, skeletal muscle and cortical bone was 2.12 mg/cc (0.06% BMD error) and 1.13 mg/cc (0.02 % BMD error) for the left and right femur, respectively. Providing error bounds for internal calibration provides a method to explore the influence of internal reference tissues and confidence for BMD estimates.

Accuracy of photon-counting computed tomography for the measurement of bone quality in the knee.

Visualization and quantification of bone microarchitecture in the human knee allows gaining insight into normal bone structure, and into the structural changes occurring in the onset and progression of bone diseases such as osteoporosis and osteoarthritis. However, current imaging modalities have limitations in capturing the intricacies of bone microarchitecture. Photon counting computed tomography (PCCT) is a promising imaging modality that presents high-resolution three-dimensional visualization of bone with a large field of view. However, the potential of PCCT in assessing trabecular microstructure has not been investigated yet. Therefore, this study aimed to evaluate the accuracy of PCCT in quantifying bone microstructure and bone mechanics in the knee. Five human cadaveric knees were scanned ex vivo using a PCCT scanner (Naetom alpha, Siemens, Germany) with an in-plane resolution of 146.5 µm and slice thickness of 100 µm. To assess accuracy, the specimens were also scanned with a high-resolution peripheral quantitative computed tomography (HR-pQCT; XtremeCT II, Scanco Medical, Switzerland) with a nominal isotropic voxel size of 60.7 µm as well as with micro-computed tomography (micro-CT; TESCAN UniTOM XL, Czech Republic) with a nominal isotropic voxel size of 25 µm which can be considered gold standards for in vivo and ex vivo scanning, respectively. The thickness and porosity of the subchondral bone and the microstructure of the underlying trabecular bone were assessed in the load bearing regions of the proximal tibia and distal femur. The apparent Young's modulus was determined by micro-finite element (µFE) analysis of subchondral trabecular bone (STB) in the load bearing regions of the proximal tibia using PCCT, HR-pQCT and micro-CT images. The correlation between PCCT measurements and micro-CT and HR-pQCT, respectively, was calculated. The coefficients of determination (R2) between PCCT and micro-CT based parameters, ranged from 0.69 to 0.87. The coefficients of determination between PCCT and HR-pQCT were slightly higher and ranged from 0.71 to 0.91. Apparent Young's modulus, assessed by µFE analysis of PCCT images, correlated well with that of micro-CT (R2 = 0.80, mean relative difference = 19 %). However, PCCT overestimated the apparent Young's modulus by 47 %, but the correlation (R2 = 0.84) remained strong when compared to HR-pQCT. The results of this study suggest that PCCT can be used to quantify bone microstructure in the knee.

Pluvicto-Induced 18 F-PSMA PET Bone Flare.

ABSTRACT: A 79-year-old man with a history of metastatic prostate cancer was initially treated with Eligard and switched to relugolix in 2021. The 2022 bone scan presented superscan and extensive osseous metastatic lesions; some had intense PSMA uptake on the initial PSMA PET scan without nodal or visceral metastatic lesions. We treated him with Pluvicto and relugolix. The intermediate PSMA scan demonstrated prominent bone marrow PSMA uptake. However, PSA decreased 58.5%. We hypothesized that the patient might have a bone flare. The final PSMA scan confirmed our hypothesis. Based on our knowledge, this is the first case of Pluvicto-induced bone flare.

Ultrasound attenuation of cortical bone correlates with biomechanical, microstructural, and compositional properties.

BACKGROUND: We investigated the relationship of two commonly used quantitative ultrasound (QUS) parameters, speed of sound (SoS) and attenuation coefficient (α), with water and macromolecular contents of bovine cortical bone strips as measured with ultrashort echo time (UTE) magnetic resonance imaging (MRI). METHODS: SoS and α were measured in 36 bovine cortical bone strips utilizing a single-element transducer with nominal 5 MHz center frequency based on the time of flight principles after accommodating for reflection losses. Specimens were then scanned using UTE MRI to measure total, bound, and pore water proton density (TWPD, BWPD, and PWPD) as well as macromolecular proton fraction and macromolecular transverse relaxation time (T2-MM). Specimens were also scanned using microcomputed tomography (µCT) at 9-µm isometric voxel size to measure bone mineral density (BMD), porosity, and pore size. The elastic modulus (E) of each specimen was measured using a 4-point bending test. RESULTS: α demonstrated significant positive Spearman correlations with E (R = 0.69) and BMD (R = 0.44) while showing significant negative correlations with porosity (R = -0.41), T2-MM (R = -0.47), TWPD (R = -0.68), BWPD (R = -0.67), and PWPD (R = -0.45). CONCLUSIONS: The negative correlation between α and T2-MM is likely indicating the relationship between QUS and collagen matrix organization. The higher correlations of α with BWPD than with PWPD may indicate that water organized in finer structure (bound to matrix) provides lower acoustic impedance than water in larger pores, which is yet to be investigated thoroughly. RELEVANCE STATEMENT: This study highlights the importance of future investigations exploring the relationship between QUS measures and all major components of the bone, including the collagenous matrix and water. Investigating the full potential of QUS and its validation facilitates a more affordable and accessible tool for bone health monitoring in clinics. KEY POINTS: • Ultrasound attenuation demonstrated significant positive correlations with bone mechanics and mineral density. • Ultrasound attenuation demonstrated significant negative correlations with porosity and bone water contents. • This study highlights the importance of future investigations exploring the relationship between QUS measures and all major components of the bone.

Bone Biomarkers Based on Magnetic Resonance Imaging.

Magnetic resonance imaging (MRI) is increasingly used to evaluate the microstructural and compositional properties of bone. MRI-based biomarkers can characterize all major compartments of bone: organic, water, fat, and mineral components. However, with a short apparent spin-spin relaxation time (T2*), bone is invisible to conventional MRI sequences that use long echo times. To address this shortcoming, ultrashort echo time MRI sequences have been developed to provide direct imaging of bone and establish a set of MRI-based biomarkers sensitive to the structural and compositional changes of bone. This review article describes the MRI-based bone biomarkers representing total water, pore water, bound water, fat fraction, macromolecular fraction in the organic matrix, and surrogates for mineral density. MRI-based morphological bone imaging techniques are also briefly described.

Quantitative Skeletal Imaging and Image-Based Modeling in Pediatric Orthopaedics.

PURPOSE OF REVIEW: Musculoskeletal imaging serves a critical role in clinical care and orthopaedic research. Image-based modeling is also gaining traction as a useful tool in understanding skeletal morphology and mechanics. However, there are fewer studies on advanced imaging and modeling in pediatric populations. The purpose of this review is to provide an overview of recent literature on skeletal imaging modalities and modeling techniques with a special emphasis on current and future uses in pediatric research and clinical care. RECENT FINDINGS: While many principles of imaging and 3D modeling are relevant across the lifespan, there are special considerations for pediatric musculoskeletal imaging and fewer studies of 3D skeletal modeling in pediatric populations. Improved understanding of bone morphology and growth during childhood in healthy and pathologic patients may provide new insight into the pathophysiology of pediatric-onset skeletal diseases and the biomechanics of bone development. Clinical translation of 3D modeling tools developed in orthopaedic research is limited by the requirement for manual image segmentation and the resources needed for segmentation, modeling, and analysis. This paper highlights the current and future uses of common musculoskeletal imaging modalities and 3D modeling techniques in pediatric orthopaedic clinical care and research.

In Vivo Assessment of Bone Quality Without X-rays.

PURPOSE OF REVIEW: This review summarizes recent advances in the assessment of bone quality using non-X-ray techniques. RECENT FINDINGS: Quantitative ultrasound (QUS) provides multiple measurements of bone characteristics based on the propagation of sound through bone, the attenuation of that sound, and different processing techniques. QUS parameters and model predictions based on backscattered signals can discriminate non-fracture from fracture cases with accuracy comparable to standard bone mineral density (BMD). With advances in magnetic resonance imaging (MRI), bound water and pore water, or a porosity index, can be quantified in several long bones in vivo. Since such imaging-derived measurements correlate with the fracture resistance of bone, they potentially provide new BMD-independent predictors of fracture risk. While numerous measurements of mineral, organic matrix, and bound water by Raman spectroscopy correlate with the strength and toughness of cortical bone, the clinical assessment of person's bone quality using spatially offset Raman spectroscopy (SORS) requires advanced spectral processing techniques that minimize contaminating signals from fat, skin, and blood. Limiting exposure of patients to ionizing radiation, QUS, MRI, and SORS has the potential to improve the assessment of fracture risk and track changes of new therapies that target bone matrix and micro-structure.

Does ethnicity influence bone health index in children? A pilot study.

BACKGROUND: Several pathological conditions can lead to variations in bone mineral content during growth. When assessing bone age, bone mineral content can be estimated without supplementary cost and irradiation. Manual assessment of bone quality using the Exton-Smith index (ESI) and automated assessment of the bone health index (BHI) provided by the BoneXpert® software are available but still not validated in different ethnic groups. OBJECTIVE: Our aim is to provide normative values of the ESI and BHI for healthy European Caucasian and first-generation children of North Africans living in Europe. MATERIALS AND METHODS: A sex- and aged-match population of 214 girls (107 European-Caucasian and 107 North African) and 220 boys (111 European-Caucasian and 109 North African) were retrospectively and consecutively included in the study. Normal radiographs of the left hand and wrist from healthy children were retrieved from those performed in a single institution from 2008 to 2017 to rule out a left-hand fracture. Radiographs were processed by BoneXpert® to obtain the BHI and BHI standard deviation score (SDS). One radiologist, blinded to BHI values, manually calculated ESI for each patient. The variability for both methods was assessed and compared using the standard deviation (SD) of the median (%) for each class of age and sex, and ESI and BHI trends were compared by sex and ethnic group. RESULTS: The final population comprised 434 children ages 3 to 15 years (214 girls). Overall, BHI was lower in North African children (mean = 4.23 for girls and 4.17 in boys) than in European Caucasians (mean = 4.50 for girls and 4.68 in boys) (P < 0.001). Regardless of ethnicity, 29 girls (13.6%) and 34 boys (15.5%) had BHI more than 2 SD from the mean. While correlated to BHI, ESI has a higher variability than BHI and is more pronounced from 8-12 years for both sexes (mean ESI in European Caucasian girls and boys 17.47 and 20.87, respectively) (P < 0.001). ESI showed more than 15% variability in European girls from 8-12 years and a plateau in North African boys from 12 years to 16 years. However, the BHI has less than 15% variability regardless of age and ethnic group. CONCLUSION: BHI may be a reliable tool to detect children with abnormal bone mineral content, with lower variability compared to ESI and with specific trends depending on sex and ethnicity.