Novel techniques for assessment of bone tissue material properties.

PURPOSE OF REVIEW: The purpose of this review will be to shed light on novel techniques for assessment of bone tissue material properties. RECENT FINDINGS: Recently there has been an increase in modalities to investigate bone tissue material properties. Historically, clinicians treating patients with bone disorders have relied upon the use of bone mineral density (BMD) as assessed by dual-energy X-ray absorptiometry (DXA). Although DXA provides an ability to screen at a large-scale population level, it only explains about 60% of the fracture risk. Recent advances include the use of imaging modalities, responses to load, and novel infrared (IR) techniques. SUMMARY: These newer techniques have not reached a point for population level screening; however, they may inform the science of bone biology further and help discern various bone disease states.

Assessment of central cartilaginous tumor of the appendicular bone: inter-observer and intermodality agreement and comparison of diagnostic performance of CT and MRI.

BACKGROUND: Diagnostic performance, inter-observer agreement, and intermodality agreement between computed tomography (CT) and magnetic resonance imaging (MRI) in the depiction of the major distinguishing imaging features of central cartilaginous tumors have not been investigated. PURPOSE: To determine the inter-observer and intermodality agreement of CT and MRI in the evaluation of central cartilaginous tumors of the appendicular bones, and to compare their diagnostic performance. MATERIAL AND METHODS: Two independent radiologists retrospectively reviewed preoperative CT and MRI. Inter-observer and intermodality agreement between CT and MRI in the assessment of distinguishing imaging features, including lesion size, deep endosteal scalloping, cortical expansion, cortical disruption, pathologic fracture, soft tissue extension, and peritumoral edema, were evaluated. The agreement with histopathology and the accuracy of the radiologic diagnoses made with CT and MRI were also analyzed. RESULTS: A total of 72 patients were included. CT and MRI showed high inter-observer and intermodality agreements with regard to size, deep endosteal scalloping, cortical expansion, cortical disruption, and soft tissue extension (ICC = 0.96-0.99, k = 0.60-0.90). However, for the evaluation of pathologic fracture, MRI showed only moderate inter-observer agreement (k = 0.47). Peritumoral edema showed only fair intermodality agreement (k = 0.28-0.33) and moderate inter-observer agreement (k = 0.46) on CT. Both CT and MRI showed excellent diagnostic performance, with high agreement with the histopathology (k = 0.89 and 0.87, respectively) and high accuracy (91.7% for both CT and MRI). CONCLUSION: CT and MRI showed high inter-observer and intermodality agreement in the assessment of several distinguishing imaging features of central cartilaginous tumors of the appendicular bones and demonstrated comparable diagnostic performance.

Neuro-musculoskeletal flexible multibody simulation yields a framework for efficient bone failure risk assessment.

Fragility fractures are a major socioeconomic problem. A non-invasive, computationally-efficient method for the identification of fracture risk scenarios under the representation of neuro-musculoskeletal dynamics does not exist. We introduce a computational workflow that integrates modally-reduced, quantitative CT-based finite-element models into neuro-musculoskeletal flexible multibody simulation (NfMBS) for early bone fracture risk assessment. Our workflow quantifies the bone strength via the osteogenic stresses and strains that arise due to the physiological-like loading of the bone under the representation of patient-specific neuro-musculoskeletal dynamics. This allows for non-invasive, computationally-efficient dynamic analysis over the enormous parameter space of fracture risk scenarios, while requiring only sparse clinical data. Experimental validation on a fresh human femur specimen together with femur strength computations that were consistent with literature findings provide confidence in the workflow: The simulation of an entire squat took only 38 s CPU-time. Owing to the loss (16% cortical, 33% trabecular) of bone mineral density (BMD), the strain measure that is associated with bone fracture increased by 31.4%; and yielded an elevated risk of a femoral hip fracture. Our novel workflow could offer clinicians with decision-making guidance by enabling the first combined in-silico analysis tool using NfMBS and BMD measurements for optimized bone fracture risk assessment.

A PET/MR Imaging Approach for the Integrated Assessment of Chemotherapy-induced Brain, Heart, and Bone Injuries in Pediatric Cancer Survivors: A Pilot Study.

Purpose To develop a positron emission tomography (PET)/magnetic resonance (MR) imaging protocol for evaluation of the brain, heart, and joints of pediatric cancer survivors for chemotherapy-induced injuries in one session. Materials and Methods Three teams of experts in neuroimaging, cardiac imaging, and bone imaging were tasked to develop a 20-30-minute PET/MR imaging protocol for detection of chemotherapy-induced tissue injuries of the brain, heart, and bone. In an institutional review board-approved, HIPAA-compliant, prospective study from April to July 2016, 10 pediatric cancer survivors who completed chemotherapy underwent imaging of the brain, heart, and bone with a 3-T PET/MR imager. Cumulative chemotherapy doses and clinical symptoms were correlated with the severity of MR imaging abnormalities by using linear regression analyses. MR imaging measures of brain perfusion and metabolism were compared among eight patients who were treated with methotrexate and eight untreated age-matched control subjects by using Wilcoxon rank-sum tests. Results Combined brain, heart, and bone examinations were completed within 90 minutes. Eight of 10 cancer survivors had abnormal findings on brain, heart, and bone images, including six patients with and two patients without clinical symptoms. Cumulative chemotherapy doses correlated significantly with MR imaging measures of left ventricular ejection fraction and end-systolic volume, but not with the severity of brain or bone abnormalities. Methotrexate-treated cancer survivors had significantly lower cerebral blood flow and metabolic activity in key brain areas compared with control subjects. Conclusion The feasibility of a single examination for assessment of chemotherapy-induced injuries of the brain, heart, and joints was shown. Earlier detection of tissue injuries may enable initiation of timely interventions and help to preserve long-term health of pediatric cancer survivors. © RSNA, 2017 Online supplemental material is available for this article.

Ultrasonographic assessment of bone erosions in the different subtypes of systemic lupus erythematosus arthritis: comparison with computed tomography.

BACKGROUND: The aim was to determine the accuracy of high-resolution ultrasonography (US) for detecting erosion in the metacarpophalangeal (MCP) and wrist joints of patients with different subtypes of systemic lupus erythematosus (SLE) arthritis, using computed tomography (CT) as the gold-standard reference method. METHOD: The ulnar head, radiocarpal and second to fifth MCP joints in 26 patients with SLE - 9 classified as having rhupus syndrome, 10 as having Jaccoud's arthropathy (JA) and 7 as having non-deforming non-erosive (NDNE) arthritis - were subdivided into areas and bilaterally evaluated for the presence of bone erosion by CT and US. On CT, erosion volume was scored according to the outcome measures in rheumatology-rheumatoid arthritis magnetic resonance imaging (OMERACT-RAMRIS) score. On US, erosions were semi-quantitatively scored 0-3 according to scoring by ultrasound structural erosion (ScUSSe) systems. RESULTS: Erosions were detected by CT in 92/728 areas (12.6 %) and by US in 43/728 areas (5.9 %). Sensitivity, specificity and accuracy of US overall was 36 %, 98 % and 90 % compared with 57 %, 98 % and 93 % in the dorsal and lateral aspects of the second and fifth MCP, which were identified as areas with the best US reliability. Adding wrist joints would capture a larger number of erosions without affecting the accuracy. US detected 90.0 % of CT erosions with bone volume loss >20 % and 51.2 % of erosions with bone volume loss >10 %. Patients with rhupus had a greater number of larger erosions than those with JA or NDNE arthritis, with prevalent involvement of the MCP joints. Overall reliability of US in detecting bone erosions was moderate for rhupus syndrome (0.55) and JA (0.58), but poor for NDNE arthritis (0.10). CONCLUSION: US had moderate sensitivity and excellent specificity for detection and semi-quantitative assessment of bone erosions in SLE.

[Imaging assessment of bone and cartilage destruction in rheumatoid arthritis].

Rheumatoid arthritis (RA) is characterized by synovitis and subsequent joint destruction involving bone and cartilage. Recent therapeutic development have improved outcomes including disease activity and structural progression in RA, and standardized procedures of imaging assessment including modified total Sharp score (mTSS) have contributed largely for the development of therapeutic strategy. In addition, ultrasonography and MRI of joints have been recently emerging as novel imaging methods for RA. Here, we review current imaging assessments of bone and cartilage destruction in RA.

Assessment of scapular morphology and surgical technique as predictors of notching in reverse shoulder arthroplasty.

There has been increased focus on understanding risk factors for scapular notching in reverse shoulder arthroplasty (RSA). We conducted a study to evaluate the scapular notching index and other factors associated with the occurrence of scapular notching. Ninety-one patients treated with primary RSA were followed for a minimum of 24 months. Patients' radiographic assessments were grouped by Nerot grade of scapular notching (group 1, grades 0 and 1; group 2, grades 2, 3, 4). Group mean differences were compared for preoperative scapular neck angle (SNA), prosthesis-scapular neck angle (PSNA), peg glenoid rim distance (PGRD), notching index, and clinical outcomes. There was no significant difference in mean (SD) notching index between group 1, 31.8 (4.4), and group 2, 33.1 (7.3), and there were no significant differences in SNA (102.8° vs 105.4°; P=.3), PSNA (125.8° vs 125.4°; P=.82), PGRD (15.4 vs 16.8 mm; P=.47), or clinical outcomes between the groups. Our results suggest that Grammont-style prostheses have a higher rate of notching regardless of optimal PGRD and variations in PSNA. Perhaps with certain scapular morphology, prosthetic design may be a more significant contributor to notching.

Computed tomography assessment of bone lesions in patients with POEMS syndrome.

OBJECTIVES: To describe the imaging findings on computed tomography (CT) and skeletal survey (SS) in patients with POEMS syndrome. METHODS: We retrospectively reviewed, with institutional review board approval, the dysproteinemia database at our institution for patients with new diagnosis of POEMS syndrome between January 1998 and December 2008. Twenty-four patients were identified with PET/CT or CT and had skeletal survey (SS) available for review. RESULTS: Twenty-four patients were included in the study group with median age of 47 years. All CTs demonstrated at least one sclerotic lesion. The most common pattern was multiple small lesions, with 18 patients (75%) having at least 5 lesions less than 1 cm. The larger lesions had a central lytic component and were FDG avid. SS had a false negative rate of 36% (8 patients). Serial CT after treatment showed a decrease in size and number of sclerotic lesions in 53% of cases (13 patients), the majority showing increased sclerosis. Two patients had complete resolution of sclerotic lesions. CONCLUSIONS: CT identified sclerotic lesions in all study patients with POEMS syndrome, the majority being less than 1 cm in size, which were not identified radiographically. CT may demonstrate increased sclerosis or even resolution of sclerotic lesions corresponding to treatment response. KEY POINTS: • CT has high sensitivity in identifying sclerotic lesions in POEMS syndrome • Most common CT patterns are multiple, less than 1 cm, sclerotic lesions • Larger lesions have lytic centres and sclerotic margins • Skeletal surveys may have a false negative rate of 36% • Treatment response includes increased sclerosis, decrease in size or resolution of lesions.

Methods of assessment of tophus and bone erosions in gout using dual-energy CT: reproducibility analysis.

This study aims to evaluate the intraobserver and interobserver reproducibility of the tophus urate volume, erosion volume, and the erosion score measurements in patients with gout by using dual-energy CT (DECT) scans comparing their bone erosion volumes against bone erosion scores and also to determine a valid measure of joint destruction in chronic gout. Sixty-six subjects underwent DECT scans of the hands or feet. Two independent observers measured the tophus urate volumes and bone erosion volumes using automated volume assessment software and the erosion scores based on the rheumatoid arthritis magnetic resonance imaging score (RAMRIS). The intraobserver and interobserver reproducibility were analyzed by intraclass correlation coefficient (ICC) and limits of agreements analysis. The relationship between erosion volumes and erosion scores was analyzed. The intraobserver and interobserver ICC for tophus urate volume measurements (n = 636) were 1.000 (95 % confidence interval (95 % CI) 1.000 to 1.000) and 1.000 (95 % CI 1.000 to 1.000), 0.999 (0.999, 0.999) and 0.999 (0.999, 0.999) for bone erosion volumes (n = 350), 0.937 (0.928, 0.946) and 0.899 (0.883, 0.912) for erosion scores (n = 350). Strong positive correlations were demonstrated between individual erosion volumes and scores (r s = 0.914, p < 0.001) as well as total erosion volume and score per patient (r = 0.838-0.867, p < 0.001). This study demonstrated a high reproducibility of tophus urate volumes, erosion volumes, and erosion score measurements using DECT. Erosion volumes show to be a more direct and accurate method to evaluate bone erosion compared with erosion score, strongly supporting it as a superior and standard measure of structural joint damage in gout.

Diagnostic value of high-resolution peripheral quantitative computed tomography (HR-pQCT) in the qualitative assessment of cribra orbitalia: a preliminary study.

Cribra orbitalia are a porotic or sieve-like lesions in the bony orbital roof. This characteristic has frequently been detected in palaeopathological skulls from many parts of the world and has been the object of extensive research. Our objective was to determine if high-resolution peripheral quantitative computed tomography (HR-pQCT) could produce reliable information in the study of cribra orbitalia. Seven skulls displaying cribra orbitalia were investigated by HR-pQCT. The two-dimensional slices were compared with histological sections. The HR-pQCT images and histological sections showed similar results, i.e. two groups of lesions with different characteristics. HR-pQCT can be of great value in palaeopathological research. It is a nondestructive, fast and precise technique that allows an easy evaluation of the bone architecture without destruction of the sample.

Assessment of bone health in children with disabilities.

Evaluating the bone health of children with disabilities is challenging and requires consideration of many factors in clinical decision-making. Feeding problems and growth deficits, immobility/inability to bear weight, effect of medications, and the nature of his or her disease can all directly affect a child's overall picture of bone health. Familiarity with the tools available to assess bone health is important for practitioners. The most commonly used method to assess bone density, dual energy x-ray absorptiometry, can be performed effectively when one appreciates the techniques that make scanning patients with disabilities possible. There are specific techniques that are especially useful for measuring bone density in children with disabilities; standard body sites are not always obtainable. Consideration of clinical condition and treatment must be considered when interpreting dual energy x-ray absorptiometry scans. Serial measurements have been shown to be effective in monitoring change in bone content and in providing information on which to base decisions regarding medical treatment.

Tarsal navicular bone size in diabetics: radiographic assessment.

OBJECTIVE: To test the anecdotal observation that isolated navicular collapse is associated with diabetes mellitus, we quantified the size of the tarsal navicular bone in subjects with and without diabetes and tested for association of size with age, height, weight, body mass index (BMI), gender, smoking, bone mineral density (BMD), duration, and level of control of diabetes. MATERIALS AND METHODS: Ankle radiographs of 200 patients (122 female; 78 male; mean age 58 years [27-89]), 100 with type II diabetes and 100 age- and gender-matched controls were selected and reviewed. The anteroposterior (AP) dimension of the mid-navicular bone was measured from lateral radiographs. For standardization, the supero-inferior (SI) dimension of the calcaneal was measured and the navicular-calcaneus ratio calculated. Statistical evaluation included independent sample t tests and linear regression analyses. RESULTS: Diabetic subjects had a significantly smaller navicular AP dimension and navicular-calcaneus ratio compared with controls (p = 0.02 and p = 0.0001 respectively). Age, gender, height and duration of diabetes had no association with the navicular-calcaneus ratio. The navicular-calcaneus ratio was inversely correlated with weight (p = 0.01) and BMI (p < 0.001) and directly correlated with smoking (p = 0.04). Reliability of the radiographic measurements was excellent (ICC 0.80-0.97; SEM 0.3-1.7 mm). CONCLUSION: The anteroposterior dimension of the navicular is smaller in type II diabetic subjects than in age- and gender-matched controls. We hypothesize that this might be due to navicular collapse of multifactorial causes.

Routine perinatal and paediatric post-mortem radiography: detection rates and implications for practice.

BACKGROUND: Routine perinatal and paediatric post-mortem plain radiography allows for the diagnosis and assessment of skeletal dysplasias, fractures and other bony abnormalities. OBJECTIVE: The aim of this study was to review the diagnostic yield of this practice. MATERIALS AND METHODS: We identified 1,027 cases performed in a single institution over a 2½-year period, including babygrams (whole-body examinations) and full skeletal surveys. Images were reported prior to autopsy in all cases. Radiology findings were cross-referenced with the autopsy findings using an autopsy database. We scored each case from 0 to 4 according to the level of diagnostic usefulness. RESULTS: The overall abnormality rate was 126/1,027 (12.3%). There was a significantly higher rate of abnormality when a skeletal survey was performed (18%) rather than a babygram (10%; P < 0.01); 90% (665/739) of babygrams were normal. Of the 74 abnormal babygrams, we found 33 incidental non-contributory cases, 19 contributory, 20 diagnostic, and 2 false-positive cases. There were only 2 cases out of 739 (0.27%) in whom routine post-mortem imaging identified potentially significant abnormalities that would not have been detected if only selected imaging had been performed. A policy of performing selected, rather than routine, foetal post-mortem radiography could result in a significant cost saving. CONCLUSION: Routine post-mortem paediatric radiography in foetuses and neonates is neither diagnostically useful nor cost-effective. A more evidence-based, selective protocol should yield significant cost savings.

The assessment of round lytic lesions in sternotomies.

OBJECTIVE: The aims of this study were to define imaging findings and to identify any predisposing factors for the development of the round lytic lesion across the margins of sternotomy during the process of bone healing. METHODS: We searched all chest CT scans performed between 2007 and 2012 and selected patients who had three studies performed in the recent, late and latest post-operative periods. Patients presenting any complications related to wound healing were excluded from the study. CT features of the sternotomy and possible instability factors were assessed. RESULTS: From 15689 chest CT images analysed, 68 patients fulfilled the criteria. The development of a round lytic lesion was observed in 35 and 39 patients in the late and latest post-operative periods, respectively, and there was an association between mild misalignment of margins in the recent post-operative period and the development of a round lesion in the follow-up periods (p=0.010 and p=0.002, respectively). CONCLUSION: Sternotomies exhibit a delayed and unusual pattern of bone healing, and minimal instability factors during bone closure could trigger the development of a lytic lesion that is part of the normal healing process. ADVANCES IN KNOWLEDGE: This lytic bone lesion is part of the bone healing, and its appearance should not be mistaken as infection or malignancy, even in a suggestive clinical setting.

Phalangeal quantitative ultrasound: cheaper methods for screening and follow-up of bone pathologies in HIV-infected women?

This study estimated the prevalence of bone pathologies in a cohort of HIV-infected women in comparison with a cohort of HIV-negative women. Bone mineral density was measured by phalangeal quantitative ultrasound (AD-SoS: amplitude- dependent speed of sound; UBPI: ultrasound bone profile index). Risk of fracture, expressed by UBPI, was considered for value <0.39. Comparisons between groups and multivariate analyses were carried out using an ANOVA model. Correlations were evaluated using the Pearson correlation coefficient. Osteopenia and osteoporosis were present in 34.4% and 2% of patients, respectively. UBPI was pathologic in 5.7%. In a multivariate linear regression model significant correlations were found between AD-SoS z-score, duration of HIV-infection and BMI value. We also compared our cohort with 499 HIV-negative women as a historical control group of healthy subjects. AdSoS (2100 versus 2070 m/s) and UBPI (0.89 versus 0.74) were lower in HIV-infected women (p<0.001). Significant differences were also found in T-score values (p = 0.0013). These data show a high prevalence of bone diseases in women with HIV infection, correlated with duration of HIV-infection and BMI values. This non-invasive technique opens up new interesting perspectives, suggesting a possible use for bone mass screening in HIV-infected women.

Establishment of efficacy and safety assessment of human adipose tissue-derived mesenchymal stem cells (hATMSCs) in a nude rat femoral segmental defect model.

Human adipose tissue-derived mesenchymal stem cell (hATMSC) have emerged as a potentially powerful tool for bone repair, but an appropriate evaluation system has not been established. The purpose of this study was to establish a preclinical assessment system to evaluate the efficacy and safety of cell therapies in a nude rat bone defect model. Segmental defects (5 mm) were created in the femoral diaphyses and transplanted with cell media (control), hydroxyapatite/tricalcium phosphate scaffolds (HA/TCP, Group I), hATMSCs (Group II), or three cell-loading density of hATMSC-loaded HA/TCP (Group III-V). Healing response was evaluated by serial radiography, micro-computed tomography and histology at 16 weeks. To address safety-concerns, we conducted a GLP-compliant toxicity study. Scanning electron microscopy studies showed that hATMSCs filled the pores/surfaces of scaffolds in a cell-loading density-dependent manner. We detected significant increases in bone formation in the hATMSC-loaded HA/TCP groups compared with other groups. The amount of new bone formation increased with increases in loaded cell number. In a toxicity study, no significant hATMSC-related changes were found in body weights, clinical signs, hematological/biochemical values, organ weights, or histopathological findings. In conclusion, hATMSCs loaded on HA/TCP enhance the repair of bone defects and was found to be safe under our preclinical efficacy/safety hybrid assessment system.

Diabetes and bone: advantages and limitations of radiological, radionuclide and hybrid techniques in the assessment of diabetic foot.

A common cause of morbidity and mortality in diabetic patients are foot infection/complications often leading to amputation of lower extremities. Various radiological and radionuclide techniques are available for the assessment of diabetic patients with bone or soft tissue infections. However, there are several advantages and limitations. The major limitation of all these techniques is their inability to accurately differentiate osteomyelitis from charcot's/neuropathic joints. Radiologically, magnetic resonance imaging (MRI) is the technique of choice and a radiolobeled white cell scan is a useful nuclear medicine technique in the evaluation of diabetic patients with suspected foot infection. In this review we discuss the efficacy of radiological and radionuclide techniques in the assessment of diabetic foot infection.

Utility of delayed whole-body bone scintigraphy after directed three-phase scintigraphy.

OBJECTIVE: The purpose of this study was to determine the diagnostic yield and clinical importance of delayed whole-body bone scintigraphy in directed three-phase examinations. MATERIALS AND METHODS: The records of 400 consecutively registered patients who underwent combined three-phase and delayed whole-body (99m)Tc-methylene diphosphonate bone scintigraphy for a variety of indications were reviewed. Clinical indications, findings, recommendations, and outcome were assessed. RESULTS: Three-phase bone scintigraphy was performed on 156 men and boys and 244 women and girls (61%). Fifty-two patients (13%) were 17 years old or younger, and 236 patients (59%) were older than 40 years. The mean increase in study duration due to whole-body imaging was 25 minutes (range, 21-31 minutes). Excluding the three-phase area of interest, the whole-body examination had a normal tracer distribution in 131 examinations (33%), showed solely degenerative changes in 103 (26%), and showed findings unrelated to the area of interest in 166 patients (41%). In no case did the findings outside the area of interest alter the diagnosis or diagnostic certainty in the three-phase study, but those findings did generate 82 recommendations for additional diagnostic investigation. As a direct result of the recommendations, clinicians requested 18 radiographic, two CT, one MRI, and one ultrasound examinations, one additional bone scan, and two referrals to a consultant. Recommendations based on findings outside the three-phase area of interest affected treatment in one case: Temporomandibular joint uptake resulted in a referral for physical therapy. CONCLUSION: For most indications, delayed whole-body imaging after directed three-phase bone scintigraphy does not improve diagnostic yield, does not alter patient care, and may be an unnecessary use of medical resources.