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Ultrasound imaging for bone is a difficult task in the field of medical ultrasound. Compared with other phase array techniques, the synthetic aperture (SA) has a better lateral resolution but a limited imaging depth due to the limited ultrasonic energy emitted by the single emitter in each transmission. In contrast, the virtual source (VS) synthetic aperture allows a simultaneous multi-element emission and could provide a higher ultrasonic incident energy in each transmission. Therefore, the VS might achieve a high imaging quality at a deeper depth for bone imaging than the traditional SA. In this study, we proposed the virtual source phase shift migration (VS-PSM) method to achieve ultrasonic imaging of the deeper bone defect featured in the multilayer structure. The proposed VS-PSM method was validated using standard soft tissue phantom and printed bone phantom with artificial defects. The image quality was evaluated in terms of contrast-to-noise ratios (CNR) and amplitudes of scatters and defects at different imaging depths. The results showed that the VS-PSM method could achieve a high imaging quality of the soft tissues with a significant improvement in the scattering amplitude and without a significant sacrifice of the lateral and axial resolution. The PSM was superior to the DAS in suppressing the background noise in the images. Compared with the traditional SA-PSM, the VS-PSM method could image deeper bone defects at different ultrasonic frequencies, with an average improvement of 50% in CNR. In conclusion, this study demonstrated that the proposed VS-PSM method could image deeper bone defects and might help the diagnosis of bone disease using ultrasonic imaging. [ABSTRACT FROM AUTHOR]

Acidic amino acid peptides have a high affinity for bone. Previously, we demonstrated that radiogallium complex-conjugated oligo-acidic amino acids possess promising properties as bone-seeking radiopharmaceuticals. Here, to elucidate the effect of stereoisomers of Glu in Glu-containing peptides [(Glu)14] on their accumulation in the kidney, the biodistributions of [67Ga]Ga-N,N′-bis-[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N′-diacetic acid-conjugated (l-Glu)14 ([67Ga]Ga-HBED-CC-(l-Glu)14), [67Ga]Ga-HBED-CC-(d-Glu)14, [67Ga]Ga-HBED-CC-(dl-Glu)14, and [67Ga]Ga-HBED-CC-(d-Glu-l-Glu)7 were compared. Although the accumulation of these compounds in the bone was comparable, their kidney accumulation and retention were strikingly different, with [67Ga]Ga-HBED-CC-(d-Glu-l-Glu)7 exhibiting the lowest level of kidney accumulation among these compounds. Repeated d- and l-peptides may be a useful method for reducing renal accumulation in some cases. [ABSTRACT FROM AUTHOR]

Imaging plays a central role in the management of patients with bone tumors. A number of imaging modalities are available, with different techniques having unique applications that render their use advantageous for various clinical purposes. Coupled with detailed clinical assessment, radiological imaging can assist clinicians in reaching a proper diagnosis, determining appropriate management, evaluating response to treatment, and monitoring for tumor recurrence. Although radiography is still the initial imaging test of choice for a patient presenting with a suspected bone tumor, technological innovations in the last decades have advanced the role of other imaging modalities for assessing bone tumors, including advances in computed tomography, magnetic resonance imaging, scintigraphy, and hybrid imaging techniques that combine two existing modalities, providing clinicians with diverse tools for bone tumor imaging applications. Determining the most suitable modality to use for a particular application requires familiarity with the modality in question, its advancements, and its limitations. This review highlights the various imaging techniques currently available and emphasizes the latest developments in imaging, offering a framework that can help guide the imaging of patients with bone tumors. [ABSTRACT FROM AUTHOR]

Abstract Background Relapsing Polychondritis(RP) is a rare rheumatic immune disease. As with most diseases, if intervention is delayed, the patient’s prognosis is worse. Currently, the diagnostic criteria used in clinical practice do not include CT, PET/CT, SPECT/CT and other new imaging examinations that have developed rapidly in recent years. However, these examinations have some special manifestations for RP, which can help clinicians diagnose RP earlier and distinguish it from other diseases. Case presentation These five RP patients all had respiratory symptoms such as cough and wheezing as the first symptom, which could not be diagnosed in time according to the previous diagnostic criteria. The clinical data of the five patients are listed in Table 1. The relatively specific manifestations of SPECT/CT examination provided clinicians with very valuable clues to help them advance the diagnosis time. Conclusions The application of SPECT/CT bone imaging in early diagnosing RP proves to be effective, enabling clinicians to intervene promptly and enhance the overall well-being and quality of life for individuals affected by this condition.

Background: Relapsing Polychondritis(RP) is a rare rheumatic immune disease. As with most diseases, if intervention is delayed, the patient's prognosis is worse. Currently, the diagnostic criteria used in clinical practice do not include CT, PET/CT, SPECT/CT and other new imaging examinations that have developed rapidly in recent years. However, these examinations have some special manifestations for RP, which can help clinicians diagnose RP earlier and distinguish it from other diseases. Case presentation: These five RP patients all had respiratory symptoms such as cough and wheezing as the first symptom, which could not be diagnosed in time according to the previous diagnostic criteria. The clinical data of the five patients are listed in Table 1. The relatively specific manifestations of SPECT/CT examination provided clinicians with very valuable clues to help them advance the diagnosis time. Conclusions: The application of SPECT/CT bone imaging in early diagnosing RP proves to be effective, enabling clinicians to intervene promptly and enhance the overall well-being and quality of life for individuals affected by this condition. [ABSTRACT FROM AUTHOR]

This study aims at assessing approaches for generating high‐resolution magnetic resonance imaging‐ (MRI‐) based synthetic computed tomography (sCT) images suitable for orthopedic care using a deep learning model trained on low‐resolution computed tomography (CT) data. To that end, paired MRI and CT data of three anatomical regions were used: high‐resolution knee and ankle data, and low‐resolution hip data. Four experiments were conducted to investigate the impact of low‐resolution training CT data on sCT generation and to find ways to train models on low‐resolution data while providing high‐resolution sCT images. Experiments included resampling of the training data or augmentation of the low‐resolution data with high‐resolution data. Training sCT generation models using low‐resolution CT data resulted in blurry sCT images. By resampling the MRI/CT pairs before the training, models generated sharper images, presumably through an increase in the MRI/CT mutual information. Alternatively, augmenting the low‐resolution with high‐resolution data improved sCT in terms of mean absolute error proportionally to the amount of high‐resolution data. Overall, the morphological accuracy was satisfactory as assessed by an average intermodal distance between joint centers ranging from 0.7 to 1.2 mm and by an average intermodal root‐mean‐squared distances between bone surfaces under 0.7 mm. Average dice scores ranged from 79.8% to 87.3% for bony structures. To conclude, this paper proposed approaches to generate high‐resolution sCT suitable for orthopedic care using low‐resolution data. This can generalize the use of sCT for imaging the musculoskeletal system, paving the way for an MR‐only imaging with simplified logistics and no ionizing radiation. [ABSTRACT FROM AUTHOR]

Acidic amino acid peptides have a high affinity for bone. Previously, we demonstrated that radiogallium complex-conjugated oligo-acidic amino acids possess promising properties as bone-seeking radiopharmaceuticals. Here, to elucidate the effect of stereoisomers of Glu in Glu-containing peptides [(Glu)14] on their accumulation in the kidney, the biodistributions of [67Ga]Ga-N,N′-bis-[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N′-diacetic acid-conjugated (l-Glu)14 ([67Ga]Ga-HBED-CC-(l-Glu)14), [67Ga]Ga-HBED-CC-(d-Glu)14, [67Ga]Ga-HBED-CC-(dl-Glu)14, and [67Ga]Ga-HBED-CC-(d-Glu-l-Glu)7 were compared. Although the accumulation of these compounds in the bone was comparable, their kidney accumulation and retention were strikingly different, with [67Ga]Ga-HBED-CC-(d-Glu-l-Glu)7 exhibiting the lowest level of kidney accumulation among these compounds. Repeated d- and l-peptides may be a useful method for reducing renal accumulation in some cases.

MR bone imaging is a recently introduced technique, that allows visualization of bony structures in good contrast against adjacent structures, like CT. Although CT has long been considered the modality of choice for bone imaging, MR bone imaging allows visualization of the bone without radiation exposure while simultaneously allowing conventional MR images to be obtained. Accordingly, MR bone imaging is expected as a new imaging technique for the diagnosis of miscellaneous spinal diseases. This review presents several sequences used in MR bone imaging including black bone imaging, ultrashort/zero echo time (UTE/ZTE) sequences, and T1-weighted 3D gradient-echo sequence. We also illustrate clinical cases in which spinal lesions could be effectively demonstrated on MR bone imaging, performed in most cases using a 3D gradient-echo sequence at our institution. The lesions presented herein include degenerative diseases, tumors and similar diseases, fractures, infectious diseases, and hemangioma. Finally, we discuss the differences between MR bone imaging and previously reported techniques, and the limitations and future perspectives of MR bone imaging. [ABSTRACT FROM AUTHOR]

X-ray-induced acoustic computed tomography (XACT) is a unique hybrid imaging modality that combines high X-ray absorption contrast with high ultrasonic resolution. X-ray radiography and computerized tomography (CT) are currently the gold standards for 2-D and 3-D imaging of skeletal tissues though there are important properties of bone, such as elasticity and speed of sound (SOS), that these techniques cannot measure. Ultrasound is capable of measuring such properties though current clinical ultrasound scanners cannot be used to image the interior morphology of bones because they fail to address the complicated physics involved for exact image reconstruction; bone is heterogeneous and composed of layers of both cortical and trabecular bone, which violates assumptions in conventional ultrasound imaging of uniform SOS. XACT, in conjunction with the time-reversal algorithm, is capable of generating precise reconstructions, and by combining elements of both X-ray and ultrasound imaging, XACT is potentially capable of obtaining more information than any single of these techniques at low radiation dose. This article highlights X-ray-induced acoustic detection through linear scanning of an ultrasound transducer and the time-reversal algorithm to produce the first-ever XACT image of a bone sample. The results of this study should prove to enhance the potential of XACT imaging in the evaluation of bone diseases for future clinical use.

Ultra-short echo time (UTE) MRI with post-processing is a promising technique in bone imaging that produces a similar contrast to computed tomography (CT). Here, we propose a 3D slab-selective ultrashort echo time (UTE) sequence together with image post-processing to image bone structures in the lumbar spine. We also explore the intermodality agreement between the UTE and CT images. The lumbar spines of two healthy volunteers were imaged with 3D UTE using five different resolutions to determine the best imaging protocol. Then, four patients with low back pain were imaged with both the 3D UTE sequence and CT to investigate agreement between the imaging methods. Two other patients with low back pain were then imaged with the 3D UTE sequence and clinical conventional T1-weighted and T2-weighted fast spin-echo (FSE) MRI sequences for qualitative comparison. The 3D UTE sequence together with post-processing showed high contrast images of bone and high intermodality agreement with CT images. In conclusion, post-processed slab-selective UTE imaging is a feasible approach for highlighting bone structures in the lumbar spine and demonstrates significant anatomical correlation with CT images.

Bone microarchitecture has several clinical implications over and above estimating bone strength. Computed tomography (CT) analysis mainly uses high-resolution peripheral quantitative CT and micro-CT, research imaging techniques, most often limited to peripheral skeleton assessment. Ultra-high-resolution (UHR) CT and photon-counting detector CT, two commercially available techniques, provide images that can approach the spatial resolution of the trabeculae, bringing bone microarchitecture analysis into clinical practice and improving depiction of bone vascularization, tumor matrix, and cortical and periosteal bone. This review presents bone microarchitecture anatomy, principles of analysis, reference measurements, and an update on the performance and potential clinical applications of these new CT techniques. We also share our clinical experience and technical considerations using an UHR-CT device. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a common degenerative joint disease that affects millions of people worldwide. Magnetic resonance imaging (MRI) has emerged as a powerful tool for the evaluation and monitoring of OA due to its ability to visualize soft tissues and bone with high resolution. This review aims to provide an overview of the current state of MRI in OA, with a special focus on the knee, including protocol recommendations for clinical and research settings. Furthermore, new developments in the field of musculoskeletal MRI are highlighted in this review. These include compositional MRI techniques, such as T2 mapping and T1rho imaging, which can provide additional important information about the biochemical composition of cartilage and other joint tissues. In addition, this review discusses semiquantitative joint assessment based on MRI findings, which is a widely used method for evaluating OA severity and progression in the knee. We analyze the most common scoring methods and discuss potential benefits. Techniques to reduce acquisition times and the potential impact of deep learning in MR imaging for OA are also discussed, as these technological advances may impact clinical routine in the future. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to develop an optimized formulation for labeling a third-generation bisphosphonate, zoledronic acid with [99mTc] Tc to achieve the best formulation in preparing an ideal skeletal radiotracer. Radiocomplex yield and purity, stability, biodistribution and imaging in normal rat were investigated. Methods: The samples containing different amounts of zoledronic acid, ascorbic acid and stannous chloride were prepared and labeled with [99mTc]technetium pertechnetate. TLC methods were used to determine the radiochemical purity. The stability was determined in saline and human serum solutions. Lipophilicity was calculated by measuring radio-complex that was divided between organic and aqueous phases. In vitro bone affinity was studied through hydroxyapatite binding assays. Considering the decomposition of radioactivity, biodistribution of radio-complex was assessed based on the percentage of injected activity per gram of organ (% IA/g). Results: [99mTc]Tc-zoledronic acid was prepared easily with high yield while 100 µg, 0.34 µmol of zoledronic acid as a ligand and 100 µg, 0.44 µmol SnCl2 as a reducing agent were used. Radiochemical purity of radio-complex was more than 99% with specific activity of 8050 MBq/µmol. The radio-complex showed rapid blood washout along with high bone uptake value (4.53 ± 0.14 % IA/g at 2 h post injection). Conclusion: Under optimized condition, [99mTc]Tc-zoledronic acid was prepared with high purity and stability together with high bone affinity and rapid blood clearance, make this radio-complex an ideal agent with great potential for skeletal imaging. [ABSTRACT FROM AUTHOR]

Recommendations on study designs that adequately evaluate the in-life effects leading to juvenile bone toxicity, the various imaging modalities that can aid interpretation of the bone effects, biomarkers that may be useful, and regulatory issues were presented in this 2020 ACT symposium. The pathologies encountered in past studies were briefly mentioned. The first speaker covered study design and the numbers of juveniles that may be necessary to power the evaluation. Changes in the International Council for Harmonisation (IHC) guidelines were reviewed. The second speaker launched the rest of the symposium by describing the tools that may help assess juvenile bone toxicity, specifically those used to monitor bone toxicity, healing, and remodeling as they relate or drive the study design including model, species selection, and age. The third speaker addressed in more depth the micro-Computed Tomography (CT) applications in juvenile toxicology for evaluation of skeletal elements and bone growth in both embryo-fetal development (EFD) and pre and postnatal development (PPND) studies. Lastly, a regulatory perspective on strategies to assess juvenile bone toxicity and the concerns of the regulatory agency with respect to these potential changes in the juvenile population was addressed. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the added value of ultra-short echo time (UTE) and fast field echo resembling a CT using restricted echo-spacing (FRACTURE) MR sequences in the assessment of the osseous cervical spine using CT as reference. Materials and methods: Twenty-seven subjects underwent postmortem CT and MRI within 48 h. Datasets were anonymized and analyzed retrospectively by two radiologists. Morphological cervical spine alterations were rated on CT, UTE and FRACTURE images. Afterward, neural foraminal stenosis was graded on standard MR and again after viewing additional UTE/FRACTURE sequences. To evaluate interreader and intermodality reliability, intra-class correlation coefficients (ICC) and for stenosis grading Wilcoxon-matched-pairs testing with multiple comparison correction were calculated. Results: Moderate interreader reliability (ICC = 0.48–0.71) was observed concerning morphological findings on all modalities. Intermodality reliability was good between modalities regarding degenerative vertebral and joint alterations (ICC = 0.69–0.91). Compared to CT neural stenosis grades were more often considered as nonsignificant on all analyzed MR sequences. Neural stenosis grading scores differed also significantly between specific bone imaging sequences, UTE and FRACTURE, to standard MR sequences. However, no significant difference was observed between UTE and FRACTURE sequences. Conclusion: Compared to CT as reference, UTE or FRACTURE sequence added to standard MR sequences can deliver comparable information on osseous cervical spine status. Both led to changes in clinically significant stenosis gradings when added to standard MR, mainly reducing the severity of neural foramina stenosis. [ABSTRACT FROM AUTHOR]

Objective: To investigate the impact of reduced SPECT acquisition time on reconstructed image quality for diagnostic purposes. Method: Data from five patients referred for a routine bone SPECT/CT using the standard multi-bed SPECT/CT protocol were reviewed. The acquisition time was 900 s using gating technique; SPECT date was resampled into reduced data sets of 480 s, 450 s, 360 s and 180 s acquisition duration per bed position. Each acquisition time was reconstructed using a fixed number of subsets (8 subsets) and 4, 8, 12, and 16 iterations, followed by a post-reconstruction 3D Gaussian filter of 8 mm FWHM. Two Nuclear Medicine physicians analysed all images independently to score image quality, noise and diagnostic confidence based on a pre-defined 4-point scale. Results: Our result showed that the most frequently selected categories for 480 s and 450 s images were good image quality, average noise and fair confidence, particularly at lower iteration numbers 4 and 8. For the shortened acquisition time of 360 s and 180 s, statistical significance was observed in most reconstructed images compared with 900 s. Conclusion: The SPECT/CT can significantly shorten the acquisition time with maintained image quality, noise and diagnostic confidence. Therefore, acquiring data over 480 s and 450 s is feasible for WB-SPECT/CT bone scans to provide an optimal balance between acquisition time and image quality. [ABSTRACT FROM AUTHOR]

The estimation of BMD with CT scans requires a calibration method, usually based on a phantom. In asynchronous calibration, the phantom is scanned separately from the patient. A standardized acquisition protocol must be used to avoid variations between patient and phantom. However, variations can still be induced, for example, by temporal fluctuations or patient characteristics. Based on the further use of 739 forensic and 111 clinical CT scans, this study uses the proximal femur BMD value ("total hip") to assess asynchronous calibration accuracy, using in-scan calibration as ground truth. It identifies the parameters affecting the calibration accuracy and quantifies their impact. For time interval and table height, the impact was measured by calibrating the CT scan twice (once using the phantom scan with closest acquisition parameters and once using a phantom scan with standard values) and comparing the calibration accuracy. For other parameters such as body weight, the impact was measured by computing a linear regression between parameter values and calibration accuracy. Finally, this study proposes correction methods to reduce the effect of these parameters and improve the calibration accuracy. The BMD error of the asynchronous calibration, using the phantom scan with the closest acquisition parameters, was −1.2 ± 1.7% for the forensic and − 1.6 ± 3.5% for the clinical dataset. Among the parameters studied, time interval and body weight were identified as the main sources of error for asynchronous calibration, followed by table height and reconstruction kernel. Based on these results, a correction method was proposed to improve the calibration accuracy. Lay Summary: In musculoskeletal radiology and biomechanics, BMD is a commonly used parameter to assess bone quality, bone strength, and identify bone pathologies, such as osteoporosis. BMD values can be extracted from CT scans, which are routinely performed in radiology centers. Obtaining BMD values requires an additional calibration step to transform the original CT into quantitative CT scans. The calibration method is typically based on a reference object with known densities, the calibration phantom, which is scanned with the patient or separately. In case the phantom is scanned separately, the calibration accuracy can be affected by various parameters related to the patient or to the CT acquisition protocol. In this study, we aim to identify these parameters, quantify their impact and propose a correction method to improve the calibration accuracy. Among the parameters studied, we found that the time interval between phantom and patient scans and the patient's body weight had the largest impact on the resulting BMD accuracy. Therefore, we recommend performing the phantom scan as soon as possible before or after the patient scan and applying a weight correction to the scan. Graphical Abstract [ABSTRACT FROM AUTHOR]

PurposeTo develop quantitative susceptibility mapping (QSM) of bone using an ultrashort echo time (UTE) gradient echo (GRE) sequence for signal acquisition and a bone-specific effective transverse relaxation rate ( R2*) to model water-fat MR signals for field mapping.MethodsThree-dimensional radial UTE data (echo times ≥ 40 μs) was acquired on a 3 Tesla scanner and fitted with a bone-specific signal model to map the chemical species and susceptibility field. Experiments were performed ex vivo on a porcine hoof and in vivo on healthy human subjects (n = 7). For water-fat separation, a bone-specific model assigning R2* decay mostly to water was compared with the standard models that assigned the same decay for both fat and water. In the ex vivo experiment, bone QSM was correlated with CT.ResultsCompared with standard models, the bone-specific R2* method significantly reduced errors in the fat fraction within the cortical bone in all tested data sets, leading to reduced artifacts in QSM. Good correlation was found between bone CT and QSM values in the porcine hoof (R2  = 0.77). Bone QSM was successfully generated in all subjects.ConclusionsThe QSM of bone is feasible using UTE with a conventional echo time GRE acquisition and a bone-specific R2* signal model. Magn Reson Med 79:121-128, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

PurposeTo develop quantitative susceptibility mapping (QSM) of bone using an ultrashort echo time (UTE) gradient echo (GRE) sequence for signal acquisition and a bone-specific effective transverse relaxation rate ( R2*) to model water-fat MR signals for field mapping.MethodsThree-dimensional radial UTE data (echo times ≥ 40 μs) was acquired on a 3 Tesla scanner and fitted with a bone-specific signal model to map the chemical species and susceptibility field. Experiments were performed ex vivo on a porcine hoof and in vivo on healthy human subjects (n = 7). For water-fat separation, a bone-specific model assigning R2* decay mostly to water was compared with the standard models that assigned the same decay for both fat and water. In the ex vivo experiment, bone QSM was correlated with CT.ResultsCompared with standard models, the bone-specific R2* method significantly reduced errors in the fat fraction within the cortical bone in all tested data sets, leading to reduced artifacts in QSM. Good correlation was found between bone CT and QSM values in the porcine hoof (R2  = 0.77). Bone QSM was successfully generated in all subjects.ConclusionsThe QSM of bone is feasible using UTE with a conventional echo time GRE acquisition and a bone-specific R2* signal model. Magn Reson Med 79:121-128, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

[18F]sodium fluoride ([18F]NaF) is recognised to be superior to [99mTc]-methyl diphosphate ([99mTc]Tc-MDP) and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) in bone imaging. However, there is concern that [18F]NaF uptake is not cancer-specific, leading to a higher number of false-positive interpretations. Therefore, in this work, [18F]AlF-NOTA-pamidronic acid was prepared, optimised, and tested for its in vitro uptake. NOTA-pamidronic acid was prepared by an N-Hydroxysuccinimide (NHS) ester strategy and validated by liquid chromatography-mass spectrometry analysis (LC-MS/MS). Radiolabeling of [18F]AlF-NOTA-pamidronic acid was optimised, and it was ensured that all quality control analysis requirements for the radiopharmaceuticals were met prior to the in vitro cell uptake studies. NOTA-pamidronic acid was successfully prepared and radiolabeled with 18F. The radiolabel was prepared in a 1:1 molar ratio of aluminium chloride (AlCl3) to NOTA-pamidronic acid and heated at 100 °C for 15 min in the presence of 50% ethanol (v/v), which proved to be optimal. The preliminary in vitro results of the binding of the hydroxyapatite showed that [18F]AlF-NOTA-pamidronic acid was as sensitive as [18F]sodium fluoride ([18F]NaF). Normal human osteoblast cell lines (hFOB 1.19) and human osteosarcoma cell lines (Saos-2) were used for the in vitro cellular uptake studies. It was found that [18F]NaF was higher in both cell lines, but [18F]AlF-NOTA-pamidronic acid showed promising cellular uptake in Saos-2. The preliminary results suggest that further preclinical studies of [18F]AlF-NOTA-pamidronic acid are needed before it is transferred to clinical research. [ABSTRACT FROM AUTHOR]

Bone diseases are common and can result in various musculoskeletal conditions (MC). An estimated 1.71 billion patients suffer from musculoskeletal problems worldwide. Apart from musculoskeletal fractures, femoral neck injuries, knee osteoarthritis, and fractures are very common bone diseases, and the rate is expected to double in the next 30 years. Therefore, proper and timely diagnosis and treatment of a fractured patient are crucial. Contrastingly, missed fractures are a common prognosis failure in accidents and emergencies. This causes complications and delays in patients' treatment and care. These days, artificial intelligence (AI) and, more specifically, deep learning (DL) are receiving significant attention to assist radiologists in bone fracture detection. DL can be widely used in medical image analysis. Some studies in traumatology and orthopaedics have shown the use and potential of DL in diagnosing fractures and diseases from radiographs. In this systematic review, we provide an overview of the use of DL in bone imaging to help radiologists to detect various abnormalities, particularly fractures. We have also discussed the challenges and problems faced in the DL-based method, and the future of DL in bone imaging. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a common degenerative joint disease that affects millions of people worldwide. Magnetic resonance imaging (MRI) has emerged as a powerful tool for the evaluation and monitoring of OA due to its ability to visualize soft tissues and bone with high resolution. This review aims to provide an overview of the current state of MRI in OA, with a special focus on the knee, including protocol recommendations for clinical and research settings. Furthermore, new developments in the field of musculoskeletal MRI are highlighted in this review. These include compositional MRI techniques, such as T2 mapping and T1rho imaging, which can provide additional important information about the biochemical composition of cartilage and other joint tissues. In addition, this review discusses semiquantitative joint assessment based on MRI findings, which is a widely used method for evaluating OA severity and progression in the knee. We analyze the most common scoring methods and discuss potential benefits. Techniques to reduce acquisition times and the potential impact of deep learning in MR imaging for OA are also discussed, as these technological advances may impact clinical routine in the future.

Summary: Background: The number of dialysis patients is steadily increasing. Associated comorbidities include impaired bone and mineral metabolism, termed chronic kidney disease-mineral and bone disorder (CKD-MBD), leading to a high fracture risk, increased morbidity and mortality and impaired quality of life. While the bone density is assessed with dual-energy X‑ray absorptiometry (DXA), the trabecular bone score (TBS) captures the image texture as a potential index of skeletal microarchitecture. The aim of this study was to evaluate the clinical relevance of DXA and TBS in dialysis patients with and without prevalent fractures. Methods: Bone disorders were evaluated in 82 dialysis patients (37% female) at the University Hospital of Graz, Austria, by DXA including the assessment of the TBS based on a patient interview and the local routine patient database software. The patient cohort was stratified by having sustained a fragility fracture in the past or not. Descriptive statistics, t‑tests for continuous variables and χ2-tests for nominal variables including results of DXA and TBS were performed to compare these groups considering the dialysis modality and duration as well as the number of kidney transplantations. Results: Of the 82 patients, 32 (39%) had a positive history of fractures. There was a significant association between dialysis duration and fracture prevalence (p < 0.05) as well as musculoskeletal pain (p < 0.01). No significant correlation between DXA/TBS parameters and musculoskeletal pain could be established. The DXA scores did not correlate with fracture prevalence with the exception of DXA radius measurements; however, fracture prevalence significantly correlated inversely with TBS (p < 0.001). Conclusion: The use of DXA has a limited role in fracture prediction in dialysis patients; however, the TBS seems to add information as an additional tool for fracture risk estimation in this patient population. [ABSTRACT FROM AUTHOR]

Teaching Point: Synthetic CT images can improve evaluation of bony lesions on MRI and show potential for fracture evaluation, but validation is needed.

Erdheim-Chester disease (ECD) is a rare and systemic non-Langerhans cell histiocytosis. Recently, ECD was classified as an inflammatory medullary tumor that affects a diverse group of organ systems. The purpose of this report is to present the radiological features of this disease in a 51-year-old man with intestinal obstruction as the initial presentation. In this case, X-ray computed tomography (CT) and emission computed tomography (ECT) clearly showed lesions in various systems, especially in the skeletal images. The survival benefit of treatment with interferon α (IFN-α) and BRAF inhibitors is well established, while other treatments focus on symptom relief. [ABSTRACT FROM AUTHOR]

Erdheim-Chester disease (ECD) is a rare and systemic non-Langerhans cell histiocytosis. Recently, ECD was classified as an inflammatory medullary tumor that affects a diverse group of organ systems. The purpose of this report is to present the radiological features of this disease in a 51-year-old man with intestinal obstruction as the initial presentation. In this case, X-ray computed tomography (CT) and emission computed tomography (ECT) clearly showed lesions in various systems, especially in the skeletal images. The survival benefit of treatment with interferon α (IFN-α) and BRAF inhibitors is well established, while other treatments focus on symptom relief.

Bone stress injuries (BSI) are a common musculoskeletal condition among exercising and military populations and present a major burden to military readiness. The purpose of this investigation was to determine whether baseline measures of bone density, geometry, and strength, as assessed via peripheral quantitative computed tomography (pQCT), are predictive of tibial BSI during Marine Officer Candidates School training. Tibial pQCT scans were conducted prior to the start of physical training (n = 504; Male n = 382; Female n = 122) to measure volumetric bone mineral density (vBMD), geometry, robustness, and estimates of bone strength. Bone parameters were assessed at three tibial sites including the distal metaphysis (4% of tibial length measured from the distal endplate), mid-diaphysis (38% of tibial length measured from the distal endplate), and proximal diaphysis (66% of tibial length measured from the distal endplate). Injury surveillance data was collected throughout training. Four percent (n = 21) of the sample were diagnosed with a BSI at any anatomical site during training, 10 injuries were of the tibia. Baseline bone parameters were then tested for associations with the development of a tibial BSI during training and it was determined that cortical bone measures at diaphyseal (38 and 66%) sites were significant predictors of a prospective tibial BSI. At the mid-diaphysis (38% site), in a simple model and after adjusting for sex, age, and body size, total area [Odds Ratio (OR): 0.987, 0.983], endosteal circumference (OR: 0.853, 0.857), periosteal circumference (OR: 0.863, 0.824), and estimated bending strength (SSI; OR: 0.998, 0.997) were significant predictors of a BSI during training, respectively, such that lower values were associated with an increased likelihood of injury. Similarly, at the proximal diaphysis (66% site), total area (OR: 0.989, 0.985), endosteal circumference (OR: 0.855, 0.854), periosteal circumference (OR: 0.867, 0.823), robustness (OR: 0.007, 0.003), and SSI (OR: 0.998, 0.998) were also significant predictors of BSI in the simple and adjusted models, respectively, such that lower values were associated with an increased likelihood of injury. Results from this investigation support that narrower bones, with reduced circumference, lower total area, and lower estimated strength are associated with increased risk for tibial BSI during military training. [ABSTRACT FROM AUTHOR]

Ultra-short echo time (UTE) MRI with post-processing is a promising technique in bone imaging that produces a similar contrast to computed tomography (CT). Here, we propose a 3D slab-selective ultrashort echo time (UTE) sequence together with image post-processing to image bone structures in the lumbar spine. We also explore the intermodality agreement between the UTE and CT images. The lumbar spines of two healthy volunteers were imaged with 3D UTE using five different resolutions to determine the best imaging protocol. Then, four patients with low back pain were imaged with both the 3D UTE sequence and CT to investigate agreement between the imaging methods. Two other patients with low back pain were then imaged with the 3D UTE sequence and clinical conventional T1-weighted and T2-weighted fast spin-echo (FSE) MRI sequences for qualitative comparison. The 3D UTE sequence together with post-processing showed high contrast images of bone and high intermodality agreement with CT images. In conclusion, post-processed slab-selective UTE imaging is a feasible approach for highlighting bone structures in the lumbar spine and demonstrates significant anatomical correlation with CT images. [ABSTRACT FROM AUTHOR]

X-ray based radiography, the main modality for diagnostic imaging of bone structures and fractures, provides sensitive images, but it inherently involves potentially harmful X-ray exposure. As non-ionizing alternatives, various optical imaging methods have been explored. Here, we demonstrate non-ionizing, label-free, multispectral photoacoustic (PA) imaging of bones in small animals in vivo. in situ. and ex vivo. Using near-infrared light excitation and acoustic detection, the spine and ribs were successfully visualized in high-resolution PA images. PA 3D volume images of the spine and ribs were clearly visualized together with blood vessels and several organs including the spleen, liver, and cecum, without using any exogenous contrast agent nor ionizing radiation. Quantification results of multispectral PA signals from blood vessels and bones were in good agreement with their absorption coefficients. Further, a rib fracture was photoacoustically imaged. Our results demonstrate PA imaging's potential as a non-ionizing and label-free technique for imaging bone tissues.

Bone stress injuries (BSI) are a common musculoskeletal condition among exercising and military populations and present a major burden to military readiness. The purpose of this investigation was to determine whether baseline measures of bone density, geometry, and strength, as assessed via peripheral quantitative computed tomography (pQCT), are predictive of tibial BSI during Marine Officer Candidates School training. Tibial pQCT scans were conducted prior to the start of physical training (n = 504; Male n = 382; Female n = 122) to measure volumetric bone mineral density (vBMD), geometry, robustness, and estimates of bone strength. Bone parameters were assessed at three tibial sites including the distal metaphysis (4% of tibial length measured from the distal endplate), mid-diaphysis (38% of tibial length measured from the distal endplate), and proximal diaphysis (66% of tibial length measured from the distal endplate). Injury surveillance data was collected throughout training. Four percent (n = 21) of the sample were diagnosed with a BSI at any anatomical site during training, 10 injuries were of the tibia. Baseline bone parameters were then tested for associations with the development of a tibial BSI during training and it was determined that cortical bone measures at diaphyseal (38 and 66%) sites were significant predictors of a prospective tibial BSI. At the mid-diaphysis (38% site), in a simple model and after adjusting for sex, age, and body size, total area [Odds Ratio (OR): 0.987, 0.983], endosteal circumference (OR: 0.853, 0.857), periosteal circumference (OR: 0.863, 0.824), and estimated bending strength (SSI; OR: 0.998, 0.997) were significant predictors of a BSI during training, respectively, such that lower values were associated with an increased likelihood of injury. Similarly, at the proximal diaphysis (66% site), total area (OR: 0.989, 0.985), endosteal circumference (OR: 0.855, 0.854), periosteal circumference (OR: 0.867, 0.823), robustness (OR: 0.007, 0.003), and SSI (OR: 0.998, 0.998) were also significant predictors of BSI in the simple and adjusted models, respectively, such that lower values were associated with an increased likelihood of injury. Results from this investigation support that narrower bones, with reduced circumference, lower total area, and lower estimated strength are associated with increased risk for tibial BSI during military training.

Ultra-short echo time (UTE) MRI with post-processing is a promising technique in bone imaging that produces a similar contrast to computed tomography (CT). Here, we propose a 3D slab-selective ultrashort echo time (UTE) sequence together with image post-processing to image bone structures in the lumbar spine. We also explore the intermodality agreement between the UTE and CT images. The lumbar spines of two healthy volunteers were imaged with 3D UTE using five different resolutions to determine the best imaging protocol. Then, four patients with low back pain were imaged with both the 3D UTE sequence and CT to investigate agreement between the imaging methods. Two other patients with low back pain were then imaged with the 3D UTE sequence and clinical conventional T1-weighted and T2-weighted fast spin-echo (FSE) MRI sequences for qualitative comparison. The 3D UTE sequence together with post-processing showed high contrast images of bone and high intermodality agreement with CT images. In conclusion, post-processed slab-selective UTE imaging is a feasible approach for highlighting bone structures in the lumbar spine and demonstrates significant anatomical correlation with CT images.

The aim of the study was to assess the quality and reproducibility of reducing the injected [18F] sodium fluoride ([18F]NaF) dose while maintaining diagnostic imaging quality in bone imaging in a preclinical skeletal model using digital photon counting PET (dPET) detector technology. Beagles (n = 9) were administered three different [18F]NaF doses: 111 MBq (n = 5), 20 MBq (n = 5), and 1.9 MBq (n = 9). Imaging started ≃45 min post-injection for ≃30 min total acquisition time. Images were reconstructed using Time-of-Flight, ultra-high definition (voxel size of 1 × 1 × 1 mm3), with 3 iterations and 3 subsets. Point spread function was modeled and Gaussian filtering was applied. Skeleton qualitative and quantitative molecular image assessment was performed. The overall diagnostic quality of all images scored excellent (61%) and acceptable (39%) by all the reviewers. [18F]NaF SUVmean showed no statistically significant differences among the three doses in any of the region of interest assessed. This study demonstrated that a 60-fold [18F]NaF dose reduction was not significantly different from the highest dose, and it had not significant effect on overall image quality and quantitative accuracy. In the future, ultra-low dose [18F]NaF dPET/CT imaging may significantly decrease PET radiation exposure to preclinical subjects and personnel.

Vertebral fractures are the most common osteoporotic fractures, but clinical means for assessment of vertebral bone integrity are limited in accuracy, as they typically use surrogate measures that are indirectly related to mechanics. The objective of this study was to examine the extent to which intravertebral strain distributions and changes in cancellous bone texture generated by a load of physiological magnitude can be characterized using a clinically available imaging modality. We hypothesized that digital tomosynthesis-based digital volume correlation (DTS-DVC) and image texture-based metrics of cancellous bone microstructure can detect development of mechanical strains under load. Isolated cadaveric T11 vertebrae and L2-L4 vertebral segments were DTS imaged in a nonloaded state and under physiological load levels. Axial strain, maximum principal strain, maximum compressive and tensile principal strains, and von Mises equivalent strain were calculated using the DVC technique. The change in textural parameters (line fraction deviation, anisotropy, and fractal parameters) under load was calculated within the cancellous centrum. The effect of load on measured strains and texture variables was tested using mixed model analysis of variance, and relationships of strain and texture variables with donor age, bone density parameters, and bone size were examined using regression models. Magnitudes and heterogeneity of intravertebral strain measures correlated with applied loading and were significantly different from background noise. Image texture parameters were found to change with applied loading, but these changes were not observed in the second experiment testing L2-L4 segments. DTS-DVC-derived strains correlated with age more strongly than did bone mineral density (BMD) for T11. [ABSTRACT FROM AUTHOR]

Advance diagnostic and treatment modalities have improved outcomes for renal cell carcinoma (RCC) patients, but the prognosis for those with metastatic disease (mRCC) remains poor. As given metastatic distribution is critical in guiding treatment decisions for mRCC patients, we evaluated evolving metastatic patterns to assess if our current practice standards effectively address patient needs. A systematic literature review was performed to identify all publicly available prospective clinical trials in metastatic renal cell carcinoma (mRCC) from 1990 to 2018. A total of 16,899 mRCC patients from 127 qualified phase I-III clinical trials with metastatic site documentations were included for analysis for incidence of metastases to lung, liver, bone, and lymph nodes (LNs) over time. Studies were categorized into three treatment eras based on the timing of regulatory approval: Cytokine Era (1990-2004), vascular endothelial growth factor/tyrosine kinase inhibitor (TKI) Era (2005-2016), and immune checkpoint inhibitor/TKI Era (ICI-TKI, 2017-2018) and also classified as first-line only (FLO) or second-line and beyond (SLB). Overall, an increase in the incidence of bone and LNs metastases in FLO and SLB, and lung metastases in FLO, was seen over the three treatment eras. Generally, the burden of disease is higher in SLB when compared with FLO. Importantly, in the ICI-TKI era, the incidences of bone metastasis are 28% in FLO and 29% in SLB settings. The disease burden in patients with mRCC has increased steadily over the past three decades. Given the unexpectedly high rate of bone metastasis, routine dedicated bone imaging should be considered in all patients with mRCC. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) mineral bone disorder has long-term effects on skeletal integrity and growth. Abnormalities in serum markers of mineral metabolism are evident early in pediatric CKD. Bone deformities, poor linear growth, and high rates of fractures are common in children with CKD. Newer imaging modalities such as high-resolution peripheral quantitative computed tomography shows promise in assessing bone mineral density more comprehensively and predicting incident fractures. A lack of large-scale studies that provide a comprehensive assessment of bone histology and correlations with serum biomarkers has contributed to the absence of evidence-based guidelines and suboptimal management of CKD mineral bone disorder in children with CKD. [ABSTRACT FROM AUTHOR]

Objective: To investigate the impact of reduced SPECT acquisition time on reconstructed image quality for diagnostic purposes. Method: Data from five patients referred for a routine bone SPECT/CT using the standard multi-bed SPECT/CT protocol were reviewed. The acquisition time was 900 s using gating technique; SPECT date was resampled into reduced data sets of 480 s, 450 s, 360 s and 180 s acquisition duration per bed position. Each acquisition time was reconstructed using a fixed number of subsets (8 subsets) and 4, 8, 12, and 16 iterations, followed by a post-reconstruction 3D Gaussian filter of 8 mm FWHM. Two Nuclear Medicine physicians analysed all images independently to score image quality, noise and diagnostic confidence based on a pre-defined 4-point scale. Results: Our result showed that the most frequently selected categories for 480 s and 450 s images were good image quality, average noise and fair confidence, particularly at lower iteration numbers 4 and 8. For the shortened acquisition time of 360 s and 180 s, statistical significance was observed in most reconstructed images compared with 900 s. Conclusion: The SPECT/CT can significantly shorten the acquisition time with maintained image quality, noise and diagnostic confidence. Therefore, acquiring data over 480 s and 450 s is feasible for WB-SPECT/CT bone scans to provide an optimal balance between acquisition time and image quality.

Bone diseases are common and can result in various musculoskeletal conditions (MC). An estimated 1.71 billion patients suffer from musculoskeletal problems worldwide. Apart from musculoskeletal fractures, femoral neck injuries, knee osteoarthritis, and fractures are very common bone diseases, and the rate is expected to double in the next 30 years. Therefore, proper and timely diagnosis and treatment of a fractured patient are crucial. Contrastingly, missed fractures are a common prognosis failure in accidents and emergencies. This causes complications and delays in patients’ treatment and care. These days, artificial intelligence (AI) and, more specifically, deep learning (DL) are receiving significant attention to assist radiologists in bone fracture detection. DL can be widely used in medical image analysis. Some studies in traumatology and orthopaedics have shown the use and potential of DL in diagnosing fractures and diseases from radiographs. In this systematic review, we provide an overview of the use of DL in bone imaging to help radiologists to detect various abnormalities, particularly fractures. We have also discussed the challenges and problems faced in the DL-based method, and the future of DL in bone imaging.

Nowadays, the use of a digital prototype in numerical modeling is one of the main approaches to calculating the elements of an inhomogeneous structure under the influence of external forces. The article considers a finite element analysis method based on computed tomography data. The calculations used a three-dimensional isoparametric finite element of a continuous medium developed by the authors with a linear approximation, based on weighted integration of the local stiffness matrix. The purpose of this study is to describe a general algorithm for constructing a numerical model that allows static calculation of objects with a porous structure according to its computed tomography data. Numerical modeling was carried out using kinematic boundary conditions. To evaluate the results obtained, computational and postprocessor grids were introduced. The qualitative assessment of the modeling data was based on the normalized error. Three-point bending of bone specimens of the pig forelimbs was considered as a model problem. The numerical simulation results were compared with the data obtained from a physical experiment. The relative error ranged from 3 to 15%, and the crack location, determined by the physical experiment, corresponded to the area where the ultimate strength values were exceeded, determined by numerical modeling. The results obtained reflect not only the effectiveness of the proposed approach, but also the agreement with experimental data. This method turned out to be relatively non-resource-intensive and time-efficient.

In this study, phosphate-buffered saline solution (PBS) was successfully radiolabeled with technetium-99m. The biodistribution profile and bone accumulation of the [99mTc]Tc-PBS system were evaluated in healthy swiss mice. The radiolabeling of the system was successfully obtained, yielding around 90 % of radiochemical purity. The system stability was tested in the presence of saline medium at 25 ºC and mouse plasma at 37 ºC, and results revealed that [99mTc]Tc-PBS showed excellent stability over time, in both media. It was observed a biphasic clearance profile, with fast elimination from the bloodstream by renal filtration. The radiolabeled system revealed a high specificity bone accumulation was observed, demonstrating an uptake behavior from 20 to 50 times higher than muscle, used as control. From all results obtained, the system constituted by [99mTc]Tc-PBS can be considered a potential selective agent for bone imaging. [ABSTRACT FROM AUTHOR]

Osteoporosis is a condition of deterioration of bone quality and quantity, making it susceptible to fractures. The current therapy, with its associated risks and also approval for only short period makes the search for better molecules on priority imperative for effective treatment. Esculetin, a phytoconstituent, known to inhibit osteoclast differentiation in vitro and increase bone density in vivo, could serve to cure osteoporosis. Here, we studied the effect of esculetin on the microarchitecture of long bones in the ovariectomized rat model. The cellular cause for in vivo effect was sought by studying its effect on the pre-osteoblastic cell line. Osteopenia was induced by bilateral ovariectomy. Esculetin @1.0 or 10 mg/kg was administered for three months to osteopenic rats. Micro-CT of tibias and femurs was performed. The effect of esculetin on pre-osteoblastic MC3T3-E1 cells was studied. Cell viability in the presence of esculetin was determined by MTT assay. Alkaline phosphatase activity was determined using p-nitrophenol as a substrate. Bone nodules were stained with Alizarin Red S. Esculetin treated groups showed a significant worsening of microarchitecture parameters in the trabecular and cortical regions of the femur and tibia. This deterioration was more evident in the trabecular region than the cortical region. Esculetin augmented bone loss in estrogen-deficient rats without affecting the cell viability of MC3T3-E1 cells up to a concentration of 10 µg/mL. However, it affected the alkaline phosphatase activity and mineralization effect in preosteoblastic cells in addition to its in vivo effect in ovariectomized rats. [ABSTRACT FROM AUTHOR]

Purpose: We identified the risk predictors related to prostate cancer (PCa) metastasis using contemporary data in a community setting. Then, we assessed the performance of indications for bone imaging recommended from the NCCN, AUA and EAU guidelines. Methods: Using the Surveillance, Epidemiology, and End Results database (2010–2015), we collected clinicopathological information from PCa patients. The associated risk factors found by multivariate analyses were used to establish forest plots and nomograms for distant metastasis (DM) and bone(s)-only metastasis (BM). We next evaluated the NCCN, AUA and EAU guidelines indications for the discovery of certain subgroups of patients who should receive bone imaging. Results: A total of 120,136 patients were eligible for analysis, of which 96.7% had no metastasis. The odds ratios of positive DM and BM results were 13.90 times and 15.87 times higher in patients with a histologic grade group (GG) 5 than in the reference group. The concordance index of the nomograms based on race, age, T/N stage, PSA, GG, percentage of positive scores for predicting DM and BM was 0.942 and 0.928, respectively. Performance of the NCCN, AUA and EAU guidelines was high and relatively similar in terms of sensitivity (93.2–96.9%) and negative predictive value (99.8–99.9%). NCCN guidelines had the highest accuracy, specificity and positive likelihood ratio, while negative likelihood ratio was lowest in AUA guideline. Conclusion: Histologic GG 5 was the foremost factor for DM and BM. NCCN-based recommendations may be more rational in clinical practice. Nomograms predicting metastasis demonstrate high accuracy. [ABSTRACT FROM AUTHOR]

Massive bone allografts enable the reconstruction of critical bone defects in numerous conditions (e.g. tumoral, infection or trauma). Unfortunately, their biological integration remains insufficient and the reconstruction may suffer from several postoperative complications. Perfusion-decellularization emerges as a tissue engineering potential solution to enhance osseointegration. Therefore, an intrinsic vascular study of this novel tissue engineering tool becomes essential to understand its efficacy and applicability. 32 porcine long bones (humeri and femurs) were used to assess the quality of their vascular network prior and after undergoing a perfusion-decellularization protocol. 12 paired bones were used to assess the vascular matrix prior (N = 6) and after our protocol (N = 6) by immunohistochemistry. Collagen IV, Von Willebrand factor and CD31 were targeted then quantified. The medullary macroscopic vascular network was evaluated with 12 bones: 6 were decellularized and the other 6 were, as control, not treated. All 12 underwent a contrast-agent injection through the nutrient artery prior an angio CT-scan acquisition. The images were processed and the length of medullary vessels filled with contrast agent were measured on angiographic cT images obtained in control and decellularized bones by 4 independent observers to evaluate the vascular network preservation. The microscopic cortical vascular network was evaluated on 8 bones: 4 control and 4 decellularized. After injection of gelatinous fluorochrome mixture (calcein green), non-decalcified fluoroscopic microscopy was performed in order to assess the perfusion quality of cortical vascular lacunae. The continuity of the microscopic vascular network was assessed with Collagen IV immunohistochemistry (p -value = 0.805) while the decellularization quality was observed through CD31 and Von Willebrand factor immunohistochemistry (p -values <0.001). The macroscopic vascular network was severely impaired after perfusion-decellularization; nutrient arteries were still patent but the amount of medullary vascular channels measured was significantly higher in the control group compared to the decellularized group (p -value <0.001). On average, the observers show good agreement on these results, except in the decellularized group where more inter-observer discrepancies were observed. The microscopic vascular network was observed with green fluoroscopic signal in almost every canals and lacunae of the bone cortices, in three different bone locations (proximal metaphysis, diaphysis and distal metaphysis). Despite the aggressiveness of the decellularization protocol on medullary vessels, total porcine long bones decellularized by perfusion retain an acellular cortical microvascular network. By injection through the intact nutrient arteries, this latter vascular network can still be used as a total bone infusion access for bone tissue engineering in order to enhance massive bone allografts prior implantation. [Display omitted] • This study shows how a total bone can be used as a pediculed whole organ for tissue engineering purpose. • This study brings insights in the understanding of total bone decellularization by perfusion. • This study is a step forward a new generation of massive bone allografts. • This study reinforces the importance and complexity of bone vascularization. [ABSTRACT FROM AUTHOR]

Abstract Background We investigated the clinical performance of a quantitative multi-modal SPECT/CT reconstruction platform for yielding radioactivity concentrations of bone imaging with 99mTc-methylene diphosphonate (MDP) or 99mTc-dicarboxypropane diphosphonate (DPD). The novel reconstruction incorporates CT-derived tissue information while preserving the delineation of tissue boundaries. We assessed image-based reader concordance and confidence, and determined lesion classification and SUV thresholds from ROC analysis. Methods Seventy-two cancer patients were scanned at three US and two German clinical sites, each contributing two experienced board-certified nuclear medicine physicians as readers. We compared four variants of the reconstructed data resulting from the Flash3D (F3D) and the xSPECT Bone™ (xB) iterative reconstruction methods and presented images to the readers with and without a fused CT, resulting in four combinations. We used an all-or-none approach for inclusion, compiling results only when a reader completed all reads in a subset. After the final read, we conducted a “surrogate truth” reading, presenting all data to each reader. For any remaining discordant lesions, we conducted a consensus read. We next undertook ROC analysis to determine SUV thresholds for differentiating benign and lesional uptake. Results On a five-point rating scale of image quality, xB was deemed better by almost two points in resolution and one point better in overall acceptance compared to F3D. The absolute agreement of the rendered decision between the nine readers was significantly higher with CT information either inside the reconstruction (xB, xBCT) or simply through image fusion (F3DCT): 0.70 (xBCT), 0.67 (F3DCT), 0.64 (xB), and 0.46 (F3D). The confidence level to characterize the lesion was significantly higher (3.03x w/o CT, 1.32x w/CT) for xB than for F3D. There was high correlation between xB and F3D scores for lesion detection and classification, but lesion detection confidence was 41% higher w/o CT, and 21% higher w/CT for xB compared to F3D. Without CT, xB had 6.6% higher sensitivity, 7.1% higher specificity, and 6.9% greater AUC compared to F3D, and similarly with CT-fusion. The overall SUV-criterion (SUVc) of xB (12) exceeded that for xSPECT Quant™ (xQ; 9), an approach not using the tissue delineation of xB. SUV critical numbers depended on lesion volume and location. For non-joint lesions > 6 ml, the AUC for xQ and xB was 94%, with SUVc > 9.28 (xQ) or > 9.68 (xB); for non-joint lesions ≤ 6 ml, AUCs were 81% (xQ) and 88% (xB), and SUVc > 8.2 (xQ) or > 9.1 (xB). For joint lesions, the AUC was 80% (xQ) and 83% (xB), with SUVc > 8.61 (xQ) or > 13.4 (xB). Conclusion The incorporation of high-resolution CT-based tissue delineation in SPECT reconstruction (xSPECT Bone) provides better resolution and detects smaller lesions (6 ml), and the CT component facilitates lesion characterization. Our approach increases confidence, concordance, and accuracy for readers with a wide range of experience. The xB method retained high reading accuracy, despite the unfamiliar image presentation, having greatest impact for smaller lesions, and better localization of foci relative to bone anatomy. The quantitative assessment yielded an SUV-threshold for sensitively distinguishing benign and malignant lesions. Ongoing efforts shall establish clinically usable protocols and SUV thresholds for decision-making based on quantitative SPECT.

Teaching Point: Synthetic CT images can improve evaluation of bony lesions on MRI and show potential for fracture evaluation, but validation is needed. [ABSTRACT FROM AUTHOR]

Objective To investigate the relationship between total prostate specific antigen (TPSA), free prostate specific antigen/total prostate specific antigen [RAT(FIT)], Gleason score, other factors and the whole-body bone phme imaging which was used to evaluate the bone metastasis of prostate cancer (PCa), and the diagnostic value of the abnormal concentration of bone imaging agent for single lesion. Methods A retrospective analysis of 99Tc100 -methylene diphosphonate (99Tc100-MOP) whole-body bone imaging data of 93 patients with confirmed PCa in The First Hospital of Shanxi Medical University from Jan 2018 to Jan 2019 was conducted. The hone metastasis was diagnosed by whole-body bone imaging. The factors related to PCa bone metastasis, including age, TPSA, RAT (FIT), Gleason score were analysed by Chi-square test and logstic two-class regression. The optimal cut-off point of TPSA was defined by receiver operating characteristic (ROC) curve. The region of interest (ROI) Techni clue was used to repeatedly delineate the lesion (T) and the background area (NT) outside the bone and calculate the abnormal concentration value of bone imaging agent (T-NT)INT, and the ROC curve was used to determine its diagnostic value. Results The result of Chi-square analysis showed that Gleason score, TPSA and RAT (F/T) were associated with hone metastasis (P<0.05). Logistic regression analysis showed that TPSA and RAT (F/T) were associated with hone metastasis (P<0.01). TPSA >92.82 ng/ml was the best diagnosis for bone metastasis, and the sensitivity and specificity were 77.1%. and 81.0%, respectively. There were 320 sites of high concentration of imaging agents in the whole-body bone imaging of PCa patients (194 in the metastatic group and 126 in the non-metastasis group). The (T-NT)/NT in the hone metastasis group was 7111±0.29, the non-bone metastasis group was 2.69±0.20. (T-NT)/Nf >3.52 was the best diagnosis for bone metastasis of single lesion, and the sensitivity and specificity were 86.1% and 80.2%, respectively. Conclusions Gleason score, RAT (FIT) and TPSA arc important risk factors of PCa hone metastasis. TPSA >92.82 ng/ml is the most supportive diagnosis for PCa bone metastasis. The abnormal concentration of bone imaging agent >3.52 owns the best diagnosis effect for the single lesion of PCa. [ABSTRACT FROM AUTHOR]

• Current techniques for assessing vertebral fracture risk are limited in accuracy. • DTS-DVC allows for clinical assessment of vertebral bone deformation. • Displacement spatial distributions qualitatively agreed between DTS-DVC and μCT-DVC. • DTS-DVC derived displacement and stiffness were strongly correlated with μCT values. • Results support use of DTS-DVC for clinical evaluation of vertebral bone quality. Digital tomosynthesis (DTS) is a clinically available modality that allows imaging of a patient's spine in supine and standing positions. The purpose of this study was to establish the extent to which vertebral displacement and stiffness derived from DTS-based digital volume correlation (DTS-DVC) are correlated with those from a reference method, i.e., microcomputed tomography-based DVC (μCT-DVC). T11 vertebral bodies from 11 cadaveric donors were DTS imaged twice in a nonloaded state and once under a fixed load level approximating upper body weight. The same vertebrae were µCT imaged in nonloaded and loaded states (40 μm voxel size). Vertebral displacements were calculated at each voxel using DVC with pairs of nonloaded and loaded images, from which endplate-to-endplate axial displacement (D DVC) and vertebral stiffness (S DVC) were calculated. Both D DVC and S DVC demonstrated strong positive correlations between DTS-DVC and μCT-DVC, with correlations being stronger when vertebral displacement was calculated using the median (R2=0.80; p <0.0002 and R2=0.93; p <0.0001, respectively) rather than average displacement (R2=0.63; p <0.004 and R2=0.69; p <0.002, respectively). In conclusion, the demonstrated relationship of DTS-DVC with the μCT standard supports further development of a biomechanics-based clinical assessment of vertebral bone quality using the DTS-DVC technique. [ABSTRACT FROM AUTHOR]