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The noninvasive quantification of peripheral compartment-specific bone microarchitecture is feasible with high-resolution peripheral quantitative computed tomography (HR-pQCT) and high-resolution magnetic resonance imaging (HR-MRI). In addition to classic morphometric indices, both techniques provide a suitable basis for virtual biomechanical testing using finite element (FE) analyses. Methodical limitations, morphometric parameter definition, and motion artifacts have to be considered to achieve optimal data interpretation from imaging studies. With increasing availability of in vivo high-resolution bone imaging techniques, special emphasis should be put on quality control including multicenter, cross-site validations. Importantly, conclusions from interventional studies investigating the effects of antiosteoporotic drugs on bone microarchitecture should be drawn with care, ideally involving imaging scientists, translational researchers, and clinicians.

The detection of bone metastasis in early stages requires the development of high-affinity bone imaging radiopharmaceuticals for the improvement of the diagnostic accuracy of routine bone scanning and effective management of these medical cases. This study aimed to provide a convenient synthesis of 1-thioethylidene-l,l-disodiumphosphonate (TEDP) and an improved preparation of its 99mTc-TEDP complex. The results showed that the radiochemical purity of 99mTc-TEDP was found to be 95 ± 2% and that its stability was up to 6 h. Biodistribution study showed high and long uptake of 99mTc-TEDP in bone starting from 15 min (39 ± 4 ID/g) to 3 h (53 ± 2.4 ID/g) showing high affinity of 99mTc-TEDP complex to bones. This research could introduce a novel radiopharmaceutical that could be used in scanning body bones starting from 15 min between injection of 99mTc-TEDP and bone imaging, minimizing the burden on patients in terms of the total length of the examination and the dose of radiation absorbed and showing high specificity and efficacy in bone scintigraphy.

Background Bone deformities are typically identified through standard radiograms. Since X-ray examinations are easily applied and offer high quality imaging, noninvasive techniques are not commonly used in bone diagnostics. Nevertheless, nonradiological techniques are considered necessary because of the harmful effects of X-ray radiation. Methods The paper presents a new noninvasive system for bone imaging. The system allows the physician to create self-defined templates of the measured geometrical parameters and to measure the bone geometry according to the planned procedures. Results The proposed system was verified by determining the fiducial location error, the fiducial registration error and the target registration error. The tests were performed on sawbones and a measuring plate. In order to verify the accuracy of reconstruction, tests on the three-dimensional phantoms were carried out. The system has been tested in clinical conditions: results of limb geometrical parameters measured on five probands were compared with MRI-based evaluation. Conclusions The system supplies critical data supporting the standard radiological examination. In the future, after further improvements it may replace invasive X-ray imaging. The main advantage of ultrasonography is noninvasive imaging (using mechanical waves), however, it demands considerable experience. Copyright © 2011 John Wiley & Sons, Ltd.

The primary role of radiographic imaging in dental health has been the detection and localization of disease as a guide for surgical intervention. In this role, it appears to differ from the primary role of postcranial skeletal radiography, evaluation of the structural integrity of the bone. However, in both cases, the radiographic information ultimately is used in an attempt to restore or maintain function in the affected osseous structure. This structure-function relationship can be used as a framework within which the potential of new technologies developed for evaluation of the postcranial skeleton can be assessed relative to craniofacial imaging. Within this context, I treat first the use of newer imaging modalities, followed by methods to assess bone properties, and finally the coupling of these technologies with other analytic tools to obtain direct information about the structure-function relationship in the cranioskeleton.

Horses undergoing skeletal scintigraphy can have decreased radiopharmaceutical bone uptake in the limbs. This reduces the diagnostic value of the scan. The aim of the present study was to measure the changes in count density caused by vasodilatation and increased blood flow associated with intravenous injection of acepromazine during bone scintigraphy in normal horses. A three-phase bone scan was performed twice in 11 adult horses to study the effects of acepromazine on the count density of the resultant scintigrams. With acepromazine, there was a statistically significant mean difference of 12 s for initial blood flow and 21 s for peak flow. The time to initial blood flow and time to peak flow occurred earlier for the scans in which acepromazine was used. There were no significant differences in the bone to soft tissue ratios during the soft tissue and bone phases of the scan between procedures. Intravenous administration of acepromazine increases peripheral blood flow causing an earlier onset of the vascular phase during the three-phase bone scan. Acepromazine did not increase the count density of the bone phase scintigrams. As expected, the vasodilatation and increased blood flow associated with intravenous injection of acepromazine affected the count density of the vascular phase of the bone scan.

Purpose: To investigate the 3D geometric distortion of four potential MR sequences for radiotheraptic applications, and its dependency on sequence-type, acquisition-orientation and receiver-bandwidth from a dedicated 1.5T 700mm-wide bore MR-simulator (Magnetom-Aera, Sienmens Healthcare, Erlangen, Germany), using a large customized geometric accuracy phantom. Methods: This work studied 3D gradient-echo (VIBE) and spin-echo (SPACE) sequences for anatomical imaging; a specific ultra-short-TE sequence (PETRA) potentially for bone imaging and MR-based dosimetry; and a motion-insensitive sequence (BLADE) for dynamic applications like 4D-MRI. Integrated geometric-correction was employed, three orthogonal acquisition-orientations and up to three receiver-bandwidths were used, yielding 27 acquisitions for testing (Table 1a).A customized geometric accuracy phantom (polyurethane, MR/CT invisible, W×L×H:55×55×32.5cm3) was constructed and filled with 3892 spherical markers (6mm diameter, MR/CT visible) arranged on a 25mm-interval 3D isotropic-grid (Fig.1). The marker positions in MR images were quantitatively calculated and compared against those in the CT-reference using customized MatLab scripts. Results: The average distortion within various diameter-of-spherical-volumes (DSVs) and the usable DSVs under various distortion limits were measured (Tables 1b-c). It was observed that distortions fluctuated when sequence-type, acquisition-orientation or receiver-bandwidth changed (e.g. within 300mm-DSV, the lowest/highest average distortions of VIBE were 0.40mm/0.59mm, a 47.5% difference). According to AAPM-TG66 (

Purpose: Clinical use of 18F-Sodium Fluoride (NaF) PET/CT in metastatic settings often lacks technology to quantitatively measure full disease dynamics due to high tumor burden. This study assesses radiomics-based extraction of NaF PET/CT measures, including global metrics of overall burden and local metrics of disease heterogeneity, in metastatic prostate cancer for correlation to clinical outcomes. Methods: Fifty-six metastatic Castrate-Resistant Prostate Cancer (mCRPC) patients had NaF PET/CT scans performed at baseline and three cycles into chemotherapy (N=16) or androgen-receptor (AR) inhibitors (N=39). A novel technology, Quantitative Total Bone Imaging (QTBI), was used for analysis. Employing hybrid PET/CT segmentation and articulated skeletal-registration, QTBI allows for response assessment of individual lesions. Various SUV metrics were extracted from each lesion (iSUV). Global metrics were extracted from composite lesion-level statistics for each patient (pSUV). Proportion of detected lesions and those with significant response (%-increase or %-decrease) was calculated for each patient based on test-retest limits for iSUV metrics. Cox proportional hazard regression analyses were conducted between imaging metrics and progression-free survival (PFS). Results: Functional burden (pSUVtotal) assessed mid-treatment was the strongest univariate predictor of PFS (HR=2.03; p

Nuclear medical bone imaging was used in combination with targeted radiography to detect metastatic or multicentric lesions in 23 dogs with skeletal neoplasms. Each dog with a radiographically diagnosed skeletal neoplasm was injected with Technetium-99m labeled methylene diphosphonate (99mTc-MDP) (15.0 mCi intravenously) for whole body imaging. All areas with increased uptake of 99mTc-MDP were radiographed. In 19 dogs, the amount of bone shaft involvement in primary sites indicated by bone imaging was larger than the amount indicated by radiography. Eighteen dogs had secondary areas of increased 99mTc-MDP uptake, six of which had secondary areas that were suspected radiographically to be neoplastic. Four dogs had lesions characterized histologically as neoplasia, one as bone infarction and one as normal cortical bone. Positive predictive value for this strategy was 66.7%. Results of this study suggest that nuclear medical bone imaging with targeted radiography is a quick, noninvasive technique with a good positive predictive value for evaluation of the skeleton for metastatic or multicentric sites of neoplasia.

Purpose: Although the anatomy of interest should be positioned as close as possible to the isocenter of CT scanners, off-centering may be inevitable during certain exams in clinical practice such as lumbar spine and elbow imaging. Off-centering degrades image sharpness, generates streak artifacts, and sometimes creates blooming artifacts due to truncation. The purpose of this work was to investigate whether the use of model-based image reconstruction (MBIR) can alleviate the negative impacts of off-centering to achieve high quality CT bone imaging. Methods: Both an anthropomorphic phantom and an ex vivo swine elbow sample were scanned at centered and off-centered positions using clinical CT bone scan protocols. The magnitude of off-centering was determined from localizer radiographs. Both FBP and MBIR reconstructions were performed. For FBP, both standard and Bone Plus kernels commonly used in bone imaging were used. Objective assessment of image sharpness, noise standard deviation, and noise nonuniformity were performed. Additionally, we retrospectively analyzed human subject data acquired under off-centered conditions as a validation study. Results: In FBP images of the phantom, off-centering by 10 cm led to a 14% increase in noise (p

Purpose: To demonstrate how both the positioning of an object in the scan field of view (SFOV) and the size of the reconstructed field of view (RFOV) can both significantly affect and degrade the image sharpness. Methods: Clinical CT scans of the shoulders and elbows were inspected for image sharpness. GE scanners were used for the imaging with a “Bone Plus” reconstruction algorithm. In all scans the anatomy of interest was significantly displaced from the center of the SFOV (away from the scanner iso-center). Radial and azimuthal image sharpness measurements using the Modulation Transfer Function (MTF) were made using the same RFOV at the center of the SFOV and at varying distances from the center. These MTF measurements were also made with varying values of the RFOV. Results: Clinical images with the bone anatomy of interest positioned farther from the center of the SFOV showed increasing image softness occasionally to the point of being non-diagnostic. The MTF measurements showed that the resolution degraded significantly, by more than a factor of 2, moving from the center toward the periphery of the SFOV: from 12 cycles/cm to less than 6 cycles/cm at distances of 15 cm or more from the center of the SFOV. Increasing the RFOV beyond 20 cm also degraded the resolution, though less significantly. Conclusion: When preservation of bone detail is important one must not only use the proper bone reconstruction algorithm, but also must keep the body part as close to the center of the SFOV as possible. Though this may be difficult with some imaging tasks, such as imaging of the shoulder and elbow, every effort should be made to this end. For the best resolution, the RFOV should also be kept small, ideally to 20 cm or less. Partial research funding from GE HealthCare.

Schnitzler’s syndrome is an autoinflammatory disorder characterized by the association of a monoclonal IgM (or IgG) gammopathy, a chronic urticarial rash, and signs and symptoms of systemic inflammation, including fever, arthralgias and bone pain. It was first described in 1972. This review summarizes the clinical features, efficacy of therapies, and follow-up data of the 281 cases that have been reported to date. Also, the results of skin histology, bone imaging, laboratory investigations, and studies of the pathogenesis will be discussed, including the pivotal role of interleukin-1 beta in this disorder. Electronic supplementary material The online version of this article (doi:10.1186/2045-7022-4-41) contains supplementary material, which is available to authorized users.

Purpose: MRI only radiation therapy has been increasingly gaining research interests. Conventionally, MRIs are fused with CT to take advantage of its superior soft tissue contrast. Such an approach has drawbacks such as additional uncertainty from fusion and extra cost. To achieve MR‐based simulation for radiation therapy, bone imaging is an important challenge that needs to be overcome. The ultra‐short T2 and T1 of cortical bone Result in low signal intensity, which presents difficulty for both dose calculation and patient setup in terms of digitally reconstructed radiograph (DRR) generation. Current solutions will either require manual bone contouring or multiple MR scans. We present a technique to generate brain DRR using bone MRI with a single Ultra Short Echo Time (UTE) sequence. Methods: Healthy volunteers were scanned at 1.5 Tesla using a radial UTE sequence. The sequence acquires two images at two different echo times (0.07ms and 3.6ms). The two images were processed using in‐house software, which performs pixel‐by‐pixel magnitude subtraction of the two images. The difference image was subsequently divided pixel‐by‐pixel to the long TE (3.6ms) image. As the cortical bone has larger percentile difference between the UTE and long TE image compared with other tissues, the bone is bright in the processed image. The resultant bone images were subsequently loaded into commercial treatment planning system to generate DRRs. Results: The majority of cranial, facial and vertebral bones are well visualized in both volunteers. The fused image of the long TE image with the processed bone image demonstrates the accuracy of automatic bone identification using our technique. The generated DRR is of acceptable quality. Conclusion: This study shows the potential of DRR generation with single MR sequence. Further work will be needed on MR sequence development and post‐processing procedure to achieve MR bone image with comparable quality to CT.

Purpose: Prostate cancer is the most prevalent cancer among males in the US, and over 90% of patients develop bone metastases. Current treatment response evaluation metrics, such as RECIST, are not suited for assessing bone lesions. The aim of this work is to present an automated segmentation method that identifies and characterizes bone lesions and determine its sensitivity to thresholding. Methods: Patients with metastatic prostate cancer were treated with molecular target therapy and received whole body [F‐18]NaF (bone imaging) PET/CT scans during the course of treatment. Scans were evaluated using the Quantitative Total Bone Imaging (QTBI) methodology, which assesses total bone and individual bone lesions in patients with bone metastases. Individual lesions were segmented using thresholds ranging from 20% to 80% of the maximum standardized uptake value (SUV) in bone. The mean SUV, total SUV, and volume of the total bone and individual lesions were determined as well as the number of lesions. Treatment response was assessed as the percent change in the imaging metrics relative to pre‐treatment. Results: The QTBI methodology was able to identify and characterize bone lesions. Of the treatment response metrics, change in number of lesions showed the greatest dependence on the threshold. The standard deviation of patient responses ranged from 13.5 to 34.5. Change in mean SUV had the least sensitivity to threshold (SD=0.5–2.0). Change in total SUV and volume both showed intermediate variation (SD=7.5–11.5 and 11.0–12.5, respectively). Conclusions: The QTBI methodology is able to identify and characterize bone lesions. However, because most imaging metric responses vary with different thresholds, careful selection of SUV threshold for segmentation is necessary to accurately identify and characterize bone lesions and assess treatment response. With further refinement, this methodology can be a clinically useful tool to improve patient care and test new therapies for use in metastatic bone disease.

Objective 18F‐Fluorodeoxyglucose (FDG) is a metabolic activity marker with limited use for skeletal lesions. Sodium18F‐flouride (NaF) is a bone imaging agent that complements the FDG limitations for skeletal lesions. The kinetic analysis of combined NaF/FDG PET scan promises concurrent determination of both tumor metabolism and vasculature parameters as well as successful separation of each tracer uptake. The aim of this work is to optimize the combined NaF/FDG PET scanning protocol in order to maximize accuracy in kinetic model estimation of the tumor's parameters. Materials and Methods Simulations assessed the feasibility and accuracy of kinetic analysis of combined NaF/FDG PETimages. Tissue time activity curves (tTAC) were generated with randomized parameters and PET voxel‐wise noise level. Various time delays between NaF and FDG injection times were simulated while keeping the total scan duration at 60 minutes. Parameters were estimated with two simplified versions of the model used for tTAC's generation. Estimated parameters were compared against the simulated parameters. The optimized sequence was tested on canine NaF/FDG PET data.Results Parameter estimation accuracy was maximized if the NaF was injected first followed by the FDG injection of at least 40 minutes later. The estimation accuracy for k1 parameters ranged from 15% to 20% for FDG and 25% to 30% for NaF. Ki estimation accuracy ranged from 40% to 55% for FDG and 10% to 25% for NaF. Vasculature fraction estimation accuracy ranged from 20% to 40%. Results of clinical data kinetic analysis shows that both k1 parameters are highly correlated which implies that it might be common for both radiopharmaceuticals in our model._Conclusions This study has shown that kinetic analysis of combined NaF/FDG PETimages is feasible using an optimized injection and scanning protocol. For the given cases we found the optimal scanning protocol and quantified parameter estimation accuracy.

A reproducible technique of bone scanning in prostatic cancer is described that helps ensure the production of successive studies of highly comparable technical quality. Through an analysis of survival data based on changes in distribution, anatomic extent, and intensity of bone scan abnormalities in patients with advanced prostatic cancer, it is demonstrated that alterations in the appearance of the bone scan correlate closely with disease activity and have great prognostic significance.

A focal area of increased uptake of radioactivity was observed in muscle during bone imaging with 99mTcMDP. The area was previously the site of a peripheral nerve block with mepivacaine hydrochloride. Additional experiments were done to document the action of the local anesthetic. The effect on uptake decreased over several days.

One hundred and twenty-seven patients with locally advanced prostatic cancer were evaluated for the presence and progress of bone metastases before and during hormonal therapy, by serial radionuclide imaging and frequent measurement of plasma acid (tartrate-labile) and alkaline phosphatase. For comparison, serial changes in imaging and phosphatases were classified in each patient into one of six groups. Of 71 patients with negative imaging before treatment, 82% had normal alkaline phosphatase levels and 83% had normal acid phosphatase levels. Of 56 patients with bone metastases at presentation, false negative alkaline and acid phosphatase levels were noted in 18% and 36% respectively, though a few patients eventually developed abnormal levels. Serial plasma biochemistry and particularly alkaline phosphatase showed a response to treatment which was not always obvious on imaging. An assessment of the hepatic component of alkaline phosphatase by reference to plasma gamma glutamyl transpeptidase and isoenzyme electrophoresis was helpful in the evaluation of a false positive result but unnecessary where imaging was positive and phosphatase elevated. It is concluded that serial alkaline phosphatase estimation is essential in the follow-up of patients with prostatic cancer and bone metastases, and probably renders serial imaging studies superfluous once the presence of skeletal metastases has been proven. By comparison, acid phosphatase is a much less effective marker.

Bone scintigraphy is a valuable aid in the evaluation of lameness in horses. This review describes the principles of bone radiolabeling, scanning, and scan interpretation. Examples are used to illustrate how bone imaging can contribute significantly to a diagnosis after equivocal physical examination or radiographic findings.

SUMMARY Bone imaging with Technetium-99m labelled phosphate complexes is safe and convenient. The pyrophosphate, triphosphate and polyphosphate were compared in human and mouse studies. Information on bone accumulation, blood disappearance and urinary excretion in 18 patients with these agents indicates an injection to scanning time of 2 hours gives best information yield.

Bone imaging techniques are a sensitive and accurate method for the detection of primary and secondary neoplastic disease of the skeleton. Such procedures have been demonstrated to be superior to evaluation via blood chemistry levels or routine skeletal radiographic surveys. These techniques are also helpful in establishing sites for biopsy and for objective evaluation of therapeutic modalities. They suffer the disadvantage of being nonspecific, and as a result, all positive areas identified by scanning techniques should be correlated with radiographic changes.

Chondrosarcoma is a rare complication in hereditary multiple exostoses. The six patients in this study have had a complete follow-up and constitute the largest group of such cases to have been studied so far. Five patients had histologic evidence of malignancy. Since histologic examination can be very difficult, any other diagnostic features, may it be clinical, radiologic, or scintigraphical, should be taken into account for early surgical treatment. Bone scintigraphic examination is a valuable adjunct to early diagnosis of malignant change by showing highest uptake in malignant areas. It is also very useful for posttherapeutic follow-up.

Bone imaging is a valuable procedure in the evaluation of patients suspected of having metastatic disease to bone. Its use has been well established in many clinical studies. Several radionuclides are available that can detect the presence of metastatic disease before X-ray changes occur. Because other nonmalignant conditions may produce positive bone scans, the procedure must be used in conjunction with the appropriate X-ray and other diagnostic studies. Fluorine-18 approaches the ideal bone-imaging radionuclide. As it becomes more available commercially, fluorine-18 will probably replace strontium-85 as the main radionuclide for bone imaging. Although fluorine-18 bone imaging with a whole body scanner and the positron camera affords a most optimal combination, the use of strontium-85 with conventional imaging equipment provides the physician with important clinical information that cannot be obtained by other studies.

If bone biopsies are performed after the sites are located under radionuclide guidance, the chances of sampling the pathologic tissue are greatly improved. After bone scanning, two to three areas for biopsy are chosen and locating is done with 0.05 ml of Tc-99m in a tuberculin syringe under an Anger camera. Methylene blue-xylocaine is injected into the skin up to the periosteum for marking the site of the biopsy. Using this technique, 27 biopsies in 20 patients have been performed (four were open and 23 were closed needle). Pathology was found in 25 biopsies (92.6%), cancer in 22 (81.5%), benign lesions in three (11.1%), and normal bone in two (7.4%).

SUMMARY Spleen is a rare site for extraosseous localisation of 99m Tc-lahelled bone imaging agents. Intrasplenic localisation of 99m Tc-pyrophosphate (but not 99mTc-polyphosphate) was encountered in a patient with neoplastic splenic cysts due to undifferentiated histiocytic lymphoma.