Clinical Super-Resolution Computed Tomography of Bone Microstructure: Application in Musculoskeletal and Dental Imaging.

PURPOSE: Clinical cone-beam computed tomography (CBCT) devices are limited to imaging features of half a millimeter in size and cannot quantify the tissue microstructure. We demonstrate a robust deep-learning method for enhancing clinical CT images, only requiring a limited set of easy-to-acquire training data. METHODS: Knee tissue from five cadavers and six total knee replacement patients, and 14 teeth from eight patients were scanned using laboratory CT as training data for the developed super-resolution (SR) technique. The method was benchmarked against ex vivo test set, 52 osteochondral samples are imaged with clinical and laboratory CT. A quality assurance phantom was imaged with clinical CT to quantify the technical image quality. To visually assess the clinical image quality, musculoskeletal and maxillofacial CBCT studies were enhanced with SR and contrasted to interpolated images. A dental radiologist and surgeon reviewed the maxillofacial images. RESULTS: The SR models predicted the bone morphological parameters on the ex vivo test set more accurately than conventional image processing. The phantom analysis confirmed higher spatial resolution on the SR images than interpolation, but image grayscales were modified. Musculoskeletal and maxillofacial CBCT images showed more details on SR than interpolation; however, artifacts were observed near the crown of the teeth. The readers assessed mediocre overall scores for both SR and interpolation. The source code and pretrained networks are publicly available. CONCLUSION: Model training with laboratory modalities could push the resolution limit beyond state-of-the-art clinical musculoskeletal and dental CBCT. A larger maxillofacial training dataset is recommended for dental applications.

Deep learning enables time-efficient soft tissue enhancement in CBCT: Proof-of-concept study for dentomaxillofacial applications.

PURPOSE: The use of iterative and deep learning reconstruction methods, which would allow effective noise reduction, is limited in cone-beam computed tomography (CBCT). As a consequence, the visibility of soft tissues is limited with CBCT. The study aimed to improve this issue through time-efficient deep learning enhancement (DLE) methods. METHODS: Two DLE networks, UNIT and U-Net, were trained with simulated CBCT data. The performance of the networks was tested with three different test data sets. The quantitative evaluation measured the structural similarity index measure (SSIM) and the peak signal-to-noise ratio (PSNR) of the DLE reconstructions with respect to the ground truth iterative reconstruction method. In the second assessment, a dentomaxillofacial radiologist assessed the resolution of hard tissue structures, visibility of soft tissues, and overall image quality of real patient data using the Likert scale. Finally, the technical image quality was determined using modulation transfer function, noise power spectrum, and noise magnitude analyses. RESULTS: The study demonstrated that deep learning CBCT denoising is feasible and time efficient. The DLE methods, trained with simulated CBCT data, generalized well, and DLE provided quantitatively (SSIM/PSNR) and visually similar noise-reduction as conventional IR, but with faster processing time. The DLE methods improved soft tissue visibility compared to the conventional Feldkamp-Davis-Kress (FDK) algorithm through noise reduction. However, in hard tissue quantification tasks, the radiologist preferred the FDK over the DLE methods. CONCLUSION: Post-reconstruction DLE allowed feasible reconstruction times while yielding improvements in soft tissue visibility in each dataset.

Thermographic findings related to facial pain - a survey of 40 subjects.

Objective: The purpose of this study was to assess how thermography findings relate painful symptoms and signs of temporomandibular disorders (TMD).Methods: Thermography, combined with chewing of paraffin wax, was performed on 40 subjects. The results were analyzed according to gender and pain-related TMD symptoms and clinical signs.Results: The overall temperatures after chewing were higher in TMD patients than in controls. For females, the most significant findings were the thermal increase between the relaxed state and subjects' state after chewing in temporal and temporomandibular joint (TMJ) regions. For males, all calculated parameters demonstrated a poor ability to discriminate TMD from controls.Conclusion: Thermography could be a potential tool in diagnostics of female TMD patients. The results suggest that the thermal information assessed in specific facial areas could help to discriminate TMD patients from non-TMD patients and could be used to quantify the pain associated with TMD.

Quality and Findings of Bitewing Radiographs among Twenty-Year-Old Conscripts in Finland.

OBJECTIVES: Bitewing radiographs are mainly used to confirm clinical findings in caries diagnostics. The objective here was to investigate the quality of bitewing radiographs after short brush-up training and additional findings besides caries in a low-caries population. METHODS: The material of this cross-sectional study comprised 377 pairs of bitewing radiographs of 19- to 20-year-olds taken by dentists. Radiography was considered indicated if one dentinal caries lesion was present on clinical examination. A senior oral radiologist evaluated quality and diagnosed the findings afterwards unaware of clinical status. The association between variables was analysed using cross tabulation and chi-squared testing. RESULTS: Almost half of the images were of compromised quality (44.1%). Dentinal caries lesions were detected in 82.3% and enamel lesions in 73.5% of the subjects. On average, the subjects had 1.7 (SD 0.52) dentinal lesions. Fillings were found in 81.8%, fractures/cracks in 11.7%, and attrition in 7.4% of the subjects. Signs of excessive bite force were recorded in 19.4%, whereas marginal bone loss was detected in 6.4%. No significant correlation was detected between fractures, attrition, and excessive bite forces. CONCLUSIONS: Effort must be taken to ensure high quality of bitewing radiographs. In addition to caries detection, bitewing radiographs offer additional value, such as detecting excessive bite forces, tooth wear, and marginal bone loss among young adults.

Effect of display type, DICOM calibration and room illuminance in bitewing radiographs.

OBJECTIVES: To compare observer performance in the detection of both anatomical structures and caries in bitewing radiographs using consumer grade displays with and without digital imaging and communications in medicine (DICOM) calibration, tablets (third generation iPad; Apple, Cupertino, CA) and 6-megapixel (MP) displays under different lighting. METHODS: 30 bitewing radiographs were blindly evaluated on four displays under bright (510 lx) and dim (16 lx) ambient lighting by two observers. The dentinoenamel junction, enamel and dentinal caries, and the cortical border of the alveolar crests were evaluated. Consensus was considered as reference. Intraobserver agreement was determined. The proportion of equivalent ratings and weighted kappa were used to assess reliability. RESULTS: The proportion of equivalent ratings with consensus differed significantly between uncalibrated and DICOM-calibrated consumer grade display in enamel caries in upper and lower molars in bright (p = 0.013 and p = 0.003) lighting, and in dentinal caries in lower molars in both bright (p = 0.022) and dim (p = 0.004) lighting. The proportion also differed significantly between DICOM-calibrated consumer grade and 6-MP display in dentinal caries in lower molars in bright lighting (p = 0.039), tablet and consumer grade display in enamel caries in upper molars (p = 0.017) in bright lighting, tablet and 6-MP display in dentinal caries in lower molars (p = 0.003) in bright lighting and in enamel caries in lower molars (p = 0.012) in dim lighting. CONCLUSIONS: DICOM calibration improves the detection of enamel and dentinal caries in bitewing radiographs, particularly in bright lighting. Therefore, a calibrated consumer grade display can be recommended as a diagnostic tool for viewing bitewing radiographs.

Endostatin affects osteoblast behavior in vitro, but collagen XVIII/endostatin is not essential for skeletal development in vivo.

Endostatin, a fragment of collagen XVIII, can inhibit vascular endothelial growth factor (VEGF) signaling. VEGF is known to be crucial for bone development. The aims of this study were to investigate the influences of endostatin on osteoblast behavior in vitro and the roles of collagen XVIII/endostatin on bone development in vivo. For the in vitro experiments, MC3T3-E1 osteoblasts were treated with VEGF-A, 2 microg/ml endostatin, 20 microg/ml endostatin, VEGF-A + 2 microg/ml endostatin, or VEGF-A + 20 microg/ml endostatin. Osteoblast proliferation and matrix mineralization were analyzed. Faxitron, pQCT, and histological analyses were performed on hindleg bones of transgenic mice overexpressing endostatin (ES-tg) and mice lacking collagen XVIII (Col18a1 (-/-)) to study bone development in vivo. Treatment of cells with endostatin decreased osteoblast proliferation. Moreover, VEGF-A together with endostatin (2 microg/ml) decreased osteoblast proliferation and matrix mineralization. In vivo, Col18a1 (-/-) and ES-tg mice displayed no differences in bone density or mineral content during bone development, but ES-tg bones grew in length more slowly compared to the controls. The formation of secondary ossification centers was delayed in Col18a1 (-/-) mice. Immunohistochemistry revealed collagen XVIII in basement membranes of periosteal and bone marrow vessels and at muscle attachment sites. In conclusion, endostatin affects osteoblast behavior in vitro, the effects being boosted by simultaneous treatment with VEGF. In vivo, Col18a1 (-/-) and ES-tg mice show mild delays in bone development. These changes are transitory and suggest that collagen XVIII/endostatin does not play an indispensable role in skeletal development.

Endostatin inhibits VEGF-A induced osteoclastic bone resorption in vitro.

BACKGROUND: Endostatin is a C-terminal fragment of collagen XVIII which is a component of basement membranes with the structural properties of both collagens and proteoglycans. Endostatin has a major role in angiogenesis which is intimately associated with bone development and remodeling. Signaling between the endothelial cells and the bone cells, for example, may have a role in recruitment of osteoclastic precursor cells. Our study aims at exploring a possibility that endostatin, either as a part of basement membrane or as a soluble molecule, may control osteoclastogenesis and osteoclastic bone resorption in vitro. METHODS: Rat pit formation assay was employed in order to examine the effect of endostatin alone or in combination with vascular endothelial growth factor-A (VEGF-A) on bone resorption in vitro. Effect of these agents on osteoclast differentiation in vitro was also tested. Osteoclastogenesis and the number of osteoclasts were followed by tartrate resistant acid phosphatase (TRACP) staining and resorption was evaluated by measuring the area of excavated pits. RESULTS: Endostatin inhibited the VEGF-A stimulated osteoclastic bone resorption, whereas endostatin alone had no effect on the basal resorption level in the absence of VEGF-A. In addition, endostatin could inhibit osteoclast differentiation in vitro independent of VEGF-A. CONCLUSION: Our in vitro data indicate that collagen XVIII/endostatin can suppress VEGF-A induced osteoclastic bone resorption to the basal level. Osteoclastogenesis is also inhibited by endostatin. The regulatory effect of endostatin, however, is not critical since endostatin alone does not modify the basal bone resorption.

Adenoviral VEGF-A gene transfer induces angiogenesis and promotes bone formation in healing osseous tissues.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis. VEGF has been safely and efficiently applied to stimulate neovascularization in ischemic tissues in atherosclerotic patients. VEGF has an important role in bone repair by promoting angiogenesis and by stimulating major skeletal cell populations, chondrocytes, osteoblasts and osteoclasts. METHODS: We studied the effect of VEGF-A on the recovery of bone drilling defects in rat femur delivered with first-generation adenoviral vector. The virus was injected into the muscle layer surrounding the bone defect made by drilling and the healing was followed for 1, 2, and 4 weeks. RESULTS: The VEGF effect was first demonstrated with an increased number of FVIII-related antigen-positive blood vessels in the defect area 1 week after the procedure. The proportional area of remaining reparative tissue was significantly reduced in the VEGF-treated animals 2 weeks after the injury suggesting favorable effect on bone healing. Increased periosteal cartilage was seen at the early phases of healing suggesting endochondral ossification. VEGF overexpression, however, completed the endochondral phase earlier compared with the control condition. Bone mineral content was enhanced in the VEGF-treated femurs measured with peripheral quantitative computed tomography at a 2-week time point. CONCLUSIONS: Our data confirm the important role of VEGF in bone healing. We show for the first time that adenoviral VEGF-A gene transfer may modify bone defect healing in a rodent model.