Semi-automatic method for pre-surgery scoliosis classification on X-ray images using Bending Asymmetry Index.

PURPOSE: Bending Asymmetry Index (BAI) has been proposed to characterize the types of scoliotic curve in three-dimensional ultrasound imaging. Scolioscan has demonstrated its validity and reliability in scoliosis assessment with manual assessment-based X-ray imaging. The objective of this study is to investigate the ultrasound-derived BAI method to X-ray imaging of scoliosis, with supplementary information provided for the pre-surgery planning. METHODS: About 30 pre-surgery scoliosis subjects (9 males and 21 females; Cobb: 50.9 ± 19.7°, range 18°-115°) were investigated retrospectively. Each subject underwent three-posture X-ray scanning supine on a plain mattress on the same day. BAI is an indicator to distinguish structural or non-structural curves through the spine flexibility information obtained from lateral bending spinal profiles. BAI was calculated semi-automatically with manual annotation of vertebral centroids and pelvis level inclination adjustment. BAI classification was validated with the scoliotic curve type and traditional Lenke classification using side-bending Cobb angle measurement (S-Cobb). RESULTS: 82 curves from 30 pre-surgery scoliosis patients were included. The correlation coefficient was R2 = 0.730 (p < 0.05) between BAI and S-Cobb. In terms of scoliotic curve type classification, all curves were correctly classified; out of 30 subjects, 1 case was confirmed as misclassified when applying to Lenke classification earlier, thus has been adjusted. CONCLUSION: BAI method has demonstrated its inter-modality versatility in X-ray imaging application. The curve type classification and the pre-surgery Lenke classification both indicated promising performances upon the exploratory dataset. A fully-automated of BAI measurement is surely an interesting direction to continue our endeavor. Deep learning on the vertebral-level segmentation should be involved in further study.

Low-Intensity Pulsed Ultrasound Stimulation for Bone Fractures Healing: A Review.

Low-intensity pulsed ultrasound (LIPUS) is a developing technology, which has been proven to improve fracture healing process with minimal thermal effects. This noninvasive treatment accelerates bone formation through various molecular, biological, and biomechanical interactions with tissues and cells. Although LIPUS treatment has shown beneficial effects on different bone fracture locations, only very few studies have examined its effects on deeper bones. This study provides an overview on therapeutic ultrasound for fractured bones, possible mechanisms of action, clinical evidences, current limitations, and its future prospects.

Using Ultrasound to Screen for Scoliosis to Reduce Unnecessary Radiographic Radiation: A Prospective Diagnostic Accuracy Study on 442 Schoolchildren.

Scoliosis screening is important for timely initiation of brace treatment to mitigate curve progression in skeletally immature children and adolescents. School scoliosis screening programs in Hong Kong follow the protocol of referring children screened positive with a scoliometer and Moiré topography for confirmatory standard radiography. Despite being highly sensitive (88%) in detecting those who require specialist referral, the screening program was found to have a false-positive rate >50%, which could lead to unnecessary X-ray radiation. Radiation-free ultrasound has been reported to be valid and reliable for quantitative assessment of curve severity in scoliosis patients. The aim of this prospective diagnostic accuracy study was to determine the accuracy of ultrasound in determining the threshold of referral that requires X-ray for children screened positive with the scoliometer and Moiré topography. Our study recruited 442 schoolchildren with a mean Cobb angle of 14.0 ± 6.6°. The sensitivity and specificity of ultrasound in predicting the correct referral status, confirmed by X-ray, were 92.3% and 51.6%, with positive and negative predictive values of 29.0% and 96.9%, respectively. Receiver operating characteristic curve analysis revealed area under the curve values of 0.735 for ultrasound alone and 0.832 for ultrasound in combination with measurement of angle of trunk rotation. The finding supports the accuracy of using ultrasound to determine referral status, which could result in a >50% reduction of unnecessary radiation for children undergoing scoliosis screening.

Validation of Scolioscan Air-Portable Radiation-Free Three-Dimensional Ultrasound Imaging Assessment System for Scoliosis.

To diagnose scoliosis, the standing radiograph with Cobb's method is the gold standard for clinical practice. Recently, three-dimensional (3D) ultrasound imaging, which is radiation-free and inexpensive, has been demonstrated to be reliable for the assessment of scoliosis and validated by several groups. A portable 3D ultrasound system for scoliosis assessment is very much demanded, as it can further extend its potential applications for scoliosis screening, diagnosis, monitoring, treatment outcome measurement, and progress prediction. The aim of this study was to investigate the reliability of a newly developed portable 3D ultrasound imaging system, Scolioscan Air, for scoliosis assessment using coronal images it generated. The system was comprised of a handheld probe and tablet PC linking with a USB cable, and the probe further included a palm-sized ultrasound module together with a low-profile optical spatial sensor. A plastic phantom with three different angle structures built-in was used to evaluate the accuracy of measurement by positioning in 10 different orientations. Then, 19 volunteers with scoliosis (13F and 6M; Age: 13.6 ± 3.2 years) with different severity of scoliosis were assessed. Each subject underwent scanning by a commercially available 3D ultrasound imaging system, Scolioscan, and the portable 3D ultrasound imaging system, with the same posture on the same date. The spinal process angles (SPA) were measured in the coronal images formed by both systems and compared with each other. The angle phantom measurement showed the measured angles well agreed with the designed values, 59.7 ± 2.9 vs. 60 degrees, 40.8 ± 1.9 vs. 40 degrees, and 20.9 ± 2.1 vs. 20 degrees. For the subject tests, results demonstrated that there was a very good agreement between the angles obtained by the two systems, with a strong correlation (R2 = 0.78) for the 29 curves measured. The absolute difference between the two data sets was 2.9 ± 1.8 degrees. In addition, there was a small mean difference of 1.2 degrees, and the differences were symmetrically distributed around the mean difference according to the Bland-Altman test. Scolioscan Air was sufficiently comparable to Scolioscan in scoliosis assessment, overcoming the space limitation of Scolioscan and thus providing wider applications. Further studies involving a larger number of subjects are worthwhile to demonstrate its potential clinical values for the management of scoliosis.

Chemotherapy-Enriched THBS2-Deficient Cancer Stem Cells Drive Hepatocarcinogenesis through Matrix Softness Induced Histone H3 Modifications.

The physical microenvironment is a critical mediator of tumor behavior. However, detailed biological and mechanistic insight is lacking. The present study reveals the role of chemotherapy-enriched CD133+ liver cancer stem cells (CSCs) with THBS2 deficiency. This subpopulation of cells contributes to a more aggressive cancer and functional stemness phenotype in hepatocellular carcinoma (HCC) by remodeling the extracellular matrix (ECM) through the regulation of matrix metalloproteinase (MMP) activity, collagen degradation, and matrix stiffness. The local soft spots created by these liver CSCs can enhance stemness and drug resistance and provide a route of escape to facilitate HCC metastasis. Interestingly, a positive feed-forward loop is identified where a local soft spot microenvironment in the HCC tumor is enriched with CD133 expressing cells that secrete markedly less ECM-modifying THBS2 upon histone H3 modification at its promoter region, allowing the maintenance of a localized soft spot matrix. Clinically, THBS2 deficiency is also correlated with low HCC survival, where high levels of CSCs with low THBS2 expression in HCC are associated with decreased collagen fiber deposits and an invasive tumor front. The findings have implications for the treatment of cancer stemness and for the prevention of tumor outgrowth through disseminated tumor cells.

Cross-validation of ultrasound imaging in adolescent idiopathic scoliosis.

PURPOSE: Adolescent idiopathic scoliosis (AIS) patients are exposed to 9-10 times more radiation and a fivefold increased lifetime cancer risk. Radiation-free imaging alternatives are needed. Ultrasound imaging of spinal curvature was shown to be accurate, however, systematically underestimating the Cobb angle. The purpose of this study is to create and cross-validate an equation that calculates the expected Cobb angle using ultrasound spinal measurements of AIS patients. METHODS: Seventy AIS patients with upright radiography and spinal ultrasound were split randomly in a 4:1 ratio to the equation creation (n = 54) or validation (n = 16) group. Ultrasound angles based on the spinous processes shadows were measured automatically by the ultrasound system (Scolioscan, Telefield, Hong Kong). For thoracic and lumbar curves separately, the equation: expected Cobb angle = regression coefficient × ultrasound angle, was created and subsequently cross-validated in the validation group. RESULTS: Linear regression analysis between ultrasound angles and radiographic Cobb angles (thoracic: R2 = 0.968, lumbar: R2 = 0.923, p < 0.001) in the creation group resulted in the equations: thoracic Cobb angle = 1.43 × ultrasound angle and lumbar Cobb angle = 1.23 × ultrasound angle. With these equations, expected Cobb angles in the validation group were calculated and showed an excellent correlation with the radiographic Cobb angles (thoracic: R2 = 0.959, lumbar: R2 = 0.936, p < 0.001). The mean absolute differences were 6.5°-7.3°. Bland-Altman plots showed good accuracy and no proportional bias. CONCLUSION: The equations from ultrasound measurements to Cobb angles were valid and accurate. This supports the implementation of ultrasound imaging, possibly leading to less frequent radiography and reducing ionizing radiation in AIS patients.

Automatic Segmentation of 3D Ultrasound Spine Curvature Using Convolutional Neural Network.

Scoliosis is a 3D spinal deformation where the spine takes a lateral curvature, which generates an angle in a coronal plane. For periodic detection of scoliosis, safe and economic imaging modality is needed as continuous exposure to radiative imaging may cause cancer. 3D ultrasound imaging is a cost-effective and radiation-free imaging modality which gives volume projection image. Identification of mid-spine line using manual, semi-automatic and automatic methods have been published. Still, there are some difficulties like variations in human measurement, slow processing of data associated with them. In this paper, we propose an unsupervised ground truth generation and automatic spine curvature segmentation using U- Net. This approach of the application of Convolutional Neural Network on ultrasound spine image, to perform automatic detection of scoliosis, is a novel one.

Miniaturized Water-Jet Ultrasound Indentation System for Quantitative Assessment of Articular Cartilage Degeneration: A Validation Study.

Osteoarthritis is a common joint disease affecting a large population especially the elderly where cartilage degeneration is one of its hallmark symptoms. There is a need to develop new devices and instruments for the early detection and treatment of cartilage degeneration. In this study, we describe the development of a miniaturized water-jet ultrasound indentation probe for this purpose. To evaluate the system, we applied it to characterize the degeneration of articular cartilage with the measurement of its morphologic, acoustic, and mechanical properties, using the enzymatic digestions of cartilage as a model of OA. Fifty cartilage samples were tested with 10 of them used for the reproducibility study and the other 40 for collagenase and trypsin digestions. Thickness, integrated reflection coefficient (IRC), effective stiffness, and energy dissipation ratio (EDR) were used to quantify the change of articular cartilage before and after degeneration. The measurement reproducibility as represented by the standardized coefficient of variation (SCV) was 2.6%, 10.2%, 11.5%, and 12.8% for thickness, IRC, stiffness, and EDR, respectively. A significant change of IRC, stiffness, and EDR was detected after degeneration by the designed probe (p < 0.05). There was also a significant difference of IRC, stiffness, and EDR between trypsin and collagenase digestions (p < 0.001). In conclusion, a miniaturized water-jet ultrasound indentation probe has been designed, which has been successfully used to detect and differentiate cartilage degeneration simulated by enzymatic digestions. This probe, with future development, can be potentially suitable for quantitative assessment of cartilage degeneration with an arthroscopic operation.

Is Radiation-Free Ultrasound Accurate for Quantitative Assessment of Spinal Deformity in Idiopathic Scoliosis (IS): A Detailed Analysis With EOS Radiography on 952 Patients.

Radiation exposure with repeated radiography required at follow-up poses serious health concerns for scoliosis patients. Although spinous process angle (SPA) measurement of spinal curvatures with ultrasound has been reported with promising results, an evidence-based account on its accuracy for translational application remains undefined. This prospective study involved 952 idiopathic scoliosis patients (75.7% female, mean age 16.7 ± 3.0 y, Cobb 28.7 ± 11.6°). Among 1432 curves (88.1%) detected by ultrasound, there was good correlation between radiologic Cobb angles measured manually on EOS (E_Cobb) whole-spine radiographs and automatic ultrasound SPA measurement for upper spinal curves (USCs) (r = 0.873, apices T7-T12/L1 intervertebral disc) and lower spinal curves (LSCs) (r = 0.740, apices L1 or below) (p < 0.001). Taller stature was associated with stronger correlation. For E_Cobb <30°, 66.6% USCs and 62.4% LSCs had absolute differences between E_Cobb and predicted Cobb angle calculated from SPA ≤5°. Ultrasound could be a viable option in lieu of radiography for measuring coronal curves with apices at T7 or lower and Cobb angle <30°.

Experimental spinal cord injury and behavioral tests in laboratory rats.

Traumatic spinal cord injury (SCI) results in some serious neurophysiological consequences that alter healthy body functions and devastate the quality of living of individuals. To find a cure for SCI, researchers around the world are working on different neurorepair and neurorehabilitation modalities. To test a new treatment for SCI as well as to understand the mechanism of recovery, animal models are being widely used. Among them, SCI rat models are arguably the most prominent. Furthermore, it is important to select a suitable behavioral test to evaluate both the motor and sensory recovery following any therapeutic intervention. In this paper, we review the rat models of spinal injury and commonly used behavioral tests to serve as a useful guideline for neuroscientists in the field of SCI research.

Diagnosis and treatment of diastematomyelia in children: a perspective cohort study.

Study design: Cohort study. Objectives: The objectives of this study were examination, observation and surgical interventions of pediatric patients with diastematomyelia, a rare congenital deformity of the spinal cord. Setting: Spine surgery and neurosurgery clinic under ministry of health, the Russian Federation. Methods: Twenty children (1-18 years of age) with diastematomyelia participated in this study. Diagnosis was based on subjects' medical history, results of clinical examination, spine radiography in anteroposterior and lateral views, and neurophysiological examinations. Septum resection surgery was done in seventeen subjects. Results: All the subjects had skin manifestations along the midline of the back. Neurological symptoms were noted in 17 subjects: paraparesis in 11, urinary incontinence in 2, monoparesis in 4, and spasticity in 2 subjects. Three subjects did not show any neurological deficit. Orthopedic examination revealed spinal deformities of various degrees of severity. In 4 subjects, partial restorations of neurological functions were observed; and in 1 subject, bladder incontinence developed after the surgery. Conclusions: Patients who have limb length discrepancy, congenital scoliosis, skin manifestations should be examined for the presence of diastematomyelia. Patients having neither neurological deficit nor orthopedic deterioration should be monitored, and in case of deterioration, surgical treatment should be reserved. We advocate for performing resection of the septum in patients with diastematomyelia prior to surgical correction of scoliosis or orthopedic correction of lower limb deformities.

HCBP6 Is Involved in the Development of Hepatic Steatosis Induced by High-Fat Diet and CCL4 in Rats.

INTRODUCTION AND AIM: Hepatitis C virus core-binding protein 6 (HCBP6) was previously found to be an hepatitis C virus corebinding protein, its biological function remains unclear. Our research aims to investigate the role of HCBP6 in the development of hepatic steatosis induced by high-fat diet and carbon tetrachloride (CCL4) in rats. MATERIAL AND METHODS: Eighteen Wistar rats were randomly allocated into 3 groups: control group, model group 1, and model group 2. The control group was treated with a standard diet for 5 weeks. Model groups were treated with high-fat diet and CCL4 injection twice a week for 3 weeks in Group 1 and 5 weeks in Group 2, respectively. After the intervention, hepatic steatosis was observed by histological staining with hematoxylin and eosin (H&E) and Oil Red O staining. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total colesterol (TC), and triglycerides (TGs) were measured. The TG content in liver homogenates was evaluated. Expressions of HCBP6 and SREBP-1c were determined by immunofluorescence, quantitative real-time PCR, and Western blot analysis. RESULTS: Hepatic steatosis was successfully induced in model groups. ALT, AST, TC, and TGs elevated in model groups compared with those in control group (P < 0.05). Hepatic steatosis induced by high-fat diet and CCL4 resulted in low expression of HCBP6 and high expression of SREBP-1c in the liver of rats (P < 0.05). CONCLUSION: HCBP6 is involved in the development of high-fat diet- and CCL4-induced hepatic steatosis and related negatively with SREBP-1c.

Hepatitis transactivator protein X promotes extracellular matrix modification through HIF/LOX pathway in liver cancer.

Hepatocellular carcinoma (HCC), accounting for 90% of primary liver cancer, is a lethal malignancy that is tightly associated with chronic hepatitis B virus (HBV) infection. HBV encodes a viral onco-protein, transactivator protein X (HBx), which interacts with proteins of hepatocytes to promote oncogenesis. Our current study focused on the interaction of HBx with a transcription factor, hypoxia-inducible factor-1α (HIF-1α), which is stabilized by low O2 condition (hypoxia) and is found to be frequently overexpressed in HCC intra-tumorally due to poor blood perfusion. Here, we showed that overexpression of HBx by tetracycline-inducible systems further stabilized HIF-1α under hypoxia in HBV-negative HCC cell lines. Reversely, knockdown of HBx reduced HIF-1α protein stabilization under hypoxia in HBV-positive HCC cell lines. More intriguingly, overexpression of HBx elevated the mRNA and protein expression of a family of HIF-1α target genes, the lysyl oxidase (LOX) family in HCC. The LOX family members function to cross-link collagen in the extracellular matrix (ECM) to promote cancer progression and metastasis. By analyzing the collagens under scanning electron microscope, we found that collagen fibers were significantly smaller in size when incubated with conditioned medium from HBx knockdown HCC cells as compared to control HCC cells in vitro. Transwell invasion assay further revealed that less cells were able to invade through the matrigel which was pre-treated with conditioned medium from HBx knockdown HCC cells as compared to control HCC cells. Orthotopic and subcutaneous HCC models further showed that knockdown of HBx in HCC cells reduced collagen crosslinking and stiffness in vivo and repressed HCC growth and metastasis. Taken together, our in vitro and in vivo studies showed the HBx remodeled the ECM through HIF-1α/LOX pathway to promote HCC metastasis.

A reliability and validity study for Scolioscan: a radiation-free scoliosis assessment system using 3D ultrasound imaging.

BACKGROUND: Radiographic evaluation for patients with scoliosis using Cobb method is the current gold standard, but radiography has radiation hazards. Several groups have recently demonstrated the feasibility of using 3D ultrasound for the evaluation of scoliosis. Ultrasound imaging is radiation-free, comparatively more accessible, and inexpensive. However, a reliable and valid 3D ultrasound system ready for clinical scoliosis assessment has not yet been reported. Scolioscan is a newly developed system targeted for scoliosis assessment in clinics by using coronal images of spine generated by a 3D ultrasound volume projection imaging method. The aim of this study is to test the reliability of spine deformity measurement of Scolioscan and its validity compared to the gold standard Cobb angle measurements from radiography in adolescent idiopathic scoliosis (AIS) patients. METHODS: Prospective study divided into two stages: 1) Investigation of intra- and inter- reliability between two operators for acquiring images using Scolioscan and among three raters for measuring spinal curves from those images; 2) Correlation between the Cobb angle obtained from radiography by a medical doctor and the spine curve angle obtained using Scolioscan (Scolioscan angle). The raters for ultrasound images and the doctors for evaluating radiographic images were mutually blinded. The two stages of tests involved 20 (80 % females, total of 26 angles, age of 16.4 ± 2.7 years, and Cobb angle of 27.6 ± 11.8°) and 49 (69 % female, 73 angles, 15.8 ± 2.7 years and 24.8 ± 9.7°) AIS patients, respectively. Intra-class correlation coefficients (ICC) and Bland-Altman plots and root-mean-square differences (RMS) were employed to determine correlations, which interpreted based on defined criteria. RESULTS: We demonstrated a very good intra-rater and intra-operator reliability for Scolioscan angle measurement with ICC larger than 0.94 and 0.88, respectively. Very good inter-rater and inter-operator reliability was also demonstrated, with both ICC larger than 0.87. For the thoracic deformity measurement, the RMS were 2.5 and 3.3° in the intra- and inter-operator tests, and 1.5 and 3.6° in the intra- and inter-rater tests, respectively. The RMS differences were 3.1, 3.1, 1.6, 3.7° in the intra- and inter-operator and intra- and inter-rater tests, respectively, for the lumbar angle measurement. Moderate to strong correlations (R(2) > 0.72) were observed between the Scolioscan angles and Cobb angles for both the thoracic and lumbar regions. It was noted that the Scolioscan angle slightly underestimated the spinal deformity in comparison with Cobb angle, and an overall regression equation y = 1.1797x (R(2) = 0.76) could be used to translate the Scolioscan angle (x) to Cobb angle (y) for this group of patients. The RMS difference between Scolioscan angle and Cobb angle was 4.7 and 6.2°, with and without the correlation using the overall regression equation. CONCLUSIONS: We showed that Scolioscan is reliable for measuring coronal deformity for patients with AIS and appears promising in screening large numbers of patients, for progress monitoring, and evaluation of treatment outcomes. Due to it being radiation-free and relatively low-cost, Scolioscan has potential to be widely implemented and may contribute to reducing radiation dose during serial monitoring.

Clinical Evaluation of a 3-D Automatic Annotation Method for Breast Ultrasound Imaging.

The routine clinical breast ultrasound annotation method is limited by the time it consumes, inconsistency, inaccuracy and incomplete notation. A novel 3-D automatic annotation method for breast ultrasound imaging has been developed that uses a spatial sensor to track and record conventional B-mode scanning so as to provide more objective annotation. The aim of the study described here was to test the feasibility of the automatic annotation method in clinical breast ultrasound scanning. An ultrasound scanning procedure using the new method was established. The new method and the conventional manual annotation method were compared in 46 breast cancer patients (49 ± 12 y). The time used for scanning a patient was recorded and compared for the two methods. Intra-observer and inter-observer experiments were performed, and intra-class correlation coefficients (ICCs) were calculated to analyze system reproducibility. The results revealed that the new annotation method had an average scanning time 36 s (42.9%) less than that of the conventional method. There were high correlations between the results of the two annotation methods (r = 0.933, p < 0.0001 for distance; r = 0.995, p < 0.0001 for radial angle). Intra-observer and inter-observer reproducibility was excellent, with all ICCs > 0.92. The results indicated that the 3-D automatic annotation method is reliable for clinical breast ultrasound scanning and can greatly reduce scanning time. Although large-scale clinical studies are still needed, this work verified that the new annotation method has potential to be a valuable tool in breast ultrasound examination.

Subarray coherence based postfilter for eigenspace based minimum variance beamformer in ultrasound plane-wave imaging.

This paper introduces a new beamformer, which combines the eigenspace based minimum variance (ESBMV) beamformer with a subarray coherence based postfilter (SCBP), for improving the quality of ultrasound plane-wave imaging. The ESBMV beamformer has been validated in improving the imaging contrast, but the difficulty in dividing the signal subspace limits the usage of it in the low signal-to-noise ratio (SNR) scenarios. Coherence factor (CF) based methods could optimize the output of a distortionless beamformer to reduce sidelobes, but the influence by the subarray decorrelation technique on the postfilter design has not attracted enough concern before. Accordingly, an ESBMV-SCBP beamformer was proposed in this paper, which used the coherence of the subarray signal to compute an SCBP to optimize the ESBMV results. Simulated and experimental data were used to evaluate the performance of the proposed method. The results showed that the ESBMV-SCBP method achieved an improved imaging quality compared with the ESBMV beamformer. In the simulation study, the contrast ratio (CR) for an anechoic cyst was improved by 9.88 dB and the contrast-to-noise ratio (CNR) was improved by 0.97 over the ESBMV. In the experimental study, the CR improvements for two anechoic cysts were 7.32 dB and 9.45 dB, while the CNRs were improved by 1.27 and 0.66, respectively. The ESBMV-SCBP also showed advantages over the ESBMV-Wiener beamformer in preserving a less grainy speckle, which is closer to that of distortionless beamformers and benefits the imaging contrast. With a relatively small extra computational load, the proposed method has potential to enhance the quality of the ultrasound plane-wave imaging.

A novel breast ultrasound system for providing coronal images: system development and feasibility study.

Breast ultrasound images along coronal plane contain important diagnosis information. However, conventional clinical 2D ultrasound cannot provide such images. In order to solve this problem, we developed a novel ultrasound system aimed at providing breast coronal images. In this system, a spatial sensor was fixed on an ultrasound probe to obtain the image spatial data. A narrow-band rendering method was used to form coronal images based on B-mode images and their corresponding spatial data. Software was developed for data acquisition, processing, rendering and visualization. In phantom experiments, 20 inclusions with different size (5-20 mm) were measured using this new system. The results obtained by the new method well correlated with those measured by a micrometer (y=1.0147x, R(2)=0.9927). The phantom tests also showed that this system had excellent intra- and inter-operator repeatability (ICC>0.995). Three subjects with breast lesions were scanned in vivo using this new system and a commercially available three-dimensional (3D) probe. The average scanning times for the two systems were 64 s and 74 s, respectively. The results revealed that this new method required shorter scanning time. The tumor sizes measured on the coronal plane provided by the new method were smaller by 5.6-11.9% in comparison with the results of the 3D probe. The phantom tests and preliminary subject tests indicated the feasibility of this system for clinical applications by providing additional information for clinical breast ultrasound diagnosis.

Assessment of ocular biomechanics using dynamic ultra high-speed Scheimpflug imaging in keratoconic and normal eyes.

PURPOSE: To introduce several new ocular biomechanical parameters for comparison between keratoconic and normal eyes using an analysis method based on corneal dynamic deformation video recorded by corneal visualization Scheimpflug technology (Corvis ST; Oculus Optikgeräte GmbH, Wetzlar, Germany). METHODS: This comparative study comprised 52 keratoconic eyes of 43 patients with keratoconus and 52 normal eyes of 52 controls. An analysis method (PolyU [Labview 2009; National Instrument, Austin, TX]) was developed to introduce several new ocular biomechanical parameters and to compare the difference between keratoconic and normal eyes. The repeatability of the new parameters measurement was evaluated and compared with the Corvis ST measurement. Receiver operating characteristic curves were used to establish a cutoff value for the new biomechanical parameters. RESULTS: Intraclass correlation coefficients of the deformation amplitude, peak distance, corneal concave radius of curvature, maximum deformation area, maximum corneal inward velocity and outward velocity (Vin, max and Vout, max) were high in both the keratoconic and normal eyes (all intraclass correlation coefficients > 0.75). The measurement agreement of the PolyU analysis method and Corvis ST was good. Most of the biomechanical parameters of patients with keratoconus were significantly different from those of the controls. In the receiver operating characteristic analysis, the Vin, max was the best predictive parameter with an area under the curve of 0.79. CONCLUSIONS: The corneal deformation video recorded by the Corvis ST provides useful information for the study of ocular biomechanics. Most of the new ocular biomechanical parameters were significantly different between keratoconic and normal eyes. Further research is needed to develop more comprehensive clinical applications with these new ocular biomechanical parameters.

Lysyl oxidase-like 2 is critical to tumor microenvironment and metastatic niche formation in hepatocellular carcinoma.

UNLABELLED: Poor prognosis of cancers, including hepatocellular carcinoma (HCC), is mainly associated with metastasis; however, the underlying mechanisms remain poorly understood. This article investigates the role of lysyl oxidase-like 2 (LOXL-2) in the biology of HCC metastasis. First, we showed that HCC metastasis relies on a collagen-modifying enzyme, LOXL2, which was significantly overexpressed in tumorous tissues and sera of HCC patients, indicating that LOXL2 may be a good diagnostic marker for HCC patients. Second, we delineated a complex, interlinked signaling network that involves multiple regulators, including hypoxia, transforming growth factor beta (TGF-ß), and microRNAs (miRNAs), converging to control the expression of LOXL2. We found not only that LOXL2 was regulated by hypoxia/hypoxia-inducible factor 1 alpha (HIF-1α), but also that TGF-ß activated LOXL2 transcription through mothers against decapentaplegic homolog 4 (Smad4), whereas two frequently underexpressed miRNA families, miR-26 and miR-29, cooperatively suppressed LOXL2 transcription through interacting with the 3' untranslated region of LOXL2. Third, we demonstrated the imperative roles of LOXL2 in modifying the extracellular matrix components in the tumor microenvironment and metastatic niche of HCC. LOXL2 promoted intrahepatic metastasis by increasing tissue stiffness, thereby enhancing the cytoskeletal reorganization of HCC cells. Furthermore, LOXL2 facilitated extrahepatic metastasis by enhancing recruitment of bone-marrow-derived cells to the metastatic site. CONCLUSION: These findings integrate the clinical relevance, molecular regulation, and functional implications of LOXL2 in HCC metastasis.

An ultrasound biomicroscopic and water jet ultrasound indentation method for detecting the degenerative changes of articular cartilage in a rabbit model of progressive osteoarthritis.

It is important to assess the early degeneration of articular cartilage associated with osteoarthritis (OA) for early intervention and treatment planning. Previously, we have developed a high frequency ultrasound and water jet indentation method for the morphologic, acoustic and mechanical assessment of articular cartilage, using the enzymatic digestion as a model of osteoarthritic degeneration. No naturally degenerated articular cartilage has been tested with the developed method. In this study, we aimed to determine the usefulness of the developed method for detecting the natural degeneration of articular cartilage in a standard surgical model of OA in rabbits. Forty adult New Zealand white female rabbits were used in this study, which included 30 experimental rabbits undergoing the right anterior cruciate ligament transection surgery and 10 control rabbits. At the 3rd, 6th, and 9th week post-surgery, 10 experimental rabbits were sacrificed, respectively, for assessment of the knee cartilage quality. The cartilage at the medial and lateral femoral condyles and tibial plateaus (four points) was measured by the high frequency ultrasound biomicroscopy, the water jet ultrasound indentation and a contact mechanical indentation test before a histopathologic analysis for grading of degeneration severity. Measured parameters were compared among different groups classified either by post-surgery time or by histopathologic grade. The results showed a general trend of increase for ultrasound roughness index and a general trend of decrease for integrated reflection coefficient, stiffness coefficient from water-jet indentation and Young's modulus (E) from the mechanical indentation with the increase of post-surgery time. Comparisons among groups with different histopathologic grades showed similar trend with the increase of degeneration severity. The water jet ultrasound indentation method was demonstrated to be an effective method to measure the mechanical properties of the articular cartilage and with further development of arthroscopic ultrasound probe; it has the ability to assess the early degeneration of articular cartilage with measurement of morphologic, acoustic and mechanical properties of the cartilage in vivo.