Effect of angiotensin II type I receptor blocker losartan on bone deterioration in orchiectomized male hypertensive and normotensive rats.

BACKGROUND: Epidemiological study showed that the use of angiotensin-converting enzyme inhibitors was associated with higher bone mineral density (BMD) in older people, especially male subjects, which suggested that angiotensin II may have a detrimental effect on bone. Therefore, blocking its effect may have a beneficial effect on bone health. METHODS: Six-month-old male spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) were used. Animals of each model were randomly assigned to the following four groups: Group 1, SHAM operated+vehicle; Group 2, orchidectomy (ORX)+vehicle; Group 3, ORX+low-dose losartan (10 mg×kg(-1)×d(-1)); and Group 4, ORX+high-dose losartan (25 mg×kg(-1)×d(-1)). Blood pressure was recorded weekly. SHAM and ORX operations were performed, followed by daily losartan and vehicle treatment from day 4 after operation for 16 weeks. Serum and 24-hour urine samples were collected for measurement of bone turnover markers before euthanasia and then the left femur was collected for measurements of BMD and microarchitecture before mechanical test. RESULTS: Urine deoxypyridinoline/urine creatinine (DPD/Cr) ratio was significantly higher in SHR than in WKY. BMD and microarchitecture parameters also showed bone deterioration in SHR. After ORX, serum osteocalcin concentration decreased and urine DPD/Cr ratio increased significantly accompanied by a significant decrease in cortical and trabecular BMD and cortical bone thickness in both WKY and SHR. High-dose losartan significantly increased DPD in urine in both SHR and WKY. Apart from marginal favorable changes in bone architecture in WKY treated with high-dose losartan, losartan did not show significant effect on BMD, bone area, bone microarchitecture, and mechanical properties in both SHR and WKY. CONCLUSION: Angiotensin II type I receptor blocker losartan was not able to demonstrate significant effect on ORX-induced bone deterioration in both hypertensive and normotensive rats.

Potential reproductive toxicity of Largehead Atractylodes Rhizome, the most commonly used Chinese medicine for threatened miscarriage.

BACKGROUND: Largehead Atractylodes Rhizome (LAR) is the most commonly used Chinese medicine to prevent early pregnancy loss due to threatened miscarriage. However, its safety profile during pregnancy is still not available. Here we aimed to identify the potential adverse effects of LAR on embryo-fetal development as well as prenatal and post-natal growth. METHODS: Pregnant mice, rats and rabbits were orally administered with LAR extracts in various doses (from 1×, 2×, 3× and up to 6× clinical doses) at different gestational periods (implantation, gastrulation, organogenesis, maturation and whole gestation). Maternal effects on weight loss, implantation failure and fetal resorption and perinatal effects on developmental delay, growth restriction and congenital malformations were studied. RESULTS: In mice, with early LAR exposure, a significant decrease in fetal growth parameters and a significant increase in post-implantation loss were identified. With late LAR exposure, significant increases in gestational duration as well as prenatal and post-natal mortality were found. At high clinical doses, congenital skeletal malformations were recorded. In rabbits, fetal resorption, hydrops fetalis and short ear anomaly were observed. No significant adverse effects were found in rats. CONCLUSIONS: Potential reproductive toxicity of LAR in pregnant animals was identified within the clinical dose. Caution should be taken in clinical applications of LAR during pregnancy.

A novel statistical morphometry imaging method for differentiating long bone geometry: methodological development and application with adolescent idiopathic scoliosis (AIS) patients.

Non-invasive quantification of bone shape is crucial in orthopaedic research. The primary objective of this study was to develop an automated statistical morphometry method for comparing the cross-sectional images of normal and diseased bones. The secondary objective involved demonstrating the effectiveness of the proposed method in distinguishing AIS patients from normal controls. This framework is composed of bone segmentation followed by measurements of maximum and minimum bone diameters, inter-group and intra-group statistical morphometry, and statistical analysis of bone thickness. The proposed framework was applied to detect bone morphological abnormality in adolescent idiopathic scoliosis (AIS) patients. The forearm bones in cross-sectional peripheral quantitative computed tomography (pQCT) images from 23 AIS patients and 16 normal controls were analyzed. The radius outer contour was found to be rounder and the radius cortical bone was thinner in AIS patients compared to normal controls.

Fast and accurate 3-D registration of HR-pQCT images.

High-resolution peripheral quantitative computed tomography (HR-pQCT) is a new noninvasive bone imaging technology that generates high-resolution 3-D images for quantitatively analysis of the bone microarchitecture in human. To enable quantitative evaluation of bone changes, either bone gain or loss, accurate alignment between the baseline and follow-up scans of the same individual is necessary. The major difficulties in achieving efficient and automatic registration of the HR-pQCT data are the large data size, deformations in the nonskeletal structures, and the complexity of the trabecular bone geometry. In this paper, we propose an automatic surface-based approach for fast and accurate registration of the HR-pQCT data, where the rigid registration is applied on the surfaces of the bony structures extracted from the grayscale HR-pQCT. The bony structure segmentation is performed via an automatic method that can adaptively determine the thresholds for separating the bony structure from the background and nonskeletal tissues. Experimental results performed on ten pairs of baseline and follow-up wrist scans of five adolescents and five elderly patients with osteoporosis showed the advantage of the proposed method in the high degree of automation, while the resultant parameters describing bone mineral density and trabecular architecture after registration were comparable with the outputs of the scanner's software. This automatic and accurate matching procedure may contribute to the clinical application and research of HR-pQCT.

Morphological and functional electrophysiological evidence of relative spinal cord tethering in adolescent idiopathic scoliosis.

STUDY DESIGN: Magnetic resonance (MR) imaging and multiplanar reconstruction was used to evaluate the morphology and relative position of the spinal cord in adolescent idiopathic scoliosis (AIS). OBJECTIVE: To determine the longitudinal and cross-sectional morphology of spinal cord in AIS subjects versus normal controls and their correlation with relative position of cerebellar tonsils and somatosensory cortical evoked potentials (SSEP). SUMMARY OF BACKGROUND DATA: Our previous studies revealed significantly reduced spinal cord to vertebral column length ratios in AIS patients with severe scoliotic curves suggesting the presence of disproportional growth between the neural and skeletal system. A possible neural origin of etiopathogenesis of AIS is suggested. METHODS: MR multiplanar reconstruction was performed in 97 adolescent girls (35 moderate, 26 severe AIS with right-sided thoracic/thoracolumbar curve, and 36 age-matched controls). Measurements of the ratio of anteroposterior (AP) and transverse (TS) diameter of the cord, the concave and convex lateral cord space (LCS) were obtained at the apical level in AIS subjects. Same parameters were obtained in normal controls at matched vertebral levels. Correlations were made with cord to vertebral column length ratio, cerebellar tonsil position and SSEP findings. RESULTS: AP/TS cord ratio and LCS ratio were increased in AIS subjects in the presence of reduced spinal cord to vertebral length ratio when compared with normal controls (P < 0.05). The above ratios were exaggerated in AIS subjects with abnormal SSEP findings. The AP/TS cord ratio and LCS ratio were negatively correlated with the cord to vertebral column length ratio (rho = -0.410 and -0.313, P < 0.01) and cerebellar tonsillar level (rho = -0.309 and -0.432, P < 0.01). CONCLUSION: Our study suggests presence of tethering and increased tension along the longitudinal axis of spinal cord with associated morphologic changes of cross-sectional shape and relative position of the cord.

MR analysis of regional brain volume in adolescent idiopathic scoliosis: neurological manifestation of a systemic disease.

PURPOSE: To investigate whether regional brain volumes in adolescent idiopathic scoliosis (AIS) patients differ from matched control subjects as AIS subjects are reported to have poor performance on combined visual and proprioceptive testing and impaired postural balance in previous studies. MATERIALS AND METHODS: Twenty AIS female patients with typical right-convex thoracic curve (age range,11-18 years; mean, 14.1 years) and 26 female controls (mean age, 14.8 years) underwent three-dimensional magnetization prepared rapid acquisition gradient echo (3D-MPRAGE) MR imaging. Volumes of 99 preselected neuroanatomical regions were compared by statistical parametric mapping and atlas-based hybrid warping. RESULTS: Analysis of variance statistics revealed significant mean volumetric differences in 22 brain regions between AIS and controls. Ten regions were larger in AIS including the left frontal gyri and white matter in left frontal, parietal, and temporal regions, corpus callosum and brainstem. Twelve regions were smaller in AIS, including right-sided descending white matter tracts (anterior and posterior limbs of the right internal capsule and the cerebral peduncle) and deep nucleus (caudate), bilateral perirhinal cortices, left hippocampus and amygdala, bilateral precuneus gyri, and left middle and inferior occipital gyri. CONCLUSION: Regional brain volume difference in AIS subjects may help to explain neurological abnormalities in this group.

Landmark correspondence optimization for coupled surfaces.

Volumetric layers are often encountered in medical images. Unlike solid structures, volumetric layers are characterized by double and nested bounding surfaces. It is expected that better statistical models can be built by utilizing the surface coupleness rather than simply applying the landmarking method on each of them separately. We propose an approach to optimizing the landmark correspondence on the coupled surfaces by minimizing the description length that incorporates local thickness gradient. The evaluations are performed on a set of 2-D synthetic close coupled contours and a set of real-world open surfaces, the skull vaults. Compared with performing landmarking separately on the coupled surfaces, the proposed method constructs models that have better generalization ability and specificity.

A detailed morphologic and functional magnetic resonance imaging study of the craniocervical junction in adolescent idiopathic scoliosis.

STUDY DESIGN: Conventional and phase-contrast magnetic resonance (MR) imaging were used to evaluate the morphology and cerebrospinal fluid (CSF) flow dynamics at craniocervical junction in adolescent idiopathic scoliosis (AIS). OBJECTIVES: To determine the morphology of cerebellar tonsil, foramen magnum, and dynamic flow of CSF at the craniocervical junction in AIS patients versus normal controls and their correlation with somatosensory cortical evoked potentials (SSEP). SUMMARY OF BACKGROUND DATA: Previous studies have documented obstructed CSF flow in patients with Chiari I malformation. Low-lying cerebellar tonsils and syringomyelia are also observed in AIS patients. We sought to investigate whether disturbed CSF flow is also evident in AIS subjects at the foramen magnum level and its association with level of cerebellar tonsils and dimensions of foramen magnum. METHODS: Conventional and phase-contrast MR were performed in 105 adolescent girls (69 AIS subjects and 36 age-matched controls). Measurements of cerebellar tonsillar level related to the basion-opsithion (BO) line, anteroposterior (AP), transverse (TS) diameter, and area of foramen magnum, and peak velocity of CSF flow in both the anterior and posterior subarachnoid space through foramen magnum were obtained. Correlations were made among different parameters and SSEP findings. RESULTS: A total of 42% of subjects in the AIS group had the cerebellar tonsillar tip positioned 1 mm below the BO line. The cerebellar tonsillar level in AIS subjects was significantly lower than the median tonsillar level in normal controls (P < 0.01). The AP diameter and area of foramen magnum were significantly larger in AIS subjects when compared with normal controls (P < 0.05), but the peak CSF velocities through foramen magnum showed no significant difference (P > 0.05). CONCLUSION: Peak CSF velocities through foramen magnum were not significantly different in AIS subjects despite the presence of low-lying cerebellar tonsils. This might be explained by the compensatory effect of larger foramen magnum in AIS subjects.

Morphometric analysis for pathological abnormality detection in the skull vaults of adolescent idiopathic scoliosis girls.

In this paper, we present a comprehensive framework to detect morphological changes in skull vaults of adolescent idiopathic scoliosis girls. To our knowledge, this is the first attempt to use a combination of medical knowledge, image analysis techniques, statistical learning tools, and scientific visualization methods to detect skull morphological changes. The shape analysis starts from a reliable 3-D segmentation of the skull using thresholding and math-morphological operations. The gradient vector flow is used to model the skull vault surface, which is followed by a spherically uniform sampling. The scale-normalized distances from the shape centroid to sample points are defined as the features. The most discriminative features are selected using recursive feature elimination for support vector machine. The results of this study specify the skull vault surface changes and shed light on building the evidence of bone formation abnormality in AIS girls.