Engineering three-dimensional microenvironments towards in vitro disease models of the central nervous system.

The central nervous system (CNS) has a highly complex biophysical and biochemical environment. Despite decades of intensive research, it is still an enormous challenge to restore its functions and regenerate lost or damaged CNS tissues. Current treatment strategies remain sub-optimal because of (1) the hostile microenvironment created post CNS injury, and (2) insufficient understanding of the pathophysiology of acute and chronic CNS diseases. Two-dimensional (2D) in vitro models have provided tremendous insights into a wide range of cellular interactions. However, they fail to recapitulate the complex cellular, topographical, biochemical, and mechanical stimuli found within the natural three-dimensional (3D) CNS. Also, the growing ethical needs to use fewer animals for research further necessitates 3D in vitro models to mimic all or part of the CNS. In this review, we critically appraise the status quo and design considerations of 3D in vitro neural disease and injury models that resemble in vivo conditions. This review mainly focuses on the most recent advances in tissue engineering techniques such as microfluidics, organs-on-a-chip and stem cell technology. Furthermore, we review recent models aiming to elucidate the underlying pathophysiology of CNS diseases. If armed with deeper understanding, it will be possible to develop high-throughput drug screening platforms and new treatments for CNS diseases and injuries.

Ultrasound Volume Projection Imaging for Assessment of Scoliosis.

The standing radiograph is used as a gold standard to diagnose spinal deformity including scoliosis, a medical condition defined as lateral spine curvature > 10°. However, the health concern of X-ray and large inter-observer variation of measurements on X-ray images have significantly restricted its application, particularly for scoliosis screening and close follow-up for adolescent patients. In this study, a radiation-free freehand 3-D ultrasound system was developed for scoliosis assessment using a volume projection imaging method. Based on the obtained coronal view images, two measurement methods were proposed using transverse process and spinous profile as landmarks, respectively. As a reliability study, 36 subjects (age: 30.1 ±14.5; male: 12; female: 24) with different degrees of scoliosis were scanned using the system to test the inter- and intra-observer repeatability. The intra- and inter-observer tests indicated that the new assessment methods were repeatable, with ICC larger than 0.92. Small intra- and inter-observer variations of measuring spine curvature were observed for the two measurement methods (intra-: 1.4 ±1.0° and 1.4 ±1.1°; inter-: 2.2 ±1.6° and 2.5 ±1.6°). The results also showed that the spinal curvature obtained by the new method had good linear correlations with X-ray Cobb's method (R2 = 0.8, p < 0.001, 29 subjects). These results suggested that the ultrasound volume projection imaging method can be a promising approach for the assessment of scoliosis, and further research should be followed up to demonstrate its potential clinical applications for mass screening and curve progression and treatment outcome monitoring of scoliosis patients.

Freehand three-dimensional ultrasound system for assessment of scoliosis.

BACKGROUND/OBJECTIVE: Standing radiograph with Cobb's method is routinely used to diagnose scoliosis, a medical condition defined as a lateral spine curvature > 10° with concordant vertebral rotation. However, radiation hazard and two-dimensional (2-D) viewing of 3-D anatomy restrict the application of radiograph in scoliosis examination. METHODS: In this study, a freehand 3-D ultrasound system was developed for the radiation-free assessment of scoliosis. Bony landmarks of the spine were manually extracted from a series of ultrasound images with their spatial information recorded to form a 3-D spine model for measuring its curvature. To validate its feasibility, in vivo measurements were conducted in 28 volunteers (age: 28.0 ± 13.0 years, 9 males and 19 females). A significant linear correlation (R2 = 0.86; p < 0.001) was found between the spine curvatures as measured by Cobb's method and the 3-D ultrasound imaging with transverse process and superior articular process as landmarks. The intra- and interobserver tests indicated that the proposed method is repeatable. RESULTS: The 3-D ultrasound method using bony landmarks tended to underestimate the deformity, and a proper scaling is required. Nevertheless, this study demonstrated the feasibility of the freehand 3-D ultrasound system to assess scoliosis in the standing posture with the proposed methods and 3-D spine profile. CONCLUSION: Further studies are required to understand the variations that exist between the ultrasound and radiograph results with a larger number of volunteers, and to demonstrate its potential clinical applications for monitoring of scoliosis patients. Through further clinical trials and development, the reported 3-D ultrasound imaging system can potentially be used for scoliosis mass screening and frequent monitoring of progress and treatment outcome because of its radiation-free and easy accessibility feature.

Development of 3-D ultrasound system for assessment of adolescent idiopathic scoliosis (AIS): and system validation.

Adolescent idiopathic scoliosis (AIS) is a common spinal disease and the prevalence of AIS is 2 to 4 % of the youngsters in the United States. Radiograph based Cobb's method is regarded as the gold standard. AIS patients normally have to undergo regular X-ray assessment every 4 to 6 months until skeletal maturity is reached. Because of radiation hazard, X-ray images cannot be taken frequently, and thus it is difficult to perform close monitoring for the disease progression and treatment outcomes. In this study, a free-hand 3D ultrasound imaging system has been successfully developed for the radiation-free assessment of AIS. A series of B-mode ultrasound images with their spatial information were exploited to form a spine model for measuring the spine curvature. Sixteen spine phantoms with different simulated deformity were scanned by both conventional X-ray imaging and the 3D ultrasound system. The results showed that there was a strong correlation (R(2) = 0.759) between the Cobb's angles obtained by the two methods. The results also demonstrated a very good intra- and inter-observer reproducibility with ICC of 0.99 and 0.89, repectively. The findings suggest that it is feasible to use 3D ultrasound imaging for the assessment of scoliosis and deserves further clinical tests on patients with spine deformity.