Inter-vertebral rotational deformity after endoscopic anterior scoliosis correction may contribute to rib hump recurrence after two years

Introduction. Endoscopic anterior scoliosis correction has been employed recently as a less invasive and level-sparing approach compared with open surgical techniques. We have previously demonstrated that during the two-year post-operative period, there was a mean loss of rib hump correction by 1.4 degrees. The purpose of this study was to determine whether intra- or inter-vertebral rotational deformity during the post-operative period could account for the loss of rib hump correction. Materials and Methods. Ten consecutive patients diagnosed with adolescent idiopathic scoliosis were treated with an endoscopic anterior scoliosis correction. Low-dose computed tomography scans of the instrumented segment were obtained post-operatively at 6 and 24 months following institutional ethical approval and patient consent. Three-dimensional multi-planar reconstruction software (Osirix Imaging Software, Pixmeo, Switzerland) was used to create axial slices of each vertebral level, corrected in both coronal and sagittal planes. Vertebral rotation was measured using Ho’s method for every available superior and inferior endplate at 6 and 24 months. Positive changes in rotation indicate a reduction and improvement in vertebral rotation. Intra-observer variability analysis was performed on a subgroup of images. Results. Mean change in rotation for vertebral endplates between 6 and 24 months post-operatively was -0.26˚ (range -3.5 to 4.9˚) within the fused segment and +1.26˚ (range -7.2 to 15.1˚) for the un-instrumented vertebrae above and below the fusion. Mean change in clinically measured rib hump for the 10 patients was -1.6˚ (range -3 to 0˚). The small change in rotation within the fused segment accounts for only 16.5% of the change in rib hump measured clinically whereas the change in rotation between the un-instrumented vertebrae above and below the construct accounts for 78.8%. There was no clear association between rib hump recurrence and intra- or inter-vertebral rotation in individual patients. Intra-rater variability was ± 3˚. Conclusions. Intra- and inter-vertebral rotation continues post-operatively both within the instrumented and un-instrumented segments of the immature spine. Rotation between the un-instrumented vertebrae above and below the fusion was +1.26˚, suggesting that the un-instrumented vertebrae improved and de-rotated slightly after surgery. This may play a role in rib hump recurrence, however this remains clinically insignificant.

Quantitative evaluation of polymer gel dosimeters by broadband ultrasound attenuation

Ultrasound has been examined previously as an alternative readout method for irradiated polymer gel dosimeters, with authors reporting varying dose response to ultrasound transmission measurements. In this current work we extend previous work to measure the broadband ultrasound attenuation (BUA) response of irradiated PAGAT gel dosimeters, using a novel ultrasound computed tomography system.

Segmental torso masses and gravity-induced coronal plane joint moments in adolescent idiopathic scoliosis

Introduction: Calculating segmental (vertebral level-by-level) torso masses in Adolescent Idiopathic Scoliosis (AIS) patients allows the gravitational loading on the scoliotic spine during relaxed standing to be estimated. This study used supine CT scans of AIS patients to measure segmental torso masses and explored the joint moments in the coronal plane, particularly at the apex of a scoliotic major curve. Methods: Existing low dose CT data from the Paediatric Spine Research Group was used to calculate vertebral level-by-level torso masses and joint moments occurring in the spine for a group of 20 female AIS patients with right sided thoracic curves. The mean age was 15.0 ± 2.7 years and all curves were classified Lenke Type 1 with a mean Cobb angle 52 ± 5.9°. Image processing software, ImageJ (v1.45 NIH USA) was used to create reformatted coronal plane images, reconstruct vertebral level-by-level torso segments and subsequently measure the torso volume corresponding to each vertebral level. Segment mass was then determined by assuming a tissue density of 1.04x103 kg/m3. Body segment masses for the head, neck and arms were taken from published anthropometric data (Winter 2009). Intervertebral joint moments in the coronal plane at each vertebral level were found from the position of the centroid of the segment masses relative to the joint centres with the segmental body mass data. Results and Discussion: The magnitude of the torso masses from T1-L5 increased inferiorly, with a 150% increase in mean segmental torso mass from 0.6kg at T1 to 1.5kg at L5. The magnitudes of the calculated coronal plane joint moments during relaxed standing were typically 5-7 Nm at the apex of the curve, with the highest apex joint torque of 7Nm. The CT scans were performed in the supine position and curve magnitudes are known to be 7-10° smaller than those measured in standing, due to the absence of gravity acting on the spine. Hence, it can be expected that the moments produced by gravity in the standing individual will be greater than those calculated here.

Segmentation of cone-beam CT using a hidden Markov random field with informative priors

Purpose: Flat-detector, cone-beam computed tomography (CBCT) has enormous potential to improve the accuracy of treatment delivery in image-guided radiotherapy (IGRT). To assist radiotherapists in interpreting these images, we use a Bayesian statistical model to label each voxel according to its tissue type. Methods: The rich sources of prior information in IGRT are incorporated into a hidden Markov random field (MRF) model of the 3D image lattice. Tissue densities in the reference CT scan are estimated using inverse regression and then rescaled to approximate the corresponding CBCT intensity values. The treatment planning contours are combined with published studies of physiological variability to produce a spatial prior distribution for changes in the size, shape and position of the tumour volume and organs at risk (OAR). The voxel labels are estimated using the iterated conditional modes (ICM) algorithm. Results: The accuracy of the method has been evaluated using 27 CBCT scans of an electron density phantom (CIRS, Inc. model 062). The mean voxel-wise misclassification rate was 6.2%, with Dice similarity coefficient of 0.73 for liver, muscle, breast and adipose tissue. Conclusions: By incorporating prior information, we are able to successfully segment CBCT images. This could be a viable approach for automated, online image analysis in radiotherapy.

The effect of polystyrene sodium sulfonate grafting on polyethylene terephthalate artificial ligaments on in vitro mineralisation and in vivo bone tissue integration

This study investigates the impact of polystyrene sodium sulfonate (PolyNaSS) grafting onto the osseo-integration of a polyethylene terephthalate artificial ligament (Ligament Advanced Reinforcement System, LARS™) used for Anterior Cruciate Ligament (ACL). The performance of grafted and non-grafted ligaments was assessed in vitro by culturing human osteoblasts under osteogenic induction and this demonstrated that the surface modification was capable of up-regulating the secretion of ALP and induced higher level of mineralisation as measured 6 weeks post-seeding by Micro-Computed Tomography. Grafted and non-grafted LARS™ were subsequently implanted in an ovine model for ACL reconstruction and the ligament-to-bone interface was evaluated by histology and biomechanical testings 3 and 12 months post-implantation. The grafted ligaments exhibited more frequent direct ligament-to-bone contact and bone formation in the core of the ligament at the later time point than the non-grafted specimens, the grafting also significantly reduced the fibrous encapsulation of the ligament 12 months post-implantation. However, this improved osseo-integration was not translated into a significant increase in the biomechanical pull-out loads. These results provide evidences that PolyNaSS grafting improved the osseo-integration of the artificial ligament within the bone tunnels. This might positively influence the outcome of the surgical reconstructions, as higher ligament stability is believed to limit micro-movement and therefore permits earlier and enhanced healing.

Segmentation of cone-beam CT using a hidden Markov random field with informative priors

Cone-beam computed tomography (CBCT) has enormous potential to improve the accuracy of treatment delivery in image-guided radiotherapy (IGRT). To assist radiotherapists in interpreting these images, we use a Bayesian statistical model to label each voxel according to its tissue type. The rich sources of prior information in IGRT are incorporated into a hidden Markov random field model of the 3D image lattice. Tissue densities in the reference CT scan are estimated using inverse regression and then rescaled to approximate the corresponding CBCT intensity values. The treatment planning contours are combined with published studies of physiological variability to produce a spatial prior distribution for changes in the size, shape and position of the tumour volume and organs at risk. The voxel labels are estimated using iterated conditional modes. The accuracy of the method has been evaluated using 27 CBCT scans of an electron density phantom. The mean voxel-wise misclassification rate was 6.2\%, with Dice similarity coefficient of 0.73 for liver, muscle, breast and adipose tissue. By incorporating prior information, we are able to successfully segment CBCT images. This could be a viable approach for automated, online image analysis in radiotherapy.

Segmental torso masses and joint torques produced by gravity in the adolescent scoliotic spine

Introduction Calculating segmental torso masses in Adolescent Idiopathic Scoliosis (AIS) patients allows the gravitational loading on the scoliotic spine during relaxed standing to be estimated. Methods Low dose CT data was used to calculate vertebral level-by-level torso masses and spinal joint torques for 20 female AIS patients (mean age 15.0 ± 2.7 years, mean Cobb angle 53 ± 7.1°). ImageJ software (v1.45 NIH USA) was used to threshold the T1 to L5 CT images and calculate the segmental torso volume and mass for each vertebral level. Masses for the head, neck and arms were taken from published data.1 Intervertebral joint torques in the coronal and sagittal planes at each vertebral level were found from the position of the centroid of the segment masses relative to the joint centres (assumed to be at the centre of the intervertebral disc). The joint torque at each level was found by summing torque contributions for all segments above that joint. Results Segmental torso mass increased from 0.6kg at T1 to 1.5kg at L5. The coronal plane joint torques due to gravity were 5-7Nm at the apex of the curve; sagittal torques were 3-5.4Nm. Conclusion CT scans were in the supine position and curve magnitudes are known to be smaller than those in standing.2 Hence, this study has shown that gravity produces joint torques potentially of higher than 7Nm in the coronal plane and 5Nm in the sagittal plane during relaxed standing in scoliosis patients. The magnitude of these torques may help to explain the mechanics of AIS progression and the mechanics of bracing. This new data on torso segmental mass in AIS patients will assist biomechanical models of scoliosis.

Toxicity profile of the immunomodulatory thalidomide analogue, lenalidomide : Phase I clinical trial of three dosing schedules in patients with solid malignancies

Thalidomide is an anti-angiogenic agent currently used to treat patients with malignant cachexia or multiple myeloma. Lenalidomide (CC-5013) is an immunomodulatory thalidomide analogue licensed in the United States of America (USA) for the treatment of a subtype of myelodysplastic syndrome. This two-centre, open-label phase I study evaluated dose-limiting toxicities in 55 patients with malignant solid tumours refractory to standard chemotherapies. Lenalidomide capsules were consumed once daily for 12 weeks according to one of the following three schedules: (I) 25 mg daily for the first 7 d, the daily dose increased by 25 mg each week up to a maximum daily dose of 150 mg; (II) 25 mg daily for 21 d followed by a 7-d rest period, the 4-week cycle repeated for 3 cycles; (III) 10 mg daily continuously. Twenty-six patients completed the study period. Two patients experienced a grade 3 hypersensitivity rash. Four patients in cohort I and 4 patients in cohort II suffered grade 3 or 4 neutropaenia. In 2 patients with predisposing medical factors, grade 3 cardiac dysrhythmia was recorded. Grade 1 neurotoxicity was detected in 6 patients. One complete and two partial radiological responses were measured by computed tomography scanning; 8 patients had stable disease after 12 weeks of treatment. Fifteen patients remained on treatment as named patients; 1 with metastatic melanoma remains in clinical remission 3.5 years from trial entry. This study indicates the tolerability and potential clinical efficacy of lenalidomide in patients with advanced solid tumours who have previously received multi-modality treatment. Depending on the extent of myelosuppressive pre-treatment, dose schedules (II) or (III) are advocated for large-scale trials of long-term administration. © 2006 Elsevier Ltd. All rights reserved.

A feasibility study of multislice x-ray CT imaging of gel dosimeters using the “zero scan” method

This study extends the ‘zero scan’ method for CT imaging of polymer gel dosimeters to include multi-slice acquisitions. Multi slice CT images consisting of 24 slices of 1.2 mm thickness were acquired of an irradiated polymer gel dosimeter, and processed with the zero scan technique. The results demonstrate that zero scan based gel readout can be successfully applied to generate a three dimensional image of the irradiated gel field. Compared to the raw CT images the processed figures and cross gel profiles demonstrated reduced noise and clear visibility of the penumbral region. Moreover these improved results further highlight the suitability of this method in volumetric reconstruction with reduced CT data acquisition per slice. This work shows that 3D volumes of irradiated polymer gel dosimeters can be acquired and processed with x-ray CT.

Response variation of optically stimulated luminescence dosimeters

This study investigates the variability in response of optically stimulated luminescence dosimeters (OSLDs). Examining the source of sensitivity variations in these dosimeters allows for a more comprehensive understanding of the Landauer nanoDots and their potential for current and future applications. In this work, OSLDs were scanned with a MicroCT scanner to determine potential sources for the variation in relative sensitivity across a selection of Landauer nanoDot dosimeters. Specifically, the correlation between a dosimeters relative sensitivity and the loading density of Al2O3:C powder was determined. When extrapolating the sensitive volume's radiodensity from the CT data, it was shown that there is a non-uniform distribution in crystal growth. It was calculated that a 0.05% change in the nominal volume of the chip produces a 1% change in the overall response. Additionally, the ‘true’ volume of an OSLD's sensitive material is, on average, 18% less than that which has been reported in literature, mainly due to the presence of air cavities in the material's structure. This work demonstrated that the amount of sensitive material is approximately linked to the total correction factor.

Quantitative estimation of bioturbation based on digital image analysis

Quantitative determination of modification of primary sediment features, by the activity of organisms (i.e., bioturbation) is essential in geosciences. Some methods proposed since the 1960s are mainly based on visual or subjective determinations. The first semiquantitative evaluations of the Bioturbation Index, Ichnofabric Index, or the amount of bioturbation were attempted, in the best cases using a series of flashcards designed in different situations. Recently, more effective methods involve the use of analytical and computational methods such as X-rays, magnetic resonance imaging or computed tomography; these methods are complex and often expensive. This paper presents a compilation of different methods, using Adobe® Photoshop® software CS6, for digital estimation that are a part of the IDIAP (Ichnological Digital Analysis Images Package), which is an inexpensive alternative to recently proposed methods, easy to use, and especially recommended for core samples. The different methods — “Similar Pixel Selection Method (SPSM)”, “Magic Wand Method (MWM)” and the “Color Range Selection Method (CRSM)” — entail advantages and disadvantages depending on the sediment (e.g., composition, color, texture, porosity, etc.) and ichnological features (size of traces, infilling material, burrow wall, etc.). The IDIAP provides an estimation of the amount of trace fossils produced by a particular ichnotaxon, by a whole ichnocoenosis or even for a complete ichnofabric. We recommend the application of the complete IDIAP to a given case study, followed by selection of the most appropriate method. The IDIAP was applied to core material recovered from the IODP Expedition 339, enabling us, for the first time, to arrive at a quantitative estimation of the discrete trace fossil assemblage in core samples.

Geometric sensitivity of patient-specific finite element models of the spine to variability in user-selected anatomical landmarks

Software to create individualised finite element (FE) models of the osseoligamentous spine using pre-operative computed tomography (CT) data-sets for spinal surgery patients has recently been developed. This study presents a geometric sensitivity analysis of this software to assess the effect of intra-observer variability in user-selected anatomical landmarks. User-selected landmarks on the osseous anatomy were defined from CT data-sets for three scoliosis patients and these landmarks were used to reconstruct patient-specific anatomy of the spine and ribcage using parametric descriptions. The intra-observer errors in landmark co-ordinates for these anatomical landmarks were calculated. FE models of the spine and ribcage were created using the reconstructed anatomy for each patient and these models were analysed for a loadcase simulating clinical flexibility assessment. The intra-observer error in the anatomical measurements was low in comparison to the initial dimensions, with the exception of the angular measurements for disc wedge and zygapophyseal joint (z-joint) orientation and disc height. This variability suggested that CT resolution may influence such angular measurements, particularly for small anatomical features, such as the z-joints, and may also affect disc height. The results of the FE analysis showed low variation in the model predictions for spinal curvature with the mean intra-observer variability substantially less than the accepted error in clinical measurement. These findings demonstrate that intra-observer variability in landmark point selection has minimal effect on the subsequent FE predictions for a clinical loadcase.

Evaluation of BMP-2 gene-activated muscle grafts for cranial defect repair

Large, osseous, segmental defects heal poorly. Muscle has a propensity to form bone when exposed to an osteogenic stimulus such as that provided by transfer and expression of cDNA encoding bone morphogenetic protein-2 (BMP-2). The present study evaluated the ability of genetically modified, autologous muscle to heal large cranial defects in rats. Autologous grafts (8 mm � 2 mm) were punched from the biceps femoris muscle and transduced intraoperatively with recombinant adenovirus vector containing human BMP-2 or green fluorescent protein cDNA. While the muscle biopsies were incubating with the vector, a central parietal 8 mm defect was surgically created in the calvarium of the same animal. The gene-activated muscle graft was then implanted into the cranial defect. After 8 weeks, crania were examined radiographically, histologically, and by micro-computed tomography and dual energy X-ray absorptiometry. Although none of the defects were completely healed in this time, muscle grafts expressing BMP-2 deposited more than twice as much new bone as controls. Histology confirmed the anatomical integrity of the newly formed bone, which was comparable in thickness and mineral density to the original cranial bone. This study confirms the in vivo osteogenic properties of genetically modified muscle and suggests novel strategies for healing bone. � 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1095–1102, 2012

Multiphasic construct studied in an ectopic osteochondral defect model

In vivo osteochondral defect models predominantly consist of small animals, such as rabbits. Although they have an advantage of low cost and manageability, their joints are smaller and more easily healed compared with larger animals or humans. We hypothesized that osteochondral cores from large animals can be implanted subcutaneously in rats to create an ectopic osteochondral defect model for routine and high-throughput screening of multiphasic scaffold designs and/or tissue-engineered constructs (TECs). Bovine osteochondral plugs with 4 mm diameter osteochondral defect were fitted with novel multiphasic osteochondral grafts composed of chondrocyte-seeded alginate gels and osteoblast-seeded polycaprolactone scaffolds, prior to being implanted in rats subcutaneously with bone morphogenic protein-7. After 12 weeks of in vivo implantation, histological and micro-computed tomography analyses demonstrated that TECs are susceptible to mineralization. Additionally, there was limited bone formation in the scaffold. These results suggest that the current model requires optimization to facilitate robust bone regeneration and vascular infiltration into the defect site. Taken together, this study provides a proof-of-concept for a high-throughput osteochondral defect model. With further optimization, the presented hybrid in vivo model may address the growing need for a cost-effective way to screen osteochondral repair strategies before moving to large animal preclinical trials.

Segmental torso masses in adolescent idiopathic scoliosis

Background Adolescent Idiopathic Scoliosis is the most common type of spinal deformity whose aetiology remains unclear. Studies suggest that gravitational forces in the standing position play an important role in scoliosis progression, therefore anthropometric data are required to develop biomechanical models of the deformity. Few studies have analysed the trunk by vertebral level and none have performed investigations of the scoliotic trunk. The aim of this study was to determine the centroid, thickness, volume and estimated mass, for sections of the trunk in Adolescent Idiopathic Scoliosis patients. Methods Existing low-dose Computed Tomography scans were used to estimate vertebral level-by-level torso masses for 20 female Adolescent Idiopathic Scoliosis patients. ImageJ processing software was used to analyse the Computed Tomography images and enable estimation of the segmental torso mass corresponding to each vertebral level. Findings The patients’ mean age was 15.0 (SD 2.7) years with mean major Cobb Angle of 52° (SD 5.9) and mean patient weight of 58.2 (SD 11.6) kg. The magnitude of torso segment mass corresponding to each vertebral level increased by 150% from 0.6kg at T1 to 1.5kg at L5. Similarly, the segmental thickness corresponding to each vertebral level from T1-L5 increased inferiorly from a mean 18.5 (SD 2.2) mm at T1 to 32.8 (SD 3.4) mm at L5. The mean total trunk mass, as a percentage of total body mass, was 27.8 (SD 0.5) % which was close to values reported in previous literature. Interpretation This study provides new anthropometric reference data on segmental (vertebral level-by-level) torso mass in Adolescent Idiopathic Scoliosis patients, useful for biomechanical models of scoliosis progression and treatment.