Automatic grading of intervertebral disc degeneration in lumbar dog spines.

Background: Intervertebral disc degeneration is frequent in dogs and can be associated with symptoms and functional impairments. The degree of disc degeneration can be assessed on T2-weighted MRI scans using the Pfirrmann classification scheme, which was developed for the human spine. However, it could also be used to quantify the effectiveness of disc regeneration therapies. We developed and tested a deep learning tool able to automatically score the degree of disc degeneration in dog spines, starting from an existing model designed to process images of human patients. Methods: MRI midsagittal scans of 5991 lumbar discs of dog patients were collected and manually evaluated with the Pfirrmann scheme and a modified scheme with transitional grades. A deep learning model was trained to classify the disc images based on the two schemes and tested by comparing its performance with the model processing human images. Results: The determination of the Pfirrmann grade showed sensitivities higher than 83% for all degeneration grades, except for grade 5, which is rare in dog spines, and high specificities. In comparison, the correspondent human model had slightly higher sensitivities, on average 90% versus 85% for the canine model. The modified scheme with the fractional grades did not show significant advantages with respect to the original Pfirrmann grades. Conclusions: The novel tool was able to accurately and reliably score the severity of disc degeneration in dogs, although with a performance inferior than that of the human model. The tool has potential in the clinical management of disc degeneration in canine patients as well as in longitudinal studies evaluating regenerative therapies in dogs used as animal models of human disorders.

The move-C cervical artificial disc can restore intact range of motion and 3-D kinematics.

BACKGROUND CONTEXT: In contrast to cervical discectomy and fusion, total disc replacement (TDR) aims at preserving the motion at the treated vertebral level. Spinal motion is commonly evaluated with the range of motion (ROM). However, more qualitative information about cervical kinematics before and after TDR is still lacking. PURPOSE: The aim of this in vitro study was to investigate the influence of cervical TDR on ROM, instantaneous centers of rotation (ICR) and three-dimensional helical axes. STUDY DESIGN: An in vitro study with human spine specimens under pure moment loading was conducted to evaluate the kinematics of the intact cervical spine and compare it to cervical TDR. METHODS: Six fresh frozen human cervical specimens (C4-5, median age 28 years, range 19-47 years, two female and four male) were biomechanically characterized in the intact state and after implantation of a cervical disc prosthesis (MOVE-C, NGMedical, Germany). To mimic in vivo conditions regarding temperature and humidity, water steam was used to create a warm and humid test environment with 37°C. Each specimen was quasistatically loaded with pure moments up to ±2.5 Nm in flexion/extension (FE), lateral bending (LB) and axial rotation (AR) in a universal spine tester for 3.5 cycles at 1 °/s. For each third cycle of motion the ROM was evaluated and an established method was used to determine the helical axis and COR and to project them into three planar X-rays. Statistical analysis was conducted using a Friedman-test and post hoc correction with Dunn-Bonferroni-tests (p<.05). RESULTS: After TDR, total ROM was increased in FE from 19.1° to 20.1°, decreased in LB from 14.6° to 12.6° and decreased in AR from 17.7° to 15.5°. No statistical differences between the primary ROM in the intact condition and ROM after TDR were detected. Coupled rotation between LB and AR were also maintained. The position and orientation of the helical axes after cervical TDR was in good agreement with the results of the intact specimens in all three motion directions. The ICR in FE and AR before and after TDR closely matched, while in LB the ICR after TDR were more caudal. The intact in vitro kinematics we found also resembled in vivo results of healthy individuals. CONCLUSION: The results of this in vitro study highlight the potential of artificial cervical disc implants to replicate the quantity as well as the quality of motion of the intact cervical spine. CLINICAL SIGNIFICANCE: Physiological motion preservation was a driving factor in the development of cervical TDR. Our results demonstrate the potential of cervical TDR to replicate in vivo kinematics in all three motion directions.

An externally validated deep learning model for the accurate segmentation of the lumbar paravertebral muscles.

PURPOSE: Imaging studies about the relevance of muscles in spinal disorders, and sarcopenia in general, require the segmentation of the muscles in the images which is very labour-intensive if performed manually and poses a practical limit to the number of investigated subjects. This study aimed at developing a deep learning-based tool able to fully automatically perform an accurate segmentation of the lumbar muscles in axial MRI scans, and at validating the new tool on an external dataset. METHODS: A set of 60 axial MRI images of the lumbar spine was retrospectively collected from a clinical database. Psoas major, quadratus lumborum, erector spinae, and multifidus were manually segmented in all available slices. The dataset was used to train and validate a deep neural network able to segment muscles automatically. Subsequently, the network was externally validated on images purposely acquired from 22 healthy volunteers. RESULTS: The median Jaccard index for the individual muscles calculated for the 22 subjects of the external validation set ranged between 0.862 and 0.935, demonstrating a generally excellent performance of the network, although occasional failures were noted. Cross-sectional area and fat fraction of the muscles were in agreement with published data. CONCLUSIONS: The externally validated deep neural network was able to perform the segmentation of the paravertebral muscles in an accurate and fully automated manner, although it is not without limitations. The model is therefore a suitable research tool to perform large-scale studies in the field of spinal disorders and sarcopenia, overcoming the limitations of non-automated methods.

Morphological patterns of the rib cage and lung in the healthy and adolescent idiopathic scoliosis.

The morphology of the rib cage affects both the biomechanics of the upper body's musculoskeletal structure and the respiratory mechanics. This becomes particularly important when evaluating skeletal deformities, as in adolescent idiopathic scoliosis (AIS). The aim of this study was to identify morphological characteristics of the rib cage in relation to the lung in patients with non-deformed and scoliotic spines. Computed tomography data of 40 patients without any visible spinal abnormalities (healthy group) and 21 patients with AIS were obtained retrospectively. All bony structures as well as the right and left lung were reconstructed using image segmentation. Morphological parameters were calculated based on the distances between characteristic morphological landmarks. These parameters included the rib position, length, and area, the rib cage depth and width, and the rib inclination angle on either side, as well as the spinal height and length. Furthermore, we determined the left and right lung volumes, and the area of contact between the rib cage and lung. Differences between healthy and scoliotic spines were statistically analysed using the t-test for unpaired data. The rib cage of the AIS group was significantly deformed in the dorso-ventral and medio-lateral directions. The anatomical proximity of the lung to the ribs was nearly symmetrical in the healthy group. By contrast, within the AIS group, the lung covered a significantly greater area on the left side of the rib cage at large thoracic deformities. Within the levels T1-T6, no significant difference in the rib length, depth to width relationship, or area was observed between the healthy and AIS groups. Inferior to the lung (T7-T12), these parameters exhibited greater variability. The ratio between the width of the rib cage at T6 and the thoracic spinal height (T1-T12) was significantly increased within the thoracic AIS group (1.1 ± 0.08) compared with the healthy group (1.0 ± 0.05). No statistical differences were found between the lung volumes among all the groups. While the rib cage was frequently strongly deformed in the AIS group, the lung and its surrounding ribs appeared to be normally developed. The observed rib hump in AIS appeared to be formed particularly by a more ventral position of the ribs on the concave side. Furthermore, the rib cage width to spinal height ratio suggested that the spinal height of the thoracic AIS-spine is reduced. This indicates that the spine would gain its growth-related height after correcting the spinal deformity. These are the important aspects to consider in the aetiology research and orthopaedic treatment of AIS.

The impact of age, sex, disc height loss and T1 slope on the upper and lower cervical lordosis: a large-scale radiologic study.

PURPOSE: To clarify the relative influence of age, sex, disc height loss and T1 slope on upper (Occiput-C2) and lower cervical lordosis (C2-C7). METHODS: Standing lateral cervical radiographs of 865 adult subjects were evaluated. The presence and severity of disc height loss from C2/C3 to C6/C7 (a total of 4325 discs) were assessed using a validated grading system. The total disc height loss score for each subject was calculated as the sum of the score of each disc space. Sagittal radiographic parameters included: occipital slope, occiput-C2 (Oc-C2) lordosis, C2-C7 lordosis and T1 slope. Multivariable regression analyses were performed to examine the relative influence of the multiple factors on upper and lower cervical lordosis. RESULTS: This study included 360 males and 505 females, with a mean age of 40.2 ± 16.0 years (range, 20-95 years). Linear multivariate regression analyses showed that greater age, male sex, greater T1 slope were each found to be significantly and independently associated with greater C2-C7 lordosis, whereas total disc height loss score was negatively associated with C2-C7 lordosis. T1 slope had the most independent influence on C2-C7 lordosis among these factors. Age, sex and disc height loss were not independently associated with Oc-C2 lordosis. CONCLUSIONS: Results from our large-scale radiologic analysis may enhance the understanding of the factors that affect cervical lordosis, indicating that age, sex, disc height loss and T1 slope were each independently associated with C2-C7 lordosis. However, age, sex and disc height loss were not independently associated with upper cervical lordosis.

Sagittal wedging of intervertebral discs and vertebral bodies in the cervical spine and their associations with age, sex and cervical lordosis: A large-scale morphological study.

Many recent studies have focused on the functional and clinical importance of cervical lordosis. However, there is little accurate knowledge of the anatomical parameters that constitute cervical lordosis (i.e., the sagittal wedging angles of intervertebral discs and vertebral bodies) and their associations with age and sex. Standing lateral cervical radiographs of 1020 subjects (424 males, 596 females) with a mean age of 36.6 ± 17.0 years (range 7-95 years) were evaluated retrospectively. Cervical lordosis, the sum of intervertebral disc wedging angles from C2/C3 to C6/C7 and the sum of vertebral body wedging angles from C3 to C7 were measured. The sum of intervertebral disc wedging and the sum of vertebral body wedging were 20.6° ± 14.7° and -12.8° ± 10.3°, respectively. The sum of intervertebral disc wedging increased significantly with age and was significantly greater in males than females, whereas there was no sex-related difference in the sum of vertebral body wedging. The sum of intervertebral disc wedging was negatively correlated with sum of vertebral body wedging. Wedging of discs contributed to C2-C7 cervical lordosis more significantly than wedging of vertebral bodies. There were moderate positive correlations between cervical lordosis and intervertebral disc wedging angles at C3/C4, C4/C5 and C5/C6; weak correlations were observed at C2/C3 and C6/C7. This study constitutes the largest currently available analysis comprehensively documenting the anatomical characteristics of sagittal wedging of intervertebral discs and vertebral bodies in the cervical spine. The findings could improve understanding of the internal architecture of cervical lordosis among clinicians.

Influences of functional structures on the kinematic behavior of the cervical spine.

BACKGROUND CONTEXT: A few studies have already investigated the influences of functional structures of the cervical spine on its biomechanical behavior. In most studies, this has been done by measuring the range of motion. However, this parameter lacks of qualitative information about the overall kinematic behavior, such as coupled motions or translations. These data are essential for future development of cervical implants and surgical techniques. PURPOSE: An investigation of the influences of cervical structures on the kinematic behavior of the cervical spine under in vivo conditions is almost impossible due to ethical reasons. Therefore, an in vitro study was conducted which allowed the analysis of these influences using three-dimensional helical axes. STUDY DESIGN/SETTING: An in vitro test applying pure moments on mono-segmental specimens was designed in order to investigate the influences of a series of structures on the kinematic behavior of the cervical spine using three-dimensional helical axes. METHODS: In this study we extracted motion segments C2-C3, C4-C5, and C6-C7 from 6 human cadaveric specimens with an average age of 48 years. The specimens were carefully selected using X-ray images. For the in vitro experiments, seven states were defined. The first state represented the intact state of each specimen. The remaining six states correspond with the subsequent resection of the following structures in the given order: interspinous ligament, ligamentum flavum, facet capsule, vertebral arch, posterior longitudinal ligament, and anterior longitudinal ligament. Each state was tested using a well-established spine tester. Each test sequence included 3.5 quasi-static motion cycles in all three bending directions using pure moments of 1 Nm. All motions were recorded using a motion tracking device and six reflective markers which were attached to the specimens. The recordings were then used to calculate the 3D helical axes, which were matched with the X-ray images. Due to the small number of specimens, qualitative results, such as the helical axes, were analyzed using descriptive statistics. RESULTS: In general, the overall range of motion was increased in all loading directions due to the resection steps. The least change in the kinematic behavior of the cervical spine was observed during flexion/extension. For lateral bending and axial rotation the greatest change in the pattern of the helical axes was observed during the resection of the vertebral arch. For some specimens, however, typical patterns regarding the orientation of the helical axes remained until the last state. For lateral bending, it could be observed that the deviation in the axes' orientation increased whereas for axial rotation it decreased. CONCLUSION: Resection of the cervical ligaments are much less crucial than the removal of guiding structures such as the facet joint. Furthermore, coupled motions not only result from the orientations of the articular surfaces of the facet joints but also from the overall shape of the cervical vertebrae including the uncinate processes. CLINICAL SIGNIFICANCE: It is well-known that coupled motions play a substantial role in cervical kinematics. However, the influences of cervical structures on the overall kinematic behavior of the cervical spine are not yet fully understood. Knowledge of these influences could help to reduce or even prevent iatrogenic degeneration after surgical intervention. Furthermore, the data provided by this study can be helpful for future developments of cervical implants as well as finite element models for more advanced numerical investigations.

Thoracic spinal kinematics is affected by the grade of intervertebral disc degeneration, but not by the presence of the ribs: An in vitro study.

BACKGROUND CONTEXT: Thoracic spinal three-dimensional kinematics is widely unknown. For the evaluation of surgical treatments and the complete validation of numerical models, however, kinematic data of the thoracic spine are essential. PURPOSE: To identify possible effects of rib presence and grade of intervertebral disc degeneration on thoracic spinal kinematics including three-plane helical axes and instantaneous centers of rotation. DESIGN/SETTING: Radiological grading of intervertebral disc degeneration and in vitro tests using n=8 human thoracic functional spinal units of the segmental levels T1-T2, T3-T4, T5-T6, T7-T8, T9-T10, and T11-T12, respectively, were performed with as well as without ribs to analyze the specific kinematic properties. METHODS: Specimens were loaded with pure moments of 5 Nm and constant loading rates of 1°/s in flexion/extension, lateral bending, and axial rotation. Optical motion tracking was performed to visualize helical axes and instantaneous centers of rotation on three-plane X-rays and to evaluate primary ranges of motion (ROMs) and coupled motions. RESULTS: Motion segments with no or mild disc degeneration showed reproducible kinematics in all motion planes, whereas medium or severely degenerated specimens offered high variations and shifts of the rotational axes to the distal direction as well as lower ROM. Coupled motions were generally not detected. CONCLUSIONS: With progressing disc degeneration, the rotational axes show higher variation and tend to shift in distal direction, especially in flexion/extension with a shift to the anterior direction, whereas rib resection does not affect thoracic spinal kinematics but its stability. Rib resections as part of spinal deformity treatment destabilize the thoracic spine, but do not alter its kinematics. Young and healthy discs, however, could be affected by surgical treatments of the thoracic spine regarding thoracic spinal kinematics.

Neck mobility in the Jurassic plesiosaur Cryptoclidus eurymerus: finite element analysis as a new approach to understanding the cervical skeleton in fossil vertebrates.

The sauropterygian clade Plesiosauria arose in the Late Triassic and survived to the very end of the Cretaceous. Plesiosauria evolved the greatest species diversity of any marine reptile clade, attaining a global distribution. Plesiosauria consist of two clades, Rhomaleosauridae and Neoplesiosauria. Basal Neoplesiosauria have long necks with at least 30 cervicals, but show qualitative osteological evidence for a stiff neck. Here we quantify neck mobility in lateral, ventral, and dorsal directions based on finite element modeling of neck vertebrae from the Middle Jurassic plesiosaur Cryptoclidus eurymerus. We model the mobility in a single motion segment, consisting of two adjacent cervical vertebrae and the joints connecting them. Based on the model with a maximum intervertebral spacing of 3 mm, we find that in Cryptoclidus, the maximum angle of lateral deflection in the motion segment was 2°. The maximum angle of ventral deflection was 5° and of dorsal deflection was 5°. When these values are multiplied by the number of cervical vertebrae, it becomes apparent that neck mobility was limited in all directions. The maximum angle of total lateral deflection in the neck was 67°. The maximum angle of total ventral deflection was 148° and of total dorsal deflection was 157°. This raises the question of the function of such a long, multi-segment but immobile neck. We posit that the long neck served in hydrodynamic and visual camouflage, hiding the bulk of the body from the small but abundant prey, such as schooling fish and squid. Neck immobility may have been advantageous in withstanding strong hydrodynamic forces acting on the neck during predatory strikes.

Uncertainty analysis of material properties and morphology parameters in numerical models regarding the motion of lumbar vertebral segments.

The kinematics of a spinal motion segment is determined by the material properties of the soft-tissue and the morphology. The material properties can vary within subjects and between vertebral levels, leading to a wide possible range of motion of a spinal segment independently on its morphology. The goal of this numerical study was to identify the most influential material parameters concerning the kinematics of a spinal motion segment and their plausible ranges. Then, a method was tested to deduce the material properties automatically, based on a given ROM and morphology. A fully parametric finite element model of the morphology and material properties of a lumbar spinal motion segment was developed. The impact of uncertainty of twelve spinal material parameters, as well as the size of the gap between the articular surfaces of the facet joints was examined. The simulation results were compared to our own in vitro data. The flexibility of a lumbar segment was especially influenced by the properties of the anterior annulus region, the facet gap size and the interspinous ligament. The high degree of uncertainty in the material properties and facet gap size published in the literature can lead to a wide scatter in the motion of a spinal segment, with a range of 6°-17° in the intact condition in flexion/extension, from 5°-22° in lateral bending and from 3°-14° in axial rotation. Statistical analysis of the variability might help to estimate the sensitivity and total uncertainty propagated through biomechanical simulations, affecting the reliability of the predictions.

Comparison of three-dimensional helical axes of the cervical spine between in vitro and in vivo testing.

BACKGROUND CONTEXT: The range of motion is a well-accepted parameter for the assessment and evaluation of cervical motion. However, more qualitative data of the kinematics of the cervical spine are needed for the development and success of cervical disc arthroplasty. PURPOSE: The aim of this study was to provide basic information about helical axes of human cervical spine under in vitro conditions. Furthermore, it should clarify whether the three-dimensional helical axes of cervical motion gained from in vitro experiments are in agreement with those gained from in vivo experiments, and therefore to prove its reliability. STUDY DESIGN/SETTING: An in vitro test with pure moments and mono-segmental specimens was designed to investigate and compare the helical axes of the cervical spine. METHODS: Six human cadaveric specimens (three male and three female) with an average age of 47.5 years (range: 34-58 years) were carefully selected. Each specimen was divided into three motion segments: C2-C3, C4-C5, and C6-C7. We performed 3.5 full cycles of rotation about all axes, flexion-extension, lateral bending, and axial rotation, by applying pure moments of 1.5 Nm without any preload. Following the in vitro tests, the three-dimensional helical axes were calculated and projected into the x-ray images. RESULTS: Rotation analysis of all three directions revealed similar results for all six specimens. All calculated helical axes were similar to the published in vivo data. Furthermore, the instantaneous centers of rotation were in agreement with in vivo data. CONCLUSIONS: The data gained from this study verify cervical kinematics during in vitro testing using pure moments. It can be assumed that other soft tissue such as muscles are not necessarily needed to simulate cervical kinematics in vitro.

In Vivo Evaluation of Fracture Callus Development During Bone Healing in Mice Using an MRI-compatible Osteosynthesis Device for the Mouse Femur.

Endochondral fracture healing is a complex process involving the development of fibrous, cartilaginous, and osseous tissue in the fracture callus. The amount of the different tissues in the callus provides important information on the fracture healing progress. Available in vivo techniques to longitudinally monitor the callus tissue development in preclinical fracture-healing studies using small animals include digital radiography and µCT imaging. However, both techniques are only able to distinguish between mineralized and non-mineralized tissue. Consequently, it is impossible to discriminate cartilage from fibrous tissue. In contrast, magnetic resonance imaging (MRI) visualizes anatomical structures based on their water content and might therefore be able to noninvasively identify soft tissue and cartilage in the fracture callus. Here, we report the use of an MRI-compatible external fixator for the mouse femur to allow MRI scans during bone regeneration in mice. The experiments demonstrated that the fixator and a custom-made mounting device allow repetitive MRI scans, thus enabling longitudinal analysis of fracture-callus tissue development.

A novel finite element model of the ovine lumbar intervertebral disc with anisotropic hyperelastic material properties.

The Ovine spine is an accepted model to investigate the biomechanical behaviour of the human lumbar one. Indeed, the use of animal models for in vitro studies is necessary to investigate the mechanical behaviour of biological tissue, but needs to be reduced for ethical and social reasons. The aim of this study was to create a finite element model of the lumbar intervertebral disc of the sheep that may help to refine the understanding of parallel in vitro experiments and that can be used to predict when mechanical failure occurs. Anisotropic hyperelastic material properties were assigned to the annulus fibrosus and factorial optimization analyses were performed to find out the optimal parameters of the ground substance and of the collagen fibers. For the ground substance of the annulus fibrosus the investigation was based on experimental data taken from the literature, while for the collagen fibers tensile tests on annulus specimens were conducted. Flexibility analysis in flexion-extension, lateral bending and axial rotation were conducted. Different material properties for the anterior, lateral and posterior regions of the annulus were found. The posterior part resulted the stiffest region in compression whereas the anterior one the stiffest region in tension. Since the flexibility outcomes were in a good agreement with the literature data, we considered this model suitable to be used in conjunction with in vitro and in vivo tests to investigate the mechanical behaviour of the ovine lumbar disc.

Evaluation of high-resolution In Vivo MRI for longitudinal analysis of endochondral fracture healing in mice.

Mice are extensively used for experimental bone-healing studies. However, there are few established nondestructive in vivo techniques for longitudinal fracture-healing analysis in mice, including in vivo micro-computed tomography (µCT) and radiography. Importantly, none of the established methods can discriminate between non-mineralized fibrous tissue and cartilage in the soft fracture callus. Therefore, the objective was to establish high-resolution in vivo magnetic resonance imaging (MRI) for the longitudinal assessment of soft callus formation during bone healing in mice. C57BL/6J mice received a femur osteotomy stabilized using an external fixator and were randomly assigned to five groups. Group 1 mice were scanned three times longitudinally during fracture healing using an optimized MRI scanning protocol to establish an algorithm to characterize the different fracture-callus tissues. Mice of groups 2-4 were scanned once on day 10, 14 or 21, respectively, euthanized after scanning and their femurs subjected to ex vivo µCT and histomorphometric analysis to compare the data assessed by MRI with µCT and histology. Control group 5 mice were not scanned. After 28 days, mice of groups 1 and 5 were euthanized and the fracture-healing outcome was evaluated by bending-test, µCT and histology to determine whether the repeated anesthesia, handling and the MRI measurements themselves influenced fracture healing. The callus-tissue values determined by MRI were mostly comparable to those obtained by µCT and histomorphometric analysis. However, at time points characterized by small relative bone or cartilage areas, MRI measurements were weakly comparable to histomorphometric data, possibly due to the inferior spatial resolution. Importantly, at the early and intermediate phases of healing, cartilage and fibrous-tissue values obtained by MRI were highly accurate. Furthermore, repeated anesthesia, handling and MRI scans did not impact bone healing. Therefore, we demonstrated the feasibility of high-resolution in vivo MRI for longitudinal assessment of soft callus formation during murine endochondral fracture healing.

A comparison of free anterolateral thigh and latissimus dorsi flaps in soft tissue reconstruction of extensive defects in the head and neck region.

Tailoring the most suitable reconstructive approach to each patient remains challenging especially in the head and neck region. To compare the applicability of the latissimus dorsi (LD) and anterolateral thigh (ALT) flap, we retrospectively analyzed patients who had reconstruction of extensive and/or bulky composite tissue defects in the head and neck area. We performed 85 free tissue transfers (44 LD and 41 ALT flaps). LD mean flap surface was 115.8 cm(2). ALT mean flap surface was 67.0 cm(2). Pedicle length ranged from 8 to 16 cm in LD and 11-16 cm in ALT flaps. The survival rate was 93% in ALT and 91% in LD flaps. Donor site morbidity occurred in 5% (ALT) and 7% (LD). A Two-team-approach was possible in 24% of the LD group, whereas all ALT flaps were raised in a Two-team-approach. Both flaps present excellent opportunities for the reconstruction of extensive and/or bulky defects. They largely meet the requirements of an ideal soft tissue flap in terms of versatility, skin texture and tissue stock. Both flaps can be raised with a double skin paddle. The advantages and disadvantages of each flap have to be weighed up against each other and both flaps should be in the repertoire of every microvascular surgeon.

A three-dimensional finite element model of human atrial anatomy: new methods for cubic Hermite meshes with extraordinary vertices.

High-order cubic Hermite finite elements have been valuable in modeling cardiac geometry, fiber orientations, biomechanics, and electrophysiology, but their use in solving three-dimensional problems has been limited to ventricular models with simple topologies. Here, we utilized a subdivision surface scheme and derived a generalization of the "local-to-global" derivative mapping scheme of cubic Hermite finite elements to construct bicubic and tricubic Hermite models of the human atria with extraordinary vertices from computed tomography images of a patient with atrial fibrillation. To an accuracy of 0.6 mm, we were able to capture the left atrial geometry with only 142 bicubic Hermite finite elements, and the right atrial geometry with only 90. The left and right atrial bicubic Hermite meshes were G1 continuous everywhere except in the one-neighborhood of extraordinary vertices, where the mean dot products of normals at adjacent elements were 0.928 and 0.925. We also constructed two biatrial tricubic Hermite models and defined fiber orientation fields in agreement with diagrammatic data from the literature using only 42 angle parameters. The meshes all have good quality metrics, uniform element sizes, and elements with aspect ratios near unity, and are shared with the public. These new methods will allow for more compact and efficient patient-specific models of human atrial and whole heart physiology.

Monitoring in microvascular tissue transfer by measurement of oxygen partial pressure: four years experience with 125 microsurgical transplants.

In a prospective study, the characteristics and benefit of an invasive measurement of oxygen partial pressure (pO(2)) with the aid of a polarographic sensor were investigated in 125 microsurgical reconstructions of the head and neck area over a period of 45 months. Measurements were performed over 96 h in eight different types of microsurgically revascularized flaps for extra- and intraoral reconstructions and were evaluated separately for each flap type. Of 125 reconstructions the system indicated malperfusion in 18 cases. Salvage surgery was performed in 17 cases due to venous thrombosis (6 cases), arterial thrombosis (3 cases), a combination of arterial and venous thrombosis (2 cases), rheological problems (3 cases), venous insufficiency by hematoma (2 cases) and kinking of vessels (1 case). In 10 cases salvage surgery was successful, 7 flaps were lost despite salvage surgery. In all these cases, the polarographic probe indicated the necessity of salvage surgery correctly. After 96 h no malperfusion was seen. Postoperatively, a common and characteristic development of the oxygen partial pressure in different types of flaps was seen. Initially, a clear increase of pO(2) could be measured. During 96 h, a slow decrease of pO(2) was observed. In conclusion polarographic measurement of pO(2) can be an excellent apparative supplement for the postoperative clinical control of microsurgically revascularized transplants. In buried flaps, this technique represents the only reliable method for transplant monitoring.

Genotoxic activity of four metabolites of the soy isoflavone daidzein.

Products containing phytoestrogens are increasingly promoted as the "natural" alternative to estrogen replacement therapy. In the present study, we have used the in vitro micronucleus assay in L5178Y mouse lymphoma cells to investigate the genotoxic potential of the isoflavone daidzein, and of four daidzein metabolites known to be formed in humans. Whereas no induction of micronuclei was observed with daidzein up to the limit of solubility (100 microM), all four daidzein metabolites, i.e. equol (2.3-fold induction at 100 microM), O-desmethylangolensin (6.2-fold induction at 10 microM), 4',6,7-isoflavone (6.7-fold induction at 100 microM) and 3',4',7-isoflavone (8.2-fold induction at 100 microM) induced micronuclei in a concentration-dependent manner. Thus, both reductive and oxidative metabolites of the soy isoflavone daidzein exhibit genotoxic potential in vitro.