Sonographic bridging callus: An early predictor of fracture union.

BACKGROUND: There is currently a lack of agreed criteria for sonographic assessment of callus and reliability between reviewers. The primary aim of this study was to determine criteria and reviewer agreement for sonographic bridging callus (SBC) on ultrasound. The secondary aim was to analyse the use of ultrasound to detect bridging callus in a prospective cohort of patients with a conservatively managed clavicle fracture. METHODS: A prospective cohort of conservatively managed displaced midshaft clavicle fractures underwent ultrasound scanning at three-, six- and 12-weeks post-injury. The main outcome was nonunion confirmed at six months on CT scanning. Five patients with confirmed nonunion were compared against a control group of 15 patients with timely union at three months. The ultrasound scans were interpreted by two blinded reviewers to evaluate sonographic callus features with agreement determined by weighted kappa. A further validation study was undertaken by four blinded reviewers using the intraclass-correlation-coefficient (ICC) using the most clinically relevant findings of the pilot work. RESULTS: At three weeks post-injury fibrocartilaginous material was present in 80% of patients (16/20). When detected this was associated with union (sensitivity 93%, specificity 60%, p = 0.03) with the inter-observer agreement rated 'fair' on kappa (0.44). At six weeks only 10% (2/20) of patients had bridging callus on radiograph but 60% (12/20) had sonographic bridging callus (SBC) and when present all united (sensitivity 80%, specificity 100%, p = 0.002). At 12 weeks, bridging callus was present on both radiographs and ultrasound in all patients that united (n = 15, sensitivity 100%, specificity 100%, p < 0.001). No patient that developed a nonunion at six months post-injury had SBC at any time point. At six-weeks the absence of SBC had a positive predictive value for nonunion of 63% of patients (5/8) and by 12 weeks it was 100% (5/5). The SBC detection rated 'very strong' for intra- (kappa 0.92) and inter-observer agreement (kappa 0.84). The ICC of SBC at six-weeks with four blinded reviewers was 0.82 (95% confidence interval 0.68-0.91). CONCLUSIONS: This is the first study to establish time specific ultrasound fracture findings with a repeatable technique and assess the agreement between blinded reviewers.

What is the role of ultrasound in fracture management?: Diagnosis and therapeutic potential for fractures, delayed unions, and fracture-related infection.

OBJECTIVES: The aim of this study was to review the current evidence and future application for the role of diagnostic and therapeutic ultrasound in fracture management. METHODS: A review of relevant literature was undertaken, including articles indexed in PubMed with keywords "ultrasound" or "sonography" combined with "diagnosis", "fracture healing", "impaired fracture healing", "nonunion", "microbiology", and "fracture-related infection". RESULTS: The use of ultrasound in musculoskeletal medicine has expanded rapidly over the last two decades, but the diagnostic use in fracture management is not routinely practised. Early studies have shown the potential of ultrasound as a valid alternative to radiographs to diagnose common paediatric fractures, to detect occult injuries in adults, and for rapid detection of long bone fractures in the resuscitation setting. Ultrasound has also been shown to be advantageous in the early identification of impaired fracture healing; with the advent of 3D image processing, there is potential for wider adoption. Detection of implant-related infection can be improved by ultrasound mediated sonication of microbiology samples. The use of therapeutic ultrasound to promote union in the management of acute fractures is currently a controversial topic. However, there is strong in vitro evidence that ultrasound can stimulate a biological effect with potential clinical benefit in established nonunions, which supports the need for further investigation. CONCLUSION: Modern ultrasound image processing has the potential to replace traditional imaging modalities in several areas of trauma practice, particularly in the early prediction of impaired fracture healing. Further understanding of the therapeutic application of ultrasound is required to understand and identify the use in promoting fracture healing.Cite this article: J. A. Nicholson, S. T. J. Tsang, T. J. MacGillivray, F. Perks, A. H. R. W. Simpson. What is the role of ultrasound in fracture management? Diagnosis and therapeutic potential for fractures, delayed unions, and fracture-related infection. Bone Joint Res 2019;8:304-312. DOI: 10.1302/2046-3758.87.BJR-2018-0215.R2.

Positron Emission Tomography and Magnetic Resonance Imaging of Cellular Inflammation in Patients with Abdominal Aortic Aneurysms.

OBJECTIVES: Inflammation is critical in the pathogenesis of abdominal aortic aneurysm (AAA) disease. Combined (18)F-fludeoxyglucose ((18)F-FDG) positron emission tomography with computed tomography (PET-CT) and ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) are non-invasive methods of assessing tissue inflammation. The aim of this study was to compare these techniques in patients with AAA. MATERIALS AND METHODS: Fifteen patients with asymptomatic AAA with diameter 46 ± 7 mm underwent PET-CT with (18)F-FDG, and T2*-weighted MRI before and 24 hours after administration of USPIO. The PET-CT and MRI data were then co-registered. Standardised uptake values (SUVs) were calculated to measure (18)F-FDG activity, and USPIO uptake was determined using the change in R2*. Comparisons between the techniques were made using a quadrant analysis and a voxel-by-voxel evaluation. RESULTS: When all areas of the aneurysm were evaluated, there was a modest correlation between the SUV on PET-CT and the change in R2* on USPIO-enhanced MRI (n = 70,345 voxels; r = .30; p < .0001). Although regions of increased (18)F-FDG and USPIO uptake co-localised on occasion, this was infrequent (kappa statistic 0.074; 95% CI 0.026-0.122). (18)F-FDG activity was commonly focused in the shoulder region whereas USPIO uptake was more apparent in the main body of the aneurysm. Maximum SUV was lower in patients with mural USPIO uptake. CONCLUSIONS: Both (18)F-FDG PET-CT and USPIO-MRI uptake identify vascular inflammation associated with AAA. Although they demonstrate a modest correlation, there are distinct differences in the pattern and distribution of uptake, suggesting a differential detection of macrophage glycolytic and phagocytic activity respectively.

Nanoparticle enhanced MRI scanning to detect cellular inflammation in experimental chronic renal allograft rejection.

Objectives. We investigated whether ultrasmall paramagnetic particles of iron oxide- (USPIO-) enhanced magnetic resonance imaging (MRI) can detect experimental chronic allograft damage in a murine renal allograft model. Materials and Methods. Two cohorts of mice underwent renal transplantation with either a syngeneic isograft or allograft kidney. MRI scanning was performed prior to and 48 hours after USPIO infusion using T2(∗)-weighted protocols. R2(∗) values were calculated to indicate the degree of USPIO uptake. Native kidneys and skeletal muscle were imaged as reference tissues and renal explants analysed by histology and electron microscopy. Results. R2(∗) values in the allograft group were higher compared to the isograft group when indexed to native kidney (median 1.24 (interquartile range: 1.12 to 1.36) versus 0.96 (0.92 to 1.04), P < 0.01). R2(∗) values were also higher in the allograft transplant when indexed to skeletal muscle (6.24 (5.63 to 13.51)) compared to native kidney (2.91 (1.11 to 6.46) P < 0.05). Increased R2(∗) signal in kidney allograft was associated with macrophage and iron staining on histology. USPIO were identified within tissue resident macrophages on electron microscopy. Conclusion. USPIO-enhanced MRI identifies macrophage.

Retinal imaging as a source of biomarkers for diagnosis, characterization and prognosis of chronic illness or long-term conditions.

The black void behind the pupil was optically impenetrable before the invention of the ophthalmoscope by von Helmholtz over 150 years ago. Advances in retinal imaging and image processing, especially over the past decade, have opened a route to another unexplored landscape, the retinal neurovascular architecture and the retinal ganglion pathways linking to the central nervous system beyond. Exploiting these research opportunities requires multidisciplinary teams to explore the interface sitting at the border between ophthalmology, neurology and computing science. It is from the detail and depth of retinal phenotyping that novel metrics and candidate biomarkers are likely to emerge. Confirmation that in vivo retinal neurovascular measures are predictive of microvascular change in the brain and other organs is likely to be a major area of research activity over the next decade. Unlocking this hidden potential within the retina requires integration of structural and functional data sets, that is, multimodal mapping and longitudinal studies spanning the natural history of the disease process. And with further advances in imaging, it is likely that this area of retinal research will remain active and clinically relevant for many years to come. Accordingly, this review looks at state-of-the-art retinal imaging and its application to diagnosis, characterization and prognosis of chronic illness or long-term conditions.

Imaging techniques for the assessment of fracture repair.

Imaging of a healing fracture provides a non-invasive and often instructive reproduction of the fracture repair progress and the healing status of bone. However, the interpretation of this reproduction is often qualitative and provides only an indirect and surrogate measure of the mechanical stability of the healing fracture. Refinements of the available imaging techniques have been suggested to more accurately determine the healing status of bone. Plain radiographs provide the ability to determine the degree of bridging of the fracture gap and to quantify the amount of periosteal callus formation. Absorptiometric measures including dual X-ray absorptiometry and computed tomography provide quantitative information on the amount and the density of newly formed bone around the site of the fracture. To include the effect of spatial distribution of newly formed bone, finite element models of healing fracture can be employed to estimate its load bearing capacity. Ultrasound technology not only avoids radiation doses to the patients but also provides the ability to additionally measure vascularity in the surrounding soft tissue of the fracture and in the fracture itself.

Automatic retinal vessel classification using a Least Square-Support Vector Machine in VAMPIRE.

It is important to classify retinal blood vessels into arterioles and venules for computerised analysis of the vasculature and to aid discovery of disease biomarkers. For instance, zone B is the standardised region of a retinal image utilised for the measurement of the arteriole to venule width ratio (AVR), a parameter indicative of microvascular health and systemic disease. We introduce a Least Square-Support Vector Machine (LS-SVM) classifier for the first time (to the best of our knowledge) to label automatically arterioles and venules. We use only 4 image features and consider vessels inside zone B (802 vessels from 70 fundus camera images) and in an extended zone (1,207 vessels, 70 fundus camera images). We achieve an accuracy of 94.88% and 93.96% in zone B and the extended zone, respectively, with a training set of 10 images and a testing set of 60 images. With a smaller training set of only 5 images and the same testing set we achieve an accuracy of 94.16% and 93.95%, respectively. This experiment was repeated five times by randomly choosing 10 and 5 images for the training set. Mean classification accuracy are close to the above mentioned result. We conclude that the performance of our system is very promising and outperforms most recently reported systems. Our approach requires smaller training data sets compared to others but still results in a similar or higher classification rate.

Retinal vessel classification: sorting arteries and veins.

For the discovery of biomarkers in the retinal vasculature it is essential to classify vessels into arteries and veins. We automatically classify retinal vessels as arteries or veins based on colour features using a Gaussian Mixture Model, an Expectation-Maximization (GMM-EM) unsupervised classifier, and a quadrant-pairwise approach. Classification is performed on illumination-corrected images. 406 vessels from 35 images were processed resulting in 92% correct classification (when unlabelled vessels are not taken into account) as compared to 87.6%, 90.08%, and 88.28% reported in [12] [14] and [15]. The classifier results were compared against two trained human graders to establish performance parameters to validate the success of classification method. The proposed system results in specificity of (0.8978, 0.9591) and precision (positive predicted value) of (0.9045, 0.9408) as compared to specificity of (0.8920, 0.7918) and precision of (0.8802, 0.8118) for (arteries, veins) respectively as reported in [13]. The classification accuracy was found to be 0.8719 and 0.8547 for veins and arteries, respectively.

Association of retinal arteriolar dilatation with lower verbal memory: the Edinburgh Type 2 Diabetes Study.

AIMS/HYPOTHESIS: Retinal vascular calibre changes may reflect early subclinical microvascular disease in diabetes. Because of the considerable homology between retinal and cerebral microcirculation, we examined whether retinal vascular calibre, as a proxy of cerebral microvascular disease, was associated with cognitive function in older people with type 2 diabetes. METHODS: A cross-sectional analysis of 954 people aged 60-75 years with type 2 diabetes from the population-based Edinburgh Type 2 Diabetes Study was performed. Participants underwent standard seven-field binocular digital retinal photography and a battery of seven cognitive function tests. The Mill Hill Vocabulary Scale was used to estimate pre-morbid cognitive ability. Retinal vascular calibre was measured from an image field with the optic disc in the centre using a validated computer-based program. RESULTS: After age and sex adjustment, larger retinal arteriolar and venular calibres were significantly associated with lower scores for the Wechsler Logical Memory test, with standardised regression coefficients -0.119 and -0.084, respectively (p < 0.01), but not with other cognitive tests. There was a significant interaction between sex and retinal vascular calibre for logical memory. In male participants, the association of increased retinal arteriolar calibre with logical memory persisted (p < 0.05) when further adjusted for vocabulary, venular calibre, depression, cardiovascular risk factors and macrovascular disease. In female participants, this association was weaker and not significant. CONCLUSIONS/INTERPRETATION: Retinal arteriolar dilatation was associated with poorer memory, independent of estimated prior cognitive ability in older men with type 2 diabetes. The sex interaction with stronger findings in men requires confirmation. Nevertheless, these data suggest that impaired cerebral arteriolar autoregulation in smooth muscle cells, leading to arteriolar dilatation, may be a possible pathogenic mechanism in verbal declarative memory decrements in people with diabetes.

VAMPIRE: Vessel assessment and measurement platform for images of the REtina.

We present VAMPIRE, a software application for efficient, semi-automatic quantification of retinal vessel properties with large collections of fundus camera images. VAMPIRE is also an international collaborative project of four image processing groups and five clinical centres. The system provides automatic detection of retinal landmarks (optic disc, vasculature), and quantifies key parameters used frequently in investigative studies: vessel width, vessel branching coefficients, and tortuosity. The ultimate vision is to make VAMPIRE available as a public tool, to support quantification and analysis of large collections of fundus camera images.

The resolution integral: visual and computational approaches to characterizing ultrasound images.

The resolution integral is a figure of merit that characterizes ultrasound images in terms of the ratio of the penetration of an ultrasound beam in soft tissue to the ultrasound beam width. This concept has been implemented using a novel tissue mimicking test object (the Edinburgh pipe phantom) that comprises a series of anechoic cylinders of different diameters embedded in a block of tissue-mimicking material. The resolution integral is calculated by imaging each cylinder in turn and measuring the depth range over which it can be detected. We have carried out these measurements using two complementary approaches: by visual assessment and using a computational approach. Data were collected from 12 transducers used on 12 different models of ultrasound scanner of various makes, ages and clinical performance. Transducer centre frequencies were in the range of 3 to 7.5 MHz. The computational approach makes use of standard image processing techniques to detect and segment anechoic structures in images of the test object. This was optimized against visual assessment results for one of the transducers, and subsequently used to evaluate the resolution integral for the others. The values of the resolution integral ranged from 40 to 69 and computed values were within +/-11% of the corresponding visual assessments. The repeatability of both approaches was +/-2-3%. The computational approach functions well compared to visual assessment and adds to the overall robustness of resolution integral measurements by providing an objective assessment algorithm.

Fractal analysis of retinal vessels suggests that a distinct vasculopathy causes lacunar stroke.

OBJECTIVES: Lacunar strokes account for 25% of all ischemic strokes and may represent the cerebral manifestation of a systemic small vessel vasculopathy of unknown etiology. Altered retinal vessel fractal dimensions may act as a surrogate marker for diseased cerebral vessels. We used a cross-sectional study to investigate fractal properties of retinal vessels in lacunar stroke. METHODS: We recruited patients presenting with lacunar stroke and patients with minor cortical stroke as controls. All patients were examined by a stroke expert and had MRI at presentation. Digital retinal photographs were taken of both eyes. Monofractal and multifractal analyses were performed with custom-written semiautomated software. RESULTS: We recruited 183 patients. Seventeen were excluded owing to poor photographic quality, leaving 166 patients (86 with lacunar and 80 with cortical stroke). The mean age was 67.3 years (SD 11.5 years). The patients with lacunar stroke were younger but the prevalence of diabetes, hypertension, and white matter hyperintensities did not differ between the groups. The mean Dbox (monofractal dimension) was 1.42 (SD 0.02), the mean D0 (multifractal dimension) 1.67 (SD 0.03). With multivariate analysis, decreased Dbox and D0 (both representing decreased branching complexity) were associated with increasing age and lacunar stroke subtype after correcting for hypertension, diabetes, stroke severity, and white matter hyperintensity scores. CONCLUSIONS: Lacunar stroke subtype and increasing age are associated with decreased fractal dimensions, suggesting a loss of branching complexity. Further studies should concentrate on longitudinal associations with other manifestations of cerebral small vessel disease.

Differences in retinal vessels support a distinct vasculopathy causing lacunar stroke.

BACKGROUND: Lacunar stroke is common, but the etiology of the small vessel abnormality is unknown. Retinal vessels share ontogeny, size, and physiologic characteristics with cerebral small vessels, and retinopathy is associated with stroke. We compared retinal microvessel appearance as a surrogate for cerebral small vessels in patients with lacunar and large artery cortical ischemic stroke. METHODS: We prospectively recruited patients with lacunar ischemic stroke and cortical stroke controls. We took digital retinal photographs of each eye. We assessed central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) diameters and arteriovenous ratios (AVRs) using semiautomated computer software methods and quantified arteriovenous nicking and focal arteriolar narrowing. RESULTS: Among 212 patients (105 lacunar, 107 cortical strokes) of mean age 68 years (SD 12 years), AVR was decreased (0.76 vs 0.78, p = 0.03) and CRVE was increased (44.9 pixels/218 microm vs 42.8 pixels/208 microm, p = 0.01) in lacunar patients compared with cortical patients, but CRAE did not differ (33.2 pixels/161 microm vs 33.7 pixels/163 microm, p = 0.4). On multivariable analysis, increased CRVE was associated with lacunar stroke subtype (p = 0.03) and younger age (p < 0.001) after correcting for other vascular risk factors. Arteriovenous nicking and focal arteriolar narrowing did not differ between ischemic stroke subtypes. CONCLUSIONS: Retinal venules are wider and arteriovenous ratios are smaller in patients with lacunar strokes compared with those in patients with cortical strokes.

Fractal analysis of the retinal vascular network in fundus images.

Complexity of the retinal vascular network is quantified through the measurement of fractal dimension. A computerized approach enhances and segments the retinal vasculature in digital fundus images with an accuracy of 94% in comparison to the gold standard of manual tracing. Fractal analysis was performed on skeletonized versions of the network in 40 images from a study of stroke. Mean fractal dimension was found to be 1.398 (with standard deviation 0.024) from 20 images of the hypertensives sub-group and 1.408 (with standard deviation 0.025) from 18 images of the non-hypertensives subgroup. No evidence of a significant difference in the results was found for this sample size. However, statistical analysis showed that to detect a significant difference at the level seen in the data would require a larger sample size of 88 per group.

A reliability study of fractal analysis of the skeletonised vascular network using the "box-counting" technique.

Binary vascular networks of the human retina were obtained by computerized processing of digital fundus images. Fractal analysis was performed on skeletonised versions. The effect of three parameters in the vascular segmentation and skeletonization algorithm was quantified, with threshold level found to have the greatest influence. The results were compared to fractal analysis of skeletons derived by manual tracing. The mean difference in fractal dimension between 2 observers is 0.004 (0.3%) and the coefficient of repeatability is +/- 0.050 (3.4%). Between a single observer and the computerized approach the mean difference is 0.012 (0.8%) and the coefficient is +/- 0.038 (2.6%). The computerized approach demonstrated a superior reliability compared to manual segmentation.

Cognitive correlates of cerebral white matter lesions and water diffusion tensor parameters in community-dwelling older people.

BACKGROUND: The biological basis of cognitive ageing is unknown. One underlying process might be disruption of white matter tracts connecting cortical regions. White matter lesions (WML) seen on structural MRI may disrupt cortical connections, but diffusion tensor MRI (DT-MRI) parameters - mean diffusivity () and fractional anisotropy (FA) - may reflect more subtle changes in white matter integrity. Here the relationships between WML load, DT-MRI parameters and cognition in a large cohort of elderly subjects with a very narrow age range were investigated. METHODS: 105 community-dwelling volunteers underwent MRI and neuropsychological assessment. Seventy-two (68.6%) were female, and their mean age was 78.4 (SD 1.5) years. Scans were rated for WML load. and FA were measured from regions of interest in normal-appearing frontal and occipital white matter, and centrum semiovale. RESULTS: and FA differed significantly among the three brain regions studied (p << 0.01). increased with age (r = 0.22 to 0.35, p < 0.03), and was negatively correlated with FA (r = -0.20 to -0.51, p < 0.05) in all three regions. There was a trend towards increased WML load correlating with poorer cognitive function, and this was statistically significant for the Mini-Mental State Examination (rho = -0.23, p = 0.02). was generally negatively correlated with cognitive test score, and FA was positively correlated. This pattern was more consistent for than for FA, and particularly for verbal fluency (: r = -0.22 to -0.27, p < 0.03), which measures executive function. CONCLUSIONS: DT-MRI parameters, in particular , are sensitive to early ultrastructural changes underlying cognitive ageing. Executive function may be the cognitive domain most sensitive to age-related decline in white matter tract integrity.

Structural disconnectivity in schizophrenia: a diffusion tensor magnetic resonance imaging study.

BACKGROUND: There is growing evidence that schizophrenia is a disorder of cortical connectivity. Specifically, frontotemporal and frontoparietal connections are thought to be functionally impaired. Diffusion tensor magnetic resonance imaging (DT-MRI) is a technique that has the potential to demonstrate structural disconnectivity in schizophrenia. AIMS: To investigate the structural integrity of frontotemporal and frontoparietal white matter tracts in schizophrenia. METHOD: Thirty patients with DSM-IV schizophrenia and thirty matched control subjects underwent DT-MRI and structural MRI. Fractional anisotropy - an index of the integrity of white matter tracts - was determined in the uncinate fasciculus, the anterior cingulum and the arcuate fasciculus and analysed using voxel-based morphometry. RESULTS: There was reduced fractional anisotropy in the left uncinate fasciculus and left arcuate fasciculus in patients with schizophrenia compared with controls. CONCLUSIONS: The findings of reduced white matter tract integrity in the left uncinate fasciculus and left arcuate fasciculus suggest that there is frontotemporal and frontoparietal structural disconnectivity in schizophrenia.

Long-term results and determinants of mortality after surgery for native and prosthetic valve endocarditis.

BACKGROUND AND AIM OF THE STUDY: The study aim was to describe the long-term results and determinants of mortality after operative treatment of native and prosthetic valve endocarditis at a single institution. METHODS: Between March 1985 and October 1999, 171 patients underwent surgery for native (NVE) or prosthetic valve endocarditis (PVE). NVE was present in 98 patients (57%), and PVE in 73 patients (43%). Mean follow up was 5.6+/-3.9 years (range: 0 to 15 years). RESULTS: Overall hospital mortality was 9.9% (n = 17). Hospital mortality was higher among patients with PVE (15.1%) than those with NVE (6.1%; p = 0.05). Overall survival at 10 years was 46+/-5%. Patients with NVE had a higher 10-year survival rate (53+/-7%) than those with PVE (37+/-7%; p = 0.02). At 10 years, overall freedom from any late complication was 47+/-6% and from residual or recurrent endocarditis was 78+/-5%. Predictors of hospital death were emergency surgery (p <0.003) and preoperative renal insufficiency (p <0.008). Predictors of late death were age >70 years (p <0.002), renal failure (p <0.03) and fungal endocarditis (p <0.04). CONCLUSION: These findings demonstrate the increased perioperative, as well as postoperative, risks associated with PVE versus NVE. Cardiac and extracardiac manifestations of the disease, as well as fungal organisms, but not the activity of the endocarditis, were significant adverse determinants of late outcome.