Human papillomavirus assay design is a crucial consideration for self-collection based cervical screening.

No abstract provided.

Performance of image guided navigation in laparoscopic liver surgery - A systematic review.

BACKGROUND: Compared to open surgery, minimally invasive liver resection has improved short term outcomes. It is however technically more challenging. Navigated image guidance systems (IGS) are being developed to overcome these challenges. The aim of this systematic review is to provide an overview of their current capabilities and limitations. METHODS: Medline, Embase and Cochrane databases were searched using free text terms and corresponding controlled vocabulary. Titles and abstracts of retrieved articles were screened for inclusion criteria. Due to the heterogeneity of the retrieved data it was not possible to conduct a meta-analysis. Therefore results are presented in tabulated and narrative format. RESULTS: Out of 2015 articles, 17 pre-clinical and 33 clinical papers met inclusion criteria. Data from 24 articles that reported on accuracy indicates that in recent years navigation accuracy has been in the range of 8-15 mm. Due to discrepancies in evaluation methods it is difficult to compare accuracy metrics between different systems. Surgeon feedback suggests that current state of the art IGS may be useful as a supplementary navigation tool, especially in small liver lesions that are difficult to locate. They are however not able to reliably localise all relevant anatomical structures. Only one article investigated IGS impact on clinical outcomes. CONCLUSIONS: Further improvements in navigation accuracy are needed to enable reliable visualisation of tumour margins with the precision required for oncological resections. To enhance comparability between different IGS it is crucial to find a consensus on the assessment of navigation accuracy as a minimum reporting standard.

Evaluation of the Roche MagNA Pure 96 nucleic acid extraction platform for the Seegene Anyplex II HPV28 detection assay.

AIM: Validate the Roche, MagNAPure96 (MP96) nucleic acid extraction platform for Seegene Anyplex II HPV28 (Anyplex28) detection of Human Papillomavirus. METHODS AND RESULTS: Comparisons were made for Anyplex28 genotyping from 115 cervical samples extracted on the Hamilton, STARlet and the MP96. Two DNA concentrations were used for the MP96, one matched for sample input to the STARlet and another 5× concentration (laboratory standard). Agreement of HPV detection was 89·8% (κ = 0·798; P = 0·007), with HPV detected in 10 more samples for the MP96. There was a high concordance of detection for any oncogenic HPV genotype (κ = 0·77; P = 0·007) and for any low-risk HPV genotype (κ = 0·85; P = 0·008). DNA extracted at laboratory standard had a lower overall agreement 85·2% (κ = 0·708; P < 0·001), with 17/115 discordant positive samples that tested negative after STARlet extraction. Of the discordant genotypes, 72·7% were detected in the lowest signal range for Anyplex28 ('+'). CONCLUSIONS: MP96 performed with high concordance to STARlet, although produced DNA with a higher analytical sensitivity on the Anyplex28. SIGNIFICANCE AND IMPACT OF THE STUDY: This analysis supports the use of samples extracted on the MP96 for HPV genotyping using the Anyplex28. Furthermore, an increase in DNA concentration increased analytical sensitivity of the Anyplex28, particularly appropriate for prevalence studies.

Comparison of manual and semi-automatic registration in augmented reality image-guided liver surgery: a clinical feasibility study.

BACKGROUND: The laparoscopic approach to liver resection may reduce morbidity and hospital stay. However, uptake has been slow due to concerns about patient safety and oncological radicality. Image guidance systems may improve patient safety by enabling 3D visualisation of critical intra- and extrahepatic structures. Current systems suffer from non-intuitive visualisation and a complicated setup process. A novel image guidance system (SmartLiver), offering augmented reality visualisation and semi-automatic registration has been developed to address these issues. A clinical feasibility study evaluated the performance and usability of SmartLiver with either manual or semi-automatic registration. METHODS: Intraoperative image guidance data were recorded and analysed in patients undergoing laparoscopic liver resection or cancer staging. Stereoscopic surface reconstruction and iterative closest point matching facilitated semi-automatic registration. The primary endpoint was defined as successful registration as determined by the operating surgeon. Secondary endpoints were system usability as assessed by a surgeon questionnaire and comparison of manual vs. semi-automatic registration accuracy. Since SmartLiver is still in development no attempt was made to evaluate its impact on perioperative outcomes. RESULTS: The primary endpoint was achieved in 16 out of 18 patients. Initially semi-automatic registration failed because the IGS could not distinguish the liver surface from surrounding structures. Implementation of a deep learning algorithm enabled the IGS to overcome this issue and facilitate semi-automatic registration. Mean registration accuracy was 10.9 ± 4.2 mm (manual) vs. 13.9 ± 4.4 mm (semi-automatic) (Mean difference - 3 mm; p = 0.158). Surgeon feedback was positive about IGS handling and improved intraoperative orientation but also highlighted the need for a simpler setup process and better integration with laparoscopic ultrasound. CONCLUSION: The technical feasibility of using SmartLiver intraoperatively has been demonstrated. With further improvements semi-automatic registration may enhance user friendliness and workflow of SmartLiver. Manual and semi-automatic registration accuracy were comparable but evaluation on a larger patient cohort is required to confirm these findings.

Analytical performance of HPV assays on vaginal self-collected vs practitioner-collected cervical samples: the SCoPE study.

BACKGROUND: In the last decade, human papillomavirus (HPV) testing has been evaluated extensively for cervical screening, with studies finding increased sensitivity compared to cytology. Another advantage of HPV based-screening is the ability to test vaginal samples that can be collected by women themselves. Self-collection has the potential to extend cervical screening coverage by increasing participation rates, particularly among women who are under-screened or have never screened. This could have a significant impact on cervical cancer prevention, as the majority of invasive cervical cancer cases occur among under-screened women. Both the Netherlands and Australia have transitioned their national programs from cytology to HPV as the primary screening test and both countries include a pathway for self-collection. OBJECTIVES: We evaluated the relative sensitivity for HPV detection of self-collection compared with practitioner-collected cervical specimens in the context of the Australian National Cervical Screening Program (NCSP). STUDY DESIGN: 303 women aged ≥18 years attending a single tertiary referral centre took their own sample using a flocked-swab, and then had a practitioner-collected sample taken at colposcopy. All samples were tested at a single laboratory on the six PCR-based HPV assays which can be utilised in the NCSP; Roche cobas 4800 and cobas, Abbott RealTime, BD Onclarity, Cepheid Xpert, and Seegene Anyplex. RESULTS: HPV16/18 results had high observed agreement between self- and practitioner-collected samples on all assays (range: 0.94-0.99), with good agreement for non-HPV16/18 oncogenic HPV types (range: 0.64-0.73). CONCLUSIONS: Self-collection for HPV-based cervical screening shows good concordance and relative sensitivity when compared to practitionercollected samples across assays in the NCSP.

Nonrigid reconstruction of 3D breast surfaces with a low-cost RGBD camera for surgical planning and aesthetic evaluation.

Accounting for 26% of all new cancer cases worldwide, breast cancer remains the most common form of cancer in women. Although early breast cancer has a favourable long-term prognosis, roughly a third of patients suffer from a suboptimal aesthetic outcome despite breast conserving cancer treatment. Clinical-quality 3D modelling of the breast surface therefore assumes an increasingly important role in advancing treatment planning, prediction and evaluation of breast cosmesis. Yet, existing 3D torso scanners are expensive and either infrastructure-heavy or subject to motion artefacts. In this paper we employ a single consumer-grade RGBD camera with an ICP-based registration approach to jointly align all points from a sequence of depth images non-rigidly. Subtle body deformation due to postural sway and respiration is successfully mitigated leading to a higher geometric accuracy through regularised locally affine transformations. We present results from 6 clinical cases where our method compares well with the gold standard and outperforms a previous approach. We show that our method produces better reconstructions qualitatively by visual assessment and quantitatively by consistently obtaining lower landmark error scores and yielding more accurate breast volume estimates.

3-D Pose Estimation of Articulated Instruments in Robotic Minimally Invasive Surgery.

Estimating the 3-D pose of instruments is an important part of robotic minimally invasive surgery for automation of basic procedures as well as providing safety features, such as virtual fixtures. Image-based methods of 3-D pose estimation provide a non-invasive low cost solution compared with methods that incorporate external tracking systems. In this paper, we extend our recent work in estimating rigid 3-D pose with silhouette and optical flow-based features to incorporate the articulated degrees-of-freedom (DOFs) of robotic instruments within a gradient-based optimization framework. Validation of the technique is provided with a calibrated ex-vivo study from the da Vinci Research Kit (DVRK) robotic system, where we perform quantitative analysis on the errors each DOF of our tracker. Additionally, we perform several detailed comparisons with recently published techniques that combine visual methods with kinematic data acquired from the joint encoders. Our experiments demonstrate that our method is competitively accurate while relying solely on image data.

Completing the cervical screening pathway: Factors that facilitate the increase of self-collection uptake among under-screened and never-screened women, an Australian pilot study.

OBJECTIVES: To examine factors that enhance under-screened and never-screened women's completion of the self-collection alternative pathway of the Renewed National Cervical Screening Program (ncsp) in Victoria, Australia. BACKGROUND: With the Australian ncsp changing, starting on 1 December 2017, the Medical Services Advisory Committee (msac) recommended implementing human papillomavirus (hpv) testing using a self-collected sample for under-screened and never-screened populations. In response, a multi-agency group implemented an hpv self-collection pilot project to trial self-collection screening pathways for eligible women. METHODS: Quantitative data were collected on participation rates and compliance rates with follow-up procedures across three primary health care settings. Forty women who self-collected were interviewed in a semi-structured format, and seven agency staff completed in-depth interviews. Qualitative data were used to identify and understand clinical and personal enablers that assisted women to complete self-collection cervical screening pathways successfully. RESULTS: Eighty-five per cent (10 women) of participants who tested positive for hpv successfully received their results and completed follow-up procedures as required. Two remaining participants also received hpv-positive results. However, agencies were unable to engage them in follow-up services and procedures. The overall participation rate in screening (self-collection or Pap test) was 85.7% (84 women), with 79 women self-collecting. Qualitative data indicated that clear explanations on self-collection, development of trusting, empathetic relationships with health professionals, and recognition of participants' past experiences were critical to the successful completion of the self-collection pathway. When asked about possible inhibitors to screening and to following up on results and appointments, women cited poor physical and mental health, as well as financial and other structural barriers. CONCLUSION: A well-implemented process, led by trusted, knowledgeable, and engaged health care professionals who can provide appropriate support and information, can assist under-screened and never-screened women to complete the hpv self-collection pathway successfully.

Self-collection for under-screened women in a National Cervical Screening Program: pilot study.

BACKGROUND: Commencing 1 December 2017, Australia introduced human papillomavirus (hpv)-based cervical screening. As part of this Australian renewed National Cervical Screening Program (ncsp) women who are either never- or under-screened and who refuse a practitioner collected sample will be able to collect their own sample for cervical screening. The aim of this study is to examine the quantitative results of a pilot study into the acceptability of the self-collection alternative pathway. METHODS: Eligible participants were offered the opportunity to collect their own sample. Those who agreed were given a flocked swab and an instruction sheet and took their own sample in an area of the health care clinic that afforded them adequate privacy. These samples were then given to clinic staff who returned them to Victorian Cytology Service (vcs) Pathology for hpv nucleic acid testing. RESULTS: Of 98 eligible women, seventy-nine undertook self-collection for hpv-based cervical screening. Seventy-seven produced valid results, 14 were positive for oncogenic hpv, with 10 undertaking follow-up. Three women were found to have cervical squamous abnormalities with two of those being high-grade intraepithelial squamous lesions. CONCLUSION: The pilot study for self-collection for cervical screening produced quantitative data that were similar to that already reported in the literature, but had a much higher rate of acceptance compared with self-collection programs based in the home.

Critiquing operative fracture fixation: the development of an assessment tool.

PURPOSE: Assessments are fundamentally important for training surgeons. Currently, there are no formal means of assessing operative fracture fixation. An assessment tool has been developed which can be used by trainers to critique the quality of a trainee's operative fracture fixation. The tool is based on the AO principles of fracture management. The reliability and validity of the assessment were tested in a prospective study. METHODS: The assessment tool comprises of 4 domains focusing on the different factors pertinent to fracture fixation (reduction, stability, implant and overall impression). Reliability and validity were evaluated by asking 10 consultant trauma and orthopaedic surgeons to score 20 test cases on two different occasions at least 7 weeks apart. Internal consistency was assessed by Cronbach's alpha. Inter-rater reliability and test-retest reliability were assessed by the inter-class correlation coefficient (ICC) and content validity by the content validity ratio (CVR). RESULTS: Cronbach's alpha was 0.976, with all component criteria correlating well with each other. Total score inter-rater reliability, for a single assessor, as given by the ICC, was 0.708. Overall test-retest reliability was 0.961. The CVR for the assessment tool was 0.65 (which is above the critical value for establishing validity with 10 assessors). CONCLUSIONS: Internal consistency is demonstrated by the excellent Cronbach's alpha with substantial single assessor and excellent test-retest reliability also shown. The CVR above the critical value illustrates that the assessment is valid. The assessment tool has a number of applications within training and service evaluation that could benefit the global orthopaedic community.

Expanding the Clinical Spectrum Associated With GLIS3 Mutations.

CONTEXT: GLIS3 (GLI-similar 3) is a member of the GLI-similar zinc finger protein family encoding for a nuclear protein with 5 C2H2-type zinc finger domains. The protein is expressed early in embryogenesis and plays a critical role as both a repressor and activator of transcription. Human GLIS3 mutations are extremely rare. OBJECTIVE: The purpose of this article was determine the phenotypic presentation of 12 patients with a variety of GLIS3 mutations. METHODS: GLIS3 gene mutations were sought by PCR amplification and sequence analysis of exons 1 to 11. Clinical information was provided by the referring clinicians and subsequently using a questionnaire circulated to gain further information. RESULTS: We report the first case of a patient with a compound heterozygous mutation in GLIS3 who did not present with congenital hypothyroidism. All patients presented with neonatal diabetes with a range of insulin sensitivities. Thyroid disease varied among patients. Hepatic and renal disease was common with liver dysfunction ranging from hepatitis to cirrhosis; cystic dysplasia was the most common renal manifestation. We describe new presenting features in patients with GLIS3 mutations, including craniosynostosis, hiatus hernia, atrial septal defect, splenic cyst, and choanal atresia and confirm further cases with sensorineural deafness and exocrine pancreatic insufficiency. CONCLUSION: We report new findings within the GLIS3 phenotype, further extending the spectrum of abnormalities associated with GLIS3 mutations and providing novel insights into the role of GLIS3 in human physiological development. All but 2 of the patients within our cohort are still alive, and we describe the first patient to live to adulthood with a GLIS3 mutation, suggesting that even patients with a severe GLIS3 phenotype may have a longer life expectancy than originally described.

Detection and modelling of contacts in explicit finite-element simulation of soft tissue biomechanics.

PURPOSE: Realistic modelling of soft tissue biomechanics and mechanical interactions between tissues is an important part of biomechanically-informed surgical image-guidance and surgical simulation. This submission details a contact-modelling pipeline suitable for implementation in explicit matrix-free FEM solvers. While these FEM algorithms have been shown to be very suitable for simulation of soft tissue biomechanics and successfully used in a number of image-guidance systems, contact modelling specifically for these solvers is rarely addressed, partly because the typically large number of time steps required with this class of FEM solvers has led to a perception of them being a poor choice for simulations requiring complex contact modelling. METHODS: The presented algorithm is capable of handling most scenarios typically encountered in image-guidance. The contact forces are computed with an evolution of the Lagrange-multiplier method first used by Taylor and Flanagan in PRONTO 3D extended with spatio-temporal smoothing heuristics for improved stability and edge-edge collision handling, and a new friction model. For contact search, a bounding-volume hierarchy (BVH) is employed, which is capable of identifying self-collisions by means of the surface-normal bounding cone of Volino and Magnenat-Thalmann, in turn computed with a novel formula. The BVH is further optimised for the small time steps by reducing the number of bounding-volume refittings between iterations through identification of regions with mostly rigid motion and negligible deformation. Further optimisation is achieved by integrating the self-collision criterion in the BVH creation and updating algorithms. RESULTS: The effectiveness of the algorithm is demonstrated on a number of artificial test cases and meshes derived from medical image data. It is shown that the proposed algorithm reduces the cost of BVH refitting to the point where it becomes a negligible part of the overall computation time of the simulation. It is also shown that the proposed surface-normal cone computation formula leads to about 40 % fewer BVH subtrees that must be checked for self-collisions compared with the widely used method of Provot. The proposed contact-force formulation and friction model are evaluated on artificial test cases that allow for a comparison with a ground truth. The quality of the proposed contact forces is assessed in terms of trajectories and energy conservation; a [Formula: see text]0.4 % drop off in total energy and highly plausible trajectories are found in the experiments. The friction model is evaluated through a benchmark problem with an analytical solution and a maximum displacement error of 8.2 %, and excellent agreement in terms of the stick/slip boundary is found. Finally, we show with realistic image-guidance examples that the entire contact-modelling pipeline can be executed within a timeframe that is of the same order of magnitude as that required for standard FEM computations.

Patient-specific respiratory models using dynamic 3D MRI: preliminary volunteer results.

Organ and tumour motion has a significant impact on the planning and delivery of radiotherapy treatment. At present imaging modality such as four-dimensional computer tomography (4DCT) cannot be used to measure the variability of motion between different respiratory cycles. To create reliable motion models, one needs to acquire volumetric data sets of the lungs with sufficient sampling of the breathing cycle. In this paper we investigate the use of highly parallel MRI to acquire such data. A 32 channel coil in conjunction with a balanced SSFP sequence and a SENSE factor of 6 were used to acquire volumetric data sets in five healthy volunteers. The acquisition was repeated for seven series of different breathing patterns. The data acquired was of sufficient spatial resolution (5 × 5 × 5 mm(3)) and image quality to carry out automated non-rigid registration. The acquisition rate (c.a. 2 volumes per second) allowed for a meaningful sampling of the different respiratory curves that were automatically obtained from the skin surface motion. This acquisition technique should provide images of high enough quality to create statistical respiratory models.

WE-E-213CD-03: Inverse-Consistent Symmetric Registration of Inner Colon Surfaces Derived from Prone and Supine CT Colonography.

PURPOSE: Robust registration of prone and supine colonie surfaces acquired during CT colonography may lead to faster and more accurate detection of colorectal cancer and polyps. Any directional bias when registering one surface to the other could precipitate incorrect anatomical correspondence and engender reader error. Despite this, non-rigid registration methods are often implemented asymmetrically, which could negatively influence the registration. We aimed to reduce directional bias and so increase robustness by adapting a cylindrical registration algorithm to be both symmetric and inverse-consistent. METHODS: The registration task can be simplified by mapping both prone and supine colonie surfaces onto regular cylinders. Spatial correspondence can then be established in cylindrical space using the original surfaces' local shape indices. We implemented a symmetric formulation of the popular non-rigid B-spline image registration method in cylindrical space. A symmetric similarity measure computes the sum of squared differences between both cylindrical representations of prone-to-supine and supine-to-prone directions simultaneously. Inverse consistency of the transformation is enforced by adding an appropriately weighted penalty term to the optimisation function. RESULTS: We selected 8 CT colonography patient cases with marked variation in luminal distension and surface morphology. We randomly allocated 4 of these for tuning an optimal set of registration parameters and 4 for validation. The mean inverse-consistency error was reduced by 32% from 4.8mm to 3.2mm by the new symmetric formulation. The mean registration error improved from 8.2mm to 7.3mm for 330 manually chosen reference points on the 4 validation sets. CONCLUSIONS: A symmetric formulation of prone and supine surface registration improves the quality of registration. Information from both prone-to-supine and supine-to-prone directions helps enforce convergence towards a more accurate solution due to reduced directional bias. A more robust and accurate registration will facilitate interpretation of CT colonography and has the potential to improve existing computer-aided detection methods. The authors gratefully acknowledge financial support for this work from the NIHR program: â€Å“Imaging diagnosis of colorectal cancer: Interventions for efficient and acceptable diagnosis in symptomatic and screening populationsâ€.

The effect of motion correction on pharmacokinetic parameter estimation in dynamic-contrast-enhanced MRI.

A dynamic-contrast-enhanced magnetic resonance imaging (DCE-MRI) dataset consists of many imaging frames, often acquired both before and after contrast injection. Due to the length of time spent acquiring images, patient motion is likely and image re-alignment or registration is required before further analysis such as pharmacokinetic model fitting. Non-rigid image registration procedures may be used to correct motion artefacts; however, a careful choice of registration strategy is required to reduce misregistration artefacts associated with enhancing features. This work investigates the effect of registration on the results of model-fitting algorithms for 52 DCE-MR mammography cases for 14 patients. Results are divided into two sections: a comparison of registration strategies in which a DCE-MRI-specific algorithm is preferred in 50% of cases, followed by an investigation of parameter changes with known applied deformations, inspecting the effect of magnitude and timing of motion artefacts. Increased motion magnitude correlates with increased model-fit residual and is seen to have a strong influence on the visibility of strongly enhancing features. Motion artefacts in images close to the contrast agent arrival have a disproportionate effect on discrepancies in parameter estimation. The choice of algorithm, magnitude of motion and timing of the motion are each shown to influence estimated pharmacokinetic parameters even when motion magnitude is small.

Novel GLIS3 mutations demonstrate an extended multisystem phenotype.

INTRODUCTION: Mutations in the GLI-similar 3 (GLIS3) gene encoding the transcription factor GLIS3 are a rare cause of neonatal diabetes and congenital hypothyroidism with six affected cases from three families reported to date. Additional features, described previously, include congenital glaucoma, hepatic fibrosis, polycystic kidneys, developmental delay and facial dysmorphism. SUBJECTS: We report two new cases from unrelated families with distinct novel homozygous partial GLIS3 deletions. Both patients presented with neonatal diabetes mellitus, severe resistant hypothyroidism in the presence of elevated thyroglobulin and normal thyroid anatomy, degenerative liver disease, cystic renal dysplasia, recurrent infections and facial dysmorphism. These novel mutations have also resulted in osteopenia, bilateral sensorineural deafness and pancreatic exocrine insufficiency, features that have not previously been associated with GLIS3 mutations. Gene dosage analysis showed that the parents were carriers of a deletion encompassing exons 1-2 (case 1) or exons 1-4 (case 2) of the 11 exon gene. Genome-wide SNP analysis did not reveal a common ancestral GLIS3 haplotype in patient 2. CONCLUSIONS: Our results confirm partial gene deletions as the most common type of GLIS3 mutations, accounting for four of five families identified to date. We propose that mutations in GLIS3 lead to a wider clinical phenotype than previously recognised. We also report the first case of a recessive GLIS3 mutation causing neonatal diabetes and congenital hypothyroidism in a child from a non-consanguineous pedigree, highlighting the importance of molecular genetic testing in any patient with this phenotype.

Inter-fraction variations in respiratory motion models.

Respiratory motion can vary dramatically between the planning stage and the different fractions of radiotherapy treatment. Motion predictions used when constructing the radiotherapy plan may be unsuitable for later fractions of treatment. This paper presents a methodology for constructing patient-specific respiratory motion models and uses these models to evaluate and analyse the inter-fraction variations in the respiratory motion. The internal respiratory motion is determined from the deformable registration of Cine CT data and related to a respiratory surrogate signal derived from 3D skin surface data. Three different models for relating the internal motion to the surrogate signal have been investigated in this work. Data were acquired from six lung cancer patients. Two full datasets were acquired for each patient, one before the course of radiotherapy treatment and one at the end (approximately 6 weeks later). Separate models were built for each dataset. All models could accurately predict the respiratory motion in the same dataset, but had large errors when predicting the motion in the other dataset. Analysis of the inter-fraction variations revealed that most variations were spatially varying base-line shifts, but changes to the anatomy and the motion trajectories were also observed.

A subject-specific technique for respiratory motion correction in image-guided cardiac catheterisation procedures.

We describe a system for respiratory motion correction of MRI-derived roadmaps for use in X-ray guided cardiac catheterisation procedures. The technique uses a subject-specific affine motion model that is quickly constructed from a short pre-procedure MRI scan. We test a dynamic MRI sequence that acquires a small number of high resolution slices, rather than a single low resolution volume. Additionally, we use prior knowledge of the nature of cardiac respiratory motion by constraining the model to use only the dominant modes of motion. During the procedure the motion of the diaphragm is tracked in X-ray fluoroscopy images, allowing the roadmap to be updated using the motion model. X-ray image acquisition is cardiac gated. Validation is performed on four volunteer datasets and three patient datasets. The accuracy of the model in 3D was within 5mm in 97.6% of volunteer validations. For the patients, 2D accuracy was improved from 5 to 13mm before applying the model to 2-4mm afterwards. For the dynamic MRI sequence comparison, the highest errors were found when using the low resolution volume sequence with an unconstrained model.