Neuroprotection is improved by watertightness of fetal spina bifida repair in the sheep model.

OBJECTIVES: A contributing factor to unsuccessful prenatal spina bifida aperta (SBA) repair via an open approach may be incomplete neurosurgical repair causing persistent in-utero leakage of cerebrospinal fluid (CSF) and exposure of the fetal spinal cord to amniotic fluid. We aimed to investigate the neurostructural and neurofunctional efficacy of watertight prenatal SBA repair in a validated SBA fetal lamb model. METHODS: A well-powered superiority study was conducted in the validated SBA fetal lamb model (n = 7 per group). The outcomes of lambs which underwent watertight or non-watertight multilayer repair through an open approach were compared to those of unrepaired SBA lambs (historical controls) at delivery (term = 145 days). At ∼75 days, fetal lambs underwent standardized induction of lumbar SBA. At ∼100 days, they were assigned to an either watertight or non-watertight layered repair group based on an intraoperative watertightness test using subcutaneous fluorescein injection. At 1-2 days postnatally, as primary outcome, we assessed reversal of hindbrain herniation using magnetic resonance imaging (MRI). Secondary proxies of neuroprotection were: absence of CSF leakage at the repair site; hindlimb motor function based on joint-movement score, locomotor grade and Motor Evoked Potential (MEP); four-score neuroprotection scale, encompassing live birth, complete hindbrain herniation reversal, absence of CSF leakage and joint-movement score ≥ 9/15; and brain and spinal cord histology and immunohistochemistry. As the watertightness test cannot be used clinically due to its invasiveness, we developed a potential surrogate intraoperative three-score skin-repair-quality scale based on visual assessment of the quality of the skin repair (suture inter-run distance ≤ 3 mm, absence of tear and absence of ischemia), with high quality defined by a score ≥ 2/3 and low quality by a score < 2/3, and assessed its relationship with improved outcome. RESULTS: Compared with unrepaired lambs, lambs with watertight repair achieved a high level of neuroprotection (neuroprotection score of 4/4 in 5/7 vs 0/7 lambs) as evidenced by: a significant 100% (vs 14%) reversal of hindbrain herniation on MRI; low CSF leakage (14% vs 100%); better hindlimb motor function, with higher joint-movement score, locomotor grade and MEP area under the curve and peak-to-peak amplitude; higher neuronal density in the hippocampus and corpus callosum; and higher reactive astrogliosis at the SBA lesion epicenter. Conversely, lambs with non-watertight SBA repair did not achieve the same level of neuroprotection (score of 4/4 in 1/7 lambs) compared with unrepaired lambs, with: a non-significant 86% (vs 14%) reversal of hindbrain herniation; high CSF leakage (43% vs 100%); no improvement in motor function; low brain neuron count in both the hippocampus and corpus callosum; and small spinal astroglial cell area at the epicenter. Both watertight layered repair and high (≥ 2/3) intraoperative skin-repair-quality score were associated with improved outcome, but the watertightness test and skin-repair-quality scale could not be used interchangeably due to result discrepancies. CONCLUSIONS: Watertight layered fetal SBA repair is neuroprotective since it improves brain and spinal-cord structure and function in the fetal lamb model. This translational research has important clinical implications. A neurosurgical technique that achieves watertightness should be adopted in all fetal centers to improve neuroprotection. Future clinical studies could assess whether a high skin-repair-quality score (≥ 2/3) correlates with neuroprotection. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Cranial findings detected by second-trimester ultrasound in fetuses with myelomeningocele: a systematic review.

BACKGROUND: Abnormal intracranial findings are often detected at mid-trimester ultrasound (US) in fetuses with myelomeningocele (MMC). It is unclear whether these findings constitute a spectrum of the disease or are an independent finding, which should contraindicate fetal surgery. OBJECTIVE: To ascertain the spectrum and frequency of US-detected cranial findings in fetuses with MMC. SEARCH STRATEGY: MEDLINE, Embase, Web of Science and CENTRAL were searched from January 2000 to June 2020. SELECTION CRITERIA: Study reporting incidence of cranial US findings in consecutive cases of second-trimester fetuses with MMC. DATA COLLECTION AND ANALYSIS: Publication quality was assessed by Newcastle-Ottawa Scale (NOS) and modified NOS. Meta-analysis could not be performed as a result of high clinical diversity and study heterogeneity. MAIN RESULTS: Fourteen cranial US findings were reported in 15 studies. Findings in classic Chiari II malformation (CIIM) spectrum included posterior fossa funnelling (96%), small transcerebellar diameter (82-96%), 'banana' sign (50-100%), beaked tectum (65%) and 'lemon' sign (53-100%). Additional cranial findings were small biparietal diameter (BPD) and head circumference (HC) (<5th centile; 53 and 71%, respectively), ventriculomegaly (45-89%), abnormal pointed shape of the occipital horn (77-78%), thinning of the posterior cerebrum, perinodular heterotopia (11%), abnormal gyration (3%), corpus callosum disorders (60%) and midline interhemispheric cyst (42%). CONCLUSIONS: We identified 14 cranial findings by second-trimester US in fetuses with MMC. The relatively high incidence of these findings and their unclear prognostic significance might not contraindicate fetal surgery in the case of normal fetal genetic testing. Some cranial findings may independently affect postnatal outcome, however. Long-term detailed follow-up is required to investigate this. TWEETABLE ABSTRACT: A high rate of cranial abnormalities found on second-trimester ultrasound in fetuses with myelomeningocele.

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.

Artificial intelligence for the real-time classification of intrapapillary capillary loop patterns in the endoscopic diagnosis of early oesophageal squamous cell carcinoma: A proof-of-concept study.

Background: Intrapapillary capillary loops (IPCLs) represent an endoscopically visible feature of early squamous cell neoplasia (ESCN) which correlate with invasion depth - an important factor in the success of curative endoscopic therapy. IPCLs visualised on magnification endoscopy with Narrow Band Imaging (ME-NBI) can be used to train convolutional neural networks (CNNs) to detect the presence and classify staging of ESCN lesions. Methods: A total of 7046 sequential high-definition ME-NBI images from 17 patients (10 ESCN, 7 normal) were used to train a CNN. IPCL patterns were classified by three expert endoscopists according to the Japanese Endoscopic Society classification. Normal IPCLs were defined as type A, abnormal as B1-3. Matched histology was obtained for all imaged areas. Results: This CNN differentiates abnormal from normal IPCL patterns with 93.7% accuracy (86.2% to 98.3%) and sensitivity and specificity for classifying abnormal IPCL patterns of 89.3% (78.1% to 100%) and 98% (92% to 99.7%), respectively. Our CNN operates in real time with diagnostic prediction times between 26.17 ms and 37.48 ms. Conclusion: Our novel and proof-of-concept application of computer-aided endoscopic diagnosis shows that a CNN can accurately classify IPCL patterns as normal or abnormal. This system could be used as an in vivo, real-time clinical decision support tool for endoscopists assessing and directing local therapy of ESCN.

Interactive virtual 3D models of renal cancer patient anatomies alter partial nephrectomy surgical planning decisions and increase surgeon confidence compared to volume-rendered images.

PURPOSE: To determine whether the interactive visualisation of patient-specific virtual 3D models of the renal anatomy influences the pre-operative decision-making process of urological surgeons for complex renal cancer operations. METHODS: Five historic renal cancer patient pre-operative computed tomography (CT) datasets were retrospectively selected based on RENAL nephrectomy score and variety of anatomy. Interactive virtual 3D models were generated for each dataset using image segmentation software and were made available for online visualisation and manipulation. Consultant urologists were invited to participate in the survey which consisted of CT and volume-rendered images (VRI) for the control arm, and CT with segmentation overlay and the virtual 3D model for the intervention arm. A questionnaire regarding anatomical structures, surgical approach, and confidence was administered. RESULTS: Twenty-five participants were recruited (54% response rate), with 19/25 having > 5 years of renal surgery experience. The median anatomical clarity score increased from 3 for the control to 5 for the intervention arm. A change in planned surgical approach was reported in 19% of cases. Virtual 3D models increased surgeon confidence in the surgical decisions in 4/5 patient datasets. There was a statistically significant improvement in surgeon opinion of the potential utility for decision-making purposes of virtual 3D models as compared to VRI at the multidisciplinary team meeting, theatre planning, and intra-operative stages. CONCLUSION: The use of pre-operative interactive virtual 3D models for surgery planning influences surgical decision-making. Further studies are needed to investigate if the use of these models changes renal cancer surgery outcomes.

Somatosensory function and pain in extremely preterm young adults from the UK EPICure cohort: sex-dependent differences and impact of neonatal surgery.

BACKGROUND: Surgery or multiple procedural interventions in extremely preterm neonates influence neurodevelopmental outcome and may be associated with long-term changes in somatosensory function or pain response. METHODS: This observational study recruited extremely preterm (EP, <26 weeks' gestation; n=102, 60% female) and term-born controls (TC; n=48) aged 18-20 yr from the UK EPICure cohort. Thirty EP but no TC participants had neonatal surgery. Evaluation included: quantitative sensory testing (thenar eminence, chest wall); clinical pain history; questionnaires (intelligence quotient; pain catastrophising; anxiety); and structural brain imaging. RESULTS: Reduced thermal threshold sensitivity in EP vs TC participants persisted at age 18-20 yr. Sex-dependent effects varied with stimulus intensity and were enhanced by neonatal surgery, with reduced threshold sensitivity in EP surgery males but increased sensitivity to prolonged noxious cold in EP surgery females (P<0.01). Sex-dependent differences in thermal sensitivity correlated with smaller amygdala volume (P<0.05) but not current intelligence quotient. While generalised decreased sensitivity encompassed mechanical and thermal modalities in EP surgery males, a mixed pattern of sensory loss and sensory gain persisted adjacent to neonatal scars in males and females. More EP participants reported moderate-severe recurrent pain (22/101 vs 4/48; χ2=0.04) and increased pain intensity correlated with higher anxiety and pain catastrophising. CONCLUSIONS: After preterm birth and neonatal surgery, different patterns of generalised and local scar-related alterations in somatosensory function persist into early adulthood. Sex-dependent changes in generalised sensitivity may reflect central modulation by affective circuits. Early life experience and sex/gender should be considered when evaluating somatosensory function, pain experience, or future chronic pain risk.

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.

Evaluation of a multi-atlas CT synthesis approach for MRI-only radiotherapy treatment planning.

BACKGROUND AND PURPOSE: Computed tomography (CT) imaging is the current gold standard for radiotherapy treatment planning (RTP). The establishment of a magnetic resonance imaging (MRI) only RTP workflow requires the generation of a synthetic CT (sCT) for dose calculation. This study evaluates the feasibility of using a multi-atlas sCT synthesis approach (sCTa) for head and neck and prostate patients. MATERIAL AND METHODS: The multi-atlas method was based on pairs of non-rigidly aligned MR and CT images. The sCTa was obtained by registering the MRI atlases to the patient's MRI and by fusing the mapped atlases according to morphological similarity to the patient. For comparison, a bulk density assignment approach (sCTbda) was also evaluated. The sCTbda was obtained by assigning density values to MRI tissue classes (air, bone and soft-tissue). After evaluating the synthesis accuracy of the sCTs (mean absolute error), sCT-based delineations were geometrically compared to the CT-based delineations. Clinical plans were re-calculated on both sCTs and a dose-volume histogram and a gamma analysis was performed using the CT dose as ground truth. RESULTS: Results showed that both sCTs were suitable to perform clinical dose calculations with mean dose differences less than 1% for both the planning target volume and the organs at risk. However, only the sCTa provided an accurate and automatic delineation of bone. CONCLUSIONS: Combining MR delineations with our multi-atlas CT synthesis method could enable MRI-only treatment planning and thus improve the dosimetric and geometric accuracy of the treatment, and reduce the number of imaging procedures.

Music-of-light stethoscope: a demonstration of the photoacoustic effect.

In this paper we present a system aimed at demonstrating the photoacoustic (PA) effect for educational purposes. PA imaging is a hybrid imaging modality that requires no contrast agent and has a great potential for spine and brain lesion characterisation, breast cancer and blood flow monitoring notably in the context of fetal surgery. It relies on combining light excitation with ultrasound reception. Our brief was to present and explain PA imaging in a public-friendly way suitable for a variety of ages and backgrounds. We developed a simple, accessible demonstration unit using readily available materials. We used a modulated light emitting diode (LED) torch and an electronic stethoscope. The output of a music player was used for light modulation and the chest piece of the stethoscope covered by a black tape was used as an absorbing target and an enclosed chamber. This demonstration unit was presented to the public at the Bloomsbury Festival On Light in October 2015. Our stall was visited by over 100 people of varying ages. Twenty families returned in-depth evaluation questionnaires, which show that our explanations of the photoacoustic effect were well understood. Their interest in biomedical engineering was increased.

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.

Abdominal Palpation Haptic Device for Colonoscopy Simulation Using Pneumatic Control.

In this paper, we describe the development of a haptic device to be used in a simulator aiming to train the skills of gastroenterology assistants in abdominal palpation during colonoscopy, as well as to train team interaction skills for the colonoscopy team. To understand the haptic feedback forces to be simulated by the haptic device, we conducted an experiment with five participants of varying BMI. The applied forces and displacements were measured and hysteresis modeling was used to characterize the experimental data. These models were used to determine the haptic feedback forces required to simulate a BMI case in response to the real-time user interactions. The pneumatic haptic device consisted of a sphygmomanometer bladder as the haptic interface and a fuzzy controller to regulate the bladder pressure. The haptic device showed good steady state and dynamic response was adequate for simulating haptic interactions. Tracking accuracy averaged 94.2 percent within 300 ms of the reference input while the user was actively applying abdominal palpation and minor repositioning.

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.

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.

High-speed nonlinear finite element analysis for surgical simulation using graphics processing units.

The use of biomechanical modelling, especially in conjunction with finite element analysis, has become common in many areas of medical image analysis and surgical simulation. Clinical employment of such techniques is hindered by conflicting requirements for high fidelity in the modelling approach, and fast solution speeds. We report the development of techniques for high-speed nonlinear finite element analysis for surgical simulation. We use a fully nonlinear total Lagrangian explicit finite element formulation which offers significant computational advantages for soft tissue simulation. However, the key contribution of the work is the presentation of a fast graphics processing unit (GPU) solution scheme for the finite element equations. To the best of our knowledge, this represents the first GPU implementation of a nonlinear finite element solver. We show that the present explicit finite element scheme is well suited to solution via highly parallel graphics hardware, and that even a midrange GPU allows significant solution speed gains (up to 16.8 x) compared with equivalent CPU implementations. For the models tested the scheme allows real-time solution of models with up to 16,000 tetrahedral elements. The use of GPUs for such purposes offers a cost-effective high-performance alternative to expensive multi-CPU machines, and may have important applications in medical image analysis and surgical simulation.