Pilot survey reveals ophidiomycosis in dice snakes Natrix tessellata from Lake Garda, Italy.

Ophidiomycosis is an emerging infectious disease caused by the fungus Ophidiomyces ophidiicola (Oo). To date, Oo presence or associated disease condition has been recorded in wild and/or captive snakes from North America, Europe, Asia and Australia, but the data is still scarce outside the Nearctic. Although Italy is a country with a high snake biodiversity in the European panorama, and animals with clinical signs compatible with Oo infection have been documented, to date no investigations have reported the disease in the wild. Therefore, a pilot survey for the Italian territory was performed in conjunction with setting up a complete diagnostic workflow including SYBR Green-based real-time PCR assay for the detection of Oo genomic and mitochondrial DNA combined with histopathology of scale clips. Oo presence was investigated in 17 wild snake specimens from four different species. Four snakes were sampled in a targeted location where the mycosis was suspected via citizen science communications (i.e. North of the Lake Garda), whereas other ophidians were collected following opportunistic sampling. Oo genomic and mitochondrial DNA were detected and sequenced from all four Lake Garda Natrix tessellata, including three juveniles with macroscopic signs such as discolouration and skin crusts. From histopathological examination of scale clips, the three young positive individuals exhibited ulceration, inflammation and intralesional hyphae consistent with Oo infection, and two of them also showed the presence of arthroconidial tufts and solitary cylindrical arthrospores, allowing "Ophidiomycosis and Oo shedder" categorisation. For the remaining snake samples, the real-time PCR tested negative for Oo. This pilot survey permitted to localise for the first time Oo infection in free-ranging ophidians from Italy. Ophidiomycosis from Lake Garda highlights the need to increase sampling efforts in this area as well as in other northern Italian lakes to assess the occurrence of the pathogen, possible risk factors of the infection, its impact on host population fitness and the disease ecology of Oo in European snakes.

Intraoperative 3D ultrasound-guided resection of diffuse low-grade gliomas: radiological and clinical results.

OBJECTIVE: Extent of resection (EOR) and residual tumor volume are linked to prognosis in low-grade glioma (LGG) and there are various methods for facilitating safe maximal resection in such patients. In this prospective study the authors assess radiological and clinical results in consecutive patients with LGG treated with 3D ultrasound (US)-guided resection under general anesthesia. METHODS: Consecutive LGGs undergoing primary surgery guided with 3D US between 2008 and 2015 were included. All LGGs were classified according to the WHO 2016 classification system. Pre- and postoperative volumetric assessments were performed, and volumetric results were linked to overall and malignant-free survival. Pre- and postoperative health-related quality of life (HRQoL) was evaluated. RESULTS: Forty-seven consecutive patients were included. Twenty LGGs (43%) were isocitrate dehydrogenase (IDH)-mutated, 7 (14%) were IDH wild-type, 19 (40%) had both IDH mutation and 1p/19q codeletion, and 1 had IDH mutation and inconclusive 1p/19q status. Median resection grade was 93.4%, with gross-total resection achieved in 14 patients (30%). An additional 24 patients (51%) had small tumor remnants < 10 ml. A more conspicuous tumor border (p = 0.02) and lower University of California San Francisco prognostic score (p = 0.01) were associated with less remnant tumor tissue, and overall survival was significantly better with remnants < 10 ml (p = 0.03). HRQoL was maintained or improved in 86% of patients at 1 month. In both cases with severe permanent deficits, relevant ischemia was present on diffusion-weighted postoperative MRI. CONCLUSIONS: Three-dimensional US-guided LGG resections under general anesthesia are safe and HRQoL is preserved in most patients. Effectiveness in terms of EOR appears to be consistent with published studies using other advanced neurosurgical tools. Avoiding intraoperative vascular injury is a key factor for achieving good functional outcome.

Brain atlas for assessing the impact of tumor location on perioperative quality of life in patients with high-grade glioma: A prospective population-based cohort study.

BACKGROUND: Tumor location is important for surgical decision making. Particular attention is paid to regions that contain sensorimotor and language functions, but it is unknown if these are the most important regions from the patients' perspective. OBJECTIVE: To develop an atlas for depicting and assessing the potential importance of tumor location for perioperative health-related quality of life (HRQoL) in patients with newly diagnosed high-grade glioma. METHODS: Patient-reported HRQoL data and semi-automatically segmented preoperative 3D MRI-images were combined in 170 patients. The images were registered to a standardized space where the individual tumors were given the values and color intensity of the corresponding HRQoL. Descriptive brain maps of HRQoL, defined quantitative analyses, and voxel-based lesion symptom mapping comparing patients with tumors in different locations were made. RESULTS: There was no statistical difference in overall perioperative HRQoL between patients with tumors located in left or right hemisphere, between patients with tumors in different lobes, or between patients with tumors located in non-eloquent, near eloquent, or eloquent areas. Patients with tumors involving the internal capsule, and patients with preoperative motor symptoms and postoperative motor deficits, reported significantly worse overall HRQoL-scores. CONCLUSIONS: The impact of anatomical tumor location on overall perioperative HRQoL seems less than frequently believed, and the distinction between critical and less critical brain regions seems more unclear according to the patients than perhaps when judged by physicians. However, worse HRQoL was found in patients with tumors in motor-related regions, indicating that these areas are crucial also from the patients' perspective.

Automatic Intraoperative Correction of Brain Shift for Accurate Neuronavigation.

BACKGROUND: Unreliable neuronavigation owing to inaccurate patient-to-image registration and brain shift is a major problem in conventional magnetic resonance imaging-guided neurosurgery. We performed a prospective intraoperative validation of a system for fully automatic correction of this inaccuracy based on intraoperative three-dimensional ultrasound and magnetic resonance imaging-to-ultrasound registration. METHODS: The system was tested intraoperatively in 13 tumor resection cases, and performance was evaluated intraoperatively and postoperatively. RESULTS: Intraoperatively, the system was accurate enough for tumor resection guidance in 9 of 13 cases. Manually placed anatomic landmarks showed improvement of alignment from 5.12 mm to 2.72 mm (median) after intraoperative correction. Postoperatively, the limitations of the current system were identified and modified for the system to be sufficiently accurate in all cases. CONCLUSIONS: Automatic and accurate correction of spatially unreliable neuronavigation is feasible within the constraints of surgery. The current limitations of the system were also identified and addressed.

Automatic intraoperative estimation of blood flow direction during neurosurgical interventions.

PURPOSE: In neurosurgery, reliable information about blood vessel anatomy and flow direction is important to identify, characterize, and avoid damage to the vasculature. Due to ultrasound Doppler angle dependencies and the complexity of the vascular architecture, clinically valuable 3-D flow direction information is currently not available. In this paper, we aim to clinically validate and demonstrate the intraoperative use of a fully automatic method for estimation of 3-D blood flow direction from freehand 2-D Doppler ultrasound. METHODS: A 3-D vessel model is reconstructed from 2-D Doppler ultrasound and used to determine the vessel architecture. The blood flow direction is then estimated automatically using the model in combination with Doppler velocity data. To enable testing and validation during surgery, the method was implemented as part of the open-source navigation system CustusX ( www.custusx.org ). RESULTS: Ten patients were included prospectively. Data from four patients were processed postoperatively, and data from six patients were processed intraoperatively. In total, the blood flow direction was estimated for 48 different blood vessels with a success rate of 98%. CONCLUSIONS: In this work, we have shown that the proposed method is suitable for fully automatic estimation of the blood flow direction in intracranial vessels during neurosurgical interventions. The method has the potential to make the understanding of the complex vascular anatomy and flow pattern more intuitive for the surgeon. The method is compatible with intraoperative use, and results can be presented within the limited time frame where they still are of clinical interest.

Highlighting nerves and blood vessels for ultrasound-guided axillary nerve block procedures using neural networks.

Ultrasound images acquired during axillary nerve block procedures can be difficult to interpret. Highlighting the important structures, such as nerves and blood vessels, may be useful for the training of inexperienced users. A deep convolutional neural network is used to identify the musculocutaneous, median, ulnar, and radial nerves, as well as the blood vessels in ultrasound images. A dataset of 49 subjects is collected and used for training and evaluation of the neural network. Several image augmentations, such as rotation, elastic deformation, shadows, and horizontal flipping, are tested. The neural network is evaluated using cross validation. The results showed that the blood vessels were the easiest to detect with a precision and recall above 0.8. Among the nerves, the median and ulnar nerves were the easiest to detect with an F -score of 0.73 and 0.62, respectively. The radial nerve was the hardest to detect with an F -score of 0.39. Image augmentations proved effective, increasing F -score by as much as 0.13. A Wilcoxon signed-rank test showed that the improvement from rotation, shadow, and elastic deformation augmentations were significant and the combination of all augmentations gave the best result. The results are promising; however, there is more work to be done, as the precision and recall are still too low. A larger dataset is most likely needed to improve accuracy, in combination with anatomical and temporal models.

Automatic Segmentation and Probe Guidance for Real-Time Assistance of Ultrasound-Guided Femoral Nerve Blocks.

Ultrasound-guided regional anesthesia can be challenging, especially for inexperienced physicians. The goal of the proposed methods is to create a system that can assist a user in performing ultrasound-guided femoral nerve blocks. The system indicates in which direction the user should move the ultrasound probe to investigate the region of interest and to reach the target site for needle insertion. Additionally, the system provides automatic real-time segmentation of the femoral artery, the femoral nerve and the two layers fascia lata and fascia iliaca. This aids in interpretation of the 2-D ultrasound images and the surrounding anatomy in 3-D. The system was evaluated on 24 ultrasound acquisitions of both legs from six subjects. The estimated target site for needle insertion and the segmentations were compared with those of an expert anesthesiologist. Average target distance was 8.5 mm with a standard deviation of 2.5 mm. The mean absolute differences of the femoral nerve and the fascia segmentations were about 1-3 mm.

Registration of Real-Time 3-D Ultrasound to Tomographic Images of the Abdominal Aorta.

The purpose of this study was to develop an image-based method for registration of real-time 3-D ultrasound to computed tomography (CT) of the abdominal aorta, targeting future use in ultrasound-guided endovascular intervention. We proposed a method in which a surface model of the aortic wall was segmented from CT, and the approximate initial location of this model relative to the ultrasound volume was manually indicated. The model was iteratively transformed to automatically optimize correspondence to the ultrasound data. Feasibility was studied using data from a silicon phantom and in vivo data from a volunteer with previously acquired CT. Through visual evaluation, the ultrasound and CT data were seen to correspond well after registration. Both aortic lumen and branching arteries were well aligned. The processing was done offline, and the registration took approximately 0.2 s per ultrasound volume. The results encourage further patient studies to investigate accuracy, robustness and clinical value of the approach.

CustusX: an open-source research platform for image-guided therapy.

PURPOSE: CustusX is an image-guided therapy (IGT) research platform dedicated to intraoperative navigation and ultrasound imaging. In this paper, we present CustusX as a robust, accurate, and extensible platform with full access to data and algorithms and show examples of application in technological and clinical IGT research. METHODS: CustusX has been developed continuously for more than 15 years based on requirements from clinical and technological researchers within the framework of a well-defined software quality process. The platform was designed as a layered architecture with plugins based on the CTK/OSGi framework, a superbuild that manages dependencies and features supporting the IGT workflow. We describe the use of the system in several different clinical settings and characterize major aspects of the system such as accuracy, frame rate, and latency. RESULTS: The validation experiments show a navigation system accuracy of [Formula: see text]1.1 mm, a frame rate of 20 fps, and latency of 285 ms for a typical setup. The current platform is extensible, user-friendly and has a streamlined architecture and quality process. CustusX has successfully been used for IGT research in neurosurgery, laparoscopic surgery, vascular surgery, and bronchoscopy. CONCLUSIONS: CustusX is now a mature research platform for intraoperative navigation and ultrasound imaging and is ready for use by the IGT research community. CustusX is open-source and freely available at http://www.custusx.org.

Intra-operative correction of brain-shift.

BACKGROUND: Brain-shift is a major source of error in neuronavigation systems based on pre-operative images. In this paper, we present intra-operative correction of brain-shift using 3D ultrasound. METHODS: The method is based on image registration of vessels extracted from pre-operative MRA and intra-operative power Doppler-based ultrasound and is fully integrated in the neuronavigation software. RESULTS: We have performed correction of brain-shift in the operating room during surgery and provided the surgeon with updated information. Here, we present data from seven clinical cases with qualitative and quantitative error measures. CONCLUSION: The registration algorithm is fast enough to provide the surgeon with updated information within minutes and accounts for large portions of the experienced shift. Correction of brain-shift can make pre-operative data like fMRI and DTI reliable for a longer period of time and increase the usefulness of the MR data as a supplement to intra-operative 3D ultrasound in terms of overview and interpretation.

Model-based correction of velocity measurements in navigated 3-D ultrasound imaging during neurosurgical interventions.

In neurosurgery, information of blood flow is important to identify and avoid damage to important vessels. Three-dimensional intraoperative ultrasound color-Doppler imaging has proven useful in this respect. However, due to Doppler angle-dependencies and the complexity of the vascular architecture, clinical valuable 3-D information of flow direction and velocity is currently not available. In this work, we aim to correct for angle-dependencies in 3-D flow images based on a geometric model of the neurovascular tree generated on-the-fly from free-hand 2-D imaging and an accurate position sensor system. The 3-D vessel model acts as a priori information of vessel orientation used to angle-correct the Doppler measurements, as well as provide an estimate of the average flow direction. Based on the flow direction we were also able to do aliasing correction to approximately double the measurable velocity range. In vitro experiments revealed a high accuracy and robustness for estimating the mean direction of flow. Accurate angle-correction of axial velocities were possible given a sufficient beam-to-flow angle for at least parts of a vessel segment . In vitro experiments showed an absolute relative bias of 9.5% for a challenging low-flow scenario. The method also showed promising results in vivo, improving the depiction of flow in the distal branches of intracranial aneurysms and the feeding arteries of an arteriovenous malformation. Careful inspection by an experienced surgeon confirmed the correct flow direction for all in vivo examples.