A new acoustic coupling fluid with ability to reduce ultrasound imaging artefacts in brain tumour surgery-a phase I study.

BACKGROUND: A novel acoustic coupling fluid (ACF), with the potential to reduce surgically induced image artefacts during intraoperative ultrasound imaging in brain tumour surgery, has been evaluated with respect to image quality and safety in a clinical phase 1 study. METHODS: Fifteen patients with glioblastoma (WHO grade IV) were included. All adverse events were registered in a 6-month study period. During acquisition of 3D ultrasound image volumes, three different concentrations of the ACF and Ringer's solution were filled into the resection cavity. The effect of ACF on the ultrasound images was rated by the operating surgeon, and by five independent neurosurgeons evaluating a pair of blinded images from all patients. Images from all patients were analysed by comparing pixel brightness in a noise-affected region and a reference region. RESULTS: The operating surgeon deemed the ACF images to have less noise than images obtained with Ringers's solution. The blinded evaluations by the independent neurosurgeons were significantly in favour of ACF (p < 0.0001). The analyses of pixel intensities showed that the ACF images had lower amount of noise than images obtained with Ringer's solution. No radiological sign of inflammation nor circulatory changes was found in the early postoperative MR images. Of the nine complications registered as serious events in the study period, none was deemed to be caused by the ACF. CONCLUSION: The ultrasound (US) images obtained using ACF have significantly less noise than US images obtained with Ringer's solution. The rate of adverse events was comparable to what has been reported for similar groups of patients.

Using the CustusX toolkit to create an image guided bronchoscopy application: Fraxinus.

PURPOSE: The aim of this paper is to show how a specialized planning and guidance application called Fraxinus, can be built on top of the CustusX platform (www.custusx.org), which is an open source image-guided intervention software platform. Fraxinus has been customized to meet the clinical needs in navigated bronchoscopy. METHODS: The application requirements for Fraxinus were defined in close collaboration between research scientists, software developers and clinicians (pulmonologists), and built on top of CustusX. Its superbuild system downloads specific versions of the required libraries and builds them for the application in question, including the selected plugins. New functionality is easily added through the plugin framework. The build process enables the creation of specialized applications, adding additional documentation and custom configurations. The toolkit's libraries offer building blocks for image-guided applications. An iterative development process was applied, where the clinicians would test and provide feedback during the entire process. RESULTS: Fraxinus has been developed and is released as an open source planning and guidance application built on top of CustusX. It is highly specialized for bronchoscopy. The proposed workflow is adapted to the different steps in this procedure. The user interface of CustusX has been modified to enhance information, quality assurance and user friendliness with the intention to increase the overall yield for the patient. As the workflow of the procedure is relatively constant, some actions are predicted and automatically performed by the application, according to the requirements from the clinicians. CONCLUSIONS: The CustusX platform facilitates development of new and specialized applications. The toolkit supports the process and makes important extension and injection points available for customization.

Noninvasive Transorbital Assessment of the Optic Nerve Sheath in Children: Relationship Between Optic Nerve Sheath Diameter, Deformability Index, and Intracranial Pressure.

BACKGROUND: Measurement of optic nerve sheath diameter (ONSD) is a promising technique for noninvasive assessment of intracranial pressure (ICP), but has certain limitations. A recent study showed that the deformability index (DI), a dynamic parameter quantifying the pulsatile nature of the optic nerve sheath, could differentiate between patients with high vs normal ICP. OBJECTIVE: To further evaluate the diagnostic accuracy of the DI, when interpreted together with ONSD. METHODS: This prospective study included children undergoing invasive ICP measurement as part of their clinical management. Ultrasound images of the optic nerve sheath were acquired prior to measuring ICP, the images were further processed to obtain the DI. Patients were dichotomized into high (≥20 mm Hg) or normal ICP groups and compared using the Mann-Whitney U-test. Diagnostic accuracy was described using area under the receiver operating characteristic curve (AUC), sensitivity and specificity, correlation between DI, ONSD, and ICP was investigated using linear regression. RESULTS: A total of 28 patients were included (19 high ICP). The DI was lower in the high ICP group (0.105 vs 0.28, P = .001). AUC was 0.87, and a cut-off value of DI ≤ 0.185 demonstrated sensitivity of 89.5% and specificity of 88.9%. Diagnostic accuracy improved when combining DI with ONSD (AUC 0.98, sensitivity 94.7%, specificity 88.9%) and correlation with ICP improved when combined analysis of DI and ONSD was performed (Pearson correlation coefficient: 0.82 vs 0.42, respectively, P = .012). CONCLUSION: The DI was significantly lower for patients with high vs normal ICP. This relationship improved further when the DI and ONSD were interpreted together.

Pulsatile Dynamics of the Optic Nerve Sheath and Intracranial Pressure: An Exploratory In Vivo Investigation.

BACKGROUND: Raised intracranial pressure (ICP) may lead to increased stiffness of the optic nerve sheath (ONS). OBJECTIVE: To develop a method for analyzing ONS dynamics from transorbital ultrasound and investigate a potential difference between patients with raised ICP vs normal ICP. METHODS: We retrospectively analyzed data from 16 patients (≤12 years old) for whom ultrasound image sequences of the ONS had been acquired from both eyes just before invasive measurement of ICP. Eight patients had an ICP ≥20 mm Hg. The transverse motion on each side of the ONS was estimated from ultrasound, and Fourier analysis was used to extract the magnitude of the displacement corresponding to the heart rate. By calculating the normalized absolute difference between the displacements on each side of the ONS, a measure of ONS deformation was obtained. This parameter was referred to as the deformability index. According to our hypothesis, because deformability is inversely related to stiffness, we expected this parameter to be lower for ICP ≥20 mm Hg compared with ICP <20 mm Hg. The one-sided Mann-Whitney U test was used for statistical comparison. RESULTS: The deformability index was significantly lower in the group with ICP ≥20 mm Hg (median value 0.11 vs 0.24; P = .002). CONCLUSION: We present a method for assessment of ONS pulsatile dynamics using transorbital ultrasound imaging. A significant difference was noted between the patient groups, indicating that deformability of the ONS may be relevant as a noninvasive marker of raised ICP. The clinical implications are promising and should be investigated in future clinical studies. ABBREVIATIONS: AUC, area under curveICP, intracranial pressureONS, optic nerve sheathONSD, optic nerve sheath diameterROC, receiver operating characteristic.

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.

Transsellar Ultrasound in Pituitary Surgery With a Designated Probe: Early Experiences.

BACKGROUND: Anatomic orientation in transsphenoidal surgery can be difficult, and residual tumors are common. A major limitation of both direct microscopy and endoscopic visualization is the inability to see below the surface of the surgical field to confirm the location of vessels, nerves, tumor remnants, and normal pituitary tissue. OBJECTIVE: To present our initial experience with a new forward-looking, custom-designed ultrasound probe for transsellar imaging. METHODS: The center frequency of the prototype tightly curved linear array, bayonet-shaped probe is 12 MHz. Twenty-four patients with pituitary adenomas were included after informed consent. RESULTS: With the use of transsellar ultrasound, we could confirm the location of important neurovascular structures and improve the extent of resection in 4 of 24 cases, as rated subjectively by the operating surgeons. Image quality was good. In 17 patients (71%), biochemical cures and/or complete resections were confirmed at 3 months. CONCLUSION: We found the images from our custom-designed ultrasound probe to be clinically helpful for anatomic orientation during surgery, and the technology is potentially helpful for improving the extent of resection during transsphenoidal surgery. This quick and flexible form of intraoperative imaging in transsphenoidal surgery could be of great support for surgeons in both routine use and difficult cases. The concept of transsellar intraoperative ultrasound imaging can be further refined and developed.

Animal study assessing safety of an acoustic coupling fluid that holds the potential to avoid surgically induced artifacts in 3D ultrasound guided operations.

BACKGROUND: Use of ultrasound in brain tumor surgery is common. The difference in attenuation between brain and isotonic saline may cause artifacts that degrade the ultrasound images, potentially affecting resection grades and safety. Our research group has developed an acoustic coupling fluid that attenuates ultrasound energy like the normal brain. We aimed to test in animals if the newly developed acoustic coupling fluid may have harmful effects. METHODS: Eight rats were included for intraparenchymal injection into the brain, and if no adverse reactions were detected, 6 pigs were to be included with injection of the coupling fluid into the subarachnoid space. Animal behavior, EEG registrations, histopathology and immunohistochemistry were used in assessment. RESULTS: In total, 14 animals were included, 8 rats and 6 pigs. We did not detect any clinical adverse effects, seizure activity on EEG or histopathological signs of tissue damage. CONCLUSION: The novel acoustic coupling fluid intended for brain tumor surgery appears safe in rats and pigs under the tested circumstances.

Three-dimensional ultrasound-guided placement of ventricular catheters.

OBJECTIVE: Many studies demonstrate that the accuracy of freehand catheter placement for cerebrospinal fluid drainage is suboptimal. The aim of placement should be a single pass with a free-floating catheter tip in the intended position. The objective of this study was to achieve an accurate and user-friendly system for three-dimensional (3D) ultrasound-navigated catheter placement through a regular burr hole. METHODS: A new phased-array ultrasound burr hole probe (4-10 MHz, 8 mm×9 mm footprint) was especially developed and optimized for navigated 3D ultrasound with the SonoWand Invite system. A catheter holder for optical tracking was also developed. Head immobilization was achieved with a vacuum cushion. With the described setup, 4 patients underwent surgery. RESULTS: Ultrasound image quality and visualization of the ventricles was good in all cases. Optimal placement of the catheter was achieved in a single pass in all patients. One of the trajectories was slightly more medial on postoperative computed tomography than anticipated from the neuronavigation system. None of the patients experienced any adverse event related to the procedure. CONCLUSIONS: 3D ultrasound with the described setup is a promising technique for accurate, fast, and user-friendly navigated placement of catheters for cerebrospinal fluid diversion.

Ultrasound imaging in neurosurgery: approaches to minimize surgically induced image artefacts for improved resection control.

BACKGROUND: Intraoperative ultrasound imaging is used in brain tumor surgery to identify tumor remnants. The ultrasound images may in some cases be more difficult to interpret in the later stages of the operation than in the beginning of the operation. The aim of this paper is to explain the causes of surgically induced ultrasound artefacts and how they can be recognized and reduced. METHODS: The theoretical reasons for artefacts are addressed and the impact of surgery is discussed. Different setups for ultrasound acquisition and different acoustic coupling fluids to fill up the resection cavity are evaluated with respect to improved image quality. RESULTS: The enhancement artefact caused by differences in attenuation of the resection cavity fluid and the surrounding brain is the most dominating surgically induced ultrasound artefact. The influence of the artefact may be reduced by inserting ultrasound probes with small footprint into the resection cavity for a close-up view of the areas with suspected tumor remnants. A novel acoustic coupling fluid developed for use during ultrasound imaging in brain tumor surgery has the potential to reduce surgically induced ultrasound artefacts to a minimum. CONCLUSIONS: Surgeons should be aware of artefacts in ultrasound images that may occur during brain tumor surgery. Techniques to identify and reduce image artefacts are useful and should be known to users of ultrasound in brain tumor surgery.

Comparison of contrast in brightness mode and strain ultrasonography of glial brain tumours.

BACKGROUND: Image contrast between normal tissue and brain tumours may sometimes appear to be low in intraoperative ultrasound. Ultrasound imaging of strain is an image modality that has been recently explored for intraoperative imaging of the brain. This study aims to investigate differences in image contrast between ultrasound brightness mode (B-mode) images and ultrasound strain magnitude images of brain tumours. METHODS: Ultrasound radiofrequency (RF) data was acquired during surgery in 15 patients with glial tumours. The data were subsequently processed to provide strain magnitude images. The contrast in the B-mode images and the strain images was determined in assumed normal brain tissue and tumour tissue at selected regions of interest (ROI). Three measurements of contrast were done in the ultrasound data for each patient. The B-mode and strain contrasts measurements were compared using the paired samples t- test. RESULTS: The statistical analysis of a total of 45 measurements shows that the contrasts in the strain magnitude images are significantly higher than in the conventional ultrasound B-mode images (P < 0.0001). CONCLUSIONS: The results indicate that ultrasound strain imaging provides better discrimination between normal brain tissue and glial tumour tissue than conventional ultrasound B-mode imaging. Ultrasound imaging of tissue strain therefore holds the potential of becoming a valuable adjunct to conventional intraoperative ultrasound imaging in brain tumour surgery.

Intra-operative imaging with 3D ultrasound in neurosurgery.

In recent years the quality of ultrasound (US) imaging has improved considerably. The integration of three dimensional (3D) US with neuronavigation technology has created an efficient and inexpensive tool for intra-operative imaging in neurosurgery. Our experience is based on more than 900 operations with the intra-operative 3D ultrasound equipment SonoWand® and some operations with the research equipment Custux X. The technology has been applied to improve surgery of intraparencymal brain tumours, but has also been found to be useful in a wide range of other procedures, such as operations for cavernomas, skull base tumours, medulla lesions, arteriovenous malformations (AVMs) and for endoscopy guidance. Compared to intraoperative magnetic resonance imaging (ioMRI), 3D US technology is advantageous in different ways: it is flexible and can be used in any operation theatre. There is no need for special instruments, and no need for radiologists or technicians. It adds very little extra time to the operation, and the investment-costs are considerably lower than for ioMRI.

Ultrasound-guided operations in unselected high-grade gliomas--overall results, impact of image quality and patient selection.

BACKGROUND: A number of tools, including intraoperative ultrasound, are reported to facilitate surgical resection of high-grade gliomas. However, results from selected surgical series do not necessarily reflect the effectiveness in common neurosurgical practice. Delineation of seemingly similar brain tumours vary in different ultrasound-guided operations, perhaps limiting usefulness in certain patients. METHODS: We explore and describe the results associated with use of the SonoWand system with intraoperative ultrasound in a population-based, unselected, high-grade glioma series. Surgeons filled out questionnaires about presumed extent of resection, use of ultrasound and ultrasound image quality just after surgery. We evaluate the impact of ultrasound image quality. We also explore the importance of patient selection for surgical results. RESULTS: Of 156 consecutive malignant glioma operations, 142 (91%) were resections whilst 14 (9%) were only biopsies. We achieved gross total resection (GTR) in 37% of all high-grade glioma resections, whilst worsening of functional status was seen in 13%. The risk of getting worse was significantly higher in reoperations, resections in eloquent locations, resections in cases with poor ultrasound image quality, resection when surgeons' resection grade estimates were inaccurate and in cases with surgery-related complications. Aiming for GTR, unifocality of lesion, non-eloquent location and medium or good ultrasound image quality were identified as independent factors associated with achieving GTR. CONCLUSION: We report good overall results, both in terms of resection grades and functional outcome in consecutive malignant glioma resections, in which intraoperative ultrasound was used in 95%. We observed a seeming dose-response relationship between ultrasound image quality and clinical and radiological results. This may suggest that better ultrasound facilitates better surgery. The study also clearly demonstrates that, in terms of surgical results, the selection of patients seems to be much more important than the selection of surgical tools.

Functional magnetic resonance imaging and diffusion tensor tractography incorporated into an intraoperative 3-dimensional ultrasound-based neuronavigation system: impact on therapeutic strategies, extent of resection, and clinical outcome.

BACKGROUND: Functional neuronavigation with intraoperative 3-dimensional (3D) ultrasound may facilitate safer brain lesion resections than conventional neuronavigation. OBJECTIVE: In this study, functional magnetic resonance imaging (fMRI) and diffusion tensor tractography (DTT) were used to map eloquent areas. We assessed the use of fMRI and DTT for preoperative assessments and determined whether using these data together with 3D ultrasound during surgery enabled safer lesion resection. METHODS: We reviewed 51 consecutive patients with intracranial lesions in whom fMRI with or without DTT was used to map eloquent areas. To assess a possible impact of fMRI/DTT, we reviewed and analyzed the quality of the fMRI/DTT data, any change in therapeutic strategies, lesion to eloquent area distance (LEAD), extent of resection, and clinical outcome. RESULTS: As a result of the fMRI/DTT mapping, the therapeutic strategies were changed in 4 patients. The median tumor residue for glioma patients was 11% (n = 33) and 0% for nonglioma lesions (n = 12). For gliomas, there was a significant correlation between decreasing LEAD and increasing tumor residue. Of the glioma patients, 42% underwent gross total resection (>or= 95%) and 12% suffered neurological worsening after surgery as a result of complications. Of glioma patients with an LEAD of

Laparoscopic ultrasound: a survey of its current and future use, requirements, and integration with navigation technology.

BACKGROUND: Laparoscopic ultrasound (LUS) increases surgical safety by allowing the surgeon to see beyond the organ surface, by visualizing vascular structures and by improving surgical precision of tumor resection. A questionnaire-based survey was used to investigate the current use and future expectations of LUS technology. METHODS: A questionnaire consisting of 26 questions was distributed manually at four different conferences (60% at the European Association for Endoscopic Surgery (EAES) conference, Stockholm 2008). The answers were summarized with descriptive statistics and nonparametric tests at a significance level of 0.05. RESULTS: The questionnaire was answered by 177 surgeons from 40 different countries (85% from Europe). Of these surgeons, 43% use ultrasound during laparoscopic procedures. Generally, more LUS users are found at university hospitals than at general community hospitals. Surgeons use LUS primarily in procedures related to the liver (67% of the surgeons who use LUS), but LUS also is used in other procedures related to the pancreas, biliary tract, and colon. In a 5-year perspective, 82% of surgeons believe in an increased use of LUS, and 79% of surgeons also think that the use of LUS combined with navigation technology will increase and that the most important requirements for such a system are good image quality, easy interpretation, and a high degree of precision. CONCLUSIONS: Although the surgeons believe LUS has advantages, only 43% of the respondents reported using it. The surveyed surgeons were largely positive toward an increased use of LUS in a 5-year perspective and believe that LUS combined with navigation technology will contribute to improving the surgical precision of tumor resection.

Tissue motion and strain in the human brain assessed by intraoperative ultrasound in glioma patients.

The objective of the study was to investigate tissue motion and strain imposed by cardiovascular pulsation in pathologic and normal brain parenchyma, as quantified from in vivo ultrasound data. Ultrasound acquired during surgery of 16 patients with glial tumors was retrospectively processed and analyzed. The tissue velocity was quantified at depths of 1cm, 2cm and 3cm from brain cortex to investigate spatial dependency with depth. Comparison of strain and velocity in tumor and adjacent normal parenchyma was performed by selecting two regions-of-interest in the hyperechoic tumor and two regions in the low-echogenic areas interpreted as mainly normal tissue with some degree of tumor cell infiltration. The absolute maximum tissue velocity is seen to increase with increasing depths in 14 of 16 cases (87.5%). The maximum tissue velocities in the four regions close to the ultrasound visible tumor border are not statistically different (p=0.163 to p=0.975). The strain magnitudes are significantly higher in the regions with expected normal brain parenchyma than in regions with expected glial tumor tissue, both for the two regions being closest to the tumor border (p=0.0004) and for the two regions further away from the tumor border (p=0.0009). We conclude that the velocity of the brain parenchyma imposed by arterial pulsation during a cardiac cycle is generally increasing with increasing depth from cortex. The maximum velocity appears to be similar in regions with expected normal brain and tumor tissue, thus, does not seem to be affected by pathology. Strain magnitude is, however, a suitable parameter for discrimination of glial tumor and normal brain parenchyma. (E-mail: Tormod.Selbekk@sintef.no).

Intrasellar ultrasound in transsphenoidal surgery: a novel technique.

OBJECTIVE: Residual tumor masses are common after transsphenoidal surgery. The risk of a residual mass increases with tumor size and parasellar or suprasellar growth. Transsphenoidal surgery is usually performed without image guidance. We aimed to investigate a new technical solution developed for intraoperative ultrasound imaging during transsphenoidal surgery, with respect to potential clinical use and the ability to identify neuroanatomy and tumor. METHODS: In 9 patients with pituitary macroadenomas, intrasphenoidal and intrasellar ultrasound was assessed during transsphenoidal operations. Ultrasound B-mode, power-Doppler and color-Doppler images were acquired using a small prototype linear array, side-looking probe. The long probe tip measures only 3 x 4 mm. We present images and discuss the potential of intrasphenoidal and intrasellar and ultrasound in transsphenoidal surgery. RESULTS: We present 2-dimensional, high-resolution ultrasound images. A small side-looking, high-frequency ultrasound probe can be used to ensure orientation in the midline for the surgical approach to identify important neurovascular structures to be avoided during surgery and for resection control and identification of normal pituitary tissue. The image resolution is far better than what can be achieved with current clinical magnetic resonance imaging technology. CONCLUSION: We believe that the concept of intrasellar ultrasound can be further developed to become a flexible and useful tool in transsphenoidal surgery.

Navigated resection of giant intracranial meningiomas based on intraoperative 3D ultrasound.

BACKGROUND: Surgical resection of giant meningiomas may pose different challenges. Normal brain tissue is often compressed to the limit and is vulnerable to further traction. In addition, severe intraoperative bleeding may be a problem as many giant meningiomas are vascularised with deep feeding vessels entering from the skull base. Neuronavigation based on preoperative imaging can be of limited use as there may be extensive brain shifts during surgery. METHOD: We have retrospectively evaluated navigated resection based on intraoperative 3D ultrasound in a series of 15 giant meningiomas with a diameter of more than 5 cm. A pre- and postoperative MRI was preformed in all patients. Preoperative and postoperative neurological function was assessed. FINDINGS: We were able to safely perform ultrasound-guided intracapsular gross total resection of tumour tissue in all patients. Twelve out of 15 patients were radically operated (Simpson grade I and II). Major feeding arteries and adjacent normal arteries could be identified by ultrasound power Doppler angiography. In one patient we were not able to indentify important venous structures. All patients experienced postoperative improvement of their symptoms. Postoperative MRIs did not reveal significant ischemic changes in adjacent normal brain tissue. The mean duration of hospitalisation after surgery was 4.9 days. CONCLUSION: We present a method of ultrasound-guided resection of giant meningiomas. The method enables image-guided resection through narrow approaches that minimise traction. Power Doppler angiography allows the identification of feeding vessels that may be coagulated to limit bleeding. Likewise, normal arteries can be avoided during surgery. The tumour capsule is often surprisingly easy to remove from the arachnoid membrane after gross intracapsular tumour reduction.

Comparison of navigated 3D ultrasound findings with histopathology in subsequent phases of glioblastoma resection.

OBJECTIVE: The purpose of the study was to compare the ability of navigated 3D ultrasound to distinguish tumour and normal brain tissue at the tumour border zone in subsequent phases of resection. MATERIALS AND METHODS: Biopsies were sampled in the tumour border zone as seen in the US images before and during surgery. After resection, biopsies were sampled in the resection cavity wall. Histopathology was compared with the surgeon's image findings. RESULTS: Before resection, the tumour border was delineated by ultrasound with high specificity and sensitivity (both 95%). During resection, ultrasound had acceptable sensitivity (87%), but poor specificity (42%), due to biopsies falsely classified as tumour by the surgeon. After resection, sensitivity was poor (26%), due to tumour or infiltrated tissue in several biopsies deemed normal by ultrasound, but the specificity was acceptable (88%). CONCLUSIONS: Our study shows that although glioblastomas are well delineated prior to resection, there seem to be overestimation of tumour tissue during resection. After resection tumour remnants and infiltrated brain tissue in the resection cavity wall may be undetected. We believe that the benefits of intraoperative ultrasound outweigh the shortcomings, but users of intraoperative ultrasound should keep the limitations shown in our study in mind.