3D ultrasound-guided resection of low-grade gliomas: principles and clinical examples.

3D ultrasound (US) is a convenient tool for guiding the resection of low-grade gliomas, seemingly without deterioration in patients' quality of life. This article offers an update of the intraoperative workflow and the general principles behind the 3D US acquisition of high-quality images.The authors also provide case examples illustrating the technique in two small mesial temporal lobe lesions and in one insular glioma. Due to the ease of acquiring new images for navigation, the operations can be guided by updated image volumes throughout the entire course of surgery. The high accuracy offered by 3D US systems, based on nearly real-time images, allows for precise and safe resections. This is especially useful when an operation is performed through very narrow transcortical corridors.

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.

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.

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.

The Diagnostic Properties of Intraoperative Ultrasound in Glioma Surgery and Factors Associated with Gross Total Tumor Resection.

OBJECTIVE: In glioma operations, we sought to analyze sensitivity, specificity, and predictive values of intraoperative 3-dimensional ultrasound (US) for detecting residual tumor compared with early postoperative magnetic resonance imaging (MRI). Factors possibly associated with radiologic complete resection were also explored. METHODS: One hundred forty-four operations for diffuse supratentorial gliomas were included prospectively in an unselected, population-based, single-institution series. Operating surgeons answered a questionnaire immediately after surgery, stating whether residual tumor was seen with US at the end of resection and rated US image quality (e.g., good, medium, poor). Extent of surgical resection was estimated from preoperative and postoperative MRI. RESULTS: Overall specificity was 85% for "no tumor remnant" seen in US images at the end of resection compared with postoperative MRI findings. Sensitivity was 46%, but tumor remnants seen on MRI were usually small (median, 1.05 mL) in operations with false-negative US findings. Specificity was highest in low-grade glioma operations (94%) and lowest in patients who had undergone prior radiotherapy (50%). Smaller tumor volume and superficial location were factors significantly associated with gross total resection in a multivariable logistic regression analysis, whereas good ultrasound image quality did not reach statistical significance (P = 0.061). CONCLUSIONS: The specificity of intraoperative US is good, but sensitivity for detecting the last milliliter is low compared with postoperative MRI. Tumor volume and tumor depth are the predictors of achieving gross total resection, although ultrasound image quality was not.

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.

Tumor Volume Assessment in Low-Grade Gliomas: A Comparison of Preoperative Magnetic Resonance Imaging to Coregistered Intraoperative 3-Dimensional Ultrasound Recordings.

BACKGROUND: Image guidance based on magnetic resonance imaging (MRI) and/or ultrasound (US) is widely used to aid decision making in glioma surgery, but tumor delineation based on these 2 modalities does not always correspond. OBJECTIVE: To analyze volumes of diffuse low-grade gliomas (LGGs) based on preoperative 3-D FLAIR MRIs compared to intraoperative 3-D US image recordings to quantitatively assess potential discrepancies between the 2 imaging modalities. METHODS: Twenty-three patients with supratentorial WHO grade II gliomas undergoing primary surgery guided by neuronavigation based on preoperative FLAIR MRI and navigated 3-D US were included. Manual volume segmentation was performed twice in 3-D Slicer version 4.0.0 to assess intrarater variabilities and compare modalities with regard to tumor volume. Factors possibly related to correspondence between MRI and US were also explored. RESULTS: In 20 out of 23 patients (87%), the LGG tumor volume segmented from intraoperative US data was smaller than the tumor volume segmented from the preoperative 3-D FLAIR MRI. The median difference between MRI and US volumes was 7.4 mL (range: -4.9-58.7 mL, P < .001) with US LGG volumes corresponding to a median of 74% (range: 42%-183%) of the MRI LGG volumes. However, there was considerable intraobserver variability for US volumes. The correspondence between MRI and US data was higher for astrocytomas (92%). CONCLUSION: The tumor volumes of LGGs segmented from intraoperative US images were most often smaller than the tumor volumes segmented from preoperative MRIs. There was a much better match between the 2 modalities in astrocytomas.

REtroSpective Evaluation of Cerebral Tumors (RESECT): A clinical database of pre-operative MRI and intra-operative ultrasound in low-grade glioma surgeries.

PURPOSE: The advancement of medical image processing techniques, such as image registration, can effectively help improve the accuracy and efficiency of brain tumor surgeries. However, it is often challenging to validate these techniques with real clinical data due to the rarity of such publicly available repositories. ACQUISITION AND VALIDATION METHODS: Pre-operative magnetic resonance images (MRI), and intra-operative ultrasound (US) scans were acquired from 23 patients with low-grade gliomas who underwent surgeries at St. Olavs University Hospital between 2011 and 2016. Each patient was scanned by Gadolinium-enhanced T1w and T2-FLAIR MRI protocols to reveal the anatomy and pathology, and series of B-mode ultrasound images were obtained before, during, and after tumor resection to track the surgical progress and tissue deformation. Retrospectively, corresponding anatomical landmarks were identified across US images of different surgical stages, and between MRI and US, and can be used to validate image registration algorithms. Quality of landmark identification was assessed with intra- and inter-rater variability. DATA FORMAT AND ACCESS: In addition to co-registered MRIs, each series of US scans are provided as a reconstructed 3D volume. All images are accessible in MINC2 and NIFTI formats, and the anatomical landmarks were annotated in MNI tag files. Both the imaging data and the corresponding landmarks are available online as the RESECT database at https://archive.norstore.no (search for "RESECT"). POTENTIAL IMPACT: The proposed database provides real high-quality multi-modal clinical data to validate and compare image registration algorithms that can potentially benefit the accuracy and efficiency of brain tumor resection. Furthermore, the database can also be used to test other image processing methods and neuro-navigation software platforms.

Standardized reporting of adverse events after microvascular decompression of cranial nerves; a population-based single-institution consecutive series.

OBJECTIVE: To investigate frequencies of adverse events occurring within 30 days after microvascular decompression (MVD) surgery using a standardized report form of adverse events. METHODS: We conducted a retrospective review of 98 adult patients (≥16 years) treated with MVD between 1 January 1994 and 1 June 2013. Adverse events occurring within 30 days were classified according to the Landriel Ibanez classification for neurosurgical complications: grade I represents any non-life threatening complication treated without invasive procedures; grade II is complications requiring invasive management; grade III is life-threatening adverse events requiring treatment in an intensive care unit (ICU); grade IV is death as a result of complications. We sought to compare our results with reports from the literature. RESULTS: Patients' median age was 61 years (range 26-83), and 64 (65 %) were females. Indications for MVD were trigeminal neuralgia (n = 77, 79 %), glossopharyngeal neuralgia (n = 4, 4 %), hemifacial spasm (n = 16, 16 %) and combined trigeminal neuralgia and hemifacial spasm (n = 1, 1 %). The overall 30-day complication rate was 20 %, with 14 % grade I complications, 5 % grade II complications and 1 % grade III complications. The comparison with the literature was hampered by the diverse and unsystematic way of reporting complications. CONCLUSION: We provide a standardized report of postoperative complications in a consecutive patient series undergoing MVD. Due to the heterogeneous and non-standardized reporting of complications in the literature, it is difficult to know if our 20 % complication rate is low or high. Standardized reporting is a necessity for meaningful and more valid comparisons across studies. The safety of MVD, a fairly standardized neurosurgical procedure, is well suited for comparisons across centers provided that complications are reported in a standardized manner.

Clinical experience with navigated 3D ultrasound angiography (power Doppler) in microsurgical treatment of brain arteriovenous malformations.

INTRODUCTION: We have previously described a method that has the potential to improve surgery of arteriovenous malformations (AVMs). In the present paper, we present our clinical results. MATERIALS AND METHODS: Of 78 patients referred for AVMs to our University Hospital from our geographical catchment region from 2005 through 2013, 31 patients were operated on with microsurgical technique. 3D MR angiography (MRA) with neuronavigation was used for planning. Navigated 3D ultrasound angiography (USA) was used to identify and clip feeders in the initial phase of the operation. None of our patients was embolized preoperatively as part of the surgical procedure. The niduses were extirpated based on the 3D USA. After extirpation, controls were done with 3D USA to verify that the AVMs were completely removed. The Spetzler three-tier classification of the patients was: A: 21, B: 6, C: 4. RESULTS: Sixty-eight feeders were identified on preoperative MRA and DSA and 67 feeders were identified and clipped by guidance of intraoperative 3D USA. Six feeders identified preoperatively were missed by 3D USA, while five preoperatively unknown feeders were found and clipped. The overall average bleeding was 440 ml. There was a significant reduction in average bleeding in the last 15 operations compared to the first 16 (340 vs. 559 ml, p = 0.019). We had no serious morbidity (GOS 3 or less). New deficits due to surgery were two patients with quadrantanopia (one class B and one class C), the latter (C) also acquired epilepsy. One patient (class A) acquired a hardly noticeable paresis in two fingers. One hundred percent angiographic cure was achieved in all patients, as evaluated by postoperative DSA. CONCLUSIONS: Navigated intraoperative 3D USA is a useful tool to identify and clip AVM feeders. Microsurgical extirpation assisted by navigated 3D USA is an effective and safe method for removing AVMs.

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.

Surgically acquired deficits and diffusion weighted MRI changes after glioma resection--a matched case-control study with blinded neuroradiological assessment.

BACKGROUND: Acquired deficits following glioma resection may not only occur due to accidental resection of normal brain tissue. The possible importance of ischemic injuries in causing neurological deficits after brain tumor surgery is not much studied. We aimed to study the volume and frequency of early postoperative circulatory changes (i.e. infarctions) detected by diffusion weighted resonance imaging (DWI) in patients with surgically acquired neurological deficits compared to controls. METHODS: We designed a 1 ∶ 1 matched case-control study in patients with diffuse gliomas (WHO grade II-IV) operated with 3D ultrasound guided resection. 42 consecutive patients with acquired postoperative dysphasia and/or new motor deficits were compared to 42 matched controls without acquired deficits. Controls were matched with respect to histopathology, preoperative tumor volumes, and eloquence of location. Two independent radiologists blinded for clinical status assessed the postoperative DWI findings. RESULTS: Postoperative peri-tumoral infarctions were more often seen in patients with acquired deficits (63% versus 41%, p = 0.046) and volumes of DWI abnormalities were larger in cases than in controls with median 1.08 cm3 (IQR 0-2.39) versus median 0 cm3 (IQR 0-1.67), p = 0.047. Inter-rater agreement was substantial (67/82, κ = 0.64, p<0.001) for diagnosing radiological significant DWI abnormalities. CONCLUSION: Peri-tumoral infarctions were more common and were larger in patients with acquired deficits after glioma surgery compared to glioma patients without deficits when assessed by early postoperative DWI. Infarctions may be a frequent and underestimated cause of acquired deficits after glioma resection. DWI changes may be an attractive endpoint in brain tumor surgery with both good inter-rater reliability among radiologists and clinical relevance.

Surgical strategies in low-grade gliomas and implications for long-term quality of life.

Reports on long-term health related quality of life (HRQL) after surgery for World Health Organization grade II diffuse low-grade gliomas (LGG) are rare. We aimed to compare long-term HRQL in two hospital cohorts with different surgical strategies. Biopsy and watchful waiting was favored in one hospital, while early resections guided with three-dimensional (3D) ultrasound was favored in the other. With a population-based approach 153 patients with histologically verified LGG treated from 1998-2009 were included. Patients still alive were contacted for HRQL assessment (n=91) using generic (EQ-5D; EuroQol Group, Rotterdam, The Netherlands) and disease specific (EORTC QLQ-C30 and BN20; EORTC Quality of Life Department, Brussels, Belgium) questionnaires. Results on HRQL were available in 79 patients (87%), 25 from the hospital that favored biopsy and 54 from the hospital that favored early resection. Among living patients there was no difference in EQ-5D index scores (p=0.426). When imputing scores defined as death (zero) in patients dead at follow-up, a clinically relevant difference in EQ-5D score was observed in favor of early resections (p=0.022, mean difference 0.16, 95% confidence interval 0.02-0.29). In EORTC questionnaires pain, depression and concern about disruption in family life were more common with a strategy of initial biopsy only (p=0.043, p=0.032 and p=0.045 respectively). In long-term survivors an aggressive surgical approach using intraoperative 3D ultrasound image guidance in LGG does not lower HRQL compared to a more conservative surgical approach. This finding further weakens a possible role for watchful waiting in LGG.

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.

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.