Intraoperative Ultrasound (iUS) in Glioma Surgery

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Intraoperative ultrasound (iUS) has emerged as a valuable tool in glioma surgery, offering real-time imaging for tumor localization, resection guidance, and assessment of residual tumor. It complements other intraoperative imaging modalities like MRI and neuronavigation, providing a cost-effective, accessible, and versatile option.

• Real-Time Guidance: Provides continuous imaging during surgery without interrupting workflow.
• Cost-Effectiveness: iUS is significantly more affordable than intraoperative MRI (iMRI).
• Portability: Compact and easy to integrate into any operating room.
• Adaptability: Useful for various glioma grades and locations.
• Reduced Risk: Assists in minimizing damage to adjacent critical structures.

• Pre-resection Imaging: iUS helps delineate tumor margins, particularly for high-grade gliomas where boundaries can be challenging to visualize.
• Guidance During Resection: Real-time feedback enables the surgeon to adapt their strategy, especially in complex or deep-seated tumors.
• Assessment of Residual Tumor: Post-resection, iUS can identify any remaining tumor tissue, improving the extent of resection (EOR).
• Integration with Navigation Systems: iUS data can be fused with neuronavigation platforms for enhanced precision.

• Learning Curve: Accurate interpretation of iUS images requires significant training and experience.
• Resolution Limitations: Compared to iMRI, iUS may have lower resolution, particularly for differentiating low-grade gliomas.
• Brain Shift: iUS images can be distorted due to intraoperative brain shift, though modern techniques like elastography are mitigating this issue.
• Artifacts: Blood, air, and retraction-induced artifacts may complicate image clarity.

• Contrast-Enhanced Ultrasound (CEUS): Improves visualization of vascularized tumor tissue, particularly useful for distinguishing tumor margins from normal brain tissue.
• Ultrasound Elastography: Offers data on tissue stiffness, aiding in the differentiation of gliomas from surrounding edematous or healthy tissue.
• 3D Ultrasound: Provides volumetric imaging to improve orientation and resection planning.

• Versus iMRI: While iMRI offers superior resolution, iUS is faster, less expensive, and doesn't require the patient to be moved.
• Versus Fluorescence-Guided Surgery (e.g., 5-ALA): iUS offers an additional imaging perspective, especially when fluorescence is insufficient for certain gliomas.

Studies demonstrate that iUS-guided glioma resections achieve higher EOR, which correlates with improved survival rates and quality of life. When used in combination with other modalities, iUS maximizes the safety and efficacy of glioma surgeries.

• Development of AI-based interpretation tools for iUS images.
• Advanced probes with higher resolution and ergonomic designs.
• Integration with augmented reality (AR) systems to enhance the surgical interface.

Intraoperative ultrasound is a powerful adjunct in glioma surgery, improving the surgeon's ability to achieve maximal safe resection. While it has limitations, ongoing advancements in technology and training are expanding its utility and reliability in neuro-oncological practice.

Databases were searched until April 21, 2023 for randomized controlled trials (RCTs) and observational cohort studies that compared surgical outcomes for patients with HGG or GBM with the use of either iUS in addition to standard approach or CNN. The primary outcome was overall survival (OS). Secondary outcomes include volumetric extent of resection (EOR), gross total resection (GTR), and progression-free survival (PFS). Outcomes were analyzed by determining pooled relative risk ratios (RR), mean difference (MD), and standardized mean difference (SMD) using random-effects model.

Results: Of the initial 867 articles, only 7 articles specifically met the inclusion criteria (1 RCT and 6 retrospective cohorts). The analysis included 732 patients. Compared to CNN, the use of iUS was associated with higher OS (SMD = 0.26,95%CI=[0.12,0.39]) and GTR (RR = 2.02; 95% CI=[1.31,3.1]) for both HGG and GBM. There was no significant difference in PFS or EOR.

Conclusion: The use of iUS in surgical resections for HGG and GBM can improve OS and GTR compared to CNN, but it did not affect PFS. These results suggest that iUS reduces mortality associated with HGG and GBM but not the risk of recurrence. These results can provide valuable cost-effective interventions for neurosurgeons in HGG and GBM surgery ¹⁾.

This study provides valuable insights into the role of iUS in neurosurgical oncology, particularly in enhancing OS and GTR. Despite its limitations, the research highlights iUS as a promising, cost-effective tool. Nonetheless, the absence of significant benefits in PFS and EOR warrants cautious interpretation. Future research should focus on addressing the methodological limitations and exploring the underlying mechanisms by which iUS influences surgical outcomes.

Wei et al. in a review stated that glioma surgery, methods such as intraoperative computed tomography (ICT), intraoperative magnetic resonance imaging (IMRI), navigation, 5-aminolevulinic acid (5-ALA), and intraoperative ultrasound (IOUS) are used to achieve an expanded resection during the surgical procedure. IOUS has been increasingly used in the surgery of high-grade gliomas and various tumors due to its convenient intraoperative use, its flexible repeatability, and the relatively low cost of operating room construction. With the continuous upgrading of ultrasound equipment, IOUS has been able to better assist surgeons in achieving an increased extent of resection. ²⁾

The excerpt effectively outlines the growing utility of IOUS in high-grade glioma surgery, emphasizing its convenience, repeatability, and cost-effectiveness. However, the lack of a critical comparison with other modalities and the absence of supporting clinical data limit its impact. A more nuanced discussion that includes the limitations, operator dependency, and specific technological advancements would provide a more comprehensive and balanced analysis.

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.

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).

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 ³⁾

The study highlights the strengths and limitations of IOUS in glioma surgery, demonstrating good specificity but limited sensitivity for detecting small residual tumors. While tumor volume and depth are significant predictors of GTR, IOUS image quality's lack of statistical significance and the technology's variability in certain subgroups (e.g., post-radiotherapy patients) underscore the need for further advancements. Integrating IOUS with other modalities and correlating findings with long-term outcomes will be essential to fully realize its potential in glioma surgery.

Intraoperative ultrasonography (iUS) is considered an accurate, safe, and cost-effective tool to estimate the extent of resection of both high-grade glioma and low-grade diffuse gliomas (DGs). However, it is currently missing an evidence-based assessment of iUS diagnostic accuracy in DGs surgery.

IOUS-based quantitative texture analysis in glioblastomas is feasible. Radiomic tumor region characteristics in B-mode and elastography appear to be significantly associated with OS ⁴⁾.

The objective of review is to perform a systematic review and meta-analysis of the diagnostic performance of iUS in detecting tumor residue after DGs resection. A comprehensive literature search for studies published through October 2018 was performed according to PRISMA-DTA and STARD 2015 guidelines, using the following algorithm: (“ultrasound” OR “ultrasonography” OR “ultra-so*” OR “echo*” OR “eco*”) AND (“brain” OR “nervous”) AND (“tumor” OR “tumour” OR “lesion” OR “mass” OR “glio*” OR “Glioblastoma”) AND (“surgery” OR “surgical” OR “microsurg*” OR “neurosurg*”). Pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), and diagnostic odds ratio (DOR) of iUS in DGs were calculated. A subgroup analysis for HGGs and DLGGs was also conducted. Thirteen studies were included in the systematic review (665 DGs). Ten articles (409 DGs) were selected for the meta-analysis with the following results: sensitivity 72.2%, specificity 93.5%, LR- 0.29, LR+ 3, and DOR 9.67. Heterogeneity among studies was non-significant. Subgroup analysis demonstrates a better diagnostic performance of iUS for DLGGs compared with HGGs. iUS is an effective technique in assessing DGs resection. No significant differences are seen regarding iUS modality and transducer characteristics. Its diagnostic performance is higher in DLGGs than HGGs and could be worsened by previous treatments, surgical artifacts, and small tumor residue volumes ⁵⁾.

In Low-grade glioma (LGG) surgery, intraoperative differentiation between tumor and most likely tumor-free brain tissue can be challenging. Intraoperative ultrasound can facilitate tumor resection.

In 13 patients harboring a LGG of WHO Grade II. After assumed near total removal, a resection control was performed using navigated conventional intraoperative ultrasound (cioUS), navigated linear array ultrasound lioUS, and intraoperative high-field MRI (iMRI).

30 navigated biopsies from the resection cavity was compared in reference to the histopathological findings with the respective imaging results. Spearman's rho was calculated to test for significant correlations. Sensitivity and specificity as well as receiver operating characteristics (ROC) were calculated to assess test performance of each imaging modality.

Imaging results of lioUS correlated significantly (p < 0.009) with iMRI. Both iMRI and lioUS correlated significantly with final histopathological diagnosis (p < 0.006, p < 0.014). cioUS did not correlate with other imaging findings or with final diagnosis. The highest sensitivity for residual tumor detection was found in iMRI (83 %), followed by lioUS (79 %). The sensitivity of cioUS was only 21 %. Specificity was highest in cioUS (100 %), whereas iMRI and lioUS both achieved 67 %. ROC curves showed fair results for iMRI and lioUS and a poor result for cioUS.

Intraoperative resection control in LGGs using lioUS reaches a degree of accuracy close to iMRI. Test results of lioUS are superior to cioUS. cioUS often fails to discriminate solid tumors from “normal” brain tissue during resection control. Only in lesions <10 cc cioUS does show good accuracy ⁶⁾.