High-grade glioma: combined use of 5-aminolevulinic acid and intraoperative ultrasound for resection and a predictor algorithm for detection

J Neurosurg 143:323–331, 2025

Combining 5-aminolevulinic acid (5-ALA) fluorescence and intraoperative ultrasound (ioUS) significantly improved the sensitivity and specificity for detecting high-grade glioma during surgery, compared to either technique alone. A machine learning algorithm (HGGPredictor) further enhanced intraoperative tumor margin prediction, suggesting a new standard for safer, more effective resections.

• Combining 5-ALA fluorescence and intraoperative ultrasound (ioUS) improves the accuracy of high-grade glioma (HGG) resection compared to using either method alone.

• 5-ALA shows higher sensitivity (84.9%), while ioUS provides higher specificity (84.5%); combined, they reach sensitivity of 91% and specificity of 86%.

• The combined approach is especially valuable for maximizing tumor removal while minimizing neurological damage, particularly near eloquent brain regions.

• A machine learning algorithm (HGGPredictor) was developed to predict tumor presence during surgery based on 5-ALA and ioUS results.

• The study included 72 patients and 301 biopsies, with histological analysis as the reference standard.

• The benefit of combination is greatest for strong fluorescence or hyperechogenicity; ioUS is particularly helpful when 5-ALA fluorescence is weak.

• The combined method is accessible and can be integrated into existing surgical protocols without major additional costs.

• Limitations include single-center design and lack of a control group, but results suggest a new standard for HGG resection.

 

The diagnostic value of the lumbar infusion test to predict symptomatic improvement after shunting for normal pressure hydrocephalus. A meta‑analysis

Acta Neurochirurgica (2025) 167:180

This meta-analysis found that the lumbar infusion test (LIT) has poor negative predictive value for predicting non-response to shunting in normal pressure hydrocephalus. LIT cannot reliably exclude patients from shunt surgery and should not be used for this purpose in its current form.

• The lumbar infusion test (LIT) is used to predict which normal pressure hydrocephalus (NPH) patients will benefit from CSF shunting.

• This meta-analysis pooled sensitivity, specificity, and negative predictive value (NPV) of LIT from 10 studies.

• Sensitivity of LIT (using Rout) was moderate (77–82%) at lower cutoffs (12–14 mmHg/ml/min), but specificity was low (34–37%).

• Higher Rout cutoff (18 mmHg/ml/min) increased specificity (78%) but decreased sensitivity (37%).

• NPV was consistently low for all cutoffs (≤33%), meaning LIT is poor at ruling out shunt responders.

• No other LIT parameters (e.g., plateau pressure, CSF amplitude) showed better diagnostic value.

• The test cannot be used to exclude patients from shunt implantation due to high false negative rates.

• Future research should focus on improving the negative predictive value of LIT for NPH.

Linear array ultrasound in low-grade glioma surgery: histology-based assessment of accuracy in comparison to conventional intraoperative ultrasound and intraoperative MRI

Linear array ultrasound in low-grade glioma surgery

Acta Neurochir (2015) 157:195–206

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. The aim of this study is to evaluate the accuracy of linear array ultrasound in comparison to conventional intraoperative ultrasound (cioUS) and intraoperative high-field MRI (iMRI).

Methods We prospectively enrolled 13 patients harboring a LGG of WHO Grade II. After assumed near total removal, a resection control was performed using navigated cioUS, navigated lioUS, and iMRI. We harvested 30 navigated biopsies from the resection cavity and compared 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.

Results 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.

Conclusions 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.

5-Aminolevulinic Acid-derived Tumor Fluorescence: The Diagnostic Accuracy of Visible Fluorescence Qualities as Corroborated by Spectrometry and Histology and Postoperative Imaging

5_Aminolevulinic_Acid_derived_Tumor_Fluorescence__

Neurosurgery 74:310–320, 2014

5-Aminolevulinic acid is used for fluorescence-guided resections. During resection, different macroscopic fluorescence qualities (“strong,” “weak”) can be distinguished that help guide resections.

OBJECTIVE: This prospective study was designed to assess the reliability of visible fluorescence qualities by spectrometry, pathology, and imaging.

METHODS: Thirty-three patients with malignant gliomas received 5-aminolevulinic acid (20 mg/kg). After debulking surgery, standardized biopsies were obtained from tissues with “weak” and “strong” fluorescence and from nonfluorescing near and distant brain for blinded assessment of cell density and tissue type (necrosis, solid or infiltrating tumor, normal tissue). The positive predictive value was calculated. Unresected fluorescing tissue was navigated for blinded correlation to postoperative magnetic resonance imaging (MRI). Receiver operating characteristic curves were generated for assessing the classification efficiency of spectrometry.

RESULTS: “Strong” fluorescence corresponded to greater spectrometric fluorescence, solidly proliferating tumor, and high cell densities, whereas “weak” fluorescence corresponded to lower spectrometric fluorescence, infiltrating tumor, and medium cell densities. The positive predictive value was 100% in strongly fluorescing tissue and 95% in weakly fluorescing tissue. Spectrometric fluorescence was detected in marginal tissue without macroscopic fluorescence. Depending on the threshold, spectrometry displayed greater sensitivity but lower specificity (accuracy 88.4%). Residual MRI enhancement in the tumor bed was detected in 15 of 23 (65%) patients with residual fluorescence, but in none of the patients without residual fluorescence.

CONCLUSION: Macroscopic fluorescence qualities predict solid and infiltrating tumor, providing useful information during resection. Fluorescence appears superior to contrast enhancement on MRI for indicating residual tumor. Spectrometry, on the other hand, is more sensitive but less specific, depending on threshold definition.

A Detailed Analysis of Functional Magnetic Resonance Imaging in the Frontal Language Area: A Comparative Study With Extraoperative Electrocortical Stimulation

Neurosurgery 69:590–597, 2011 DOI: 10.1227/NEU.0b013e3182181be1

Functional magnetic resonance imaging (fMRI) is a less invasive way of mapping brain functions. The reliability of fMRI for localizing language-related function is yet to be determined.

OBJECTIVE: We performed a detailed analysis of language fMRI reliability by comparing the results of 3-T fMRI with maps determined by extraoperative electrocortical stimulation (ECS).

METHODS: This study was performed on 8 epileptic patients who underwent subdural electrode placement. The tasks performed during fMRI included verb generation, abstract/ concrete categorization, and picture naming. We focused on the frontal lobe, which was effectively activated by these tasks. In extraoperative ECS, 4 tasks were combined to determine the eloquent areas: spontaneous speech, picture naming, reading, and comprehension. We calculated the sensitivity and specificity with different Z score thresholds for each task and appropriate matching criteria. For further analysis, we divided the frontal lobe into 5 areas and investigated intergyrus variations in sensitivity and specificity.

RESULTS: The abstract/concrete categorization task was the most sensitive and specific task in fMRI, whereas the picture naming task detected eloquent areas most efficiently in ECS. The combination of the abstract/concrete categorization task and a 3-mm matching criterion gave the best tradeoff (sensitivity, 83%; specificity, 61%) when the Z score was 2.24. As for intergyrus variation, the posterior inferior frontal gyrus showed the best tradeoff (sensitivity, 91%; specificity, 59%), whereas the anterior middle frontal gyrus had low specificity.

CONCLUSION: Despite different tasks for fMRI and extraoperative ECS, the relatively low specificity might be caused by a fundamental discrepancy between the 2 techniques. Reliability of language fMRI activation might differ, depending on the brain region.