Identifying tumor cells infiltrating normal-appearing brain tissue is critical to achieve a total glioma resection. Raman spectroscopy (RS) is an optical technique with potential for real-time glioma detection. Most RS reports are based on formalin-fixed or frozen samples, with only a few studies deployed on fresh untreated tissue. We aimed to probe RS on untreated brain biopsies exploring novel Raman bands useful in distinguishing glioma and normal brain tissue. Sixty-three fresh tissue biopsies were analyzed within few minutes after resection. A total of 3450 spectra were collected, with 1377 labelled as Healthy and 2073 as Tumor. Machine learning methods were used to classify spectra compared to the histo-pathological standard. The algorithms extracted information from 60 different Raman peaks identified as the most representative among 135 peaks screened. We were able to distinguish between tumor and healthy brain tissue with accuracy and precision of 83% and 82%, respectively. We identified 19 new Raman shifts with known biological significance. Raman spectroscopy was effective and accurate in discriminating glioma tissue from healthy brain ex-vivo in fresh samples. This study added new spectroscopic data that can contribute to further develop Raman Spectroscopy as an intraoperative tool for in-vivo glioma detection.

A key aspect of cognitive control is the management of conflicting incoming information to achieve a goal, termed ‘interference control’. Although the role of the right frontal lobe in interference control is evident, the white matter tracts subserving this cognitive process remain unclear. To investigate this, we studied the effect of transient network disruption (by means of direct electrical stimulation) and permanent disconnection (resulting from neurosurgical resection) on interference control processes, using the Stroop test in the intraoperative and extraoperative neurosurgical setting. We evaluated the sites at which errors could be produced by direct electrical stimulation during an intraoperative Stroop test in 34 patients with frontal right hemisphere glioma. Lesion-symptom mapping was used to evaluate the relationship between the resection cavities and postoperative performance on the Stroop test of this group compared with an additional 29 control patients who did not perform the intraoperative test (63 patients in total aged 17–77 years; 28 female). We then examined tract disruption and disconnection in a subset of eight patients who underwent both the intraoperative Stroop test and high angular resolution diffusion imaging (HARDI) tractography. The results showed that, intraoperatively, the majority of sites associated with errors during Stroop test performance and concurrent subcortical stimulation clustered in a region of white matter medial to the right inferior frontal gyrus, lateral and superior to the striatum. Patients who underwent the intraoperative test maintained cognitive control ability at the 1-month follow-up (P = 0.003). Lesion-symptom analysis showed resection of the right inferior frontal gyrus was associated with slower postoperative Stroop test ability (corrected for multiple comparisons, 5000 permutations). The stimulation sites associated with intraoperative errors most commonly corresponded with the inferior fronto-striatal tracts and anterior thalamic radiation (over 75% of patients), although the latter was commonly resected without postoperative deficits on the Stroop test (in 60% of patients). Our results show converging evidence to support a critical role for the inferior frontal gyrus in interference control processes. The intraoperative data combined with tractography suggests that cortico-subcortical tracts, over cortico-cortical connections, may be vital in maintaining efficiency of cognitive control processes. This suggests the importance of their preservation during resection of right frontal tumours.

OBJECTIVE: The goal of surgery for gliomas is maximal tumor removal while preserving the patient’s full functional integrity. At present during frontal tumor removal, this goal is mostly achieved, although the risk of impairing the executive functions (EFs), and thus the quality of life, remains significant. The authors investigated the accuracy of an intraoperative version of the Stroop task (iST), adapted for intraoperative mapping, to detect EF-related brain sites by evaluating the impact of the iST brain mapping on preserving functional integrity following a maximal tumor resection.METHODS: Forty-five patients with nondominant frontal gliomas underwent awake surgery; brain mapping was used to establish the functional boundaries for the resection. In 18 patients language, praxis, and motor functions, but not EFs (control group), were mapped intraoperatively at the cortical-subcortical level. In 27 patients, in addition to language, praxis, and motor functions, EFs were mapped with the iST at the cortical-subcortical level (Stroop group). In both groups the EF performance was evaluated preoperatively, at 7 days and 3 months after surgery.RESULTS: The iST was successfully administered in all patients. Consistent interferences, such as color-word inversion/latency, were obtained by stimulating precise white matter sites below the inferior and middle frontal gyri, anterior to the insula and over the putamen, and these were used to establish the posterior functional limit of the resection. Procedures implemented with iST dramatically reduced the EF deficits at 3 months. The EOR was similar in Stroop and control groups.CONCLUSIONS: Brain mapping with the iST allows identification and preservation of the frontal lobe structures involved in inhibition of automatic responses, reducing the incidence of postoperative EF deficits and enhancing the further posterior and inferior margin of tumor resection.

OBJECTIVE: Surgery for low-grade gliomas (LGGs) aims to achieve maximal tumor removal and maintenance of patients’ functional integrity. Because extent of resection is one of the factors affecting the natural history of LGGs, surgery could be extended further than total resection toward a supratotal resection, beyond tumor borders detectable on FLAIR imaging. Supratotal resection is highly debated, mainly due to a lack of evidence of its feasibility and safety. The authors explored the intraoperative feasibility of supratotal resection and its short- and long-term impact on functional integrity in a large cohort of patients. The role of some putative factors in the achievement of supratotal resection was also studied.METHODS: Four hundred forty-nine patients with a presumptive radiological diagnosis of LGG consecutively admitted to the neurosurgical oncology service at the University of Milan over a 5-year period were enrolled. In all patients, a policy was adopted to perform surgery according to functional boundaries, aimed at achieving a supratotal resection whenever possible, without any patient or tumor a priori selection. Feasibility, general safety, and tumor or patient putative factors possibly affecting the achievement of a supratotal resection were analyzed. Postsurgical patient functional performance was evaluated in five cognitive domains (memory, language, praxis, executive functions, and fluid intelligence) using a detailed neuropsychological evaluation and quality of life (QOL) examination.RESULTS: Total resection was feasible in 40.8% of patients, and supratotal resection in 32.3%. The achievement of a supratotal versus total resection was independent of age, sex, education, tumor volume, deep extension, location, handedness, appearance of tumor border, vicinity to eloquent sites, surgical mapping time, or surgical tools applied. Supratotal resection was associated with a long clinical history and histological grade II, suggesting that reshaping of brain networks occurred. Although a consistent amount of apparently MRI-normal brain was removed with this approach, the procedure was safe and did not carry additional risk to the patient, as demonstrated by detailed neuropsychological evaluation and QOL examination. This approach also improved seizure control.CONCLUSIONS: Supratotal resection is feasible and safe in routine clinical practice. These results show that a long clinical history may be the main factor associated with its achievement.

Brain mapping techniques (intraoperative neurophysiology and neuropsychology) represent the gold standard in glioma surgery, and particularly in glioma resection. Since the introduction of MRI in the clinical practice, several advanced applications have been developed, like functional MRI (fMRI) and diffusion imaging-based tractography (DTI), which both have an application in glioma surgery. fMRI allows to identify cortical areas related to a specific function, DTI allows to reconstruct a model of the sub-cortical connectivity. This paper describes the clinical application of fMRI and DTI, enlightening sensitivity and specificity in comparison to gold standard and underlining their limitations in surgical decision making.

OBJECTIVE: Brain mapping techniques allow one to effectively approach tumors involving the primary motor cortex (M1). Tumor resectability and maintenance of patient integrity depend on the ability to successfully identify motor tracts during resection by choosing the most appropriate neurophysiological paradigm for motor mapping. Mapping with a high-frequency (HF) stimulation technique has emerged as the most efficient tool to identify motor tracts because of its versatility in different clinical settings. At present, few data are available on the use of HF for removal of tumors predominantly involving M1.METHODS: The authors retrospectively analyzed a series of 102 patients with brain tumors within M1, by reviewing the use of HF as a guide. The neurophysiological protocols adopted during resections were described and correlated with patients’ clinical and tumor imaging features. Feasibility of mapping, extent of resection, and motor function assessment were used to evaluate the oncological and functional outcome to be correlated with the selected neurophysiological parameters used for guiding resection. The study aimed to define the most efficient protocol to guide resection for each clinical condition.RESULTS: The data confirmed HF as an efficient tool for guiding resection of M1 tumors, affording 85.3% complete resection and only 2% permanent morbidity. HF was highly versatile, adapting the stimulation paradigm and the probe to the clinical context. Three approaches were used. The first was a “standard approach” (HF “train of 5,” using a monopolar probe) applied in 51 patients with no motor deficit and seizure control, harboring a well-defined tumor, showing contrast enhancement in most cases, and reaching the M1 surface. Complete resection was achieved in 72.5%, and 2% had permanent morbidity. The second approach was an “increased train approach,” that is, an increase in the number of pulses (7–9) and of pulse duration, using a monopolar probe. This second approach was applied in 8 patients with a long clinical history, previous treatment (surgery, radiation therapy, chemotherapy), motor deficit at admission, poor seizure control, and mostly high-grade gliomas or metastases. Complete resection was achieved in 87.5% using this approach, along with 0% permanent morbidity. The final approach was a “reduced train approach,” which was the combined use of train of 2 or train of 1 pulses associated with the standard approach, using a monopolar or bipolar probe. This approach was used in 43 patients with a long clinical history and poorly controlled seizures, harboring tumors with irregular borders without contrast enhancement (low or lower grade), possibly not reaching the cortical surface. Complete resection was attained in 88.4%, and permanent morbidity was found in 2.3%.CONCLUSIONS: Resection of M1 tumors is feasible and safe. By adapting the stimulation paradigm and probe appropriately to the clinical context, the best resection and functional results can be achieved.