Experimental Reconstruction of the Optic Nerve with a Sural Nerve Graft: An in Vivo Experimental Study.

BACKGROUND: Neurosurgical interventions and trauma are common causes of damage to the optic nerve. This determines the relevance of research for solutions aimed at restoration of the nerve's anatomical integrity, electrical conductivity, and subsequently - restoration of its function. Restore a damaged (cut) optic nerve using n. suralis autograft in vivo. METHODS: The experiment involved reconstruction of the optic nerve through injury modulation, graft placement and restored nerve harvest and evaluation. Injury modulation included removal of a fragment of the optic nerve. Autograft harvesting and placement involved resection of a fragment of the sural (sensory) nerve and its subsequent anastomosis in place of the removed fragment of the optic nerve. As an experimental model, a rabbit of the "Burgundy" breed was used. The animal was previously examined for the presence of infectious and other diseases to confirm its health. RESULTS: Four months post operatively when stimulating the operated right eye, low-amplitude components altered in shape are registered. Thus, signs of mild restoration of electrical conductivity on the treated optic nerve were seen. CONCLUSIONS: Our initial experience shows the technical feasibility of reconstructing the optic nerve using an autograft, the possibility of axonal growth through the graft and, in the future, using this method for direct optic nerve reconstruction, as well as a bypass method for damage to the optic nerve with various tumor diseases of the optic nerve, tumors of the chiasmatic-sellar localization, orbital injuries.

Perifocal Zone of Brain Gliomas: Application of Diffusion Kurtosis and Perfusion MRI Values for Tumor Invasion Border Determination.

(1) Purpose: To determine the borders of malignant gliomas with diffusion kurtosis and perfusion MRI biomarkers. (2) Methods: In 50 high-grade glioma patients, diffusion kurtosis and pseudo-continuous arterial spin labeling (pCASL) cerebral blood flow (CBF) values were determined in contrast-enhancing area, in perifocal infiltrative edema zone, in the normal-appearing peritumoral white matter of the affected cerebral hemisphere, and in the unaffected contralateral hemisphere. Neuronavigation-guided biopsy was performed from all affected hemisphere regions. (3) Results: We showed significant differences between the DKI values in normal-appearing peritumoral white matter and unaffected contralateral hemisphere white matter. We also established significant (p < 0.05) correlations of DKI with Ki-67 labeling index and Bcl-2 expression activity in highly perfused enhancing tumor core and in perifocal infiltrative edema zone. CBF correlated with Ki-67 LI in highly perfused enhancing tumor core. One hundred percent of perifocal infiltrative edema tissue samples contained tumor cells. All glioblastoma samples expressed CD133. In the glioblastoma group, several normal-appearing white matter specimens were infiltrated by tumor cells and expressed CD133. (4) Conclusions: DKI parameters reveal changes in brain microstructure invisible on conventional MRI, e.g., possible infiltration of normal-appearing peritumoral white matter by glioma cells. Our results may be useful for plotting individual tumor invasion maps for brain glioma surgery or radiotherapy planning.

Magnetic resonance relaxometry in quantitative imaging of brain gliomas: A literature review.

Magnetic resonance (MR) relaxometry is a quantitative imaging method that measures tissue relaxation properties. This review discusses the state of the art of clinical proton MR relaxometry for glial brain tumors. Current MR relaxometry technology also includes MR fingerprinting and synthetic MRI, which solve the inefficiencies and challenges of earlier techniques. Despite mixed results regarding its capability for brain tumor differential diagnosis, there is growing evidence that MR relaxometry can differentiate between gliomas and metastases and between glioma grades. Studies of the peritumoral zones have demonstrated their heterogeneity and possible directions of tumor infiltration. In addition, relaxometry offers T2* mapping that can define areas of tissue hypoxia not discriminated by perfusion assessment. Studies of tumor therapy response have demonstrated an association between survival and progression terms and dynamics of native and contrast-enhanced tumor relaxometric profiles. In conclusion, MR relaxometry is a promising technique for glial tumor diagnosis, particularly in association with neuropathological studies and other imaging techniques.

Sensitivity of three-dimensional time-of-flight 3.0 ​T magnetic resonance angiography in visualizing the number and course of lenticulostriate arteries in patients with insular gliomas.

Background: Neurosurgical resection of insular gliomas is complicated by the possibility of iatrogenic injury to the lenticulostriate arteries (LSAs) and is associated with devastating neurological complications, hence the need to accurately assess the number of LSAs and their relationship to the tumor preoperatively. Methods: The study included 24 patients with insular gliomas who underwent preoperative 3D-TOF MRA to visualize LSAs. The agreement of preoperative magnetic resonance imaging with intraoperative data in terms of the number of LSAs and their invasion by the tumor was assessed using the Kendall rank correlation coefficient and Cohen's Kappa with linear weighting. Agreement between experts performing image analysis was estimated using Cohen's Kappa with linear weighting. Results: The number of LSAs arising from the M1 segment varied from 0 to 9 (mean 4.3 â€‹± â€‹0.37) as determined by 3D-TOF MRA and 2-6 (mean 4.25 â€‹± â€‹0.25) as determined intraoperatively, κ â€‹= â€‹0.51 (95% CI: 0.25-0.76) and τ â€‹= â€‹0.64 (p â€‹< â€‹0.001). LSAs were encased by the tumor in 11 patients (confirmed intraoperatively in 9 patients). LSAs were displaced medially in 8 patients (confirmed intraoperatively in 8 patients). The tumor partially involved the LSAs and displaced them in 5 patients (confirmed intraoperatively in 7 patients), κ â€‹= â€‹0.87 (95% CI: 0.70-1), τ â€‹= â€‹0.93 (p â€‹< â€‹0.001). 3D-TOF MRA demonstrated high sensitivity (100%, 95% CI: 0.63-1) and high specificity (86.67%, 95% CI: 0.58-0.98) in determining the LSA-tumor interface. Conclusions: 3D-TOF MRA at 3T demonstrated sensitivity in determining the LSA-tumor interface and the number of LSAs in patients with insular gliomas.

5-ALA-guided tumor resection during awake speech mapping in gliomas located in eloquent speech areas: Single-center experience.

Background: Achieving maximal functionally safe resection of gliomas located within the eloquent speech areas is challenging, and there is a lack of literature on the combined use of 5-aminolevulinic acid (5-ALA) guidance and awake craniotomy. Objective: The aim of this study was to describe our experience with the simultaneous use of 5-ALA fluorescence and awake speech mapping in patients with left frontal gliomas located within the vicinity of eloquent speech areas. Materials and methods: A prospectively collected database of patients was reviewed. 5-ALA was administered at a dose of 20 mg/kg 2 h prior to operation, and an operating microscope in BLUE400 mode was used to visualize fluorescence. All patients underwent surgery using the "asleep-awake-asleep" protocol with monopolar and bipolar electrical stimulation to identify the proximity of eloquent cortex and white matter tracts and to guide safe limits of resection along with fluorescence guidance. Speech function was assessed by a trained neuropsychologist before, during, and after surgery. Results: In 28 patients operated with cortical mapping and 5-ALA guidance (12 Grade 4, 6 Grade 3, and 10 Grade 2 gliomas), Broca's area was identified in 23 cases and Wernicke's area was identified in 5 cases. Fluorescence was present in 14 cases. Six tumors had residual fluorescence due to the positive speech mapping in the tumor bed. Transient aphasia developed in 14 patients, and permanent aphasia developed in 4 patients. In 6 patients operated with cortical and subcortical speech mapping and 5-ALA guidance (4 Grade 4, 1 Grade 3, and 1 Grade 2 gliomas), cortical speech areas were mapped in 5 patients and subcortical tracts were encountered in all cases. In all cases, resection was stopped despite the presence of residual fluorescence due to speech mapping findings. Transient aphasia developed in 6 patients and permanent aphasia developed in 4 patients. In patients with Grade 2-3 gliomas, targeted biopsy of focal fluorescence areas led to upgrading the grade and thus more accurate diagnosis. Conclusion: 5-ALA guidance during awake speech mapping is useful in augmenting the extent of resection for infiltrative high-grade gliomas and identifying foci of anaplasia in non-enhancing gliomas, while maintaining safe limits of functional resection based on speech mapping. Positive 5-ALA fluorescence in diffuse Grade 2 gliomas may be predictive of a more aggressive disease course.

Arterial Spin Labeling Perfusion in Determining the IDH1 Status and Ki-67 Index in Brain Gliomas.

The aim of the study was to evaluate the relationship between tumor blood flow (TBF) measured by the pseudo-continuous arterial spin labeling (PCASL) method and IDH1 mutation status of gliomas as well as Ki-67 proliferative index. Methods. The study included 116 patients with newly diagnosed gliomas of various grades. They received no chemotherapy or radiotherapy before MRI. IDH1 status assessment was performed after tumor removal in 106 cases­48 patients were diagnosed with wildtype gliomas (Grade 1−2­6 patients, Grade 3−4­42 patients) and 58 patients were diagnosed with mutant forms of gliomas (Grade 1−2­28 patients, Grade 3−4­30 patients). In 64 cases out of 116 Ki-67 index was measured. Absolute and normalized tumor blood flow values were measured on 3D PCASL maps. Results. TBF and normalized TBF (nTBF) in wildtype gliomas were significantly higher than in IDH1-mutant gliomas (p < 0.001). ASL perfusion showed high values of sensitivity and specificity in the differential diagnosis of gliomas with distinct IDH1 status (for TBF: specificity 75%, sensitivity 77.6%, AUC 0.783, cutoff 80.57 mL/100 g/min, for nTBF: specificity 77.1%, sensitivity 79.3%, AUC 0.791, cutoff 4.7). TBF and nTBF in wildtype high-grade gliomas (HGG) were significantly higher than in mutant forms (p < 0.001). ASL perfusion showed the following values of sensitivity and specificity in the diagnosis of mutant HGG and wildtype HGG (for TBF: specificity 83.3%, sensitivity 60%, AUC 0.719, cutoff 84.18 mL/100 g/min, for nTBF: specificity 88.1%, sensitivity 60%, AUC 0.729, cutoff 4.7). There was a significant positive correlation between tumor blood flow and Ki-67 (for TBF Rs = 0.63, for nTBF Rs = 0.61). Conclusion. ASL perfusion may be an informative factor in determining the IDH1 status in brain gliomas preoperative and tumor proliferative activity.

Radiochemical Synthesis of 4-[18F]FluorobenzylAzide and Its Conjugation with EGFR-Specific Aptamers.

Central nervous system tumors related to gliomas are of neuroectodermal origin and cover about 30% of all primary brain tumors. Glioma is not susceptible to any therapy and surgical attack remains one of the main approaches to its treatment. Preoperative tumor imaging methods, such as positron emission tomography (PET), are currently used to distinguish malignant tissue to increase the accuracy of glioma removal. However, PET is lacking a specific visualization of cells possessing certain molecular markers. Here, we report an application of aptamers to enhancing specificity in imaging tumor cells bearing the epidermal growth factor receptor (EGFR). Glioblastoma is characterized by increased EGFR expression, as well as mutations of this receptor associated with active division, migration, and adhesion of tumor cells. Since 2021, EGFR has been included into the WHO classification of gliomas as a molecular genetic marker. To obtain conjugates of aptamers GR20 and GOL1-specific to EGFR, a 4-[18F]fluorobenzylazide radiotracer was used as a synthon. For the production of the synthon, a method of automatic synthesis on an Eckert & Ziegler research module was adapted and modified using spirocyclic iodonium ylide as a precursor. Conjugation of 4-[18F]fluorobenzylazide and alkyne-modified aptamers was carried out using Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) with/without the TBTA ligand. As a result, it was possible to obtain 18F-labelled conjugates with 97% radiochemical purity for [18F]FB-GR20 and 98% for [18F]FB-GOL1. The obtained conjugates can be used for further studies in PET analysis on model animals with grafted glioblastoma.

Prediction of Intraoperative Fluorescence of Brain Gliomas: Correlation between Tumor Blood Flow and the Fluorescence.

INTRODUCTION: The prediction of the fluorescent effect of 5-aminolevulinic acid (5-ALA) in patients with diffuse gliomas can improve the selection of patients. The degree of enhancement of gliomas has been reported to predict 5-ALA fluorescence, while, at the same time, rarer cases of fluorescence have been described in non-enhancing gliomas. Perfusion studies, in particular arterial spin labeling perfusion, have demonstrated high efficiency in determining the degree of malignancy of brain gliomas and may be better for predicting fluorescence than contrast enhancement. The aim of the study was to investigate the relationship between tumor blood flow, measured by ASL, and intraoperative fluorescent glow of gliomas of different grades. MATERIALS AND METHODS: Tumoral blood flow was assessed in 75 patients by pCASL (pseudo-continuous arterial spin labeling) within 1 week prior to surgery. In all cases of tumor removal, 5-ALA had been administered preoperatively. Maximum values of tumoral blood flow (TBF max) were measured, and normalized tumor blood flow (nTBF) was calculated. RESULTS: A total of 76% of patients had significant contrast enhancement, while 24% were non-enhancing. The histopathology revealed 17 WHO grade II gliomas, 12 WHO grade III gliomas and 46 glioblastomas. Overall, there was a relationship between the degree of intraoperative tumor fluorescence and ASL-TBF (Rs = 0.28, p = 0.02 or the TBF; Rs = 0.34, p = 0.003 for nTBF). Non-enhancing gliomas were fluorescent in 9/18 patients, with nTBF in fluorescent gliomas being 54.58 ± 32.34 mL/100 mg/s and in non-fluorescent gliomas being 52.99 ± 53.61 mL/100 g/s (p > 0.05). Enhancing gliomas were fluorescent in 53/57 patients, with nTBF being 170.17 ± 107.65 mL/100 g/s in fluorescent and 165.52 ± 141.71 in non-fluorescent gliomas (p > 0.05). CONCLUSION: Tumoral blood flow levels measured by non-contrast ASL perfusion method predict the fluorescence by 5-ALA; however, the additional value beyond contrast enhancement is not clear. ASL is, however, useful in cases with contraindication to contrast.

A vascular-task response dependency and its application in functional imaging of brain tumors.

PURPOSE: Preoperative functional MRI (fMRI) is limited by a muted BOLD response caused by abnormal vasoreactivity and resultant neurovascular uncoupling adjacent to malignant brain tumors. We propose to overcome this limitation and more accurately identify eloquent areas adjacent to brain tumors by independently assessing vasoreactivity using breath-holding and incorporating these data into the fMRI analysis. METHODS: Local vasoreactivity using a breath-holding paradigm with the same timing as the functional motor and language tasks was determined in 16 patients (9 glioblastomas, 1 anaplastic astrocytoma, 5 low grade astrocytomas, and 1 metastasis) and 6 healthy control subjects. We derived an fMRI model based on an observed vaso-task response dependency that takes into account the altered hemodynamics adjacent to brain tumors. RESULTS: In both healthy controls and brain tumor subjects, we found a statistical dependency between breath-hold and task BOLD response. In tumor subjects, activation maps that take into account this vaso-task dependency demonstrated clinically meaningful areas of activation that were not seen using the task-only analysis in about half of the cases studied. This included localization of language areas adjacent to brain tumors. CONCLUSIONS: The present preliminary results demonstrate that neurovascular uncoupling known to affect the accuracy of BOLD fMRI adjacent to brain tumors may be, at least partially, overcome by incorporating an observed vaso-task dependency in the BOLD signal analysis.

Pineal Cyst-Related Aqueductal Stenosis as Cause of Intractable Headaches in Nonhydrocephalic Patients.

BACKGROUND: Pineal cysts (PCs) are histologically benign lesions of the pineal gland. Although the majority of PCs are asymptomatic, some cases are ambiguous and accompanied by nonspecific symptoms of variable severity. We suggested that disabling headache in nonhydrocephalic patients with PCs is associated with cerebral aqueduct (CAq) stenosis. METHODS: A retrospective analysis was conducted in patients with PCs suffering from headache without secondary hydrocephalus who underwent surgical resection at Burdenko Neurosurgery Center between 1995 and 2016. All available medical records and radiographic images were retrospectively assessed in these patients. The comparison groups included 22 patients with nonoperated PCs and 25 healthy individuals. Specific magnetic resonance imaging measures were selected to assess the morphometry of the CAq and degree of the stenosis. RESULTS: In 25 patients (82%) we observed clinical improvement after surgery in a follow-up period. Among those with improvement, 10 of them (40%) experienced total relief and 15 of them (60%) had marked headache diminishment. In 5 patients the headache remained persistent. The preoperative rostral CAq diameter appeared to be significantly narrower (P = 0.0011045), and the preoperative rostral/caudal diameter ratio (Rd/Cd) was found to be lower (P = 0.004391) in patients who recovered from headache versus those who did not. CONCLUSION: The results indicate a statistically significant relationship between the changes in the CAq morphometrics and the clinical outcome in postoperative period. Surgical removal of symptomatic pineal cysts in patients without hydrocephalus can be considered as an effective treatment. However, a thorough preoperative examination and patient selection should be conducted in every case.

Validation of DWI pre-processing procedures for reliable differentiation between human brain gliomas.

Diffusion magnetic resonance imaging (dMRI) is a powerful tool in clinical applications, in particular, in oncology screening. dMRI demonstrated its benefit and efficiency in the localisation and detection of different types of human brain tumours. Clinical dMRI data suffer from multiple artefacts such as motion and eddy-current distortions, contamination by noise, outliers etc. In order to increase the image quality of the derived diffusion scalar metrics and the accuracy of the subsequent data analysis, various pre-processing approaches are actively developed and used. In the present work we assess the effect of different pre-processing procedures such as a noise correction, different smoothing algorithms and spatial interpolation of raw diffusion data, with respect to the accuracy of brain glioma differentiation. As a set of sensitive biomarkers of the glioma malignancy grades we chose the derived scalar metrics from diffusion and kurtosis tensor imaging as well as the neurite orientation dispersion and density imaging (NODDI) biophysical model. Our results show that the application of noise correction, anisotropic diffusion filtering, and cubic-order spline interpolation resulted in the highest sensitivity and specificity for glioma malignancy grading. Thus, these pre-processing steps are recommended for the statistical analysis in brain tumour studies.

Differentiation of glioma malignancy grade using diffusion MRI.

Modern diffusion MR protocols allow one to acquire the multi-shell diffusion data with high diffusion weightings in a clinically feasible time. In the present work we assessed three diffusion approaches based on diffusion and kurtosis tensor imaging (DTI, DKI), and neurite orientation dispersion and density imaging (NODDI) as possible biomarkers for human brain glioma grade differentiation based on the one diffusion protocol. We used three diffusion weightings (so called b-values) equal to 0, 1000, and 2500s/mm2 with 60 non-coplanar diffusion directions in the case of non-zero b-values. The patient groups of the glioma grades II, III, and IV consist of 8 subjects per group. We found that DKI, and NODDI scalar metrics can be effectively used as glioma grade biomarkers with a significant difference (p<0.05) for grading between low- and high-grade gliomas, in particular, for glioma II versus glioma III grades, and glioma III versus glioma IV grades. The use of mean/axial kurtosis and intra-axonal fraction/orientation dispersion index metrics allowed us to obtain the most feasible and reliable differentiation criteria. For example, in the case of glioma grades II, III, and IV the mean kurtosis is equal to 0.31, 0.51, and 0.90, and the orientation dispersion index is equal to 0.14, 0.30, and 0.59, respectively. The limitations and perspectives of the biophysical diffusion models based on intra-/extra-axonal compartmentalisation for glioma differentiation are discussed.

Use of CT perfusion to discriminate between brain metastases from different primaries.

Thirty-six metastases in 22 patients were studied prospectively using computed tomography perfusion. Regions of interests were drawn around: the enhancing part of the tumor, necrotic central part, periphery, peritumoral edema, and normal white matter. Cerebral blood volume, cerebral blood flow, and mean transit time were calculated for each zone. The enhancing part of the tumor significantly differed from the other zones in 11 of 12. Metastases of different primaries can be differentiated from one another with statistically significance (P<.05) by at least one perfusion parameter in 57% of cases.

Partial disconnection procedure in a patient with bilateral lesions (case report).

PURPOSE: The method of temporal lobectomy and parietooccipital disconnection has been applied in the treatment of patients with monolateral widespread cortical lesions and with hand motor function intact. There are no data regarding the use of this method in the treatment of patients with bilateral lesions. CASE REPORT: A case history of a 15-year-old female patient with medically refractory epilepsy is presented. Magnetic resonance imaging revealed bilateral periventricular nodular heterotopia associated with cortical dysplasia (CD) in the right temporo-parietal region. The left hemisphere had no signs of CD. Invasive monitoring revealed rhythmic theta-delta activity during the interictal period and fast activity during the ictal onset in the right temporal and parietal regions. The surgery procedure consisted of anterior temporal lobectomy, the removal of the right heterotopy nodus, the dissection of the posterior part of the corpus callosum, and the detachment of the temporo-parieto-occipital complex by dissection behind the sensorimotor cortex. Histological examination of the cortex revealed CD type I. The patient has been seizure-free for 4 years after surgery. CONCLUSION: Partial disconnection procedures may be effective in cases where total hemispherotomy is not indicated in patients with bilateral lesions and a well-lateralized epileptogenic zone localized in the temporo-parieto-occipital region.

Quantification of dispersion of Gd-DTPA from the initial area of enhancement into the peritumoral zone of edema in brain tumors.

To evaluate Gd-DTPA contrast enhancement of brain tumors over time and to describe the dispersion of contrast into the zone of peritumoral edema. We performed MR imaging with a dose of 0.4 mmol Gd-DTPA/kg on eleven patients diagnosed with 5 different supratentorial tumors. MR imaging was done at five intervals between 5 min and 6 h. The change in zone of enhancement was measured for each time point, and a linear measurement was made of the furthest dispersion of contrast from the original volume of enhancement. An increase in the zone of enhancement over time was seen for all tumors; the average increase in volume of contrast was 14.76 +/- 3.35 cm(3) (mean +/- standard deviation). The largest changes in the zone of contrast enhancement, 18.6 +/- 4.63 cm(3), were seen in glioblastoma multiforme. The expansion of contrast enhancement assumed the morphology of the surrounding edema. The dispersion of Gd-DTPA over time into the zone of peritumoral edema is a potential source of error in clinical settings when there is a delay between Gd-DTPA injection and scanning.