Open Microsurgical Cerebral Aneurysm Treatment After Failed Endovascular Therapy: An Evaluation of Aneurysm Treatment Frequencies in All Neurovascular Centers Across Austria and the Czech Republic Over 20 Years.

BACKGROUND AND OBJECTIVES: Endovascular treatment of cerebral aneurysms has tremendously advanced over the past decades. Nevertheless, aneurysm residual and recurrence remain challenges after embolization. The objective of this study was to elucidate the portion of embolized aneurysms requiring open surgery and evaluate whether newer endovascular treatments have changed the need for open surgery after failed embolization. METHODS: All 15 cerebrovascular centers in Austria and the Czech Republic provided overall aneurysm treatment frequency data and retrospectively reviewed consecutive cerebral aneurysms treated with open surgical treatment after failure of embolization from 2000 to 2022. All endovascular modalities were included. RESULTS: On average, 1362 aneurysms were treated annually in the 2 countries. The incidence increased from 0.006% in 2005 to 0.008% in 2020 in the overall population. Open surgery after failed endovascular intervention was necessary in 128 aneurysms (0.8%), a proportion that remained constant over time. Subarachnoid hemorrhage was the initial presentation in 70.3% of aneurysms. The most common location was the anterior communicating artery region (40.6%), followed by the middle cerebral artery (25.0%). The median diameter was 6 mm (2-32). Initial endovascular treatment included coiling (107 aneurysms), balloon-assist (10), stent-assist (4), intrasaccular device (3), flow diversion (2), and others (2). Complete occlusion after initial embolization was recorded in 40.6%. Seventy-one percent of aneurysms were operated within 3 years after embolization. In 7%, the indication for surgery was (re-)rupture and, in 88.3%, reperfusion. Device removal was performed in 16.4%. Symptomatic intraoperative and postoperative complications occurred in 10.2%. Complete aneurysm occlusion after open surgery was achieved in 94%. CONCLUSION: Open surgery remains a rare indication for cerebral aneurysms after failed endovascular embolization even in the age of novel endovascular technology, such as flow diverters and intrasaccular devices. Regardless, it is mostly performed for ruptured aneurysms initially treated with primary coiling that are in the anterior circulation.

Multi-Dynamic-Multi-Echo-based MRI for the Pre-Surgical Determination of Sellar Tumor Consistency: a Quantitative Approach for Predicting Lesion Resectability.

PURPOSE: Pre-surgical information about tumor consistency could facilitate neurosurgical planning. This study used multi-dynamic-multi-echo (MDME)-based relaxometry for the quantitative determination of pituitary tumor consistency, with the aim of predicting lesion resectability. METHODS: Seventy-two patients with suspected pituitary adenomas, who underwent preoperative 3 T MRI between January 2020 and January 2022, were included in this prospective study. Lesion-specific T1-/T2-relaxation times (T1R/T2R) and proton density (PD) metrics were determined. During surgery, data about tumor resectability were collected. A Receiver Operating Characteristic (ROC) curve analysis was performed to investigate the diagnostic performance (sensitivity/specificity) for discriminating between easy- and hard-to-remove by aspiration (eRAsp and hRAsp) lesions. A Mann-Whitney-U-test was done for group comparison. RESULTS: A total of 65 participants (mean age, 54 years ± 15, 33 women) were enrolled in the quantitative analysis. Twenty-four lesions were classified as hRAsp, while 41 lesions were assessed as eRAsp. There were significant differences in T1R (hRAsp: 1221.0 ms ± 211.9; eRAsp: 1500.2 ms ±â€¯496.4; p = 0.003) and T2R (hRAsp: 88.8 ms ± 14.5; eRAsp: 137.2 ms ± 166.6; p = 0.03) between both groups. The ROC analysis revealed an area under the curve of 0.72 (95% CI: 0.60-0.85) at p = 0.003 for T1R (cutoff value: 1248 ms; sensitivity/specificity: 78%/58%) and 0.66 (95% CI: 0.53-0.79) at p = 0.03 for T2R (cutoff value: 110 ms; sensitivity/specificity: 39%/96%). CONCLUSION: MDME-based relaxometry enables a non-invasive, pre-surgical characterization of lesion consistency and, therefore, provides a modality with which to predict tumor resectability.

Long-term outcome after decompressive hemicraniectomy for malignant middle cerebral artery infarction.

BACKGROUND: Although decompressive hemicraniectomy (DHC) is a lifesaving treatment strategy for patients with malignant middle cerebral artery infarction (mMCAi), only one in four patients achieves low to moderate post-stroke disability according to previous studies. However, the short follow-up periods in prior studies could have overestimated the poor clinical prognosis. This study therefore examined the long-term outcome after DHC for mMCAi. METHODS: We retrospectively included all patients who had undergone DHC after mMCAi at the University Hospital Graz between 2006 and 2019. Demographics, clinical data and complications were collected from electronic clinical patient records. To investigate long-term prognosis, all patients were followed up to 14 years after stroke including quality of life (QOL) assessment. Post-stroke disability was rated according to the modified Rankin Scale (mRS). RESULTS: Of 47 patients that had undergone DHC for mMCAi, follow-up data were available in 40 patients (mean age: 48 years; 40% female). Six months after the mMCAi, 14 patients had died (35%) and nine (23%) had a low to moderate post-stroke disability (mRS 0-3). Of 26 stroke survivors, half (50%) showed further mRS improvement (≥ 1 point) during the long-term follow-up period (mean follow-up time: 8 years). At last follow-up, 17 patients had achieved an mRS score of ≤ 3 (65% versus 35% after 6 months; p = 0.008) and 55% had no signs of depression and anxiety, and 50% no signs of pain or discomfort in QOL assessment. CONCLUSION: This study shows substantial long-term improvement of functional disability and reasonable QOL in mMCAi patients after DHC.

Does High-Definition 3-Dimensional Imaging Improve Orientation During Endoscopic Transsphenoidal Surgery? A Prospective Trial.

BACKGROUND: Endoscopy has evolved as the standard visualization tool for endonasal transsphenoidal resection of sellar lesions. The most widely used 2-dimensional (2D) endoscopes harbor the problem of limited depth perception. Therefore, 3-dimensional (3D) endoscopes have been developed to enable depth perception through a stereoscopic view. OBJECTIVE: To evaluate the impact of high-definition (HD) 2D vs 3D HD endoscopes on spatial orientation within the sphenoid sinus. METHODS: In this prospective single-center study, 21 patients have been investigated (2021-2022). Eleven standardized anatomic landmarks, which were preoperatively defined on neuronavigation imaging, were intraoperatively targeted with a navigation probe using either 2D HD or 3D HD endoscopes for visualization. RESULTS: Overall, 3D HD endoscopes provided a statistically significant higher accuracy of identification of sphenoid sinus landmarks (median deviation: 5.2 mm vs 4.2 mm, P < .001). In detail: tuberculum sellae (3.0 mm vs 4.3 mm, P = .047), most anterior point of sella (3.3 mm vs 4.8 mm, P = .049), and clivus indentation (3.8 mm vs 5.3 mm, P = .035). Anatomic variations such as a complex sphenoid sinus configuration had no influence on identifying sphenoid sinus landmarks. CONCLUSION: According to our data, stereoscopic 3D HD endoscopy enhances intraoperative orientation by improved depth perception within the sphenoid sinus. This may add to the safety of endoscopic skull base procedures, especially in extended approaches and cases with distorted anatomy.

A Patient-Specific Reference Tracker for Noninvasive Electromagnetic Navigation of Endoscopic Skull Base Surgery.

BACKGROUND: Owing to the possibility of nonrigid head fixation, electromagnetic navigation (EM) is a mainstay for endoscopic skull base surgery. The currently available dynamic reference trackers (RTs) are invasive or inaccurate. OBJECTIVE: To investigate the feasibility and stability of this innovative oral tracker (OT), which is adhesive to the hard palate in comparison with a commercially available skin adhesive tracker (ST). METHODS: A prospective series of 31 patients with intrasellar lesions who underwent surgery between 2019 and 2021 using a pure endoscopic transsphenoidal approach were evaluated. A patient-specific palatal mold was designed from preoperative computed tomography data. The OT was cast using a biocompatible algin with an integrated EM tracker assembly. In comparison with a skull-mounted RT, which served as a gold standard, the deviations of OT vs those of the ST with the RT were continuously assessed. RESULTS: The OT showed significantly lower deviations from the RT than the ST during the surgical steps: start of endoscopic surgery (OT vs ST: 0.62 mm, IQR 0.36-0.89 vs 1.65 mm, IQR 1.35-2.32, P < .001), drilling phase (OT vs ST: 0.81 mm, IQR 0.51-1.32 vs 1.89 mm, IQR 1.6-2.74, P < .001), and end of endoscopic surgery (OT vs ST: 1.1 mm, IQR 0.68-1.64 vs 1.9 mm, IQR 1.6-2.72, P < .001). CONCLUSION: The OT showed significantly higher intraoperative stability than the ST. Therefore, this noninvasive and patient-specific tool could be used to achieve accurate EM guidance during endoscopic skull base surgeries.

Outcome of CRH stimulation test and overnight 8 mg dexamethasone suppression test in 469 patients with ACTH-dependent Cushing's syndrome.

Objective: To evaluate diagnostic accuracy of the corticotropin-releasing hormone (CRH) stimulation test and the overnight 8 mg dexamethasone suppression test (DST) for the differentiation of Cushing's disease (CD) and ectopic Cushing's syndrome (ECS). Methods: Retrospective study in 6 European centers. Inclusion criteria: patients with a) overt adrenocorticotropin (ACTH)-dependent Cushing's syndrome at the time of dynamic testing, b) histopathological confirmed tumors and/or c) postoperative biochemical remission and/or adrenal insufficiency. Optimal cut-offs were calculated via receiver operating characteristic (ROC) analysis using CD as reference. Results: 469 patients were analyzed [78% females; median age 43 years (IQR 19)]. CRH test and overnight 8 mg DST were performed in 420 [CD, n=394 (94%); ECS, n=26 (6%)] and 237 patients [228 CD (96%), 9 ECS (4%)]. Both tests were performed in 205 patients (44%). The post-CRH %-increase at 30 minutes of both ACTH (cut-off ≥31%, sensitivity 83%, specificity 85%, AUC 0.81) and cortisol (cut-off ≥12%, sensitivity 82%, specificity 89%, AUC 0.86) discriminated best between CD and ECS. A test duration of >60 minutes did not improve diagnostic performance of the CRH test. The optimal cortisol cut-off for the %-suppression during the 8 mg DST was ≥55% (sensitivity 80%, specificity 78%, AUC 0.75). Conclusion: The CRH test has equivalent sensitivity but higher specificity than the 8 mg DST and is therefore the test of first choice. The diagnostic outcome of ACTH and cortisol is well comparable, however, sampling beyond 60 minutes post-CRH does not provide diagnostic benefits.

Diagnostic criteria of small sellar lesions with hyperprolactinemia: Prolactinoma or else.

Objective: To evaluate the combined predictive value of MRI criteria with the prolactin-volume-ratio (PVR) to differentiate prolactinoma from non-prolactinoma, in small sellar lesions with hyperprolactinemia. Methods: Retrospective analysis of 55 patients with sellar lesions of ≤15 mm diameter on MRI and hyperprolactinemia of ≤150 ng/mL, surgically treated between 2003 and 2020 at the Medical University of Vienna, with a conclusive histopathological report. Serum prolactin levels, extent of pituitary stalk deviation, size and volume of the lesion were assessed. The PVR was calculated by dividing the preoperative prolactin level by tumor volume. Results: Our study population consisted of 39 patients (71%) with a prolactin-producing pituitary adenoma (group A), while 16 patients (29%) had another type of sellar lesion (group B). Patients in group A were significantly younger (p=0.012), had significantly higher prolactin levels at diagnosis (p<0.001) as well as smaller tumor volume (p=0.036) and lower degree of pituitary stalk deviation (p=0.009). The median PVR was significantly higher in group A (243 ng/mL per cm3) than in group B (83 ng/mL per cm3; p=0.002). Furthermore, the regression operating characteristics analysis revealed a PVR >100 ng/mL per cm3 to be predictive for distinguishing prolactin-producing lesions from other small sellar lesions. Conclusion: In patients with small sellar lesions, Prolactin-Volume-Ratios >100 represents a possible predictive marker for the diagnosis of prolactin-producing pituitary adenomas.

Clinico-pathologic predictors of dismal course in atypical meningiomas: a retrospective single-centre analysis.

BACKGROUND: Despite continuous refinement of the WHO classification for meningiomas, the biological behaviour of atypical meningiomas remains difficult to predict on the basis of this grading system alone. The aim of this study was to investigate the prognostic significance of clinical and radiological parameters in a series of atypical meningioma with long follow-up of minimum 5 years. METHODS: Of 1675 meningiomas treated at the Medical University Vienna between 1993 and 2015, 179 were atypical meningioma. Of those, 93 patients were identified with follow-up of ≥5 years. Patients were grouped by recurrence and evaluated for overall and progression free survival as well as potential prognostic parameters such as age, gender, tumor size and location, edema, irregular surface, contrast enhancement, bone invasion and hyperostosis, necrosis, EOR and MIB-1. RESULTS: From 42 (45%) patients in group recurrent and 51 (55%) patients in group nonrecurrent, seven independent factors were associated with decreased progression-free survival in univariate analysis: size ≥5 cm, age ≥60 years, male gender, subtotal resection, irregular surface, and necrosis on magnetic resonance imaging, and MIB-1 ≥6%. In multivariable analysis, only larger size, older age, necrosis and higher MIB-1 remained independent prognostic risk factors for recurrence of atypical meningioma. CONCLUSIONS: We identified larger size, older age, presence of necrosis on magnetic resonance imaging, and higher MIB-1, as detrimental parameters for recurrence of atypical meningioma. Until molecular profiling of atypical meningioma becomes routinely available, these parameters may aid the clinician in decision making about surveillance intervals and adjuvant radiation treatment.

DNA Methylation Associates With Clinical Courses of Atypical Meningiomas: A Matched Case-Control Study.

Background: Accounting for 15-20% of all meningiomas, WHO grade II meningiomas represent an intermediate group regarding risk of tumor recurrence. However, even within this subgroup varying clinical courses are observed with potential occurrence of multiple recurrences. Recently, DNA methylation profiles showed their value for distinguishing biological behaviors in meningiomas. Therefore, aim of this study was to investigate DNA methylation profiles in WHO grade II meningiomas. Methods: All patients that underwent resection of WHO grade II meningiomas between 1993 and 2015 were screened for a dismal course clinical course with ≥2 recurrences. These were matched to control cases with benign clinical courses without tumor recurrence. DNA methylation was assessed using the Infinium Methylation EPIC BeadChip microarray. Unsupervised hierarchical clustering was performed for identification of DNA methylation profiles associated with such a dismal clinical course. Results: Overall, 11 patients with WHO grade II meningiomas with ≥2 recurrences (Group dismal) and matched 11 patients without tumor recurrence (Group benign) were identified. DNA methylation profiles revealed 3 clusters-one comprising only patients of group dismal, a second cluster comprising mainly patients from group benign and a third cluster comprising one group dismal and one group benign patient. Based on differential methylation pattern associations with the Wnt and the related cadherin signaling pathway was observed. Conclusion: DNA methylation clustering showed remarkable differences between two matched subgroups of WHO grade II meningiomas. Thus, DNA methylation profiles may have the potential to support prognostic considerations regarding meningioma recurrence and radiotherapeutic treatment allocation after surgical resection.

Treatment strategies for giant pituitary adenomas in the era of endoscopic transsphenoidal surgery: a multicenter series.

OBJECTIVE: Given the anatomical complexity and frequently invasive growth of giant pituitary adenomas (GPAs), individually tailored approaches are required. The aim of this study was to assess the treatment strategies and outcomes in a large multicenter series of GPAs in the era of endoscopic transsphenoidal surgery (ETS). METHODS: This was a retrospective case-control series of 64 patients with GPAs treated at two tertiary care centers by surgeons with experience in ETS. GPAs were defined by a maximum diameter of ≥ 4 cm and a volume of ≥ 10 cm3 on preoperative isovoxel contrast-enhanced MRI. RESULTS: The primary operation was ETS in all cases. Overall gross-total resection rates were 64% in round GPAs, 46% in dumbbell-shaped GPAs, and 8% in multilobular GPAs (p < 0.001). Postoperative outcomes were further stratified into two groups based on extent of resection: group A (gross-total resection or partial resection with intracavernous remnant; 21/64, 33%) and group B (partial resection with intracranial remnant; 43/64, 67%). Growth patterns of GPAs were mostly round (11/14, 79%) in group A and multilobular (33/37, 89%) in group B. In group A, no patients required a second operation, and 2/21 (9%) were treated with adjuvant radiosurgery. In group B, early transcranial reoperation was required in 6/43 (14%) cases due to hemorrhagic transformation of remnants. For the remaining group B patients with remnants, 5/43 (12%) underwent transcranial surgery and 12/43 (28%) underwent delayed second ETS. There were no deaths in this series. Severe complications included stroke (6%), meningitis (6%), hydrocephalus requiring shunting (6%), and loss or distinct worsening of vision (3%). At follow-up (mean 3 years, range 0.5-16 years), stable disease was achieved in 91% of cases. CONCLUSIONS: ETS as a primary treatment modality to relieve mass effect in GPAs and extent of resection are dependent on GPA morphology. The pattern of residual pituitary adenoma guides further treatment strategies, including early transcranial reoperation, delayed endoscopic transsphenoidal/transcranial reoperation, and adjuvant radiosurgery.

Optimizing maximum resection of glioblastoma: Raman spectroscopy versus 5-aminolevulinic acid.

OBJECTIVE: The objective of this study was to assess and compare the potential of 5-aminolevulinic acid (5-ALA) and Raman spectroscopy (RS) in detecting tumor-infiltrated brain in patients with glioblastoma (GBM). METHODS: Between July 2020 and October 2021, the authors conducted a prospective clinical trial with 15 patients who underwent neurosurgical treatment of newly diagnosed and histologically verified GBM. A solid contrast-enhancing tumor core and peritumoral tissue were investigated intraoperatively for cancer cells by using 5-ALA and RS to achieve pathology-tailored maximum resection. In each case, a minimum of 10 biopsies were sampled from navigation-guided areas. Two neuropathologists examined the biopsies for the presence of neoplastic cells. The detection performance of 5-ALA and RS alone and in combination was assessed. Pre- and postoperative MRI, Karnofsky Performance Status (KPS), and National Institutes of Health Stroke Scale (NIHSS) scores were compared, and median progression-free survival (PFS) was evaluated. RESULTS: A total of 185 biopsy samples were harvested from the contrast-enhancing tumor core (n = 19) and peritumoral tissue (n = 166). In the tumor core, 5-ALA and RS each showed a sensitivity of 100%. In the peritumoral tissue, 5-ALA was less sensitive than RS in detecting cancer (46% vs 69%) but showed higher specificity (81% vs 57%). When the two methods were combined, the accuracy of tumor detection was increased by about 10%. Pathology-tailored resection led to a 52% increase in resection volume comparing the volume of preoperative contrast enhancement with the postoperative resection cavity on MRI (p = 0.0123). Eloquent brain involvement prevented gross-total resection in 4 patients. Four weeks after surgery, mean KPS (p = 0.7637) and NIHSS scores (p = 0.3146) were not significantly different from preoperative values. Of the 13 patients who had received postoperative chemoradiotherapy, 4 did not show any progression after a median follow-up of 14 months. The remaining 9 patients had a median PFS of 8 months. CONCLUSIONS: According to the study data, RS is capable of detecting tumor-infiltrated brain with higher sensitivity but lower specificity than the current standard of 5-ALA. With further technological and workflow advancements, RS in combination with protoporphyrin IX fluorescence may contribute to pathology-tailored glioma resection in the future.

Development of a miniaturized robotic guidance device for stereotactic neurosurgery.

OBJECTIVE: Consistently high accuracy and a straightforward use of stereotactic guidance systems are crucial for precise stereotactic targeting and a short procedural duration. Although robotic guidance systems are widely used, currently available systems do not fully meet the requirements for a stereotactic guidance system that combines the advantages of frameless surgery and robotic technology. The authors developed and optimized a small-scale yet highly accurate guidance system that can be seamlessly integrated into an existing operating room (OR) setup due to its design. The aim of this clinical study is to outline the development of this miniature robotic guidance system and present the authors' clinical experience. METHODS: After extensive preclinical testing of the robotic stereotactic guidance system, adaptations were implemented for robot fixation, software usability, navigation integration, and end-effector application. Development of the robotic system was then advanced in a clinical series of 150 patients between 2013 and 2019, including 111 needle biopsies, 13 catheter placements, and 26 stereoelectroencephalography (SEEG) electrode placements. During the clinical trial, constant modifications were implemented to meet the setup requirements, technical specifications, and workflow for each indication. For each application, specific setup, workflow, and median procedural accuracy were evaluated. RESULTS: Application of the miniature robotic system was feasible in 149 of 150 cases. The setup in each procedure was successfully implemented without adding significant OR time. The workflow was seamlessly integrated into the preexisting procedure. In the course of the study, procedural accuracy was improved. For the biopsy procedure, the real target error (RTE) was reduced from a mean of 1.8 ± 1.03 mm to 1.6 ± 0.82 mm at entry (p = 0.05), and from 1.7 ± 1.12 mm to 1.6 ± 0.72 mm at target (p = 0.04). For the SEEG procedures, the RTE was reduced from a mean of 1.43 ± 0.78 mm in the first half of the procedures to 1.12 ± 0.52 mm (p = 0.002) at entry in the second half, and from 1.82 ± 1.13 mm to 1.57 ± 0.98 mm (p = 0.069) at target, respectively. No healing complications or infections were observed in any case. CONCLUSIONS: The miniature robotic guidance device was able to prove its versatility and seamless integration into preexisting workflow by successful application in 149 stereotactic procedures. According to these data, the robot could significantly improve accuracy without adding time expenditure.

Dumbbell-shaped pituitary adenomas: prognostic factors for prediction of tumor nondescent of the supradiaphragmal component from a multicenter series.

OBJECTIVE: Dumbbell-shaped pituitary adenomas (DSPAs) are a subgroup of macroadenomas with suprasellar extension that are characterized by a smaller diameter at the level of the diaphragma sellae opening compared with the supradiaphragmal tumor component (SDTC). Hence, DSPAs may be particularly prone to a nondescending suprasellar tumor component and risk for residual tumor or postoperative bleeding. METHODS: A multicenter retrospective cohort analysis of 99 patients with DSPA operated on via direct endoscopic endonasal transsphenoidal approach between 2011 and 2020 was conducted. Patient recruitment was performed at two tertiary care centers (Medical University of Vienna and University of Southern California) with expertise in endoscopic skull base surgery. DSPA was defined as having a smaller diameter at the level of the diaphragma sellae compared with the SDTC. RESULTS: On preoperative MRI, all DSPAs were macroadenomas (maximum diameter range 17-71 mm, volume range 2-88 cm3). Tumor descent was found in 73 (74%) of 99 patients (group A), and nondescent in 26 (26%) of 99 patients (group B) intraoperatively. DSPAs in group A had a significantly smaller diameter (30 vs 42 mm, p < 0.001) and significantly smaller volume (10 vs 22 cm3, p < 0.001) than those in group B. The ratio of the minimum area at the level of the diaphragmal opening in comparison with the maximum area of the suprasellar tumor component ("neck-to-dome area") was significantly lower in group A than in group B (1.7 vs 2.7, p < 0.001). Receiver operating characteristic curve analysis revealed an area under the curve of 0.75 (95% CI 0.63-0.87). At a cutoff ratio of 1.9, the sensitivity and specificity for a nondescending suprasellar tumor component were 77% and 34%, respectively. CONCLUSIONS: In the present study, the neck-to-dome area ratio was of prognostic value for prediction of intraoperative tumor nondescent in DSPAs operated on via a direct endonasal endoscopic approach. Pituitary adenoma SDTC nondescent carried the inherent risk of hemorrhagic transformation in all cases.

Diagnosis of Pituitary Adenoma Biopsies by Ultrahigh Resolution Optical Coherence Tomography Using Neuronal Networks.

Objective: Despite advancements of intraoperative visualization, the difficulty to visually distinguish adenoma from adjacent pituitary gland due to textural similarities may lead to incomplete adenoma resection or impairment of pituitary function. The aim of this study was to investigate optical coherence tomography (OCT) imaging in combination with a convolutional neural network (CNN) for objectively identify pituitary adenoma tissue in an ex vivo setting. Methods: A prospective study was conducted to train and test a CNN algorithm to identify pituitary adenoma tissue in OCT images of adenoma and adjacent pituitary gland samples. From each sample, 500 slices of adjacent cross-sectional OCT images were used for CNN classification. Results: OCT data acquisition was feasible in 19/20 (95%) patients. The 16.000 OCT slices of 16/19 of cases were employed for creating a trained CNN algorithm (70% for training, 15% for validating the classifier). Thereafter, the classifier was tested on the paired samples of three patients (3.000 slices). The CNN correctly predicted adenoma in the 3 adenoma samples (98%, 100% and 84% respectively), and correctly predicted gland and transition zone in the 3 samples from the adjacent pituitary gland. Conclusion: Trained convolutional neural network computing has the potential for fast and objective identification of pituitary adenoma tissue in OCT images with high sensitivity ex vivo. However, further investigation with larger number of samples is required.

Reply to Stummer, W.; Thomas, C. Comment on "Hosmann et al. 5-ALA Fluorescence Is a Powerful Prognostic Marker during Surgery of Low-Grade Gliomas (WHO Grade II)-Experience at Two Specialized Centers. Cancers 2021, 13, 2540".

We greatly appreciate Dr. Stummer's and Dr. Thomas's interest in our study and their important comments [...].

Morpho-Molecular Metabolic Analysis and Classification of Human Pituitary Gland and Adenoma Biopsies Based on Multimodal Optical Imaging.

Pituitary adenomas count among the most common intracranial tumors. During pituitary oncogenesis structural, textural, metabolic and molecular changes occur which can be revealed with our integrated ultrahigh-resolution multimodal imaging approach including optical coherence tomography (OCT), multiphoton microscopy (MPM) and line scan Raman microspectroscopy (LSRM) on an unprecedented cellular level in a label-free manner. We investigated 5 pituitary gland and 25 adenoma biopsies, including lactotroph, null cell, gonadotroph, somatotroph and mammosomatotroph as well as corticotroph. First-level binary classification for discrimination of pituitary gland and adenomas was performed by feature extraction via radiomic analysis on OCT and MPM images and achieved an accuracy of 88%. Second-level multi-class classification was performed based on molecular analysis of the specimen via LSRM to discriminate pituitary adenomas subtypes with accuracies of up to 99%. Chemical compounds such as lipids, proteins, collagen, DNA and carotenoids and their relation could be identified as relevant biomarkers, and their spatial distribution visualized to provide deeper insight into the chemical properties of pituitary adenomas. Thereby, the aim of the current work was to assess a unique label-free and non-invasive multimodal optical imaging platform for pituitary tissue imaging and to perform a multiparametric morpho-molecular metabolic analysis and classification.

5-ALA Fluorescence Is a Powerful Prognostic Marker during Surgery of Low-Grade Gliomas (WHO Grade II)-Experience at Two Specialized Centers.

The prediction of the individual prognosis of low-grade glioma (LGG) patients is limited in routine clinical practice. Nowadays, 5-aminolevulinic acid (5-ALA) fluorescence is primarily applied for improved intraoperative visualization of high-grade gliomas. However, visible fluorescence is also observed in rare cases despite LGG histopathology and might be an indicator for aggressive tumor behavior. The aim of this study was thus to investigate the value of intraoperative 5-ALA fluorescence for prognosis in LGG patients. We performed a retrospective analysis of patients with newly diagnosed histopathologically confirmed LGG and preoperative 5-ALA administration at two independent specialized centers. In this cohort, we correlated the visible intraoperative fluorescence status with progression-free survival (PFS), malignant transformation-free survival (MTFS) and overall survival (OS). Altogether, visible fluorescence was detected in 7 (12%) of 59 included patients in focal intratumoral areas. At a mean follow-up time of 5.3 ± 2.9 years, patients with fluorescing LGG had significantly shorter PFS (2.3 ± 0.7 vs. 5.0 ± 0.4 years; p = 0.01), MTFS (3.9 ± 0.7 vs. 8.0 ± 0.6 years; p = 0.03), and OS (5.4 ± 1.0 vs. 10.3 ± 0.5 years; p = 0.01) than non-fluorescing tumors. Our data indicate that visible 5-ALA fluorescence during surgery of pure LGG might be an already intraoperatively available marker of unfavorable patient outcome and thus close imaging follow-up might be considered.

Prevalence Rate of Coexisting Rathke Cleft Cysts and Pineal Cysts: A Multicenter Cross-Sectional Study.

BACKGROUND: Rathke cleft cysts (RCCs) are benign sellar lesions originating from remnants of primitive ectoderm. They have not been previously linked to other cystic lesions, such as pineal cysts (PCs). Our objective was to perform a multicenter cross-sectional neuroimaging study to examine prevalence rates of coexisting RCC and PC. METHODS: We retrospectively queried prospectively maintained, institutional review board-approved, databases from the authors' centers. All patients undergoing transsphenoidal surgery for RCC between the years of 2011 and 2020 were included for analysis. Preoperative magnetic resonance imaging was reviewed to identify the coexistence of a PC. Patient demographics and neuroimaging characteristics were recorded. A control cohort comprised of 100 age- and sex-matched patients with nonfunctional pituitary adenoma (NFPA) who also underwent surgical intervention was utilized. RESULTS: Eighty-four patients with RCC were identified for analysis. A coexistent PC was identified in 40.5% (n = 34) of patients with RCC compared with 14.3% (n = 12) in the NFPA cohort (P < 0.001). There was no significant difference in PC size between patients with RCC and PA (8 vs. 8.8 mm, respectively; P = 0.77). Although the majority (85.7%; n = 72) of the RCC cohort were female patients, there was no sex predominance with respect to coexisting PC in either the RCC or PA cohort. CONCLUSIONS: This is the first study to report an increased prevalence of coexisting PC and RCC, possibly because of an embryologic link or other propensity for intracranial cyst formation. Additional studies in more generalizable populations can further explore the relation between RCC and PC, or other cyst formation.

Single Burr-Hole Extended Transforaminal Approach for Concurrent Endoscopic Surgery in the Third Ventricle Posterior to the Foramen of Monro and Ventriculostomy: Clinical Series and Planning Steps.

OBJECTIVE: For endoscopic surgery of third ventricular lesions posterior to the foramen of Monro that frequently require a third ventriculostomy during the same procedure, the extended transforaminal approach (ETFA) through the choroid fissure has been proposed. This study reports clinical results and provides anatomic background and guidelines for individual planning of a single burr-hole approach and a safe transchoroid entry zone. METHODS: A retrospective review was undertaken of 25 cases of concurrent third ventricle surgery and third ventriculostomy via ETFA. Assessment was made of a safe transchoroidal entry zone on cadavers (6 hemispheres) and of planning guidelines on magnetic resonance imaging showing occlusive hydrocephalus (30 sides). RESULTS: ETFA was feasible in all 25 cases. The safe transchoroid entry zone was sufficient in 16 cases; in 9 cases, additional transchoroid opening with transection of the anterior septal vein was required without clinical consequences. The anatomic study showed a safe transchoroid entry zone of 5 mm (3-6 mm) for posterior enlargement of the foramen of Monro. Individual planning on magnetic resonance imaging of patients with enlarged third ventricles showed an optimal burr-hole position 22 mm (10-30 mm) lateral to the midline and 8 mm (27 to -23 mm) precoronal; a foramen of Monro diameter of 7 mm (3-11 mm) and a safe transchoroid entry zone of 6 mm (3-12 mm). CONCLUSIONS: According to our data, concurrent endoscopic surgery of third ventricular lesions posterior to the foramen of Monro and ventriculostomy are feasible through a single burr hole and a transchoroid extension of the transforaminal approach. Precise preoperative planning is recommended for anticipating the individual anatomic nuances.

Utility of indocyanine green in the detection of radiologically silent hemangioblastomas: case report.

Hemangioblastomas (HBs) are rare, benign, hypervascularized tumors. Fluorescent imaging with indocyanine green (ICG) can visualize tumor angioarchitecture. The authors report a case of multiple HBs involving two radiologically silent lesions only detected intraoperatively by ICG fluorescence. A 26-year-old woman presented with a cystic cerebellar mass on the tentorial surface of the left cerebellar hemisphere on MRI. A left paramedian suboccipital approach was performed to remove the mural nodule with the aid of ICG injection. The first injection, applied just prior to removing the nodule, highlighted the tumor and vessels. After resection, two new lesions, invisible on the preoperative MRI, surprisingly enhanced on fluorescent imaging 35 minutes after the ICG bolus. Both silent lesions were removed. Histological analysis of all three lesions revealed they were positive for HB. The main goal of this report is to hypothesize possible explanations about the mechanism that led to the behavior of the two silent lesions. Intraoperative ICG videoangiography was useful to understand the 3D angioarchitecture and HB flow patterns to perform a safe and complete resection in this case. Understanding the HB ultrastructure and pathophysiological mechanisms, in conjunction with the properties of ICG, may expand potential applications for their diagnosis and future treatments.