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Background: Thyroid Transcription Factor-1 (TTF-1) expression in lung adenocarcinoma (LUAD) has been studied for its prognostic value in early-stage and metastatic disease. Its role in brain metastasis remains unexplored. This study investigates the predictive value and association of TTF-1 status with clinicopathological variables in patients with synchronous LUAD brain metastases., Material and Methods: In this bicentric retrospective study, 245 patients with newly diagnosed, treatment-naïve brain metastasis undergoing resection were included. Patient data were retrieved from electronic records. Outcomes included overall and progression-free survival. Statistical analysis included Kaplan-Meier estimates and Cox proportional hazards regression., Results: Mean Ki67 index in TTF-1 negative patients was 43% [95% CI 38-48%] compared to 32% [95% CI 29-35%] in TTF-1 positive (TTF-1 +) patients (p < 0.001). Tumor volume was significantly larger in TTF-1 negative (TTF-1-) patients (mean volume 24 mL [95% CI 18-31 mL]) vs. 15 mL [95% CI 12-17 mL] in TTF-1 + patients (padjust = 0.003). Perifocal edema was smaller in TTF-1- patients (mean volume: 58 mL [95% CI 45-70 mL]) vs. 84 mL [95% CI 73-94 mL] in TTF-1 + patients (padjust = 0.077). Tumor and edema volume did not correlate. TTF-1- patients showed worse overall, intracranial, and extracranial progression-free survival. In a multivariable Cox model, positive TTF-1 status was independently associated with improved outcomes. Negative TTF-1 status was associated with increased hazard for intracranial disease progression compared to extracranial progression., Conclusion: In synchronous LUAD brain metastases, TTF-1 negativity reflects an aggressive phenotype with larger proliferation capacity and tumor volume. Future research should explore the underlying cellular and molecular alterations of this phenotype., Competing Interests: Declarations. Competing interests: The authors declare no relevant financial or non-financial interests. There were no competing interests with respect to this study. Ethical approval and consent to participate: This study was approved by the local institutional review boards (EA1/399/20 and 20-1799-101). Consent for publication: Not applicable. Previous presentations: Portions of this work were presented at the annual meeting of the European Association of Neurosurgical Societies (EANS), Sofia, Bulgaria, October 13–17, 2024., (© 2024. The Author(s).)

Background: Several meta-analyses comparing the outcome of awake versus asleep deep brain stimulation procedures could not reveal significant differences concerning the postoperative improvement of motor symptoms. Only rarely information on the procedural details is provided for awake operations and how often somnolence and disorientation occurred, which might hamper the reliability of intraoperative clinical testing. The aim of our study was to investigate possible influencing factors on the occurrence of somnolence and disorientation in awake DBS procedures., Methods: We retrospectively analyzed 122 patients with Parkinson's disease having received implantation of a DBS system at our centre. Correlation analyses were performed for the duration of disease prior to surgery, number of microelectrode trajectories, AC-PC-coordinates of the planned target, UPDRS-scores, intraoperative application of sedative drugs, duration of the surgical procedure, perioperative application of apomorphine, and the preoperative L-DOPA equivalence dosage with the occurrence of intraoperative somnolence and disorientation., Results: Patients with intraoperative somnolence were significantly older (p=0.039). Increased duration of the DBS procedure (p=0.020), delayed start of the surgery (p=0.049), higher number of MER trajectories (p=0.041), and the patients' % UPDRS improvement (p=0.046) also correlated with the incidence of intraoperative somnolence. We identified the main contributing factor to intraoperative somnolence as the use of sedative drugs applied during skin incision and burr hole trepanation (p=0.019). Perioperatively applied apomorphine could reduce the occurrence of somnolent phases during the operation (p=0.026)., Conclusion: Several influencing factors were found to seemingly increase the risk of intraoperative somnolence and disorientation, while the use of sedative drugs seems to be the main contributing factor. We argue that awake DBS procedures should omit the use of sedatives for best clinical outcome. When reporting on awake DBS surgery these factors should be considered and adjusted for, to permit reliable interpretation and comparison of DBS study results., (© 2023. The Author(s).)

Background: The expression level of the programmed cell death ligand 1 (PD-L1) appears to be a predictor for response to immunotherapy using checkpoint inhibitors in patients with non-small cell lung cancer (NSCLC). As differences in terms of PD-L1 expression levels in the extracranial primary tumor and the brain metastases may occur, a reliable method for the non-invasive assessment of the intracranial PD-L1 expression is, therefore of clinical value. Here, we evaluated the potential of radiomics for a non-invasive prediction of PD-L1 expression in patients with brain metastases secondary to NSCLC., Patients and Methods: Fifty-three NSCLC patients with brain metastases from two academic neuro-oncological centers (group 1, n = 36 patients; group 2, n = 17 patients) underwent tumor resection with a subsequent immunohistochemical evaluation of the PD-L1 expression. Brain metastases were manually segmented on preoperative T1-weighted contrast-enhanced MRI. Group 1 was used for model training and validation, group 2 for model testing. After image pre-processing and radiomics feature extraction, a test-retest analysis was performed to identify robust features prior to feature selection. The radiomics model was trained and validated using random stratified cross-validation. Finally, the best-performing radiomics model was applied to the test data. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analyses., Results: An intracranial PD-L1 expression (i.e., staining of at least 1% or more of tumor cells) was present in 18 of 36 patients (50%) in group 1, and 7 of 17 patients (41%) in group 2. Univariate analysis identified the contrast-enhancing tumor volume as a significant predictor for PD-L1 expression (area under the ROC curve (AUC), 0.77). A random forest classifier using a four-parameter radiomics signature, including tumor volume, yielded an AUC of 0.83 ± 0.18 in the training data (group 1), and an AUC of 0.84 in the external test data (group 2)., Conclusion: The developed radiomics classifiers allows for a non-invasive assessment of the intracranial PD-L1 expression in patients with brain metastases secondary to NSCLC with high accuracy., (© 2023. The Author(s).)

The pathophysiology of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) is incompletely understood. Intrathecal activation of inflammatory immune cells is suspected to play a major role for the induction of DCI. The aim of this study is to identify immune cell subsets and mediators involved in the pathogenesis of DCI. We prospectively collected blood and CSF from 25 patients with aSAH at early and late time points. We performed multicolor flow cytometry of peripheral blood and CSF, analyzing immune cell activation and pro-inflammatory cyto- and chemokines. In addition to the primary immune analysis, we retrospectively analyzed immune cell dynamics in the CSF of all our SAH patients. Our results show an increased monocyte infiltration secondary to aneurysm rupture in patients with DCI. Infiltrating monocytes are defined by a non-classical (CD14 dim CD16 + ) phenotype at early stages. The infiltration is most likely triggered by the intrathecal immune activation. Here, high levels of pro-inflammatory chemokines, such as CXCL1, CXCL9, CXCL10, and CXCL11, are detected. The intrathecal cellular activation profile of monocytes was defined by upregulation of CD163 and CD86 on monocytes and a presumable later differentiation into antigen-presenting plasmacytoid dendritic cells (pDCs) and hemosiderophages. Peripheral immune activation was reflected by CD69 upregulation on T cells. Analysis of DCI prevalence, Hunt and Hess grade, and clinical outcome correlated with the degree of immune activation. We demonstrate that monocytes and T cells are activated intrathecally after aSAH and mediate a local inflammatory response which is presumably driven by chemokines. Our data shows that the distinct pattern of immune activation correlates with the prevalence of DCI, indicating a pathophysiological connection to the incidence of vasospasm.

Background and Objective: The main challenge of bypass surgery of complex MCA aneurysms is not the selection of the bypass type but the initial decision-making of how to exclude the affected vessel segment from circulation. To this end, we have previously proposed a classification for complex MCA aneurysms based on the preoperative angiography. The current study aimed to validate this new classification and assess its diagnostic reliability using the giant aneurysm registry as an independent data set., Methods: We reviewed the pretreatment neuroimaging of 51 patients with giant (> 2.5 cm) MCA aneurysms from 18 centers, prospectively entered into the international giant aneurysm registry. We classified the aneurysms according to our previously proposed Berlin classification for complex MCA aneurysms. To test for interrater diagnostic reliability, the data set was reviewed by four independent observers., Results: We were able to classify all 51 aneurysms according to the Berlin classification for complex MCA aneurysms. Eight percent of the aneurysm were classified as type 1a, 14% as type 1b, 14% as type 2a, 24% as type 2b, 33% as type 2c, and 8% as type 3. The interrater reliability was moderate with Fleiss's Kappa of 0.419., Conclusion: The recently published Berlin classification for complex MCA aneurysms showed diagnostic reliability, independent of the observer when applied to the MCA aneurysms of the international giant aneurysm registry.

Background: Aneurysmal subarachnoid hemorrhage (SAH) as a serious type of stroke is frequently accompanied by a so-called initial thunderclap headache. However, the occurrence of burdensome long-term headache following SAH has never been studied in detail so far. The aim of this study was to determine the prevalence and characteristics of long-term burdensome headache in good-grade SAH patients as well as its relation to health-related quality of life (HR-QOL)., Methods: All SAH cases treated between January 2014 and December 2016 with preserved consciousness at hospital discharge were prospectively interviewed regarding burdensome headache in 2018. Study participants were subsequently scrutinized by means of a standardized postal survey comprising validated pain and HR-QOL questionnaires. A retrospective chart review provided data on the initial treatment., Results: A total of 93 out of 145 eligible SAH patients participated in the study (62 females). A total of 41% (38/93) of subjects indicated burdensome headache at follow-up (mean 32.6 ± 9.3 months). Comparison between patients with (HA+) and without long-term headache (HA-) revealed significantly younger mean age (47.9 ± 11.8 vs. 55.6 ± 10.3 years; p < .01) as well as more favorable neurological conditions (WFNS I/II: 95% vs. 75%; p = .03) in HA+ cases. The mean average headache of the HA+ group was 3.7 ± 2.3 (10-point numeric rating scale), and the mean maximum headache intensity was 5.7 ± 2.9. Pain and HR-QOL scores demonstrated profound alterations in HA+ compared to HA- patients., Conclusions: Our results suggest that a considerable proportion of SAH patients suffers from burdensome headache even years after the hemorrhage. Moreover, long-term headache is associated with reduced HR-QOL in these cases.

Background: Giant intracranial aneurysms of the posterior circulation (GPCirA) are rare entities compressing the brainstem and adjacent structures. Previous evidence has shown that the amount of brainstem shift away from the cranial base is not associated with neurological deficits. This raises the question whether other factors may be associated with neurological deficits., Methods: All data were extracted from the Giant Intracranial Aneurysm Registry, an international multicenter prospective study on giant intracranial aneurysms. We grouped GPCirA according to the mass effect on the brainstem (lateral versus medial). Brainstem compression was evaluated with two indices: (a) brainstem compression ratio (BCR) or diameter of the compressed brainstem to the assumed normal diameter of the brainstem and (b) aneurysm to brainstem ratio (ABR) or diameter of the aneurysm to the diameter of the compressed brainstem. We examined associations between neurological deficits and GPCirA characteristics using binary regression analysis., Results: Twenty-eight GPCirA were included. Twenty GPCirA showed medial (71.4%) and 8 lateral compression of the brainstem (28.6%). Baseline characteristics did not differ between the groups for patient age, aneurysm diameter, aneurysm volume, modified Rankin Scale (mRS), motor deficit (MD), or cranial nerve deficits (CND). Mean BCR was 53.0 in the medial and 54.0 in the lateral group (p = 0.92). The mean ABR was 2.9 in the medial and 2.3 in the lateral group (p = 0.96). In the entire cohort, neither BCR nor ABR nor GPCirA volumes were associated with the occurrence of CND or MD. In contrast, disability (mRS) was significantly associated with ABR (OR 1.94 (95% CI 1.01-3.70; p = 0.045) and GPCirA volumes (OR 1.21 (95% CI 1.01-1.44); p = 0.035), but not with BCR., Conclusion: In this cohort of patients with GPCirA, neither the degree of lateral projection nor the amount of brainstem compression predicted neurological deficits. Disability was associated only with aneurysm volume. When designing treatment strategies for GPCirA, aneurysm laterality or the amount of brainstem compression should be viewed as less relevant while the high risk of rupture of such giant lesions should be emphasized., Trial Registration: The registry is listed at clinicaltrials.gov under the registration no. NCT02066493.

Background: The Woven EndoBridge (WEB) device has been increasingly used for the treatment of intracranial aneurysms after aneurysmal subarachnoid hemorrhage (SAH). Still, recent major clinical trials on patient management after SAH have defined WEB embolization as an exclusion criterion. In an analysis of an unselected patient cohort, we evaluate the early clinical course of SAH patients after WEB treatment compared to those treated with endovascular coiling or surgical clipping., Methods: Data of all patients with proven SAH who were either treated with a WEB device, coil embolization, or neurosurgical clipping between March 2015 and August 2018 was systematically reviewed. Clinical parameters on intensive care unit (ICU), medical history and mortality rates were evaluated and compared between the different treatment approaches., Results: Of all 201 patients included, 107 patients received endovascular coil embolization, 56 patients were treated with clipping and in 38 cases a WEB device was placed. The overall mortality was 17.9%. Thirteen patients (34.2%) in the WEB group had a Hunt and Hess grade > 3. Essential medical factors showed no clinically relevant differences between the treatment groups, and the analyzed blood parameters were predominantly within physiological limits without any relevant outliers. The Hunt and Hess grade but not the treatment modality was identified as independent risk-factor associated with ICU-mortality in the overall cohort (p < 0.001)., Conclusion: In this study, there was no difference in the early clinical course between those treated with WEB embolization, coil embolization, or neurosurgical clipping. Since WEB embolization is a valuable treatment alternative to coiling, it seems not justified to exclude this procedure from upcoming clinical SAH trials, yet the clinical long-term outcome, aneurysm occlusion, and retreatment rates have to be analyzed in further studies., Clinical Trial Registration Number: not applicable.

Background: Thyrotropin-producing adenomas (TSHomas) account for approximately 1-2% of all pituitary tumors. Recently, there has been debate on primary treatment as some studies suggest a high rate of hypopituitarism after transsphenoidal surgery and therefore suggest primary use of somatostatin analogs (SSA) instead. We would like to challenge this assumption by presenting our single-center experience with transsphenoidal surgery for TSHoma., Methods: Fifteen patients treated consecutively between May 2010 and December 2016 were analyzed for long-term postoperative remission and pituitary function., Results: Data on the development of TSH, fT3 and fT4 were available for 12 of 15 patients (mean follow-up was 18 months, 8 patients >12 months), showing mean TSH levels of 1.289 mU/l (0.02-2.04, SD 0.66), mean fT3 levels of 3.76 pmol/l (0.5-6.16, SD 1.8) and mean fT4 levels of 16.5 pmol/l (11.7-21.9, SD 3.66). Six of those patients were substituted with a mean of 85.4 μg L-thyroxine after a median follow-up of 20.7 months. The other six patients did not receive L-thyroxine at a median follow-up of 15.5 months. One patient with a known tumor remnant on MRI stayed euthyreotic with cabergoline at the timepoint of follow-up 22 months after the operation. Control of the corticotrop axis was also available in 12 of 15 with no patient showing a corticotroph insufficiency in the long term., Conclusions: We argue that transsphenoidal surgery for TSHoma should be considered as the treatment of choice as remission following surgery is highly probable and postoperative hypopituitarism is very unlikely if patients are referred to centers with high pituitary surgery case loads.

Background: Early prediction of increased morbidity and mortality in aneurysmal subarachnoid hemorrhage (aSAH) remains crucial to improving patient management. Most prediction models lack external validation and focus on disease-specific items without considering physiological parameters and the past medical history. The aim was to assess the validity of the established Simplified Acute Physiology Score II (SAPS-II) in an aSAH cohort for the prediction of hospital mortality and to identify additional physiological and clinical predictors., Methods: The predictive value of SAPS-II for hospital mortality was assessed in a retrospective analysis of 263 consecutive patients with aSAH. Additional physiological and clinical parameters including the past medical history were analyzed by forward selection multivariate analysis to identify independent predictors of hospital mortality and to improve the prediction model., Results: The SAPS-II predicted hospital mortality with an area under the curve (AUC) of 0.834 with an odds ratio (OR) of 1.097 [95 % confidence interval 1.067-1.128) for each additional point. Forward selection multivariate analysis identified the Glasgow Coma Scale score (P < 0.001), history of chronic headache (P = 0.01) and medication with anticoagulants (P = 0.04) as independent predictors of hospital mortality. Adding these parameters to the SAPS-II, the AUC increased to 0.86., Conclusion: This study validates the predictive accuracy of SAPS-II for hospital mortality in aSAH patients. Additional parameters from the past medical history increase its predictive power. From a practical viewpoint, SAPS-II alone already represents a sufficient and powerful score to predict hospital mortality at an early time point and may help to improve patient management.

Background: The Giant Intracranial Aneurysm Registry is a multicenter observational trial exclusively focusing on giant intracranial aneurysms (GIA). As no data exist on the interobserver variability in the radiological description of GIA, there is some uncertainty concerning the reliability of the GIA characteristics included in the registry. We have therefore designed a study to test the interobserver variability in the description of the specific GIA characteristics that are examined in the GIA registry., Methods: Six different raters analyzed imaging of five GIA concerning GIA location, GIA size, GIA shape, GIA thrombosis, and the presence of perianeurysmal edema. Interobserver variability was examined using intraclass correlation and Fleiss' kappa analysis., Results: The intraclass correlation coefficient was 0.99 (95 % CI 0.97-1.0) for the largest GIA diameter and 0.98 (95 % CI 0.94-1.0) for the largest GIA diameter in an axial imaging slice. We found perfect interobserver agreement (Fleiss' kappa 1.00) in the characterization of GIA location and the presence of perianeurysmal edema and almost perfect interobserver agreement for GIA thrombosis (Fleiss' kappa 0.86, 95 % CI 0.63-1.00). Only moderate interobserver agreement was found in the description of GIA shape (Fleiss' kappa 0.50, 95 % CI 0.27-0.73)., Conclusions: While GIA size, location, thrombosis, and the presence of perianeurysmal edema showed excellent interobserver agreement, the description of GIA shape was achieved with only moderate agreement. Data on GIA shape in multicenter studies, like the GIA registry, should therefore be discussed with caution and potentially reassessed in a centralized fashion.

Background: Giant intracranial aneurysms (GIA) are often not eligible for direct clip occlusion. Surgical alternatives include partial clip occlusion or the placement of a cerebrovascular bypass or the combination of both. These alternative indirect strategies are expected to lead to a decrease in GIA volume over time rather than instantaneously. To examine whether this is the case, we analyzed follow-up imaging results 1 year after surgery., Methods: We retrospectively screened the prospective GIA Registry's imaging database for anterior circulation GIA treated by surgical strategies other than direct clipping. We measured pre- and 1-year post-treatment GIA volume, lateral ventricle volume (LVV), and mid-line shift (MLS) in 19 cases., Results: After a mean follow-up of 466 days (standard deviation ±171) GIA volumes decreased from 9.6 cm(3) (interquartile range (IQR) 6.1-14.1) to 4.3 cm(3) (IQR 2.9-5.7; p < 0.01). Ipsilateral LVV increased from 8.6 cm(3) (IQR 6.4-24.9) to 16.0 cm(3) (IQR 9.1-27.2; p < 0.01) while contralateral LVV increased from 10.3 cm(3) (IQR 7.3-20.1) to 11.7 cm(3) (IQR 8.2-19.4; p = 0.02). MLS changed from 0.1 mm (IQR -1.9 to 2.0) to -0.9 mm (IQR -1.8 to 0.4; p = 0.03). The decrease in GIA volume correlated with the increase in ipsilateral LVV (rs = 0.60; p = 0.01) but not with the changes in MLS (rs = 0.41; p = 0.08)., Conclusions: In our patient cohort, surgical strategies other that direct clipping for the treatment of anterior circulation GIA lead to a significant decrease in GIA volume over time. The resulting decrease in mass effect was more sensitively monitored by the measurement of changes in ipsilateral LVV than changes in MLS., Clinical Trial Registration-Url: http://www.clinicaltrials.gov . Unique identifier: NCT02066493.

Background: Intracranial aneurysms (IA) are usually quantified according to their largest diameter. However, volumetry has recently been increasingly conducted as well, especially in giant intracranial aneurysms (GIAs). Since so far the true value of GIA volumetry is unknown, we designed a trial to examine correlations between GIA diameter and volume with special focus on clinical implications., Methods: Magnetic resonance imaging of 69 unruptured GIAs in 66 patients was retrospectively evaluated. The largest diameter and volume were measured. Also, potential associations to the patients' clinical conditions were examined., Results: Comparing GIA sizes of our patient cohort produced different results depending on whether GIA diameter or volume was measured. Measuring the diameter identified posterior circulation GIAs as the largest ones (39.2 mm, IQR 37.3-48.3), while measuring the volume found GIAs of the MCA to be the largest ones (12.3 cm(3), IQR 7.2-27.8). A correlation of GIA diameter and volume was only found in anterior circulation GIAs, which were predominantly saccular in shape, but not in those of the posterior circulation, of which most were fusiform. Neither GIA diameter nor GIA volume but only GIA location was associated with neurological deficits., Conclusion: Diameter and volume measurements are not interchangeable modes of GIA quantification. Our data suggest that the idea of distinguishing different sizes of GIA may be clinically less relevant than examining their location, shape or mass effect.

Background: Reliable prognostic tools to estimate the case fatality rate (CFR) and the development of chronic hydrocephalus (CHC) in aneurysmal subarachnoid hemorrhage (SAH) are not well defined. This study aims to investigate the practicability and reliability of Fisher, Graeb, and LeRoux scores for SAH patient prognosis., Methods: A total of 206 patients with aneurysmal SAH were retrospectively analyzed in prediction of CFR and CHC. Clinical data was evaluated and grading was performed using Fisher, Graeb, and LeRoux scores. Univariate and multivariate analyses were performed to identify relevant predictive parameters., Results: CFR was 17.0 % and was associated with higher age, higher Hunt & Hess (H&H) grade, lower Glasgow Coma Scale (GCS) at admission, as well as a higher Fisher, Graeb, and LeRoux score (p < 0.001). There were 19.9 % that developed CHC requiring permanent cerebrospinal fluid diversion. Low initial GCS (p = 0.003), high H&H (p < 0.001), intracerebral hematoma (p = 0.003), high Fisher (p = 0.047), Graeb and LeRoux scores (p < 0.001) were associated with a higher rate of ventricular-peritoneal shunting (VPS) in surviving patients. In multivariate analyses, Graeb score (odds ratio (OR) 1.183 [1.027, 1.363], p = 0.020), LeRoux score (OR 1.120 [1.013-1.239, p = 0.027), and H&H (OR 2.715 [1.496, 4.927], p = 0.001) remained independent prognostic factors for VPS., Conclusions: Graeb or LeRoux scores improve the prediction of shunt dependency and in parts of CFR in aneurysmal SAH patients therefore confirming the relevance of the extent and distribution of intraventricular blood for the clinical course in SAH.

A major obstacle in the treatment of gliomas is the invasive capacity of the tumor cells. Previous studies have demonstrated the capability of neural stem cells (NSCs) to target these disseminated tumor cells and to serve as therapeutic delivery vehicles. Less is known about the factors involved in brain tumor tropism of NSCs and their interactions within the tumor environment. As gliomas progress and invade, an extensive modulation of the extracellular matrix (ECM) occurs. Tumor-ECM derived from six glioblastoma cell lines, ECM produced by normal human astrocytes and purified ECM compounds known to be upregulated in the glioma environment were analyzed for their effects on NSCs motility in vitro. We found that tumor-produced ECM was highly permissive for NSC migration. Laminin was the most permissive substrate for human NSC migration, and tenascin-C the strongest inducer of a directed human NSC migration (haptotaxis). A positive correlation between the degree of adhesion and migration of NSCs on different ECM compounds exists, as for glioma cells. Our in vitro data suggest that the ECM of malignant gliomas is a modulator of NSC migration. ECM proteins preferentially expressed in areas of glioma cell invasion may provide a permissive environment for NSC tropism to disseminated tumor cells.

Assessment of therapy efficacy using animal models of tumorigenic cancer requires the ability to accurately measure changes in tumor volume over the duration of disease course. In order to be meaningful, in vivo tumor volume measurements by non-invasive techniques must correlate with tumor volume measurements from endpoint histological analysis. Tumor volume is frequently assessed by endpoint histological analyses approximating the tumor volume with geometric primitives such as spheroids and ellipsoids. In this study we investigated alternative techniques for quantifying histological volume measurements of tumors in a xenograft orthotopic mouse model of human glioblastoma multiforme, and compared these to in vivo tumor volume measurements based on magnetic resonance imaging (MRI) data. Two techniques leveraging three-dimensional (3D) image analysis methods were investigated. The first technique involves the reconstruction of a smoothed polygonal model representing the tumor volume from histological section images and is intended for accuracy and qualitative assessment of tumor burden by visualization, while a second technique which approximates the tumor volume as a series of slabs is presented as an abbreviated process intended to produce quantitatively similar volume measurements with a minimum of effort required on behalf of the investigator. New software (QuickVol) designed for use in the first technique, is also discussed. In cases where tumor growth is asymmetric and invasive, we found that 3D analysis techniques using histological section images produced volume measurements more consistent with in vivo volume measurements based on MRI data, than approximation of tumor volume using geometric primitives. Visualizations of the volumes represented by each of these techniques qualitatively support this finding, and suggest that future research using mouse models of glioblastoma multiforme (genetically engineered or xenograft) will benefit from the use of these or similar alternative tumor volume measurement techniques.