Multi-modal fusion and feature enhancement U-Net coupling with stem cell niches proximity estimation for voxel-wise GBM recurrence prediction.

OBJECTIVE: We aim to develop a Multi-modal Fusion and Feature Enhancement U-Net (MFFE U-Net) coupling with stem cell niche (SCN) proximity estimation to improve voxel-wise GBM recurrence prediction. Approach: 57 patients with pre- and post-surgery MR scans were retrospectively solicited from 4 databases. Post-surgery MR scans included two months before the clinical diagnosis of recurrence and the day of the radiologically confirmed recurrence. The recurrences were manually annotated on the T1ce. The high-risk recurrence (HRR) region was first determined. Then, a sparse multi-modal feature fusion U-Net was developed. The 50 patients from 3 databases were divided into 70% training, 10% validation, and 20% testing. 7 patients from the 4th institution were used as external testing with transfer learning. Model performance was evaluated by recall, precision, F1-score, and Hausdorff Distance at the 95% percentile (HD95). The proposed MFFE U-Net was compared to the support vector machine (SVM) model and two state-of-the-art neural networks. An ablation study was performed. Main results: The MFFE U-Net achieved a precision of 0.79±0.08, a recall of 0.85±0.11, and an F1-score of 0.82±0.09. Statistically significant improvement was observed when comparing MFFE U-Net with proximity estimation couple SVM (SVMPE), mU-Net, and Deeplabv3. The HD95 was 2.75±0.44mm and 3.91±0.83mm for the 10 patients used in the model construction and 7 patients used for external testing, respectively. The ablation test showed that all five MR sequences contributed to the performance of the final model, with T1ce contributing the most. Convergence analysis, time efficiency analysis, and visualization of the intermediate results further discovered the characteristics of the proposed method. Significance: We present an advanced multi-modal fusion and feature enhancement learning framework, MFFE U-Net, for effective voxel-wise GBM recurrence prediction. MFFE U-Net performs significantly better than the state-of-the-art networks and can potentially guide early RT intervention of the disease recurrence.

Endoscopic Endonasal Transsphenoidal Resection of Pituitary Adenomas in Patients Presenting With Monocular Blindness.

BACKGROUND AND OBJECTIVES: Suprasellar tumors, particularly pituitary adenomas (PAs), commonly present with visual decline, and the endoscopic endonasal transsphenoidal approach (EETA) is the primary management for optic apparatus decompression. Patients presenting with complete preoperative monocular blindness comprise a high-risk subgroup, given concern for complete blindness. This retrospective cohort study evaluates outcomes after EETA for patients with PA presenting with monocular blindness. METHODS: Retrospective analysis of all EETA cases at our institution from June 2012 to August 2023 was performed. Inclusion criteria included adults with confirmed PA and complete monocular blindness, defined as no light perception, and a relative afferent pupillary defect secondary to tumor mass effect. RESULTS: Our cohort includes 15 patients (9 males, 6 females), comprising 2.4% of the overall PA cohort screened. The mean tumor diameter was 3.8 cm, with 6 being giant PAs (>4 cm). The mean duration of preoperative monocular blindness was 568 days. Additional symptoms included contralateral visual field defects (n = 11) and headaches (n = 10). Two patients presented with subacute PA apoplexy. Gross total resection was achieved in 46% of patients, reflecting tumor size and invasiveness. Postoperatively, 2 patients experienced improvement in their effectively blind eye and 2 had improved visual fields of the contralateral eye. Those with improvements were operated within 10 days of presentation, and no patients experienced worsened vision. CONCLUSION: This is the first series of EETA outcomes in patients with higher-risk PA with monocular blindness on presentation. In these extensive lesions, vision remained stable for most without further decline and improvement from monocular blindness was observed in a small subset of patients with no light perception and relative afferent pupillary defect. Timing from vision loss to surgical intervention seemed to be associated with improvement. From a surgical perspective, caution is warranted to protect remaining vision and we conclude that EETA is safe in the management of these patients.

A Neuroradiologist's Guide to Operationalizing the Response Assessment in Neuro-Oncology (RANO) Criteria Version 2.0 for Gliomas in Adults.

Radiographic assessment plays a crucial role in the management of patients with central nervous system (CNS) tumors, aiding in treatment planning and evaluation of therapeutic efficacy by quantifying response. Recently, an updated version of the Response Assessment in Neuro-Oncology (RANO) criteria (RANO 2.0) was developed to improve upon prior criteria and provide an updated, standardized framework for assessing treatment response in clinical trials for gliomas in adults. This article provides an overview of significant updates to the criteria including (1) the use of a unified set of criteria for high and low grade gliomas in adults; (2) the use of the post-radiotherapy MRI scan as the baseline for evaluation in newly diagnosed high-grade gliomas; (3) the option for the trial to mandate a confirmation scan to more reliably distinguish pseudoprogression from tumor progression; (4) the option of using volumetric tumor measurements; and (5) the removal of subjective non-enhancing tumor evaluations in predominantly enhancing gliomas (except for specific therapeutic modalities). Step-by-step pragmatic guidance is hereby provided for the neuroradiologist and imaging core lab involved in operationalization and technical execution of RANO 2.0 in clinical trials, including the display of representative cases and in-depth discussion of challenging scenarios.ABBREVIATIONS: BTIP = Brain Tumor Imaging Protocol; CE = Contrast-Enhancing; CNS = Central Nervous System; CR = Complete Response; ECOG = Eastern Cooperative Oncology Group; HGG = High-Grade Glioma; IDH = Isocitrate Dehydrogenase; IRF = Independent Radiologic Facility; LGG = Low-Grade Glioma; KPS = Karnofsky Performance Status; MR = Minor Response; mRANO = Modified RANO; NANO = Neurological Assessment in Neuro-Oncology; ORR = Objective Response Rate; OS = Overall Survival; PD = Progressive Disease; PFS = Progression-Free Survival; PR = Partial Response; PsP = Pseudoprogression; RANO = Response Assessment in Neuro-Oncology; RECIST = Response Evaluation Criteria In Solid Tumors; RT = Radiation Therapy; SD = Stable Disease; Tx = Treatment.

Structural and practical identifiability of contrast transport models for DCE-MRI.

Contrast transport models are widely used to quantify blood flow and transport in dynamic contrast-enhanced magnetic resonance imaging. These models analyze the time course of the contrast agent concentration, providing diagnostic and prognostic value for many biological systems. Thus, ensuring accuracy and repeatability of the model parameter estimation is a fundamental concern. In this work, we analyze the structural and practical identifiability of a class of nested compartment models pervasively used in analysis of MRI data. We combine artificial and real data to study the role of noise in model parameter estimation. We observe that although all the models are structurally identifiable, practical identifiability strongly depends on the data characteristics. We analyze the impact of increasing data noise on parameter identifiability and show how the latter can be recovered with increased data quality. To complete the analysis, we show that the results do not depend on specific tissue characteristics or the type of enhancement patterns of contrast agent signal.

Clinical Implications of Pituitary Adenomas Exhibiting Dual Transcription Factor Staining: A Case Series of 27 Patients.

OBJECTIVE: According to the 2017 World Health Organization classification of neuro-endocrine tumors, pituitary adenomas (PAs) are classified according to immunoexpression of the pituitary-specific transcription factors (TFs). A small subset of PAs exhibit multiple TF staining on immunohistochemistry and we present a series of 27 pathologically-confirmed cases of dual TF staining PAs (dsTF-PAs), and report clinically relevant implications. METHODS: A retrospective chart review of a multi-institutional database of patients with PAs surgically resected between 2008-2021 was performed. PAs expressing immunopositivity 2+ TFs. Patient demographics, neuro-imaging characteristics, histopathologic findings, and clinical data were collected. RESULTS: Twenty-seven patients had pathologically verified dsTF-PAs, of whom 17 were female (63%), with ages ranging from 20-84 years. Twenty-three (85.2%) patients harbored functional PAs, with acromegaly being the most common functional subtype (86.4%). The most common combination of TFs within a single tumor was PIT-1/SF-1 (85.2%). Six PAs exhibited Knosp cavernous sinus invasion grades of 3 or 4 and the Ki-67 labeling index was ≥3% in 6 patients (24.0%) and all stained for PIT-1/SF-1. Hormonal remission was achieved in 78% of functional dsTF-PAs. No PAs showed evidence of recurrence or progression over the mean follow-up period of 28.5 months. CONCLUSIONS: PAs exhibiting dsTF-PAs represent a small but clinically relevant diagnostic subset of PAs according to the 2021 World Health Organization criteria, as a majority are GH-producing. Precise classification using TF staining plays a key role in understanding the biology of these tumors. Favorable outcomes can be achieved in this subset of PAs with evolving TF classification.

Tumor characteristics guiding selection of channel-based versus open microscopic approaches for resection of atrial intraventricular meningiomas: patient series.

BACKGROUND: Atrial intraventricular meningiomas (AIMs) are relatively rare and typically deep-seated tumors that can mandate resection. Compared with transsulcal or transcortical open microscopic approaches, port- or channel-based exoscopic approaches have facilitated a less invasive alternative of tumor access and resection. The authors present a case series of seven patients with AIMs who underwent open microscopic versus channel-based exoscopic resection by a senior neurosurgeon at their institution between 2012 and 2022 to understand patient and tumor features that lent themselves to selection of a particular approach. OBSERVATIONS: In the patients harboring three AIMs selected for channel-based resection, the average AIM diameter (2.9 vs 5.2 cm) was smaller, the AIMs were deeper from the cortical surface (2.5 vs 1.1 cm), and the patients had a shorter average postoperative length of stay (3.3 vs 5.8 days) compared with the four patients who underwent open resection. Gross-total resection was achieved in all cases. Complications for both groups included transient homonymous hemianopsia and aphasia. No recurrences were identified over the follow-up period. LESSONS: The authors demonstrate that channel-based exoscopic resection is safe and effective for AIMs 3 cm in diameter and over 2 cm deep. This may help guide neurosurgeons in future approach selection based on tumor features, including size/volume, location, and depth from cortical surface.

A cross-sectional study to test equivalence of low- versus intermediate-flip angle dynamic susceptibility contrast MRI measures of relative cerebral blood volume in patients with high-grade gliomas at 1.5 Tesla field strength.

Introduction: 1.5 Tesla (1.5T) remain a significant field strength for brain imaging worldwide. Recent computer simulations and clinical studies at 3T MRI have suggested that dynamic susceptibility contrast (DSC) MRI using a 30° flip angle ("low-FA") with model-based leakage correction and no gadolinium-based contrast agent (GBCA) preload provides equivalent relative cerebral blood volume (rCBV) measurements to the reference-standard acquisition using a single-dose GBCA preload with a 60° flip angle ("intermediate-FA") and model-based leakage correction. However, it remains unclear whether this holds true at 1.5T. The purpose of this study was to test this at 1.5T in human high-grade glioma (HGG) patients. Methods: This was a single-institution cross-sectional study of patients who had undergone 1.5T MRI for HGG. DSC-MRI consisted of gradient-echo echo-planar imaging (GRE-EPI) with a low-FA without preload (30°/P-); this then subsequently served as a preload for the standard intermediate-FA acquisition (60°/P+). Both normalized (nrCBV) and standardized relative cerebral blood volumes (srCBV) were calculated using model-based leakage correction (C+) with IBNeuro™ software. Whole-enhancing lesion mean and median nrCBV and srCBV from the low- and intermediate-FA methods were compared using the Pearson's, Spearman's and intraclass correlation coefficients (ICC). Results: Twenty-three HGG patients composing a total of 31 scans were analyzed. The Pearson and Spearman correlations and ICCs between the 30°/P-/C+ and 60°/P+/C+ acquisitions demonstrated high correlations for both mean and median nrCBV and srCBV. Conclusion: Our study provides preliminary evidence that for HGG patients at 1.5T MRI, a low FA, no preload DSC-MRI acquisition can be an appealing alternative to the reference standard higher FA acquisition that utilizes a preload.

Endoscopic endonasal approach for MRI-Negative Cushing's microadenoma.

A 54-year-old male with a history of diabetes mellitus type 2 for 12 years and hypertension was seen in the clinic due to poorly controlled diabetes. Inferior petrosal sinus sampling (IPSS) confirmed Cushing's disease with primary adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma on the right. However, 3T and subsequent 7T MRI showed no visible tumor. An endoscopic transsphenoidal approach was selected to explore the pituitary gland and resect the presumed microadenoma. Tumor was identified in the lateral recess along the right medial cavernous sinus wall and gross-total resection (GTR) was performed. The normal pituitary gland was preserved, and the patient went into remission. The video can be found here: https://stream.cadmore.media/r10.3171/2023.4.FOCVID2324.

Validation of Myc-Associated Protein X (MAX) regulation in growth hormone secreting and nonfunctional pituitary adenoma.

INTRODUCTION: Many patients with growth hormone-secreting pituitary adenoma (GHPA) fail to achieve biochemical remission, warranting investigation into epigenetic and molecular signatures associated with tumorigenesis and hormonal secretion. Prior work exploring the DNA methylome showed Myc-Associated Protein X (MAX), a transcription factor involved in cell cycle regulation, was differentially methylated between GHPA and nonfunctional pituitary adenoma (NFPA). We aimed to validate the differential DNA methylation and related MAX protein expression profiles between NFPA and GHPA. METHODS: DNA methylation levels were measured in 52 surgically resected tumors (37 NFPA, 15 GHPA) at ~100,000 known MAX binding sites derived using ChIP-seq analysis from ENCODE. Findings were correlated with MAX protein expression using a constructed tissue microarray (TMA). Gene ontology analysis was performed to explore downstream genetic and signaling pathways regulated by MAX. RESULTS: GHPA had more hypomethylation events across all known MAX binding sites. Of binding sites defined using ChIP-seq analysis, 1,551 sites had significantly different methylation patterns between the two cohorts; 432 occurred near promoter regions potentially regulated by MAX, including promoters of TNF and MMP9. Gene ontology analysis suggested enrichment in genes involved in oxygen response, immune system regulation, and cell proliferation. Thirteen MAX binding sites were within coding regions of genes. GHPA demonstrated significantly increased expression of MAX protein compared to NFPA. CONCLUSION: GHPA have significantly different DNA methylation and downstream protein expression levels of MAX compared to NFPA. These differences may influence mechanisms involved with cellular proliferation, tumor invasion and hormonal secretion.

Association of Relative Cerebral Blood Volume from Dynamic Susceptibility Contrast-Enhanced Perfusion MR with HER2 Status in Breast Cancer Brain Metastases.

RATIONALE AND OBJECTIVES: With the development of HER2-directed therapies, identifying non-invasive imaging biomarkers of HER2 expression in breast cancer brain metastases has become increasingly important. The purpose of this study was to investigate whether relative cerebral blood volume (rCBV) from dynamic susceptibility contrast-enhanced (DSC) perfusion MR could help identify the HER2 status of breast cancer brain metastases. MATERIALS AND METHODS: With IRB approval for this HIPAA-compliant cross-sectional study and a waiver of informed consent, we queried our institution's electronic medical record to derive a cohort of 14 histologically proven breast cancer brain metastases with preoperative DSC perfusion MR and HER2 analyses of the resected/biopsied brain specimens from 2011-2021. The rCBV of the lesions was measured and compared using Mann-Whitney tests. Receiver operating characteristic analyses were performed to evaluate the performance of rCBV in identifying HER2 status. RESULTS: The study cohort was comprised of 14 women with a mean age of 56 years (range: 32-81 years) with a total of 14 distinct lesions. The rCBV of HER2-positive breast cancer brain metastases was significantly greater than the rCBV of HER2-negative lesions (8.02 vs 3.97, U=48.00, p=0.001). rCBV differentiated HER2-positive lesions from HER2-negative lesions with an area under the curve of 0.98 (standard error=0.032, p<0.001). The accuracy-maximizing rCBV threshold (4.8) was associated with an accuracy of 93% (13/14), a sensitivity of 100% (7/7), and a specificity of 86% (6/7). CONCLUSION: rCBV may assist in identifying the HER2 status of breast cancer brain metastases, if validated in a large prospective trial.

MR multitasking-based dynamic imaging for cerebrovascular evaluation (MT-DICE): Simultaneous quantification of permeability and leakage-insensitive perfusion by dynamic T 1 / T 2 * mapping.

PURPOSE: To develop an MR multitasking-based dynamic imaging for cerebrovascular evaluation (MT-DICE) technique for simultaneous quantification of permeability and leakage-insensitive perfusion with a single-dose contrast injection. METHODS: MT-DICE builds on a saturation-recovery prepared multi-echo fast low-angle shot sequence. The k-space is randomly sampled for 7.6 min, with single-dose contrast agent injected 1.5 min into the scan. MR multitasking is used to model the data into six dimensions, including three spatial dimensions for whole-brain coverage, a saturation-recovery time dimension, and a TE dimension for dynamic T 1 $$ {\mathrm{T}}_1 $$ and T 2 * $$ {\mathrm{T}}_2^{\ast } $$ quantification, respectively, and a contrast dynamics dimension for capturing contrast kinetics. The derived pixel-wise T 1 / T 2 * $$ {\mathrm{T}}_1/{\mathrm{T}}_2^{\ast } $$ time series are converted into contrast concentration-time curves for calculation of kinetic metrics. The technique was assessed for its agreement with reference methods in T 1 $$ {\mathrm{T}}_1 $$ and T 2 * $$ {\mathrm{T}}_2^{\ast } $$ measurements in eight healthy subjects and, in three of them, inter-session repeatability of permeability and leakage-insensitive perfusion parameters. Its feasibility was also demonstrated in four patients with brain tumors. RESULTS: MT-DICE T 1 / T 2 * $$ {\mathrm{T}}_1/{\mathrm{T}}_2^{\ast } $$ values of normal gray matter and white matter were in excellent agreement with reference values (intraclass correlation coefficients = 0.860/0.962 for gray matter and 0.925/0.975 for white matter ). Both permeability and perfusion parameters demonstrated good to excellent intersession agreement with the lowest intraclass correlation coefficients at 0.694. Contrast kinetic parameters in all healthy subjects and patients were within the literature range. CONCLUSION: Based on dynamic T 1 / T 2 * $$ {\mathrm{T}}_1/{\mathrm{T}}_2^{\ast } $$ mapping, MT-DICE allows for simultaneous quantification of permeability and leakage-insensitive perfusion metrics with a single-dose contrast injection.

Structural and practical identifiability of contrast transport models for DCE-MRI.

Compartment models are widely used to quantify blood flow and transport in dynamic contrast-enhanced magnetic resonance imaging. These models analyze the time course of the contrast agent concentration, providing diagnostic and prognostic value for many biological systems. Thus, ensuring accuracy and repeatability of the model parameter estimation is a fundamental concern. In this work, we analyze the structural and practical identifiability of a class of nested compartment models pervasively used in analysis of MRI data. We combine artificial and real data to study the role of noise in model parameter estimation. We observe that although all the models are structurally identifiable, practical identifiability strongly depends on the data characteristics. We analyze the impact of increasing data noise on parameter identifiability and show how the latter can be recovered with increased data quality. To complete the analysis, we show that the results do not depend on specific tissue characteristics or the type of enhancement patterns of contrast agent signal.

Ultra-high field 7 T MRI localizes regional brain volume recovery following corticotroph adenoma resection and hormonal remission in Cushing's disease: A case series.

Background: Cushing's disease (CD) is defined by glucocorticoid excess secondary to the increased section of corticotropin by a pituitary adenoma. Magnetic resonance imaging (MRI) studies performed at 1.5 or 3 Tesla (T) have demonstrated correlations between regional changes in brain structure and the progression of CD. In this report, we examine the changes in brain volume following corticotroph pituitary adenoma resection using ultra-high field 7 T MRI to increase the accuracy of our volumetric analyses. Methods: Thirteen patients were referred to the endocrinology clinic at our institution from 2017 to 2020 with symptoms of cortisol excess and were diagnosed with ACTH-dependent endogenous Cushing syndrome. Five patients had follow-up 7 T imaging at varying time points after a transsphenoidal resection. Results: Symmetrized percent change in regional volumes demonstrated a postoperative increase in cortical volume that was relatively larger than that of cerebral white matter or subcortical gray matter (percent changes = 0.0172%, 0.0052%, and 0.0120%, respectively). In the left cerebral hemisphere, the medial orbitofrontal, lateral orbitofrontal, and pars opercularis cortical regions experienced the most robust postoperative percent increases (percent changes = 0.0166%, 0.0122%, and 0.0068%, respectively). In the right cerebral hemisphere, the largest percent increases were observed in the pars triangularis, rostral portion of the middle frontal gyrus, and superior frontal gyrus (percent changes = 0.0156%, 0.0120%, and 0.0158%). Conclusion: Cerebral volume recovery following pituitary adenoma resection is driven by changes in cortical thickness predominantly in the frontal lobe, while subcortical white and gray matter volumes increase more modestly.

Chronic Stroke Sensorimotor Impairment Is Related to Smaller Hippocampal Volumes: An ENIGMA Analysis.

Background Persistent sensorimotor impairments after stroke can negatively impact quality of life. The hippocampus is vulnerable to poststroke secondary degeneration and is involved in sensorimotor behavior but has not been widely studied within the context of poststroke upper-limb sensorimotor impairment. We investigated associations between non-lesioned hippocampal volume and upper limb sensorimotor impairment in people with chronic stroke, hypothesizing that smaller ipsilesional hippocampal volumes would be associated with greater sensorimotor impairment. Methods and Results Cross-sectional T1-weighted magnetic resonance images of the brain were pooled from 357 participants with chronic stroke from 18 research cohorts of the ENIGMA (Enhancing NeuoImaging Genetics through Meta-Analysis) Stroke Recovery Working Group. Sensorimotor impairment was estimated from the FMA-UE (Fugl-Meyer Assessment of Upper Extremity). Robust mixed-effects linear models were used to test associations between poststroke sensorimotor impairment and hippocampal volumes (ipsilesional and contralesional separately; Bonferroni-corrected, P<0.025), controlling for age, sex, lesion volume, and lesioned hemisphere. In exploratory analyses, we tested for a sensorimotor impairment and sex interaction and relationships between lesion volume, sensorimotor damage, and hippocampal volume. Greater sensorimotor impairment was significantly associated with ipsilesional (P=0.005; ß=0.16) but not contralesional (P=0.96; ß=0.003) hippocampal volume, independent of lesion volume and other covariates (P=0.001; ß=0.26). Women showed progressively worsening sensorimotor impairment with smaller ipsilesional (P=0.008; ß=-0.26) and contralesional (P=0.006; ß=-0.27) hippocampal volumes compared with men. Hippocampal volume was associated with lesion size (P<0.001; ß=-0.21) and extent of sensorimotor damage (P=0.003; ß=-0.15). Conclusions The present study identifies novel associations between chronic poststroke sensorimotor impairment and ipsilesional hippocampal volume that are not caused by lesion size and may be stronger in women.

Association between socioeconomic status and presenting characteristics and extent of disease in patients with surgically resected nonfunctioning pituitary adenoma.

OBJECTIVE: The aim of this study was to evaluate the association between zip code-level socioeconomic status (SES) and presenting characteristics and short-term clinical outcomes in patients with nonfunctioning pituitary adenoma (NFPA). METHODS: A retrospective review of prospectively collected data from the University of Southern California Pituitary Center was conducted to identify all patients undergoing surgery for pituitary adenoma (PA) from 2000 to 2021 and included all patients with NFPA with recorded zip codes at the time of surgery. A normalized socioeconomic metric by zip code was then constructed using data from the American Community Survey estimates, which was categorized into tertiles. Multiple imputation was used for missing data, and multivariable linear and logistic regression models were constructed to estimate mean differences and multivariable-adjusted odds ratios for the association between zip code-level SES and presenting characteristics and outcomes. RESULTS: A total of 637 patients were included in the overall analysis. Compared with patients in the lowest SES tertile, those in the highest tertile were more likely to be treated at a private (rather than safety net) hospital, and were less likely to present with headache, vision loss, and apoplexy. After multivariable adjustment for age, sex, and prior surgery, SES in the highest compared with lowest tertile was inversely associated with tumor size at diagnosis (-4.9 mm, 95% CI -7.2 to -2.6 mm, p < 0.001) and was positively associated with incidental diagnosis (multivariable-adjusted OR 1.72, 95% CI 1.02-2.91). Adjustment for hospital (private vs safety net) attenuated the observed associations, but disparities by SES remained statistically significant for tumor size. Despite substantial differences at presentation, there were no significant differences in length of stay or odds of an uncomplicated procedure by zip code-level SES. Patients from lower-SES zip codes were more likely to require postoperative steroid replacement and less likely to achieve gross-total resection. CONCLUSIONS: In this series, lower zip code-level SES was associated with more severe disease at the time of diagnosis for NFPA patients, including larger tumor size and lower rates of incidental diagnosis. Despite these differences at presentation, no significant differences were observed in short-term postoperative complications, although patients with higher zip code-level SES had higher rates of gross-total resection.

Growth hormone secreting pituitary adenomas show distinct extrasellar extension patterns compared to nonfunctional pituitary adenomas.

PURPOSE: Patterns of extension of pituitary adenomas (PA) may vary according to PA subtype. Understanding extrasellar extension patterns in growth hormone PAs (GHPA) vis-a-vis nonfunctional PAs (NFPAs) may provide insights into the biology of GHPA and future treatment avenues. METHODS: Preoperative MR imaging (MRI) in 179 consecutive patients treated surgically for NFPA (n = 139) and GHPA (n = 40) were analyzed to determine patterns of extrasellar growth. Extension was divided into two principal directions: cranio-caudal (measured by infrasellar/suprasellar extension), and lateral cavernous sinus invasion (CSI) determined by Knosp grading score of 3-4. Suprasellar extension was defined as tumor extension superior to the tuberculum sellae- dorsum sellae line, and inferior extension as invasion through the sellar floor into the sphenoid sinus or clivus. Categorical analysis was performed using Fisher's exact test. RESULTS: GHPAs were overall more likely to remain purely intrasellar compared to NFPA (50% vs 26%, p < 0.001). GHPAs, however, were 7 times more likely to exhibit isolated infrasellar extension compared to NFPA (20% vs 2.8%, p = 0.001). Conversely, NFPAs were twice as likely to exhibit isolated suprasellar extension compared to GHPA (60% vs 28%, p < 0.001), as well as combined suprasellar/infrasellar extension (25% vs 3%, p = 0.011). There were no overall differences in CSI between the two subgroups. DISCUSSION: GHPA and NFPA demonstrate distinct extrasellar extension patterns on MRI. GHPAs show proclivity for inferior extension with bony invasion, whereas NFPAs are more likely to exhibit suprasellar extension through the diaphragmatic aperture. These distinctions may have implications into the biology and future treatment of PAs.

Minocycline decreases blood-brain barrier permeability following aneurysmal subarachnoid hemorrhage: a randomized, double-blind, controlled trial.

OBJECTIVE: Aneurysmal subarachnoid hemorrhage (aSAH)-induced vasospasm is linked to increased inflammatory cell trafficking across a permeable blood-brain barrier (BBB). Elevations in serum levels of matrix metalloprotease 9 (MMP9), a BBB structural protein, have been implicated in the pathogenesis of vasospasm onset. Minocycline is a potent inhibitor of MMP9. The authors sought to detect an effect of minocycline on BBB permeability following aSAH. METHODS: Patients presenting within 24 hours of symptom onset with imaging confirmed aSAH (Fisher grade 3 or 4) were randomized to high-dose (10 mg/kg) minocycline or placebo. The primary outcome of interest was BBB permeability as quantitated by contrast signal intensity ratios in vascular regions of interest on postbleed day (PBD) 5 magnetic resonance permeability imaging. Secondary outcomes included serum MMP9 levels and radiographic and clinical evidence of vasospasm. RESULTS: A total of 11 patients were randomized to minocycline (n = 6) or control (n = 5) groups. No adverse events or complications attributable to minocycline were reported. High-dose minocycline administration was associated with significantly lower permeability indices on imaging analysis (p < 0.01). There was no significant difference with respect to serum MMP9 levels between groups, although concentrations trended upward in both cohorts. Radiographic vasospasm was noted in 6 patients (minocycline = 3, control = 3), with only 1 patient developing symptoms of clinical vasospasm in the minocycline cohort. There was no difference between cohorts with respect to Lindegaard ratios, transcranial Doppler values, or onset of vasospasm. CONCLUSIONS: Minocycline at high doses is well tolerated in the ruptured cerebral aneurysm population. Minocycline curtails breakdown of the BBB following aSAH as evidenced by lower permeability indices, though minocycline did not significantly alter serum MMP9 levels. Larger randomized clinical trials are needed to assess minocycline as a neuroprotectant against aSAH-induced vasospasm. Clinical trial registration no.: NCT04876638 (clinicaltrials.gov).

5-Aminolevulinic acid-enhanced fluorescence-guided treatment of high-grade glioma using angled endoscopic blue light visualization: technical case series with preliminary follow-up.

OBJECTIVE: 5-Aminolevulinic acid (5-ALA)-enhanced fluorescence-guided resection of high-grade glioma (HGG) using microscopic blue light visualization offers the ability to improve extent of resection (EOR); however, few descriptions of HGG resection performed using endoscopic blue light visualization are currently available. In this report, the authors sought to describe their surgical experience and patient outcomes of 5-ALA-enhanced fluorescence-guided resection of HGG using primary or adjunctive endoscopic blue light visualization. METHODS: The authors performed a retrospective review of prospectively collected data from 30 consecutive patients who underwent 5-ALA-enhanced fluorescence-guided biopsy or resection of newly diagnosed HGG was performed. Patient demographic data, tumor characteristics, surgical technique, EOR, tumor fluorescence patterns, and progression-free survival were recorded. RESULTS: In total, 30 newly diagnosed HGG patients were included for analysis. The endoscope was utilized for direct 5-ALA-guided port-based biopsy (n = 9), microscopic to endoscopic (M2E; n = 18) resection, or exoscopic to endoscopic (E2E; n = 3) resection. All endoscopic biopsies of fluorescent tissue were diagnostic. 5-ALA-enhanced tumor fluorescence was visible in all glioblastoma cases, but only in 50% of anaplastic astrocytoma cases and no anaplastic oligodendroglioma cases. Gross-total resection (GTR) was achieved in 10 patients in whom complete resection was considered safe, with 11 patients undergoing subtotal resection. In all cases, endoscopic fluorescence was more avid than microscopic fluorescence. The endoscope offered the ability to diagnose and resect additional tumor not visualized by the microscope in 83.3% (n = 10/12) of glioblastoma cases, driven by angled lenses and increased fluorescence facilitated by light source delivery within the cavity. Mean volumetric EOR was 90.7% in all resection patients and 98.8% in patients undergoing planned GTR. No complications were attributable to 5-ALA or blue light endoscopy. CONCLUSIONS: The blue light endoscope is a viable primary or adjunctive visualization platform for optimization of 5-ALA-enhanced HGG fluorescence. Implementation of the blue light endoscope to guide resection of HGG glioma is feasible and ergonomically favorable, with a potential advantage of enabling increased detection of tumor fluorescence in deep surgical cavities compared to the microscope.

Voxelwise Prediction of Recurrent High-Grade Glioma via Proximity Estimation-Coupled Multidimensional Support Vector Machine.

PURPOSE: To provide early and localized glioblastoma (GBM) recurrence prediction, we introduce a novel postsurgery multiparametric magnetic resonance-based support vector machine (SVM) method coupling with stem cell niche (SCN) proximity estimation. METHODS AND MATERIALS: This study used postsurgery magnetic resonance imaging (MRI) scans from 50 patients with recurrent GBM, obtained approximately 2 months before clinically diagnosed recurrence. The main prediction pipeline consisted of a proximity-based estimator to identify regions with high risk of recurrence (HRRs) and an SVM classifier to provide voxelwise prediction in HRRs. The HRRs were estimated using the weighted sum of inverse distances to 2 possible origins of recurrence-the SCN and the tumor cavity. Subsequently, multiparametric voxels (from T1, T1 contrast-enhanced, fluid-attenuated inversion recovery, T2, and apparent diffusion coefficient) within the HRR were grouped into recurrent (warped from the clinical diagnosis) and nonrecurrent subregions and fed into the proximity estimation-coupled SVM classifier (SVMPE). The cohort was randomly divided into 40% and 60% for training and testing, respectively. The trained SVMPE was then extrapolated to an earlier time point for earlier recurrence prediction. As an exploratory analysis, the SVMPE predictive cluster sizes and the image intensities from the 5 magnetic resonance sequences were compared across time to assess the progressive subclinical traces. RESULTS: On 2-month prerecurrence MRI scans from 30 test cohort patients, the SVMPE classifier achieved a recall of 0.80, a precision of 0.69, an F1-score of 0.73, and a mean boundary distance of 7.49 mm. Exploratory analysis at early time points showed spatially consistent but significantly smaller subclinical clusters and significantly increased T1 contrast-enhanced and apparent diffusion coefficient values over time. CONCLUSIONS: We demonstrated a novel voxelwise early prediction method, SVMPE, for GBM recurrence based on clinical follow-up MR scans. The SVMPE is promising in localizing subclinical traces of recurrence 2 months ahead of clinical diagnosis and may be used to guide more effective personalized early salvage therapy.