From molecular signatures to radiomics: tailoring neurooncological strategies through forecasting of glioma growth.

OBJECTIVE: Contemporary oncological paradigms for adjuvant treatment of low- and intermediate-grade gliomas are often guided by a limited array of parameters, overlooking the dynamic nature of the disease. The authors' aim was to develop a comprehensive multivariate glioma growth model based on multicentric data, to facilitate more individualized therapeutic strategies. METHODS: Random slope models with subject-specific random intercepts were fitted to a retrospective cohort of grade II and III gliomas from the database at Kepler University Hospital (n = 191) to predict future mean tumor diameters. Deep learning-based radiomics was used together with a comprehensive clinical dataset and evaluated on an external prospectively collected validation cohort from University Hospital Zurich (n = 9). Prediction quality was assessed via mean squared prediction error. RESULTS: A mean squared prediction error of 0.58 cm for the external validation cohort was achieved, indicating very good prognostic value. The mean ± SD time to adjuvant therapy was 28.7 ± 43.3 months and 16.1 ± 14.6 months for the training and validation cohort, respectively, with a mean of 6.2 ± 5 and 3.6 ± 0.7, respectively, for number of observations. The observed mean tumor diameter per year was 0.38 cm (95% CI 0.25-0.51) for the training cohort, and 1.02 cm (95% CI 0.78-2.82) for the validation cohort. Glioma of the superior frontal gyrus showed a higher rate of tumor growth than insular glioma. Oligodendroglioma showed less pronounced growth, anaplastic astrocytoma-unlike anaplastic oligodendroglioma-was associated with faster tumor growth. Unlike the impact of extent of resection, isocitrate dehydrogenase (IDH) had negligible influence on tumor growth. Inclusion of radiomics variables significantly enhanced the prediction performance of the random slope model used. CONCLUSIONS: The authors developed an advanced statistical model to predict tumor volumes both pre- and postoperatively, using comprehensive data prior to the initiation of adjuvant therapy. Using radiomics enhanced the precision of the prediction models. Whereas tumor extent of resection and topology emerged as influential factors in tumor growth, the IDH status did not. This study emphasizes the imperative of advanced computational methods in refining personalized low-grade glioma treatment, advocating a move beyond traditional paradigms.

Whole Spine Segmentation Using Object Detection and Semantic Segmentation.

OBJECTIVE: Virtual and augmented reality have enjoyed increased attention in spine surgery. Preoperative planning, pedicle screw placement, and surgical training are among the most studied use cases. Identifying osseous structures is a key aspect of navigating a 3-dimensional virtual reconstruction. To automate the otherwise time-consuming process of labeling vertebrae on each slice individually, we propose a fully automated pipeline that automates segmentation on computed tomography (CT) and which can form the basis for further virtual or augmented reality application and radiomic analysis. METHODS: Based on a large public dataset of annotated vertebral CT scans, we first trained a YOLOv8m (You-Only-Look-Once algorithm, Version 8 and size medium) to detect each vertebra individually. On the then cropped images, a 2D-U-Net was developed and externally validated on 2 different public datasets. RESULTS: Two hundred fourteen CT scans (cervical, thoracic, or lumbar spine) were used for model training, and 40 scans were used for external validation. Vertebra recognition achieved a mAP50 (mean average precision with Jaccard threshold of 0.5) of over 0.84, and the segmentation algorithm attained a mean Dice score of 0.75 ± 0.14 at internal, 0.77 ± 0.12 and 0.82 ± 0.14 at external validation, respectively. CONCLUSION: We propose a 2-stage approach consisting of single vertebra labeling by an object detection algorithm followed by semantic segmentation. In our externally validated pilot study, we demonstrate robust performance for our object detection network in identifying individual vertebrae, as well as for our segmentation model in precisely delineating the bony structures.

TomoRay: Generating Synthetic Computed Tomography of the Spine From Biplanar Radiographs.

OBJECTIVE: Computed tomography (CT) imaging is a cornerstone in the assessment of patients with spinal trauma and in the planning of spinal interventions. However, CT studies are associated with logistical problems, acquisition costs, and radiation exposure. In this proof-of-concept study, the feasibility of generating synthetic spinal CT images using biplanar radiographs was explored. This could expand the potential applications of x-ray machines pre-, post-, and even intraoperatively. METHODS: A cohort of 209 patients who underwent spinal CT imaging from the VerSe2020 dataset was used to train the algorithm. The model was subsequently evaluated using an internal and external validation set containing 55 from the VerSe2020 dataset and a subset of 56 images from the CTSpine1K dataset, respectively. Digitally reconstructed radiographs served as input for training and evaluation of the 2-dimensional (2D)-to-3-dimentional (3D) generative adversarial model. Model performance was assessed using peak signal to noise ratio (PSNR), structural similarity index (SSIM), and cosine similarity (CS). RESULTS: At external validation, the developed model achieved a PSNR of 21.139 ± 1.018 dB (mean ± standard deviation). The SSIM and CS amounted to 0.947 ± 0.010 and 0.671 ± 0.691, respectively. CONCLUSION: Generating an artificial 3D output from 2D imaging is challenging, especially for spinal imaging, where x-rays are known to deliver insufficient information frequently. Although the synthetic CT scans derived from our model do not perfectly match their ground truth CT, our proof-of-concept study warrants further exploration of the potential of this technology.

Automated volumetric assessment of pituitary adenoma.

PURPOSE: Assessment of pituitary adenoma (PA) volume and extent of resection (EOR) through manual segmentation is time-consuming and likely suffers from poor interrater agreement, especially postoperatively. Automated tumor segmentation and volumetry by use of deep learning techniques may provide more objective and quick volumetry. METHODS: We developed an automated volumetry pipeline for pituitary adenoma. Preoperative and three-month postoperative T1-weighted, contrast-enhanced magnetic resonance imaging (MRI) with manual segmentations were used for model training. After adequate preprocessing, an ensemble of convolutional neural networks (CNNs) was trained and validated for preoperative and postoperative automated segmentation of tumor tissue. Generalization was evaluated on a separate holdout set. RESULTS: In total, 193 image sets were used for training and 20 were held out for validation. At validation using the holdout set, our models (preoperative / postoperative) demonstrated a median Dice score of 0.71 (0.27) / 0 (0), a mean Jaccard score of 0.53 ± 0.21/0.030 ± 0.085 and a mean 95th percentile Hausdorff distance of 3.89 ± 1.96./12.199 ± 6.684. Pearson's correlation coefficient for volume correlation was 0.85 / 0.22 and -0.14 for extent of resection. Gross total resection was detected with a sensitivity of 66.67% and specificity of 36.36%. CONCLUSIONS: Our volumetry pipeline demonstrated its ability to accurately segment pituitary adenomas. This is highly valuable for lesion detection and evaluation of progression of pituitary incidentalomas. Postoperatively, however, objective and precise detection of residual tumor remains less successful. Larger datasets, more diverse data, and more elaborate modeling could potentially improve performance.

Development and external validation of clinical prediction models for pituitary surgery.

Introduction: Gross total resection (GTR), Biochemical Remission (BR) and restitution of a priorly disrupted hypothalamus pituitary axis (new improvement, IMP) are important factors in pituitary adenoma (PA) resection surgery. Prediction of these metrics using simple and preoperatively available data might help improve patient care and contribute to a more personalized medicine. Research question: This study aims to develop machine learning models predicting GTR, BR, and IMP in PA resection surgery, using preoperatively available data. Material and methods: With data from patients undergoing endoscopic transsphenoidal surgery for PAs machine learning models for prediction of GTR, BR and IMP were developed and externally validated. Development was carried out on a registry from Bologna, Italy while external validation was conducted using patient data from Zurich, Switzerland. Results: The model development cohort consisted of 1203 patients. GTR was achieved in 207 (17.2%, 945 (78.6%) missing), BR in 173 (14.4%, 992 (82.5%) missing) and IMP in 208 (17.3%, 167 (13.9%) missing) cases. In the external validation cohort 206 patients were included and GTR was achieved in 121 (58.7%, 32 (15.5%) missing), BR in 46 (22.3%, 145 (70.4%) missing) and IMP in 42 (20.4%, 7 (3.4%) missing) cases. The AUC at external validation amounted to 0.72 (95% CI: 0.63-0.80) for GTR, 0.69 (0.52-0.83) for BR, as well as 0.82 (0.76-0.89) for IMP. Discussion and conclusion: All models showed adequate generalizability, performing similarly in training and external validation, confirming the possible potentials of machine learning in helping to adapt surgical therapy to the individual patient.

DeepEOR: automated perioperative volumetric assessment of variable grade gliomas using deep learning.

PURPOSE: Volumetric assessments, such as extent of resection (EOR) or residual tumor volume, are essential criterions in glioma resection surgery. Our goal is to develop and validate segmentation machine learning models for pre- and postoperative magnetic resonance imaging scans, allowing us to assess the percentagewise tumor reduction after intracranial surgery for gliomas. METHODS: For the development of the preoperative segmentation model (U-Net), MRI scans of 1053 patients from the Multimodal Brain Tumor Segmentation Challenge (BraTS) 2021 as well as from patients who underwent surgery at the University Hospital in Zurich were used. Subsequently, the model was evaluated on a holdout set containing 285 images from the same sources. The postoperative model was developed using 72 scans and validated on 45 scans obtained from the BraTS 2015 and Zurich dataset. Performance is evaluated using Dice Similarity score, Jaccard coefficient and Hausdorff 95%. RESULTS: We were able to achieve an overall mean Dice Similarity Score of 0.59 and 0.29 on the pre- and postoperative holdout sets, respectively. Our algorithm managed to determine correct EOR in 44.1%. CONCLUSION: Although our models are not suitable for clinical use at this point, the possible applications are vast, going from automated lesion detection to disease progression evaluation. Precise determination of EOR is a challenging task, but we managed to show that deep learning can provide fast and objective estimates.

Machine learning-based clinical outcome prediction in surgery for acromegaly.

PURPOSE: Biochemical remission (BR), gross total resection (GTR), and intraoperative cerebrospinal fluid (CSF) leaks are important metrics in transsphenoidal surgery for acromegaly, and prediction of their likelihood using machine learning would be clinically advantageous. We aim to develop and externally validate clinical prediction models for outcomes after transsphenoidal surgery for acromegaly. METHODS: Using data from two registries, we develop and externally validate machine learning models for GTR, BR, and CSF leaks after endoscopic transsphenoidal surgery in acromegalic patients. For the model development a registry from Bologna, Italy was used. External validation was then performed using data from Zurich, Switzerland. Gender, age, prior surgery, as well as Hardy and Knosp classification were used as input features. Discrimination and calibration metrics were assessed. RESULTS: The derivation cohort consisted of 307 patients (43.3% male; mean [SD] age, 47.2 [12.7] years). GTR was achieved in 226 (73.6%) and BR in 245 (79.8%) patients. In the external validation cohort with 46 patients, 31 (75.6%) achieved GTR and 31 (77.5%) achieved BR. Area under the curve (AUC) at external validation was 0.75 (95% confidence interval: 0.59-0.88) for GTR, 0.63 (0.40-0.82) for BR, as well as 0.77 (0.62-0.91) for intraoperative CSF leaks. While prior surgery was the most important variable for prediction of GTR, age, and Hardy grading contributed most to the predictions of BR and CSF leaks, respectively. CONCLUSIONS: Gross total resection, biochemical remission, and CSF leaks remain hard to predict, but machine learning offers potential in helping to tailor surgical therapy. We demonstrate the feasibility of developing and externally validating clinical prediction models for these outcomes after surgery for acromegaly and lay the groundwork for development of a multicenter model with more robust generalization.