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Physics-Regularized Multi-Modal Image Assimilation for Brain Tumor Localization

Neural Information Processing Systems

Physical models in the form of partial differential equations serve as important priors for many under-constrained problems. One such application is tumor treatment planning, which relies on accurately estimating the spatial distribution of tumor cells within a patient's anatomy. While medical imaging can detect the bulk of a tumor, it cannot capture the full extent of its spread, as low-concentration tumor cells often remain undetectable, particularly in glioblastoma, the most common primary brain tumor. Machine learning approaches struggle to estimate the complete tumor cell distribution due to a lack of appropriate training data. Consequently, most existing methods rely on physics-based simulations to generate anatomically and physiologically plausible estimations. However, these approaches face challenges with complex and unknown initial conditions and are constrained by overly rigid physical models. In this work, we introduce a novel method that integrates data-driven and physics-based cost functions, akin to Physics-Informed Neural Networks (PINNs).


Generative design and validation of therapeutic peptides for glioblastoma based on a potential target ATP5A

Qian, Hao, You, Pu, Zeng, Lin, Zhou, Jingyuan, Huang, Dengdeng, Li, Kaicheng, Tu, Shikui, Xu, Lei

arXiv.org Artificial Intelligence

Glioblastoma (GBM) remains the most aggressive tumor, urgently requiring novel therapeutic strategies. Here, we present a dry-to-wet framework combining generative modeling and experimental validation to optimize peptides targeting ATP5A, a potential peptide-binding protein for GBM. Our framework introduces the first lead-conditioned generative model, which focuses exploration on geometrically relevant regions around lead peptides and mitigates the combinatorial complexity of de novo methods. Specifically, we propose POTFlow, a \underline{P}rior and \underline{O}ptimal \underline{T}ransport-based \underline{Flow}-matching model for peptide optimization. POTFlow employs secondary structure information (e.g., helix, sheet, loop) as geometric constraints, which are further refined by optimal transport to produce shorter flow paths. With this design, our method achieves state-of-the-art performance compared with five popular approaches. When applied to GBM, our method generates peptides that selectively inhibit cell viability and significantly prolong survival in a patient-derived xenograft (PDX) model. As the first lead peptide-conditioned flow matching model, POTFlow holds strong potential as a generalizable framework for therapeutic peptide design.


DeepVRegulome: DNABERT-based deep-learning framework for predicting the functional impact of short genomic variants on the human regulome

Dutta, Pratik, Obusan, Matthew, Sathian, Rekha, Chao, Max, Surana, Pallavi, Papineni, Nimisha, Ji, Yanrong, Zhou, Zhihan, Liu, Han, Yurovsky, Alisa, Davuluri, Ramana V

arXiv.org Artificial Intelligence

Whole-genome sequencing (WGS) has revealed numerous non-coding short variants whose functional impacts remain poorly understood. Despite recent advances in deep-learning genomic approaches, accurately predicting and prioritizing clinically relevant mutations in gene regulatory regions remains a major challenge. Here we introduce Deep VRegulome, a deep-learning method for prediction and interpretation of functionally disruptive variants in the human regulome, which combines 700 DNABERT fine-tuned models, trained on vast amounts of ENCODE gene regulatory regions, with variant scoring, motif analysis, attention-based visualization, and survival analysis. We showcase its application on TCGA glioblastoma WGS dataset in prioritizing survival-associated mutations and regulatory regions. The analysis identified 572 splice-disrupting and 9,837 transcription-factor binding site altering mutations occurring in greater than 10% of glioblastoma samples. Survival analysis linked 1352 mutations and 563 disrupted regulatory regions to patient outcomes, enabling stratification via non-coding mutation signatures. All the code, fine-tuned models, and an interactive data portal are publicly available.


PREDICT-GBM: Platform for Robust Evaluation and Development of Individualized Computational Tumor Models in Glioblastoma

Zimmer, L., Weidner, J., Balcerak, M., Kofler, F., Ezhov, I., Menze, B., Wiestler, B.

arXiv.org Artificial Intelligence

Glioblastoma is the most prevalent primary brain malignancy, distinguished by its highly invasive behavior and exceptionally high rates of recurrence. Conventional radiation therapy, which employs uniform treatment margins, fails to account for patient-specific anatomical and biological factors that critically influence tumor cell migration. To address this limitation, numerous computational models of glioblastoma growth have been developed, enabling generation of tumor cell distribution maps extending beyond radiographically visible regions and thus informing more precise treatment strategies. However, despite encouraging preliminary findings, the clinical adoption of these growth models remains limited. To bridge this translational gap and accelerate both model development and clinical validation, we introduce PREDICT-GBM, a comprehensive integrated pipeline and dataset for modeling and evaluation. This platform enables systematic benchmarking of state-of-the-art tumor growth models using an expert-curated clinical dataset comprising 255 subjects with complete tumor segmentations and tissue characterization maps. Our analysis demonstrates that personalized radiation treatment plans derived from tumor growth predictions achieved superior recurrence coverage compared to conventional uniform margin approaches for two of the evaluated models. This work establishes a robust platform for advancing and systematically evaluating cutting-edge tumor growth modeling approaches, with the ultimate goal of facilitating clinical translation and improving patient outcomes.


Multimodal Sheaf-based Network for Glioblastoma Molecular Subtype Prediction

Idrissova, Shekhnaz, Rekik, Islem

arXiv.org Artificial Intelligence

Glioblastoma is a highly invasive brain tumor with rapid progression rates. Recent studies have shown that glioblastoma molecular subtype classification serves as a significant biomarker for effective targeted therapy selection. However, this classification currently requires invasive tissue extraction for comprehensive histopathological analysis. Existing multimodal approaches combining MRI and histopathology images are limited and lack robust mechanisms for preserving shared structural information across modalities. In particular, graph-based models often fail to retain discriminative features within heterogeneous graphs, and structural reconstruction mechanisms for handling missing or incomplete modality data are largely underexplored. To address these limitations, we propose a novel sheaf-based framework for structure-aware and consistent fusion of MRI and histopathology data. Our model outperforms baseline methods and demonstrates robustness in incomplete or missing data scenarios, contributing to the development of virtual biopsy tools for rapid diagnostics. Our source code is available at https: //github.com/basiralab/MMSN/.


Physics-Regularized Multi-Modal Image Assimilation for Brain Tumor Localization

Neural Information Processing Systems

Physical models in the form of partial differential equations serve as important priors for many under-constrained problems. One such application is tumor treatment planning, which relies on accurately estimating the spatial distribution of tumor cells within a patient's anatomy. While medical imaging can detect the bulk of a tumor, it cannot capture the full extent of its spread, as low-concentration tumor cells often remain undetectable, particularly in glioblastoma, the most common primary brain tumor. Machine learning approaches struggle to estimate the complete tumor cell distribution due to a lack of appropriate training data. Consequently, most existing methods rely on physics-based simulations to generate anatomically and physiologically plausible estimations. However, these approaches face challenges with complex and unknown initial conditions and are constrained by overly rigid physical models.


MRI Radiomics for IDH Genotype Prediction in Glioblastoma Diagnosis

Kozák, Stanislav

arXiv.org Artificial Intelligence

Radiomics is a relatively new field which utilises automatically identified features from radiological scans. It has found a widespread application, particularly in oncology because many of the important oncological biomarkers are not visible to the naked eye. The recent advent of big data, including in medical imaging, and the development of new ML techniques brought the possibility of faster and more accurate oncological diagnosis. Furthermore, standardised mathematical feature extraction based on radiomics helps to eliminate possible radiologist bias. This paper reviews the recent development in the oncological use of MRI radiomic features. It focuses on the identification of the isocitrate dehydrogenase (IDH) mutation status, which is an important biomarker for the diagnosis of glioblastoma and grade IV astrocytoma.


Brain implants to treat epilepsy, arthritis, or even incontinence? They may be closer than you think

The Guardian

Oran Knowlson, a British teenager with a severe type of epilepsy called Lennox-Gastaut syndrome, became the first person in the world to trial a new brain implant last October, with phenomenal results – his daytime seizures were reduced by 80%. "It's had a huge impact on his life and has prevented him from having the falls and injuring himself that he was having before," says Martin Tisdall, a consultant paediatric neurosurgeon at Great Ormond Street Hospital (Gosh) in London, who implanted the device. "His mother was talking about how he's had such a improvement in his quality of life, but also in his cognition: he's more alert and more engaged." Oran's neurostimulator sits under the skull and sends constant electrical signals deep into his brain with the aim of blocking abnormal impulses that trigger seizures. The implant, called a Picostim and about the size of a mobile phone battery, is recharged via headphones and operates differently between day and night. "The device has the ability to record from the brain, to measure brain activity, and that allows us to think about ways in which we could use that information to improve the efficacy of the stimulation that the kids are getting," says Tisdall. "What we really want to do is to deliver this treatment on the NHS."


Overcoming challenges of translating deep-learning models for glioblastoma: the ZGBM consortium

Shuaib, Haris, Barker, Gareth J, Sasieni, Peter, De Vita, Enrico, Chelliah, Alysha, Andrei, Roman, Ashkan, Keyoumars, Beaumont, Erica, Brazil, Lucy, Rowland-Hill, Chris, Lau, Yue Hui, Luis, Aysha, Powell, James, Swampillai, Angela, Tenant, Sean, Thust, Stefanie C, Wastling, Stephen, Young, Tom, Booth, Thomas C

arXiv.org Artificial Intelligence

Objective: To report imaging protocol and scheduling variance in routine care of glioblastoma patients in order to demonstrate challenges of integrating deep-learning models in glioblastoma care pathways. Additionally, to understand the most common imaging studies and image contrasts to inform the development of potentially robust deep-learning models. Methods: MR imaging data were analysed from a random sample of five patients from the prospective cohort across five participating sites of the ZGBM consortium. Reported clinical and treatment data alongside DICOM header information were analysed to understand treatment pathway imaging schedules. Results: All sites perform all structural imaging at every stage in the pathway except for the presurgical study, where in some sites only contrast-enhanced T1-weighted imaging is performed. Diffusion MRI is the most common non-structural imaging type, performed at every site. Conclusion: The imaging protocol and scheduling varies across the UK, making it challenging to develop machine-learning models that could perform robustly at other centres. Structural imaging is performed most consistently across all centres. Advances in knowledge: Successful translation of deep-learning models will likely be based on structural post-treatment imaging unless there is significant effort made to standardise non-structural or peri-operative imaging protocols and schedules.


Brain Tumor Radiogenomic Classification

Mohamed, Amr, Rabea, Mahmoud, Sameh, Aya, Kamal, Ehab

arXiv.org Artificial Intelligence

Related Work methylation[2] is an important biomarker for glioblastoma[9], the most common and Brain tumor detection from MRI scan has seen aggressive form of brain cancer in adults.By great advancements over the past few years, introducing a Radiogenomic based imaging Abdusalomov et al. [10] proposed a deep method, the process of detecting the presence of learning approach using pre-trained YOLOv7 brain tumor shall be less invasive which will for object detection, Bi-directional Feature eventually improve the survival and prospects of Pyramid Network (BiFPN) for feature patients with brain cancer. Also, knowing the extraction, and Channel and Spatial Attention methylation status helps guide treatment module (CBAM) for improved attention decisions, as tumors with methylation are more mechanisms. Their model achieved a responsive to certain therapies.