Akhil Kondepudi

Todd C. Hollon, Cheng Jiang, Asadur Chowdury et al.

Molecular classification has transformed the management of brain tumors by enabling more accurate prognostication and personalized treatment. However, timely molecular diagnostic testing for patients with brain tumors is limited, complicating surgical and adjuvant treatment and obstructing clinical trial enrollment. In this study, we developed DeepGlioma, a rapid ($< 90$ seconds), artificial-intelligence-based diagnostic screening system to streamline the molecular diagnosis of diffuse gliomas. DeepGlioma is trained using a multimodal dataset that includes stimulated Raman histology (SRH); a rapid, label-free, non-consumptive, optical imaging method; and large-scale, public genomic data. In a prospective, multicenter, international testing cohort of patients with diffuse glioma ($n=153$) who underwent real-time SRH imaging, we demonstrate that DeepGlioma can predict the molecular alterations used by the World Health Organization to define the adult-type diffuse glioma taxonomy (IDH mutation, 1p19q co-deletion and ATRX mutation), achieving a mean molecular classification accuracy of $93.3\pm 1.6\%$. Our results represent how artificial intelligence and optical histology can be used to provide a rapid and scalable adjunct to wet lab methods for the molecular screening of patients with diffuse glioma.

Cheng Jiang, Xinhai Hou, Akhil Kondepudi et al.

Learning high-quality, self-supervised, visual representations is essential to advance the role of computer vision in biomedical microscopy and clinical medicine. Previous work has focused on self-supervised representation learning (SSL) methods developed for instance discrimination and applied them directly to image patches, or fields-of-view, sampled from gigapixel whole-slide images (WSIs) used for cancer diagnosis. However, this strategy is limited because it (1) assumes patches from the same patient are independent, (2) neglects the patient-slide-patch hierarchy of clinical biomedical microscopy, and (3) requires strong data augmentations that can degrade downstream performance. Importantly, sampled patches from WSIs of a patient's tumor are a diverse set of image examples that capture the same underlying cancer diagnosis. This motivated HiDisc, a data-driven method that leverages the inherent patient-slide-patch hierarchy of clinical biomedical microscopy to define a hierarchical discriminative learning task that implicitly learns features of the underlying diagnosis. HiDisc uses a self-supervised contrastive learning framework in which positive patch pairs are defined based on a common ancestry in the data hierarchy, and a unified patch, slide, and patient discriminative learning objective is used for visual SSL. We benchmark HiDisc visual representations on two vision tasks using two biomedical microscopy datasets, and demonstrate that (1) HiDisc pretraining outperforms current state-of-the-art self-supervised pretraining methods for cancer diagnosis and genetic mutation prediction, and (2) HiDisc learns high-quality visual representations using natural patch diversity without strong data augmentations.

Cheng Jiang, Asadur Chowdury, Xinhai Hou et al.

Accurate intraoperative diagnosis is essential for providing safe and effective care during brain tumor surgery. Our standard-of-care diagnostic methods are time, resource, and labor intensive, which restricts access to optimal surgical treatments. To address these limitations, we propose an alternative workflow that combines stimulated Raman histology (SRH), a rapid optical imaging method, with deep learning-based automated interpretation of SRH images for intraoperative brain tumor diagnosis and real-time surgical decision support. Here, we present OpenSRH, the first public dataset of clinical SRH images from 300+ brain tumors patients and 1300+ unique whole slide optical images. OpenSRH contains data from the most common brain tumors diagnoses, full pathologic annotations, whole slide tumor segmentations, raw and processed optical imaging data for end-to-end model development and validation. We provide a framework for patch-based whole slide SRH classification and inference using weak (i.e. patient-level) diagnostic labels. Finally, we benchmark two computer vision tasks: multiclass histologic brain tumor classification and patch-based contrastive representation learning. We hope OpenSRH will facilitate the clinical translation of rapid optical imaging and real-time ML-based surgical decision support in order to improve the access, safety, and efficacy of cancer surgery in the era of precision medicine. Dataset access, code, and benchmarks are available at opensrh.mlins.org.

Yiwei Lyu, Sung Jik Cha, Cheng Jiang et al.

High-quality, high-resolution medical imaging is essential for clinical care. Raman-based biomedical optical imaging uses non-ionizing infrared radiation to evaluate human tissues in real time and is used for early cancer detection, brain tumor diagnosis, and intraoperative tissue analysis. Unfortunately, optical imaging is vulnerable to image degradation due to laser scattering and absorption, which can result in diagnostic errors and misguided treatment. Restoration of optical images is a challenging computer vision task because the sources of image degradation are multi-factorial, stochastic, and tissue-dependent, preventing a straightforward method to obtain paired low-quality/high-quality data. Here, we present Restorative Step-Calibrated Diffusion (RSCD), an unpaired diffusion-based image restoration method that uses a step calibrator model to dynamically determine the number of steps required to complete the reverse diffusion process for image restoration. RSCD outperforms other widely used unpaired image restoration methods on both image quality and perceptual evaluation metrics for restoring optical images. Medical imaging experts consistently prefer images restored using RSCD in blinded comparison experiments and report minimal to no hallucinations. Finally, we show that RSCD improves performance on downstream clinical imaging tasks, including automated brain tumor diagnosis and deep tissue imaging. Our code is available at https://github.com/MLNeurosurg/restorative_step-calibrated_diffusion.

Yiwei Lyu, Chenhui Zhao, Soumyanil Banerjee et al.

Training vision models with language supervision enables general and transferable representations. However, many visual domains, especially non-object-centric domains such as medical imaging and remote sensing, contain itemized text annotations: multiple text items describing distinct and semantically independent findings within a single image. Such supervision differs from standard multi-caption supervision, where captions are redundant or highly overlapping. Here, we introduce ItemizedCLIP, a framework for learning complete and explainable visual representations from itemized text supervision. ItemizedCLIP employs a cross-attention module to produce text item-conditioned visual embeddings and a set of tailored objectives that jointly enforce item independence (distinct regions for distinct items) and representation completeness (coverage of all items). Across four domains with naturally itemized text supervision (brain MRI, head CT, chest CT, remote sensing) and one additional synthetically itemized dataset, ItemizedCLIP achieves substantial improvements in zero-shot performance and fine-grained interpretability over baselines. The resulting ItemizedCLIP representations are semantically grounded, item-differentiable, complete, and visually interpretable. Our code is available at https://github.com/MLNeurosurg/ItemizedCLIP.

Akhil Kondepudi, Akshay Rao, Chenhui Zhao et al.

Frontier artificial intelligence (AI) models, such as OpenAI's GPT-5 and Meta's DINOv3, have advanced rapidly through training on internet-scale public data, yet such systems lack access to private clinical data. Neuroimaging, in particular, is underrepresented in the public domain due to identifiable facial features within MRI and CT scans, fundamentally restricting model performance in clinical medicine. Here, we show that frontier models underperform on neuroimaging tasks and that learning directly from uncurated data generated during routine clinical care at health systems, a paradigm we call health system learning, yields high-performance, generalist neuroimaging models. We introduce NeuroVFM, a visual foundation model trained on 5.24 million clinical MRI and CT volumes using a scalable volumetric joint-embedding predictive architecture. NeuroVFM learns comprehensive representations of brain anatomy and pathology, achieving state-of-the-art performance across multiple clinical tasks, including radiologic diagnosis and report generation. The model exhibits emergent neuroanatomic understanding and interpretable visual grounding of diagnostic findings. When paired with open-source language models through lightweight visual instruction tuning, NeuroVFM generates radiology reports that surpass frontier models in accuracy, clinical triage, and expert preference. Through clinically grounded visual understanding, NeuroVFM reduces hallucinated findings and critical errors, offering safer clinical decision support. These results establish health system learning as a paradigm for building generalist medical AI and provide a scalable framework for clinical foundation models.

Chenhui Zhao, Yiwei Lyu, Asadur Chowdury et al.

The scalability of current language-image pre-training for 3D medical imaging, such as CT and MRI, is constrained by the need for radiologists to manually curate raw clinical studies. In this work, we pioneer pre-training directly on uncurated studies, which both aligns more closely with the radiologist's workflow and provides a natural path to scalability. However, the unique structure of such data presents new challenges for existing model architectures, which were originally designed for 2D slices or single 3D scans. To address this, we introduce a novel hierarchical attention mechanism inspired by the intrinsic hierarchy of radiology data: slice, scan, and study. We denote our framework as Hierarchical attention for Language-Image Pre-training (HLIP). Trained on 220K studies with 3.13 million scans for brain MRI and 240K studies with 1.44 million scans for head CT, HLIP achieves state-of-the-art performance, e.g., +10.5% balanced ACC on the proposed publicly available brain MRI benchmark Pub-Brain-5; +8.3% and +1.7% macro AUC on head CT benchmarks CQ500 and RSNA, respectively. HLIP also exhibits strong generalizability on existing 3D medical language-image pre-training benchmarks, e.g., +4.3% macro AUC on the Rad-ChestCT benchmark when pre-trained on CT-RATE. These results demonstrate that, with HLIP, directly pre-training on uncurated clinical datasets is a scalable and effective direction for language-image pre-training in 3D medical imaging. The code is available at https://github.com/Zch0414/hlip.

Xinhai Hou, Cheng Jiang, Akhil Kondepudi et al.

Whole slide imaging is fundamental to biomedical microscopy and computational pathology. Previously, learning representations for gigapixel-sized whole slide images (WSIs) has relied on multiple instance learning with weak labels, which do not annotate the diverse morphologic features and spatial heterogeneity of WSIs. A high-quality self-supervised learning method for WSIs would provide transferable visual representations for downstream computational pathology tasks, without the need for dense annotations. We present Slide Pre-trained Transformers (SPT) for gigapixel-scale self-supervision of WSIs. Treating WSI patches as tokens, SPT combines data transformation strategies from language and vision modeling into a general and unified framework to generate views of WSIs for self-supervised pretraining. SPT leverages the inherent regional heterogeneity, histologic feature variability, and information redundancy within WSIs to learn high-quality whole slide representations. We benchmark SPT visual representations on five diagnostic tasks across three biomedical microscopy datasets. SPT significantly outperforms baselines for histopathologic diagnosis, cancer subtyping, and genetic mutation prediction. Finally, we demonstrate that SPT consistently improves whole slide representations when using off-the-shelf, in-domain, and foundational patch encoders for whole slide multiple instance learning.

Cheng Jiang, Alexander Gedeon, Yiwei Lyu et al.

Volumetric biomedical microscopy has the potential to increase the diagnostic information extracted from clinical tissue specimens and improve the diagnostic accuracy of both human pathologists and computational pathology models. Unfortunately, barriers to integrating 3-dimensional (3D) volumetric microscopy into clinical medicine include long imaging times, poor depth / z-axis resolution, and an insufficient amount of high-quality volumetric data. Leveraging the abundance of high-resolution 2D microscopy data, we introduce masked slice diffusion for super-resolution (MSDSR), which exploits the inherent equivalence in the data-generating distribution across all spatial dimensions of biological specimens. This intrinsic characteristic allows for super-resolution models trained on high-resolution images from one plane (e.g., XY) to effectively generalize to others (XZ, YZ), overcoming the traditional dependency on orientation. We focus on the application of MSDSR to stimulated Raman histology (SRH), an optical imaging modality for biological specimen analysis and intraoperative diagnosis, characterized by its rapid acquisition of high-resolution 2D images but slow and costly optical z-sectioning. To evaluate MSDSR's efficacy, we introduce a new performance metric, SliceFID, and demonstrate MSDSR's superior performance over baseline models through extensive evaluations. Our findings reveal that MSDSR not only significantly enhances the quality and resolution of 3D volumetric data, but also addresses major obstacles hindering the broader application of 3D volumetric microscopy in clinical diagnostics and biomedical research.

Yiwei Lyu, Samir Harake, Asadur Chowdury et al.

Neuroimaging is a ubiquitous tool for evaluating patients with neurological diseases. The global demand for magnetic resonance imaging (MRI) studies has risen steadily, placing significant strain on health systems, prolonging turnaround times, and intensifying physician burnout \cite{Chen2017-bt, Rula2024-qp-1}. These challenges disproportionately impact patients in low-resource and rural settings. Here, we utilized a large academic health system as a data engine to develop Prima, the first vision language model (VLM) serving as an AI foundation for neuroimaging that supports real-world, clinical MRI studies as input. Trained on over 220,000 MRI studies, Prima uses a hierarchical vision architecture that provides general and transferable MRI features. Prima was tested in a 1-year health system-wide study that included 30K MRI studies. Across 52 radiologic diagnoses from the major neurologic disorders, including neoplastic, inflammatory, infectious, and developmental lesions, Prima achieved a mean diagnostic area under the ROC curve of 92.0, outperforming other state-of-the-art general and medical AI models. Prima offers explainable differential diagnoses, worklist priority for radiologists, and clinical referral recommendations across diverse patient demographics and MRI systems. Prima demonstrates algorithmic fairness across sensitive groups and can help mitigate health system biases, such as prolonged turnaround times for low-resource populations. These findings highlight the transformative potential of health system-scale VLMs and Prima's role in advancing AI-driven healthcare.

Xinhai Hou, Akhil Kondepudi, Cheng Jiang et al.

The importance of rapid and accurate histologic analysis of surgical tissue in the operating room has been recognized for over a century. Our standard-of-care intraoperative pathology workflow is based on light microscopy and H\&E histology, which is slow, resource-intensive, and lacks real-time digital imaging capabilities. Here, we present an emerging and innovative method for intraoperative histologic analysis, called Intelligent Histology, that integrates artificial intelligence (AI) with stimulated Raman histology (SRH). SRH is a rapid, label-free, digital imaging method for real-time microscopic tumor tissue analysis. SRH generates high-resolution digital images of surgical specimens within seconds, enabling AI-driven tumor histologic analysis, molecular classification, and tumor infiltration detection. We review the scientific background, clinical translation, and future applications of intelligent histology in tumor neurosurgery. We focus on the major scientific and clinical studies that have demonstrated the transformative potential of intelligent histology across multiple neurosurgical specialties, including neurosurgical oncology, skull base, spine oncology, pediatric tumors, and periperal nerve tumors. Future directions include the development of AI foundation models through multi-institutional datasets, incorporating clinical and radiologic data for multimodal learning, and predicting patient outcomes. Intelligent histology represents a transformative intraoperative workflow that can reinvent real-time tumor analysis for 21st century neurosurgery.

Cheng Jiang, Abhishek Bhattacharya, Joseph Linzey et al.

Background: Accurate diagnosis of skull base tumors is essential for providing personalized surgical treatment strategies. Intraoperative diagnosis can be challenging due to tumor diversity and lack of intraoperative pathology resources. Objective: To develop an independent and parallel intraoperative pathology workflow that can provide rapid and accurate skull base tumor diagnoses using label-free optical imaging and artificial intelligence. Method: We used a fiber laser-based, label-free, non-consumptive, high-resolution microscopy method ($<$ 60 sec per 1 $\times$ 1 mm$^\text{2}$), called stimulated Raman histology (SRH), to image a consecutive, multicenter cohort of skull base tumor patients. SRH images were then used to train a convolutional neural network (CNN) model using three representation learning strategies: cross-entropy, self-supervised contrastive learning, and supervised contrastive learning. Our trained CNN models were tested on a held-out, multicenter SRH dataset. Results: SRH was able to image the diagnostic features of both benign and malignant skull base tumors. Of the three representation learning strategies, supervised contrastive learning most effectively learned the distinctive and diagnostic SRH image features for each of the skull base tumor types. In our multicenter testing set, cross-entropy achieved an overall diagnostic accuracy of 91.5%, self-supervised contrastive learning 83.9%, and supervised contrastive learning 96.6%. Our trained model was able to identify tumor-normal margins and detect regions of microscopic tumor infiltration in whole-slide SRH images. Conclusion: SRH with trained artificial intelligence models can provide rapid and accurate intraoperative analysis of skull base tumor specimens to inform surgical decision-making.