Cheng Jiang

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, 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.

Edward S. Harake, Joseph R. Linzey, Cheng Jiang et al.

Objective. Achieving appropriate spinopelvic alignment has been shown to be associated with improved clinical symptoms. However, measurement of spinopelvic radiographic parameters is time-intensive and interobserver reliability is a concern. Automated measurement tools have the promise of rapid and consistent measurements, but existing tools are still limited by some degree of manual user-entry requirements. This study presents a novel artificial intelligence (AI) tool called SpinePose that automatically predicts spinopelvic parameters with high accuracy without the need for manual entry. Methods. SpinePose was trained and validated on 761 sagittal whole-spine X-rays to predict sagittal vertical axis (SVA), pelvic tilt (PT), pelvic incidence (PI), sacral slope (SS), lumbar lordosis (LL), T1-pelvic angle (T1PA), and L1-pelvic angle (L1PA). A separate test set of 40 X-rays was labeled by 4 reviewers, including fellowship-trained spine surgeons and a fellowship-trained radiologist with neuroradiology subspecialty certification. Median errors relative to the most senior reviewer were calculated to determine model accuracy on test images. Intraclass correlation coefficients (ICC) were used to assess inter-rater reliability. Results. SpinePose exhibited the following median (interquartile range) parameter errors: SVA: 2.2(2.3)mm, p=0.93; PT: 1.3(1.2)°, p=0.48; SS: 1.7(2.2)°, p=0.64; PI: 2.2(2.1)°, p=0.24; LL: 2.6(4.0)°, p=0.89; T1PA: 1.1(0.9)°, p=0.42; and L1PA: 1.4(1.6)°, p=0.49. Model predictions also exhibited excellent reliability at all parameters (ICC: 0.91-1.0). Conclusions. SpinePose accurately predicted spinopelvic parameters with excellent reliability comparable to fellowship-trained spine surgeons and neuroradiologists. Utilization of predictive AI tools in spinal imaging can substantially aid in patient selection and surgical planning.

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.

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.