Research

"The purpose of computation is insight, not numbers." -Richard Hamming

Stimulated Raman Histology and AI

A major focus of the MLiNS lab is to combine stimulated Raman histology (SRH), a rapid label-free, optical imaging method, with deep learning and computer vision techniques to discover the molecular, cellular, and microanatomic features of skull base and malignant brain tumors. We are using SRH in our operating rooms to improve the speed and accuracy of brain tumor diagnosis. Our group has focused on deep learning-based computer vision methods for automated image interpretation, intraoperative diagnosis, and tumor margin delineation. Our work culminated in a multicenter, prospective, clinical trial, which demonstrated that AI interpretation of SRH images was equivalent in diagnostic accuracy to pathologist interpretation of conventional histology. We were able to show, for the first time, that a deep neural network is able to learn recognizable and interpretable histologic image features (e.g. tumor cellularity, nuclear morphology, infiltrative growth pattern, etc) in order to make a diagnosis. Our future work is directed at going beyond human-level interpretation towards identifying molecular/genetic features, single-cell classification, and predicting patient prognosis.


Featured Publications:

Near real-time intraoperative brain tumor diagnosis using stimulated Raman histology and deep neural networks

TC Hollon, B Pandian, AR Adapa, E Urias, AV Save, SSS Khalsa, ...

Nature medicine 26 (1), 52-58. 2020

https://pubmed.ncbi.nlm.nih.gov/31907460/


Rapid, label-free detection of diffuse glioma recurrence using intraoperative stimulated Raman histology and deep neural networks

TC Hollon, B Pandian, E Urias, AV Save, AR Adapa, S Srinivasan, ...

Neuro-oncology 23 (1), 144-155. 2021

https://pubmed.ncbi.nlm.nih.gov/32672793/


Rapid intraoperative histology of unprocessed surgical specimens via fibre-laser-based stimulated Raman scattering microscopy

DA Orringer, B Pandian, YS Niknafs, TC Hollon, J Boyle, S Lewis, ...

Nature biomedical engineering 1 (2), 1-13. 2017

https://pubmed.ncbi.nlm.nih.gov/28955599/


Rapid intraoperative diagnosis of pediatric brain tumors using stimulated Raman histology

TC Hollon, S Lewis, B Pandian, YS Niknafs, MR Garrard, H Garton, ...

Cancer research 78 (1), 278-289. 2018

https://pubmed.ncbi.nlm.nih.gov/29093006/


Improving the accuracy of brain tumor surgery via Raman-based technology

TC Hollon, S Lewis, CW Freudiger, XS Xie, DA Orringer

Neurosurgical focus 40 (3), E9. 2016

https://pubmed.ncbi.nlm.nih.gov/26926067/

Predicting patient outcomes

Machine learning has the potential to revolutionize the way we predict patient outcomes. Electronic medical records (EMR) have streamlined data collection and made it easier than ever to use ML algorithms to assist in patient care. Our work has focused on predicting (1) how well patients will recover after surgery and (2) what will ultimately affect their long-term outcome and survival. We use ML algorithms that allow for transparency and interpretability, both of which are essential to trust the recommendations of ML decision-support tools in healthcare. By identifying the specific set of symptoms, radiographic findings, laboratory values, etc. that our models use for prediction, physicians can use ML recommendations in the appropriate clinical context for personalized treatment decisions.


Featured Publications

A machine learning approach to predict early outcomes after pituitary adenoma surgery

TC Hollon, A Parikh, B Pandian, J Tarpeh, DA Orringer, AL Barkan, ...

Neurosurgical focus 45 (5), E8. 2018

https://pubmed.ncbi.nlm.nih.gov/30453460/


Clinical factors associated with ICU-specific care following supratentorial brain tumor resection and validation of a risk prediction score

LR Franko, T Hollon, J Linzey, C Roark, V Rajajee, K Sheehan, M Teig, ...

Critical care medicine 46 (8), 1302-1308. 2018

https://pubmed.ncbi.nlm.nih.gov/29742589/


Supratentorial hemispheric ependymomas: an analysis of 109 adults for survival and prognostic factors

T Hollon, V Nguyen, BW Smith, S Lewis, L Junck, DA Orringer

Journal of neurosurgery 125 (2), 410-418. 2016

https://pubmed.ncbi.nlm.nih.gov/26745489/


Ventriculoscopic Surgery for Cystic Retrochiasmatic Craniopharyngiomas: Indications, Surgical Technique, and Short-Term Patient Outcomes

TC Hollon, LE Savastano, D Altshuler, AL Barkan, SE Sullivan

Operative Neurosurgery 15 (2), 109-119.2018

https://pubmed.ncbi.nlm.nih.gov/29048572/

Automated brain segmentation

Computed tomography (CT) and magnetic resonance imaging (MRI) are an indispensable part of neurosurgery. Currently, interpretation of CT and MRI scans requires a skilled neuroradiologist and is mainly qualitative, meaning the radiologist provides a written narrative of their findings with little or no quantitative measurements. These measurements are time- and labor-intensive, making it infeasible to have neuroradiologists perform them in the vast majority of scans. Therefore, the MLiNS lab has set out to automate the process of measuring specific features of MR and CT scans that can affect treatment decisions and patient outcomes. For example, the volume of the cerebral ventricles is an essential part of the diagnosis and long-term management of hydrocephalus. The problem is that (1) cerebral ventricle volumes can vary widely between patients and (2) detecting subtle changes in ventricle volume can be challenging, even by trained neuroradiologists and neurosurgeons. We have developed a method for automated segmentation and volumetric assessment of cerebral ventricles in both normal controls and hydrocephalus patients to assist in treatment decisions. We have applied similar methods to measure the hematoma burden in subarachnoid hemorrhage patients and morphologic assessment of the posterior fossa in Chiari malformations.


Featured Publications

Normal cerebral ventricular volume growth in childhood

NS Cutler, S Srinivasan, BL Aaron, SK Anand, MS Kang, DB Altshuler, ...

Journal of Neurosurgery: Pediatrics 26 (5), 517-524. 2021

https://pubmed.ncbi.nlm.nih.gov/32823266/


Volumetric quantification of aneurysmal subarachnoid hemorrhage independently predicts hydrocephalus and seizures.

Daou BJ, Khalsa SSS, Anand SK, Williamson CA, Cutler NS, Aaron BL, Srinivasan S, Rajajee V, Sheehan K, Pandey AS.J Neurosurg. 2021 Feb 5:1-9.

https://pubmed.ncbi.nlm.nih.gov/33545677/


Morphometric and volumetric comparison of 102 children with symptomatic and asymptomatic Chiari malformation Type I.

Khalsa SSS, Geh N, Martin BA, Allen PA, Strahle J, Loth F, Habtzghi D, Urbizu Serrano A, McQuaide D, Garton HJL, Muraszko KM, Maher CO.

J Neurosurg Pediatr. 2018 Jan;21(1):65-71

https://pubmed.ncbi.nlm.nih.gov/29125445/


Comparison of posterior fossa volumes and clinical outcomes after decompression of Chiari malformation Type I.

Khalsa SSS, Siu A, DeFreitas TA, Cappuzzo JM, Myseros JS, Magge SN, Oluigbo CO, Keating RF.

J Neurosurg Pediatr. 2017 May;19(5):511-517.

https://pubmed.ncbi.nlm.nih.gov/28291422/


The images on the left are real images sampled from the The Cancer Genome Atlas. The images on the right are synthetic, or fake, images created using generative adversarial networks. We use the fake images to improve brain tumor diagnosis.

Augmenting intraoperative pathology

The use of AI in digital pathology has grown significantly over the previous decade. The majority of research in this area has focused on the automated interpretation of formalin-fixed, paraffin-embedded permanent specimens. However, our lab has focused on applying AI to frozen sections performed during surgery, which is a much more challenging computer vision task. Accurate intraoperative diagnosis is essential for providing safe and effective care for brain tumor patients. Surgical goals are divergent depending on intraoperative diagnosis, which necessitates a pathology workflow that is timely and accurate. Conventional intraoperative pathology requires freezing and sectioning, which introduces artifacts into the specimen and can make interpretation challenging and decrease accuracy. Moreover, each fresh intraoperative specimen must be individually reviewed by a neuropathologist, which can be time-consuming. Our lab aims to provide decision support and computer-augmented diagnostic tools to improve the speed and accuracy intraoperative diagnosis. Specifically, we have trained deep neural networks to classify the most common brain tumor types using frozen sections alone. Because the availability of frozen whose-slide images is limited, we use synthetic images for data augmentation to improve classification performance. We train a neural network model, called a generative adversarial network, to generate "fake" images that can be used to train a classifier network to improve diagnostic accuracy. We have worked closely on this project with our collaborators at Synthetaic, a start-up AI company that uses synthetic data to improve AI for real-world applications.


Featured Publications

Automated Intraoperative Frozen Diagnosis of Brain Tumors Using Machine Learning

SSS Khalsa, T Hollon, N Jairath, A Adapa, E Urias, K Eddy, J Szczepanski, ...

JOURNAL OF NEUROSURGERY 132 (4), 85-85.2020

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341168/


Automated histologic diagnosis of CNS tumors with machine learning

SSS Khalsa, TC Hollon, A Adapa, E Urias, S Srinivasan, N Jairath, ...

CNS oncology 9 (2), CNS56.2020

https://pubmed.ncbi.nlm.nih.gov/32602745/


Human images from TCGA

Finding oncostreams in gliomas

Our collaborators, Drs. Pedro Lowenstein and Maria Castro, have discovered that within gliomas are self-organizing structures, called oncostreams, which determine the spatial heterogeneity and malignant behavior of these deadly tumors. The MLiNS lab was able to assist in this discovery by developing deep neural networks that can detect and quantify oncostreams in whole-slide images from glioma mouse models and patient's tumors. Using the latest computer vision methods for biomedical image segmentation, we were able to demonstrate that a higher density of oncostreams, detected using our trained model, correlates with tumor grade and decreased survival. These results were confirmed using whole-slide images from The Cancer Genome Atlas (TCGA).


Featured Publications

The dynamic tumor microenvironment: Oncostreams are self-organizing structures that modulate glioma progression and treatment

A Comba, S Motsch, P Dunn, T Hollon, D Zamler, A Argento, A Kahana, ...

Cancer Research 81 (5 Supplement), PR005-PR005. 2021

https://cancerres.aacrjournals.org/content/81/5_Supplement/PR005


Oncostreams: Self-organization and dynamics determine spatial heterogeneity and malignant behavior in gliomas

A Comba, S Motsch, PJ Dunn, TC Hollon, DB Zamler, AE Argento, ...

bioRxiv. 2020

https://www.biorxiv.org/content/10.1101/2020.12.01.404970v1