Neurosurgery Research Publications

2017
Rahul Sastry, Wenya Linda Bi, Steve Pieper, Sarah Frisken, Tina Kapur, William Wells, and Alexandra J Golby. 2017. “Applications of Ultrasound in the Resection of Brain Tumors.” J Neuroimaging, 27, 1, Pp. 5-15.Abstract

Neurosurgery makes use of preoperative imaging to visualize pathology, inform surgical planning, and evaluate the safety of selected approaches. The utility of preoperative imaging for neuronavigation, however, is diminished by the well-characterized phenomenon of brain shift, in which the brain deforms intraoperatively as a result of craniotomy, swelling, gravity, tumor resection, cerebrospinal fluid (CSF) drainage, and many other factors. As such, there is a need for updated intraoperative information that accurately reflects intraoperative conditions. Since 1982, intraoperative ultrasound has allowed neurosurgeons to craft and update operative plans without ionizing radiation exposure or major workflow interruption. Continued evolution of ultrasound technology since its introduction has resulted in superior imaging quality, smaller probes, and more seamless integration with neuronavigation systems. Furthermore, the introduction of related imaging modalities, such as 3-dimensional ultrasound, contrast-enhanced ultrasound, high-frequency ultrasound, and ultrasound elastography, has dramatically expanded the options available to the neurosurgeon intraoperatively. In the context of these advances, we review the current state, potential, and challenges of intraoperative ultrasound for brain tumor resection. We begin by evaluating these ultrasound technologies and their relative advantages and disadvantages. We then review three specific applications of these ultrasound technologies to brain tumor resection: (1) intraoperative navigation, (2) assessment of extent of resection, and (3) brain shift monitoring and compensation. We conclude by identifying opportunities for future directions in the development of ultrasound technologies.

Lauren J O'Donnell, Yannick Suter, Laura Rigolo, Pegah Kahali, Fan Zhang, Isaiah Norton, Angela Albi, Olutayo Olubiyi, Antonio Meola, Walid I Essayed, Prashin Unadkat, Pelin Aksit Ciris, William M Wells, Yogesh Rathi, Carl-Fredrik Westin, and Alexandra J Golby. 2017. “Automated White Matter Fiber Tract Identification in Patients with Brain Tumors.” Neuroimage Clin, 13, Pp. 138-53.Abstract

We propose a method for the automated identification of key white matter fiber tracts for neurosurgical planning, and we apply the method in a retrospective study of 18 consecutive neurosurgical patients with brain tumors. Our method is designed to be relatively robust to challenges in neurosurgical tractography, which include peritumoral edema, displacement, and mass effect caused by mass lesions. The proposed method has two parts. First, we learn a data-driven white matter parcellation or fiber cluster atlas using groupwise registration and spectral clustering of multi-fiber tractography from healthy controls. Key fiber tract clusters are identified in the atlas. Next, patient-specific fiber tracts are automatically identified using tractography-based registration to the atlas and spectral embedding of patient tractography. Results indicate good generalization of the data-driven atlas to patients: 80% of the 800 fiber clusters were identified in all 18 patients, and 94% of the 800 fiber clusters were found in 16 or more of the 18 patients. Automated subject-specific tract identification was evaluated by quantitative comparison to subject-specific motor and language functional MRI, focusing on the arcuate fasciculus (language) and corticospinal tracts (motor), which were identified in all patients. Results indicate good colocalization: 89 of 95, or 94%, of patient-specific language and motor activations were intersected by the corresponding identified tract. All patient-specific activations were within 3mm of the corresponding language or motor tract. Overall, our results indicate the potential of an automated method for identifying fiber tracts of interest for neurosurgical planning, even in patients with mass lesions.

Michael A Silva, Alfred P See, Walid I Essayed, Alexandra J Golby, and Yanmei Tie. 2017. “Challenges and Techniques for Presurgical Brain Mapping with Functional MRI.” Neuroimage Clin, 17, Pp. 794-803.Abstract
Functional magnetic resonance imaging (fMRI) is increasingly used for preoperative counseling and planning, and intraoperative guidance for tumor resection in the eloquent cortex. Although there have been improvements in image resolution and artifact correction, there are still limitations of this modality. In this review, we discuss clinical fMRI's applications, limitations and potential solutions. These limitations depend on the following parameters: foundations of fMRI, physiologic effects of the disease, distinctions between clinical and research fMRI, and the design of the fMRI study. We also compare fMRI to other brain mapping modalities which should be considered as alternatives or adjuncts when appropriate, and discuss intraoperative use and validation of fMRI. These concepts direct the clinical application of fMRI in neurosurgical patients.
Ruizhi Liao, Lipeng Ning, Zhenrui Chen, Laura Rigolo, Shun Gong, Ofer Pasternak, Alexandra J Golby, Yogesh Rathi, Lauren J O'Donnell, and JV ckovic. 2017. “Performance of Unscented Kalman Filter Tractography in Edema: Analysis of the Two-tensor Model.” Neuroimage Clin, 15, Pp. 819-31.Abstract
Diffusion MRI tractography is increasingly used in pre-operative neurosurgical planning to visualize critical fiber tracts. However, a major challenge for conventional tractography, especially in patients with brain tumors, is tracing fiber tracts that are affected by vasogenic edema, which increases water content in the tissue and lowers diffusion anisotropy. One strategy for improving fiber tracking is to use a tractography method that is more sensitive than the traditional single-tensor streamline tractography. We performed experiments to assess the performance of two-tensor unscented Kalman filter (UKF) tractography in edema. UKF tractography fits a diffusion model to the data during fiber tracking, taking advantage of prior information from the previous step along the fiber. We studied UKF performance in a synthetic diffusion MRI digital phantom with simulated edema and in retrospective data from two neurosurgical patients with edema affecting the arcuate fasciculus and corticospinal tracts. We compared the performance of several tractography methods including traditional streamline, UKF single-tensor, and UKF two-tensor. To provide practical guidance on how the UKF method could be employed, we evaluated the impact of using various seed regions both inside and outside the edematous regions, as well as the impact of parameter settings on the tractography sensitivity. We quantified the sensitivity of different methods by measuring the percentage of the patient-specific fMRI activation that was reached by the tractography. We expected that diffusion anisotropy threshold parameters, as well as the inclusion of a free water model, would significantly influence the reconstruction of edematous WM fiber tracts, because edema increases water content in the tissue and lowers anisotropy. Contrary to our initial expectations, varying the fractional anisotropy threshold and including a free water model did not affect the UKF two-tensor tractography output appreciably in these two patient datasets. The most effective parameter for increasing tracking sensitivity was the generalized anisotropy (GA) threshold, which increased the length of tracked fibers when reduced to 0.075. In addition, the most effective seeding strategy was seeding in the whole brain or in a large region outside of the edema. Overall, the main contribution of this study is to provide insight into how UKF tractography can work, using a two-tensor model, to begin to address the challenge of fiber tract reconstruction in edematous regions near brain tumors.
Ma Luo, Sarah F Frisken, Jared A Weis, Logan W Clements, Prashin Unadkat, Reid C Thompson, Alexandra J Golby, and Michael I Miga. 2017. “Retrospective Study Comparing Model-Based Deformation Correction to Intraoperative Magnetic Resonance Imaging for Image-Guided Neurosurgery.” J Med Imaging (Bellingham), 4, 3, Pp. 035003.Abstract
Brain shift during tumor resection compromises the spatial validity of registered preoperative imaging data that is critical to image-guided procedures. One current clinical solution to mitigate the effects is to reimage using intraoperative magnetic resonance (iMR) imaging. Although iMR has demonstrated benefits in accounting for preoperative-to-intraoperative tissue changes, its cost and encumbrance have limited its widespread adoption. While iMR will likely continue to be employed for challenging cases, a cost-effective model-based brain shift compensation strategy is desirable as a complementary technology for standard resections. We performed a retrospective study of [Formula: see text] tumor resection cases, comparing iMR measurements with intraoperative brain shift compensation predicted by our model-based strategy, driven by sparse intraoperative cortical surface data. For quantitative assessment, homologous subsurface targets near the tumors were selected on preoperative MR and iMR images. Once rigidly registered, intraoperative shift measurements were determined and subsequently compared to model-predicted counterparts as estimated by the brain shift correction framework. When considering moderate and high shift ([Formula: see text], [Formula: see text] measurements per case), the alignment error due to brain shift reduced from [Formula: see text] to [Formula: see text], representing [Formula: see text] correction. These first steps toward validation are promising for model-based strategies.
Isaiah Norton, Walid Ibn Essayed, Fan Zhang, Sonia Pujol, Alex Yarmarkovich, Alexandra J Golby, Gordon Kindlmann, Demian Wasserman, Raul San Jose Estepar, Yogesh Rathi, Steve Pieper, Ron Kikinis, Hans J Johnson, Carl-Fredrik Westin, and Lauren J O'Donnell. 2017. “SlicerDMRI: Open Source Diffusion MRI Software for Brain Cancer Research.” Cancer Res, 77, 21, Pp. e101-e103.Abstract
Diffusion MRI (dMRI) is the only noninvasive method for mapping white matter connections in the brain. We describe SlicerDMRI, a software suite that enables visualization and analysis of dMRI for neuroscientific studies and patient-specific anatomic assessment. SlicerDMRI has been successfully applied in multiple studies of the human brain in health and disease, and here, we especially focus on its cancer research applications. As an extension module of the 3D Slicer medical image computing platform, the SlicerDMRI suite enables dMRI analysis in a clinically relevant multimodal imaging workflow. Core SlicerDMRI functionality includes diffusion tensor estimation, white matter tractography with single and multi-fiber models, and dMRI quantification. SlicerDMRI supports clinical DICOM and research file formats, is open-source and cross-platform, and can be installed as an extension to 3D Slicer (www.slicer.org). More information, videos, tutorials, and sample data are available at dmri.slicer.org Cancer Res; 77(21); e101-3. ©2017 AACR.
Walid I Essayed, Fan Zhang, Prashin Unadkat, Rees G Cosgrove, Alexandra J Golby, and Lauren J O'Donnell. 2017. “White Matter Tractography for Neurosurgical Planning: A Topography-based Review of the Current State of the Art.” Neuroimage Clin, 15, Pp. 659-72.Abstract
We perform a review of the literature in the field of white matter tractography for neurosurgical planning, focusing on those works where tractography was correlated with clinical information such as patient outcome, clinical functional testing, or electro-cortical stimulation. We organize the review by anatomical location in the brain and by surgical procedure, including both supratentorial and infratentorial pathologies, and excluding spinal cord applications. Where possible, we discuss implications of tractography for clinical care, as well as clinically relevant technical considerations regarding the tractography methods. We find that tractography is a valuable tool in variable situations in modern neurosurgery. Our survey of recent reports demonstrates multiple potentially successful applications of white matter tractography in neurosurgery, with progress towards overcoming clinical challenges of standardization and interpretation.
2016
Zhenrui Chen, Yanmei Tie, Olutayo Olubiyi, Fan Zhang, Alireza Mehrtash, Laura Rigolo, Pegah Kahali, Isaiah Norton, Ofer Pasternak, Yogesh Rathi, Alexandra J Golby, and Lauren J O'Donnell. 2016. “Corticospinal Tract Modeling for Neurosurgical Planning by Tracking through Regions of Peritumoral Edema and Crossing Fibers using Two-tensor Unscented Kalman Filter Tractography.” Int J Comput Assist Radiol Surg, 11, 8, Pp. 1475-86.Abstract

PURPOSE: The aim of this study was to present a tractography algorithm using a two-tensor unscented Kalman filter (UKF) to improve the modeling of the corticospinal tract (CST) by tracking through regions of peritumoral edema and crossing fibers. METHODS: Ten patients with brain tumors in the vicinity of motor cortex and evidence of significant peritumoral edema were retrospectively selected for the study. All patients underwent 3-T magnetic resonance imaging (MRI) including functional MRI (fMRI) and a diffusion-weighted data set with 31 directions. Fiber tracking was performed using both single-tensor streamline and two-tensor UKF tractography methods. A two-region-of-interest approach was used to delineate the CST. Results from the two tractography methods were compared visually and quantitatively. fMRI was applied to identify the functional fiber tracts. RESULTS: Single-tensor streamline tractography underestimated the extent of tracts running through the edematous areas and could only track the medial projections of the CST. In contrast, two-tensor UKF tractography tracked fanning projections of the CST despite peritumoral edema and crossing fibers. Based on visual inspection, the two-tensor UKF tractography delineated tracts that were closer to motor fMRI activations, and it was apparently more sensitive than single-tensor streamline tractography to define the tracts directed to the motor sites. The volume of the CST was significantly larger on two-tensor UKF than on single-tensor streamline tractography ([Formula: see text]). CONCLUSION: Two-tensor UKF tractography tracks a larger volume CST than single-tensor streamline tractography in the setting of peritumoral edema and crossing fibers in brain tumor patients.

Roy G Torcuator, Maher M Hulou, Vamsidhar Chavakula, Ferenc A Jolesz, and Alexandra J Golby. 2016. “Intraoperative Real-time MRI-guided Stereotactic Biopsy Followed by Laser Thermal Ablation for Progressive Brain Metastases after Radiosurgery.” J Clin Neurosci, 24, Pp. 68-73.Abstract

Stereotactic radiosurgery is one of the treatment options for brain metastases. However, there are patients who will progress after radiosurgery. One of the potential treatments for this subset of patients is laser ablation. Image-guided stereotactic biopsy is important to determine the histopathological nature of the lesion. However, this is usually based on preoperative, static images, which may affect the target accuracy during the actual procedure as a result of brain shift. We therefore performed real-time intraoperative MRI-guided stereotactic aspiration and biopsies on two patients with symptomatic, progressive lesions after radiosurgery followed immediately by laser ablation. The patients tolerated the procedure well with no new neurologic deficits. Intraoperative MRI-guided stereotactic biopsy followed by laser ablation is safe and accurate, providing real-time updates and feedback during the procedure.

Fa Ke Lu, David Calligaris, Olutayo I Olubiyi, Isaiah Norton, Wenlong Yang, Sandro Santagata, Sunney X Xie, Alexandra J Golby, and Nathalie YR Agar. 2016. “Label-Free Neurosurgical Pathology with Stimulated Raman Imaging.” Cancer Res, 76, 12, Pp. 3451-62.Abstract

The goal of brain tumor surgery is to maximize tumor removal without injuring critical brain structures. Achieving this goal is challenging as it can be difficult to distinguish tumor from nontumor tissue. While standard histopathology provides information that could assist tumor delineation, it cannot be performed iteratively during surgery as freezing, sectioning, and staining of the tissue require too much time. Stimulated Raman scattering (SRS) microscopy is a powerful label-free chemical imaging technology that enables rapid mapping of lipids and proteins within a fresh specimen. This information can be rendered into pathology-like images. Although this approach has been used to assess the density of glioma cells in murine orthotopic xenografts models and human brain tumors, tissue heterogeneity in clinical brain tumors has not yet been fully evaluated with SRS imaging. Here we profile 41 specimens resected from 12 patients with a range of brain tumors. By evaluating large-scale stimulated Raman imaging data and correlating this data with current clinical gold standard of histopathology for 4,422 fields of view, we capture many essential diagnostic hallmarks for glioma classification. Notably, in fresh tumor samples, we observe additional features, not seen by conventional methods, including extensive lipid droplets within glioma cells, collagen deposition in gliosarcoma, and irregularity and disruption of myelinated fibers in areas infiltrated by oligodendroglioma cells. The data are freely available in a public resource to foster diagnostic training and to permit additional interrogation. Our work establishes the methodology and provides a significant collection of reference images for label-free neurosurgical pathology. Cancer Res; 76(12); 3451-62. ©2016 AACR.

Pablo A Valdés, David W Roberts, Fa-Ke Lu, and Alexandra Golby. 2016. “Optical Technologies for Intraoperative Neurosurgical Guidance.” Neurosurg Focus, 40, 3, Pp. E8.Abstract

Biomedical optics is a broadly interdisciplinary field at the interface of optical engineering, biophysics, computer science, medicine, biology, and chemistry, helping us understand light-tissue interactions to create applications with diagnostic and therapeutic value in medicine. Implementation of biomedical optics tools and principles has had a notable scientific and clinical resurgence in recent years in the neurosurgical community. This is in great part due to work in fluorescence-guided surgery of brain tumors leading to reports of significant improvement in maximizing the rates of gross-total resection. Multiple additional optical technologies have been implemented clinically, including diffuse reflectance spectroscopy and imaging, optical coherence tomography, Raman spectroscopy and imaging, and advanced quantitative methods, including quantitative fluorescence and lifetime imaging. Here we present a clinically relevant and technologically informed overview and discussion of some of the major clinical implementations of optical technologies as intraoperative guidance tools in neurosurgery.

David B Fischer, David L Perez, Sashank Prasad, Laura Rigolo, Lauren O'Donnell, Diler Acar, Mary-Ellen Meadows, Gaston Baslet, Aaron D Boes, Alexandra J Golby, and Barbara A Dworetzky. 2016. “Right Inferior Longitudinal Fasciculus Lesions Disrupt Visual-emotional Integration.” Soc Cogn Affect Neurosci, 11, 6, Pp. 945-51.Abstract

The mechanism by which the brain integrates visual and emotional information remains incompletely understood, and can be studied through focal lesions that selectively disrupt this process. To date, three reported cases of visual hypoemotionality, a vision-specific form of derealization, have resulted from lesions of the temporo-occipital junction. We present a fourth case of this rare phenomenon, and investigate the role of the inferior longitudinal fasciculus (ILF) in the underlying pathophysiology. A 50-year-old right-handed male was found to have a right medial temporal lobe tumor following new-onset seizures. Interstitial laser ablation of the lesion was complicated by a right temporo-parieto-occipital intraparenchymal hemorrhage. The patient subsequently experienced emotional estrangement from visual stimuli. A lesion overlap analysis was conducted to assess involvement of the ILF by this patient's lesion and those of the three previously described cases, and diffusion tensor imaging was acquired in our case to further investigate ILF disruption. All four lesions specifically overlapped with the expected trajectory of the right ILF, and diminished structural integrity of the right ILF was observed in our case. These findings implicate the ILF in visual hypoemotionality, suggesting that the ILF is critical for integrating visual information with its emotional content.

Fatih Incekara, Olutayo Olubiyi, Aysegul Ozdemir, Tom Lee, Laura Rigolo, and Alexandra Golby. 2016. “The Value of Pre- and Intraoperative Adjuncts on the Extent of Resection of Hemispheric Low-Grade Gliomas: A Retrospective Analysis.” J Neurol Surg A Cent Eur Neurosurg, 77, 2, Pp. 79-87.Abstract

Background To achieve maximal resection with minimal risk of postoperative neurologic morbidity, different neurosurgical adjuncts are being used during low-grade glioma (LGG) surgery. Objectives To investigate the effect of pre- and intraoperative adjuncts on the extent of resection (EOR) of hemispheric LGGs. Methods Medical records were reviewed to identify patients of any sex, ≥ 18 years of age, who underwent LGG surgery at X Hospital between January 2005 and July 2013. Patients were divided into eight subgroups based on the use of various combinations of a neuronavigation system alone (NN), functional MRI-diffusion tensor imaging (fMRI-DTI) guided neuronavigation (FD), intraoperative MRI (MR), and direct electrical stimulation (DES). Initial and residual tumors were measured, and mean EOR was compared between groups. Results Of all 128 patients, gross total resection was achieved in 23.4%. Overall mean EOR was 81.3% ± 20.5%. Using DES in combination with fMRI-DTI (mean EOR: 86.7% ± 12.4%) on eloquent tumors improved mean EOR significantly after adjustment for potential confounders when compared with NN alone (mean EOR: 76.4% ± 25.5%; p = 0.001). Conclusions Using DES in combination with fMRI and DTI significantly improves EOR when LGGs are located in eloquent areas compared with craniotomies in which only NN was used.

2015
Sonia Pujol, William M Wells III, Carlo Pierpaoli, Caroline Brun, James Gee, Guang Cheng, Baba Vemuri, Olivier Commowick, Sylvain Prima, Aymeric Stamm, Maged Goubran, Ali Khan, Terry Peters, Peter Neher, Klaus H Maier-Hein, Yundi Shi, Antonio Tristan-Vega, Gopalkrishna Veni, Ross Whitaker, Martin Styner, Carl-Fredrik Westin, Sylvain Gouttard, Isaiah Norton, Laurent Chauvin, Hatsuho Mamata, Guido Gerig, Arya Nabavi, Alexandra Golby, and Ron Kikinis. 2015. “The DTI Challenge: Toward Standardized Evaluation of Diffusion Tensor Imaging Tractography for Neurosurgery.” J Neuroimaging, 25, 6, Pp. 875-82.Abstract

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) tractography reconstruction of white matter pathways can help guide brain tumor resection. However, DTI tracts are complex mathematical objects and the validity of tractography-derived information in clinical settings has yet to be fully established. To address this issue, we initiated the DTI Challenge, an international working group of clinicians and scientists whose goal was to provide standardized evaluation of tractography methods for neurosurgery. The purpose of this empirical study was to evaluate different tractography techniques in the first DTI Challenge workshop. METHODS: Eight international teams from leading institutions reconstructed the pyramidal tract in four neurosurgical cases presenting with a glioma near the motor cortex. Tractography methods included deterministic, probabilistic, filtered, and global approaches. Standardized evaluation of the tracts consisted in the qualitative review of the pyramidal pathways by a panel of neurosurgeons and DTI experts and the quantitative evaluation of the degree of agreement among methods. RESULTS: The evaluation of tractography reconstructions showed a great interalgorithm variability. Although most methods found projections of the pyramidal tract from the medial portion of the motor strip, only a few algorithms could trace the lateral projections from the hand, face, and tongue area. In addition, the structure of disagreement among methods was similar across hemispheres despite the anatomical distortions caused by pathological tissues. CONCLUSIONS: The DTI Challenge provides a benchmark for the standardized evaluation of tractography methods on neurosurgical data. This study suggests that there are still limitations to the clinical use of tractography for neurosurgical decision making.

Olutayo Olubiyi, Aysegul Ozdemir, Fatih Incekara, Yanmei Tie, Parviz Dolati, Liangge Hsu, Sandro Santagata, Zhenrui Chen, Laura Rigolo, and Alexandra J Golby. 2015. “Intraoperative Magnetic Resonance Imaging in Intracranial Glioma Resection: A Single-Center, Retrospective Blinded Volumetric Study.” World Neurosurg, 84, 2, Pp. 528-36.Abstract

BACKGROUND: Intraoperative magnetic resonance imaging (IoMRI) was devised to overcome brain shifts during craniotomies. Yet, the acceptance of IoMRI is limited. OBJECTIVE: To evaluate impact of IoMRI on intracranial glioma resection outcome including overall patient survival. METHODS: A retrospective review of records was performed on a cohort of 164 consecutive patients who underwent resection surgery for newly diagnosed intracranial gliomas either with or without IoMRI technology performed by 2 neurosurgeons in our center. Patient follow-up was at least 5 years. Extent of resection (EOR) was calculated using pre- and postoperative contrast-enhanced and T2-weighted MR-images. Adjusted analysis was performed to compare gross total resection (GTR), EOR, permanent surgery-associated neurologic deficit, and overall survival between the 2 groups. RESULTS: Overall median EOR was 92.1%, and 97.45% with IoMRI use and 89.9% without IoMRI, with crude (unadjusted) P < 0.005. GTR was achieved in 49.3% of IoMRI cases, versus in only 21.4% of no-IoMRI cases, P < 0.001. GTR achieved was more with the use of IoMRI among gliomas located in both eloquent and noneloquent brain areas, P = 0.017 and <0.001, respectively. Permanent surgery-associated neurologic deficit was not (statistically) more significant with no-IoMRI, P = 0.284 (13.8% vs. 6.7%). In addition, the IoMRI group had better 5-year overall survival, P < 0.001. CONCLUSION: This study shows that the use of IoMRI was associated with greater rates of EOR and GTR, and better overall 5-year survival in both eloquent brain areas located and non-eloquent brain areas located gliomas, with no increased risk of neurologic complication.

2014
Sandro Santagata, Livia S Eberlin, Isaiah Norton, David Calligaris, Daniel R Feldman, Jennifer L Ide, Xiaohui Liu, Joshua S Wiley, Matthew L Vestal, Shakti H Ramkissoon, Daniel A Orringer, Kristen K Gill, Ian F Dunn, Dora Dias-Santagata, Keith L Ligon, Ferenc A Jolesz, Alexandra J Golby, Graham R Cooks, and Nathalie YR Agar. 2014. “Intraoperative Mass Spectrometry Mapping of an Onco-metabolite to Guide Brain Tumor Surgery.” Proc Natl Acad Sci U S A, 111, 30, Pp. 11121-6.Abstract

For many intraoperative decisions surgeons depend on frozen section pathology, a technique developed over 150 y ago. Technical innovations that permit rapid molecular characterization of tissue samples at the time of surgery are needed. Here, using desorption electrospray ionization (DESI) MS, we rapidly detect the tumor metabolite 2-hydroxyglutarate (2-HG) from tissue sections of surgically resected gliomas, under ambient conditions and without complex or time-consuming preparation. With DESI MS, we identify isocitrate dehydrogenase 1-mutant tumors with both high sensitivity and specificity within minutes, immediately providing critical diagnostic, prognostic, and predictive information. Imaging tissue sections with DESI MS shows that the 2-HG signal overlaps with areas of tumor and that 2-HG levels correlate with tumor content, thereby indicating tumor margins. Mapping the 2-HG signal onto 3D MRI reconstructions of tumors allows the integration of molecular and radiologic information for enhanced clinical decision making. We also validate the methodology and its deployment in the operating room: We have installed a mass spectrometer in our Advanced Multimodality Image Guided Operating (AMIGO) suite and demonstrate the molecular analysis of surgical tissue during brain surgery. This work indicates that metabolite-imaging MS could transform many aspects of surgical care.

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