Ambient mass spectrometry for the intraoperative molecular diagnosis of human brain tumors

Eberlin, Lívia S.; Norton, Isaiah; Orringer, Daniel A.; Dunn, Ian F.; Liu, Xiaohui; Ide, Jennifer L.; Jarmusch, Alan K.; Ligon, Keith L.; Jólesz, Ferenc A.; Golby, Alexandra J.; Santagata, Sandro; Agar, Nathalie Y.R.; Cooks, R. Graham

doi:10.1073/pnas.1215687110

Cited by 254 publications

(227 citation statements)

References 30 publications

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“…This unique peak pattern identification enables the diagnosis of cancerous tissue in seconds. This property has already been explored intraoperatively in neurosurgery, allowing for definition of margins and guidance of tumor resection (59,75).…”

Section: Discussionmentioning

confidence: 99%

Application of desorption electrospray ionization mass spectrometry imaging in breast cancer margin analysis

Calligaris

Caragacianu

Liu

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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211

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Distinguishing tumor from normal glandular breast tissue is an important step in breast-conserving surgery. Because this distinction can be challenging in the operative setting, up to 40% of patients require an additional operation when traditional approaches are used.Here, we present a proof-of-concept study to determine the feasibility of using desorption electrospray ionization mass spectrometry imaging (DESI-MSI) for identifying and differentiating tumor from normal breast tissue. We show that tumor margins can be identified using the spatial distributions and varying intensities of different lipids. Several fatty acids, including oleic acid, were more abundant in the cancerous tissue than in normal tissues. The cancer margins delineated by the molecular images from DESI-MSI were consistent with those margins obtained from histological staining. Our findings prove the feasibility of classifying cancerous and normal breast tissues using ambient ionization MSI. The results suggest that an MSbased method could be developed for the rapid intraoperative detection of residual cancer tissue during breast-conserving surgery.B reast cancer is the most commonly diagnosed carcinoma in women in the United States and Western countries. Breast conservation surgery (BCS) has become the preferred treatment option for many women with early-stage breast cancer (1). BCS entails resection of the tumor, with a clean margin of normal tissue around it. Surgery is usually followed by radiation therapy. Results from seven large randomized prospective studies, with the largest two having over 20 y of follow-up, have shown equal survival when comparing BCS coupled with whole-breast radiation and mastectomy (2, 3).Normally, breast surgeons aim to remove a patient's tumor, along with a rim of normal tissue that is free of cancer. Preoperative mammography, ultrasonography, or MRI may be used by the surgeon to guide adequate resection (4-6). Despite numerous improvements in imaging and surgical technique, the need for reexcision to achieve complete tumor resection in the United States typically ranges from 20-40% (7-15), and has been reported as being as high as 60% (16). The importance of reexcision is underscored by numerous studies, which have shown that incomplete resection of tumor and positive margins are associated with increased locoregional recurrence compared with negative margins (12,(17)(18)(19)(20). Furthermore, the landmark meta-analysis performed by the Early Breast Cancer Trialists' Collaborative Group (18, 21) directly linked local recurrence to survival, placing great emphasis on the surgeon's role in minimizing local recurrence by obtaining adequate margins.Breast tumor reexcisions are accompanied by a number of undesirable problems: The completion of therapy is delayed, infection rates are increased, cost is increased, there can be a negative psychological impact on the patient, and there can be diminished aesthetic outcomes (22-24). The development of an intraoperative technique that allows the fast and accurate ident...

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Section: Discussionmentioning

confidence: 99%

Application of desorption electrospray ionization mass spectrometry imaging in breast cancer margin analysis

Calligaris

Caragacianu

Liu

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

211

186

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“…Similar methods of ionization have been used for the detection of lipids from lung (21) and brain cancer (22). DESI-MS imaging of stereotactically registered brain tumor samples (23) gave results that correlated with histopathology and illustrated the potential for determining tumor cell concentration near the resection margins (10). The analysis of gastric cancer surgical margins has been reported recently, including pixel by pixel classification of heterogeneous tissue sections (8).…”

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confidence: 99%

“…Previous studies (3)(4)(5)(6)(7)(8)(9)(10)(11) have shown tissue discrimination by mass spectral profiles (m/z values and associated abundances) characteristic of different tissue types, including different disease states. Rapid and direct analysis of tissue provides molecular information on multiple compounds and is obtained on a timescale of seconds to a few minutes.…”

mentioning

confidence: 99%

“…In each case, the recorded pattern of lipid signals allows the differentiation of cancer from normal tissue. DESI-MS has been previously used to explore chemical differences among glioma subtypes, grades, and tumor cell concentrations (relative percentage of tumor compared with parenchyma) (9,10). Meningiomas have also been studied previously and were distinguished from normal dura mater (11).…”

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confidence: 99%

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Lipid and metabolite profiles of human brain tumors by desorption electrospray ionization-MS

Jarmusch

Pirro

Baird

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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162

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Examination of tissue sections using desorption electrospray ionization (DESI)-MS revealed phospholipid-derived signals that differ between gray matter, white matter, gliomas, meningiomas, and pituitary tumors, allowing their ready discrimination by multivariate statistics. A set of lower mass signals, some corresponding to oncometabolites, including 2-hydroxyglutaric acid and N-acetylaspartic acid, was also observed in the DESI mass spectra, and these data further assisted in discrimination between brain parenchyma and gliomas. The combined information from the lipid and metabolite MS profiles recorded by DESI-MS and explored using multivariate statistics allowed successful differentiation of gray matter (n = 223), white matter (n = 66), gliomas (n = 158), meningiomas (n = 111), and pituitary tumors (n = 154) from 58 patients. A linear discriminant model used to distinguish brain parenchyma and gliomas yielded an overall sensitivity of 97.4% and a specificity of 98.5%. Furthermore, a discriminant model was created for tumor types (i.e., glioma, meningioma, and pituitary), which were discriminated with an overall sensitivity of 99.4% and a specificity of 99.7%. Unsupervised multivariate statistics were used to explore the chemical differences between anatomical regions of brain parenchyma and secondary infiltration. Infiltration of gliomas into normal tissue can be detected by DESI-MS. One hurdle to implementation of DESI-MS intraoperatively is the need for tissue freezing and sectioning, which we address by analyzing smeared biopsy tissue. Tissue smears are shown to give the same chemical information as tissue sections, eliminating the need for sectioning before MS analysis. These results lay the foundation for implementation of intraoperative DESI-MS evaluation of tissue smears for rapid diagnosis. ambient ionization | MS imaging | multivariate statistics | pathology | neurosurgery M S is increasingly being used in medicine (e.g., in clinical chemistry, pharmaceutical development, and proteomics). Ambient ionization methods generate ions under atmospheric conditions, with minimal to no sample preparation (1). Desorption electrospray ionization (DESI), an ambient method that uses a spray of charged solvent as the projectile, provides rapid chemical information while preserving tissue and cellular morphology, allowing subsequent histopathology on the same specimen (2). This feature allows integration of DESI-MS into current workflows and postacquisition pathology. DESI-MS has been used to study prostate cancer (3), bladder cancer (4), kidney cancer (5), seminoma (6), lymphoma (7), gastrointestinal cancer (8), and others. In each case, the recorded pattern of lipid signals allows the differentiation of cancer from normal tissue. DESI-MS has been previously used to explore chemical differences among glioma subtypes, grades, and tumor cell concentrations (relative percentage of tumor compared with parenchyma) (9, 10). Meningiomas have also been studied previously and were distinguished from normal dura mater (11).T...

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“…6 The major drawback of this technique is that it cannot be used for in vivo analysis as it includes use of organic solvent sprays, high-pressure nebulizing gas, and high voltages. 3,7,8 It is also known to have lower spatial resolution (180-200 μm). 6 The MS coupled with ultraviolet lasers and infrared lasers is a laser desorption ionization (LDI)-MS analysis.…”

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confidence: 99%

Is the Pen really Mightier than the Scalpel?

Sarode

Choudhary

Sarode

et al. 2017

The Journal of Contemporary Dental Practice

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Ambient mass spectrometry for the intraoperative molecular diagnosis of human brain tumors

Cited by 254 publications

References 30 publications

Application of desorption electrospray ionization mass spectrometry imaging in breast cancer margin analysis

Application of desorption electrospray ionization mass spectrometry imaging in breast cancer margin analysis

Lipid and metabolite profiles of human brain tumors by desorption electrospray ionization-MS

Is the Pen really Mightier than the Scalpel?

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