Translating Pre-Clinical Research to Clinical Patient Care™

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Golden West Diagnostics


Brian Kelly

SCIEX


A Focused Agenda for Pathologists Interested in Spatial Mass Spectrometry

Tuesday - Thursday, March 19-21

Seeking Anatomic Pathologists interested in participating in the development, translation and implementation of Intraoperative and Histological Mass Spectrometry.

Earn CME credit in Monterey, California where researchers and pathologists will come together to discuss the latest advancements and opportunities for improving patient care.

MSACL 2024 and members of the Mass Spectrometry Imaging community are building a specialized 3-day program, March 19-21, on Spatial Mass Spectrometry as a Driver of NextGen Dx (see below).

Educational grants are available for Trainees (registration and 4 nights hotel) and practicing early career Pathologists (registration). Apply for educational grants.

Exhibit booths and industry workshops are available.

Please share with your local Anatomic Pathologists and MSI friends!

Can't make it to Monterey? Mark September 21-26, 2025 on your calendar for the next edition to be held in Montreal, Canada.

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Time

Sessions

Workshop : Concepts in Histology and Histopathologic Diagnosis for Researchers

Location: De Anza 1 (Portola Hotel > Ground Floor)

Albert Tsai, MD, PhD

Stanford

How pathologists diagnose human tissue samples differs markedly from how many researchers study them. Research approaches often seek to reduce two-dimensional tissue imaging to single cell data, i.e. cytometry-on-a-slide. However, these methods are complicated by technical aspects of tissue processing, and they may miss the overarching histologic patterns which underlie pathologic diagnosis. Thus, early engagement with pathologists is useful not only for obtaining tissue samples, but also for understanding structure-function relationships and relevance to disease. Furthermore, pathologists regularly integrate multiple data modalities to classify diseases, e.g. histology with antibody-based protein detection and DNA sequencing. Their understanding of the utilities of each modality within the larger diagnostic context is helpful for identifying potential roles for new technologies.

Get-the-Basics : MALDI Mass Spectrometry Imaging – A New Method in Pathology?

Location: De Anza 1 (Portola Hotel > Ground Floor)

Kristina Schwamborn, MD, PhD

Technical University of Munich

Matrix assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI) combines the excellence in molecular characterization of mass spectrometry with microscopic imaging capabilities of stained tissue samples, enabling the precise location of different analyte classes (e.g., proteins, peptides, lipids, glycans) directly within intact tissue. In particular in the field of pathology, that can aid in tumor diagnosis, tumor subtyping, biomarker identification, prognostic prediction, and characterization of tumor margins during tumor resection procedures. Since MALDI MSI goes far beyond microscopy, it is ideal for these endeavors. It can generate molecular maps of tissue sections that can elucidate the underlying biochemistry or provide information on how therapeutics or toxins influence the function or misfunction of an organ. Thus, it has the potential to overcome limitations of other approaches in the identification and routine diagnostic measurement of new marker molecules/profiles.

Different applications in the field of pathology/ oncology will be presented that highlight possible applications of MALDI MSI in Pathology. Combining MALDI MSI, histology, and statistical analysis allows for reliable and fast subtyping in a number of different tumor types while also conserving material that could be used for additional testing.

Industry Lunch Workshop : Ionpath

Location: San Carlos 4 (Marriott > Mezzanine | Stairs from Lobby or SkyBridge from Conference Ctr)

Workshop : Surgical Mass Spectrometry – Delivering the Technology to the Operating Room

Location: De Anza 1 (Portola Hotel > Ground Floor)

Zoltan Takats, PhD

Imperial College

Lauren Ford, BSc (Hons), PhD

Imperial College London

Objectives

To identify methods to deliver mass spectrometry guided surgery to become routinely used in the clinical interventional world. The workshop will focus on the interpretation of clinical information/data and how this should be fed back to healthcare professionals and ultimately patients. The workshop will highlight the limitations of current technologies and developments enabling clinical adoption.

Summary

The need for in-situ, real time tissue identification has been dramatically increasing with the development and deployment of robotic and other high-precision surgical approaches. While surgical mass spectrometry techniques have been continuously developed, published, and demonstrated in human surgical theatres, none of these approaches have reached regulatory approval and routine application in surgery. We will use this interactive setting to discuss overcoming current roadblocks to delivering technology for patients and healthcare professionals. The workshop will give an overview of the current mass spectrometry technology developed and the strengths and weaknesses in each approach. This will be followed by discussing the embedding of the approach both into existing oncology and clinical diagnostic systems. Using Mass Spectrometry in surgery will change how interventional cancer care is delivered, hence it is important to ensure data tools are developed which can be relied on. Delivery of the obtained clinical information in the operating theatre is also important to explore. As part of this workshop, we will discuss data visualisation strategies such as in the virtual reality space, delivery of feedback to the clinical healthcare professionals and tools developed to advance usability, such as navigation. Data interpretation in the wider context of clinical oncology will also be explored.

Syllabus/Topics

• Surgical mass spectrometry methods – strengths, weaknesses, applications and future perspectives
• Embedding of technology into healthcare systems. How to deliver clinical information, data interpretation, navigation guidance and feedback.
• Regulatory and health economics aspects.

Plenary : Mass Spectrometry as a Driver for Discovery of Biomarkers and Therapeutic Targets in Lymphoma

Location: Steinbeck Ballroom (Conference Ctr > 2nd Floor)

Kojo Elenitoba-Johnson, MD

Memorial Sloan Kettering Cancer Center

Declaration of Competing Interests

Dr. Elenitoba-Johnson declares no conflicts of interest.

Plenary : Steroid Metabolomics for Diagnostic and Prognostic Biomarker Development

Location: Steinbeck Ballroom (Conference Ctr > 2nd Floor)

Wiebke Arlt, MD DSc FRCP FMedSci

Medical Research Council Laboratory of Medical Sciences

I will discuss steroid metabolomics, the combination of mass spectrometry-based steroid profiling with machine learning-based steroid data analysis. I will provide two clinically relevant examples: (1) the development of a new diagnostic biomarker test for the detection of adrenal cancer, with a timeline covering the last 15 years and including discovery, optimisation and prospective validation - adrenal cancer is rare but regularly discovered upon the investigation of incidentally discovered adrenal nodules, which are detected in 5% of all cross-sectional imaging scans; (2) the exploration of the steroid metabolome in a large comprehensively phenotyped cohort of newly diagnosed and treatment naïve women with polycystic ovary syndrome (PCOS), a condition affecting 10-15% of women worldwide and associated with significantly increased metabolic disease risk. Showing our data from this cohort, I will describe the potential of steroid metabolomics for detailed phenotyping, mechanistic exploration, prognostic prediction and therapeutic stratification in this underserved population.

Declaration of Competing Interests

Dr. Arlt declares no conflicts of interest.

Plenary : Graham Cooks Lifetime Achievement Award & Mini-Lecture : Mass Spectrometry in Diagnostics and Therapeutics: the Long View

Location: Steinbeck Ballroom (Conference Ctr > 2nd Floor)

R. Graham Cooks, PhD

Purdue University

R. Graham Cooks1,2, Nicolás Morato1,2, Andrew Mesecar1,3
1Department of Chemistry, 2Department of Biochemistry, and 3Purdue Institute for Cancer Research, Purdue University. West Lafayette, IN 47907

This talk covers an as-yet-unfinished journey. It describes a suite of methods and instrumentation that is the work of many individuals over a long period. Applications to diagnostics, especially intraoperative diagnostics, are ongoing for brain and other cancers. The long view espoused here, describes a series of steps that stretches from half-century old mass spectrometry to new drug candidates, specifically for the case of prostate cancer.

1. MS and MS/MS: because mass spectrometry (MS) is a well suited to characterizing organic compounds, it can be used to characterize complex mixtures, provided sample ionization produces a corresponding mixture of molecular ions. This 1:1 transformation (molecule -> molecular ion) was first achieved by the then-new method of chemical ionization. This allowed two stages of mass analysis, MS/MS, to became an alternative to GC/MS (and later to LC/MS) for mixture analysis.[1]

2. Ambient ionization: the simplest, most direct form of MS, ionizes objects/materials/samples in the open air. Electrospray ionization provided the lead on atmospheric pressure ionization, but ambient ionization [2] goes further and avoids sample manipulation or purification. Desorption electrospray ionization (DESI) effects ionization by localized solvent extraction.[3]

3. MS imaging: any directed ionizing agent (ions in SIMS, neutrals in FAB, photons in LDI, droplets in DESI) is inherently an imaging method.[4]

4. Biomarker discovery: Comparisons of diseased and healthy tissue point to potential biomarkers, e.g. DESI MS/MS analysis of prostate tissue showed preferential localization of cholesterol sulfate in diseased tissue.[5].

5. Target validation: knockdown studies established an association of cholesterol sulfate transferase with prostate cancer.[6]

6. Late stage functionalization: High throughput DESI instrumentation [7] uses accelerated reactions in microdroplets [8,9] to synthesize large numbers of new drug candidates on the millisecond time scale.[10]

7. Enzyme inhibition: Collection of the functionalized products followed by enzyme kinetic measurements [10] validated inhibition for several particular compounds as potential prostate cancer drugs. 8. Animal, safety and efficacy studies lie in the future.

Support from NCATS and Waters, Inc. is gratefully acknowledged.

[1] R. W. Kondrat and R. G. Cooks, Anal. Chem. 50 (1978) 81A
[2] R. Graham Cooks, Zheng Ouyang, Zoltan Takats, Justin M. Wiseman, Science, 311 (2006) 1566-1570
[3] Zoltán Takáts, Justin Wiseman, Bogdan Gologan and R. Graham Cooks, Science, 306 (2004) 471 – 473
[4] Justin M. Wiseman, Demian R. Ifa, Qingyu Song, R. Graham Cooks”, Angew. Chem. Int. Ed. 45 (2006) 7188 – 7192
[5] Livia S. Eberlin; Allison L. Dill; Anthony B. Costa; Demian R. Ifa; Liang Cheng; Timothy Masterson; Michael Koch; Timothy L. Ratliff; R. Graham Cooks, Anal. Chem., 82 (2010) 3430–3434
[6] Renee E Vickman, Scott A. Crist, Kevin Kerian, Livia Eberlin, R. Graham Cooks, Grant N. Burcham, Kimberly K Buhman, Chang-Deng Hu, Andrew D. Mesecar, Laing Cheng and Timothy Ratliff, Mol. Cancer Res. 14 (2016) 776 – 786
[7] Michael Wleklinski, Bradley P. Loren, Christina R. Ferreira, Zinia Jaman, Larisa Avramova, Tiago J. P. Sobreira, David H. Thompson and R. Graham Cooks, Chem. Sci. 9 (2018) 1647 – 1653
[8] Xin Yan, Ryan M. Bain, and R. Graham Cooks Angew. Chem. Int. Ed. 55 (2016) 12960-12972
[9] R. Graham Cooks, Yunfei Feng, Kai-Hung Huang, Nicolás M. Morato, and Lingqi Qiu, Israel J. Chem. 63 (2023) e202300034
[10] Kai-Hung Huang, Nicolás M. Morato, Yunfei Feng, and R. Graham Cooks Angew. Chem. (2023) e202300956

Declaration of Competing Interests

The Cooks lab receives grant support from Waters.

Scientific Session 1

Location: De Anza 1 (Portola Hotel > Ground Floor)

Desorption Electrospray Ionisation: 22 Successful Years and Still Counting
Zoltan Takats, PhD
Imperial College

Desorption Ionization Mass Spectrometry for Intraoperative Cancer Diagnostics
Hannah Brown, PhD
Washington University School of Medicine in St. Louis

Intra-operative Mass Spectrometry in Neurosurgery
Diogo Garcia, MD
Mayo Clinic

Scientific Session 2

Location: De Anza 1 (Portola Hotel > Ground Floor)

Providing In Vivo Tissue Sensing Capabilities to Surgeons with the MasSpec Pen: Challenges and Opportunities
Livia Eberlin, PhD
Baylor College of Medicine

Discussion Group : NIH Funding to Support Technology Development, Translation, and Transfer

Location: De Anza 1 (Portola Hotel > Ground Floor)

Kelly Crotty, PhD

National Cancer Institute (NCI)

Technical innovation can improve and transform our ability to understand, prevent, diagnose, and treat human disease. NIH drives early-stage innovative technology development and the translation of emerging tools into laboratory and clinical use through several technology-focused grant programs. Dr. Crotty will discuss several of these programs and the diverse technologies that have been supported through them, as well as resources for tech transfer that are offered through NIH.

Discussion Group : FDA Regulation of LDTs

Location: Bonsai (Portola Hotel > Ground Floor)

E. Ellen Jones, PhD

National Center for Toxicological Research, FDA

Regulation of LDTs or laboratory developed tests by the FDA has long been a topic of interest and discussion. With the advent of new technologies and approaches there remains a gap between what is analytically possible with newer instrumentation versus what is currently allowed for regulatory use. Clearly, the FDA is aware of new analytical methods and capabilities and knows that new guidance’s are needed. This workshop will discuss some of the historical information on these LDT’s and provide a perspective from a non-regulatory FDA research scientist who is also working on incorporating novel technologies to inform regulatory decision making within the FDA.

Spatial Proteomics: Considerations for Clinical and Research Applications

Location: De Anza 1 (Portola Hotel > Ground Floor)

Megan Lim, MD, PhD

Memorial Sloan Kettering Cancer Center

20 minute Presentation followed by a Group Discussion.

Scientific Session 3

Location: De Anza 1 (Portola Hotel > Ground Floor)

15 Years of iKnife; Applications, Advances, and Breakthroughs
Lauren Ford, BSc (Hons), PhD
Imperial College London

MS Imaging-Based Prediction of Cell Population Ratio: Towards Real-Time Digital Twins for Margin Delineation and Cancer Prognosis
Léa Ledoux
Laboratoire Prism Inserm U1192

Navigated 3D MS for Intra-operative Tissue Margin Assessment during Breast Cancer Surgery – Changing the Standard of Cancer Care through Metabolic Image Guidance
John Rudan, PhD, FRCSC
Queen's University

Scientific Session 4

Location: De Anza 1 (Portola Hotel > Ground Floor)

Intraoperative Workflows, MALDI MSI of Tissue, and Data Visualization in MRI
Michael Regan
Brigham and Women's Hospital

Imaging of Brain Signaling Molecules
Per Andrén, PhD
Uppsala University

Discussion on the Pros and Cons of Working with Fresh Frozen versus FFPE Tissue
Discussion Session
Scientific Session 5

Location: De Anza 1 (Portola Hotel > Ground Floor)

The Extracellular Microenvironment as a Pathological Differentiator
Peggi Angel, PhD
MUSC Proteomics Center

Integration of Multiplexed Spatial Multi-omics for Deeper Understanding of Cancer Biology
Erin Seeley, PhD
University of Texas at Austin

Spatial Framework for Understanding Immune Tolerance in Human Health and Disease
Michael Angelo, MD, PhD
Stanford University School of Medicine

Scientific Session 6

Location: De Anza 1 (Portola Hotel > Ground Floor)

Molecular Heterogeneity in Human Pancreas, Kidney, and Eye Revealed by Multimodal Spatial Atlases
Angela Kruse, PhD
Vanderbilt

The Human Protein Atlas – an open access resource providing expression references in tissues and cells
Evelina Sjostedt, PhD
SciLifeLab
(Top-down) Mass Spectrometry Histochemistry on sections of FFPE Tissue Banks: current status and future perspectives
Peter Verhaert, Prof. PhD
ProteoFormiX