Unraveling Nature’s Complexity with Molecular Imaging

Unraveling Nature’s Complexity with Molecular Imaging


On this interview carried out at Pittcon 2023 in Philadelphia, Pennsylvania, we spoke to Ron Heeran, a speaker on the 2023 James L. Waters Symposium.

Please might you introduce your self, and inform us about your private background and what first attracted you to this discipline?

I’m Ron Heeren, a distinguished professor of molecular imaging at Maastricht College within the Netherlands. I’m additionally the director of the Maastricht MultiModal Molecular Imaging Institute. I used to be educated as a physicist, then developed a profession in biochemistry, and now I’m instructing in a medical middle.

I’ve all the time questioned concerning the complexity of nature. Considered one of my heroes, Richard Feynman, as soon as stated that you need to cease and give it some thought to essentially admire nature’s complexity; the inconceivable nature of nature.

I really like that quote as a result of it describes what triggered me to enter science: to fulfill my curiosity and perceive the complexity of the world round me. The great thing about molecular imaging is that it does exactly that. It exhibits the inconceivable complexity of nature on a microscope slide.

What’s secondary ion mass spectrometry?

The sector I’m partaking in is molecular imaging utilizing . There are basically two methods of producing pictures with a mass spectrometer. The primary is firing lasers at a floor to evaporate and ionize molecules, then analyzing them within the mass spectrometer. The second makes use of an ion beam, the place a major ion generates secondary ions which can be then analyzed by a mass spectrometer.

The latter is the sector of secondary ion mass spectrometry. In my work, we use each in live performance as a result of every know-how has complementary options. The great thing about SIMS is that it might obtain spatial resolutions, similar to no different method in imaging mass spectrometry.

What’s molecular imaging extra broadly and what are its benefits?

Molecular imaging is a type of molecular pictures the place we take snapshots of the molecules on extremely advanced surfaces, similar to tissue sections or biopsies of most cancers sufferers, photo voltaic cells, and even leaves with microbes rising on them, and we attempt to visualize them.

Unraveling Nature’s Complexity with Molecular Imaging

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Molecular imaging produces a map or {a photograph} of the spatial location of the molecules mixed with the identification of the molecules themselves.

How can secondary ion mass spectrometry be employed in molecular imaging?

The great thing about secondary ion mass spectrometry is its unbelievable spatial decision. These ion beams may be centered right down to an especially small spot, right down to 50 nanometers. With molecular imaging, we are able to generate very small pixels, which supplies an perception into what’s going on in a single cell within the context of an entire tissue.

Basically, SIMS brings very excessive spatial decision. One added benefit is that we are able to examine a person single cell, layer by layer, and create a three-dimensional map of all molecules in that single cell.

In what medical fields can advances in digital molecular pathology have an effect?

Molecular imaging is getting into digital pathology, a pathologist taking a look at digital pictures slightly than by means of a microscope. As molecular imaging utilizing mass spectrometers generates digital pictures, they are often shared simply with the pathologist.

They are often layered on high of the optical pictures that they have already got. Now, the pathologist can increase how they take a look at the issue with molecular info. One instance is detecting tumor cells in biopsy tissue. We are able to take a look at tissue sections from cartilage from broken knees to grasp the therapeutic course of and design new medication.

We are able to take a look at pharmaceutical and animal fashions, the place we observe the place the drug finally ends up, how it’s metabolized, and if it has an impact. These are all issues in a spatial context. These applied sciences may be utilized with a gold star in biomedicine and pharmaceutical analysis.

How can progressive imaging applied sciences supply new insights into life’s complexity?

We see these pictures in additional molecular element as our mass spectrometers enhance. A few of these molecular adjustments that set off a illness course of or that folks need to intervene with when designing a brand new drug (to avoid a illness) are associated to minute molecular adjustments.

Fashionable mass spectrometers allow us to see issues like isomeric species. This lipid has a double bond very near the glycerol spine or very distant, two very completely different buildings. We are able to now visualize the place that construction differs in a tissue or cell.

Image Credit: Intothelight Photography/Shutterstock.com

Picture Credit score: Intothelight Images/Shutterstock.com

Mass spectrometry imaging can unravel this complexity at spatial and molecular element ranges. We are able to take a look at the identification of a molecule, the place the molecule is within the cell, the place that cell is in a bit of tissue, and the place that tissue comes from in a affected person. This allows the outline of your entire translational imaging chain.

The thirty fourth James L. Waters Symposium highlights the event, industrial development, and up to date advances in instrumentation and its functions. What are among the current developments in secondary ion mass spectrometry?

The James L. Waters Symposium highlights instrumentation advances, similar to focused pathology, the place folks use labeled antibodies to look at focused proteome processes intimately. One other know-how offered that we labored on is utilizing a detector from CERN within the molecular pathology discipline to speed up the speed at which we are able to generate these pictures.

We might take maybe 100 to a thousand pixels per second on a typical industrial instrument. Every pixel corresponds to the mass spectrum. These new detectors from CERN allow the acquisition of a thousands and thousands of pixels per second, so we’re very near reaching our present objective of scanning one tissue slide in a single minute.

This will likely be completely in sync with the pathology workflow. Our applied sciences with SIMS and CERN would seamlessly match into the digital pathology workflow.

How necessary is it to grasp the historical past of the necessary contributions and cooperations on this discipline?

The significance of historical past can’t be confused sufficient as a result of all of us stand on the shoulders of giants. One of many approaches that we’re nonetheless working with was developed within the Nineteen Sixties, however now we now have leapfrogged away with all the brand new applied sciences that weren’t accessible again then, however the fundamental concepts stay the identical.

These early concepts are actually accelerating due to all the brand new accessible applied sciences. This symposium superbly highlighted that because it introduced collectively all these completely different components: instrumentation, engineering, software within the clinic, focused pathology, and the historical past on which all of it was based mostly.

What are the present challenges inside the secondary ion mass spectrometry-based molecular imaging discipline?

Considered one of our greatest challenges is the sheer quantity of knowledge we produce. One facet of that is information storage, as we’re obliged by regulation to maintain affected person information for as much as 15 years. If I generate three terabytes in 10 minutes and retailer it for 10 or 15 years, then my storage invoice will outweigh my electrical energy invoice in a short time.

Researchers are wanting into smarter options for storing information, perhaps solely buying related information to scale back the quantity of knowledge we generate.

Image Credit: Gorodenkoff/Shutterstock.com

Picture Credit score: Gorodenkoff/Shutterstock.com

The opposite facet is what we do with the info and the way we interpret it. We have now one million spectra per second; no human thoughts might undergo these spectra individually. We want extra progressive synthetic intelligence, machine studying, and neural community instruments to discover the info and discover the related info we search to grasp the complexity of well being and illness.

How do you hope your work will assist overcome among the challenges you talked about?

I’m afraid my work will solely worsen these two challenges as a result of we’re producing extra information in a shorter time. Nonetheless, whereas we’re doing that, we additionally face these challenges. We have now many bioinformaticians that we collaborate with to sort out these issues utilizing machine studying and neural networks.

I believe my group’s contribution to this discipline is that we see that to unravel these challenges, we want researchers from many alternative disciplines. It isn’t simply the software we develop to unravel information evaluation challenges however easy methods to collaborate throughout the boundaries of disciplines.

That is one factor that imaging mass spectrometry excels at as a result of there’s the basic facet, instrumentation, software growth, and information dealing with. All of them have to come back collectively. Our contribution is bringing these folks collectively within the institute across the acceptable infrastructure to sort out these challenges.

What are you presently engaged on that you’re notably enthusiastic about?

One challenge we’re enthusiastic about is single-cell imaging utilizing our to construct libraries of molecular profiles of immune cells after which routinely acknowledge these cells in a bit of tissue.

This permits us to grasp how the metabolic phenotype of an immune cell adjustments within the presence of a tumor and as a response to the space to the tumor. A lot extra complexity is but to be found and understood, which can considerably contribute to that.

About Professor Ron Heeran

Prof. Dr. Ron M.A. Heeren obtained a PhD diploma in technical physics in 1992 on the College of Amsterdam on plasma-surface interactions. He began to work on molecular imaging instrumentation and its software as a analysis group chief at FOM-AMOLF, Amsterdam. In 2001, he grew to become professor on the chemistry college of Utrecht College lecturing on the bodily facets of biomolecular mass spectrometry. In 2014 he began as distinguished professor and Limburg Chair at Maastricht College. He’s the founder and scientific director of M4I, the Maastricht MultiModal Molecular Imaging institute on the Brightlands Maastricht Well being campus. He was awarded the celebrated 2019 Physics Valorization prize by the Dutch group for scientific Analysis, NWO and the 2020 Thomson medal of the worldwide mass spectrometry basis. In 2021 he was elected as a member of the Royal Dutch Academy of Sciences, KNAW. His educational analysis pursuits are mass spectrometry based mostly personalised medication, translational molecular imaging and “omics” analysis, high-throughput bioinformatics and the event and validation of progressive molecular analytical imaging methods throughout the scientific disciplines. 

About Pittcon

is the world’s largest annual premier convention and exposition on laboratory science. Pittcon attracts greater than 16,000 attendees from business, academia and authorities from over 90 nations worldwide.

Their mission is to sponsor and maintain academic and charitable actions for the development and advantage of scientific endeavor.

Pittcon’s target market isn’t just “analytical chemists,” however all laboratory scientists — anybody who identifies, quantifies, analyzes or exams the chemical or organic properties of compounds or molecules, or who manages these laboratory scientists.

Having grown past its roots in analytical chemistry and spectroscopy, Pittcon has developed into an occasion that now additionally serves a various constituency encompassing life sciences, pharmaceutical discovery and QA, meals security, environmental, bioterrorism and different rising markets.