• GUEST: Fabian Kiessling, Aachen

Welcome to the Christmas edition of "Dive into imaging science"! Giannis and Tim have their festive hats on and are wearing their dodgy Christmas jumpers, ready for a cracker (!) of an episode. And we have a very special guest on the show – none other than our current past president, Fabian Kiessling, who heads up the Institute of Experimental Molecular Imaging and the Helmholtz Institute for Biomedical Engineering at Aachen University.

We explore how to ‘make the visible invisible’ in the groundbreaking paper from the lab of Guosong Hong at Stanford by achieving optical transparency in live animals using a food dye that’s an ingredient in many potato chips! We conclude that this isn’t, in fact, the end of non-invasive imaging; instead, it opens a new frontier for optical and photoacoustic techniques.

Along the way, we learn that Fabian could have been a policeman if only he hadn’t been “a little bit weak in differentiating red and green” and that being a scientist is very much like being an artist. We discuss reproducibility in science, the importance of co-locating labs and people, and were swept along by Fabian’s passion for imaging science.

Cocktail - Continuing our tradition, we enjoy a special cocktail : It’s a Christmas and Aachen special so what better way to celebrate it with a twist on the Gluehwein Cretan style: Giannis’ own home-made brandy and raki (cretan grappa that is), red wine, cinnamon sticks, cloves, honey and a red orange slice from his garden.

Selected Publication: Ou Z, Duh YS, Rommelfanger NJ, Keck CHC, Jiang S, Brinson K Jr, Zhao S, Schmidt EL, Wu X, Yang F, Cai B, Cui H, Qi W, Wu S, Tantry A, Roth R, Ding J, Chen X, Kaltschmidt JA, Brongersma ML, Hong G. Achieving optical transparency in live animals with absorbing molecules. Science. 2024 Sep 6;385(6713):eadm6869. doi: 10.1126/science.adm6869. Epub 2024 Sep 6. PMID: 39236186.

Further information on the European Society for Molecular Imaging:
https://e-smi.eu/
Contact: office@e-smi.eu

• GUEST: Elisa Konofagou, New York

We continue at full speed with back to back podcasts hosting leaders in the field of molecular imaging. In this edition we welcome Elisa Konofagou and share her passion for ultrasound imaging and its unique capabilities for visualising biology inside the human body. Her group has developed methods for estimating minute deformation as a result of physiological function, such as in the heart and vessels, and displacements induced by the ultrasound wave itself, such as in tumours and nerves. She is particularly interested in translating these technologies to a clinical setting and impacting the improvement of healthcare.

The use of innovative ultrasound imaging to solve a clinical problem is the focus of this edition. The discussion revolves around a paper presenting an artful application of ultrasound localization microscopy to image the hemodynamics of myocardial microvasculature in patients. The paper was recently published from the group of Meng-Xing Tang at Imperial College London in Nature Biomedical Engineering.

We discover their breakthrough approach in achieving super resolution, that is resolution beyond the diffraction limit of ultrasound waves, by localizing the position and following the path of circulating microbubbles in the vasculature in a beating human heart. This study presents the potential of ultrasound localisation microscopy to improve the understanding of myocardial microcirculation with a great impact on patients with cardiac microvasculature and coronary heart disease. As a bonus discussion before the end we briefly touch upon the art of choosing how to write a paper: when should we write a detailed paper for a very specific audience, vs making it accessible to generalists?

Continuing our tradition, we enjoy a special cocktail dedicated to Elisa’s French connection as well as the chosen paper. For this edition the “French 75”, invented some 100 years ago in Paris. If you want to try it while listening here’s the recipe: 1 measure Gin, ½ measure fresh lemon juice, ½ measure sugar syrup, top up with champagne for some microbubbles! Serve in a flute and garnish with a lemon twist.

Selected Publication: Yan J, Huang B, Tonko J, Toulemonde M, Hansen-Shearer J, Tan Q, Riemer K, Ntagiantas K, Chowdhury RA, Lambiase PD, Senior R, Tang MX. Transthoracic ultrasound localization microscopy of myocardial vasculature in patients. Nat Biomed Eng. 2024 Jun;8(6):689-700. doi: 10.1038/s41551-024-01206-6. Epub 2024 May 6. PMID: 38710839; PMCID: PMC11250254.

Further information on the European Society for Molecular Imaging:
https://e-smi.eu/
Contact: office@e-smi.eu

• GUEST: John Ronald, London (ON, Canada)

Welcome back! It has been a while but we are back with a bang, having our good friend John Ronald from The Robarts Research Institute in London, Ontario as our guest. John’s group combines advances in molecular and synthetic biology with a multimodal imaging perspective to build new tools for early detection and treatment of cancer, as well as non-invasive monitoring of cell, gene and genome therapies.

One of John’s passions is gene reporter imaging, which is also the main focus of this edition. The paper up for discussion comes from Cynthia Dunbar’s lab at NIH, Bethesda which was recently published in Cell Stem Cell. We discover their approach to non-invasively follow engraftment and maturation of pluripotent stem cells in rhesus macaques with myocardial infarctions, discuss some of the technicalities of engineering autologous cells, and fall in love with the beautiful RNAScope images that are presented. We discuss what makes a good imaging reporter, why one size doesn’t always fit all, and a future where not just cells, but activation states can be imaged.

Along the way, John also shares advices received from the wonderful Sanjiv Sam Gambhir on how to improve the chances of getting your grants funded and that supposedly crazy ideas should not be discarded... they might even lead to high impact publications.

And of course, true to our tradition, we enjoy a special cocktail. For this edition the “Angry Canadian”, obviously. For the curious listeners: a good measure of Whisky, 2 tablespoons of fine Canadian Maple syrup, a few drops of bitters and 1 teaspoon lemon juice, then top up with soda water.

Selected Publication: Lin Y, Sato N, Hong S, Nakamura K, Ferrante EA, Yu ZX, Chen MY, Nakamura DS, Yang X, Clevenger RR, Hunt TJ, Taylor JL, Jeffries KR, Keeran KJ, Neidig LE, Mehta A, Schwartzbeck R, Yu SJ, Kelly C, Navarengom K, Takeda K, Adler SS, Choyke PL, Zou J, Murry CE, Boehm M, Dunbar CE. Long-term engraftment and maturation of autologous iPSC-derived cardiomyocytes in two rhesus macaques. Cell Stem Cell. 2024 Jul 5;31(7):974-988.e5. doi: 10.1016/j.stem.2024.05.005. Epub 2024 Jun 5. PMID: 38843830; PMCID: PMC11227404. https://www.cell.com/cell-stem-cell/abstract/S1934-5909(24)00182-6

Further information on the European Society for Molecular Imaging:
https://e-smi.eu/
Contact: office@e-smi.eu

GUEST: Kevin Brindle, Cambridge
In this episode we welcome the one and only Kevin Brindle from University of Cambridge.

During his long and illustrious career, Kevin pioneered hyperpolarized magnetic resonance spectroscopy as a method to map metabolic flux in cancer and other diseases, with implications for treatment response monitoring.

We explore how deuterium imaging and [18F]FDG PET can be used to track the metabolic changes that occur soon after stroke and during the recovery phase. We discuss the complementary information that these two techniques provide and whether they could be used to improve clinical outcomes.

Along the way, we learn how Kevin could have worked in structural biology or been a painter and decorator... and how he used to meet his wife-to-be in the cold room when he was a postdoc at Oxford.

Selected Publication: In vivo imaging of cerebral glucose metabolism informs on subacute to chronic post-stroke tissue status - A pilot study combining PET and deuterium metabolic imaging. Meerwaldt AE, Straathof M, Oosterveld W, van Heijningen CL, van Leent MM, Toner YC, Munitz J, Teunissen AJ, Daemen CC, van der Toorn A, van Vliet G, van Tilborg GA, De Feyter HM, de Graaf RA, Hol EM, Mulder WJ, Dijkhuizen RM. J Cereb Blood Flow Metab. 2023 May;43(5):778-790. doi: 10.1177/0271678X221148970. Epub 2023 Jan 6.
https://journals.sagepub.com/doi/10.1177/0271678X221148970

Further information on the European Society for Molecular Imaging:
https://e-smi.eu/
Contact: office@e-smi.eu

GUEST: Mikhail Shapiro, Pasadena
In this episode we welcome our famous guest Mikhail Shapiro from Caltech. Mikhail exquisitely combines ultrasound with synthetic biology for gene regulation, imaging, and therapy - and Synthetic biology is surely the common thread in this podcast edition.

We discover how an engineered receptor and an intracellular signalling domain, known as ‘synNotch’ can be used to visualise cell-cell communication in vivo. And how this system can be used to identify immune-cancer cell interactions, why it provides far more information than just knowing where the immune cells reside, and the various merits of the three different reporter genes employed for visualisation across scales.

We also reveal some insider information into the review process for the selected paper from the senior author John Ronald. Along the way, we speculate why the synNotch system improves NK cell kill and Tim ends up dreaming of sheep jumping over logic gates!

Selected Publication: Visualizing cell–cell communication using synthetic notch activated MRI. TianDuo Wang, Yuanxin Chen, Nivin N Nystrom, Shirley Liu, Yanghao Fu, Francisco M Martinez, Timothy J Scholl, and John A Ronald. Proc Natl Acad Sci U S A. 2023 Mar 14; 120(11):e2216901120. doi: 10.1073/pnas.2216901120.
https://www.pnas.org/doi/abs/10.1073/pnas.2216901120

Further information on the European Society for Molecular Imaging:
https://e-smi.eu/
Contact: office@e-smi.eu

GUEST: Jason Lewis, New York
In this episode we discuss and learn about new PSMA-binding ligands with 161Tb, their biodistribution, dosimetry, preclinical therapy, and their comparison with conventional PSMA ligands. Our guest is one of the leading scientists in radiochemistry for cancer detection and therapy, the wonderful Jason Lewis.

We talk about the importance of using 161Tb - this novel radionuclide for radioligand therapy - and its favorable decay characteristics as compared to 177Lu. We learn about the added value of the emission of Auger electrons which can effectively eliminate micro-metastasis and when combined with ibuprofen-based PSMA ligands offering albumin-binding properties, tumor uptake and therapeutic efficacy are significantly boosted.

Besides this fascinating science, don't miss some very important advice from a very successful scientist in a very competitive environment about work-life balance, prioritising expectations and goals - just never forget to "smell the roses"…

Selected Publication: Albumin-Binding and Conventional PSMA Ligands in Combination with 161Tb: Biodistribution, Dosimetry, and Preclinical Therapy. Viviane J. Tschan, Sarah D. Busslinger, Peter Bernhardt, Pascal V. Grundler, Jan Rijn Zeevaart, Ulli Köster, Nicholas P. van der Meulen, Roger Schibli, Cristina Müller. Journal of Nuclear Medicine Jul 2023, jnumed.123.265524; DOI: 10.2967/jnumed.123.265524
https://jnm.snmjournals.org/content/early/2023/07/13/jnumed.123.265524

Further information on the European Society for Molecular Imaging:
https://e-smi.eu/
Contact: office@e-smi.eu

GUEST: Annemie Van Der Linden, Antwerp
In this edition of ‘Dive into Imaging Science’ we discuss the brain and the mechanisms that it employs to clear unwanted waste material whilst we sleep with our former ESMI President and Emeritus Professor Annemie Van Der Linden - an outstanding figure and incomparable scientist.

We learn how closely coupled this system - known as the glymphatics - is to blood circulation, and how physical stimulation can enhance glymphatic flow in anaesthetised but not awake mice. Along the way, we learn how curiosity and a wondering mind has led Annemie to use a wide range of models to study the brain, from fish to song birds.

Selected Publication: Glymphatic influx and clearance are accelerated by neurovascular coupling. Holstein-Rønsbo S, Gan Y, Giannetto MJ, Rasmussen MK, Sigurdsson B, Beinlich FRM, Rose L, Untiet V, Hablitz LM, Kelley DH, Nedergaard M. Nat Neurosci. 2023 Jun;26(6):1042-1053. doi: 10.1038/s41593-023-01327-2.

Publication reference: Holstein-Rønsbo S, Gan Y, Giannetto MJ, Rasmussen MK, Sigurdsson B, Beinlich FRM, Rose L, Untiet V, Hablitz LM, Kelley DH, Nedergaard M. Glymphatic influx and clearance are accelerated by neurovascular coupling. Nat Neurosci. 2023 Jun;26(6):1042-1053. doi: 10.1038/s41593-023-01327-2. Epub 2023 Jun 1. PMID: 37264158. https://www.nature.com/articles/s41593-023-01327-2

Further information on the European Society for Molecular Imaging:
https://e-smi.eu/
Contact: office@e-smi.eu

GUEST: Elisabeth de Vries, Groningen
In this episode we talk about nectin-4 - an emerging biomarker for cancer diagnosis and therapy - with one of the most influential and distinguished scientists in medical oncology, Elisabeth de Vries.
We talk about the first-in-human study of a radioligand that can target nectin-4 and learn what medical oncologists need to get out from imaging data so that these powerful tools continue to make an impact on patient outcomes.
We learn about the importance and best practices for robust clinical trials and the hurdles to both design and finance them.
Along the way, we get a glimpse into Elisabeth’s career path and how her research combines nuclear with optical imaging modalities as methods to improve patient diagnosis and treatment.

Selected Publication: "First-in-human study of the radioligand 68Ga-N188 targeting nectin-4 for PET/CT imaging of advanced urothelial carcinoma" published in Clinical Cancer research by the authors X. Duan, L. Xia, Z. Zhang, Y. Ren, M. G. Pomper, S. P. Rowe, X. Li, N. Li, N. Zhang, H. Zhu 6, Z. Yang, X. Sheng, X. Yang (groups from Beijing University and Johns Hopkins University Baltimore).

Publication reference: Xiaojiang Duan, Lei Xia, Zhuochen Zhang, Yanan Ren, Martin G Pomper, Steven P Rowe, Xuesong Li, Nan Li, Ning Zhang, Hua Zhu 6, Zhi Yang, Xinan Sheng, Xing Yang. First-in-human study of the radioligand 68Ga-N188 targeting nectin-4 for PET/CT imaging of advanced urothelial carcinoma. Clin Cancer Res. 2023 Apr 24;CCR-23-0609. doi: 10.1158/1078-0432.CCR-23-0609. https://aacrjournals.org/clincancerres/article-abstract/doi/10.1158/1078-0432.CCR-23-0609/726342/First-in-Human-Study-of-the-Radioligand-68Ga-N188

Further information on the European Society for Molecular Imaging:
https://e-smi.eu/
Contact: office@e-smi.eu