Ultrasensitive plasma-based monitoring of tumor burden using machine-learning-guided signal enrichment Chadi Ibrahim, MD, MSc, PhD July 1, 2024
Liquid biopsy Offers to fundamentally change cancer care Non-invasive detection and monitoring of plasma circulating tumor DNA 2
Liquid biopsy It is being extended to low tumor fraction (TF) settings After surgical removal of tumor to detect minimal residual disease (MRD) Therapeutic response monitoring 3
Problem of ctDNA sparsity Employs deep-targeted sequencing with current assays missing detection frequently 4
Bespoke panels Custom designed panels based on specific mutations present on an individual tumor 5
Common cancer driven genes Not individual but target mutations frequently involved in cancer 6
Background: vascularization Ultrasequencing If sample does not have the mutation, it cannot be detected 7
Background: vascularization Alternative methods Increasing sequencing breadth rather than depth examining a wider range of DNA regions across the entire genome Integration of multiple single nucleotide variants (SNVs) and copy variants using whole genome sequencing (WGS) 8
Background: vascularization MRDetect 9
Background: v MRD-EDGE 10
Background: v 11
Background: v Conventional neural network (CNN) and multilayer perception (MLP) model 12
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Results In clinical validation, MRD-EDGE effectively detected MRD in stage III CRC pre and postoperatively with high sensitivity/specificity 23
Peripheral neuropathy 24
Diabetic Peripheral neuropathy 25
Why do we need to visualize peripheral nerves? Chair of Biological Imaging (CBI) & Institute of Biological and Medical Imaging (IBMI) 26
1 – forehead bar, 2 – CCD camera, 3 – chin rest, 4 – fixation target, 5 – corneal module, 6 – knobs to align the CCM, 7 – CCM live image, 8 – CCD camera live image. 27 Corneal Confocal Microscopy (CCM)
MSOT Chair of Biological Imaging (CBI) & Institute of Biological and Medical Imaging (IBMI) 28
Portable MSOT in Peripheral nerves Visualization of vasa nervosa Jüstel et al., Adv. Sci., 2023.
Portable MSOT in Peripheral nerves Visualization of internal nerve structure Jüstel et al., Adv. Sci., 2023.
Research question 2 Can AI based segmentation effectively and accurately differentiate peripheral nerves from surrounding tissue? In comparison to expert labelling 31 The Lab for AI in Medicine
Future directions More clinical studies More collaboration within our department Improve quality of images 32
Prof. Dr. Vasilis Ntziachristos Dr. Dominik Jüstel Dr. Tram Do, Sarah Franceschin , Manuel Gehmeyr, David Gorbunov, Philipp Haim, Maximillian Bader, Suhanyaa Nitkunantharajah , Lukas Scheel-Platz, Maria Begoña Rojas Lopez, Sarkis Ter Martirosyan Dr. Andreas Hillmair, Ines Baumgartner, Karla Buortmes, Dr. Ute Chambers, Dr. Corinna Lieleg, Stephanie Montag, External collaborators : Dr. Hedwig Irl, Florian Hinterwimmer Other IBMI members 33 Acknowledgments