Talk 3: Making Invisible Obvious: Computational Analysis of Medical Images
Polina Golland, Professor of Electrical Engineering and Computer Science, MIT Department of Electrical Engineering and Computer Science
Story about kids and placenta…
Placental function from MRI
Using MRI to track blood oxygenation in the placenta, with the goal of quantifying oxygen exchange in the placenta. The challenge is placental movement and noise.
To beat this challenge, they built an algorithm that tracked the movements of organs in the womb MICCAI’ 16, JMRI. They obtain curves which provide a biomarker of placental function, allowing them to make predictions about placental function.
In one study of twins where on twin had in-utero growth restriction, for every pair of twins, the baby whose placenta was fast acting on MRI was larger in terms of the 1) brain, 2) liver and 3) birth weight.
There are also applications for GI medicine.
It’s a Small World: The Power of Miniaturization in Cancer Diagnostics and Beyond
Tarek Fadel, Assistant Director, Marble Center for Cancer Nanomedicine, MIT Koch Institute for Integrative Cancer Research
At the Bhatia lab, they are looking to miniaturise medicine, similar to Moore’s law in tech. A video is above from the Exponential Medicine conference. Specifically they are focusing on biomarkers throughout the identification to monitoring phases of disease.
Blood biomarker limitations
- Lack of sensitivity is driven by background secretion of biomarkers
- dilution and degradation in blood
- analytical problems with quantifying volumes
Answer – what happens if we discovered an exogenous marker that would interrogate endogenous molecules in the tumour micro-environment, and then output that? The Bhatia lab believe this can be 1) sensitive by using signal amplification, 2) specific by multiplexing 3) actionable for staging as the the peptide outputs can be filtered through the kidney and detected.
They leak out of leaky tumour capillaries, interact with proteases in the tumour microenvironment, these markers interrogate protease activity, and the proteases cleave the substrate off the marker particles, and these marker particles are then filtered into the urine.
There are 566 endoproteases in cancer, and are important throughout the cancer life cycle including growth, survival, angiogenesis etc.
How to interrogate protease activity?
Use enzyme-responsive nanosensor with fluorophores – shown in a rat model.
Urinary synthetic biomarkers outperform CEA
Inject CEA secreting cell lines into a mouse, then 10 days later 1) measure CEA and 2) measure the synthetic biomarker in the urine by fluorescence – the biomarker was more sensitive.
Can also test this further by inhibiting proteases with Marimastat, and the urine fluorescence goes back to control level.
Multi-compartment model for predicting pharmacokinetics
Diffusion of blood into tumour, measuring pharmacokinetics of proteases from tumour to blood to bladder.
Then enhanced the sensitivity by nanosensor engineering for ovarian cancer detection. Able to identify 2mm lesions in mice…
Mass encoded synthetic biomarker barcodes enable multiplexing
Get distinct peaks in mass spectrometry depending on the mass barcode attached to the protease substrate.
Low resource setting
Can use a lateral flow assay to detect the synthetic urinary biomarker in a low resource setting, using ELISA to detect a certain biomarker.