Notes from 2017 MIT Health Sensing & Imaging Conference Sept. 19-20, 2017. Part 2

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.

Figure 4
Luo et al 2017. In Vivo Quantification of Placental Insufficiency by BOLD MRI: A Human Study. Nature Scientific Reports.Sci Rep. 2017 Jun 16;7(1):3713.

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.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5588683/

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.

https://www.nature.com/nbt/journal/v31/n1/full/nbt.2464.html

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…

https://www.nature.com/articles/s41551-017-0054

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.

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