Nav: Home

Visualizing gene expression with MRI

December 23, 2016

Genes tell cells what to do -- for example, when to repair DNA mistakes or when to die--and can be turned on or off like a light switch. Knowing which genes are switched on, or expressed, is important for the treatment and monitoring of disease. Now, for the first time, Caltech scientists have developed a simple way to visualize gene expression in cells deep inside the body using a common imaging technology.

Researchers in the laboratory of Mikhail Shapiro, assistant professor of chemical engineering and Heritage Medical Research Institute Investigator, have invented a new method to link magnetic resonance imaging (MRI) signals to gene expression in cells--including tumor cells--in living tissues. The technique, which eventually could be used in humans, would allow gene expression to be monitored non-invasively, requiring no surgical procedures such as biopsies.

The work appears in the December 23 online edition of the journal Nature Communications.

In MRI, hydrogen atoms in the body--atoms that are mostly contained in water molecules and fat--are excited using a magnetic field. The excited atoms, in turn, emit signals that can be used to create images of the brain, muscle, and other tissues, which can be distinguished based on the local physical and chemical environment of the water molecules. While this technique is widely used, it usually provides only anatomical snapshots of tissues or physiological functions such as blood flow rather than observations of the activity of specific cells.

"We thought that if we could link signals from water molecules to the expression of genes of interest, we could change the way the cell looks under MRI," says Arnab Mukherjee, a postdoctoral scholar in chemical engineering at Caltech and co-lead author on the paper.

The group turned to a protein that naturally occurs in humans, called aquaporin. Aquaporin sits within the membrane that envelops cells and acts as a gatekeeper for water molecules, allowing them to move in and out of the cell. Shapiro's team realized that increasing the number of aquaporins on a given cell made it stand out in MRI images acquired using a common clinical technique called diffusion-weighted imaging, which is sensitive to the movement of water molecules. They then linked aquaporin to genes of interest, making it what scientists call a reporter gene. This means that when a gene of interest is turned on, the cell will overexpress aquaporin, making the cell look darker under diffusion-weighted MRI.

The researchers showed that this technique was successful in monitoring gene expression in a brain tumor in mice. After implanting the tumor, they gave the mice a drug to trigger the tumor cells to express the aquaporin reporter gene, which made the tumor look darker in MRI images.

"Overexpression of aquaporin has no negative impact on cells because it is exclusive to water and simply allows the molecules to go back and forth across the cell membrane," Shapiro says. Under normal physiological conditions the number of water molecules entering and exiting an aquaporin-expressing cell is the same, so that the total amount of water in each cell does not change. "Aquaporin is a very convenient way to genetically change the way that cells look under MRI."

Though the work was done in mice, it has the potential for clinical translation, according to Shapiro. Aquaporin is a naturally occurring gene and will not cause an immune reaction. Previously developed reporter genes for MRI have been much more limited in their capabilities, requiring the use of specific metals that are not always available in some tissues.

"An effective reporter gene for MRI is a 'holy grail' in biomedical imaging because it would allow cellular function to be observed non-invasively," says Shapiro. "Aquaporins are a new way to think about this problem. It is remarkable that simply allowing water molecules to more easily get into and out of cells in a tissue gives us the ability to remotely see those cells in the middle of the body."
The paper is titled "Non-invasive imaging using reporter genes altering cellular water permeability." In addition to Shapiro and Mukherjee, other coauthors include Caltech graduate students Di Wu (MS '16 and co-lead author) and Hunter Davis. The work was funded by the Dana Foundation, a Burroughs Wellcome Career Award at the Scientific Interface, the Heritage Medical Research Institute, and the National Institutes of Health.

California Institute of Technology

Related Brain Tumor Articles:

New target found to attack an incurable brain tumor in children
Research shows that a tumor suppressor gene p16 is turned off by a histone mutation (H3.3K27M), which is found in up to 70 percent of childhood brain tumors called diffuse intrinsic pontine glioma (DIPG).
Treatment of malignant brain tumor in children gets closer
Researchers at the University of Copenhagen have identified important mechanisms underlying how a special type of malignant brain tumor arises in children.
Molecule stops fatal pediatric brain tumor
Northwestern Medicine scientists have found a molecule that stops the growth of an aggressive pediatric brain tumor.
Tumor-seeking salmonella treats brain tumors
Genetic tweaks to salmonella turn the bacteria into cancer-seeking missiles that produce self-destruct orders deep within tumors.
Molecular signature for aggressive brain tumor uncovered
Researchers from Brigham and Women's Hospital, in collaboration with colleagues at Massachusetts General Hospital, have identified genetic mutations that can distinguish aggressive rhabdoid meningiomas from more benign forms using routine laboratory tests.
Brain tumor characteristics could help predict survival in people over 70
Characteristics like seizures, location of the tumour, and pressure in the brain, give insight into length of survival and treatment options for brain tumour patients over the age of 70, according to new research* presented at the National Cancer Research Institute's (NCRI) Cancer Conference in Liverpool.
Key mechanism identified in brain tumor growth
A gene known as OSMR plays a key role in driving the growth of glioblastoma tumors, according to a new study led by a McGill University researcher and published in the journal Nature Neuroscience.
Laser treatment may boost effectiveness of brain tumor drugs
The human brain has a remarkable defense system that filters bacteria and chemicals.
Genetic cause identified in rare pediatric brain tumor
Researchers found a way of differentiating angiocentric gliomas from other low-grade pediatric brain tumors and developed a pathological test that will help children avoid unnecessary and potentially damaging additional therapies.
New way to identify brain tumor aggressiveness
A comprehensive analysis of the molecular characteristics of gliomas -- the most common malignant brain tumor -- explains why some patients diagnosed with slow-growing (low-grade) tumors quickly succumb to the disease while others with more aggressive (high-grade) tumors survive for many years.

Related Brain Tumor Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Failure can feel lonely and final. But can we learn from failure, even reframe it, to feel more like a temporary setback? This hour, TED speakers on changing a crushing defeat into a stepping stone. Guests include entrepreneur Leticia Gasca, psychology professor Alison Ledgerwood, astronomer Phil Plait, former professional athlete Charly Haversat, and UPS training manager Jon Bowers.
Now Playing: Science for the People

#524 The Human Network
What does a network of humans look like and how does it work? How does information spread? How do decisions and opinions spread? What gets distorted as it moves through the network and why? This week we dig into the ins and outs of human networks with Matthew Jackson, Professor of Economics at Stanford University and author of the book "The Human Network: How Your Social Position Determines Your Power, Beliefs, and Behaviours".