A picture says more than a thousand words – this is what makes hyperpolarization possible!

Scientific concepts are often highly complex, and the underlying details can be difficult to understand. Metaphors help make these concepts more tangible and convey their meaning in an intuitive way. This is also true for hyperpolarization in MRI and metabolic imaging, whose mechanisms are difficult to grasp without illustrative comparisons. Here is our attempt to explain hyperpolarization and metabolic MRI in an understandable way.

Hyperpolarization

Imagine you want to take a picture in a dark room. A conventional MRI scan is like a photo taken with weak lighting – the image is grainy, and details are difficult to recognize. Conventional approaches to signal enhancement with even stronger MRI magnets work, but they are like trying to brighten the photo by installing large, expensive lighting. This is not only very complicated but also quite expensive … just think of the cost of purchasing multiple floodlights and the electricity consumption!

Another problem is that the structures you want to capture in the image only appear in different shades of gray, some are almost transparent. Simply adding more light will eventually no longer improve the image. Additionally, you will likely never be able to clearly depict transparent structures.

Our approach works completely differently: Instead of making the entire image brighter, hyperpolarization selectively enhances specific objects in the image. It is as if the structures you want to capture in your image suddenly light up in color. This not only provides a clearer representation in an otherwise dark room but also allows nearly completely transparent structures (diluted metabolite) to be seen in the image that were previously hidden.

It is important to mention that these substances do not actually "glow." In general, MRI and hyperpolarization are techniques that do not involve harmful radiation, such as radioactivity. The "glow" corresponds to the magnetic alignment of atomic nuclei. This is a completely harmless physical state that disappears after a very short time and has no effects on the body.

Metabolic MRI – Visualizing Metabolism in Real Time

While classical MRI can only depict tissue, hyperpolarized MRI makes it possible to make selected metabolites appear to "glow" with very high intensity in the MRI image. The effect of this "glow" goes even further: when the molecule is absorbed and metabolized by the body, the glow is temporarily transferred to the resulting metabolic products. These products also become visible in the MRI and can even be distinguished from each other based on the "color" of their glow. We can now not only see where a substance is being metabolized but also determine into which products it is being broken down and in what ratio they are produced at each location in the human body.

Due to the high signal amplification of our technique, it is possible to visualize metabolism in real time using MRI. This is a groundbreaking development that was previously not possible in this form and simplicity – but why is this so important for diagnostics?

The Warburg Effect – Known for Over 100 Years, but Previously Invisible

 

 

The metabolism of a healthy cell follows clear rules. However, in some diseases, the metabolism changes at a cellular level. The most well-known example of a disease that alters cellular metabolism is cancer.

Cancer cells multiply uncontrollably. For this uncontrolled growth, cancer cells require a lot of energy. In the body, this energy is provided in the form of glucose (or, in its activated form, pyruvate) and oxygen. The cancer cell forms new blood vessels to obtain more sugar and oxygen. But that alone is not enough – cancer also needs an advantage over the surrounding tissue in the competition for resources. To achieve this, cancer cells use a clever mechanism: they can obtain energy from glucose in different ways. One of these ways involves metabolizing sugar without consuming oxygen.

This highly inefficient method of energy production makes the cancer cell independent of oxygen while simultaneously depriving surrounding cells of both sugar and oxygen, effectively starving them.-new space for the cancer cells to develope into.

This alteration in energy metabolism is observed in most types of cancer and is known as the Warburg Effect. More than 100 years ago, Otto Heinrich Warburg identified the altered glucose metabolism that occur in most cancer cells. We also know that these changes occur at a very early stage of cancer development. Even before cancer manifests as a classic tumor, metabolic alterations already take place at the cellular level. This represents a unique opportunity for us!

At QuantView, we aim to use hyperpolarized, activated sugar (pyruvate – an extremely fast-metabolized sugar) as a contrast agent. This sugar is eagerly taken up by cancer and precancerous cells and metabolized for energy production. As a result the cancer essentially marks itself in the MRI image by its increased sugar uptake, and revealing its presence through the distinct fingerprint of its metabolic products.

 

This Approach Offers Many Advantages:

1. 1. Early Diagnosis: Every type of cancer depends on energy, making this contrast agent applicable to nearly all types of cancer.
   2. Radiation-Free Examination: By using MRI, we completely avoid radioactive radiation. Patients are not exposed to any harmful effects, and scans can be performed as frequently as needed without concern.
   3. Fast Therapy-Monitoring The fast and easy quantification of metabolism enables a quick adjustment of therapy. Within just a few days, our contrast agent could indicate whether the tumor's metabolism is decreasing or not. This allows for a faster adaptation of treatment and improves the chances of succesfull treatment.
   4. Safe and Biocompatible: Our contrast agent contains no toxic heavy metals such as gadolinium. The sugar used (pyruvate) is a natural substance found in the human body and is completely broken down without leaving any residues. (More precisely, pyruvate is essential for human survival as it plays a central role in energy metabolism. Without pyruvate, the body would not be able to produce sufficient energy.)
   5. Cost-Efficient: Due to the enhanced MRI signal, only very weak magnetic fields are required. This reduces the technical complexity, as large MRI machines are no longer necessary. MRI scanners with conventional permanent magnets become feasible. This would not only drastically lower costs but also improve access to this groundbreaking diagnostic technology.