Each cell in the body puts in considerable energy to maintain the proper balance of water and critical electrolytes in order to survive. Researchers at Oregon Health & Science University (OHSU) have gone on to develop a way for mapping this activity in the human brain and other organs using magnetic resonance imaging, or MRI.
The breakthrough, known as metabolic activity diffusion imaging, or MADI, is opening up new avenues for cancer detection and determining if a tumor is responding to treatment. In future clinical trials involving patients with glioma brain tumors, researchers will compare MADI to positron emission tomography, or PET, which employs injected radioactive substances to provide images of cell power production rates.
In an editorial released alongside two articles describing MADI by Springer and co-authors in the journal NMR in Biomedicine, independent specialists termed it an intriguing mechanistic hypothesis.
MADI is a new method of imaging metabolic activity inside organs and tissues, as per inventor Charles Springer, Ph.D., professor at the OHSU Advanced Imaging Research Center. This strategy might be used in practically any pathology. They are currently directing it towards cancer and neurology.
The OHSU researchers have already demonstrated that MADI can detect and track brain cancers as effectively as PET, despite the requirement for injecting tracers or contrast chemicals of any type. It informs us more about what’s heading on inside cells in terms of ion transport, power generation, and water transport, and they believe it will be very useful in various types of cancer, as stated by an associate professor with the OHSU Advanced Imaging Research Centre, Martin Pike, Ph.D., and the lead researcher on the glioma studies.
MADI also produces higher-resolution images than PET. According to Springer, it can resolve areas of metabolic activity within the tumour. None of the current clinical approaches for mapping metabolic activity provide the spatial resolution required to measure differences in metabolism within the largest tumours. Ramon Barajas, M.D., an associate professor of diagnostic radiology at the OHSU School of Medicine and a collaborator on glioma studies, emphasises that figuring out how different sections of a tumour work can be very helpful in ascertaining a diagnosis.
MRI uses a high magnetic field to provide extremely detailed images of interior organs. The magnetic field induces hydrogen atom nuclei in water molecules to align with the field. The MRI scanner then sends out radio wave pulses at a predetermined frequency. In reaction, charged hydrogen nuclei re-emit radio waves, producing signals that the MRI scanner uses to generate images.
MADI is based on the diffusion-weighted MRI technique, which monitors the flow of water molecules across tissues. Diffusion-weighted MRI has been widely utilised in medicine since the 1990s, mainly for brain scans to detect injuries and treat conditions. The approach produces quick and informative findings without the use of contrast chemicals. It’s also being used to detect and research tumours and other disease processes.
However, scientists did not fully comprehend the molecular principles that govern how water molecules flow through tissues, causing alterations that became obvious indications of stroke and malignancies in diffusion MRI. Springer and colleagues investigated the concept that cell membranes play an important role in regulating the passage of molecules of water in and out of cells. Their findings revealed that the likelihood of water molecules penetrating cell membranes is substantially determined by essential enzymes known as sodium-potassium pumps. They span cell membranes and pump salt out and potassium in, a mechanism that also fuels water molecule movement. They realised they could produce MRI pictures that map the function of the sodium-potassium pumps after understanding that water exchange is connected to pump activity, said Springer.
The researchers employed mathematical modelling and computer simulations to gather insights about the movement of water molecules to measure and map sodium-potassium pump activity. The activity is so important to live cells that it can be used to calculate the rate of continuing energy consumption.
Cancer dramatically changes cell energy utilization, as evidenced by MADI research utilizing an animal version of glioma brain tumors. They have been able to diagnose cancer, monitor cancer, and track treatment in animals, as well as use PET, according to Pike. They hope to be able to demonstrate this in humans as well. The neuroradiologist, Dr. Barajas, stressed that considerable research remains to be done. They must validate this and ensure that what they are doing is scientifically correct. He believes that a more comprehensive and precise scanning procedure would be extremely beneficial to individuals with brain tumours. If they get it wrong and discontinue an effective therapy, they send them to the operating room for unnecessary surgery, he says. When they get it incorrect and the tumour is expanding when doctors say it is not, they delay the patient receiving a new therapy.
The clinical trial will enrol approximately 12 patients with glioma brain cancer. Their brains will be scanned at OHSU, which was the initial facility in the Pacific Northwest when it was rolled out in 2021. The hybrid scanner will allow researchers to immediately compare the accuracy of PET versus MADI in human participants.
If MADI is found to be effective, it may have a variety of advantages for patients. The method is non-invasive and takes less time as compared to PET. It will almost certainly be less costly and more readily accessible than PET. The best part is that MADI can also be performed with standard MRI equipment.
