Using Bioluminescence in Magnetic Resonance Imaging (MRI)

Introduction

Magnetic resonance imaging (MRI) has become a cornerstone of modern medical diagnosis, known for its ability to produce high-resolution images of internal structures and to visualise detailed internal structures without the use of ionizing radiation ⁶ . Despite its advantages, MRI has problems with sensitivity and specificity, especially in differentiating between different tissue types and detecting small or early-stage abnormalities. Bioluminescence, the emission of light from living organisms, offers a new approach to overcome these limitations. By adding bioluminescent molecules such as luciferin and luciferase, which emit the light through the biochemical reactions to MRI, researchers aim to improve contrast and provide more accurate imaging capabilities. These molecules could significantly advance medical imaging, offering deeper insights into health and disease. Utilizing strong magnetic fields and radiofrequency waves, MRI produces high-resolution images of soft tissues, making it particularly effective for examining the brain, spinal cord, muscles, and joints. This is done by aligning hydrogen nuclei in the body and detecting the signals they emit ¹⁰ .

Figure 1: Standard MRI Scan showing high-resolution images of internal structures, commonly used in medical diagnostics to visualise tissues and organs ¹⁵ .

Mechanisms of Bioluminescence in MRI

Bioluminescence occurs when certain enzymes known as luciferases catalyse reactions with substrates called luciferins, emitting light as a result. In the context of MRI, bioluminescent molecules can be modified to target specific cells, tissues, or molecular pathways. When these molecules interact with their targets, the emitted light can be detected and used to amplify the MRI signal ¹⁷ .

Bioluminescent probes:

Bioluminescent probes are designed emit light in response to specific biological processes ¹⁸ . These probes can be combined with magnetic nanoparticles or various agents that can be seen with MRI. The bioluminescence signal can be converted into an MRI signal, improving image quality, and providing additional information about the biological environment.

Figure 2: Mechanism of Bioluminescence in Firefly Luciferase, firefly bioluminescence involves the enzyme luciferase catalysing a reaction where D-luciferin, in the presence of ATP and oxygen, is converted into an excited molecule. As this molecule returns to its ground state, it emits visible light, typically yellow green. This process is highly efficient, allowing fireflies to produce light with minimal energy loss ¹³ .

Advantages of Bioluminescence-Enhanced MRI

Molecular imaging:

Bioluminescence enables molecular imaging, which allows specialists to visualise and monitor molecular processes over time. This capability is important in oncology as it can be used to track tumour growth, metastasis, and response to treatment. Bioluminescence MRI focuses on specific biomarkers that can provide information about the molecular basis of disease ¹² . Specialists are generally required to use bioluminescence-based molecular imaging effectively, given the complexity of the technology and the depth of understanding needed to interpret the results accurately.

Bioluminescence magnetic resonance is very promising for cancer diagnosis. Bioluminescent studies focus on tumour-specific markers that can show malignant cells with high accuracy, allowing early detection and accurate diagnosis of cancer. This technology makes it possible to assess the effectiveness of cancer treatment in real time to create a personalized treatment plan.

Figure 3: Time-lapse Imaging of Tumour Growth Using Bioluminescence MRI, Early frames capture the initial, small tumour, while later frames show increased bioluminescent signals as the tumour grows larger ⁸ .

Improved imaging:

One of the main advantages of incorporating bioluminescence into MRI is the significantly improved contrast. Traditional MRI relies on differences in fluid content and tissue density to produce contrast. Bioluminescence provides a different layer of information on molecular and cellular activity, which can accurately distinguish between healthy and dead tissue

Non-invasive and safe:

The biomolecules used in MRI are non-toxic and do not require ionizing radiation, so this procedure is safe for patients. The non-invasive nature of bioluminescence MRI means it can be used for repeated imaging over time, which is important for monitoring disease progress and treatment effectiveness

Clinical Applications

Musculoskeletal Disorders:

Joint Disorders:

MRI is frequently used to assess joint problems, including ligament tears, meniscus injuries, and cartilage damage, particularly in the knee, shoulder, and spine ⁹ .

Spinal Conditions:

MRI is crucial in diagnosing herniated discs, spinal stenosis, and other spinal cord abnormalities, aiding in both conservative and surgical treatment planning.

Neurological Disorders:

In neurological studies, bioluminescence MRI can be used to study brain function and monitor neurological diseases. By focusing on neurotransmitter activity or specific neural pathways, researchers can understand conditions such as Alzheimer's disease, Parkinson's disease, and epilepsy. This approach can aid in development of targeted treatments and provide insights into the progression of these diseases ¹⁴ .

Brain Function Mapping:

MRI is used to map brain activity by detecting changes in blood flow, particularly useful in pre-surgical planning for epilepsy or brain tumour surgeries ² .

Psychiatric Research:

MRI is increasingly used in research to study brain function in psychiatric disorders such as depression, schizophrenia, and anxiety ¹⁹ .

Figure 4: This image showcases various brain scanning techniques, illustrating the different methods used to visualize brain structures and functions, providing unique insights into brain anatomy and activity, essential for diagnosing neurological conditions and studying brain functions ⁵ .

Cardiovascular Diseases

Bioluminescence MRI can also be used to image the heart. By focusing on specific signs of inflammation or plaque formation, this technology can provide detailed images of the vascular system and aid in the diagnosis and treatment of diseases such as atherosclerosis and heart disease ¹ . It provides crucial information on heart function and blood vessel health, aiding in the diagnosis of cardiomyopathies and vascular malformations. Cardiac MRI is used to diagnose and monitor heart diseases, offering high-resolution images that help in assessing heart muscle, chambers, and blood flow ⁴ .

This non-invasive technique is critical for evaluating conditions like cardiomyopathies, coronary artery disease, and congenital heart defects. Additionally, MRI can detect inflammatory cytokines like interleukin-1β (IL-1β) and tumour necrosis factor-alpha (TNF-α), which are central to the progression of atherosclerosis, enabling early detection of plaque formation. MRI can visualise apoptotic processes in heart tissue after myocardial infarction and detect oxidative stress, both of which are critical for understanding the progression of heart failure. This approach provides a non-invasive, sensitive method to detect molecular and structural changes in cardiovascular diseases, aiding in early diagnosis and treatment monitoring ⁷ .

Figure 5: This image illustrates a cardiac MRI, providing a detailed view of the heart’s anatomy and function ¹¹ .

Future Challenges and Opportunities

Biodynamics is important in MRI, but there are also challenges that need to be addressed. These includes developing better bioluminescence probes, ensuring the stability and biocompatibility of these probes, and integrating bioluminescence detection with current MRI techniques Bioluminescence probes can degrade over time due to chemical reactions with the biological environment or imaging equipment, leading to diminished luminescence Probes may also undergo photobleaching when exposed to light, which reduces their luminescence Probes must remain stable in the complex physiological environment, including varying pH levels, ionic strength, and temperatures ³ . To ensure biocompatibility probes are coated with biocompatible materials like polyethylene glycol (PEG) to minimize immune reactions. Employing non-toxic luciferins and luciferases reduces potential harm ¹⁶ . Adhering to regulatory guidelines ensures probes are safe for clinical use. Future research will focus on overcoming these obstacles and expanding the clinical use of bioluminescence MRI.

Conclusion

The introduction of bioluminescence in magnetic resonance imaging represents a major advance in medical imaging. By enhancing contrast and enabling molecular imaging, bioluminescence MRI can improve the accuracy and effectiveness of diagnosis and treatment monitoring. Current research and development in bioluminescence MRI include advancements in probes, integration with MRI, and biocompatibility and stability. Major UK universities and research centres are advancing bioluminescence MRI technology, funded by UK Research and Innovation (UKRI) and through collaborative efforts among academic and healthcare institutions.  Funding for bioluminescence MRI research in the UK comes primarily from UKRI, including grants from the Medical Research Council (MRC). Major UK universities, research centres, and healthcare institutions are also involved, with collaborative efforts supported by both public and private sector funding. This financial backing is crucial for advancing bioluminescence MRI technology, particularly in developing better probes, improving MRI integration, and ensuring biocompatibility, ultimately pushing the technology toward clinical application. As research progresses, this innovative approach could revolutionise non-invasive diagnostics and personalised medicine, bringing new hope for patients and doctors.

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