Our Research

Since the original invention by Dr. Albert and Colleagues in 1994, Hyperpolarized (HP) noble gas MRI was used for functional imaging of the lungs over the globe. Imaging data acquired using HP noble gas MRI can be used to calculated as local as global pulmonological parameters of the human lungs which can be used for diagnostics and treatment monitoring of lung diseases such as asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). Figure 1 shows an example of HP ¹²⁹Xe MR images from our laboratory obtained from the healthy volunteer (A) and patients with asthma (B), COPD (C,D), and asbestosis (E). The ventilation defects associated with the disease progression can be clearly observed (B-E).

Another approach how to conduct functional MRI imaging of human lungs relies on the use of inert fluorinated gases. These gases are safe for inhalation and can be mixed with oxygen in any proportions. In addition, inert fluorinated gases are significantly cheaper compared to noble gases and require no polarization prior to inhalation. Although the fluorine signal is significantly smaller compared to HP noble gas signal, the quality of 19F images is sufficient for diagnostics purposes. To improve the performance of inert fluorinated gas MRI the study of gases with high number of fluorine atoms is needed as well as optimization of imaging parameters.

HP noble gas MRI and inert fluorinated gas MRI uses no ionizing radiation and it does not require exposing patients to the risks of chemical contrast agents that are sometimes used with conventional MRI. This allows HP gas and inert fluorinated gas MRI to be used to image patients repeatedly over time, allowing physicians to monitor how medical conditions progress, and to assess the effectiveness of specific treatments. We pursue our investigations on HP and inert gas MRI in collaborations with physicians, and with biomedical scientists, engineers, chemists, and physicists at TBRRI and a number of other universities and corporations. Currently, our investigations include work in the following areas:

1. Optimization of imaging parameters for HP noble gas and inert fluorinated gas MRI.
2. ¹⁹F lung MRI using octafluorocyclobutane development.
3. Development of HP ¹²⁹Xe imaging guidance for radiation therapy to minimize the radiation induced lung injury.
4. Image performance comparison of the inert fluorinated gases.

Molecular imaging is a medical imaging field that has a potential to revolutionize the diagnosis and management of the disease. Molecular imaging is based on the injection of the imaging biosensor (molecular probe) which selectively binds with high affinity to a disease site and quickly removes from the rest of the body. Therefore, the signal originated from the probe perfectly correlated with a pathology location. Traditionally, MRI was not suitable for molecular imaging due to the poor sensitivity of this medical imaging modality.

Recently, the novel approach of molecular imaging using hyperpolarized (HP) xenon-129 (¹²⁹Xe) chemical exchange saturation transfer (HyperCEST) effect. This methodology requires biosensors conjugated with supramolecular macrocycle (cage molecule) which can effectively encapsulate HP ¹²⁹Xe. Due to constant exchange between the cage and the dissolved pool, it becomes possible to produce sufficient contrast by irradiating the encapsulated ¹²⁹Xe using a narrow bandwidth radiofrequency pulse. The signal enhancement acquired using HyperCEST sufficient for molecular imaging purposes and recently we did the first HyperCEST imaging in the living rat (Figure 1). Together with Dr. DeBoef’s group from the University of Rhode Island we developing HyperCEST biosensors based on cucurbit[6]uril, gamma-cyclodextrin, and pillar[5]arene supramolecular cages. Figure 2 illustrated the structure of the macromolecules used in our studies.

Recently, we started to develop fluorinated biosensors for imaging of Alzheimer’s disease. Fluorine-19 (¹⁹F) can produce a sufficient amount of MRI signal and is absent into the body. Therefore, there is no endogenous signal from the body and if the developed biosensor has a high affinity to the molecular target, the signal to noise ratio should be sufficient for successful detection of the pathology. Although molecular imaging using ¹⁹F MRI was born recently, this field has a potential to become a powerful diagnostic tool in the future.

We are currently working to achieve the following goals:

1. To develop a functionalized HyperCEST biosensor for detection of amyloid-beta deposition in the brain.
2. To develop a functionalized HyperCEST biosensor for detection of hyperphosphorylated Tau protein in the brain.
3. To develop fluorinated biosensors suitable for Alzheimer’s disease detection in the living organism.

The Albert group is intensively working on the HP ¹²⁹Xe brain and cerebral blood flow imaging investigation. Due to the ability of HP ¹²⁹Xe to dissolve in blood and travel to a highly perfused organs, the HP ¹²⁹Xe can be potentially used as a contrast agent for quantitative blood flow measurement and brain imaging. The main goal of this project is to develop a method that is capable to measure a cerebral activity and cerebral perfusion directly with a high sensitivity and high contrast.

Albert and colleagues applied HP ¹²⁹Xe MRI to image ischemic areas of the brain following middle cerebral artery occlusion (Zhou et. al. 2011). Following this work, the first use of HP ¹²⁹Xe functional MRI was demonstrated in living rats. The activated areas of the rat brain were observed as a response to the pain stimulation (Mazzanti et. al. 2011). Recently, Albert’s group was able to study the perfusion changes associated with Alzheimer’s disease using HP 129Xe spectroscopy (Figure 3) and imaging (Figure 4).

It was demonstrated for the first time that dynamic HP ¹²⁹Xe imaging can quantitively measure the cerebral perfusion difference between the healthy brains and Alzheimer disease brains (Hane et. al. 2018).