Area of Reasearch

The Zhao group is focused on innovating novel approaches to improve magnetic resonance (MR) imaging physics at cellular level for early detection and therapeutic treatment of cancers, for tracking of stem cells, and for other biophysical and biomedical applications. The research topics includes:

  • 1. Cellular MR imaging: Tracking stem cells labeled with iron oxide nanoparticles
  • 2. Therapeutic treatment of cancer using SPIO nanoparticles
  • 3. MR phase gradient mapping
  • 4. Dynamic contrast enhanced MRI
  • 5. Magnetic resonance spectroscopy
  • 1. Cellular MR imaging: Tracking stem cells labeled with iron oxide nanoparticles

    MRI-based cell tracking using super-paramagnetic iron oxide (SPIO) particles provide an excellent means of cell monitoring in vivo. The magnetic nanoparticles function as T2 or T2* contrast agent and they change the transverse relaxation time of protons in surrounding water. SPIOs are ideal for in vivo cell tracking because they are non-radioactive, non-toxic, do not require viral transfection, and provide a detectable intracellular signal.

    Figure1 Left : implanted neural stem cells (pointed by red arrowheads) labeled with SPIOs into a canine brain (surrounded by red box), tracked by using a 7 Tesla MR scanner.
    Figure1 Right : implanted magnetic nanoparticles in chick embryos, monitored by using a 7 Tesla MR scanner.

    2. Cancer therapeutics using SPIO nanoparticles

    a. Tumor detection:

    SPIO nanoparticles, as T2 contrast agents, can be used for early detection of tumors. However, conventional gradient-echo based pulse sequences generate negative contrast (darker spot, see figure (a) below) due to signal loss caused by shortened relaxation time by the nanoparticles. By collaborating with the investigators (Michael Garwood et al) of the University of Minnesota, the Zhao group used a new approach, sweep imaging with Fourier transform (SWIFT) sequence integrated with saturation pulses to enhance the tumor by generating positive contrast (brighter spot, see figure (b)) and suppressing surrounding tissues (see figure (c)).

    Figure2 : Tumors grown in mouse flank, and axial (cross-sectional) images acquired using (a) gradient echo sequence, (b) SWIFT sequence, (c) SWIFT with saturation pulses.

    b. Magnetic therapeutic treatment using hyperthermia

    SPIO nanoparticle induced hyperthermia using an alternating magnetic field can be applied for treatment of various cancers. A hyperthermia system for remote heating of iron oxide nanoparticles was developed using alternating magnetic fields in Zhao’s lab to treat human head and neck cancer using a mouse xenograft model.

    Figure3 Left : Illustration of treatment of tumors using an alternating magnetic field.
    Figure3 Middle : A cross section of mouse flank (tumor enclosed with the red line).
    Figure3 Right : Histology result after tumor was treated with hyperthermia.

    c. Drug delivery

    Controlled drug release is targeted by the application of SPIO nanoparticles as drug carriers. A "therapeutic cocktail" treatment is being investigated in Zhao's lab that uses magneto-thermal effects to treat tumor cells. Small IONPs coated with polymer brushes and targeting ligands release drugs as a result of magneto-thermal effect. Molecular thermometer measures the localized coating temperature using the temperature dependent fluorescence intensity of different dyes. This is currently a collaborative work with Jason Locklin and Jin Xie, Professors of Chemistry at the UGA.

    3. MR phase gradient mapping

    a. Thermometry:

    Monitoring of temperature in real time during thermal treatment of tumor (e.g. high intensity focused ultrasound (HIFU) or hyperthermia) is crucial for evaluating treatment effect. MR phase gradient mapping (PGM), a novel technique developed in the Zhao's lab, is capable of achieving this goal.

    Figure4 Left : (a) A view of the magnitude image of the high intensity focused ultrasound (HIFU) data set. The ROI used to estimate the baseline phase map is highlighted. (b) The unwrapped baseline phase map. (c) The unwrapped post-heating phase map. The distribution of temperature estimations from the standard PRF-shift MR thermometry, Rieke's referenceless method and the proposed method implemented using the standard basis is shown in the 2nd row.
    Figure4 Right : Estimations of the internal temperature in the HIFU data set.

    b. Quantitative susceptibility mapping

    4. Dynamic contrast enhanced MRI

    Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a noninvasive imaging technique that has been widely studied as a cancer imaging tool. The Zhao's group has developed several methods for DCE-MRI data analysis, such as pharmacokinetic parameter ratios based on a reference region model.

    Figure5 : Seven canine brain tumors (pointed by double arrows) enhanced by DCEMRI.

    5. MR spectroscopy

    Multinuclear MR spectroscopy is another area that the Zhao group has focused on. Different from MR imaging, analysis of a MR spectrum provides information on the number and type of chemical entities in a molecule. Working with UGA kinesiology scientists, the Zhao group has developed a noninvasive technique for measuring muscle oxidative capacity using 31P (Phosphorus) magnetic resonance spectroscopy.