Area of Reasearch
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.
: 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.
: 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)).
: 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.
: Illustration of treatment of tumors using an alternating magnetic field.
: A cross section of mouse flank (tumor enclosed with the red line).
: 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
, Professors of Chemistry at the UGA.
3. MR phase gradient mapping
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.
: (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.
: 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.
: 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.