Research Interests
1.
Molecular-targeted OCT and OCM for cancer detection
OCT is a powerful tool for assessing
tissue architectural morphology. It enables 3D imaging with resolutions
approaching standard histopathology (a few microns), and it can be performed in vivo and in
real-time without the need to remove and process specimens. OCM combines
coherence-gated detection with confocal microscopy in
order to achieve high transverse resolutions, thus enabling 3D visualization of
cellular features. However, current OCT and OCM imaging technologies have not
been able to leverage the recent advances in molecular-targeted contrast agents
that are revolutionizing biomedicine. In this project, we will develop and
validate techniques that enable molecular contrast for 3D-OCT and OCM. The
successful completion of this project will allow both the structure and
pathological states of tissue to be imaged in 3D, in vivo, and in real time with
micron-level spatial resolutions at multiple scales. This work will lay the
foundation for a wide range of fundamental research, small animal imaging, and
future clinical applications in humans. This work will also serve as a starting
point for the OCT and OCM studies of other pathologies associated with abnormal
protein expression levels, such as neurodegenerative and cardiovascular
diseases. This work is supported by NIH/NIBIB through the Pathway to
Independence Award (K99/R00).
Molecular-targeted OCT and OCM allow
both the structure and pathological states of tissue to be imaged in 3D, in vivo, and in
real time with micron-level spatial resolutions at multiple scales. Photothermal OCT imaging was demonstrated in highly
scattering human breast tissues ex
vivo. (A) No photothermal signal is
observed from control images in saline-injected specimen. Phase modulation
signal (B) and SNR (C) images obtained from the nanoshell
(50 ul, 5 ×10^9 / ml) injected specimen at
various photothermal modulation frequencies (no
modulation, 5 kHz, 10 kHz, and 20 kHz modulation) demonstrate localized photothermal signal. (D and E) Phase modulation time curves
and frequency spectra corresponding to pixels marked in (C). Ref: Zhou et al, Opt. Lett.,
35(5):700-702, 2010.
2. OCT
and OCM Imaging in Developmental Biology and Tissue Engineering
OCT and OCM have several features that make
them attractive for applications in the fields of developmental biology and
tissue engineering. OCT and OCM provide the spatial and temporal resolutions
needed for imaging developing embryos and engineered tissues. The imaging is
non-invasive and does not perturb the natural development and growth of the
samples. This allows in
vivo imaging of the same sample at various developmental stages.
OCT and OCM can also provide real-time 3D structural and functional information
about the samples, enabling imaging applications of various dynamic processes.
Representative
M-mode OCT imaging of cardiac function in 30-day old adult Drosophila. A: Control
showed normal HR (250 BPM) and rhythm; B. Overexpression
of dPsn led to increased HR (296 BPM) and irregular
heartbeats; C: Silencing of dPsn caused reduced HR
(167 BPM), small heart chamber and irregular heartbeat. Ref: Li, Zhou et al, Curr. Alzheimer Res., 8(3):313-322, 2011.
3. 3D
OCT imaging of Brain Functions
Normal brain function depends on
delivery of oxygen and glucose, and on clearance of the byproducts
of metabolism. Thus, an understanding of the normal and pathological conditions
of oxygen supply and consumption, and measurement of blood flow is important
for basic neuroscience and clinical applications. To this end, a variety of
tools have been developed to image cerebral hemodynamics.
For example, transcranial Doppler is a common
clinical tool but is limited to measurement of blood flow within large vessels.
Functional (blood oxygen level dependent - BOLD, or arterial spin labeled - ASL) MRI provides 3D tomography of the brain with
moderate spatial resolution (a few millimeters). PET
measures cerebral blood flow and oxygen metabolism with a decreased spatial
resolution compared to MRI. Currently, the laboratory use of MRI and PET based
techniques are limited due to high cost, low spatial and temporal resolution,
and low mobility. Optical imaging techniques, such as optical intrinsic imaging
and LSI, can be used to extract cerebral blood oxygenation and blood flow
information at high spatial and temporal resolutions. However,
optical intrinsic imaging and LSI are limited to the mapping of brain functions
only in 2D.
We will develop novel OCT imaging
techniques to image 3D brain functions in animal models. Not only can OCT
provide structural information of the animal cortex at micron-scale resolution,
but can also be used to extract 3D cerebral hemodynamic information by using
Doppler (for blood flow) and spectroscopic (for blood oxygenation) OCT
techniques. The 1-2 mm penetration depth of OCT allows imaging through
thinned skull rather than opened skull, which makes longitudinal studies
possible. The combination of 3D mapping of blood flow and oxygenation
will enable for the first time imaging of cerebral oxygen metabolism in 3D at
micron-scale resolution. The successful completion of the development of
this technique will enable us to investigate 3D brain functions in
physiological (e.g. during forepaw, hind paw and whisker stimulations), and pathophysiological (eg. cortical
spreading depression, ischemic and traumatic brain injuries) conditions in
animal models.
