Research in the Zemp lab is based on core engineering competencies of acoustics, optics, modeling, algorithms, micro/nanofabrication and instrumentation as well as biological competencies in animal models, biomarkers, cancer and cardiovascular medicine to develop next generation biomedical imaging technologies to probe scales from the macroscopic to the microscopic. Research in the Zemp lab will lead to new imaging tools for biologists and clinicians to provide new functional and molecular information that aims to lead to earlier detection of cancer, non-invasive biomarker profiling to gage disease aggressiveness and response to therapy, profiling of tissue oxygenation and metabolism, and personalizing medicine. We also aim to develop tools and methods to visualize how genes are regulated in the body and how to better deliver treatments such as chemotherapy, photodynamic therapy, and high-intensity focused ultrasound with improved image-guidance, and reduced side-effects. Core projects include:
(1) Photoacoustic imaging. The PI is a world-leader in the area of photoacoustic imaging, a rapidly growing new field. In photoacoustic imaging, safe laser pulses are fired into tissues. When light is absorbed by chromophores, absorbed optical energy creates a thermoelastic expansion producing acoustic waves. These signals are detected and reconstructed to form images with optical contrast yet with high resolution, unlike previous deep-tissue optical imaging techniques. This technique is being developed in various embodiments including: (a) array-based imaging with a programmable ultrasound imaging system (b) deep-tissue photoacoustic tomography (PAT) including multiple-illumination and patterned illumination PAT (c) acoustic-resolution photoacoustic microscopy (d) optical-resolution photoacoustic microscopy (e) all-optical systems using custom nanostructured thin-film etalons and/or interferometry (f) micro-endoscopy systems for intra-cavity imaging.
The technique has been demonstrated or is under development for the following applications by our group: (a) microvasculature imaging, (b) imaging of oxygen saturation of hemoglobin, partial oxygen pressure, and oxygen flux and metabolism, (c) imaging of gene expression, (d) imaging actively or passively targeted dyes and nanoparticles for molecular imaging applications, (e) imaging of smart molecules for sensing enzyme activity including cathespin D (important in apoptosis) as well as calcium-signaling, (f) functional brain imaging, (g) tissue perfusion estimation, (h) estimating lifetimes of molecules, (i) chemical-bond-specific imaging and spectroscopy, (j) imaging tumor hypoxia and angiogenesis, (k) imaging response to therapies such as chemotherapies and photodynamic therapies (l) estimating the depth of invasion of melanomas (m) non-invasive alternatives to sentinel lymph node biopsy (n) prostate brachytherapy guidance.
New frontiers in photoacoustic imaging may play an important role in pre-clinical and clinical molecular & functional imaging & the field is ripe for ground-breaking innovations.
(1) Photoacoustic imaging. The PI is a world-leader in the area of photoacoustic imaging, a rapidly growing new field. In photoacoustic imaging, safe laser pulses are fired into tissues. When light is absorbed by chromophores, absorbed optical energy creates a thermoelastic expansion producing acoustic waves. These signals are detected and reconstructed to form images with optical contrast yet with high resolution, unlike previous deep-tissue optical imaging techniques. This technique is being developed in various embodiments including: (a) array-based imaging with a programmable ultrasound imaging system (b) deep-tissue photoacoustic tomography (PAT) including multiple-illumination and patterned illumination PAT (c) acoustic-resolution photoacoustic microscopy (d) optical-resolution photoacoustic microscopy (e) all-optical systems using custom nanostructured thin-film etalons and/or interferometry (f) micro-endoscopy systems for intra-cavity imaging.
The technique has been demonstrated or is under development for the following applications by our group: (a) microvasculature imaging, (b) imaging of oxygen saturation of hemoglobin, partial oxygen pressure, and oxygen flux and metabolism, (c) imaging of gene expression, (d) imaging actively or passively targeted dyes and nanoparticles for molecular imaging applications, (e) imaging of smart molecules for sensing enzyme activity including cathespin D (important in apoptosis) as well as calcium-signaling, (f) functional brain imaging, (g) tissue perfusion estimation, (h) estimating lifetimes of molecules, (i) chemical-bond-specific imaging and spectroscopy, (j) imaging tumor hypoxia and angiogenesis, (k) imaging response to therapies such as chemotherapies and photodynamic therapies (l) estimating the depth of invasion of melanomas (m) non-invasive alternatives to sentinel lymph node biopsy (n) prostate brachytherapy guidance.
New frontiers in photoacoustic imaging may play an important role in pre-clinical and clinical molecular & functional imaging & the field is ripe for ground-breaking innovations.
(2) MEMS Ultrasound Transducers. We have built up a fairly large research program in capacitive micromachined ultrasound transducers (CMUTs) with several industrial collaborators. These are miniature micro/nanofabricated membrane structures that can be electrostatically actuated to transmit ultrasound waves and can receive acoustic signals by sensing capacitive changes. CMUTs have a number of advantages over more traditional piezoelectric transducers, including broad bandwidth and exquisite sensitivity. We have also demonstrated unique architectures including multi-frequency CMUT arrays and Top Orthogonal to Bottom Electrode (TOBE) 2D CMUT arrays for imaging-therapy and 3D imaging applications which are not easily achieved using piezoelectrics. With promising preliminary data these devices are being developed for trans-rectal and endoscopic 3D imaging applications, for image-guided therapy applications, and for ultrasensitive photoacoustic imaging. Clinical translation is planned in the next 3 years.
(3) Ultrafast Ultrasound Imaging. Traditional ultrasound imaging is frame-rate limited by the time-of-flight of ultrasound. High frame-rate ultrasound techniques sacrifice focusing and image quality to enable imaging at thousands of frames per second. Recently we proposed novel asynchronous orthogonal codes which we call non-repeating interval (NRI) codes. By transmitting a different code from each element of an array then receiving on all elements and performing respective decoding and beamforming steps we have demonstrated fast imaging with significantly improved image quality compared to previous work. High-quality high-frame-rate imaging may have significant impact on several areas we propose to investigate, such as ultrafast functional ultrasound imaging of the brain, electromechanical wave imaging of the heart, and supersonic shear-wave imaging to map tissue stiffness.
(4) Trapping and multiplex detection of circulating tumor cells (CTCs). CTCs can be quite important for blood biomarker diagnostics but are challenging to isolate. Surface-enhanced Raman-scattering (SERS) nanoparticles are metallic-cored with a Raman reporter and silica encapsulation layer and produce a bright optical signature which is an amplified version of the Raman spectrum of the reporter molecules. Different species of Raman reporters offer a unique spectral fingerprint enabling spectral unmixing of mixtures of nanoparticles. By targeting CTCs with both magnetic and SERS nanoparticles, flowing cells can be trapped by a magnet in vitro or in vivo and SERS signals increase with magnetic trapping time with single cell sensitivity and high specificity owing to multiplex targeting.
(5) Phase-change nanodroplets. These are phospholipid-shelled with a liquid perfluorocarbon core. The shell and or core can be loaded with optically absorbing molecules such as porphyrins for photoacoustic imaging or drugs for ultrasound-stimulated drug release. Ultrasound can trigger phase-change of the nanodroplets into microbubbles for contrast-ultrasound imaging. The nanodroplets are smaller than normal microbubble contrast agents and can extravasate from leaky tumor vasculature and even accumulate in tumors due to the enhanced permeability and retention effect.
(6) Blood Biomarkers for Personalized Cancer Medicine. We use intense ultrasound to stimulate the release of biomarkers for molecular diagnostics and personalized medicine. We were the first group in the world to show that ultrasound can release mRNA, miRNA, and extracellular vesicles loaded with biomarkers from host cells and that these biomarkers have potential for clinical utility.
(7) Non-invasive diagnosis of pulmonary hypertension: We develop algorithms to discriminate pulmonary hypertension subjects from those without PH using digital auscultation measurements of heart sounds and fast ultrasound methods to discriminate heart-valve closure dynamics. The long-term goal is to develop a portable handheld device for use in developing countries.
(8) Inverse Problems and Modeling of Light Transport: We have developed fundamentally new ways of modeling light transport in scattering media and are applying these models to solve optical inverse problems.
(8) Inverse Problems and Modeling of Light Transport: We have developed fundamentally new ways of modeling light transport in scattering media and are applying these models to solve optical inverse problems.
