Ayeeshik Kole

High-sensitivity intravascular photoacoustic imaging of lipid–laden plaque with a collinear catheter design

A highly sensitive catheter probe is critical to catheter-based intravascular photoacoustic imaging. Here, we present a photoacoustic catheter probe design on the basis of collinear alignment of the incident optical wave and the photoacoustically generated sound wave within a miniature catheter housing for the first time. Such collinear catheter design with an outer diameter of 1.6 mm provided highly efficient overlap between optical and acoustic waves over an imaging depth of >6 mm in D2O medium. Intravascular photoacoustic imaging of lipid-laden atherosclerotic plaque and perivascular fat was demonstrated, where a lab-built 500 Hz optical parametric oscillator outputting nanosecond optical pulses at a wavelength of 1.7 μm was used for overtone excitation of C-H bonds. In addition to intravascular imaging, the presented catheter design will benefit other photoacoustic applications such as needle-based intramuscular imaging.

Real-Time intravascular photoacoustic-ultrasound imaging of lipid-laden plaque in human coronary artery at 16 frames per second

Intravascular photoacoustic-ultrasound (IVPA-US) imaging is an emerging hybrid modality for the detection of lipid-laden plaques, as it provides simultaneous morphological and lipid-specific chemical information of an artery wall. Real-time imaging and display at video-rate speed are critical for clinical utility of the IVPA-US imaging technology. Here, we demonstrate a portable IVPA-US system capable of imaging at up to 25 frames per second in real-time display mode. This unprecedented imaging speed was achieved by concurrent innovations in excitation laser source, rotary joint assembly, 1 mm IVPA-US catheter size, differentiated A-line strategy, and real-time image processing and display algorithms. Spatial resolution, chemical specificity, and capability for imaging highly dynamic objects were evaluated by phantoms to characterize system performance. An imaging speed of 16 frames per second was determined to be adequate to suppress motion artifacts from cardiac pulsation for in vivo applications. The translational capability of this system for the detection of lipid-laden plaques was validated by ex vivo imaging of an atherosclerotic human coronary artery at 16 frames per second, which showed strong correlation to gold-standard histopathology. Thus, this high-speed IVPA-US imaging system presents significant advances in the translational intravascular and other endoscopic applications.

Spectral analysis assisted photoacoustic imaging for lipid composition differentiation

Recent advances in atherosclerotic plaque detection have shown that not only does lipid core size and depth play important roles in plaque rupture and thrombi formation, but lipid composition, especially cholesterol deposition, is equally important in determining lesion vulnerability. Here, we demonstrate a spectral analysis assisted photoacoustic imaging approach to differentiate and map lipid compositions within an artery wall. The approach is based on the classification of spectral curves obtained from the sliding windows along time-of-flight photoacoustic signals via a numerical k-means clustering method. The evaluation result on a vessel-mimicking phantom containing cholesterol and olive oil shows accuracy and efficiency of this method, suggesting the potential to apply this approach in assessment of atherosclerotic plaques.

Human organ-on-a-chip BioMEMS devices for testing new diagnostic and therapeutic strategies

MEMS human “organs-on-a-chip” can be used to create model human organ systems for developing new diagnostic and therapeutic strategies. They represent a promising new strategy for rapid testing of new diagnostic and therapeutic approaches without the need for involving risks to human subjects. We are developing multicomponent, superparamagnetic and fluorescent nanoparticles as X-ray and MRI contrast agents for noninvasive multimodal imaging and for antibody- or peptide-targeted drug delivery to tumor and precancerous cells inside these artificial organ MEMS devices. Magnetic fields can be used to move the nanoparticles “upstream” to find their target cells in an organs-on-achip model of human ductal breast cancer. Theoretically, unbound nanoparticles can then be removed by reversing the magnetic field to give a greatly enhanced image of tumor cells within these artificial organ structures. Using branched PDMS microchannels and 3D tissue engineering of normal and malignant human breast cancer cells inside those MEMS channels, we can mimic the early stages of human ductal breast cancer with the goal to improve the sensitivity and resolution of mammography and MRI of very small tumors and test new strategies for treatments. Nanomedical systems can easily be imaged by multicolor confocal microscopy inside the artificial organs to test targeting and therapeutic responses including the differential viability of normal and tumor cells during treatments. Currently we are using 2-dimensional MEMS structures, but these studies can be extended to more complex 3D structures using new 3D printing technologies.