Ocular neovascularization occurs in various eye diseases such as diabetic retinopathy, neovascular macular degeneration, and retinopathy of prematurity. Current treatment methods including conventional laser ablation therapy and anti-vascular endothelial growth factor (VEGF) injection each has drawbacks including collateral tissue damages, frequent administration, high cost, and drug toxicity. We recently developed a novel noninvasive image-guided photo-mediated ultrasound therapy (PUT) which concurrently applies nanosecond laser pulses and millisecond ultrasound bursts to precisely and safely remove pathologic microvessels in the eye. Relying on the mechanism of photoacoustic cavitation, PUT takes advantages of high optical contrast among biological tissues, and can selectively remove microvessels without causing collateral tissue damage.
To achieve personalized treatment with optimal treatment outcome, a multi-modality eye imaging system involving advanced photoacoustic microscopy (PAM) and optical coherence tomography (OCT) has been integrated with the PUT system to provide real-time feedback and online evaluation of the treatment outcome. To assess the performance of this image-guided PUT system, experiments have been conducted on rabbit eye models. During the treatment, cavitation signals were observed and monitored by OCT with good sensitivity, suggesting that OCT can be used to evaluate treatment effect in real time. The PAM was capable of mapping the 3D distributed microvessels with excellent image quality, demonstrating that PAM can help to quantitatively evaluate the treatment outcome. As indicated by the initial results from this study, imaging guidance involving both PAM and OCT could further improve the efficacy and safety of the newly invented PUT, accelerating its translation to ophthalmology clinic.
We demonstrated the ultrasound modulated droplet lasers, in which the laser intensity from whispering gallery mode (WGM) of oil droplets can be reversibly enhanced up to 20-fold when the ultrasound pressure is beyond a certain threshold. The lasing enhancement was investigated with various ultrasound frequencies and pressures. Furthermore, the ultrasound modulation of the laser output was achieved by controlling the ultrasound pressure, the duty cycle, and the frequency of ultrasound bursts. Its potential application was explored via the study on a human whole blood vessel phantom. A theoretical analysis was also conducted, showing that the laser emission enhancement results from the directional emission from a deformed cavity under ultrasound pressure. Our studies reveal the unique capabilities of ultrasound modulated droplet lasers, which could lead to the development of laser emission-based microscopy for deep tissue imaging with high spatial resolution and detection sensitivity that may overcome the long-standing drawback of traditional fluorescence imaging.
Transrectal ultrasound (TRUS) guided biopsy is the standard procedure for evaluating the presence and aggressiveness of prostate cancer (PCa). The microarchitecture of each biopsied tissue is assigned a Gleason score, a highly prognostic architecture-based grading system for PCa. Due to the limited sensitivity of TRUS imaging to PCa, less than 10% of the sample cores are clinically significant, yet the false negative rate could be 20% at the initial biopsies. A diagnostic modality that can assess the microarchitectures within the prostates in vivo without tissue extraction could significantly reduce the unnecessary biopsy cores and the post-procedure complications. Our previous study has shown that photoacoustic physio-chemical analysis (PAPCA) can quantify the architectural heterogeneities in the prostate. Our recently developed needle PA probe has facilitated the minimally invasive acquisition of PA signals with sufficient temporal length and narrow dynamic range in deep tissue for statistics-based PAPCA.
This study investigates the PCa diagnosis by PAPCA of the signals acquired by the needle PA probe. A total of 45 interstitial measurements were acquired (21 in normal and 24 in cancerous regions) in 10 ex vivo human prostates. A significant difference was found in the architectural heterogeneities between the normal and cancerous regions (p<0.005). Areas-under-the-curve of 0.8 has been observed for identifying PCa using the quantitative features. Quantification of the architectural changes in vivo in a transgenic mouse model of PCa is under investigation. The preliminary test has shown a significant difference between the normal and cancerous mouse prostates ex vivo (p<0.005).
Photoacoustic (PA) signal of an ideal optical absorb particle is a single N-shape wave. PA signals of a complicated biological tissue can be considered as the combination of individual N-shape waves. However, the N-shape wave basis not only complicates the subsequent work, but also results in aliasing between adjacent micro-structures, which deteriorates the quality of the final PA images. In this paper, we propose a method to improve PA image quality through signal processing method directly working on raw signals, which including deconvolution and empirical mode decomposition (EMD). During the deconvolution procedure, the raw PA signals are de-convolved with a system dependent point spread function (PSF) which is measured in advance. Then, EMD is adopted to adaptively re-shape the PA signals with two constraints, positive polarity and spectrum consistence. With our proposed method, the built PA images can yield more detail structural information. Micro-structures are clearly separated and revealed. To validate the effectiveness of this method, we present numerical simulations and phantom studies consist of a densely distributed point sources model and a blood vessel model. In the future, our study might hold the potential for clinical PA imaging as it can help to distinguish micro-structures from the optimized images and even measure the size of objects from deconvolved signals.