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Vascular diseases are becoming an epidemic with an increasing aging population and increases in obesity and type II diabetes. Point-of-care (POC) diagnosis and monitoring of vascular diseases is an unmet medical need. Photoacoustic imaging (PAI) provides label-free multiparametric information of deep vasculature based on strong absorption of light photons by hemoglobin molecules. However, conventional PAI systems use bulky nanosecond lasers which hinders POC applications. Recently, light-emitting diodes (LEDs) have emerged as cost-effective and portable optical sources for the PAI of living subjects. However, state-of-art LED arrays carry significantly lower optical energy (<0.5 mJ/pulse) and high pulse repetition frequencies (PRFs) (4 KHz) compared to the high-power laser sources (100 mJ/pulse) with low PRFs of 10 Hz. Given these tradeoffs between portability, cost, optical energy and frame rate, this work systematically studies the deep tissue PAI performance of LED and laser illuminations to help select a suitable source for a given biomedical application. To draw a fair comparison, we developed a fiberoptic array that delivers laser illumination similar to the LED array and uses the same ultrasound transducer and data acquisition platform for PAI with these two illuminations. Several controlled studies on tissue phantoms demonstrated that portable LED arrays with high frame averaging show higher signal-to-noise ratios (SNRs) of up to 30 mm depth, and the high-energy laser source was found to be more effective for imaging depths greater than 30 mm at similar frame rates. Label-free in vivo imaging of human hand vasculature studies further confirmed that the vascular contrast from LED-PAI is similar to laser-PAI for up to 2 cm depths. Therefore, LED-PAI systems have strong potential to be a mobile health care technology for diagnosing vascular diseases such as peripheral arterial disease and stroke in POC and resource poor settings.

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The standard diagnostic procedure for prostate cancer (PCa) is transrectal ultrasound (TRUS)-guided needle biopsy. However, due to the low sensitivity of TRUS to cancerous tissue in the prostate, small yet clinically significant tumors can be missed. Magnetic resonance imaging (MRI) with TRUS fusion biopsy has recently been introduced as a way to improve the identification of clinically significant PCa in men. However, the spatial errors in coregistering the preprocedural MRI with the real-time TRUS causes false negatives. A real-time and intraprocedural imaging modality that can sensitively detect PCa tumors and, more importantly, differentiate aggressive from nonaggressive tumors could largely improve the guidance of biopsy sampling to improve diagnostic accuracy and patient risk stratification. In this work, we seek to fill this long-standing gap in clinical diagnosis of PCa via the development of a dual-modality imaging device that integrates the emerging photoacoustic imaging (PAI) technique with the established TRUS for improved guidance of PCa needle biopsy. Unlike previously published studies on the integration of TRUS with PAI capabilities, this work introduces a novel approach for integrating a focused light delivery mechanism with a clinical-grade commercial TRUS probe, while assuring much-needed ease of operation in the transrectal space. We further present the clinical potential of our device by (i) performing rigorous characterization studies, (ii) examining the acoustic and optical safety parameters for human prostate imaging, and (iii) demonstrating the structural and functional imaging capabilities using deep-tissue-mimicking phantoms. Our TRUSPA experimental studies demonstrated a field-of-view in the range of 130 to 150 degrees and spatial resolutions in the range of 300 μm to 400 μm at a soft tissue imaging depth of 5 cm.

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