Real-time Near-infrared Virtual Intraoperative Surgical Photoacoustic Microscopy

AbstractWe developed a near infrared (NIR) virtual intraoperative surgical photoacoustic microscopy (NIR-VISPAM) system that combines a conventional surgical microscope and an NIR light photoacoustic microscopy (PAM) system. NIR-VISPAM can simultaneously visualize PA B-scan images at a maximum display rate of 45Hz and display enlarged microscopic images on a surgeon's view plane through the ocular lenses of the surgical microscope as augmented reality. The use of the invisible NIR light eliminated the disturbance to the surgeon's vision caused by the visible PAM excitation laser in a previous report. Further, the maximum permissible laser pulse energy at this wavelength is approximately 5 times more than that at the visible spectral range. The use of a needle-type ultrasound transducer without any water bath for acoustic coupling can enhance convenience in an intraoperative environment. We successfully guided needle and injected carbon particles in biological tissues ex vivo and in melanoma-bearing mice in vivo

Review of photoacoustic imaging plus X

Photoacoustic imaging (PAI) is a novel modality in biomedical imaging technology that combines the rich optical contrast with the deep penetration of ultrasound. To date, PAI technology has found applications in various biomedical fields. In this review, we present an overview of the emerging research frontiers on PAI plus other advanced technologies, named as PAI plus X, which includes but not limited to PAI plus treatment, PAI plus new circuits design, PAI plus accurate positioning system, PAI plus fast scanning systems, PAI plus novel ultrasound sensors, PAI plus advanced laser sources, PAI plus deep learning, and PAI plus other imaging modalities. We will discuss each technology's current state, technical advantages, and prospects for application, reported mostly in recent three years. Lastly, we discuss and summarize the challenges and potential future work in PAI plus X area

Photoacoustic Imaging in Gastroenterology: Advances and Needs

Gastroenterologists routinely use optical imaging and ultrasound for the minimally invasive diagnosis and treatment of chronic inflammatory diseases and cancerous tumors in gastrointestinal tract and related organs. Recent advances in gastroenterological photoacoustics represent combination of multispectral and multiscale photoacoustic (PA), ultrasound (US), and near-infrared (NIR) fluorescent imaging. The novel PA endoscopic methods have been evaluated in preclinical models using catheter-based miniature probes either noncontact, all-optical, forward-viewing probe or contact, side-viewing probe combined with ultrasound (esophagus and colon). The deep-tissue PA tomography has been applied to preclinical research on targeted contrast agents (pancreatic cancer) using benchtop experimental setups. The clinical studies engaging human tissue ex vivo have been performed on endoscopic mucosal resection tissue with PA-US tomography system and intraoperative imaging of pancreatic tissue with PA and NIR fluorescence multimodality. These emerging PA methods are very promising for early cancer detection and prospective theranostics. The noninvasive transabdominal examination with PA-US handheld probe has been implemented into clinical trials for the assessment of inflammatory bowel disease. To facilitate translational and clinical research in PA imaging in gastroenterology, we discuss potential clinical impact and limitations of the proposed solutions and future needs

High‐speed Intraoperative Assessment of Breast Tumor Margins by Multimodal Ultrasound and Photoacoustic Tomography

Conventional methods for breast tumor margins assessment need a long turnaround time, which may lead to re‐operation for patients undergoing lumpectomy surgeries. Photoacoustic tomography (PAT) has been shown to visualize adipose tissue in small animals and human breast. Here, we demonstrate a customized multimodal ultrasound and PAT system for intraoperative breast tumor margins assessment using fresh lumpectomy specimens from 66 patients. The system provides the margin status of the entire excised tissue within 10 minutes. By subjective reading of three researchers, the results show 85.7% [95% confidence interval (CI), 42.0% ‐ 99.2%] sensitivity and 84.6% (95% CI, 53.7% ‐ 97.3%) specificity, 71.4% (95% CI, 30.3% ‐ 94.9%) sensitivity and 92.3% (95% CI, 62.1% ‐ 99.6%) specificity, and 100% (95% CI, 56.1% ‐ 100%) sensitivity and 53.9% (95% CI, 26.1% ‐ 79.6%) specificity respectively when cross‐correlated with post‐operational histology. Furthermore, a machine learning‐based algorithm is deployed for margin assessment in the challenging ductal carcinoma in situ tissues, and achieved 85.5% (95% CI, 75.2% ‐ 92.2%) sensitivity and 90% (95% CI, 79.9% ‐ 95.5%) specificity. Such results present the potential of using mutlimodal ultrasound and PAT as a high‐speed and accurate method for intraoperative breast tumor margins evaluation

Progress in Probe-Based Sensing Techniques for In Vivo Diagnosis

Advancements in robotic surgery help to improve the endoluminal diagnosis and treatment with minimally invasive or non-invasive intervention in a precise and safe manner. Miniaturized probe-based sensors can be used to obtain information about endoluminal anatomy, and they can be integrated with medical robots to augment the convenience of robotic operations. The tremendous benefit of having this physiological information during the intervention has led to the development of a variety of in vivo sensing technologies over the past decades. In this paper, we review the probe-based sensing techniques for the in vivo physical and biochemical sensing in China in recent years, especially on in vivo force sensing, temperature sensing, optical coherence tomography/photoacoustic/ultrasound imaging, chemical sensing, and biomarker sensing

A brief account of nanoparticle contrast agents for photoacoustic imaging

Photoacoustic imaging (PAI) is a hybrid, nonionizing modality offering excellent spatial resolution, deep penetration, and high soft tissue contrast. In PAI, signal is generated based on the absorption of laser-generated optical energy by endogenous tissues or exogenous contrast agents leading to acoustic emissions detected by an ultrasound transducer. Research in this area over the years has shown that PAI has the ability to provide both physiological and molecular imaging, which can be viewed alone or used in a hybrid modality fashion to extend the anatomic and hemodynamic sensitivities of clinical ultrasound. PAI may be performed using inherent contrast afforded by light absorbing molecules such as hemoglobin, myoglobin, and melanin or exogenous small molecule contrast agent such as near infrared dyes and porphyrins. However, this review summarizes the potential of exogenous nanoparticle-based agents for PAI applications including contrast based on gold particles, carbon nanotubes, and encapsulated copper compounds

Fluorescence molecular imaging during head and neck cancer surgery:visualising the invisible

Complete tumor removal is one of the most important pillars within oncologic surgery. Tumor positive resection margins, where residual cancer tissue remains after surgery, drastically reduce survival. For surgeons, it is challenging to intraoperatively distinguish tumor tissue from healthy tissue in the margin, and there is no widely used imaging modality available that can aid for this problem. In this thesis we discuss fluorescence molecular imaging, an innovative technique where cancer tissue is fluorescently labeled and visualized intraoperatively. Here, the resection margin can be analyzed real-time during surgery for the presence of tumor tissue, and remaining cancer tissue can be removed in one setting. It has previously been shown that molecular fluorescence imaging can be applied intraoperatively in patients with squamous cell carcinoma of the oral cavity. However, we are the first to conduct a large study for this indication. We have shown the exquisite sensitivity of this technique, since all tumor positive margins can be detected. In addition, we have shown that fluorescence molecular imaging can be used to distinguish healthy tissue from cancerous tissue in patients with squamous cell carcinoma of the skin, and that it is possible to reliably detect lymph node metastases. We can conclude that molecular fluorescence imaging is a promising technique that can aid the surgeon intraoperatively for different indications. Larger studies should determine whether using this technique can also improve patient outcome, to justify the implementation of this technique in standard care

Investigation of Techniques to increase the Field of View of a Staring Transducer Array for Photoacoustic Imaging

Photoacoustic imaging (PAI) is a hybrid imaging modality that takes advantage of both optical and acoustic techniques for biomedical imaging. It is believed that PAI can successfully assess the margins of lumpectomy specimens in the operating room, decreasing the number of surgeries and wait time for patients. However, current PAI systems do not have sufficient field of view (FOV) to accommodate the size of lumpectomy specimens. In this work, transducer directionality and the use of a shaped matching layer were explored as means to increase the FOV of a staring photoacoustic transducer array. The results indicated that applying a convex matching layer to the face of transducers and directing them toward the centre of the array provides optimal sensitivity throughout the imaging volume. By employing these techniques, any PAI system’s effective FOV can be increased without replacing existing transducers. The optimized system can now be investigated for lumpectomy margin assessment