Photoacoustic imaging (PAI) is drawing extensive attention and gaining rapid development as an emerging biomedical imaging technology because of its high spatial resolution, large imaging depth, and rich optical contrast. PAI has great potential applications in endoscopy, but the progress of endoscopic PAI was hindered by the challenges of manufacturing and assembling miniature imaging components. Over the last decade, microelectromechanical systems (MEMS) technology has greatly facilitated the development of photoacoustic endoscopes and extended the realm of applicability of the PAI. As the key component of photoacoustic endoscopes, micromachined ultrasound transducers (MUTs), including piezoelectric MUTs (pMUTs) and capacitive MUTs (cMUTs), have been developed and explored for endoscopic PAI applications. In this article, the recent progress of pMUTs (thickness extension mode and flexural vibration mode) and cMUTs are reviewed and discussed with their applications in endoscopic PAI. Current PAI endoscopes based on pMUTs and cMUTs are also introduced and compared. Finally, the remaining challenges and future directions of MEMS ultrasound transducers for endoscopic PAI applications are given.
19 February 2019 in Drug Delivery and Translational Research
It is highly desirable to develop novel approaches to improve patient survival rate of pancreatic cancer through early detection. Here, we present such an approach based on photoacoustic and fluorescence molecular imaging of pancreatic tumor using a miniature multimodal endoscope in combination with targeted multifunctional iron oxide nanoparticles (IONPs). A novel fan-shaped scanning mechanism was developed to minimize the invasiveness for endoscopic imaging of pancreatic tumors. The results show that the enhancements in photoacoustic and fluorescence signals using amino-terminal fragment (ATF) targeted IONPs were ~four to six times higher compared to that using non-targeted IONPs. Our study indicates the potential of the combination of the multimodal photoacoustic-fluorescence endoscopy and targeted multifunctional nanoparticles as an efficient tool to provide improved specificity and sensitivity for pancreatic cancer detection.
In this study, in vivo animal experiments with 12 nude mice bearing breast-cancer-patient-tissue-derived xenograft (PDX) tumors were performed aiming to verify the imaging capability of a novel miniaturized fluorescence molecular tomography (FMT) endoscope, in combination with targeted nanoparticle–near-infrared (NIR) dye conjugates. Tumor-bearing mice were divided into two groups by systematic injection with urokinase plasminogen activator receptor-targeted (n = 7) and nontargeted (n = 5) imaging nanoprobes as a contrast agent, respectively. Each mouse was imaged at 6, 24, and 48 h following the injection of nanoprobes using the FMT endoscope. The results show that systemic delivery of targeted nanoprobes produced a 4-fold enhancement in fluorescence signals from tumors, compared with tumors that received nontargeted nanoprobes. This study indicates that our miniaturized FMT endoscope, coupled with the targeted nanoparticle–NIR dye conjugates as a contrast agent, has high sensitivity and specificity, and thus great potential to be used for image-guided detection and removal of a primary tumor and local metastatic tumors during surgery.
We present a novel FMT endoscope by using a MEMS scanning mirror and an optical fiberscope. The diameter of this highly miniaturized FMT device is only 5 mm. To our knowledge, this is the smallest FMT device we found so far. Several phantom experiments based on indocyanine green (ICG) were conducted to demonstrate the imaging ability of this device. Two tumor-bearing mice were systematically injected with tumor-targeted NIR fluorescent probes (ATF-PEG-IO-830) and were then imaged to further demonstrate the ability of this FMT endoscope for imaging small animals.
Functional neuroimaging studies of neuropsychiatric disorders and cognitive impairment are commonly conducted in the clinic setting but less so in the acutely medically ill while hospitalized. This is largely due to technical and logistical limitations, given the lack of portable devices with high spatial and temporal resolutions. This exploratory study reports on the development and implementation of a novel diffuse optical tomography (DOT) system that can be employed for bedside three-dimensional functional neuroimaging. To test this portable DOT system, our protocol included a task-based sequence involving the Months Backwards Test with imaging centered on the bilateral prefrontal cortex. Fifteen subjects were recruited from intensive care units and the general wards of a single tertiary academic hospital and included in our final analysis. Volumetric hemoglobin analyses of the dorsolateral prefrontal cortex (DLPFC) and dorsomedial prefrontal cortex (DMPFC) were reliably captured in all our subjects. The peak value was calculated to be 3.36 µM and 0.74 µM for oxygenated-hemoglobin (HbO) and total-hemoglobin (HbT) (p < 0.042, [HbT]), respectively. The standard error was calculated to be 4.58 uM and 3.68 uM for (HbO) and (HbT). We additionally developed a seed-based correlation analysis to demonstrate the capability of DOT in studying functional connectivity. The right DLPFC was found to be moderately associated with the left DLPFC in all our subjects (r = 0.656). The DMPFC was observed to be associated with the left DLPFC but less so (r = 0.273) at the group level. Overall, the contribution of left-to-right DLPFC connectivity was significantly higher than left DLPFC to DMPFC in our group (p = 0.012). Future studies should investigate the potential of such a DOT system in the research of neuropsychiatric and neurocognitive disorders within the hospital to study different types of mechanisms, pathophysiology, and interventions that occur acutely and can advance our knowledge of these disorders.