Recent Posts

PHOTOACOUSTIC IMAGE-GUIDED DELIVERY OF PLASMONIC-NANOPARTICLE-LABELED MESENCHYMAL STEM CELLS TO THE SPINAL CORD

Authors: Eleanor M. Donnelly, Kelsey P. Kubelick, Diego S. Dumani, and Stanislav Y. Emelianov

ABSTRACT

Regenerative therapies using stem cells have great potential for treating neurodegenerative diseases and traumatic injuries in the spinal cord. In spite of significant research efforts, many therapies fail at the clinical phase. As stem cell technologies advance toward clinical use, there is a need for a minimally invasive, safe, affordable, and real-time imaging technique that allows for the accurate and safe monitoring of stem cell delivery in the operating room. In this work, we present a combined ultrasound and photoacoustic imaging tool to provide image-guided needle placement and monitoring of nanoparticle-labeled stem cell delivery into the spinal cord. We successfully tagged stem cells using gold nanospheres and provided image-guided delivery of stem cells into the spinal cord in real-time, detecting as few as 1000 cells. Ultrasound and photoacoustic imaging was used to guide needle placement for direct stem cell injection to minimize the risk of needle shear and accidental injury and to improve therapeutic outcomes with accurate, localized stem cell delivery. Following injections of various volumes of cells, three-dimensional ultrasound and photoacoustic images allowed the visualization of stem cell distribution along the spinal cord, showing the potential to monitor the migration of the cells in the future. The feasibility of quantitative imaging was also shown by correlating the total photoacoustic signal over the imaging volume to the volume of cells injected. Overall, the presented method may allow clinicians to utilize imaged-guided delivery for more accurate and safer stem cell delivery to the spinal cord.

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TECHNICAL CONSIDERATIONS IN THE VERASONICS RESEARCH ULTRASOUND PLATFORM FOR DEVELOPING A PHOTOACOUSTIC IMAGING SYSTEM

Authors: Karl Kratkiewicz1,4,Rayyan Manwar2,4, Yang Zhou, Moein Mozaffarzadeh3, Kamran Avanaki2

ABSTRACT

Photoacoustic imaging (PAI) is an emerging functional and molecular imaging technology that has attracted much attention in the past decade. Recently, many researchers have used the vantage system from Verasonics for simultaneous ultrasound (US) and photoacoustic (PA) imaging. This was the motivation to write on the details of US/PA imaging system implementation and characterization using Verasonics platform. We have discussed the experimental considerations for linear array based PAI due to its popularity, simple setup, and high potential for clinical translatability. Specifically, we describe the strategies of US/PA imaging system setup, signal generation, amplification, data processing and study the system performance.

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PRECLINICAL SMALL ANIMAL IMAGING PLATFORM PROVIDING CO-REGISTERED 3D MAPS OF PHOTOACOUSTIC RESPONSE AND FLUORESCENCE

Authors: Diego S. Dumani1,2, Anthony Yu1,2, Weylan Thompson3, Hans-Peter Brecht3, Vassili Ivanov3, Mark A. Anastasio4, Jason Cook5, Sergey A. Ermilov3, Stanislav Y. Emelianov1,2

ABSTRACT

We report on the development of a preclinical 3D imaging platform integrating photoacoustic tomography and fluorescence (PAFT). The proposed multimodal imaging concept addresses known deficiencies in sensitivity, anatomical registration, and spatial resolution of the individual imaging modalities. Multi-view photoacoustic and optical projections of the studied animal are utilized to reconstruct large (27 cm3) volumes showing vascular network and blood-rich tissues, as well as regions with induced optical/fluorescence contrast with 3D resolution exceeding 150 μm. An additional 532-nm low-energy pulsed laser excitation is implemented as a separate imaging channel for registration over skin topography and superficial vasculature. PAFT technology enables functional and molecular volumetric imaging using wide range of fluorescent and luminescent biomarkers, nanoparticles, and other photosensitive constructs mapped with high fidelity over robust anatomical structures of the studied animal model. We demonstrated the PAFT performance using phantoms and by in vivo imaging of preclinical murine models.

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DUAL-MODALITY X-RAY-INDUCED RADIATION ACOUSTIC AND ULTRASOUND IMAGING FOR REAL-TIME MONITORING OF RADIOTHERAPY

Authors: Wei Zhang,1 Ibrahim Oraiqat,2 Hao Lei,3 Paul L. Carson,1,4 Issam EI Naqa,2 and Xueding Wang1,4

ABSTRACT

Objective. The goal is to increase the precision of radiation delivery during radiotherapy by tracking the movements of the tumor and other surrounding normal tissues due to respiratory and other body motions. Introduction. This work presents the recent advancement of X-ray-induced radiation acoustic imaging (xRAI) technology and the evaluation of its feasibility for real-time monitoring of geometric and morphological misalignments of the X-ray field with respect to the target tissue by combining xRAI with established ultrasound (US) imaging, thereby improving radiotherapy tumor eradication and limiting treatment side effects. Methods. An integrated xRAI and B mode US dual-modality system was established based on a clinic-ready research US platform. The performance of this dual-modality imaging system was evaluated via experiments on phantoms and ex vivo and in vivo rabbit liver models. Results. This system can alternatively switch between the xRAI and the US modes, with spatial resolutions of 1.1 mm and 0.37 mm, respectively. 300 times signal averaging was required for xRAI to reach a satisfactory signal- to-noise ratio, and a frame rate of 1.1 Hz was achieved with a clinical linear accelerator. The US imaging frame rate was 22 Hz, which is sufficient for real-time monitoring of the displacement of the target due to internal body motion. Conclusion. Our developed xRAI, in combination with US imaging, allows for mapping of the dose deposition in biological samples in vivo, in real-time, during radiotherapy. Impact Statement. The US-based image-guided radiotherapy system presented in this work holds great potential for personalized cancer treatment and better outcomes.

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INDOCYANINE GREEN DYE BASED BIMODAL CONTRAST AGENT TESTED BY PHOTOACOUSTIC/FLUORESCENCE TOMOGRAPHY SETUP

Authors: MAKSIM D. MOKROUSOV, WEYLAN THOMPSON, SERGEY A. ERMILOV, TATIANA ABAKUMOVA, MARINA V. NOVOSELOVA, OLGA A. INOZEMTSEVA, TIMOFEI S. ZATSEPIN, VLADIMIR P. ZHAROV, EKATERINA I. GALANZHA, DMITRY A. GORIN 

ABSTRACT

Multimodal imaging systems are in high demand for preclinical research, experimental medicine, and clinical practice. Combinations of photoacoustic technology with other modalities including fluorescence, ultrasound, MRI, OCT have been already applied in feasibility studies. Nevertheless, only the combination of photoacoustics with ultrasound in a single setup is commercially available now. A combination of photoacoustics and fluorescence is another compelling approach because those two modalities naturally complement each other. Here, we presented a bimodal contrast agent based on the indocyanine green dye (ICG) as a single signalling compound embedded in the biocompatible and biodegradable polymer shell. We demonstrate its remarkable characteristics by imaging using a commercial photoacoustic/fluorescence tomography system (TriTom, PhotoSound Technologies). It was shown that photoacoustic signal of the particles depends on the amount of dye loaded into the shell, while fluorescence signal depends on the total amount of dye per particle. For the first time to our knowledge, a commercial bimodal photoacoustic/fluorescence setup was used for characterization of ICG doped polymer particles. Additionally, we conducted cell toxicity studies for these particles as well as studied biodistribution over time in vivo and ex vivo using fluorescent imaging. The obtained results suggest a potential for the application of biocompatible and biodegradable bimodal contrast agents as well as the integrated photoacoustic/fluorescence imaging system for preclinical and clinical studies.

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GOLD NANOPARTICLES CONJUGATED WITH DNA APTAMER FOR PHOTOACOUSTIC DETECTION OF HUMAN MATRIX METALLOPROTEINASE-9

Authors: Jinhwan Kim, Anthony M Yu, Kelsey P. Kubelick, Stanislav Y. Emelianov

ABSTRACT

Matrix metalloproteinase-9 (MMP-9) plays major roles in extracellular matrix (ECM) remodeling and membrane protein cleavage, suggesting a high correlation with cancer cell invasion and tumor metastasis. Here, we present a contrast agent based on a DNA aptamer that can selectively target human MMP-9 in the tumor microenvi-ronment (TME) with high affinity and sensitivity. Surface modification of plasmonic gold nanospheres with the MMP-9 aptamer and its complementary sequences allows the nanospheres to aggregate in the presence of human MMP-9 through DNA displacement and hybridization. Aggregation of gold nanospheres enhances the optical absorption in the first near-infrared window (NIR-I) due to the plasmon coupling effect, thereby allowing us to detect the aggregated gold nanospheres within the TME via ultrasound-guided photoacoustic (US/PA) imaging. Selective and sensitive detection of human MMP-9 via US/PA imaging is demonstrated in solution of nanosensors with the pre-treatment of human MMP-9, in vitro in cell culture, and in vivo in a xenograft murine model of human breast cancer.

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PHOTOACOUSTIC TOMOGRAPHY TO ASSESSACUTE VASOACTIVITY OF SYSTEMIC VASCULATURE

Author(s): Huda, Kristieª; Lawrence, Dylanª; Lindsey, Sarah; Bayer, Carolynª*

ABSTRACT

Vasoactivity is an important physiological indicator of cardiovascular health which is frequently measured using ex vivo vessels to determine functional mechanisms and evaluate pharmacological responses. Currently, there are no imaging methods available to assess vasoactivity in multiple vascular beds of living animals noninvasively. In this work, we have developed methods to use photoacoustic tomography to assess vasoactivity in vivo in systemic vasculature of living animals. A spherical-view photoacoustic tomography system was used to monitor acute vasodilation in the whole abdomen of a pregnant mouse in response to injection of G-1. After 3D image reconstruction, the diameter of the iliac artery and photoacoustic signal intensity of a placenta over time was measured. The artery and placenta had differential response to the vasodilator G-1. We validated the observed vasodilation of artery by monitoring the change in cross-sectional diameter of an individual artery using standard B-mode ultrasound imaging

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DEEP LEARNING ENABLED REAL-TIME PHOTOACOUSTIC TOMOGRAPHY SYSTEM VIA SINGLE DATA ACQUISITION CHANNEL

Authors: Hengrong Lan, Daohuai Jiang, Feng Gao, Fei Gao

ABSTRACT

Photoacoustic computed tomography (PACT) combines the optical contrast of optical imaging and the penetrability of sonography. In this work, we develop a novel PACT system to provide real-time imaging, which is achieved by a 120-elements ultrasound array only using a single data acquisition (DAQ) channel. To reduce the channel number of DAQ, we superimpose 30 nearby channels’ signals together in the analog domain, and shrinking to 4 channels of data (120/30 = 4). Furthermore, a four-to-one delay-line module is designed to combine these four channels’ data into one channel before entering the single-channel DAQ, followed by decoupling the signals after data acquisition. To reconstruct the image from four superimposed 30-channels’ PA signals, we train a dedicated deep learning model to reconstruct the final PA image. In this paper, we present the preliminary results of phantom and in-vivo experiments, which manifests its robust real-time imaging performance. The significance of this novel PACT system is that it dramatically reduces the cost of multi-channel DAQ
module (from 120 channels to 1 channel), paving the way to a portable, low-cost and real-time PACT system.

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PHOTOACOUSTIC IMAGING FOR IN VIVO QUANTIFICATION OF ALCOHOL-INDUCED STRUCTURAL AND FUNCTIONAL CHANGES IN CEREBRAL VASCULATURE IN HIGH ALCOHOL-PREFERRING MICE (HAP)

Authors: Augustine Meombe Mbolle, Hao Yang, Huabei Jiang*

ABSTRACT

Alcohol-induced structural and functional changes were studied in vivo by photoacoustic tomography (PAT) of the cerebrovascular system in selectively bred alcohol-preferring mice. High (HAP) and low (LAP) alcohol-preferring mice are replicate lines of mice selectively bred to prefer 10% (v/v) ethanol to water and water to ethanol, respectively, in a free-access two-bottle choice scenario. A cohort of 15 singly-housed alcohol-preferring mice (five HAP mice for the experimental group, five LAP mice for the control group, and five other LAP mice set aside) were given free-access two-bottle choice 10% ethanol (v/v) and water in 50-mL graduated drinking bottles mounted on each of their cages for 4 weeks prior to PAT brain scanning. A daily log of the volume of ethanol consumed over a 24-h period was kept. At the end of the fourth week, blood samples were collected from the HAP mice and blood ethanol concentrations (BECs) were measured to ascertain their levels of ethanol intoxication. The mice were then grouped into five weight-matched pairs of HAP and LAP for comparison purposes, and noninvasive in vivo PAT imaging was performed on each weight-matched pair. To mimic a binge drinking paradigm, mice were rearranged into four weight-matched groups of three animals each: an HAP mouse and two LAP mice. For each group, one HAP mouse and one LAP mouse received a 20% ethanol solution via intraperitoneal (i.p.) injection after 24 h of ethanol abstinence, in weight-based doses of 3 g/kg prior to imaging, while the last LAP mouse received a sham i.p. injection. PAT images of the brain were collected for 30 min thereafter. Cerebral vascular diameters for selected vessels of interest were extracted from the PAT images and compared between HAP mice and LAP mice. For the binge scenario, changes in vessel diameter and hemoglobin oxygen saturation were extracted from PAT images and studied over a 30-min duration. Vascular diameter was significantly smaller in HAP mice compared to LAP mice in weight-matched pairs. Hemoglobin-oxygen saturation and vessel diameter dropped more quickly in LAP mice than in HAP mice following a 20% ethanol i.p. injection (3 g/kg), with a 32% reduction in cerebrovascular diameter in a 30-min period. This study demonstrates the effectiveness of PAT in alcohol addiction imaging and diagnosis, and its feasibility in studying alcohol-induced changes in vascular structure and perfusion. It also adds to other bodies of evidence to suggest that the effects of binge drinking are more adverse in occasional drinkers than habitual drinkers.

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