Recent Posts

MASSIVE PARALLEL ULTRASOUND AND PHOTOACOUSTIC PC-BASED SYSTEM

Authors: Weylan Thompson, Hans Peter Brecht, Sergey Ermilov, Vassili Ivanov

ABSTRACT

PhotoSound Technologies specializes in the development of electronics solutions for massive parallel data acquisition applicable to the fields of photoacoustics (PA), X-ray acoustics, including 3D dosimetry, and ultrasound. PhotoSound’s Legion ADC256 R1.1, released in 2018, is a 256-channel 12-bit ADC with a sampling rate of 40 MHz. The ADC256’s average data bandwidth is limited by its USB3 PC interface, which has a data rate up to 3 Gbps per board. Multiple ADC256 boards can operate fully in parallel. On software level configurations, multiple ADC256 boards are represented as a single ADC board with increased number of channels. The incoming ultrasound (US) upgrades and modifications of ADC256 will enable combination and alternation of US and PA modes using the same probe. PhotoSound MoleculUS is a medical-grade Telemed US system combined with a PA-optimized ADC. MoleculUS utilizes clinical US probes to produce US images which can be interleaved with PA imaging by enabling optical fiber illumination. The other ADC256 modification, advanced PAUS oriented for research, will have PCIe PC interface for raw PA and US data and arbitrary software control over beamformer profiles, limited by high-voltage power only. The data in ultrasound and photoacoustics modes is user accessible in raw format and can be delivered to CUDA GPU using MATLAB parallel computing (CUDA) toolbox or other tools. Multiple PAUS boards can work in parallel in both PA and US modes.

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COMMERCIAL SMALL ANIMAL IMAGING COULD AID DISEASE DETECTION

Authors: Mark Little

ABSTRACT

The development of anticancer metastatic therapies for human clinical trials requires meticulous evaluation of efficacy and optimization of small animal test models in preclinical experimentation. Critical information on morphology and the molecular microenvironment of tumors is currently obtained and monitored using noninvasive, in vivo imaging methods. Detection of individual, small tumors (separated by 2 mm or less) pushes the limits of small animal imaging modalities currently on the market, which can prohibit noninvasive quantification of the volume of metastatic lesions. Commercial small animal imaging platforms that enable rendering and anatomical registration of metastatic lesions with true 3D isotropic submillimeter spatial resolution would help solve this problem. Such platforms would alleviate subjective interpretation and provide molecular and functional information on blood content. A multimodal approach could provide a more cost-effective implementation of all these features in a single configuration.

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A PRECLINICAL SMALL ANIMAL IMAGING PLATFORM COMBINING MULTI-ANGLE PHOTOACOUSTIC AND FLUORESCENCE PROJECTIONS INTO CO-REGISTERED 3D MAPS

Authors: Weylan Thompson, Anthony Yu, Diego S. Dumani, Jason Cook, Mark A. Anastasio, Stanislav Y. Emelianov, Sergey A. Ermilov

ABSTRACT

We present the results on development of the 3D imaging platform combining photoacoustic tomography and fluorescence (PAFT) for preclinical and biological research. This combined multimodal imaging instrument addresses known deficiencies in sensitivity, spatial resolution, and anatomical registration of the individual imaging components. Multiangle photoacoustic projections, excited by an OPO operating in the near-infrared window, of a live anesthetized animal are used to reconstruct large volumes (30 cm3) that show deep anatomical vasculature and blood-rich tissues with resolutions exceeding 150 μm. A sCMOS camera is used for simultaneous co-registered multi-angle optical imaging. The images of a fluorescent dual-contrast agent are then reconstructed into a 3D volume using a tomographic algorithm. A separate 532-nm low-energy pulsed laser excitation is used for skin topography and imaging of superficial vasculature. All three imaging channels can be combined to produce spatially accurate in vivo volumes showing an animal’s skin, deep anatomical structures, and distribution of photosensitive molecular contrast agents. PAFT’s photoacoustic sensitivity was assessed using contrast agents in a phantom study. We demonstrate biomedical imaging application of PAFT’s combined imaging modalities by observing biodistribution of a dual-contrast agent injected intravenously to in vivo preclinical murine models.

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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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