Visual tracing of diffusion and biodistribution for amphiphilic cationic nanoparticles using photoacoustic imaging after ex vivo intravitreal injections

AbstractFunctional photoacoustic imaging of the placenta could provide an innovative tool to diagnose preeclampsia, monitor fetal growth restriction, and determine the developmental impacts of gestational diabetes. However, transabdominal photoacoustic imaging is limited in imaging depth due to the tissue’s scattering and absorption of light. The aim of this paper was to investigate the impact of geometry and wavelength on transabdominal light delivery. Our methods included the development of a multilayer model of the abdominal tissue and simulation of the light propagation using Monte Carlo methods. A bifurcated light source with varying incident angle of light, distance between light beams, and beam area was simulated to analyze the effect of light delivery geometry on the fluence distribution at depth. The impact of wavelength and the effects of variable thicknesses of adipose tissue and muscle were also studied. Our results showed that the beam area plays a major role in improving the delivery of light to deep tissue, in comparison to light incidence angle or distance between the bifurcated fibers. Longer wavelengths, with incident fluence at the maximum permissible exposure limit, also increases fluence within deeper tissue. We validated our simulations using a commercially available light delivery system and ex vivo human placental tissue. Additionally, we compared our optimized light delivery to a commercially available light delivery system, and conclude that our optimized geometry could improve imaging depth more than 1.6×, bringing the imaging depth to within the needed range for transabdominal imaging of the human placenta.

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Efficient Photoacoustic Imaging With Biomimetic Mesoporous Silica-Based Nanoparticles

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2021.762956 ◽

2021 ◽

Vol 9 ◽

Author(s):

Chuangjia Huang ◽

Xiaoling Guan ◽

Hui Lin ◽

Lu Liang ◽

Yingling Miao ◽

...

Keyword(s):

Mesoporous Silica ◽

Near Infrared ◽

Ex Vivo ◽

Photoacoustic Imaging ◽

Mesoporous Silica Nanoparticles ◽

Good Biocompatibility ◽

Targeting Ability ◽

Body Clearance

Indocyanine green (ICG), a near-infrared (NIR) fluorescent dye approved by the Food and Drug Administration (FDA), has been extensively used as a photoacoustic (PA) probe for PA imaging. However, its practical application is limited by poor photostability in water, rapid body clearance, and non-specificity. Herein, we fabricated a novel biomimetic nanoprobe by coating ICG-loaded mesoporous silica nanoparticles with the cancer cell membrane (namely, CMI) for PA imaging. This probe exhibited good dispersion, large loading efficiency, good biocompatibility, and homologous targeting ability to Hela cells in vitro. Furthermore, the in vivo and ex vivo PA imaging on Hela tumor-bearing nude mice demonstrated that CMI could accumulate in tumor tissue and display a superior PA imaging efficacy compared with free ICG. All these results demonstrated that CMI might be a promising contrast agent for PA imaging of cervical carcinoma.

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Towards Clinical Translation of LED-Based Photoacoustic Imaging: A Review

Sensors ◽

10.3390/s20092484 ◽

2020 ◽

Vol 20 (9) ◽

pp. 2484 ◽

Cited By ~ 10

Author(s):

Yunhao Zhu ◽

Ting Feng ◽

Qian Cheng ◽

Xueding Wang ◽

Sidan Du ◽

...

Keyword(s):

Ex Vivo ◽

Photoacoustic Imaging ◽

Imaging Techniques ◽

Clinical Translation ◽

Key Factors ◽

Pilot Studies ◽

History Of ◽

Molecular Components ◽

Clinical Potential

Photoacoustic imaging, with the capability to provide simultaneous structural, functional, and molecular information, is one of the fastest growing biomedical imaging modalities of recent times. As a hybrid modality, it not only provides greater penetration depth than the purely optical imaging techniques, but also provides optical contrast of molecular components in the living tissue. Conventionally, photoacoustic imaging systems utilize bulky and expensive class IV lasers, which is one of the key factors hindering the clinical translation of this promising modality. Use of LEDs which are portable and affordable offers a unique opportunity to accelerate the clinical translation of photoacoustics. In this paper, we first review the development history of LED as an illumination source in biomedical photoacoustic imaging. Key developments in this area, from point-source measurements to development of high-power LED arrays, are briefly discussed. Finally, we thoroughly review multiple phantom, ex-vivo, animal in-vivo, human in-vivo, and clinical pilot studies and demonstrate the unprecedented preclinical and clinical potential of LED-based photoacoustic imaging.

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Skull’s Photoacoustic Attenuation and Dispersion Modeling with Deterministic Ray-Tracing: Towards Real-Time Aberration Correction

Sensors ◽

10.3390/s19020345 ◽

2019 ◽

Vol 19 (2) ◽

pp. 345 ◽

Cited By ~ 6

Author(s):

Leila Mohammadi ◽

Hamid Behnam ◽

Jahan Tavakkoli ◽

Mohammad Avanaki

Keyword(s):

Ray Tracing ◽

Mode Conversion ◽

Ex Vivo ◽

Photoacoustic Imaging ◽

Time Shift ◽

Dispersion Modeling ◽

Transmission Coefficients ◽

Time Domain Signal ◽

Wave Transmission Coefficients ◽

Attenuation And Dispersion

Although transcranial photoacoustic imaging has been previously investigated by several groups, there are many unknowns about the distorting effects of the skull due to the impedance mismatch between the skull and underlying layers. The current computational methods based on finite-element modeling are slow, especially in the cases where fine grids are defined for a large 3-D volume. We develop a very fast modeling/simulation framework based on deterministic ray-tracing. The framework considers a multilayer model of the medium, taking into account the frequency-dependent attenuation and dispersion effects that occur in wave reflection, refraction, and mode conversion at the skull surface. The speed of the proposed framework is evaluated. We validate the accuracy of the framework using numerical phantoms and compare its results to k-Wave simulation results. Analytical validation is also performed based on the longitudinal and shear wave transmission coefficients. We then simulated, using our method, the major skull-distorting effects including amplitude attenuation, time-domain signal broadening, and time shift, and confirmed the findings by comparing them to several ex vivo experimental results. It is expected that the proposed method speeds up modeling and quantification of skull tissue and allows the development of transcranial photoacoustic brain imaging.

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Fabrication of Coaxial and Confocal Transducer Based on Sol-Gel Composite Material for Optical Resolution Photoacoustic Microscopy

Diagnostics ◽

10.3390/diagnostics10010006 ◽

2019 ◽

Vol 10 (1) ◽

pp. 6

Author(s):

Masayuki Tanabe ◽

Tai Chieh Wu ◽

Makiko Kobayashi ◽

Che Hua Yang

Keyword(s):

Ex Vivo ◽

Photoacoustic Imaging ◽

Sol Gel ◽

Optical Resolution ◽

Maximum Amplitude ◽

Photoacoustic Signal ◽

Center Frequency ◽

Photoacoustic Microscopy ◽

3 Dimensional ◽

Pulse Echo

We have newly developed coaxial and confocal optical-resolution photoacoustic microscopy based on sol-gel composite materials. This transducer contains a concave-shaped piezoelectric layer with a focus depth of 5 mm and a hole with a diameter of 3 mm at the center to pass a laser beam into a phantom. Therefore, this system can directly detect an excited photoacoustic signal without prisms or acoustic lenses. We demonstrate the capability of the system through pulse-echo and photoacoustic imaging experiments. The center frequency of the fabricated transducer is approximately 7 MHz, and its relative bandwidth is 86%. An ex-vivo experiment is conducted, and photoacoustic signals are clearly obtained. As a result, 2- and 3-dimensional maximum amplitude projection images are reconstructed.

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Photoacoustic imaging of breast microcalcifications: A validation study with 3-dimensional ex vivo data

2012 IEEE International Ultrasonics Symposium ◽

10.1109/ultsym.2012.0008 ◽

2012 ◽

Cited By ~ 1

Author(s):

Jeeun Kang ◽

Eun-Kyung Kim ◽

Tai-kyong Song ◽

Jin Ho Chang

Keyword(s):

Validation Study ◽

Ex Vivo ◽

Photoacoustic Imaging ◽

3 Dimensional

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A feasibility study of photoacoustic imaging of ex vivo endoscopic mucosal resection tissues from Barrett’s esophagus patients

Endoscopy International Open ◽

10.1055/s-0043-111790 ◽

2017 ◽

Vol 05 (08) ◽

pp. E775-E783 ◽

Cited By ~ 3

Author(s):

Liang Lim ◽

Catherine Streutker ◽

Norman Marcon ◽

Maria Cirocco ◽

Alexandra Lao ◽

...

Keyword(s):

Barrett’S Esophagus ◽

Endoscopic Mucosal Resection ◽

Feasibility Study ◽

Barrett's Esophagus ◽

Ex Vivo ◽

Photoacoustic Imaging ◽

Esophageal Mucosa ◽

Mucosal Resection ◽

Total Hemoglobin

Abstract Background and study aims Accurate endoscopic detection of dysplasia in patients with Barrett’s esophagus (BE) remains a major clinical challenge. The current standard is to take multiple biopsies under endoscopic image guidance, but this leaves the majority of the tissue unsampled, leading to significant risk of missing dysplasia. Furthermore, determining whether there is submucosal invasion is essential for proper staging. Hence, there is a clinical need for a rapid in vivo wide-field imaging method to identify dysplasia in BE, with the capability of imaging beyond the mucosal layer. We conducted an ex vivo feasibility study using photoacoustic imaging (PAI) in patients undergoing endoscopic mucosal resection (EMR) for known dysplasia. The objective was to characterize the esophageal microvascular pattern, with the long-term goal of performing in vivo endoscopic PAI for dysplasia detection and therapeutic guidance. Materials and methods EMR tissues were mounted luminal side up. The tissues were scanned over a field of view of 14 mm (width) by 15 mm (depth) at 680, 750, and 850 nm (40 MHz acoustic central frequency). Ultrasound and photoacoustic images were simultaneously acquired. Tissues were then sliced and fixed in formalin for histopathology with hematoxylin and eosin staining. A total of 13 EMR specimens from eight patients were included in the analysis, which consisted of co-registration of the photoacoustic images with corresponding pathologist-classified histological images. We conducted mean difference test of the total hemoglobin distribution between tissue classes. Results Dysplastic and nondysplastic BE can be distinguished from squamous tissue in 84 % of region-of-interest comparisons (42/50). However, the ability of intrinsic PAI to distinguish dysplasia from NDBE, which is the clinically important challenge, was only about 33 % (10/30). Conclusion We demonstrated the technical feasibility of this approach. Based on our ex vivo data, changes in total hemoglobin content from intrinsic PAI (i. e. without exogenous contrast) can differentiate BE from squamous esophageal mucosa. However, most likely intrinsic PAI is unable to differentiate dysplastic from nondysplastic BE with adequate sensitivity for clinical translation.

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Ex vivo Characterization of Atherosclerosis using Intravascular Photoacoustic Imaging

Optics Express ◽

10.1364/oe.15.016657 ◽

2007 ◽

Vol 15 (25) ◽

pp. 16657 ◽

Cited By ~ 40

Author(s):

Shriram Sethuraman ◽

James H. Amirian ◽

Silvio H. Litovsky ◽

Richard W. Smalling ◽

Stanislav Y. Emelianov

Keyword(s):

Ex Vivo ◽

Photoacoustic Imaging

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In vivo imaging of swimming micromotors using hybrid high-frequency ultrasound and photoacoustic imaging

10.1101/2020.06.15.148791 ◽

2020 ◽

Author(s):

Azaam Aziz ◽

Joost Holthof ◽

Sandra Meyer ◽

Oliver G. Schmidt ◽

Mariana Medina-Sánchez

Keyword(s):

High Frequency ◽

Imaging System ◽

Ex Vivo ◽

Photoacoustic Imaging ◽

Imaging Techniques ◽

High Frequency Ultrasound ◽

Living Organisms ◽

And Function ◽

Frequency Ultrasound

AbstractThe fast evolution of medical micro- and nanorobots in the endeavor to perform non-invasive medical operations in living organisms boosted the use of diverse medical imaging techniques in the last years. Among those techniques, photoacoustic (PA) tomography has shown to be promising for the imaging of microrobots in deep-tissue (ex vivo and in vivo), as it possesses the molecular specificity of optical techniques and the penetration depth of ultrasound imaging. However, the precise maneuvering and function control of microrobots, in particular in living organisms, demand the combination of both anatomical and functional imaging methods. Therefore, herein, we report the use of a hybrid High-Frequency Ultrasound (HFUS) and PA imaging system for the real-time tracking of magnetically driven micromotors (single and swarms) in phantoms, ex vivo, and in vivo (in mice bladder and uterus), envisioning their application for targeted drug-delivery.

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Pharmacokinetics of Pullulan–Dexamethasone Conjugates in Retinal Drug Delivery

Pharmaceutics ◽

10.3390/pharmaceutics14010012 ◽

2021 ◽

Vol 14 (1) ◽

pp. 12

Author(s):

Eva Kicková ◽

Amir Sadeghi ◽

Jooseppi Puranen ◽

Shirin Tavakoli ◽

Merve Sen ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery Systems ◽

Ex Vivo ◽

Large Fraction ◽

Delivery Systems ◽

Intravitreal Injections ◽

Aqueous Humor Outflow ◽

Charged Nanoparticles ◽

Average Size

The treatment of retinal diseases by intravitreal injections requires frequent administration unless drug delivery systems with long retention and controlled release are used. In this work, we focused on pullulan (≈67 kDa) conjugates of dexamethasone as therapeutic systems for intravitreal administration. The pullulan–dexamethasone conjugates self-assemble into negatively charged nanoparticles (average size 326 ± 29 nm). Intravitreal injections of pullulan and pullulan–dexamethasone were safe in mouse, rat and rabbit eyes. Fluorescently labeled pullulan particles showed prolonged retention in the vitreous and they were almost completely eliminated via aqueous humor outflow. Pullulan conjugates also distributed to the retina via Müller glial cells when tested in ex vivo retina explants and in vivo. Pharmacokinetic simulations showed that pullulan–dexamethasone conjugates may release free and active dexamethasone in the vitreous humor for over 16 days, even though a large fraction of dexamethasone may be eliminated from the eye as bound pullulan–dexamethasone. We conclude that pullulan based drug conjugates are promising intravitreal drug delivery systems as they may reduce injection frequency and deliver drugs into the retinal cells.

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