Small Animal Imaging Research Articles

Mapping Arginase Expression with 18F-Fluorinated Late-Generation Arginase Inhibitors Derived from Quaternary α-Amino Acids.

Arginase hydrolyzes L-arginine and influences levels of polyamines and nitric oxide. Arginase overexpression is associated with inflammation and tumorigenesis. Thus, radiolabeled arginase inhibitors may be suitable PET tracers for staging arginase-related pathophysiologies. We report the synthesis and evaluation of 2 radiolabeled arginase inhibitors, 18F-FMARS and 18F-FBMARS, developed from α-substituted-2-amino-6-boronohexanoic acid derivatives. Methods: Arylboronic ester-derived precursors were radiolabeled via copper-mediated fluorodeboronation. Binding assays using arginase-expressing PC3 and LNCaP cells were performed. Autoradiography of lung sections from a guinea pig model of asthma overexpressing arginase and dynamic small-animal PET imaging with PC3-xenografted mice evaluated the radiotracers' specific binding and pharmacokinetics. Results:18F-fluorinated compounds were obtained with radiochemical yields of up to 5% (decay-corrected) and an average molar activity of 53 GBq⋅μmol-1 Cell and lung section experiments indicated specific binding that was blocked up to 75% after pretreatment with arginase inhibitors. Small-animal PET studies indicated fast clearance of the radiotracers (7.3 ± 0.6 min), arginase-mediated uptake, and a selective tumor accumulation (SUV, 3.0 ± 0.7). Conclusion: The new 18F-fluorinated arginase inhibitors have the potential to map increased arginase expression related to inflammatory and tumorigenic processes. 18F-FBMARS showed the highest arginase-mediated uptake in PET imaging and a significant difference between uptake in control and arginase-inhibited PC3 xenografted mice. These results encourage further research to examine the suitability of 18F-FBMARS for selecting patients for treatments with arginase inhibitors.

Effects of administration route on uptake kinetics of 18F-sodium fluoride positron emission tomography in mice

18F-sodium fluoride (18F-NaF) is a positron emission tomography (PET) radiotracer widely used in skeletal imaging and has also been proposed as a biomarker of active calcification in atherosclerosis. Like most PET radiotracers, 18F-NaF is typically administered intravenously. However in small animal research intravenous administrations can be challenging, because partial paravenous injection is common due to the small calibre of the superficial tail veins and repeat administrations via tail veins can lead to tissue injury therefore limiting the total number of longitudinal scanning points. In this paper, the feasibility of using intra-peritoneal route of injection of 8F-NaF to study calcification in mice was studied by looking at the kinetic and uptake profiles of normal soft tissues and bones versus intra-vascular injections. Dynamic PET was performed for 60 min on nineteen isoflurane-anesthetized male Swiss mice after femoral artery (n = 7), femoral vein (n = 6) or intraperitoneal (n = 6) injection of 8F-NaF. PET data were reconstructed and the standardised uptake value (SUV) and standardised uptake value ratio (SUVr) were estimated from the last three frames between 45- and 60-min and 8F-NaF uptake constant (Ki) was derived by Patlak graphical analysis. In soft tissue, the 18F-NaF perfusion phase changes depending on the type on injection route, whereas the uptake phase is similar regardless of the administration route. In bone tissue SUV, SUVr and Ki measures were not significantly different between the three administration routes. Comparison between PET and CT measures showed that bones that had the highest CT density displayed the lowest PET activity and conversely, bones where CT units were low had high 8F-NaF uptake. Intraperitoneal injection is a valid and practical alternative to the intra-vascular injections in small-animal 18F-NaF PET imaging providing equivalent pharmacokinetic data. CT outcome measures report on sites of stablished calcification whereas PET measures sites of higher complexity and active calcification.

A System-Agnostic, Adaptable and Extensible Animal Support Cradle System for Cardio-Respiratory-Synchronised, and Other, Multi-Modal Imaging of Small Animals.

Standardisation of animal handling procedures for a wide range of preclinical imaging scanners will improve imaging performance and reproducibility of scientific data. Whilst there has been significant effort in defining how well scanners should operate and how in vivo experimentation should be practised, there is little detail on how to achieve optimal scanner performance with best practices in animal welfare. Here, we describe a system-agnostic, adaptable and extensible animal support cradle system for cardio-respiratory-synchronised, and other, multi-modal imaging of small animals. The animal support cradle can be adapted on a per application basis and features integrated tubing for anaesthetic and tracer delivery, an electrically driven rectal temperature maintenance system and respiratory and cardiac monitoring. Through a combination of careful material and device selection, we have described an approach that allows animals to be transferred whilst under general anaesthesia between any of the tomographic scanners we currently or have previously operated. The set-up is minimally invasive, cheap and easy to implement and for multi-modal, multi-vendor imaging of small animals.

Design and Implementation of the Pre-Clinical DICOM Standard in Multi-Cohort Murine Studies.

The small animal imaging Digital Imaging and Communications in Medicine (DICOM) acquisition context structured report (SR) was developed to incorporate pre-clinical data in an established DICOM format for rapid queries and comparison of clinical and non-clinical datasets. Established terminologies (i.e., anesthesia, mouse model nomenclature, veterinary definitions, NCI Metathesaurus) were utilized to assist in defining terms implemented in pre-clinical imaging and new codes were added to integrate the specific small animal procedures and handling processes, such as housing, biosafety level, and pre-imaging rodent preparation. In addition to the standard DICOM fields, the small animal SR includes fields specific to small animal imaging such as tumor graft (i.e., melanoma), tissue of origin, mouse strain, and exogenous material, including the date and site of injection. Additionally, the mapping and harmonization developed by the Mouse-Human Anatomy Project were implemented to assist co-clinical research by providing cross-reference human-to-mouse anatomies. Furthermore, since small animal imaging performs multi-mouse imaging for high throughput, and queries for co-clinical research requires a one-to-one relation, an imaging splitting routine was developed, new Unique Identifiers (UID’s) were created, and the original patient name and ID were saved for reference to the original dataset. We report the implementation of the small animal SR using MRI datasets (as an example) of patient-derived xenograft mouse models and uploaded to The Cancer Imaging Archive (TCIA) for public dissemination, and also implemented this on PET/CT datasets. The small animal SR enhancement provides researchers the ability to query any DICOM modality pre-clinical and clinical datasets using standard vocabularies and enhances co-clinical studies.

Performance evaluation of an adjustable gantry PET (AGPET) for small animal PET imaging

A rectangular-shaped PET system with an adjustable gantry (AGPET) has been developed for imaging small animals. The AGPET system employs a new depth of interaction (DOI) method using a depth dependent reflector patterns and a new digital time pickoff method based on the pulse reconstruction method. To evaluate the performance of the AGPET, timing resolution, intrinsic spatial resolution and point source images were acquired. The timing resolution and intrinsic spatial resolution were measured using two detector modules and Na-22 gamma source. The PET images were acquired in two field of view (FOV) sizes, 30 mm and 90 mm, to demonstrate the characteristic of the AGPET. As a result of in the experiment results, the timing resolution was 0.9 ns using the pulse reconstruction method based on the bi-exponential model. The intrinsic spatial resolution was an average of 1.7 mm and the spatial resolution of PET images after DOI correction was 2.08 mm and 2.25 mm at the centers of 30 mm and 90 mm FOV, respectively. The results show that the proposed AGPET system provided higher sensitivity and resolution for small animal imaging.

Preparation of Programmed Cell Death-Ligand 1 Antibody Nanoparticles Based on Nude Mouse Model and Its Therapeutic Effect on Lung Cancer.

In this experiment, the advantages of both liposomes and polymer nanoparticles were used to synthesize adriamycin-loaded liposome-polymer nanoparticles and conjugate them with PD-L 1 antibody (referred to as PD-L 1 antibody nano particles). The nanoparticles were encapsulated with doxorubicin hydrochloride and the near-infrared dye DIR, and small animal imaging methods were used in animal experiments to evaluate the targeting and therapeutic effects. The results showed that the red fluorescence of doxorubicin hydrochloride entered the cells, and the red fluorescence of the PD-L1 antibody nanoparticles in the 4h group was better than that in the 2h group. The intracellular red fluorescence of PD-L1 antibody nanoparticles 4h group was stronger than that of free doxorubicin 4h group. Flow cytometry and confocal experiments showed that A549 cells took up more PD-L1 antibody nanoparticles. The results showed that the fluorescence intensity of the PD-L1 antibody nanoparticle group was significantly stronger than that of the nanoparticle group, and the tumor outline was clear, and the fluorescence intensity became stronger and stronger over time, indicating that the PD-L1 antibody nanoparticles were targeted. Has certain targeting capabilities. The PD-L1 antibody nanoparticles synthesized in this study are a good drug carrier targeting lung cancer tumor cells, which can be better taken up by A549 lung cancer cells, and can more effectively kill tumor cells, inhibit tumor growth, and wrap near-infrared dyes are more conducive to in vivo imaging of animals and are useful for observing the effects of targeted treatment of lung cancer.

Automatic rat brain image segmentation using triple cascaded convolutional neural networks in a clinical PET/MR

The purpose of this work was to develop and evaluate a deep learning approach for automatic rat brain image segmentation of magnetic resonance imaging (MRI) images in a clinical PET/MR, providing a useful tool for analyzing studies of the pathology and progression of neurological disease and to validate new radiotracers and therapeutic agents. Rat brain PET/MR images (N = 56) were collected from a clinical PET/MR system using a dedicated small-animal imaging phased array coil. A segmentation method based on a triple cascaded convolutional neural network (CNN) was developed, where, for a rectangular region of interest covering the whole brain, the entire brain volume was outlined using a CNN, then the outlined brain was fed into the cascaded network to segment both the cerebellum and cerebrum, and finally the sub-cortical structures within the cerebrum including hippocampus, thalamus, striatum, lateral ventricles and prefrontal cortex were segmented out using the last cascaded CNN. The dice score coefficient (DSC) between manually drawn labels and predicted labels were used to quantitatively evaluate the segmentation accuracy. The proposed method achieved a mean DSC of 0.965, 0.927, 0.858, 0.594, 0.847, 0.674 and 0.838 for whole brain, cerebellum, hippocampus, lateral ventricles, striatum, prefrontal cortex and thalamus, respectively. Compared with the segmentation results reported in previous publications using atlas-based methods, the proposed method demonstrated improved performance in the whole brain and cerebellum segmentation. In conclusion, the proposed method achieved high accuracy for rat brain segmentation in MRI images from a clinical PET/MR and enabled the possibility of automatic rat brain image processing for small animal neurological research.

Imaging Calreticulin for Early Detection of Immunogenic Cell Death During Anticancer Treatment.

Surface-exposed calreticulin (ecto-CRT) is a well-known "eat-me" signal exhibited by dying cells that contributes to their recognition and destruction by the immune system. We assessed the use of a CRT-specific binding peptide for imaging ecto-CRT during immunogenic cell death and its utility for early prediction of treatment response. Methods: A synthetic CRT-specific peptide, KLGFFKR (CRTpep), was labeled with fluorescein isothiocyanate or 18F, and the characteristics of ecto-CRT were evaluated in a colon cancer cell line in vitro and in vivo. Results: In vitro flow cytometry, immunofluorescence staining, and in vivo small-animal PET imaging results showed that CRTpep detected preapoptotic cells treated with immunogenic drugs or radiation but not those treated with the nonimmunogenic drug or a nontherapeutic dose of immunogenic drug. Conclusion: The present results indicate that the CRT-specific peptide would enable the prediction of therapeutic response, thereby facilitating early decisions on continuation or discontinuation of immunogenic treatment.

Research on Golay-coded excitation in real-time imaging of high frequency ultrasound biomicroscopy

High frequency ultrasonic imaging provides clinicians with high-resolution diagnostic images and more accurate measurement results. The technique is now widely used in ophthalmology, dermatology, and small animal imaging. However, since ultrasonic attenuation in tissue increases rapidly with increasing frequency, the depth of detection of high frequency ultrasound in tissue is limited to a few millimeters. In this paper, a novel method of using Golay-coded excitation as a replacement for conventional single-pulse excitation in high frequency ultrasound biomicroscopy was proposed, and real-time imaging was realized. While maintaining the transmission voltage and image resolution unchanged, the detection depth can be effectively improved. The ultrasonic transmission frequency is 30 MHz and the transmission voltage is ± 60 V p-p. In this study, 4-bit, 8-bit, and 16-bit coding sequences and decoding compression were used. To verify the effectiveness of the coding sequence in real-time imaging of ultrasound biomicroscopy, we designed a 10-μm diameter line target echo experiment, an ultrasound phantom experiment, and an in vitro porcine eye experiment. The experimental results show that the code/decode method of signal processing can not only maintain a resolution consistent with that of single-pulse transmission, but can also improve the detection depth and signal-to-noise ratio.

Arbutin attenuates LPS-induced acute kidney injury by inhibiting inflammation and apoptosis via the PI3K/Akt/Nrf2 pathway

BackgroundArbutin (Ar) has anti-oxidative and anti-inflammatory activities. However, the effects of Ar on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) are not clear. PurposeThis study aimed to investigate the effects of Ar on LPS-induced AKI in rats. MethodsThe possible data regarding the effects of Ar on AKI were collected by network pharmacology research. Histological changes in the kidney and the levels of blood urea nitrogen, serum creatinine, and kidney injury molecule 1 were measured to assess the effects of Ar on renal function in LPS-induced AKI. The levels of inflammatory were detected by live small-animal imaging, cytometric bead array and enzyme linked immunosorbent assay. The levels of reactive oxygen species and apoptosis of primary kidney cells were detected by flow cytometry. The oxidative stress-related markers were detected by the cuvette assay. The TLR4/NF-κB and PI3K/Akt/Nrf2 levels and apoptosis were detected by Western blot analysis. The effects of GDC-0068 (GDC, Akt inhibitor) on Ar interposed on LPS-induced NRK-52e cell apoptosis were investigated by flow cytometry. ResultsThe data collected by network pharmacology suggested that Ar might inhibit AKI by exerting an anti-inflammatory effect and regulating the Akt signaling pathway. The experimental results showed that Ar markedly improved renal function, and attenuated inflammation and cell apoptosis via regulating PI3K/Akt/Nrf2 pathway following LPS challenge in vivo, which blocked by GDC effectively in vitro. ConclusionIn a word, this study demonstrated that Ar attenuated LPS-induced AKI by inhibiting inflammation and apoptosis via the PI3K/Akt/Nrf2 pathway.

Accessing lanthanide-based, in situ illuminated optical turn-on probes by modulation of the antenna triplet state energy.

Luminescent lanthanides possess ideal properties for biological imaging, including long luminescent lifetimes and emission within the optical window. Here, we report a novel approach to responsive luminescent Tb(iii) probes that involves direct modulation of the antenna excited triplet state energy. If the triplet energy lies too close to the 5D4 Tb(iii) excited state (20 500 cm−1), energy transfer to 5D4 competes with back energy transfer processes and limits lanthanide-based emission. To validate this approach, a series of pyridyl-functionalized, macrocyclic lanthanide complexes were designed, and the corresponding lowest energy triplet states were calculated using density functional theory (DFT). Subsequently, three novel constructs L3 (nitro-pyridyl), L4 (amino-pyridyl) and L5 (fluoro-pyridyl) were synthesized. Photophysical characterization of the corresponding Gd(iii) complexes revealed antenna triplet energies between 25 800 and 30 400 cm−1 and a 500-fold increase in quantum yield upon conversion of Tb(L3) to Tb(L4) using the biologically relevant analyte H2S. The corresponding turn-on reaction can be monitored using conventional, small-animal optical imaging equipment in presence of a Cherenkov radiation emitting isotope as an in situ excitation source, demonstrating that antenna triplet state energy modulation represents a viable approach to biocompatible, Tb-based optical turn-on probes.

Recent advances in photoacoustic tomography.

Photoacoustic tomography (PAT) that integrates the molecular contrast of optical imaging with the high spatial resolution of ultrasound imaging in deep tissue has widespread applications in basic biological science, preclinical research and clinical trials. Recently, tremendous progress has been made in PAT regarding technical innovations, preclinical applications, and clinical translations. Here, we selectively review the recent progresses and advances in PAT, including the development of advanced PAT systems for small-animal and human imaging, newly engineered optical probes for molecular imaging, broad-spectrum PAT for label-free imaging of biological tissues, high-throughput snapshot photoacoustic topography, and integration of machine learning for image reconstruction and processing. We envision that PAT will have further technical developments and more impactful applications in biomedicine.

Deep-Learning Based Positron Range Correction of PET Images

Positron emission tomography (PET) is a molecular imaging technique that provides a 3D image of functional processes in the body in vivo. Some of the radionuclides proposed for PET imaging emit high-energy positrons, which travel some distance before they annihilate (positron range), creating significant blurring in the reconstructed images. Their large positron range compromises the achievable spatial resolution of the system, which is more significant when using high-resolution scanners designed for the imaging of small animals. In this work, we trained a deep neural network named Deep-PRC to correct PET images for positron range effects. Deep-PRC was trained with modeled cases using a realistic Monte Carlo simulation tool that considers the positron energy distribution and the materials and tissues it propagates into. Quantification of the reconstructed PET images corrected with Deep-PRC showed that it was able to restore the images by up to 95% without any significant noise increase. The proposed method, which is accessible via Github, can provide an accurate positron range correction in a few seconds for a typical PET acquisition.

A Pseudo-TOF Image Reconstruction Approach for Three-Gamma Small Animal Imaging

In this article, we propose a novel image reconstruction technique for three-gamma (3- <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$ {\gamma }$ </tex-math></inline-formula> ) imaging systems that aims at reaching high image quality with a low statistics. The proposed approach is based on the utilization of a ( <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$ {\beta +}$ </tex-math></inline-formula> , <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${\gamma }$ </tex-math></inline-formula> ) emitter and a liquid xenon (LXe) camera, the Xenon Medical Imaging System 2 (XEMIS2), that is currently being manufactured. The third gamma emitted is more energetic than the two 511-keV photons and interacts mostly through Compton scattering in LXE; therefore, we utilize the interactions’ position and the deposited energy to define a Compton cone that gives the direction from where the third gamma was emitted. The intersection point between the cone and the two coincidence photons’ lines of response (LOR) is the center of the probability distribution function (PDF), a resolution model similar to that of time-of-flight (TOF)-positron emission tomography (PET). The third gamma’s information is used to narrow the LOR portion employed during reconstruction. In this article, we show reconstruction results from simulation using highly realistic Geant4 Application for Emission Tomography (GATE) Monte Carlo simulation of the imaging device and a NEMA-like phantom.

Role of Nuclear Imaging to Understand the Neural Substrates of Brain Disorders in Laboratory Animals: Current Status and Future Prospects.

Molecular imaging, which allows the real-time visualization, characterization and measurement of biological processes, is becoming increasingly used in neuroscience research. Scintigraphy techniques such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) provide qualitative and quantitative measurement of brain activity in both physiological and pathological states. Laboratory animals, and rodents in particular, are essential in neuroscience research, providing plenty of models of brain disorders. The development of innovative high-resolution small animal imaging systems together with their radiotracers pave the way to the study of brain functioning and neurotransmitter release during behavioral tasks in rodents. The assessment of local changes in the release of neurotransmitters associated with the performance of a given behavioral task is a turning point for the development of new potential drugs for psychiatric and neurological disorders. This review addresses the role of SPECT and PET small animal imaging systems for a better understanding of brain functioning in health and disease states. Brain imaging in rodent models faces a series of challenges since it acts within the boundaries of current imaging in terms of sensitivity and spatial resolution. Several topics are discussed, including technical considerations regarding the strengths and weaknesses of both technologies. Moreover, the application of some of the radioligands developed for small animal nuclear imaging studies is discussed. Then, we examine the changes in metabolic and neurotransmitter activity in various brain areas during task-induced neural activation with special regard to the imaging of opioid, dopaminergic and cannabinoid receptors. Finally, we discuss the current status providing future perspectives on the most innovative imaging techniques in small laboratory animals. The challenges and solutions discussed here might be useful to better understand brain functioning allowing the translation of preclinical results into clinical applications.

Multimodality imaging beyond CLEM: Showcases of combined in-vivo preclinical imaging and ex-vivo microscopy to detect murine mural vascular lesions.

In imaging, penetration depth comes at the expense of lateral resolution, which restricts the scope of 3D in-vivo imaging of small animals at micrometer resolution. Bioimaging will need to expand beyond correlative light and electron microscopy (CLEM) approaches to combine insights about in-vivo dynamics in a physiologically relevant 3D environment with ex-vivo information at micrometer resolution (or beyond) within the spatial, structural and biochemical contexts. Our report demonstrates the immense potential for biomedical discovery and diagnosis made available by bridging preclinical in-vivo imaging with ex-vivo biological microscopy to zoom in from the whole organism to individual structures and by adding localized spectroscopic information to structural and functional information. We showcase the use of two novel imaging pipelines to zoom into mural lesions (occlusions/hyperplasia and micro-calcifications) in murine vasculature in a truly correlative manner, that is using exactly the same animal for all integrated imaging modalities. This correlated multimodality imaging (CMI) approach includes well-established technologies such as Positron Emission Tomography (microPET), Autoradiography, Magnetic Resonance Imaging (microMRI) and Computed Tomography (microCT), and imaging approaches that are more novel in the biomedical setting, such as X-Ray Fluorescence Spectroscopy (microXRF) and High Resolution Episcopic Microscopy (HREM). Although the current pipelines are focused on mural lesions, they would also be beneficial in preclinical and clinical investigations of vascular diseases in general.

Deep-tissue label-free quantitative optical tomography

In vivo imaging of small animals is of wide interest to the biomedical community studying biological disease and developmental processes. However, optical imaging deep in tissue is severely limited by light scattering, posing restrictions on the imaging depth, image contrast, and spatial resolution. We demonstrate optical coherence projection tomography (OCPT) as a fast three-dimensional optical imaging technique for ballistic, non-scattered light, deep-tissue imaging. OCPT is based on a novel scanning transmission sample arm to rapidly measure ballistic light projections of amplitude and phase through thick biological tissues. We demonstrate the strength of OCPT by imaging an adult zebrafish in a total volume of 1000 m m 3 acquired in 24 min. We achieve an unprecedented imaging depth of 4 mm in biological tissue without using optical clearing (up to 27 mean free paths of photon transport). A new way of analyzing optical tomographic imaging depth is demonstrated and applied to OCPT. It shows that the strong light scattering suppression in OCPT is pivotal to reach the SNR limited imaging depth. OCPT allows for a full quantitative assessment of tissue parameters, which is demonstrated by quantifying the attenuation coefficient, refractive index, surface area, and volume of various organs deep inside the zebrafish. Our work opens up the way for longitudinal in vivo small animal studies from the larval to the adult stages.

Feasibility of imaging amyloid in the brain using small-angle x-ray scattering

Small-angle x-ray scattering (SAXS) imaging may have the potential to image β-amyloid plaques in vivo in the brain without tracers for assessment of Alzheimer’s disease (AD). We use a laboratory SAXS system for planar imaging of AD model and control mouse brains slices to detect regions with high density of amyloid plaques. These regions were validated with histology methods. Using Monte Carlo techniques, we simulate SAXS computed tomography (SAXS-CT) system to study the potential of selectively differentiating amyloid targets in mouse and human head phantoms with detailed anatomy. We found contrast between amyloid and brain tissue at small q (below 0.8 nm−1) in the neocortex region of the transgenic brain slices as supported by histology. We observed similar behavior through planar SAXS imaging of an amyloid-like fibril deposit with a 0.8 mm diameter at a known location on a wild type mouse brain. In our SAXS-CT simulations, we found that 33-keV x rays provide increase plaque visibility in the mouse head for targets of at least 0.1 mm in diameter, while in the human head, 70-keV x rays were capable of detecting plaques as small as 2 mm. To increase radiation efficiency, we used a weighted-sum image visualization approach allowing the dose deposited by 70-keV x rays per SAXS-CT slice of the human head to be reduced by a factor of 10 to 71 mGy for gray matter and 63 mGy for white matter. The findings suggest that a dedicated SAXS-CT system for in vivo amyloid imaging in small animals and humans can be successfully developed with further system optimization to detect regions with amyloid plaques in the brain with a safe level of radiation dose.

Design of a Multichannel Pulser/Receiver and Optimized Damping Resistor for High-Frequency Transducer Applied to SAM System

Scanning acoustic microcopy (SAM) is widely used in biomedical and industrial applications in dermatology, ophthalmology, intravascular imaging, and small animal images, owing to SAM’s ability to photograph small structures with a good spatial resolution. One of the most important devices of this system is the pulser/receiver (P/R) (PRN-300, Ohlabs Corporation, Nam-gu Busan, Republic of Korea), which generates pulses to trigger a high-frequency transducer. This article presents the design of a pulse generator to excite high-frequency transducers with four channels. The characteristics of the pulses, such as time and frequency, can be reconfigured by using a high-speed field programmable gate array (FPGA). The configuration software was developed for communicating with the P/R device via a USB connector for easy, feasible pulse selection and real-time pulse management. Besides that, during the design and implementation of the hardware, we optimized the damping resistor value to reduce the overshoot and undershoot part of the signal, ensuring the best effect on the transducer signal. The test results show that unipolar pulses worked with transducers with frequencies over 100 MHz. The SAM systems can work simultaneously with multiple transducers, and the resulting images have different resolutions of regions.

N-(2-18F-fluoropropionyl)-l-glutamate as a potential oncology tracer for PET imaging of glioma

N-(2-18F-fluoropropionyl)-l-glutamate (18F-FPGLU), a new N-substituted 18F-labeling l-glutamate, is a potential amino acid tracer for oncology PET imaging with good tumor-to-background contrast in several tumor-bearing mice. Herein, we evaluated the potential value of 18F-FPGLU for PET imaging of glioma in orthotopic glioma-bearing SD rats. A series of competitive inhibition experiments with various types of inhibitors were conducted with C6 cells to investigate the transport mechanism of 18F-FPGLU in glioma. Establishment of orthotopic rat C6 glioma-bearing SD rats models was confirmed by MRI. Then PET imaging of 18F-FPGLU was performed on the orthotopic C6 glioma-bearing SD rats and compared with that of 18F-FDG. After the rats sacrificed, the whole brain was collected and immunofluorescence staining of glial fibrillary acidic protein (GFAP) and matrix metalloproteinase 2 (MMP2) were processed. Na+-dependent system XAG- and Na+-independent system XC- are the mainly transporters of 18F-FPGLU in C6 cells. N-methyl-d-aspartate (NMDA) receptor, which is associated with the invasiveness and proliferation of glioma cells, is also involved in the uptake of 18F-FPGLU. High uptake and retention of 18F-FPGLU was observerd in orthotopic glioma with good visualization and the tumor/background ratio reached 2.35 at 60 min post-injection, which was significantly higher than that of 18F-FDG (1.72) in small-animal PET images. High expression of MMP-2 and GFAP was observed in the immunofluorescence staining of glioma xerography slices. 18F-FPGLU seems to be a better potential PET tracer than 18F-FDG for brain glioma imaging with good visualization and ability to assess the tumor activity.