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Peroxynitrite (ONOO-) is a quintessential reactive oxygen species (ROS) and reactive nitrogen species (RNS), renowned for its potent oxidizing and nitrifying capabilities. Under normal physiological conditions, a baseline level of ONOO- is present within the body. However, its production escalates significantly in response to oxidative stress. ONOO- is highly reactive with various biomolecules in vivo, particularly proteins, lipids, and nucleic acids, thereby playing a role in a spectrum of physiological and pathological processes, such as inflammation, cancer, neurodegenerative diseases, and cardiovascular diseases. Consequently, detecting ONOO-in vivo is of paramount importance for understanding the etiology of various diseases and facilitating early diagnosis. Fluorescent probes have become a staple in the identification of biomolecules due to their ease of use, convenience, and superior sensitivity and specificity. This review highlights the recent advancements in the development of fluorescent probes for the detection of ONOO- in diverse disease models and provides an in-depth examination of their design and application. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) play a pivotal role in many cellular processes and can be either beneficial or harmful. The design of ROS-sensitive fluorophores has allowed for imaging of specific activity and has helped elucidate mechanisms of action for ROS. Understanding the oxidative role of ROS in the many roles it plays allows us to understand the human body. This review provides a concise overview of modern advances in the field of ROS imaging. Indeed, much has been learned about the role of ROS throughout the years; however, it has recently been shown that using nanoparticles, rather than individual small organic fluorophores, for ROS imaging can further our understanding of ROS.

Brain-infiltrating leukocytes contribute to multiple sclerosis (MS) and autoimmune encephalomyelitis and likely play a role in traumatic brain injury, seizure, and stroke. Brain-infiltrating leukocytes are also primary targets for MS disease-modifying therapies. However, no method exists for noninvasively visualizing these cells in a living organism. 1-(2'-deoxy-2'-18F-fluoroarabinofuranosyl) cytosine (18F-FAC) is a PET radiotracer that measures deoxyribonucleoside salvage and accumulates preferentially in immune cells. We hypothesized that 18F-FAC PET could noninvasively image brain-infiltrating leukocytes. Methods: Healthy mice were imaged with 18F-FAC PET to quantify if this radiotracer crosses the blood-brain barrier (BBB). Experimental autoimmune encephalomyelitis (EAE) is a mouse disease model with brain-infiltrating leukocytes. To determine whether 18F-FAC accumulates in brain-infiltrating leukocytes, EAE mice were analyzed with 18F-FAC PET, digital autoradiography, and immunohistochemistry, and deoxyribonucleoside salvage activity in brain-infiltrating leukocytes was analyzed ex vivo. Fingolimod-treated EAE mice were imaged with 18F-FAC PET to assess if this approach can monitor the effect of an immunomodulatory drug on brain-infiltrating leukocytes. PET scans of individuals injected with 2-chloro-2'-deoxy-2'-18F-fluoro-9-β-d-arabinofuranosyl-adenine (18F-CFA), a PET radiotracer that measures deoxyribonucleoside salvage in humans, were analyzed to evaluate whether 18F-CFA crosses the human BBB. Results: 18F-FAC accumulates in the healthy mouse brain at levels similar to 18F-FAC in the blood (2.54 ± 0.2 and 3.04 ± 0.3 percentage injected dose per gram, respectively) indicating that 18F-FAC crosses the BBB. EAE mice accumulate 18F-FAC in the brain at 180% of the levels of control mice. Brain 18F-FAC accumulation localizes to periventricular regions with significant leukocyte infiltration, and deoxyribonucleoside salvage activity is present at similar levels in brain-infiltrating T and innate immune cells. These data suggest that 18F-FAC accumulates in brain-infiltrating leukocytes in this model. Fingolimod-treated EAE mice accumulate 18F-FAC in the brain at 37% lower levels than control-treated EAE mice, demonstrating that 18F-FAC PET can monitor therapeutic interventions in this mouse model. 18F-CFA accumulates in the human brain at 15% of blood levels (0.08 ± 0.01 and 0.54 ± 0.07 SUV, respectively), indicating that 18F-CFA does not cross the BBB in humans. Conclusion: 18F-FAC PET can visualize brain-infiltrating leukocytes in a mouse MS model and can monitor the response of these cells to an immunomodulatory drug. Translating this strategy into humans will require exploring additional radiotracers.

Measurement of total kidney volume (TKV) using magnetic resonance imaging (MRI) is a valuable approach for monitoring disease progression in autosomal dominant polycystic kidney disease (PKD) and is becoming more common in preclinical studies using animal models. Manual contouring of kidney MRI areas [i.e., manual method (MM)] is a conventional, but time-consuming, way to determine TKV. We developed a template-based semiautomatic image segmentation method (SAM) and validated it in three commonly used PKD models: Cys1cpk/cpk mice, Pkd1RC/RC mice, and Pkhd1pck/pck rats (n = 10 per model). We compared SAM-based TKV with that obtained by clinical alternatives including the ellipsoid formula-based method (EM) using three kidney dimensions, the longest kidney length method (LM), and MM, which is considered the gold standard. Both SAM and EM presented high accuracy in TKV assessment in Cys1cpk/cpk mice [interclass correlation coefficient (ICC) ≥ 0.94]. SAM was superior to EM and LM in Pkd1RC/RC mice (ICC = 0.87, 0.74, and <0.10 for SAM, EM, and LM, respectively) and Pkhd1pck/pck rats (ICC = 0.59, <0.10, and <0.10, respectively). Also, SAM outperformed EM in processing time in Cys1cpk/cpk mice (3.6 ± 0.6 vs. 4.4 ± 0.7 min/kidney) and Pkd1RC/RC mice (3.1 ± 0.4 vs. 7.1 ± 2.6 min/kidney, both P < 0.001) but not in Pkhd1PCK/PCK rats (3.7 ± 0.8 vs. 3.2 ± 0.5 min/kidney). LM was the fastest ~1 min) but correlated most poorly with MM-based TKV in all studied models. Processing times by MM were longer for Cys1cpk/cpk mice, Pkd1RC/RC mice, and Pkhd1pck.pck rats (66.1 ± 7.3, 38.3 ± 7.5, and 29.2 ± 3.5 min). In summary, SAM is a fast and accurate method to determine TKV in mouse and rat PKD models. [ABSTRACT FROM AUTHOR]

The selective detection of hydrogen sulfide in physiological and pathological processes has gained substantial attention in recent years. However, the real-time detection of hydrogen sulfide remains an elusive goal. In this work, a new type of hemicyanidin-based fluorescent "turn-on" probe NTR-HS (Ex = 680 nm, Em = 760 nm) was developed to detected H2S in a very short time (3 min). The fluorescence quantum yield is 0.15 and accompanied with a noticeable color change from violet to blue that can be used to detect H2S in the range 1.04 × 10−7–4 × 10−5 M with a limit of detection of 1.04 x 10-7 M. The NTR-HS probe was also used for imaging of endogenous hydrogen sulfide and mitochondrial localization in HCT116 and HeLa cells. The detection mechanism was studied through fluorescence, UV–Vis, NMR, and mass analysis. Notably, the probe was successfully used to imaging H2S in mice and locating hydrogen sulfide in the large intestine of mice. [ABSTRACT FROM AUTHOR]

Multimodality imaging is an advanced imaging tool for monitoring tumor behavior and therapy in vivo. In this study, we have developed a novel hybrid tri-modality system that includes two molecular imaging methods: positron emission computed tomography (PET) and fluorescence molecular imaging (FMI) and the anatomic imaging modality X-ray computed tomography (CT). The following paper describes the system development. Also, its imaging performance was tested in vitro (phantom) and in vivo , in Balb/c nude mice bearing a head and neck tumor xenograft treated with novel gene therapy [a new approach to the delivery of recombinant bacterial gene (IL-24-expressing strain)]. Using the tri-modality imaging system, we simultaneously monitored the therapeutic effect, including the apoptotic and necrotic induction within the tumor in vivo. The apoptotic induction was examined in real-time using an 18F-ML-10 tracer; the cell death was detected using ICG. A CT was used to evaluate the anatomical situation. An increased tumor inhibition (including tumor growth and tumor cell apoptosis) was observed in the treatment group compared to the control groups, which further confirmed the therapeutic effect of a new IL-24-expressing strain gene therapy on the tumor in vivo. By being able to offer concurrent morphological and functional information, our system is able to characterize malignant tissues more accurately. Therefore, this new tri-modality system (PET/CT/FMI) is an effective imaging tool for simultaneously investigating and monitoring tumor progression and therapy outcomes in vivo. [ABSTRACT FROM AUTHOR]

Photoacoustic (PA) technology can be used for non-invasive imaging of blood vessels. In this paper, we report on our prototype PA imaging system with a newly designed ultrasound sensor and its visualization performance of microvascular in animal. We fabricated an experimental system for animals using a high-frequency sensor. The system has two modes: still image mode by wide scanning and moving image mode by small rotation of sensor array. Optical test target, euthanized mice and rats, and live mice were used as objects. The results of optical test target showed that the spatial resolution was about two times higher than that of our conventional prototype. The image performance in vivo was evaluated in euthanized healthy mice and rats, allowing visualization of detailed blood vessels in the liver and kidneys. In tumor-bearing mice, different results of vascular induction were shown depending on the type of tumor and the method of transplantation. By utilizing the video imaging function, we were able to observe the movement of blood vessels around the tumor. We have demonstrated the feasibility of the system as a less invasive animal experimental device, as it can acquire vascular images in animals in a non-contrast and non-invasive manner. [ABSTRACT FROM AUTHOR]

Multimodality imaging is an advanced imaging tool for monitoring tumor behavior and therapy in vivo. In this study, we have developed a novel hybrid tri-modality system that includes two molecular imaging methods: positron emission computed tomography (PET) and fluorescence molecular imaging (FMI) and the anatomic imaging modality X-ray computed tomography (CT). The following paper describes the system development. Also, its imaging performance was tested in vitro (phantom) and in vivo, in Balb/c nude mice bearing a head and neck tumor xenograft treated with novel gene therapy [a new approach to the delivery of recombinant bacterial gene (IL-24-expressing strain)]. Using the tri-modality imaging system, we simultaneously monitored the therapeutic effect, including the apoptotic and necrotic induction within the tumor in vivo. The apoptotic induction was examined in real-time using an 18F-ML-10 tracer; the cell death was detected using ICG. A CT was used to evaluate the anatomical situation. An increased tumor inhibition (including tumor growth and tumor cell apoptosis) was observed in the treatment group compared to the control groups, which further confirmed the therapeutic effect of a new IL-24-expressing strain gene therapy on the tumor in vivo. By being able to offer concurrent morphological and functional information, our system is able to characterize malignant tissues more accurately. Therefore, this new tri-modality system (PET/CT/FMI) is an effective imaging tool for simultaneously investigating and monitoring tumor progression and therapy outcomes in vivo.

Breast cancer remains a leading cause of mortality among women worldwide. Brain metastases confer extremely poor prognosis due to a lack of understanding of their specific biology, unique physiologic and anatomic features of the brain, and limited treatment strategies. A major roadblock in advancing the treatment of breast cancer brain metastases (BCBM) is the scarcity of representative experimental preclinical models. Current models are predominantly based on the use of animal xenograft models with immortalized breast cancer cell lines that poorly capture the disease's heterogeneity. Recent years have witnessed the development of patient-derived in vitro and in vivo breast cancer culturing systems that more closely recapitulate the biology from individual patients. These advances led to the development of modern patient-tissue-based experimental models for BCBM. The success of preclinical models is also based on the imaging technologies used to detect metastases. Advances in animal brain imaging, including cellular MRI and multimodality imaging, allow sensitive and specific detection of brain metastases and monitoring treatment responses. These imaging technologies, together with novel translational breast cancer models based on patient-derived cancer tissues, represent a unique opportunity to advance our understanding of brain metastases biology and develop novel treatment approaches. This review discusses the state-of-the-art knowledge in preclinical models of this disease. [ABSTRACT FROM AUTHOR]

Acoustic-resolution photoacoustic micro-scopy (AR-PAM) is an emerging biomedical imaging modality that combines superior optical sensitivity and fine ultrasonic resolution in an optical quasi-diffusive regime (~1–3 mm in tissues). AR-PAM has been explored for anatomical, functional, and molecular information in biological tissues. Heretofore, AR-PAM systems have suffered from a limited field-of-view (FOV) and/or slow imaging speed, which have precluded them from routine preclinical and clinical applications. Here, we demonstrate an advanced AR-PAM system that overcomes both limitations of previous AR-PAM systems. The new AR-PAM system demonstrates a super wide-field scanning that utilized a 1-axis water-proofing microelectromechanical systems (MEMS) scanner integrated with two linear stepper motor stages. We achieved an extended FOV of 36 × 80 mm2 by mosaicking multiple volumetric images of 36 × 2.5 mm2 with a total acquisition time of 224 seconds. For one volumetric data (i.e., 36 × 2.5 mm2), the B-scan imaging speed over the short axis (i.e., 2.5 mm) was 83 Hz in humans. The 3D volumetric image was also provided by using MEMS mirror scanning along the X-axis and stepper-motor scanning along the Y-axis. The super-wide FOV mosaic image was realized by registering and merging all individual volumetric images. Finally, we obtained multi-plane whole-body in-vivo PA images of small animals, illustrating distinct multi-layered structures including microvascular networks and internal organs. Importantly, we also visualized microvascular networks in human fingers, palm, and forearm successfully. This advanced MEMS-AR-PAM system could potentially enable hitherto not possible wide preclinical and clinical applications. [ABSTRACT FROM AUTHOR]

Breast cancer remains a leading cause of mortality among women worldwide. Brain metastases confer extremely poor prognosis due to a lack of understanding of their specific biology, unique physiologic and anatomic features of the brain, and limited treatment strategies. A major roadblock in advancing the treatment of breast cancer brain metastases (BCBM) is the scarcity of representative experimental preclinical models. Current models are predominantly based on the use of animal xenograft models with immortalized breast cancer cell lines that poorly capture the disease’s heterogeneity. Recent years have witnessed the development of patient-derived in vitro and in vivo breast cancer culturing systems that more closely recapitulate the biology from individual patients. These advances led to the development of modern patient-tissue-based experimental models for BCBM. The success of preclinical models is also based on the imaging technologies used to detect metastases. Advances in animal brain imaging, including cellular MRI and multimodality imaging, allow sensitive and specific detection of brain metastases and monitoring treatment responses. These imaging technologies, together with novel translational breast cancer models based on patient-derived cancer tissues, represent a unique opportunity to advance our understanding of brain metastases biology and develop novel treatment approaches. This review discusses the state-of-the-art knowledge in preclinical models of this disease.

Recently, there has been a great amount of interest in developing multi-modality imaging techniques for oncologic research and clinical studies with the aim of obtaining complementary information and, thus, improving the detection and characterization of tumors. In this present work, the details of a combined MR-diffuse optical imaging system for dual-modality imaging of small animals are given. As a part of this effort, a multi-spectral frequency domain diffuse optical tomography system is integrated with an MRI system. Here, a network analyzer provides the rf modulation signal for the laser diodes and measures the amplitude and the phase of the detected signals. Photomultiplier tubes are utilized to measure low-level signals. The integration of this optical imaging system with the 4T MRI system is realized by incorporating a fiber adaptive interface inside the MR magnet. Coregistration is achieved by a special probe design utilizing fiducial markers. A finite element algorithm is used to solve the diffusion equation and an inverse solver based on this forward solver is implemented to calculate the absorption and scattering maps from the acquired data. The MR a priori information is used to guide the optical reconstruction algorithm. Phantom studies show that the absorption coefficient of a 7 mm inclusion in an irregular object located in 64 mm phantom is recovered with 11 % error when MR a priori information is used. ENU induced tumor model is used to test the performance of the system in vivo.

[Display omitted] • The probe YX is a near-infrared fluorescent probe. • The probe YX can complete continuous detection Zn2+ and PPi. • The probe YX has a good application prospect in biology. • The probe can detect Zn2+ and PPi in actual samples. As the second most abundant transition metal element in the human body, zinc ions play an important role in the normal growth and development of the human body. We have successfully synthesized a near-infrared fluorescent probe with FRET effect for the detection of Zn2+. Probe DR6G has good selectivity and anti-interference ability for Zn2+. When Zn2+ is added to the probe DR6G solution, it responds completely within seconds, releasing red fluorescence with a detection limit of 2.02 × 10−8 M. As the main product of ATP hydrolysis, PPi is indispensable in various metabolic activities in cells and the human body. Due to the strong binding ability of Zn2+ and PPi, it is easy to form ZnPPi precipitation, so we added PPi to the solution to complete the Zn2+ detection, and realized the continuous detection of PPi, and the detection limit was 2.06 × 10−8 M. Since Zn2+ and PPi play an important role in vivo, it is of great practical significance to design and synthesize a fluorescent probe that can continuously detect Zn2+ and PPi. Biological experiments have shown that the probe DR6G has low cytotoxicity and can complete the detection of exogenous Zn2+ and PPi in cells and living mice in vitro. Bacterial experiments have shown that the DR6G probe also has certain research value in the field of environmental monitoring and microbiology. Due to the constant variation of the fluorescence signals of Zn2+ and PPi during detection, we designed the logic gate program. In practical applications, the probe DR6G can quantitatively detect Zn2+ in zinc-containing oral liquids and qualitatively detect PPi in toothpaste. [ABSTRACT FROM AUTHOR]

X-ray grating interferometry is a powerful emerging tool in biomedical imaging, providing access to three complementary image modalities. In addition to the conventional attenuation modality, interferometry provides a phase modality, which visualizes soft tissue structures, and a dark-field modality, which relates to the number and size of sub-resolution scattering objects. A particularly strong dark-field signal originates from the alveoli or air sacs in the lung. Dark-field lung radiographs in animal models have already shown increased sensitivity in diagnosing lung diseases, such as lung cancer or emphysema, compared to conventional X-ray chest radiography. However, to date, X-ray dark-field lung imaging has either averaged information over several breaths or has been captured during a breath hold. In this paper, we demonstrate the first time-resolved dark-field imaging of a breath cycle in a mechanically ventilated mouse, in vivo, which was obtained using a grating interferometer. We achieved a time resolution of 0.1 s, visualizing the changes in the dark-field, phase, and attenuation images during inhalation and exhalation. These measurements show that the dark-field signal depends on the air volume and, hence, the alveolar dimensions of the lung. Conducting this type of scan with animal disease models would help to locate the optimum breath point for single-image diagnostic dark-field imaging and could indicate if the changes in the dark-field signal during breath provide a diagnostically useful complementary measure. [ABSTRACT FROM AUTHOR]

Abstract: Imaging techniques are a cornerstone of contemporary biology. Over the last decades, advances in microscale imaging techniques have allowed fascinating new insights into cell and tissue morphology and internal anatomy of organisms across kingdoms. However, most studies so far provided snapshots of given reference taxa, describing organs and tissues under “idealized” conditions. Surprisingly, there is an almost complete lack of studies investigating how an organism′s internal morphology changes in response to environmental drivers. Consequently, ecology as a scientific discipline has so far almost neglected the possibilities arising from modern microscale imaging techniques. Here, we provide an overview of recent developments of X‐ray computed tomography as an affordable, simple method of high spatial resolution, allowing insights into three‐dimensional anatomy both in vivo and ex vivo. We review ecological studies using this technique to investigate the three‐dimensional internal structure of organisms. In addition, we provide practical comparisons between different preparation techniques for maximum contrast and tissue differentiation. In particular, we consider the novel modality of phase contrast by self‐interference of the X‐ray wave behind an object (i.e., phase contrast by free space propagation). Using the cricket Acheta domesticus (L.) as model organism, we found that the combination of FAE fixative and iodine staining provided the best results across different tissues. The drying technique also affected contrast and prevented artifacts in specific cases. Overall, we found that for the interests of ecological studies, X‐ray computed tomography is useful when the tissue or structure of interest has sufficient contrast that allows for an automatic or semiautomatic segmentation. In particular, we show that reconstruction schemes which exploit phase contrast can yield enhanced image quality. Combined with suitable specimen preparation and automated analysis, X‐ray CT can therefore become a promising quantitative 3D imaging technique to study organisms′ responses to environmental drivers, in both ecology and evolution. [ABSTRACT FROM AUTHOR]

Background We describe the fabrication and performance of a chronic in situ coil system designed to allow focal brain stimulation in rats while acquiring functional MRI data. New method An implantable receive-only surface radiofrequency coil (iCoil) was designed to be fitted subcutaneously, directly onto to the rat skull surface during the intracerebral cannulation procedure. The coil is fixed in place using acrylic dental cement anchored to four screws threaded into the skull. To demonstrate the use of this coil system in situ, whole-brain functional MRI scans were acquired during various stimuli, including intracranial microinfusions of bicuculline and morphine in the prefrontal cortex and ventral tegmental area, respectively. Results/Comparison to other methods SNR performance of the iCoil was superior to three commercially-available coils, in some instances by a factor of two. Widespread BOLD activation was observed in response to bicuculline and morphine microinfusions. Conclusion A new approach was demonstrated for high-SNR MR imaging of the brain in rats with intracranial implants using an implantable surface coil. This approach enables mapping the functional response to highly targeted stimuli such as intracranial microinfusions. [ABSTRACT FROM AUTHOR]

Amyloidosis is associated with a number of rare diseases and is characterized by the deposition, in abdominothoracic organs and peripheral nerves, of extracellular protein fibrils, which leads to dysfunction and severe morbidity. Effective clinical evaluation and management of patients with systemic amyloidosis are hampered by the lack of a noninvasive, quantitative method for detecting whole-body amyloid load. We have used a battery of assays including dual-energy SPECT imaging and comparative effectiveness studies in support of translation of a synthetic polybasic peptide, p5+14, as a novel radiotracer for visualization of amyloidosis by molecular imaging. These data provide support for a phase 1 positron emission tomography/computed tomography imaging trial of this reagent, labeled with iodine-124, in patients with all forms of systemic amyloidosis. [ABSTRACT FROM AUTHOR]

We have developed nanomedicine vehicle based on a biocompatible tri-block copolymer, poly(ethylene glycol)- block -poly(lactic acid)- block -poly(ethylene glycol) (PEG-PLA-PEG) by simple approach without toxic linker to escalate therapeutic efficacy of anticancer agent by enhanced targeting to metastasized breast cancers. The synthesized ABA type copolymer had a low polydispersity index and formed small, highly stable spherical micelles. Furthermore, a functional group at the end site of the copolymer can be decorated with imaging agents and targeting moieties. The doxorubicin loaded micelles (DLM) showed higher drug-loading capacity, faster drug release, and better cell toxicity compared to those using di-block copolymers. DLM efficiently delivered to the metastatic breast cancers in brain and bone and suppressed growing of metastasis. In demonstration of treating metastasized animal model, we present a tri-block copolymer as a potential nanomedicine vehicle to efficiently deliver anticancer drug and to effectively treat metastatic breast cancer. [ABSTRACT FROM AUTHOR]

Limited diffusion of oxygen in combination with increased oxygen consumption leads to chronic hypoxia in most solid malignancies. This scarcity of oxygen is known to induce radioresistance and leads to an immunosuppressive microenvironment. Carbonic anhydrase IX (CAIX) is an enzyme functioning as a catalyzer for acid export in hypoxic cells and is an endogenous biomarker for chronic hypoxia. The aim of this study is to develop a radiolabeled antibody that recognizes murine CAIX to visualize chronic hypoxia in syngeneic tumor models and to study the immune cell population in these hypoxic areas. An anti-mCAIX antibody (MSC3) was conjugated to diethylenetriaminepentaacetic acid (DTPA) and radiolabeled with indium-111 ( 111 In). CAIX expression on murine tumor cells was determined using flow cytometry, and in vitro affinity of [ 111 In]In-MSC3 was analyzed in a competitive binding assay. Ex vivo biodistribution studies were performed to determine in vivo radiotracer distribution. CAIX + tumor fractions were determined by mCAIX microSPECT/CT, and the tumor microenvironment was analyzed using immunohistochemistry and autoradiography. We showed that [ 111 In]In-MSC3 binds to CAIX-expressing (CAIX + ) murine cells in vitro and accumulates in CAIX + areas in vivo . We optimized the use of [ 111 In]In-MSC3 for preclinical imaging such that it can be applied in syngeneic mouse models and showed that we can quantitatively distinguish between tumor models with varying CAIX + fractions by ex vivo analyses and in vivo mCAIX microSPECT/CT. Analysis of the tumor microenvironment identified these CAIX + areas as less infiltrated by immune cells. Together these data demonstrate that mCAIX microSPECT/CT is a sensitive technique to visualize hypoxic CAIX + tumor areas that exhibit reduced infiltration of immune cells in syngeneic mouse models. In the future, this technique may enable visualization of CAIX expression before or during hypoxia-targeted or hypoxia-reducing treatments. Thereby, it will help optimize immuno- and radiotherapy efficacy in translationally relevant syngeneic mouse tumor models.

Purpose: In this study, the authors present a silicon photomultiplier (SiPM)-based positron emission tomography (PET) insert dedicated to small animal imaging with high system performance and robustness to temperature change. Methods: The insert consists of 64 LYSO-SiPM detector blocks arranged in 4 rings of 16 detector blocks to yield a ring diameter of 64 mm and axial field of view of 55 mm. Each detector block consists of a 9×9 array of LYSO crystals (1.2×1.2×10 mm³) and a monolithic 4×4 SiPM array. The temperature of each monolithic SiPM is monitored, and the proper bias voltage is applied according to the temperature reading in real time to maintain uniform performance. The performance of this PET insert was characterized using National Electrical Manufacturers Association NU 4-2008 standards, and its feasibility was evaluated through in vivo mouse imaging studies. Results: The PET insert had a peak sensitivity of 3.4% and volumetric spatial resolutions of 1.92 (filtered back projection) and 0.53 (ordered subset expectation maximization) mm³ at center. The peak noise equivalent count rate and scatter fraction were 42.4 kcps at 15.08 MBq and 16.5%, respectively. By applying the real-time bias voltage adjustment, an energy resolution of 14.2%±0.3% was maintained and the count rate varied ≤1.2%, despite severe temperature changes (10-30 C). The mouse imaging studies demonstrate that this PET insert can produce high-quality images useful for imaging studies on the small animals. Conclusions: The developed MR-compatible PET insert is designed for insertion into a narrow-bore magnetic resonance imaging scanner, and it provides excellent imaging performance for PET/MR preclinical studies. [ABSTRACT FROM AUTHOR]

We investigated deleterious changes that take place in mesenchymal stem cells (MSC) and its fracture healing competence in ovariectomy (Ovx)-induced osteopenia. MSC from bone marrow (BM) of ovary intact (control) and Ovx rats was isolated. Tc-HMPAO (Technitium hexamethylpropylene amine oxime) labeled MSC was systemically transplanted to rats and fracture tropism assessed by SPECT/CT. PKH26 labeled MSC (PKH26-MSC) was bound in scaffold and applied to fracture site (drill-hole in femur metaphysis). Osteoinduction was quantified by calcein binding and microcomputed tomography. Estrogen receptor (ER) antagonist, fulvestrant was used to determine ER dependence of osteo-induction by MSC. BM-MSC number was strikingly reduced and doubling time increased in Ovx rats compared to control. SPECT/CT showed reduced localization of Tc-HMPAO labeled MSC to the fracture site, 3 h post-transplantation in Ovx rats as compared with controls. Post-transplantation, Ovx MSC labeled with PKH26 (Ovx PKH26-MSC) localized less to fracture site than control PKH26-MSC. Transplantation of either control or Ovx MSC enhanced calcein binding and bone volume at the callus of control rats over placebo group however Ovx MSC had lower efficacy than control MSC. Fulvestrant blocked osteoinduction by control MSC. When scaffold bound MSC was applied to fracture, osteoinduction by Ovx PKH26-MSC was less than control PKH26-MSC. In Ovx rats, control MSC/E2 treatment but not Ovx MSC showed osteoinduction. Regenerated bone was irregularly deposited in Ovx MSC group. In conclusion, Ovx is associated with diminished BM-MSC number and its growth, and Ovx MSC displays impaired engraftment to fracture and osteoinduction besides disordered bone regeneration. [ABSTRACT FROM AUTHOR]

The portable visible and near-infrared (NIR) imaging equipment for a pre-clinical test with small animals was designed and developed in this paper. The developed equipment is composed of a CCD camera, a focusing lens, an objective lens, a NIR band pass filter and a NIR filter driving motor. An NIR ray is mainly used for imaging equipment because it has high light penetration depth in biological tissue. Therefore, NIR fluorescent agents are available for chemical conjugation to targeting molecules in vivo. This equipment can provide a visible image, NIR image and merged image simultaneously. A communication system was specifically established to check obtained images through a smart pad in real time. It is less dependent on space and time than the conventional system. [ABSTRACT FROM AUTHOR]