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Objective. 225Ac radiopharmaceuticals have tremendous potential for targeted alpha therapy, however, 225Ac (t 1/2 = 9.9 d) lacks direct gamma emissions for in vivo imaging. 226Ac (t 1/2 = 29.4 h) is a promising element-equivalent matched diagnostic radionuclide for preclinical evaluation of 225Ac radiopharmaceuticals. 226Ac has two gamma emissions (158 keV and 230 keV) suitable for SPECT imaging. This work is the first feasibility study for in vivo quantitative 226Ac SPECT imaging and validation of activity estimation. Approach. 226Ac was produced at TRIUMF (Vancouver, Canada) with its Isotope Separator and Accelerator (ISAC) facility. [226Ac]Ac3+ was radiolabelled with the bioconjugate crown-TATE developed for therapeutic targeting of neuroendocrine tumours. Mice with AR42J tumour xenografts were injected with either 2 MBq of [226Ac]Ac-crown-TATE or 4 MBq of free [226Ac]Ac3+ activity and were scanned at 1, 2.5, 5, and 24 h post injection in a preclinical microSPECT/CT. Quantitative SPECT images were reconstructed from the 158 keV and 230 keV photopeaks with attenuation, background, and scatter corrections. Image-based 226Ac activity measurements were assessed from volumes of interest within tumours and organs of interest. Imaging data was compared with ex vivo biodistribution measured via gamma counter. Main results. We present, to the best of our knowledge, the first ever in vivo quantitative SPECT images of 226Ac activity distributions. Time-activity curves derived from SPECT images quantify the in vivo biodistribution of [226Ac]Ac-crown-TATE and free [226Ac]Ac3+ activity. Image-based activity measurements in the tumours and organs of interest corresponded well with ex vivo biodistribution measurements. Significance. Here in, we established the feasibility of in vivo 226Ac quantitative SPECT imaging for accurate measurement of actinium biodistribution in a preclinical model. This imaging method could facilitate more efficient development of novel actinium labelled compounds by providing accurate quantitative in vivo pharmacokinetic information essential for estimating toxicities, dosimetry, and therapeutic potency. [ABSTRACT FROM AUTHOR]

Purpose: Preclinical imaging, with translational potential, lacks a standardized method for defining volumes of interest (VOIs), impacting data reproducibility. The aim of this study was to determine the interobserver variability of VOI sizes and standard uptake values (SUVmean and SUVmax) of different organs using the same [18F]FDG-PET and PET/CT datasets analyzed by multiple observers. In addition, the effect of a standardized analysis approach was evaluated. Procedures: In total, 12 observers (4 beginners and 8 experts) analyzed identical preclinical [18F]FDG-PET-only and PET/CT datasets according to their local default image analysis protocols for multiple organs. Furthermore, a standardized protocol was defined, including detailed information on the respective VOI size and position for multiple organs, and all observers reanalyzed the PET/CT datasets following this protocol. Results: Without standardization, significant differences in the SUVmean and SUVmax were found among the observers. Coregistering CT images with PET images improved the comparability to a limited extent. The introduction of a standardized protocol that details the VOI size and position for multiple organs reduced interobserver variability and enhanced comparability. Conclusions: The protocol offered clear guidelines and was particularly beneficial for beginners, resulting in improved comparability of SUVmean and SUVmax values for various organs. The study suggested that incorporating an additional VOI template could further enhance the comparability of the findings in preclinical imaging analyses. [ABSTRACT FROM AUTHOR]

Labeling and tracking existing and emerging cell-based immunotherapies using nuclear imaging is widely used to guide the preclinical phases of development and testing of existing and new emerging off-the-shelf cell-based immunotherapies. In fact, advancing our knowledge about their mechanism of action and limitations could provide preclinical support and justification for moving towards clinical experimentation of newly generated products and expedite their approval by the Food and Drug Administration (FDA). Here we provide the reader with a ready to use protocol describing the labeling methodologies and practical procedures to render different candidate cell therapies in vivo traceable by nuclear-based imaging. The protocol includes sufficient practical details to aid researchers at all career stages and from different fields in familiarizing with the described concepts and incorporating them into their work. [ABSTRACT FROM AUTHOR]

Objectives: Meckel scintigraphy is used to diagnose Meckel's diverticulum. Previously, premedication with ranitidine was the most frequently used method to increase the accuracy of scintigraphy. However, ranitidine can no longer be used because it is banned by the Food and Drug Administration. The aim of this study was to investigate the usability of pantoprazole as a premedication instead of ranitidine in Meckel scintigraphy. Methods: Twelve New Zealand rabbits were used in this experimental study. Rabbits were divided into two groups: pantoprazole and control. Six rabbits were premedicated with pantoprazole for three days. Meckel scintigraphy was performed on all rabbits. Counts were made and compared by drawing regions of interest from the stomach walls. Results: According to the findings of this experimental study, pantoprazole significantly increased Tc-99m-pertechnetate uptake in the stomach of rabbits on both visual and quantitative evaluation. Conclusion: Pantoprazole increases the gastric wall uptake of Tc-99m-pertechnetate in rabbits and is a potential drug for premedication in Meckel scintigraphy. [ABSTRACT FROM AUTHOR]

Aortic aneurysms, life-threatening and often undetected until they cause sudden death, occur when the aorta dilates beyond 1.5 times its normal size. This study used ultrasound scans and micro-computed tomography to monitor and measure aortic volume in preclinical settings, comparing it to the well-established measurement using ultrasound scans. The reproducibility of measurements was also examined for intra- and inter-observer variability, with both modalities used on 8-week-old C57BL6 mice. For inter-observer variability, the μCT (micro-computed tomography) measurements for the thoracic, abdominal, and whole aorta between observers were highly consistent, showing a strong positive correlation (R2 = 0.80, 0.80, 0.95, respectively) and no significant variability (p-value: 0.03, 0.03, 0.004, respectively). The intra-observer variability for thoracic, abdominal, and whole aorta scans demonstrated a significant positive correlation (R2 = 0.99, 0.96, 0.87, respectively) and low variability (p-values = 0.0004, 0.002, 0.01, respectively). The comparison between μCT and USS (ultrasound) in the suprarenal and infrarenal aorta showed no significant difference (p-value = 0.20 and 0.21, respectively). μCT provided significantly higher aortic volume measurements compared to USS. The reproducibility of USS and μCT measurements was consistent, showing minimal variance among observers. These findings suggest that μCT is a reliable alternative for comprehensive aortic phenotyping, consistent with clinical findings in human data. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to assess the potential of poly (acrylic acid)/tricalcium phosphate nanoparticles (PAA/triCaPNPs) scaffold in terms of biocompatibility and osteoconductivity properties the in-vivo evaluation as well as to investigate the performance of PAA/triCaPNPs scaffold (with or without exosomes derived from UC-MSCs) for bone regeneration of rat critical-sized defect. Methods: PAA/triCaPNPs scaffold was made from acrylic acid (AA) monomer, N,N'-methylenebisacrylamide (MBAA), sodium bicarbonate (SBC), and ammonium persulfate (APS) through freeze-drying method. For in vivo evaluation, we randomly divided 24 rats into three groups. The rat calvarial bone defects were treated as follows: (1) Control group: defects without any treatment, (2) scaffold group: defects treated with scaffold only, (3) scaffold+exo group: defects treated with scaffold enriched with exosomes (1 µg/µL, 150 µg per rat). Eight- and 12-weeks post-surgery, half of the animals were sacrificed and bone regeneration was examined through micro-computerized tomography (µ-CT), histological staining, and immunohistochemistry (IHC). Results: Quantitative analysis based on µ-CT scan images at 8 and 12 weeks post-implantation clearly indicated that healing rate for defects that were filled with scaffold enriched with exosome was significantly higher than defects filled with scaffold without exosome. The H&E and Masson staining results revealed that more new bone-like form developed in the scaffold+exo group than that in control and scaffold groups. Further, IHC staining for osteocalcin and CD31 confirmed that more bone healing in the scaffold+exo group at 12 weeks could be associated with osteogenesis and angiogenesis concurrently. Conclusion: In the present study, we aimed to investigate the therapeutic potential of PAA/triCaPNPs scaffold as a carrier of human UC-MSC-derived exosome to achieve the exosomecontrolled release on calvarial bone defect. The in vivo results indicated that the exosome-enriched scaffold could effectively minify the defect area and improve the bone healing in rat model, and as such it could be an option for exosome-based therapy. [ABSTRACT FROM AUTHOR]

Nanodiamonds (NDs) are emerging as a novel nanoparticle class with growing interest in medical applications. The surface coating of NDs can be modified by attaching binding ligands or imaging probes, turning them into multi-modal targeting agents. In this investigation, we assessed the targeting efficacy of octreotide-functionalized 68Ga-radiolabelled NDs for cancer imaging and compared it with the tumor uptake using [68Ga]Ga-DOTA-TOC. In vivo studies in mice bearing AR42J tumors demonstrated the highest accumulation of the radiolabeled functionalized NDs in the liver and spleen, with relatively low tumor uptake compared to [68Ga]Ga-DOTA-TOC. Our findings suggest that, within the scope of this study, functionalization did not enhance the tumor-targeting capabilities of NDs. [ABSTRACT FROM AUTHOR]

Preclinical imaging is a critical component in translational research with significant complexities in workflow and site differences in deployment. Importantly, the National Cancer Institute's (NCI) precision medicine initiative emphasizes the use of translational co-clinical oncology models to address the biological and molecular bases of cancer prevention and treatment. The use of oncology models, such as patient-derived tumor xenografts (PDX) and genetically engineered mouse models (GEMMs), has ushered in an era of co-clinical trials by which preclinical studies can inform clinical trials and protocols, thus bridging the translational divide in cancer research. Similarly, preclinical imaging fills a translational gap as an enabling technology for translational imaging research. Unlike clinical imaging, where equipment manufacturers strive to meet standards in practice at clinical sites, standards are neither fully developed nor implemented in preclinical imaging. This fundamentally limits the collection and reporting of metadata to qualify preclinical imaging studies, thereby hindering open science and impacting the reproducibility of co-clinical imaging research. To begin to address these issues, the NCI co-clinical imaging research program (CIRP) conducted a survey to identify metadata requirements for reproducible quantitative co-clinical imaging. The enclosed consensus-based report summarizes co-clinical imaging metadata information (CIMI) to support quantitative co-clinical imaging research with broad implications for capturing co-clinical data, enabling interoperability and data sharing, as well as potentially leading to updates to the preclinical Digital Imaging and Communications in Medicine (DICOM) standard.

In vivo imaging of 225Ac is a major challenge in the development of targeted alpha therapy radiopharmaceuticals due to the extremely low injected doses. In this paper, we present the design of a multi-modality gamma camera that integrates both proximity and Compton imaging in order to achieve the demanding sensitivities required to image 225Ac with good image quality. We consider a dual-head camera, each of the heads consisting of two planar cadmium zinc telluride detectors acting as scatterer and absorber for Compton imaging, and with the scatterer practically in contact with the subject to allow for proximity imaging. We optimize the detector's design and characterize the detector's performance using Monte Carlo simulations. We show that Compton imaging can resolve features of up to 1.5 mm for hot rod phantoms with an activity of 1 μCi, and can reconstruct 3D images of a mouse injected with 0.5 μCi after a 15 minutes exposure and with a single bed position, for both 221Fr and 213Bi. Proximity imaging is able to resolve two 1 mm-radius sources of less than 0.1 μCi separated by 1 cm and at 1 mm from the detector, as well as it can provide planar images of 221Fr and 213Bi biodistributions of the mouse phantom in 5 minutes.

Huntington's disease is an inherited disorder characterized by psychiatric, cognitive, and motor symptoms due to degeneration of medium spiny neurons in the striatum. A prodromal phase precedes the onset, lasting decades. Current biomarkers include clinical score and striatal atrophy using Magnetic Resonance Imaging (MRI). These markers lack sensitivity for subtle cellular changes during the prodromal phase. MRI and MR spectroscopy offer different contrasts for assessing metabolic, microstructural, functional, or vascular alterations in the disease. They have been used in patients and mouse models. Mouse models can be of great interest to study a specific mechanism of the degenerative process, allow better understanding of the pathogenesis from the prodromal to the symptomatic phase, and to evaluate therapeutic efficacy. Mouse models can be divided into three different constructions: transgenic mice expressing exon-1 of human huntingtin (HTT), mice with an artificial chromosome expressing fulllength human HTT, and knock-in mouse models with CAG expansion inserted in the murine htt gene. Several studies have used MRI/S to characterized these models. However, the multiplicity of modalities and mouse models available complicates the understanding of this rich corpus. The present review aims at giving an overview of results obtained using MRI/S for each mouse model of HD, to provide a useful resource for the conception of neuroimaging studies using mouse models of HD. Finally, despite difficulties in translating preclinical protocols to clinical applications, many biomarkers identified in preclinical models have already been evaluated in patients. This review also aims to cover this aspect to demonstrate the importance of MRI/S for studying HD. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer, the second-leading cause of mortality among women worldwide, is often diagnosed through invasive tissue sampling. This method may not fully represent the tumor's overall physiology, potentially leading to suboptimal treatment strategies and tumor recurrence. A non-invasive approach using MRI to quantify the hypoxic environment within the tumor could significantly enhance the accuracy of breast-cancer-subtype prediction. Our study introduces non-invasive imaging markers for hypoxia and related angiogenesis, utilizing hyperoxic-blood-oxygen-level-dependent (BOLD)-MRI and intravoxel-incoherent-motion (IVIM)-MRI techniques. These markers correlate with microvessel density and maturity as assessed by histology, enabling the distinction between the less aggressive luminal A and the more aggressive triple-negative breast cancers. Tumor neoangiogenesis is an important hallmark of cancer progression, triggered by alternating selective pressures from the hypoxic tumor microenvironment. Non-invasive, non-contrast-enhanced multiparametric MRI combining blood-oxygen-level-dependent (BOLD) MRI, which depicts blood oxygen saturation, and intravoxel-incoherent-motion (IVIM) MRI, which captures intravascular and extravascular diffusion, can provide insights into tumor oxygenation and neovascularization simultaneously. Our objective was to identify imaging markers that can predict hypoxia-induced angiogenesis and to validate our findings using multiplexed immunohistochemical analyses. We present an in vivo study involving 36 female athymic nude mice inoculated with luminal A, Her2+, and triple-negative breast cancer cells. We used a high-field 9.4-tesla MRI system for imaging and subsequently analyzed the tumors using multiplex immunohistochemistry for CD-31, PDGFR-β, and Hif1-α. We found that the hyperoxic-BOLD-MRI-derived parameter ΔR2* discriminated luminal A from Her2+ and triple-negative breast cancers, while the IVIM-derived parameter fIVIM discriminated luminal A and Her2+ from triple-negative breast cancers. A comprehensive analysis using principal-component analysis of both multiparametric MRI- and mpIHC-derived data highlighted the differences between triple-negative and luminal A breast cancers. We conclude that multiparametric MRI combining hyperoxic BOLD MRI and IVIM MRI, without the need for contrast agents, offers promising non-invasive markers for evaluating hypoxia-induced angiogenesis. [ABSTRACT FROM AUTHOR]

Background: Low‐dose positron emission tomography (LD‐PET) imaging is commonly employed in preclinical research to minimize radiation exposure to animal subjects. However, LD‐PET images often exhibit poor quality and high noise levels due to the low signal‐to‐noise ratio. Deep learning (DL) techniques such as generative adversarial networks (GANs) and convolutional neural network (CNN) have the capability to enhance the quality of images derived from noisy or low‐quality PET data, which encodes critical information about radioactivity distribution in the body. Purpose: Our objective was to optimize the image quality and reduce noise in preclinical PET images by utilizing the sinogram domain as input for DL models, resulting in improved image quality as compared to LD‐PET images. Methods: A GAN and CNN model were utilized to predict high‐dose (HD) preclinical PET sinograms from the corresponding LD preclinical PET sinograms. In order to generate the datasets, experiments were conducted on micro‐phantoms, animal subjects (rats), and virtual simulations. The quality of DL‐generated images was weighted by performing the following quantitative measures: structural similarity index measure (SSIM), root mean squared error (RMSE), peak signal‐to‐noise ratio (PSNR), signal‐to‐noise ratio (SNR), and contrast‐to‐noise ratio (CNR). Additionally, DL input and output were both subjected to a spatial resolution calculation of full width half maximum (FWHM) and full width tenth maximum (FWTM). DL outcomes were then compared with the conventional denoising algorithms such as non‐local means (NLM), block‐matching, and 3D filtering (BM3D). Results: The DL models effectively learned image features and produced high‐quality images, as reflected in the quantitative metrics. Notably, the FWHM and FWTM values of DL PET images exhibited significantly improved accuracy compared to LD, NLM, and BM3D PET images, and just as precise as HD PET images. The MSE loss underscored the excellent performance of the models, indicating that the models performed well. To further improve the training, the generator loss (G loss) was increased to a value higher than the discriminator loss (D loss), thereby achieving convergence in the GAN model. Conclusions: The sinograms generated by the GAN network closely resembled real HD preclinical PET sinograms and were more realistic than LD. There was a noticeable improvement in image quality and noise factor in the predicted HD images. Importantly, DL networks did not fully compromise the spatial resolution of the images. [ABSTRACT FROM AUTHOR]

BackgroundRadiomics can capture microscale information in medical images beyond what is visible to the naked human eye. Using a clinically relevant mouse model for endometrial cancer, the objective of this study was to develop and validate a radiomic signature (RS) predicting response to standard chemotherapy.MethodsMice orthotopically implanted with a patient-derived grade 3 endometrioid endometrial cancer organoid model (O-PDX) were allocated to chemotherapy (combined paclitaxel/carboplatin, n=11) or saline/control (n=13). During tumor progression, the mice underwent weekly T2-weighted (T2w) magnetic resonance imaging (MRI). Segmentation of primary tumor volume (vMRI) allowed extraction of radiomic features from whole-volume tumor masks. A radiomic model for predicting treatment response was derived employing least absolute shrinkage and selection operator (LASSO) statistics at endpoint images in the orthotopic O-PDX (RS_O), and subsequently applied on the earlier study timepoints (RS_O at baseline, and week 1-3). For external validation, the radiomic model was tested in a separate T2w-MRI dataset on segmented whole-volume subcutaneous tumors (RS_S) from the same O-PDX model, imaged at three timepoints (baseline, day 3 and day 10/endpoint) after start of chemotherapy (n=8 tumors) or saline/control (n=8 tumors).ResultsThe RS_O yielded rapidly increasing area under the receiver operating characteristic (ROC) curves (AUCs) for predicting treatment response from baseline until endpoint; AUC=0.38 (baseline); 0.80 (week 1), 0.85 (week 2), 0.96 (week 3) and 1.0 (endpoint). In comparison, vMRI yielded AUCs of 0.37 (baseline); 0.69 (w1); 0.83 (week 2); 0.92 (week 3) and 0.97 (endpoint). When tested in the external validation dataset, RS_S yielded high accuracy for predicting treatment response at day10/endpoint (AUC=0.85) and tended to yield higher AUC than vMRI (AUC=0.78, p=0.18). Neither RS_S nor vMRI predicted response at day 3 in the external validation set (AUC=0.56 for both).ConclusionsWe have developed and validated a radiomic signature that was able to capture chemotherapeutic treatment response both in an O-PDX and in a subcutaneous endometrial cancer mouse model. This study supports the promising role of preclinical imaging including radiomic tumor profiling to assess early treatment response in endometrial cancer models.

Abstract Background Small Animal Fast Insert for MRI detector I (SAFIR-I) is a novel Positron Emission Tomography insert for a $$7\,\hbox {T}$$ 7 T Bruker BioSpec 70/30 Ultra Shield Refrigerated Magnetic Resonance Imaging (MRI) system. It facilitates truly simultaneous quantitative imaging in mice and rats at injected activities as high as $$500\,\hbox {MBq}$$ 500 MBq . Exploitation of the resulting high count rates enables quick image formation at few seconds per frame. In this investigation, key performance parameters of SAFIR-I have been determined according to the evaluations outlined in the National Electrical Manufacturers Association (NEMA) Standards Publication NU 4-2008 (NEMA-NU4) protocol. Results Using an energy window of 391 to $$601\,\hbox {keV}$$ 601 keV and a Coincidence Timing Window of $$500\,\hbox {ps}$$ 500 ps , the following performance was observed: The average spatial resolution at $$5\,\hbox {mm}$$ 5 mm radial offset (Full Width at Half Maximum) is $$2.54\,\hbox {mm}$$ 2.54 mm when using Filtered Backprojection, 3D Reprojection reconstruction. For the mouse- and rat-like phantoms, the maximal Noise-Equivalent Count Rates (NECRs) are $$1368\,\hbox {kcps}$$ 1368 kcps at the highest tested average effective concentration of $$14.7\,\hbox {MBq}\,\hbox {cc}^{-1}$$ 14.7 MBq cc - 1 , and $$713\,\hbox {kcps}$$ 713 kcps at the highest tested average effective concentration of $$1.72\,\hbox {MBq}\,\hbox {cc}^{-1}$$ 1.72 MBq cc - 1 , respectively. The NECR peak is not yet reached for either of these cases. The peak sensitivity is $$1.46\,\%$$ 1.46 % . The Image Quality phantom uniformity standard deviation is $$4.8\,\%$$ 4.8 % . The Recovery Coefficient for the $$5\,\hbox {mm}$$ 5 mm rod is $$(1.08 \pm 0.10)$$ ( 1.08 ± 0.10 ) . The Spill-Over Ratios are $$(0.22 \pm 0.03)$$ ( 0.22 ± 0.03 ) and $$(0.22 \pm 0.02)$$ ( 0.22 ± 0.02 ) , for the water- and air-filled cylinder, respectively. An accuracy of $$4.3\,\%$$ 4.3 % was achieved for the quantitative calibration of reconstructed voxel values. Conclusions The measured performance parameters indicate that the various design goals have been achieved. SAFIR-I offers excellent performance, especially at the high activities it was designed for. This facilitates planned experiments with fast tracer kinetics in small animals. Ways to potentially improve performance can still be explored. Simultaneously, further performance gains can be expected for a forthcoming insert featuring 2.7 times longer axial coverage named Small Animal Fast Insert for MRI detector II (SAFIR-II).

Background: Small Animal Fast Insert for MRI detector I (SAFIR-I) is a novel Positron Emission Tomography insert for a 7 T Bruker BioSpec 70/30 Ultra Shield Refrigerated Magnetic Resonance Imaging (MRI) system. It facilitates truly simultaneous quantitative imaging in mice and rats at injected activities as high as 500 MBq . Exploitation of the resulting high count rates enables quick image formation at few seconds per frame. In this investigation, key performance parameters of SAFIR-I have been determined according to the evaluations outlined in the National Electrical Manufacturers Association (NEMA) Standards Publication NU 4-2008 (NEMA-NU4) protocol. Results: Using an energy window of 391 to 601 keV and a Coincidence Timing Window of 500 ps , the following performance was observed: The average spatial resolution at 5 mm radial offset (Full Width at Half Maximum) is 2.54 mm when using Filtered Backprojection, 3D Reprojection reconstruction. For the mouse- and rat-like phantoms, the maximal Noise-Equivalent Count Rates (NECRs) are 1368 kcps at the highest tested average effective concentration of 14.7 MBq cc - 1 , and 713 kcps at the highest tested average effective concentration of 1.72 MBq cc - 1 , respectively. The NECR peak is not yet reached for either of these cases. The peak sensitivity is 1.46 % . The Image Quality phantom uniformity standard deviation is 4.8 % . The Recovery Coefficient for the 5 mm rod is (1.08 ± 0.10) . The Spill-Over Ratios are (0.22 ± 0.03) and (0.22 ± 0.02) , for the water- and air-filled cylinder, respectively. An accuracy of 4.3 % was achieved for the quantitative calibration of reconstructed voxel values. Conclusions: The measured performance parameters indicate that the various design goals have been achieved. SAFIR-I offers excellent performance, especially at the high activities it was designed for. This facilitates planned experiments with fast tracer kinetics in small animals. Ways to potentially improve performance can still be explored. Simultaneously, further performance gains can be expected for a forthcoming insert featuring 2.7 times longer axial coverage named Small Animal Fast Insert for MRI detector II (SAFIR-II). [ABSTRACT FROM AUTHOR]

Purpose: Innate immune activation plays a critical role in the onset and progression of many diseases. While positron emission tomography (PET) imaging provides a non-invasive means to visualize and quantify such immune responses, most available tracers are not specific for innate immune cells. To address this need, we developed [18F]OP-801 by radiolabeling a novel hydroxyl dendrimer that is selectively taken up by reactive macrophages/microglia and evaluated its ability to detect innate immune activation in mice following lipopolysaccharide (LPS) challenge. Procedures: OP-801 was radiolabeled in two steps: [18F]fluorination of a tosyl precursor to yield [18F]3-fluoropropylazide, followed by a copper-catalyzed click reaction. After purification and stability testing, [18F]OP-801 (150-250 μCi) was intravenously injected into female C57BL/6 mice 24 h after intraperitoneal administration of LPS (10 mg/kg, n=14) or saline (n=6). Upon completing dynamic PET/CT imaging, mice were perfused, and radioactivity was measured in tissues of interest via gamma counting or autoradiography. Results: [18F]OP-801 was produced with >95% radiochemical purity, 12–52 μCi/μg specific activity, and 4.3±1.5% decay-corrected yield. Ex vivo metabolite analysis of plasma samples (n=4) demonstrated high stability in mice (97±3% intact tracer >120 min post-injection). PET/CT images of mice following LPS challenge revealed higher signal in organs known to be inflamed in this context, including the liver, lung, and spleen. Gamma counting confirmed PET findings, showing significantly elevated signal in the same tissues compared to saline-injected mice: the liver (p=0.009), lung (p=0.030), and spleen (p=0.004). Brain PET/CT images (summed 50–60 min) revealed linearly increasing [18F]OP-801 uptake in the whole brain that significantly correlated with murine sepsis score (r=0.85, p<0.0001). Specifically, tracer uptake was significantly higher in the brain stem, cortex, olfactory bulb, white matter, and ventricles of LPS-treated mice compared to saline-treated mice (p<0.05). Conclusion: [18F]OP-801 is a promising new PET tracer for sensitive and specific detection of activated macrophages and microglia that warrants further investigation. [ABSTRACT FROM AUTHOR]

Huntington’s disease is an inherited disorder characterized by psychiatric, cognitive, and motor symptoms due to degeneration of medium spiny neurons in the striatum. A prodromal phase precedes the onset, lasting decades. Current biomarkers include clinical score and striatal atrophy using Magnetic Resonance Imaging (MRI). These markers lack sensitivity for subtle cellular changes during the prodromal phase. MRI and MR spectroscopy offer different contrasts for assessing metabolic, microstructural, functional, or vascular alterations in the disease. They have been used in patients and mouse models. Mouse models can be of great interest to study a specific mechanism of the degenerative process, allow better understanding of the pathogenesis from the prodromal to the symptomatic phase, and to evaluate therapeutic efficacy. Mouse models can be divided into three different constructions: transgenic mice expressing exon-1 of human huntingtin (HTT), mice with an artificial chromosome expressing full-length human HTT, and knock-in mouse models with CAG expansion inserted in the murine htt gene. Several studies have used MRI/S to characterized these models. However, the multiplicity of modalities and mouse models available complicates the understanding of this rich corpus. The present review aims at giving an overview of results obtained using MRI/S for each mouse model of HD, to provide a useful resource for the conception of neuroimaging studies using mouse models of HD. Finally, despite difficulties in translating preclinical protocols to clinical applications, many biomarkers identified in preclinical models have already been evaluated in patients. This review also aims to cover this aspect to demonstrate the importance of MRI/S for studying HD.

Aortic aneurysms, life-threatening and often undetected until they cause sudden death, occur when the aorta dilates beyond 1.5 times its normal size. This study used ultrasound scans and micro-computed tomography to monitor and measure aortic volume in preclinical settings, comparing it to the well-established measurement using ultrasound scans. The reproducibility of measurements was also examined for intra- and inter-observer variability, with both modalities used on 8-week-old C57BL6 mice. For inter-observer variability, the μCT (micro-computed tomography) measurements for the thoracic, abdominal, and whole aorta between observers were highly consistent, showing a strong positive correlation (R2 = 0.80, 0.80, 0.95, respectively) and no significant variability (p-value: 0.03, 0.03, 0.004, respectively). The intra-observer variability for thoracic, abdominal, and whole aorta scans demonstrated a significant positive correlation (R2 = 0.99, 0.96, 0.87, respectively) and low variability (p-values = 0.0004, 0.002, 0.01, respectively). The comparison between μCT and USS (ultrasound) in the suprarenal and infrarenal aorta showed no significant difference (p-value = 0.20 and 0.21, respectively). μCT provided significantly higher aortic volume measurements compared to USS. The reproducibility of USS and μCT measurements was consistent, showing minimal variance among observers. These findings suggest that μCT is a reliable alternative for comprehensive aortic phenotyping, consistent with clinical findings in human data.

Introduction: This study aimed to assess the potential of poly (acrylic acid)/tricalcium phosphate nanoparticles (PAA/triCaPNPs) scaffold in terms of biocompatibility and osteoconductivity properties the in-vivo evaluation as well as to investigate the performance of PAA/triCaPNPs scaffold (with or without exosomes derived from UC-MSCs) for bone regeneration of rat critical-sized defect. Methods: PAA/triCaPNPs scaffold was made from acrylic acid (AA) monomer, N,N’-methylenebisacrylamide (MBAA), sodium bicarbonate (SBC), and ammonium persulfate (APS) through freeze-drying method. For in vivo evaluation, we randomly divided 24 rats into three groups. The rat calvarial bone defects were treated as follows: (1) Control group: defects without any treatment, (2) scaffold group: defects treated with scaffold only, (3) scaffold+exo group: defects treated with scaffold enriched with exosomes (1 μg/μL, 150 μg per rat). Eight- and 12-weeks post-surgery, half of the animals were sacrificed and bone regeneration was examined through micro-computerized tomography (µ-CT), histological staining, and immunohistochemistry (IHC). Results: Quantitative analysis based on µ-CT scan images at 8 and 12 weeks post-implantation clearly indicated that healing rate for defects that were filled with scaffold enriched with exosome was significantly higher than defects filled with scaffold without exosome. The H&E and Masson staining results revealed that more new bone-like form developed in the scaffold+exo group than that in control and scaffold groups. Further, IHC staining for osteocalcin and CD31 confirmed that more bone healing in the scaffold+exo group at 12 weeks could be associated with osteogenesis and angiogenesis concurrently. Conclusion: In the present study, we aimed to investigate the therapeutic potential of PAA/triCaPNPs scaffold as a carrier of human UC-MSC-derived exosome to achieve the exosome-controlled release on calvarial bone defect. The in vivo results indicated that the exosome-enriched scaffold could effectively minify the defect area and improve the bone healing in rat model, and as such it could be an option for exosome-based therapy.

Nanodiamonds (NDs) are emerging as a novel nanoparticle class with growing interest in medical applications. The surface coating of NDs can be modified by attaching binding ligands or imaging probes, turning them into multi-modal targeting agents. In this investigation, we assessed the targeting efficacy of octreotide-functionalized 68Ga-radiolabelled NDs for cancer imaging and compared it with the tumor uptake using [68Ga]Ga-DOTA-TOC. In vivo studies in mice bearing AR42J tumors demonstrated the highest accumulation of the radiolabeled functionalized NDs in the liver and spleen, with relatively low tumor uptake compared to [68Ga]Ga-DOTA-TOC. Our findings suggest that, within the scope of this study, functionalization did not enhance the tumor-targeting capabilities of NDs.

Preclinical imaging is a critical component in translational research with significant complexities in workflow and site differences in deployment. Importantly, the National Cancer Institute’s (NCI) precision medicine initiative emphasizes the use of translational co-clinical oncology models to address the biological and molecular bases of cancer prevention and treatment. The use of oncology models, such as patient-derived tumor xenografts (PDX) and genetically engineered mouse models (GEMMs), has ushered in an era of co-clinical trials by which preclinical studies can inform clinical trials and protocols, thus bridging the translational divide in cancer research. Similarly, preclinical imaging fills a translational gap as an enabling technology for translational imaging research. Unlike clinical imaging, where equipment manufacturers strive to meet standards in practice at clinical sites, standards are neither fully developed nor implemented in preclinical imaging. This fundamentally limits the collection and reporting of metadata to qualify preclinical imaging studies, thereby hindering open science and impacting the reproducibility of co-clinical imaging research. To begin to address these issues, the NCI co-clinical imaging research program (CIRP) conducted a survey to identify metadata requirements for reproducible quantitative co-clinical imaging. The enclosed consensus-based report summarizes co-clinical imaging metadata information (CIMI) to support quantitative co-clinical imaging research with broad implications for capturing co-clinical data, enabling interoperability and data sharing, as well as potentially leading to updates to the preclinical Digital Imaging and Communications in Medicine (DICOM) standard.

Introduction: The collimator design and optimization are essential in small animal molecular imaging for preclinical studies. In this study, a mathematical model was derived and used to optimize the slit collimator for small animal imaging applications. Materials and Methods: The geometric efficiency was formulated as a source-to-detector distance for a certain amount of the collimator resolution (). The first-order derivative of the derived formula gives the optimized parameters. The detector performance was modeled in terms of intrinsic resolution . Furthermore, the edge penetration effect was considered using the validated model. Results: Optimum source-to-detector distance was found as . For an ideal detector, optimal, geometric efficiency and slit aperture width were found as , and , respectively. Where and are the source-to-collimator distance and detector length, respectively. For the fixed resolution of 1.0 mm, the sensitivity for different source-to-collimator distances of 50.0, 100.0, and 150.0 mm was calculated as, , and , respectively. In addition, for a sub-millimeter resolution of 0.5 mm at 15.0, 30.0, and 50.0 mm, the geometric efficiency was calculated as, , , and . For a typical source-to-collimator distance (15.0 mm), the optimal geometric efficiencies are, , , , and for the resolutions of 0.25, 0.50, 1.0, 1.5, and 2.0 mm, respectively. Conclusion: Based on the analytic model predictions, the performance characteristics of the slit collimator in terms of geometric efficiency and resolution were extracted. The importance of the proposed model lies both in its speed and ease of application.

Over the past decade, medical imaging technologies have become increasingly significant in both clinical and preclinical research, leading to a better understanding of disease processes and the development of new diagnostic and theranostic methods. Radiomic and radiogenomic approaches have furthered this progress by exploring the relationship between imaging characteristics, genomic information, and outcomes that qualitative interpretations may have overlooked, offering valuable insights for personalized medicine. Preclinical research allows for a controlled environment where various aspects of a pathology can be replicated in animal models, providing radiomic and radiogenomic approaches with the unique opportunity to investigate the causal connection between imaging and molecular factors. The aim of this review is to present the current state of the art in the application of radiomics and radiogenomics on murine models. This review will provide a brief description of relevant articles found in the literature with a discussion on the implications and potential translational relevance of these findings. [ABSTRACT FROM AUTHOR]

BackgroundClinical attempts to find benefit from specifically targeting and boosting resistant hypoxic tumor subvolumes have been promising but inconclusive. While a first preclinical murine tumor type showed significant improved control with hypoxic tumor boosts, a more thorough investigation of efficacy from boosting hypoxic subvolumes defined by electron paramagnetic resonance oxygen imaging (EPROI) is necessary. The present study confirms improved hypoxic tumor control results in three different tumor types using a clonogenic assay and explores potential confounding experimental conditions.Materials and methodsThree murine tumor models were used for multi-modal imaging and radiotherapy: MCa-4 mammary adenocarcinomas, SCC7 squamous cell carcinomas, and FSa fibrosarcomas. Registered T2-weighted MRI tumor boundaries, hypoxia defined by EPROI as pO2 ≤ 10 mmHg, and X-RAD 225Cx CT boost boundaries were obtained for all animals. 13 Gy boosts were directed to hypoxic or equal-integral-volume oxygenated tumor regions and monitored for regrowth. Kaplan–Meier survival analysis was used to assess local tumor control probability (LTCP). The Cox proportional hazards model was used to assess the hazard ratio of tumor progression of Hypoxic Boost vs. Oxygenated Boost for each tumor type controlling for experimental confounding variables such as EPROI radiofrequency, tumor volume, hypoxic fraction, and delay between imaging and radiation treatment.ResultsAn overall significant increase in LTCP from Hypoxia Boost vs. Oxygenated Boost treatments was observed in the full group of three tumor types (p

Tumor neoangiogenesis is an important hallmark of cancer progression, triggered by alternating selective pressures from the hypoxic tumor microenvironment. Non-invasive, non-contrast-enhanced multiparametric MRI combining blood-oxygen-level-dependent (BOLD) MRI, which depicts blood oxygen saturation, and intravoxel-incoherent-motion (IVIM) MRI, which captures intravascular and extravascular diffusion, can provide insights into tumor oxygenation and neovascularization simultaneously. Our objective was to identify imaging markers that can predict hypoxia-induced angiogenesis and to validate our findings using multiplexed immunohistochemical analyses. We present an in vivo study involving 36 female athymic nude mice inoculated with luminal A, Her2+, and triple-negative breast cancer cells. We used a high-field 9.4-tesla MRI system for imaging and subsequently analyzed the tumors using multiplex immunohistochemistry for CD-31, PDGFR-β, and Hif1-α. We found that the hyperoxic-BOLD-MRI-derived parameter ΔR2* discriminated luminal A from Her2+ and triple-negative breast cancers, while the IVIM-derived parameter fIVIM discriminated luminal A and Her2+ from triple-negative breast cancers. A comprehensive analysis using principal-component analysis of both multiparametric MRI- and mpIHC-derived data highlighted the differences between triple-negative and luminal A breast cancers. We conclude that multiparametric MRI combining hyperoxic BOLD MRI and IVIM MRI, without the need for contrast agents, offers promising non-invasive markers for evaluating hypoxia-induced angiogenesis.

Preclinical imaging is the visualization of living animals for research purposes, such as drug development. Imaging modalities have long been crucial to the researcher in observing changes, either at the organ, tissue, cell, or molecular level, in animals responding to physiological or environmental changes. In vivo imaging modalities that are non-invasive have become especially important to study animal models longitudinally. Broadly speaking, these imaging systems can be categorized into primarily morphological/anatomical and primarily molecular imaging techniques. Techniques such as high-frequency micro-ultrasound, magnetic resonance imaging (MRI) and computed tomography (CT) are usually used for anatomical imaging, while optical imaging (fluorescence and bioluminescence), positron emission tomography (PET), and single photon emission computed tomography (SPECT) are usually used for molecular visualizations. These technologies require advanced engineering and scientific skills in order to develop, use and optimize them. As a leading institute for the convergence of science and technology in the field of preclinical imaging, TPCF organizes annual symposiums. Despite the difficult time we are experiencing due to the pandemic, Preclinical researches continues to grow in many areas. The 6th International TPCF preclinical imaging symposium is a key scientific and networking event yielding new partnerships that accelerate preclinical research and translation across all therapeutic areas. Preclinical imaging symposium (TPCF) is an annual event that focuses on newest trends and frontline technologies in drug discovery and translational research. In the TPIS 2022 we had 15 keynote speeches by brilliant scientists. These talks cover various aspects of preclinical imaging. We are pleased that Frontiers in Biomedical Technology (FBT) is publishing these abstracts in their journal. We at TPCF are also inviting the readers of FBT to attend our 6th annual TPIS (for more information visit our website on: www.TPCF.ir).

Purpose: To support acquisition of accurate, reproducible and high-quality preclinical imaging data, various standardisation resources have been developed over the years. However, it is unclear the impact of those efforts in current preclinical imaging practices. To better understand the status quo in the field of preclinical imaging standardisation, the STANDARD group of the European Society of Molecular Imaging (ESMI) put together a community survey and a forum for discussion at the European Molecular Imaging Meeting (EMIM) 2022. This paper reports on the results from the STANDARD survey and the forum discussions that took place at EMIM2022. Procedures: The survey was delivered to the community by the ESMI office and was promoted through the Society channels, email lists and webpages. The survey contained seven sections organised as generic questions and imaging modality-specific questions. The generic questions focused on issues regarding data acquisition, data processing, data storage, publishing and community awareness of international guidelines for animal research. Specific questions on practices in optical imaging, PET, CT, SPECT, MRI and ultrasound were further included. Results: Data from the STANDARD survey showed that 47% of survey participants do not have or do not know if they have QC/QA guidelines at their institutes. Additionally, a large variability exists in the ways data are acquired, processed and reported regarding general aspects as well as modality-specific aspects. Moreover, there is limited awareness of the existence of international guidelines on preclinical (imaging) research practices. Conclusions: Standardisation of preclinical imaging techniques remains a challenge and hinders the transformative potential of preclinical imaging to augment biomedical research pipelines by serving as an easy vehicle for translation of research findings to the clinic. Data collected in this project show that there is a need to promote and disseminate already available tools to standardise preclinical imaging practices. [ABSTRACT FROM AUTHOR]

The availability of preclinical simultaneous PET/MR imaging systems has been increasing in recent years. Therefore, this technique is progressively moving from the hands of pure physicists towards those of scientists more involved in pharmacology and biology. Unfortunately, these combined scanners can be prone to artefacts and deviation of their characteristics under the influence of external factors or mutual interference between subsystems. This may compromise the image quality as well as the quantitative aspects of PET and MR data. Hence, quality assurance is crucial to avoid loss of animals and experiments. A possible risk to the acceptance of quality control by preclinical teams is that the complexity and duration of this quality control are increased by the addition of MR and PET tests. To avoid this issue, we have selected over the past 5 years, simple tests that can be easily and quickly performed each day before starting an animal PET/MR acquisition. These tests can be performed by the person in charge of the experiment even if this person has a limited expertise in instrumentation and performance evaluation. In addition to these daily tests, other tests are suggested for an advanced system follow-up at a lower frequency. In the present paper, the proposed tests are sorted by periodicity from daily to annual. Besides, we have selected test materials that are available at moderate cost either commercially or through 3D printing. [ABSTRACT FROM AUTHOR]

Major depressive disorder is a growing and poorly understood pathology. Due to technical and ethical limitations, a significant proportion of the research on depressive disorders cannot be performed on patients, but needs to be investigated in animal paradigms. Over the years, animal studies have provided new insight in the mechanisms underlying depression. Several of these studies have used PET imaging for the non-invasive and longitudinal investigation of the brain physiology. This review summarises the findings of preclinical PET imaging in different experimental paradigms of depression and compares these findings with observations from human studies. Preclinical PET studies in animal models of depression can be divided into three main different approaches: (a) investigation of glucose metabolism as a biomarker for regional and network involvement, (b) evaluation of the availability of different neuroreceptor populations associated with depressive phenotypes, and (c) monitoring of the inflammatory response in phenotypes of depression. This review also assesses the relevance of the use of PET imaging techniques in animal paradigms for the understanding of specific aspects of the depressive-like phenotypes, in particular whether it might contribute to achieve a more detailed characterisation of the clinical depressive phenotypes for the development of new therapies for depression. [ABSTRACT FROM AUTHOR]

Hypofractionated stereotactic body radiotherapy treatments (SBRT) have demonstrated impressive results for the treatment of a variety of solid tumors. The role of tumor supporting vasculature damage in treatment outcome for SBRT has been intensely debated and studied. Fast, non-invasive, longitudinal assessments of tumor vasculature would allow for thorough investigations of vascular changes correlated with SBRT treatment response. In this paper, we present a novel theranostic system which incorporates a fluorescence molecular imager into a commercial, preclinical, microCT-guided, irradiator and was designed to quantify tumor vascular response (TVR) to targeted radiotherapy. This system overcomes the limitations of single-timepoint imaging modalities by longitudinally assessing spatiotemporal differences in intravenously-injected ICG kinetics in tumors before and after high-dose radiation. Changes in ICG kinetics were rapidly quantified by principle component (PC) analysis before and two days after 10 Gy targeted tumor irradiation. A classifier algorithm based on PC data clustering identified pixels with TVR. Results show that two days after treatment, a significant delay in ICG clearance as measured by exponential decay (40.5±16.1% P=0.0405 Paired t-test n=4) was observed. Changes in the mean normalized first and second PC feature pixel values (PC1 & PC2) were found (P=0.0559, 0.0432 paired t-test), suggesting PC based analysis accurately detects changes in ICG kinetics. The PC based classification algorithm yielded spatially-resolved TVR maps. Our first-of-its-kind theranostic system, allowing automated assessment of TVR to SBRT, will be used to better understand the role of tumor perfusion in metastasis and local control.

Abstract Background The SAFIR prototype insert is a preclinical Positron Emission Tomography (PET) scanner built to acquire dynamic images simultaneously with a 7 T Bruker Magnetic Resonance Imaging (MRI) scanner. The insert is designed to perform with an excellent coincidence resolving time of 194 ps Full Width Half Maximum (FWHM) and an energy resolution of 13.8% FWHM. These properties enable it to acquire precise quantitative images at activities as high as 500 MBq suitable for studying fast biological processes within short time frames (< 5 s). In this study, the performance of the SAFIR prototype insert is evaluated according to the NEMA NU 4-2008 standard while the insert is inside the MRI without acquiring MRI data. Results Applying an energy window of 391–601 keV and a coincidence time window of 500 ps the following results are achieved. The average spatial resolution at 5 mm radial offset is 2.6 mm FWHM when using the Filtered Backprojection 3D Reprojection (FBP3DRP) reconstruction method, improving to 1.2 mm when using the Maximum Likelihood Expectation Maximization (MLEM) method. The peak sensitivity at the center of the scanner is 1.06%. The Noise Equivalent count Rate (NECR) is 799 kcps at the highest measured activity of 537 MBq for the mouse phantom and 121 kcps at the highest measured activity of 624 MBq for the rat phantom. The NECR peak is not yet reached for any of the measurements. The scatter fractions are 10.9% and 17.8% for the mouse and rat phantoms, respectively. The uniform region of the image quality phantom has a 3.0% STD, with a 4.6% deviation from the expected number of counts per voxel. The spill-over ratios for the water and air chambers are 0.18 and 0.17, respectively. Conclusions The results satisfy all the requirements initially considered for the insert, proving that the SAFIR prototype insert can obtain dynamic images of small rodents at high activities ( $$\sim$$ ∼ 500 MBq) with a high sensitivity and an excellent count-rate performance.

Imaging has become an invaluable tool in preclinical research for its capability to non-invasively detect and monitor disease and assess treatment response. With the increased use of preclinical imaging, large volumes of image data are being generated requiring critical data management tools. Due to proprietary issues and continuous technology development, preclinical images, unlike DICOM-based images, are often stored in an unstructured data file in company-specific proprietary formats. This limits the available DICOM-based image management database to be effectively used for preclinical applications. A centralized image registry and management tool is essential for advances in preclinical imaging research. Specifically, such tools may have a high impact in generating large image datasets for the evolving artificial intelligence applications and performing retrospective analyses of previously acquired images. In this study, a web-based server application is developed to address some of these issues. The application is designed to reflect the actual experimentation workflow maintaining detailed records of both individual images and experimental data relevant to specific studies and/or projects. The application also includes a web-based 3D/4D image viewer to easily and quickly view and evaluate images. This paper briefly describes the initial implementation of the web-based application.

Simple Summary: The increased tissue stiffness associated with cancer has been found to be a significant barrier to effective treatment and indicates an increased likelihood of cancer progression. Techniques to map tumour stiffness throughout the whole tumour in three dimensions will assist with preclinical research that aims to understand the relationship between the stiffness, the underlying tumour biology, and the response of tumours to therapy. We have developed an approach that measures the tumour stiffness in murine models of cancer, which are commonly used for cancer research. This technique uses a high-frequency vibrational source, ultrasound imaging and a three-dimensional analysis, which has advantages in terms of spatial resolution and rapid acquisition times. Here we present the first successful demonstration of the non-invasive three-dimensional measurement of tumour stiffness in two preclinical tumour models and the ability of the technique to detect a change in tumour stiffness in response to an anti-cancer drug. Preclinical investigation of the biomechanical properties of tissues and their treatment-induced changes are essential to support drug-discovery, clinical translation of biomarkers of treatment response, and studies of mechanobiology. Here we describe the first use of preclinical 3D elastography to map the shear wave speed (cs), which is related to tissue stiffness, in vivo and demonstrate the ability of our novel 3D vibrational shear wave elastography (3D-VSWE) system to detect tumour response to a therapeutic challenge. We investigate the use of one or two vibrational sources at vibrational frequencies of 700, 1000 and 1200 Hz. The within-subject coefficients of variation of our system were found to be excellent for 700 and 1000 Hz and 5.4 and 6.2%, respectively. The relative change in cs measured with our 3D-VSWE upon treatment with an anti-vascular therapy ZD6126 in two tumour xenografts reflected changes in tumour necrosis. U-87 MG drug vs vehicle: Δcs = −24.7 ± 2.5 % vs 7.5 ± 7.1%, (p = 0.002) and MDA-MB-231 drug vs vehicle: Δcs = −12.3 ± 2.7 % vs 4.5 ± 4.7%, (p = 0.02). Our system enables rapid (<5 min were required for a scan length of 15 mm and three vibrational frequencies) 3D mapping of quantitative tumour viscoelastic properties in vivo, allowing exploration of regional heterogeneity within tumours and speedy recovery of animals from anaesthesia so that longitudinal studies (e.g., during tumour growth or following treatment) may be conducted frequently. [ABSTRACT FROM AUTHOR]

Reflection ultrasound computed tomography (RUCT) attains optimal image quality from objects that can be fully accessed from multiple directions, such as the human breast or small animals. Owing to the full-view tomography approach based on the compounding of images taken from multiple angles, RUCT effectively mitigates several deficiencies afflicting conventional pulse-echo ultrasound (US) systems, such as speckle patterns and interuser variability. On the other hand, the small interelement pitch required to fulfill the spatial sampling criterion in the circular transducer configuration used in RUCT typically implies the use of an excessive number of independent array elements. This increases the system’s complexity and costs, and limits the achievable imaging speed. Here, we explore acquisition schemes that enable RUCT imaging with the reduced number of transmit/receive elements. We investigated the influence of the element size in transmission and reception in a ring array geometry. The performance of a sparse acquisition approach based on partial acquisition from a subset of the elements has been further assessed. A larger element size is shown to preserve contrast and resolution at the center of the field of view (FOV), while a reduced number of elements is shown to cause uniform loss of contrast and resolution across the entire FOV. The tradeoffs of achievable FOV, contrast-to-noise ratio, and temporal and spatial resolutions are assessed in phantoms and in vivo mouse experiments. The experimental analysis is expected to aid the development of optimized hardware and image acquisition strategies for RUCT and, thus, result in more affordable imaging systems facilitating wider adoption. [ABSTRACT FROM AUTHOR]

Echocardiography (echo) is a translationally relevant ultrasound imaging modality widely used to assess cardiac structure and function in preclinical models of heart failure (HF) during research and drug development. Although echo is a very valuable tool, the image analysis is a time-consuming, resource-demanding process, and is susceptible to interreader variability. Recent advancements in deep learning have enabled researchers to automate image processing and reduce analysis time and interreader variability in the field of medical imaging. In the present study, we developed a fully automated tool, mouse-echocardiography neural net (MENN), for the analysis of both long-axis brightness (B)-mode and short-axis motion (M)-mode images of left ventricle. MENN is a series of fully convolutional neural networks that were trained and validated using manually segmented Bmode and M-mode echo images of the left ventricle. The segmented images were then used to compute cardiac structural and functional metrics. The performance of MENN was further validated in two preclinical models of HF. MENN achieved excellent correlations (Pearson's r = 0.85-0.99) and good-to-excellent agreement between automated and manual analyses. Further interreader variability analysis showed that MENN has better agreements with an expert analyst than both a trained analyst and a novice. Notably, the use of MENN reduced manual analysis time by >92%. In conclusion, we developed an automated echocardiography analysis tool that allows for fast and accurate analysis of B-mode and M-mode mouse echo data and mitigates the issue of interreader variability in manual analysis. [ABSTRACT FROM AUTHOR]

Abstract Background Non-human primates (NHP) are critical in biomedical research to better understand the pathophysiology of diseases and develop new therapies. Based on its translational and longitudinal abilities along with its non-invasiveness, PET/CT systems dedicated to non-human primates can play an important role for future discoveries in medical research. The aim of this study was to evaluate the performance of a new PET/CT system dedicated to NHP imaging, the IRIS XL-220 developed by Inviscan SAS. This was performed based on the National Electrical Manufacturers Association (NEMA) NU 4-2008 standard recommendations (NEMA) to characterize the spatial resolution, the scatter fraction, the sensitivity, the count rate, and the image quality of the system. Besides, the system was evaluated in real conditions with two NHP with 18F-FDG and (-)-[18F]FEOBV which targets the vesicular acetylcholine transporter, and one rat using 18F-FDG. Results The full width at half maximum obtained with the 3D OSEM algorithm ranged between 0.89 and 2.11 mm in the field of view. Maximum sensitivity in the 400–620 keV and 250–750 keV energy windows were 2.37% (22 cps/kBq) and 2.81% (25 cps/kBq), respectively. The maximum noise equivalent count rate (NEC) for a rat phantom was 82 kcps at 75 MBq and 88 kcps at 75 MBq for energy window of 250–750 and 400–620 keV, respectively. For the monkey phantom, the maximum NEC was 18 kcps at 126 MBq and 19 kcps at 126 MBq for energy window of 250–750 and 400–620 keV, respectively. The IRIS XL provided an excellent quality of images in non-human primates and rats using 18F-FDG. The images acquired using (-)-[18F]FEOBV were consistent with those previously reported in non-human primates. Conclusions Taken together, these results showed that the IRIS XL-220 is a high-resolution system well suited for PET/CT imaging in non-human primates.

Over the past decade, medical imaging technologies have become increasingly significant in both clinical and preclinical research, leading to a better understanding of disease processes and the development of new diagnostic and theranostic methods. Radiomic and radiogenomic approaches have furthered this progress by exploring the relationship between imaging characteristics, genomic information, and outcomes that qualitative interpretations may have overlooked, offering valuable insights for personalized medicine. Preclinical research allows for a controlled environment where various aspects of a pathology can be replicated in animal models, providing radiomic and radiogenomic approaches with the unique opportunity to investigate the causal connection between imaging and molecular factors. The aim of this review is to present the current state of the art in the application of radiomics and radiogenomics on murine models. This review will provide a brief description of relevant articles found in the literature with a discussion on the implications and potential translational relevance of these findings.

In vivo imaging in preclinical and clinical settings can enhance knowledge of the host-microbiome interactions. Imaging techniques are a crucial node between findings at the molecular level and clinical implementation in diagnostics and therapeutics. The purpose of this study was to review existing knowledge on the microbiota in the field of in vivo imaging and provide guidance for future research, emphasizing the critical role that molecular imaging plays in increasing understanding of the host-microbe interaction.Preclinical microbiota animal models lay the foundation for the clinical translatability of novel microbiota-based therapeutics. Adopting animal models in which factors such as host genetic landscape, microbiota profile, and diet can be controlled enables investigating how the microbiota contributes to immunological dysregulation and inflammatory disorders. Current preclinical imaging of gut microbiota relies on models where the bacteria can be isolated, labelled, and re-administered. In vivo, optical imaging, ultrasound and magnetic resonance imaging define the bacteria's biodistribution in preclinical models, whereas nuclear imaging investigates bacterial metabolic activity.For the clinical investigation of microbe-host interactions, molecular nuclear imaging is increasingly becoming a promising approach. Future microbiota research should develop selective imaging probes to investigate in vivo microbiota profiles and individual strains of specific microbes. Preclinical knowledge can be translated into the molecular imaging field with great opportunities for studying the microbiome.

BackgroundInterstitial lung disease (ILD) defines a group of parenchymal lung disorders, characterized by fibrosis as their common final pathophysiological stage. To improve diagnosis and treatment of ILD, there is a need for repetitive non-invasive characterization of lung tissue by quantitative parameters. In this study, we investigated whether CT image patterns found in mice with bleomycin induced lung fibrosis can be translated as prognostic factors to human patients diagnosed with ILD.MethodsBleomycin was used to induce lung fibrosis in mice (n_control = 36, n_experimental = 55). The patient cohort consisted of 98 systemic sclerosis (SSc) patients (n_ILD = 65). Radiomic features (n_histogram = 17, n_texture = 137) were extracted from microCT (mice) and HRCT (patients) images. Predictive performance of the models was evaluated with the area under the receiver-operating characteristic curve (AUC). First, predictive performance of individual features was examined and compared between murine and patient data sets. Second, multivariate models predicting ILD were trained on murine data and tested on patient data. Additionally, the models were reoptimized on patient data to reduce the influence of the domain shift on the performance scores.ResultsPredictive power of individual features in terms of AUC was highly correlated between mice and patients (r = 0.86). A model based only on mean image intensity in the lung scored AUC = 0.921 ± 0.048 in mice and AUC = 0.774 (CI95% 0.677-0.859) in patients. The best radiomic model based on three radiomic features scored AUC = 0.994 ± 0.013 in mice and validated with AUC = 0.832 (CI95% 0.745-0.907) in patients. However, reoptimization of the model weights in the patient cohort allowed to increase the model’s performance to AUC = 0.912 ± 0.058.ConclusionRadiomic signatures of experimental ILD derived from microCT scans translated to HRCT of humans with SSc-ILD. We showed that the experimental model of BLM-induced ILD is a promising system to test radiomic models for later application and validation in human cohorts.

Objective. The development of alpha-emitting radiopharmaceuticals using 225Ac (t ½ = 9.92 d) benefits from the quantitative determination of its biodistribution and is not always easy to directly measure. An element-equivalent matched-pair would allow for more accurate biodistribution and dosimetry estimates. 226Ac (t ½ = 29.4 h) is a candidate isotope for in vivo imaging of preclinical 225Ac radiopharmaceuticals, given its 158 keV and 230 keV gamma emissions making it suitable for quantitative SPECT imaging. This work aimed to conduct a performance assessment for 226Ac imaging and presents the first-ever 226Ac SPECT images. Approach. To establish imaging performance with regards to contrast and noise, image quality phantoms were scanned using a microSPECT/CT system. To assess the resolution, a hot rod phantom with cylindrical rods with diameters between 0.85 and 1.70 mm was additionally imaged. Two collimators were evaluated: a high-energy ultra-high resolution (HEUHR) collimator and an extra ultra-high sensitivity (UHS) collimator. Images were reconstructed from two distinct photopeaks at 158 keV and 230 keV. Main results. The HEUHR SPECT image measurements of high activity concentration regions were consistent with values determined independently via gamma spectroscopy, within 9% error. The lower energy 158 keV photopeak images demonstrated slightly better contrast recovery. In the resolution phantom, the UHS collimator only resolved rods ≥1.30 mm and ≥1.50 mm for the 158 keV and 230 keV photopeaks, respectively, while the HEUHR collimator clearly resolved all rods, with resolution <0.85 mm. Significance. Overall, the feasibility of preclinical imaging with 226Ac was demonstrated with quantitative SPECT imaging achieved for both its 158 keV and 230 keV photopeaks. The HEUHR collimator is recommended for imaging 226Ac activity distributions in small animals due to its resolution <0.85 mm. Future work will explore the feasibility of using 226Ac both as an element-equivalent isotope for 225Ac radiopharmaceuticals, or as a standalone therapeutic isotope. [ABSTRACT FROM AUTHOR]

In X-ray imaging, photons are transmitted through and absorbed by the target object, but are also scattered in significant quantities. Previous attempts to use scattered X-ray photons for imaging applications used pencil or fan beam illumination. Here we present 3D X-ray Scatter Tomography using full-field illumination for small-animal imaging. Synchrotron imaging experiments were performed on a phantom and the chest of a juvenile rat. Transmitted and scattered photons were simultaneously imaged with separate cameras; a scientific camera directly downstream of the sample stage, and a pixelated detector with a pinhole imaging system placed at $45{}^\circ $ to the beam axis. We obtained scatter tomogram feature fidelity sufficient for segmentation of the lungs and major airways in the rat. The image contrast in the scatter tomogram slices approached that of transmission imaging, indicating robustness to the amount of multiple scattering present in our case. This opens the possibility of augmenting full-field 2D imaging systems with additional scatter detectors to obtain complementary modes or to improve the fidelity of existing images without additional dose, potentially leading to single-shot or reduced-angle tomography or overall dose reduction for live animal studies. [ABSTRACT FROM AUTHOR]

In this study, we present a time-efficient protocol for thoracic volume calculation as a proxy for total lung volume. We hypothesize that lung volume can be calculated indirectly from this thoracic volume. We compared the measured thoracic volume with manually segmented and automatically thresholded lung volumes, with manual segmentation as the gold standard. A linear regression formula was obtained and used for calculating the theoretical lung volume. This volume was compared with the gold standard volumes. In healthy animals, thoracic volume was 887.45 mm3, manually delineated lung volume 554.33 mm3 and thresholded aerated lung volume 495.38 mm3 on average. Theoretical lung volume was 554.30 mm3. Finally, the protocol was applied to three animal models of lung pathology (lung metastasis and transgenic primary lung tumor and fungal infection). In confirmed pathologic animals, thoracic volumes were: 893.20 mm3, 860.12 and 1027.28 mm3. Manually delineated volumes were 640.58, 503.91 and 882.42 mm3, respectively. Thresholded lung volumes were 315.92 mm3, 408.72 and 236 mm3, respectively. Theoretical lung volume resulted in 635.28, 524.30 and 863.10.42 mm3. No significant differences were observed between volumes. This confirmed the potential use of this protocol for lung volume calculation in pathologic models. [ABSTRACT FROM AUTHOR]

Molecular imaging generates large volumes of heterogeneous biomedical imagery with an impelling need of guidelines for handling image data. Although several successful solutions have been implemented for human epidemiologic studies, few and limited approaches have been proposed for animal population studies. Preclinical imaging research deals with a variety of machinery yielding tons of raw data but the current practices to store and distribute image data are inadequate. Therefore, standard tools for the analysis of large image datasets need to be established. In this paper, we present an extension of XNAT for Preclinical Imaging Centers (XNAT-PIC). XNAT is a worldwide used, open-source platform for securely hosting, sharing, and processing of clinical imaging studies. Despite its success, neither tools for importing large, multimodal preclinical image datasets nor pipelines for processing whole imaging studies are yet available in XNAT. In order to overcome these limitations, we have developed several tools to expand the XNAT core functionalities for supporting preclinical imaging facilities. Our aim is to streamline the management and exchange of image data within the preclinical imaging community, thereby enhancing the reproducibility of the results of image processing and promoting open science practices. [ABSTRACT FROM AUTHOR]

Widely used classical angiography with the use of iodine contrast agents is highly problematic, particularly in patients with diabetes mellitus, cardiac and pulmonary diseases, or degree III or IV renal insufficiency. Some patients may be susceptible to allergic reaction to the iodine contrast substance. The intravenous injection of a bolus of CO2 (negative contrast) is an alternative method, which is, however, currently only used for imaging blood vessels of the lower limbs. The aim of our project was to design and test on an animal model a methodology for injecting the CO2 foam which would minimize the possibility of embolization of the brain tissue and heart infarction, leading to their damage. This is important research for the further promotion of the use of CO2, which is increasingly important for endovascular diagnosis and treatment, because carbon-dioxide-related complications are extremely rare. CO2 foam was prepared by the rapid mixing in a 2:1 ratio of CO2 and fetal bovine serum (FBS)-enriched Dulbecco's Modified Eagle Medium (DMEM). Freshly prepared CO2 foam was administered into the catheterized rat tail vein or cannulated rat abdominal aorta and inferior vena cava (IVC). CO2 foam was compared with commercially available microbubbles (lipid shell/gas core). The rat heart in its parasternal long axis was imaged in B-Mode and Non-linear Contrast Mode before/during and after the contrast administration. Samples of the brain, heart and lungs were collected and subjected to histological examination. The non-linear contrast imaging method enables the imaging of micron-sized gas microbubbles inside a rat heart. The significantly shorter lifetime of the prepared CO2 foam is a benefit for avoiding the local ischemia of tissues. [ABSTRACT FROM AUTHOR]