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The purpose of this study is to measure the concentration of gold nanoparticles (AuNPs) attached to folic acid through cysteamin as the linker (FA-Cys-AuNPs) and AuNPs in KB human nasopharyngeal cancer cells using dual-energy CT (DECT). In this study, nanoparticles with a size of ~15 nm were synthesized and characterised using UV-Vis, TEM, FTIR and ICP-OES analyses. The non-toxicity of nanoparticles was confirmed by MTT assay under various concentrations (40-100 µg/ml) and incubation times (6, 12 and 24 h). To develop an algorithm for revealing different concentrations of AuNPs in cells, a corresponding physical phantom filled with 0.5 ml vials containing FA-Cys-AuNPs was used. The CT scan was performed at two energy levels (80 and 140 kVp). One feature of DECT is material decomposition, which allows separation and identification of different elements. The values obtained from the DECT algorithm were compared with values quantitatively measured by ICP-OES. Cells were also incubated with AuNPs and FA-Cys-AuNPs at different concentrations and incubation times. Subsequently, by increasing the incubation time in the presence of FA-Cys-AuNPs, in comparison with AuNPs, DECT pixels were increased. Thus, FA-Cys-AuNPs could be a suitable candidate for targeted contrast agent in DECT molecular imaging of nasopharyngeal cancer cells. [ABSTRACT FROM AUTHOR]

The purpose of this study is to measure the concentration of gold nanoparticles (AuNPs) attached to folic acid through cysteamin as the linker (FA‐Cys‐AuNPs) and AuNPs in KB human nasopharyngeal cancer cells using dual‐energy CT (DECT). In this study, nanoparticles with a size of ∼15 nm were synthesized and characterised using UV‐Vis, TEM, FTIR and ICP‐OES analyses. The non‐toxicity of nanoparticles was confirmed by MTT assay under various concentrations (40– 100 µg/ml) and incubation times (6, 12 and 24 h). To develop an algorithm for revealing different concentrations of AuNPs in cells, a corresponding physical phantom filled with 0.5 ml vials containing FA‐Cys‐AuNPs was used. The CT scan was performed at two energy levels (80 and 140 kVp). One feature of DECT is material decomposition, which allows separation and identification of different elements. The values obtained from the DECT algorithm were compared with values quantitatively measured by ICP‐OES. Cells were also incubated with AuNPs and FA‐Cys‐AuNPs at different concentrations and incubation times. Subsequently, by increasing the incubation time in the presence of FA‐Cys‐AuNPs, in comparison with AuNPs, DECT pixels were increased. Thus, FA‐Cys‐AuNPs could be a suitable candidate for targeted contrast agent in DECT molecular imaging of nasopharyngeal cancer cells. [ABSTRACT FROM AUTHOR]

Purpose: Xtrim‐PET is a newly designed Silicon Photomultipliers (SiPMs)‐based prototype PET scanner dedicated for small laboratory animal imaging. We present the performance evaluation of the Xtrim‐PET scanner following NEMA NU‐4 2008 standards to help optimizing scanning protocols which can be achieved through standard and reliable system performance characterization. Methods: The performance assessment was conducted according to the National Electrical Manufacturers Association (NEMA) NU‐4 2008 standards in terms of spatial resolution, sensitivity, counting rate performance, scatter fraction and image quality. The in vivo imaging capability of the scanner is also showcased through scanning a normal mouse injected with 18F‐FDG. Furthermore, the performance characteristics of the developed scanner are compared with commercially available systems and current prototypes. Results: The volumetric spatial resolution at 5 mm radial offset from the central axis of the scanner is 6.81 µl, whereas a peak absolute sensitivity of 2.99% was achieved using a 250–650 keV energy window and a 10 ns timing window. The peak noise‐equivalent count rate (NECR) using a mouse‐like phantom is 113.18 kcps at 0.34 KBq/cc with 12.5% scatter fraction, whereas the NECR peaked at 82.76 kcps for an activity concentration level of 0.048 KBq/cc with a scatter fraction of 25.8% for rat‐like phantom. An excellent uniformity (3.8%) was obtained using NEMA image quality phantom. Recovery coefficients of 90%, 86%, 68%, 40% and 12% were calculated for rod diameters of 5, 4, 3, 2 and 1 mm, respectively. Spill‐over ratios for air‐filled and water‐filled chambers were 35% and 25% without applying any correction for attenuation and Compton scattering effects. Conclusion: Our findings revealed that beyond compactness, lightweight, easy installation and good energy resolution, the Xtrim‐PET prototype presents a reasonable performance making it suitable for preclinical molecular imaging‐based research. [ABSTRACT FROM AUTHOR]

Development of various cost-effective multifunctional nanoprobes for efficient targeted molecular imaging of tumors remains a great challenge in medicine. Herein, we report a simple method of forming folic acid-targeted multifunctional gold nanoparticles via cost-effective cysteamine as a template for tumor molecular computed tomography (CT) imaging technique. The formed multifunctional cysteamine-folic acid conjugated gold nanoparticles (FA-Cys-AuNPs) were characterized via different techniques. Colony assay, hematoxylin and eosin (H&E), MTT, and flow cytometry analysis were used to evaluate the cytocompatibility of the particles. We showed that the formed FA-Cys-AuNPs with an Au core size of ~15 nm are non-cytotoxic in a given concentration range and revealed greater X-ray attenuation intensity than iodine-based contrast agent under the same concentration of the active element. At 80 kVp, FA-Cys-AuNPs enable 1.77–times greater contrast per unit mass compared with iodine at a concentration of 2000 μg/ml, and importantly, the developed FA-Cys-AuNPs can be used as a contrast media for targeted CT imaging of folic acid receptor-expressing cancer cells in vitro. CT values of the targeted cells were 2-times higher than that of non-targeted cells at 80 kVp. These findings propose that the designed FA-Cys-AuNPs can be used as a promising contrast agent for molecular CT imaging. This data can be also considered for the application of gold nanostructures in radiation dose enhancement where nanoparticles with high X-ray attenuation are applied. [ABSTRACT FROM AUTHOR]

Introduction: There is a strong need for developing clinical technologies and instruments for prompt tissue assessment in a variety of oncological applications as smart methods. Elastic scattering spectroscopy (ESS) is a real-time, noninvasive, point-measurement, optical diagnostic technique for malignancy detection through changes at cellular and subcellular levels, especially important in early diagnosis of invasive skin cancer, melanoma. In fact, this preliminary study was conducted to provide a classification method for analyzing the ESS spectra. Elastic scattering spectra related to the normal skin and melanoma lesions, which were already confirmed pathologically, were provided as input from an ESS database. Materials and Methods: A program was developed in MATLAB based on singular value decomposition and K-means algorithm for classification. Results: Accuracy and sensitivity of the proposed classifying method for normal and melanoma spectra were 87.5% and 80%, respectively. Conclusion: This method can be helpful for classification of melanoma and normal spectra. However, a large body of data and modifications are required to achieve better sensitivity for clinical applications. [ABSTRACT FROM AUTHOR]

The purpose of this study is to evaluate the biodistribution of polyethylene glycol (PEG) coated superparamagnetic iron oxide nanoparticles radiolabeled with Ga in normal mice after intravenous administration of this probe. Three mice were sacrificed at specific time intervals. The biodistribution data revealed high uptake by liver and spleen (60.62 and 12.65 %ID/g at 120 min post injection for liver and spleen, respectively). The clearance of other organs was fast. These results suggest that Ga-PEG-SPIONs has magnificent capabilities for applying in (PET-MRI) as a theranostic agent for detection of liver and spleen malignancies. [ABSTRACT FROM AUTHOR]

Fluorescence molecular tomography (FMT) is a rapidly growing imaging method that facilitates the recovery of small fluorescent targets within biological tissue. The major challenge facing the FMT reconstruction method is the ill-posed nature of the inverse problem. In order to overcome this problem, the acquisition of large FMT datasets and the utilization of a fast FMT reconstruction algorithm with sparsity regularization have been suggested recently. Therefore, the use of a joint L1/total-variation (TV) regularization as a means of solving the ill-posed FMT inverse problem is proposed. A comparative quantified analysis of regularization methods based on L1-norm and TV are performed using simulated datasets, and the results show that the fast composite splitting algorithm regularization method can ensure the accuracy and robustness of the FMT reconstruction. The feasibility of the proposed method is evaluated in an in vivo scenario for the subcutaneous implantation of a fluorescent-dye-filled capillary tube in a mouse, and also using hybrid FMT and x-ray computed tomography data. The results show that the proposed regularization overcomes the difficulties created by the ill-posed inverse problem. [ABSTRACT FROM AUTHOR]

The amount of radiotracer injected into laboratory animals is still the most daunting challenge facing translational PET studies. Since low-dose imaging is characterized by a higher level of noise, the quality of the reconstructed images leaves much to be desired. Being the most ubiquitous techniques in denoising applications, edge-aware denoising filters, and reconstruction-based techniques have drawn significant attention in low-count applications. However, for the last few years, much of the credit has gone to deep-learning (DL) methods, which provide more robust solutions to handle various conditions. Albeit being extensively explored in clinical studies, to the best of our knowledge, there is a lack of studies exploring the feasibility of DL-based image denoising in low-count small animal PET imaging. Therefore, herein, we investigated different DL frameworks to map low-dose small animal PET images to their full-dose equivalent with quality and visual similarity on a par with those of standard acquisition. The performance of the DL model was also compared to other well-established filters, including Gaussian smoothing, nonlocal means, and anisotropic diffusion. Visual inspection and quantitative assessment based on quality metrics proved the superior performance of the DL methods in low-count small animal PET studies, paving the way for a more detailed exploration of DL-assisted algorithms in this domain. [Display omitted] • Low-dose imaging is characterized by higher noise level, thus impacting image quality. • The feasibility of deep-learning-based image denoising in low-count small animal PET studies has never been reported. • We assessed the potential of various deep-learning models to generate full-dose mice PET scans from the undersampled data. • Compared to other methods, deep-learning brings a multitude of advantages in terms of quality, implementation, and speed. [ABSTRACT FROM AUTHOR]

The advent of dual-modality PET/CT imaging has revolutionized the practice of clinical oncology, cardiology and neurology by improving lesions localization and the possibility of accurate quantitative analysis. In addition, the use of CT images for CT-based attenuation correction (CTAC) allows to decrease the overall scanning time and to create a noise-free attenuation map (μmap). The near simultaneous data acquisition in a fixed combination of a PET and a CT scanner in a hybrid PET/CT imaging system with a common patent table minimizes spatial and temporal mismatches between the modalities by elimination the need to move the patient in between exams. As PET/CT technology becomes more widely available, studies are beginning to appear in the literature that document the use of PET/CT in a variety of different cancers, including lung, thyroid, ovarian, lymphoma, and unknown primary cancers, and for general oncology, cardiology and neurology applications. Specific applications of PET/CT, such as those for radiation therapy planning, are also being explored. The purpose of this review paper is to introduce the principles of PET/CT imaging systems and describe the sources of error and artifact in CT-based attenuation correction algorithm. This paper also focuses on recent developments and future trends in hybrid imaging and their areas of application. It should be noted that due to limited space, the references contained herein are for illustrative purposes and are not inclusive; no implication that those chosen are better than others not mentioned is intended. [ABSTRACT FROM AUTHOR]

In this work, a correlation function based on linograms and sinograms of the projection data was introduced, implemented and evaluated in order to estimate and compensate for the patient motion. Parabolic fitting of the peak of the correlation function was utilized to improve in the motion-estimation task. In dynamic planar imaging, the method checked for motion via its separate frames similar to the SPECT work; on the other hand, in static planar imaging, the data acquisition protocol was first exchanged from static to the dynamic modality, followed by application of the motion-correction scheme, and a final combination via summation of the motion-compensated frames. The method was successfully evaluated in many cases. Our tests showed that in SPECT imaging, the time of motion starting in a specific projection and the duration of motion are very important in the motion detection process. Measuring relative error showed that the error in the images with presence of motion along the axis of patient bed was 21.1%, being reduced to 1.4% while the 24.4% error along the perpendicular axis to the patient bed was reduced to 1.5% with the inclusion of our motion correction scheme. Experimental results in planar imaging also demonstrated the ability of this method to reduce error in the maximum count from 40.7% to 9.7%, wherein intended sudden motion was introduced in static planar acquisition. Similarly, the error produced by gradual simulated motion was reduced from 37% to 1.6%. This method was clinically examined in the bone scan (static planar data) of an old man for an Osteomyelitis study, as well as in a kidney washout study (dynamic planar data) for a child. As a result, the motion artifacts shown in the images were reduced considerably. [ABSTRACT FROM AUTHOR]

The development of novel nanoparticles for diagnostic and therapeutic applications has been one of the most crucial challenges in cancer theranostics for the last decades. Herein, we functionalized iron oxide nanoparticles (IONPs) with the fourth generation (G4) of poly amidoamine (PAMAM) dendrimers (G4@IONPs) for magnetic hyperthermia treatment of breast cancer in Bagg albino strain C (BALB/c)mice. The survival of breast cancer cells significantly decreased after incubation with G4@IONPs and exposure to an alternating magnetic field (AMF) due to apoptosis and elevation of Bax (Bcl-2 associated X)/Bcl-2(B-cell lymphoma 2) ratio. After intratumoral injection of G4@IONPs, tumor-bearing BALB/c mice were exposed to AMF for 20 min; this procedure was repeated three times every other day. After the last treatment, tumor size was measured every three days. Histopathological and Immunohistochemical studies were performed on the liver, lung, and tumor tissues in treated and control mice. The results did not show any metastatic cells in the liver and lung tissues in the treatment group, while the control mice tissues contained metastatic breast cancer cells. Furthermore, the findings of the present study showed that magnetic hyperthermia treatment inhibited tumor growth by increasing cancer cell apoptosis, as well as reducing the tumor angiogenesis. [ABSTRACT FROM AUTHOR]

Corrigendum to "Targeted gold nanoparticles enable molecular CT imaging of head and neck cancer: An in vivo study" [Int. J. Biochem. The authors would like to highlight that the first 3 figures in this article show data that is either identical or similar to that reported in our previous paper published in Materials Science and Engineering: C 89, 182-193. These figures have been reproduced with permission from Elsevier and were included in response to recommendations received from the both referees who reviewed our manuscript to include characterization data on the structure of the nanoparticles used. [Extracted from the article]

Purpose: With improvements in positron emission tomography/magnetic resonance imaging (PET/MRI) over the last decade, there is a need to investigate the projected annihilation (shine‐through) artifact and resolution impact for different PET radiopharmaceuticals, magnetic field (MF) strengths, and tissues. Methods: The GATE Monte Carlo (MC) simulation was used to simulate the annihilation distribution of positrons in different tissues and MFs. The positron distribution was studied in magnetic field (MF) intensities up to 15 T for 11C, 13N, 15O, 18F, 68Ga, and 82Rb. Moreover, the image quality in terms of the occurrence of projected annihilation artifacts was investigated using the 4D anthropomorphic digital extended cardiac‐torso (XCAT) phantom. Results: Positron ranges were restricted across the directions perpendicular to the MF, but no change along the direction of the MF was detected. The projected annihilation artifacts were observed with the presence of MF in the sagittal and coronal view of PET images prepared from the XCAT phantom. The intensity of artifact was constant in MFs higher than 3 T. The significant effect of the MF on resolution improvement was observed in soft tissue for 68Ga in 7 T and 82Rb in 3 and 7 T, while higher MFs have no impact on resolution. The improvement of resolution in the lung tissue was observed for the medium‐ and high‐energy radionuclides in 7 T MF. Conclusion: The MF can create the projected annihilation artifact in the boundary of air cavities and other tissues for medium‐ and high‐energy radionuclides especially for 68Ga in clinical studies. In addition, the strength of the MFs more than 3 T was ineffective on the intensity of the projected annihilation artifact. In a clinical PET/MR scanner, MF has remarkable spatial resolution improvement in lung tissue, especially for medium‐ and high‐energy radionuclides, and negligible effect in bone and soft tissue for most radionuclides. [ABSTRACT FROM AUTHOR]

• FA-Cys-AuNPs can be employed as a promising contrast agent in CT scan imaging. • CT values of targeted cells are 2-times higher than that of non-targeted nasopharyngeal cancer cells in nude mice. • FA-Cys-AuNP reveals good blood compatible property. The development of various cost-effective multifunctional contrast agent for specific targeting molecular imaging of tumors presents a great challenge. We report here the in vivo targeting imaging of folic acid (FA) gold nanoparticles (AuNPs) through cysteamine (Cys) linking for targeted of human nasopharyngeal head and neck cancer by computed tomography (CT). The toxicity of nanoparticles in kidney, heart, spleen, brain and liver was evaluated by H&E (hematoxylin and eosin) assay. We showed that the formed FA-Cys-AuNPs with an Au core size of ˜13 nm are non-cytotoxic in the particle concentration of 3 × 103 μg/ ml. The nude mice were scanned using a 64-slice CT scan with parameters (80 kVp, slice thickness: 0.625 mm, mAs: 200, pitch: 1). CT scan was performed before and after (Three and six hours) I.V (Intra Venous) injection of AuNPs and FA-Cys-AuNPs. The distribution of nanoparticles in the nude mice was evaluated by imaging and coupled plasma optical emission spectrometry (ICP-OES) analysis. The findings clearly illustrated that a small tumor, which is undetectable via computed tomography, is enhanced by X-ray attenuation and becomes visible (4.30-times) by the molecularly targeted AuNPs. It was further demonstrated that active tumor cells targeting (FA-Cys-AuNPs) is more specific and efficient (2.03-times) than passive targeting AuNPs. According to the results, FA-Cys-AuNPs can be employed as a promising contrast agent in CT scan imaging and maybe in radiotherapy that require enhanced radiation dose. [ABSTRACT FROM AUTHOR]

Background: Recently, some studies have focused on dendrimer nanopolymers as a magnetic resonance imaging (MRI) contrast agent or a vehicle for gene and drug delivery. Considering the suitable properties of these materials, they are appropriate candidates for coating iron-oxide nanoparticles which are applied in magnetic hyperthermia. To the best of our knowledge, the novelty of this study is the investigation of fourth-generation dendrimer-coated iron-oxide nanoparticles (G4@IONPs) in magnetic hyperthermia and MRI.Methods: IONPs were synthesized via co-precipitation and coated with the fourth generation (G4) of polyamidoamine dendrimer. The cytotoxicity of G4@IONPs with different concentrations was assessed in a human breast cancer cell line (MCF7) and human fibroblast cell line (HDF1). Hemolysis and stability of G4@IONPs were investigated, and in addition, the interaction of these particles with MCF7 cells was assessed by Prussian blue staining. Heat generation and specific absorption rate (SAR) were calculated from measurement and simulation results at 200 and 300 kHz. MCF7 and HDF1 cells were incubated with G4@IONPs for 2 h and then put into the magnetic coil for 120 min. Relaxometry experiments were performed with different concentrations of G4@IONPs with T1- and T2-weighted MR images.Results: The TEM results showed that G4@IONPs were 10 ± 4 nm. The in vitro toxicity assessments showed that synthesized nanoparticles had low toxicity. The viability of MCF7 cells incubated with G4@IONPs decreased significantly after magnetic hyperthermia. In addition, MR imaging revealed that G4@IONPs improved transverse relaxivity (r2) significantly.Conclusions: Our results encouraged the future application of G4@IONPs in magnetic hyperthermia and MR imaging. [ABSTRACT FROM AUTHOR]

Objective (s): Various iterative reconstruction algorithms in nuclear medicine have been introduced in the last three decades. For each new imaging system, it is wise to select appropriate image reconstruction algorithms and evaluate their performance. In this study, three approaches of image reconstruction were developed for a novel desktop open-gantry SPECT system, PERSPECT, to assess their performance in terms of the quality of the resultant reconstructed images. Methods: In the present work, a proposed image reconstruction algorithm for the PERSPECT, referred to as quasi-simultaneous multiplicative algebraic reconstruction technique (qSMART), together with two popular image reconstruction methods, maximum-likelihood expectation-maximization (MLEM) and ordered-subsets EM (OSEM), were implemented and compared. Analytic and Monte Carlo simulations were applied for data acquisition of various phantoms including a micro-Derenzo phantom. All acquired data were reconstructed by the three algorithms using different number of iterations (1-40). A thorough set of figures-of-merit was utilized to quantitatively compare the generated images. Results: OSEM depicted reconstructed images of higher (or matching) quality in comparison to qSMART. MLEM also reached nearly similar quality as OSEM but at higher number of iterations. The graph of data discrepancy revealed that the ranking of the three approaches in terms of convergence speed is as qSMART, OSEM, and MLEM. Furthermore, bias-versus-noise curves indicated that optimal bias-noise results were achieved using OSEM. Conclusion: The results showed that although qSMART can be applied for image reconstruction if being halted in the early iterations (up to 5), the best achievable quality of images is obtained using the OSEM. [ABSTRACT FROM AUTHOR]

The application of rod‐shaped gold nanoparticles as probes and carriers in biological systems have recently attracted great interest. UV–vis spectroscopy, circular dichroism, Fourier transform infrared spectroscopy, scanning electron microscopy and atomic force microscopy were used to study optical and structural properties of rod‐shaped gold nanoparticles when interacting with DNA oligomers in phosphate sodium salt buffer. The morphological transformation process of rod‐shaped gold nanoparticles resulting from the interaction with single‐stranded DNA (ssDNA) showed the role of hexadecyltrimethylammonium bromide (CTAB) in nanostructures as the main interacting agent. The obtained results confirmed that the CTAB coat of rod‐shaped gold nanoparticles have powerful positive charges for conjugations with surface negative charges of phosphate groups on ssDNA oligomers. The CTAB also inhibit the formation of covalent sulphide bonds between the gold core of rod‐shaped nanoparticles and alkanethiol oligonucleotides. The authors found that when the nanorods were exposed to ssDNA oligonucleotides, the gold nanorods changed their shapes and sizes, and exposed some microscopic malformations which could be used in the development of colorimetric assays of nucleic acids. [ABSTRACT FROM AUTHOR]

Introduction: Reliable quantification in positron emission tomography (PET) requires accurate attenuation correction of emission data, which in turn entails accurate determination of the attenuation map (µ-map) of the object under study. One of the main steps involved in CT-based attenuation correction (CTAC) is energy-mapping, or the conversion of linear attenuation coefficients (µ) calculated at the effective CT energy to those corresponding to 511 keV.Materials and Methods: The aim of this study is to compare different energy-mapping techniques including scaling, segmentation, the hybrid method, the bilinear calibration curve technique and the dual-energy approach to generate the µ-maps required for attenuation correction. In addition, our newly proposed method involving a quadratic polynomial calibration curve was also assessed. The µ-maps generated for both phantom and clinical studies were assessed qualitatively and quantitatively. A cylindrical polyethylene phantom containing different concentrations of K(2)HPO(4) in water was scanned and the µ-maps calculated from the corresponding CT images using the above-referenced energy-mapping methods. The CT images of five whole-body data sets acquired on a GE Discovery LS PET/CT scanner were employed to generate µ-maps using different energy-mapping approaches that were compared with the µ-maps generated at 511 keV using (68)Ge/(68)Ga rod sources. In another experiment, the evaluation was performed on PET images of a clinical study corrected for attenuation using µ-maps generated using the above described methods. The evaluation was performed for three different tissue types, namely, soft tissue, lung, and bone.Results and Discussion: All energy-mapping methods yielded almost similar results for soft tissues. The mean relative differences between scaling, segmentation, hybrid, bilinear, and quadratic polynomial calibration curve methods and the transmission scan serving as reference were 6.60%, 6.56%, 6.60%, 5.96%, and 7.36%, respectively. However, the scaling method produced the largest difference (16%) for bone tissues. For lung tissues, the segmentation method produced the largest difference (14.9%). The results for reconstructed PET images followed a similar trend. For soft tissues, all energy-mapping methods yield results in nearly the same range. However, in bone tissues, the scaling method resulted in considerable bias in the µ-maps and the reconstructed PET images. The segmentation method also produced noticeable bias especially in regions with variable densities such as the lung, since a single µ is assigned to the lungs. Apart from the aforementioned case, despite small differences in the generated µ-maps, the use of different energy-mapping methods does not affect, to a visible or measurable extent, the reconstructed PET images. [ABSTRACT FROM AUTHOR]

Abstract: Background: This is the first report on the targeted delivery of fullerene-based low toxic nanocationite particles (porphyrin adducts of cyclohexyl fullerene-C60) to treat hypoxia-induced mitochondrial dysfunction in mammalian heart muscle. Methods: The magnetic isotope effect generated by the release of paramagnetic 25Mg2+ from these nanoparticles selectively stimulates the ATP overproduction in the oxygen-depleted cell. Results: Because nanoparticles are membranotropic cationites, they will only release the overactivating paramagnetic cations in response to hypoxia-induced acidic shift. The resulting changes in the heart cell energy metabolism result in ∼80% recovery of the affected myocardium in <24 h after a single injection (0.03–0.1 LD50). Conclusions: Pharmacokinetics and pharmacodynamics of the nanoparticles suggest their suitability for safe and efficient administration in either single or multi-injection (acute or chronic) therapeutic schemes for the prevention and treatment of clinical conditions involving myocardial hypoxia. [Copyright &y& Elsevier]

This is a first case ever reported on the fullerene-based low toxic nanocationite particles (porphyrin adducts of cyclohexl fullerene-C60) designed for targeted delivery of the paramagnetic magnesium stable isotope to the heart muscle providing a sharp clinical effect close to about 80% recovery of the tissue hypoxia symptoms in less than 24 h after a single injection (0.03–0.1 LD50). A whole principle of this therapy is novel: 25Mg2+-magnetic isotope effect selectively stimulates the ATP over-production in the oxygen-depleted cell due to 25Mg2+ released by nanoparticles. Being membranotropic cationites, these "smart nanoparticles" release the over-activating paramagnetic cations only in response to the metabolic acidic shift. The resulting positive changes in the heart cell energy metabolism may help to prevent and/or treat the local myocardial hypoxic disorders and, hence, to protect the heart muscle from a serious damage in a vast variety of the hypoxia-caused clinical situations including both Doxorubicin and 1-methylnicotineamide cardiotoxic side effects. Both pharmacokinetics and pharmacodynamics of the drug proposed makes it suitable for safe and efficient administration in either single or multi-injection (acute or chronic) therapeutic schemes. [ABSTRACT FROM AUTHOR]

Abstract: Background and aim: Cholestatic animals display abnormal hypothalamic responses to pyrogenic stimuli and decreased febrile response to lipopolysaccharide. The present study was undertaken to determine if obstructive cholestasis was associated with abnormal thermoregulation under thermoneutral conditions. Methods: Male Sprague–Dawley rats weighing 200–250g were randomly divided into 21 groups. Three sets of seven groups were unoperated control, sham-operated and bile duct-ligated rats. The groups of unoperated control, sham-operated and bile duct-ligated rats were treated with daily administration of isotonic saline solution, N(ω)-nitro-l-arginine methyl ester (l-NAME) (3, 10, or 20mg/kg), naltrexone (10 or 20mg/kg) or aminoguanidine (150mg/kg). Body temperatures were measured before and 1, 3, 5 and 7 days after the surgery. Results: Bile duct-ligated rats had lower body temperature than sham-operated animals at 3 (P <0.001) and 5 (P <0.01) days after surgery. l-NAME, a non-selective inhibitor of nitric oxide synthase (NOS) (10, 20mg/kg, i.p.) or aminoguanidine, a selective iNOS inhibitor (150mg/kg, i.p.), completely reversed this hypothermia (P >0.05). Naltrexone, a non-selective opioid antagonist (20mg/kg, i.p.), also completely corrected this hypothermia (P >0.05). There was a drop in temperature in the first day after the surgery in sham and BDL groups compared to unoperated controls, which was significant in some groups demonstrating the effect of surgery and anesthetic drugs on the body temperature. Conclusions: Cholestatic rats show impaired thermoregulation suggesting the involvement of nitrergic and opioidergic systems. [Copyright &y& Elsevier]

Abstract: In this study, the volume of susceptibility artifact was evaluated in T1 and T2-weighted spin echo (SE) and gradient echo (GRE) images at various parameters using registration and subtraction methods. In order to state an important misinterpretation problem in lymphography, it was demonstrated that a lymph node size may be enlarged approximately 10 times when a T2*-weighted GRE protocol is used. To overcome this problem a technical consideration using multisequence (GRE and SE) paradigm was suggested to ensure both lymph node detection and metastasis identification in lymphatic system. The paradigm was also extended by post-processing manipulation of the SE images using a registration and subtraction approach for detection of lymphatic lesions. [Copyright &y& Elsevier]

We report on development of Xtrim-PET, a prototype low-cost preclinical PET system using high-density analog silicone photomultiplier (SiPM) arrays and pixelated scintillator LYSO:Ce crystals. Channel reduction method is employed to reduce 144 SiPM signals per detector block to 16 energy and 9 fast signals in the detector head. Using these signals, a Digital Front-End (DFE) board calculates energy, position, and time information of incident gamma photon and transmits data packets to a downstream Digital Coincidence Processing Unit (DCPU) in which the coincidence events are extracted in a fully pipelined digital processing fashion for maximum count throughput. The system consists of 10 detector blocks (detector head and DFE board), a DCPU board, and an acquisition computer. Prompt and delayed coincidence events are stored in list mode in the acquisition computer where first hand corrections are applied and 3D sinogram is generated in offline mode. Two-dimensional sinograms are then generated using single-slice rebinning algorithm and iterative image reconstruction methods are employed to generate the 3D image. The developed scanner works in room temperature without additional cooling system and has 180 mm ring diameter. Tomographic image resolution of 1.6, 1.7, and 1.8 mm FWHM was calculated along radial, tangential, and axial directions, respectively. Preliminary investigations were performed using NEMA image quality phantom in addition to rat cardiac and bone scans for preclinical evaluation of the scanner. [ABSTRACT FROM AUTHOR]

Introduction: The position estimation in gamma detection system will have constant misplacements which can be corrected in the calibration procedure. In the pixelated crystal uniformly irradiation of detector will produce irregular shape due to position estimation errors. This image is called flood field image and is used to calibrate the position estimation. In this work we present a novel approach to automatically calibrate pixelated crystal array position estimation. Methods: In the flood image of a pixelated crystal array the local peaks represent the estimation of position for the gamma photons that interacted in a single crystal pixel. First, the method detects 2-D peak locations automatically in the case of blurred pixel responses in the presence of noise and disturbance of the image. The algorithm consists of a filtering step for smoothing the image followed by two rounds of local peak detection. After localizing image peaks, the correction routine will map the image locations to the crystal pixels using the thin-plate spline interpolation method. Results: The algorithm is tested for two flood images obtained from developed detector with different irregularity levels. By configuring constant parameters according to the detector configuration the method detected all crystal pixels in the image and map them correctly. The method further has been tested for10 identical blocks and the result showed automatic peak detection routine for all the blocks. Conclusion: An automatic peak detection is presented to work instead of time consuming manual calibration routines. The method shows robust performance in the presence of image noise. [ABSTRACT FROM AUTHOR]

Herein, aptamer-modified self-propelled nanomotors were used for transportation of human promyelocytic leukemia cells (HL-60) from a human serum sample. For this purpose, the fabricated manganese oxide nanosheets-polyethyleneimine decorated with nickel/gold nanoparticles (MnO 2 -PEI/Ni/Au) as nanomotors were added to a vial containing thiolated aptamer KH1C12 solution as a capture aptamer to attach to the gold nanoparticles on the surface of nanomotors covalently. The aptamer-modified self-propelled nanomotors (aptamer KH1C12 /nanomotors) were then separated by placing the vial in a magnetic stand. The aptamer-modified self-propelled nanomotors were rinsed three times with water to remove the non-attached aptamers. Then, the resulting aptamer KH1C12 /nanomotors were applied for the on-the-fly” transporting of HL-60 cancer cell from a human serum sample. To release of the captured HL-60 cancer cells, the complementary nucleotide sequences of KH1C12 aptamer solution (releasing aptamer) that has a with capture aptamer was added to phosphate buffer solution (1 M, pH 7.4) containing HL-60/aptamer KH1C12 /nanomotors. Because of the high affinity of capture aptamer to complementary nucleotide sequences of aptamer KH1C12 , the HL-60 cancer cells released on the surface of aptamer KH1C12 /nanomotors into the solution. The second goal of the present work was determining the concentration of HL-60 cancer cell in the human serum samples. The electrochemical impedance spectroscopy technique (EIS) was used for the determination of HL-60 cancer cell. The concentration of separated cancer cell was determined by aptamer/gold nanoparticles-poly(3,4-ethylene dioxythiophene) modified GC electrode (GC/PEDOT-Au nano /aptamer KH1C12 ). The proposed aptasensor exhibited a good response to the concentration of HL-60 cancer cells in the range of 2.5 × 10 1 to 5 × 10 5 cells mL -1 with a low limit of detection of 250 cells mL -1 . [ABSTRACT FROM AUTHOR]

The authors describe an electrochemical method for aptamer-based determination of insulin at femtomolar concentrations. The surface of a screen printed electrode was modified with ordered mesoporous carbon that was chemically modified with 1,3,6,8-pyrenetetrasulfonate (TPS). The amino-terminated aptamer was then covalently linked to TPS via reactive sulfonyl chloride groups. Subsequently, the redox probe Methylene Blue (MB) was interacted into the aptamer. The MB-modified binds to insulin and this results in the release of MB and a decreased signal as obtained by differential pulse voltammetry, best at a working voltage of -0.3 V (versus silver pseudo-reference electrode). Insulin can be quantified by this method in the 1.0 fM to 10.0 pM concentration range, with a 0.18 fM limit of detection (at 3σ/slope). The assay was applied to the determination of insulin in spiked human serum samples. The method is highly sensitive, selective, stable, and has a wide analytical range. [ABSTRACT FROM AUTHOR]

Herein, for the first time a visible-light-driven photoelectrochemical (PEC) aptasensor for shrimp tropomyosin determination was fabricated by using graphitic carbon nitride (g-C 3 N 4 ) and titanium dioxide (TiO 2 ) as photoactive nanomaterials, ascorbic acid (AA) as electron donor and ruthenium (III) hexaammine (Ru(NH 3 ) 6 3+ ) as signal enhancer. The surface of an ITO electrode was first modified with g-C 3 N 4 , TiO 2 , and polyethyleneimine (PEI) and then the amine terminal aptamer TROP probe was attached to PEI by the use of glutaraldehyde (GA) as cross-linker. After that, Ru(NH 3 ) 6 3+ was adsorbed on aptamer to enhance the photocurrent signal. The principle of proposed PEC aptasensor is based on the formation of a selective complex between tropomyosin and immobilized aptamer TROP probe on the surface of ITO/g-C 3 N 4 -TiO 2 /PEI/aptamer TROP -Ru(NH3) 6 +3 . After the incubation of tropomyosin with TROP aptamer probe, the photocurrent signal decreased due to releasing adsorbed Ru(NH 3 ) 6 3+ on aptamer and preventing AA from scavenging photogenerated holes to the photoactive modified electrode. Under the optimized conditions, the fabricated PEC aptasensor was used for the determination of shrimp tropomyosin in the concentration range of 1–400 ng mL −1 with a limit of detection of 0.23 ng mL −1 . The proposed PEC aptasensor exhibited high selectivity, sensitivity, and good stability. [ABSTRACT FROM AUTHOR]

In this research, we demonstrated a flow injection amperometric sandwich-type aptasensor for the determination of human leukemic lymphoblasts (CCRF-CEM) based on poly(3,4-ethylenedioxythiophene) decorated with gold nanoparticles (PEDOT-Au nano ) as a nano platform to immobilize thiolated sgc8c aptamer and multiwall carbon nanotubes decorated with palladium nanoparticles/3,4,9,10-perylene tetracarboxylic acid (MWCNTs-Pd nano /PTCA) to fabricate catalytic labeled aptamer. In the proposed sensing strategy, the CCRF-CEM cancer cells were sandwiched between immobilized sgc8c aptamer on PEDOT-Au nano modified surface electrode and catalytic labeled sgc8c aptamer (MWCNTs-Pd nano /PTCA/aptamer). After that, the concentration of CCRF-CEM cancer cells was determined in presence of 0.1 mM hydrogen peroxide (H 2 O 2 ) as an electroactive component. The attached MWCNTs-Pd nano nanocomposites to CCRF-CEM cancer cells amplified the electrocatalytic reduction of H 2 O 2 and improved the sensitivity of the sensor to CCRF-CEM cancer cells. The MWCNT-Pd nano nanocomposite was characterized with transmission electron microscopy (TEM) and energy dispersive X-ray (EDX). The electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) were used to confirm the stepwise changes in the electrochemical surface properties of the electrode. The proposed sandwich-type electrochemical aptasensor exhibited an excellent analytical performance for the detection of CCRF-CEM cancer cells ranging from 1.0 × 10 1 to 5.0 × 10 5 cells mL −1 . The limit of detection was 8 cells mL −1 . The proposed aptasensor showed high selectivity toward CCRF-CEM cancer cells. The proposed aptasensor was also applied to the determination of CCRF-CEM cancer cells in human serum samples. [ABSTRACT FROM AUTHOR]

Herein, a flow injection amperometric aptasensor was developed for the determination of adenocarcinoma gastric cell (AGS) cancer cells in presence of hydrogen peroxide (H 2 O 2 ). For this purpose, the aptamer/gold-core and silver-shell (Au@Ag) nanoparticles were synthesized as the secondary labeled aptamers using thiolated cytosine-rich aptamer. First, the thiolated aptamer was self-assembled to the gold nanoparticles (AuNPs) surface through S-AuNPs bonds. Then, this cytosine-rich aptamer/AuNPs were added to the Ag + solution to form (C-Ag + -C) n complexes. The adsorbed Ag + ions on the aptamer were then reduced to Ag shell on the surface of AuNPs core by thyme leaves extract as a green reducing agent. The surface of screen printed electrode (SPE) was also modified with multiwall carbon nanotube decorated with gold nanoparticles (MWCNT-Au nano ) as a nano-platform to increase the surface area to immobilize primary thiolated non-cytosine-rich aptamer and improve electron transfer property of electrode. The MWCNT-Au nano , AuNPs and aptamer AGS -Au@Ag nanoparticles were characterized using transmission electron microscopy (TEM) and energy dispersive X-ray (EDX). Cyclic voltammetry and electrochemical impedance spectroscopy (EIS) were used to confirm the stepwise changes in the electrochemical surface properties of the electrode. The determination processes were performed in a flow injection microchannel device under the optimized conditions. The selective interactions between primary aptamer/AGS/secondary aptamer-Au@Ag nanoparticles led to increase in the response of aptasensor to AGS cancer cell in presence of 0.1 mM H 2 O 2 because of the electrocatalytic activity of Au@Ag nanoparticles toward the reduction of H 2 O 2 . The proposed sandwich-type electrochemical aptasensor exhibited a good response to the logarithmic value of AGS cancer cells in the range of 1 × 10 1 to 5 × 10 5 cells mL −1 with a low limit of detection of 6 cells mL −1 in the flow injection amperometric determination process. The target-aptamer dissociation constant (k d ) was also calculated based on the change in current to be 104 cells mL −1 . The fabricated sandwich-type electrochemical aptasensor was applied for the determination of AGS cancer cell in the human serum sample. The proposed sandwich-type aptasensor exhibited good linear range responsibility, selectivity, and stability. [ABSTRACT FROM AUTHOR]

Here in, a high sensitive sandwich-type electrochemical immunosensor for the determination of SKBR-3 breast cancer cell has been fabricated using of green synthesized reduced graphene oxide as a platform to the immobilization of primary Herceptin antibody (Anti-HCT). The various reduced graphene oxide-tetrasodium 1, 3, 6, 8-pyrenetetrasulfonic acid/metal hexacyanoferrates (rGO-TPA/MHCF nano ) nanocomposites included rGO-TPA/FeHCF, rGO-TPA/CoHCF, rGO-TPA/NiHCF and rGO-TPA/CuHCF were used as electrochemical labels of secondary Herceptine antibody. The obtained result showed that the sensitivity of proposed sandwich-type electrochemical immunosensor for the determination of SKBR-3 breast cancer cells (30,000 cells mL −1 ) using rGO-TPA/FeHCF nano labeled secondary Herceptine antibody was higher than the other rGO-TPA/MHCF nano -labeled secondary Herceptine antibodies. The differential pulse voltammetry (DPV) technique was used for the determination of SKBR-3 breast cancer cell in the concentration range of 500–30,000 cells mL −1 with the limit of detection of 21 cells mL −1 . The proposed sandwich-type electrochemical immunosensor exhibited high selectivity, liner range responsibility and good stability. [ABSTRACT FROM AUTHOR]

Herein, a novel electrochemical bi-aptasensor using green synthesized reduced graphene-poly(amidoamine)/gold nanocomposite (rGO-PAMAM/Au nano ) as supporting matrix for covalent immobilization of flavin adenine dinucleotide (FAD) and thionine (Th) on the first (W 1 ) and second (W 2 ) surfaces of dual working electrode screen printed electrode has proposed. FAD and Th probes were immobilized by glutaraldehyde linker based on a reaction between primary amines (–NH 2 ) of FAD and Th with –NH 2 of rGO-PAMAM/Au nano modified dual working electrode for simultaneous determination of cytochrome c (CYC) and vascular endothelial growth factor (VEGF 165 ) tumor markers. The principle response of proposed bi-aptasensor was based on the selective interaction of CYC with W 1 /rGO-PAMAM-FAD/Au nano /Anti-ptamer CYC and VEGF 165 with W 2 /rGO-PAMAM-Th/Au nano /Anti-ptamer VEGF165 , respectively. This selective interaction, leads to decrease of response currents of immobilized electrochemical probes of FAD and Th that have different formal potential (E 0 ′). Electrochemical behavior of bi-aptasensor was studied by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The liner calibration curve for tumor markers determination was 2.5–320.0 pM. The limit of detections (LOD) for CYC was 1.0 pM and for VEGF 165 was 0.7 pM (3σ/S). The biomarker-aptamer dissociation constant (k d ) was calculated based on the change in current to be 63.9 pM for CYC/Anti-aptamer CYC and 38.4 pM for VEGF 165 /Anti-aptamer VEGF165 , respectively. This bi-aptasensor was used for the determination of VEGF 165 and CYC in the human serum sample. [ABSTRACT FROM AUTHOR]

Purpose: Given increasing efforts in biomedical research utilizing molecular imaging methods, development of dedicated high-performance small-animal SPECT systems has been growing rapidly in the last decade. In the present work, we propose and assess an alternative concept for SPECT imaging enabling desktop open-gantry imaging of small animals. Methods: The system, PERSPECT, consists of an imaging desk, with a set of tilted detector and pinhole collimator placed beneath it. The object to be imaged is simply placed on the desk. Monte Carlo (MC) and analytical simulations were utilized to accurately model and evaluate the proposed concept and design. Furthermore, a dedicated image reconstruction algorithm, finite-aperture-based circular projections (FABCP), was developed and validated for the system, enabling more accurate modeling of the system and higher quality reconstructed images. Image quality was quantified as a function of different tilt angles in the acquisition and number of iterations in the reconstruction algorithm. Furthermore, more complex phantoms including Derenzo, Defrise, and mouse whole body were simulated and studied. Results: The sensitivity of the PERSPECT was 207 cps/MBq. It was quantitatively demonstrated that for a tilt angle of 30°, comparable image qualities were obtained in terms of normalized squared error, contrast, uniformity, noise, and spatial resolution measurements, the latter at ~0.6 mm. Furthermore, quantitative analyses demonstrated that 3 iterations of FABCP image reconstruction (16 subsets/iteration) led to optimally reconstructed images. Conclusions: The PERSPECT, using a novel imaging protocol, can achieve comparable image quality performance in comparison with a conventional pinhole SPECT with the same configuration. The dedicated FABCP algorithm, which was developed for reconstruction of data from the PERSPECT system, can produce high quality images for small-animal imaging via accurate modeling of the system as incorporated in the forward- and back-projection steps. Meanwhile, the developed MC model and the analytical simulator of the system can be applied for further studies on development and evaluation of the system. [ABSTRACT FROM AUTHOR]

A dedicated small-animal SPECT system, HiReSPECT, was designed and developed to provide a high resolution molecular imaging modality in response to growing research demands. HiReSPECT is a dual-head system mounted on a rotating gantry. The detection system is based on pixelated CsI(Na) scintillator crystals coupled to two Hamamatsu H8500 Position Sensitive Photomultiplier Tubes in each head. Also, a high resolution parallel-hole collimator is applied to every head. The dimensions of each head are 50mm×100mm, enabling sufficient transaxial and axial fields-of-view (TFOV and AFOV), respectively, for coverage of the entire mouse in single-bed position imaging. However, a 50mm TFOV is not sufficient for transaxial coverage of rats. To address this, each head can be rotated by 90 degrees in order to align the larger dimension of the heads with the short body axis, allowing tomographic data acquisition for rats. An innovative non-linear recursive filter was used for signal processing/detection. Resolution recovery was also embedded in the modified Maximum-Likelihood Expectation Maximization (MLEM) image reconstruction code to compensate for Collimator-Detector Response (CDR). Moreover, an innovative interpolation algorithm was developed to speed up the reconstruction code. The planar spatial resolution at the head surface and the image spatial resolutions were 1.7mm and 1.2–1.6mm, respectively. The measurements followed by post-processing showed that the observed count rate at 20% count loss is about 42kcps. The system sensitivity at the collimator surface for heads 1 and 2 were 1.32cps/µCi and 1.25cps/µCi, respectively. The corresponding values were 1.18cps/µCi and 1.02cps/µCi at 8cm distance from the collimator surfaces. In addition, whole-body scans of mice demonstrated appropriate imaging capability of the HiReSPECT. [ABSTRACT FROM AUTHOR]

cysteamine (CysAm) nanostructure was generated to act as an intermediate layer between gold electrode and carbon nanotubes. A bare gold electrode was placed in a solution of CysAm to create a self-assembled monolayer on its surface. The modified electrode was then incubated with a solution of multi-walled carbon nanotubes. Cyclic voltammetry and atomic force microscopy were used to characterize the modified electrode. The results indicated that the number of functionalized MWCNTs on the surface of the electrodes increased by enhancing incubation time. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Abstract: This study has investigated different visible-light irradiation''s effect on the formation of silver nanoparticles from silver nitrate using the culture supernatant of Klebsiella pneumonia. Our study shows that visible-light emission can significantly prompt the synthesis of silver nanoparticles. Also, the study experimentally investigated the liquid mixing process effect on silver nanoparticle synthesis by visible-light irradiation. This study successfully synthesized uniformly dispersed silver nanoparticles with a uniform size and shape in the range of 1–6nm with an average size of 3nm. Furthermore, the study investigated the mechanism of the reduction of silver ions by culture supernatant of K. pneumonia, and used X-ray diffraction to characterize silver chloride as an intermediate compound. Silver chloride was prepared synthetically and used as a substrate for the synthesis of silver nanoparticles by culture supernatant of K. pneumonia. The silver nanoparticles have been prepared from silver chloride during this investigation for the first time. [Copyright &y& Elsevier]

Oral contrast is usually administered in most X-ray computed tomography (CT) examinations of the abdomen and the pelvis as it allows more accurate identification of the bowel and facilitates the interpretation of abdominal and pelvic CT studies. However, the misclassification of contrast medium with high-density bone in CT-based attenuation correction (CTAC) is known to generate artifacts in the attenuation map ( μmap), thus resulting in overcorrection for attenuation of positron emission tomography (PET) images. In this study, we developed an automated algorithm for segmentation and classification of regions containing oral contrast medium to correct for artifacts in CT-attenuation-corrected PET images using the segmented contrast correction (SCC) algorithm. The proposed algorithm consists of two steps: first, high CT number object segmentation using combined region- and boundary-based segmentation and second, object classification to bone and contrast agent using a knowledge-based nonlinear fuzzy classifier. Thereafter, the CT numbers of pixels belonging to the region classified as contrast medium are substituted with their equivalent effective bone CT numbers using the SCC algorithm. The generated CT images are then down-sampled followed by Gaussian smoothing to match the resolution of PET images. A piecewise calibration curve was then used to convert CT pixel values to linear attenuation coefficients at 511 keV. The visual assessment of segmented regions performed by an experienced radiologist confirmed the accuracy of the segmentation and classification algorithms for delineation of contrast-enhanced regions in clinical CT images. The quantitative analysis of generated μmaps of 21 clinical CT colonoscopy datasets showed an overestimation ranging between 24.4% and 37.3% in the 3D-classified regions depending on their volume and the concentration of contrast medium. Two PET/CT studies known to be problematic demonstrated the applicability of the technique in clinical setting. More importantly, correction of oral contrast artifacts improved the readability and interpretation of the PET scan and showed substantial decrease of the SUV (104.3%) after correction. An automated segmentation algorithm for classification of irregular shapes of regions containing contrast medium was developed for wider applicability of the SCC algorithm for correction of oral contrast artifacts during the CTAC procedure. The algorithm is being refined and further validated in clinical setting. [ABSTRACT FROM AUTHOR]