An fMRI-based investigation of the effects of odors on the functional connectivity network underlying the working memory.

In the human brain, the regions responsible for emotion processing, motivation, and memory are heavily influenced by olfaction, whose neural pathway is directly exposed to the outer world. In this study, we used fMRI to examine how different olfactory conditions might affect the functional connectivity circuit underlying working memory in the brain. To this end, 30 adults (aged 20-35), 13 males and 17 females, with high educational levels were chosen. Participants were screened for potential olfactory issues before undergoing the Sniffin' sticks test, which was part of the inclusion criteria. Before imaging, each participant was given the required level of training and was then asked to complete four olfactory tests involving pleasant and unpleasant odors, air, and null stimulation. The results of Seed-based analysis suggested a function connection between the inferior parietal region and the left frontal pole region upon olfactory stimulation with vanilla scent in contrast to null stimulation in this comparison, ROI-based analysis revealed an inverse synchronous among the entorhinal cortex, orbitofrontal cortex, and dorsolateral prefrontal cortex (dlPFC). Both dlPFC and hippocampus were involved in olfactory discrimination between two different stimulants. Our findings indicate the presence of inverse correlations between several regions associated with olfaction and working memory, with pleasant scents leaving a stronger impact on the working memory-related areas, particularly the inferior parietal region.

Intra and inter-regional functional connectivity of the human brain due to Task-Evoked fMRI Data classification through CNN & LSTM.

BACKGROUND AND PURPOSE: Olfaction is an early marker of neurodegenerative disease. Standard olfactory function is essential due to the importance of olfaction in human life. The psychophysical evaluation assesses the olfactory function commonly. It is patient-reported, and results rely on the patient's answers and collaboration. However, methodological difficulties attributed to the psychophysical evaluation of olfactory-related cerebral areas led to limited assessment of olfactory function in the human brain. MATERIALS AND METHODS: The current study utilized clustering approaches to assess olfactory function in fMRI data and used brain activity to parcellate the brain with homogeneous properties. Deep neural network architecture based on ResNet convolutional neural networks (CNN) and Long Short-Term Model (LSTM) designed to classify healthy with olfactory disorders subjects. RESULTS: The fMRI result obtained by k-means unsupervised machine learning model was within the expected outcome and similar to those found with the conn toolbox in detecting active areas. There was no significant difference between the means of subjects and every subject. Proposing a CRNN deep learning model to classify fMRI data in two different healthy and with olfactory disorders groups leads to an accuracy score of 97 %. CONCLUSIONS: The K-means unsupervised algorithm can detect the active regions in the brain and analyze olfactory function. Classification results prove the CNN-LSTM architecture using ResNet provides the best accuracy score in olfactory fMRI data. It is the first attempt conducted on olfactory fMRI data in detail until now.

Brain Tumor Segmentation using Hierarchical Combination of Fuzzy Logic and Cellular Automata.

Background: Magnetic resonance (MR) image is one of the most important diagnostic tools for brain tumor detection. Segmentation of glioma tumor region in brain MR images is challenging in medical image processing problems. Precise and reliable segmentation algorithms can be significantly helpful in the diagnosis and treatment planning. Methods: In this article, a novel brain tumor segmentation method is introduced as a postsegmentation module, which uses the primary segmentation method's output as input and makes the segmentation performance values better. This approach is a combination of fuzzy logic and cellular automata (CA). Results: The BraTS online dataset has been used for implementing the proposed method. In the first step, the intensity of each pixel is fed to a fuzzy system to label each pixel, and at the second step, the label of each pixel is fed to a fuzzy CA to make the performance of segmentation better. This step repeated while the performance saturated. The accuracy of the first step was 85.8%, but the accuracy of segmentation after using fuzzy CA was obtained to 99.8%. Conclusion: The practical results have shown that our proposed method could improve the brain tumor segmentation in MR images significantly in comparison with other approaches.

Correction: Synergistic effects of magnetic drug targeting using a newly developed nanocapsule and tumor irradiation by ultrasound on CT26 tumors in BALB/c mice.

Correction for 'Synergistic effects of magnetic drug targeting using a newly developed nanocapsule and tumor irradiation by ultrasound on CT26 tumors in BALB/c mice' by Ali Shakeri-Zadeh et al., J. Mater. Chem. B, 2015, 3, 1879-1887, DOI: 10.1039/C4TB01708K.

The impact of frame numbers on cardiac ECG-gated SPECT images with interpolated extra frames using echocardiography.

Background: Cardiac echocardiography and cardiac ECG-gated single-photon emission computed tomography (SPECT) are the most common modalities for left ventricle (LV) volumes and function assessment. The temporal resolution of SPECT images is limited and an ECG provides better temporal resolution. This study investigates the impact of frame numbers on images in terms of qualitative and quantitative assessments. Methods: In this study, 5 patients underwent echocardiography and cardiac ECG-gated SPECT imaging, and 5 standard views of the LV were recorded to determine LV walls boundaries and volumes. Also, 2 original images with 8 frames and 16 frames per cardiac cycle were recorded simultaneously in a single gantry orbit. Using the data extracted from the LV model, 8 extra new frames were created with interpolation between existing frames of the original 8-frame image. Three series of images (8 and 16 original and 16 interpolated) were reconstructed separately. LV volumes and ejection fraction (EF) were calculated using Quantitative Gated SPECT (QGS) software. Results: Compared to the original 8-frame gating, original 16-frame gated images resulted in larger end-diastole volume (EDV) (mean ± SD: 68.6 ± 27.11 mL vs 66.2±25.41 mL, p<0.001), smaller end-systole volume (ESV) (mean ± SD: 24.6±8.7 mL vs 26±7.3 mL, p<0.001), and higher EF (64% vs 60.2%, p<0.001). The results for the interpolated series were also different from the original images (closer to the original 16-frame series rather than 8-frame). Conclusion: Changing the frame number from 8 to 16 in cardiac ECG-gated SPECT images caused a significant change in LV volumes and EF. Frame interpolation with sophisticated algorithms can be used to improve the temporal resolution of SPECT images.

Liquid Calibration Phantoms in Ultra-Low-Dose QCT for the Assessment of Bone Mineral Density.

INTRODUCTION: Cortical bone is affected by metabolic diseases. Some studies have shown that lower cortical bone mineral density (BMD) is related to increases in fracture risk which could be diagnosed by quantitative computed tomography (QCT). Nowadays, hybrid iterative reconstruction-based (HIR) computed tomography (CT) could be helpful to quantify the peripheral bone tissue. A key focus of this paper is to evaluate liquid calibration phantoms for BMD quantification in the tibia and under hybrid iterative reconstruction-based-CT with the different hydrogen dipotassium phosphate (K2HPO4) concentrations phantoms. METHODOLOGY: Four ranges of concentrations of K2HPO4 were made and tested with 2 exposure settings. Accuracy of the phantoms with ash gravimetry and intermediate K2HPO4 concentration as hypothetical patients were evaluated. The correlations and mean differences between measured equivalent QCT BMD and ash density as a gold standard were calculated. Relative percentage error (RPE) in CT numbers of each concentration over a 6-mo period was reported. RESULTS: The correlation values (R2 was close to 1.0), suggested that the precision of QCT-BMD measurements using standard and ultra-low dose settings were similar for all phantoms. The mean differences between QCT-BMD and the ash density for low concentrations (about 93 mg/cm3) were lower than high concentration phantoms with 135 and 234 mg/cm3 biases. In regard to accuracy test for hypothetical patient, RPE was up to 16.1% for the low concentration (LC) phantom for the case of high mineral content. However, the lowest RPE (0.4 to 1.8%) was obtained for the high concentration (HC) phantom, particularly for the high mineral content case. In addition, over 6 months, the K2HPO4 concentrations increased 25% for 50 mg/cm3 solution and 0.7 % for 1300 mg/cm3 solution in phantoms. CONCLUSION: The excellent linear correlations between the QCT equivalent density and the ash density gold standard indicate that QCT can be used with submilisivert radiation dose. We conclude that using liquid calibration phantoms with a range of mineral content similar to that being measured will minimize bias. Finally, we suggest performing BMD measurements with ultra-low dose scan concurrent with iterative-based reconstruction to reduce radiation exposure.

Design and Validation of Synchronous QCT Calibration Phantom: Practical Methodology.

INTRODUCTION: Quantitative computed tomography (QCT) can supplement dual x-ray absorptiometry by enabling geometric and compartmental bone assessments. Whole-body spiral CT scanners are widely available and require a short scanning time of seconds, in contrast to peripheral QCT scanners, which require several minutes of scanning time. This study designed and evaluated the accuracy and precision of a homemade QCT calibration phantom using a whole-body spiral CT scanner. MATERIALS AND METHODS: The QCT calibration phantom consisted of K2HPO4 solutions as reference. The reference material with various concentrations of 0, 50, 100, 200, 400, 1000, and 1200 mg/cc of K2HPO4 in water were used. For designing the phantom, we used the ABAQUS software. RESULTS: The phantoms were used for performance assessment of QCT method through measurement of accuracy and precision errors, which were generally less than 5.1% for different concentrations. The correlation between CT numbers and concentration were close to one (R2 = 0.99). DISCUSSION: Because whole-body spiral CT scanners allow central bone densitometry, evaluating the accuracy and precision for the easy to use calibration phantom may improve the QCT bone densitometry test. CONCLUSION: This study provides practical directions for applying a homemade calibration phantom for bone mineral density quantification in QCT technique.

CAD system based on B-mode and color Doppler sonographic features may predict if a thyroid nodule is hot or cold.

OBJECTIVES: The aim of this study was to evaluate if the analysis of sonographic parameters could predict if a thyroid nodule was hot or cold. METHODS: Overall, 102 thyroid nodules, including 51 hyperfunctioning (hot) and 51 hypofunctioning (cold) nodules, were evaluated in this study. Twelve sonographic features (i.e., seven B-mode and five Doppler features) were extracted for each nodule type. The isthmus thickness, nodule volume, echogenicity, margin, internal component, microcalcification, and halo sign features were obtained in the B-mode, while the vascularity pattern, resistive index (RI), peak systolic velocity, end diastolic velocity, and peak systolic/end diastolic velocity ratio (SDR) were determined, based on Doppler ultrasounds. All significant features were incorporated in the computer-aided diagnosis (CAD) system to classify hot and cold nodules. RESULTS: Among all sonographic features, only isthmus thickness, nodule volume, echogenicity, RI, and SDR were significantly different between hot and cold nodules. Based on these features in the training dataset, the CAD system could classify hot and cold nodules with an area under the curve (AUC) of 0.898. Also, in the test dataset, hot and cold nodules were classified with an AUC of 0.833. CONCLUSIONS: 2D sonographic features could differentiate hot and cold thyroid nodules. The CAD system showed a great potential to achieve it automatically. KEY POINTS: • Cold nodules represent higher volume (p = 0.005), isthmus thickness (p = 0.035), RI (p = 0.020), and SDR (p = 0.044) and appear hypoechogenic (p = 0.010) in US. • Nodule volume with an AUC of 0.685 and resistive index with an AUC of 0.628 showed the highest classification potential among all B-mode and Doppler features respectively. • The proposed CAD system could distinguish hot nodules from cold ones with an AUC of 0.833 (sensitivity 90.00%, specificity 70.00%, accuracy 80.00%, PPV 87.50%, and NPV 75.00%).

MDCT-QCT, QUS, and DXA in healthy adults: An intermodality comparison.

Background: Cortical deceleration is the main reason for bone loss at peripheral sites. It was suggested that when peripheral bones were assessed for osteoporosis, management and therapy can be administered early. The main aim of this study was to assess the relationships between the central and peripheral measurements at different skeleton bone sites (spine, femur, forearm, tibia, and calcaneus) with available modalities: DXA, QUS, and MDCT-QCT. Methods: The volunteers recruited in this study did not have any history or evidence of metabolic bone disease. Blood test and DXA measurements were used as inclusion criteria to select 40 healthy participants. The selected volunteers underwent 3 imaging modalities: QCT, DXA, and QUS. DXA-based measurements were made on 3 sites, including spine, femur, and forearm. QCT and QUS measurements were done for distal of tibia and calcaneus bones, respectively. The extracted parameters from the 3 modalities were analyzed using a bivariate (Pearson) correlation (r) in statistical software. Results: The results showed moderate to good correlations between spongy bones in central and peripheral sites from all the modalities. However, there was no correlation between MDCT measures and central bone values. According to correlations between different peripheral sits, aBMD of 33% radius and trabecular vBMD in 38% distal tibia showed weak but significant relationship between peripheral bones (r=-0.342, p=0.044). Conclusion: The findings demonstrated how bones in central and peripheral sites were correlated. Multimodality imaging was used in this group of healthy volunteers. Also, it was found that QCT-based MDCT needs more optimization and requires further investigations.

Gold nanoparticle-induced sonosensitization enhances the antitumor activity of ultrasound in colon tumor-bearing mice.

PURPOSE: As a noninvasive and nonionizing radiation, ultrasound can be focused remotely, transferring acoustic energy deep in the body, thereby addressing the penetration depth barrier of the light-based therapies. In cancer therapy, the effectiveness of ultrasound can be enhanced by utilizing nanomaterials that exhibit sonosensitizing properties called as nanosonosensitizers. The gold nanoparticle (AuNP) has been recently presented as a potent nanosonosensitizer with the potential to simultaneously enhance both the thermal and mechanical interactions of ultrasound with the tissue of the human body. Accordingly, this paper attempts to evaluate the in vivo antitumor efficiency of ultrasound in combination with AuNP. METHODS: BALB/c mice-bearing CT26 colorectal tumor model was intraperitoneally injected with AuNPs and then subjected to ultrasound irradiation (1 MHz; 2 W/cm2 ; 10 min) for three sessions. Furthermore, [18 F]FDG (2-deoxy-2-[18 F]fluoro-d-glucose) positron-emission tomography (PET) imaging was performed and the radiomic features from different feature categorizes were extracted to quantify the tumors' phenotype. RESULTS: The tumors were dramatically shrunk and the mice appeared healthy over 21 days of study span without the evidence of relapse. The animals treated with AuNP + ultrasound exhibited an obvious decline in tumor metabolic parameters such as standard uptake value (SUV), total lesion glycolysis (TLG), and metabolic tumor volume (MTV) compared to other treatment groups. CONCLUSION: These findings support the use of AuNP as a potent sonosensitizing agent with the potential to use the thermal and mechanical effects of ultrasound so as to cause damage to the focused tumor site, resulting in an improved antitumor efficacy.

Predictive quantitative sonographic features on classification of hot and cold thyroid nodules.

PURPOSE: This study investigated the potentiality of ultrasound imaging to classify hot and cold thyroid nodules on the basis of textural and morphological analysis. METHODS: In this research, 42 hypo (hot) and 42 hyper-function (cold) thyroid nodules were evaluated through the proposed method of computer aided diagnosis (CAD) system. To discover the difference between hot and cold nodules, 49 sonographic features (9 morphological, 40 textural) were extracted. A support vector machine classifier was utilized for the classification of LNs based on their extracted features. RESULTS: In the training set data, a combination of morphological and textural features represented the best performance with area under the receiver operating characteristic curve (AUC) of 0.992. Upon testing the data set, the proposed model could classify the hot and cold thyroid nodules with an AUC of 0.948. CONCLUSIONS: CAD method based on textural and morphological features is capable of distinguishing between hot from cold nodules via 2-Dimensional sonography. Therefore, it can be used as a supplementary technique in daily clinical practices to improve the radiologists' understanding of conventional ultrasound imaging for nodules characterization.

The Measurement and Mathematical Analysis of 5-Fu Release from Magnetic Polymeric Nanocapsules, following the Application of Ultrasound.

OBJECTIVE: To study the effects of ultrasound irradiation on the release profile of 5-fluorouracil (5-Fu) loaded magnetic poly lactic co-glycolic acid (PLGA) nanocapsules. Also, the controlled drug-release behaviour of the nanocapsules was mathematically investigated. METHODS: The nanocapsules were synthesized, dispersed in phosphate buffered saline (PBS), transferred to a dialysis bag, and finally, irradiated by various ultrasound parameters (1 or 3MHz; 0.3-1W/cm2; 5-10 minutes). The release profile of the irradiated nanocapsules was recorded for 14 days. To find the in vitro drug release mechanism in the absence and presence of various intensities of ultrasound, the obtained data were fitted in various kinetic models for drug release. RESULTS: The results demonstrated that the ultrasound speeded up the rate of drug release from the nanocapsules. The mathematical analysis illustrated that when the ultrasound intensity is increased, the probability of controlled release behaviour of the nanocapsules is raised. We found that drug release from the irradiated nanocapsules follows an erosion-controlled mechanism with the decrease in the velocity of diffusion. CONCLUSION: In conclusion, to attain a controlled drug-delivery strategy in the area of cancer therapy, the drug release profile of the nano-carriers may be well-controlled by ultrasound.

Enhanced DNA Damages of Human Prostate Cancer Cells Induced by Radiofrequency Capacitive Hyperthermia Pre- and Post X-rays: 6 MV versus 15 MV.

OBJECTIVE: This study aimed to determine the effect of 13.56 MHz radiofrequency (RF) capacitive hyperthermia (HT) on radiosensivity of human prostate cancer cells pre and post X-ray radiation treatment (RT). MATERIALS AND METHODS: In this experimental study, the human prostate cancer cell line DU145 was cultured as 300 µm diameter spheroids. We divided the spheroids into group I: control, group II: HT at 43˚C for 30 minutes (HT), group III: 4 Gy irradiation with 6 MV X-ray [RT (6 MV)], group IV: 4 Gy irradiation with 15 MV X-ray [RT (15 MV)], group V: HT+RT (6 MV), group VI: HT+RT (15 MV), group VII: RT (6 MV)+HT, and group VIII: RT (15 MV)+HT. The alkaline comet assay was used to assess DNA damages in terms of tail moment (TM). Thermal enhancement factor (TEF) was obtained for the different treatment combinations. RESULTS: Mean TM increased with increasing photon energy. Group II had significantly greater TM compared to group I. Groups III and IV also had significantly higher TM compared to group I. Significant differences in TM existed between groups V, VII, and III (P<0.05). We observed significant differences in TM between groups VI, VIII, and IV. TEF values demonstrated that enhanced response to radiation was more pronounced in group V compared to the other combined treatments. CONCLUSION: Our results suggest that HT applied before RT leads to higher radiosensivity compared to after RT. HT at 43˚C for 30 minutes added to 6 MV X-ray causes higher enhancement of radiation compared to 15 MV X-ray.

The Role of Radiofrequency Hyperthermia in The Radiosensitization of A Human Prostate Cancer Cell Line.

OBJECTIVE: This study evaluated enhanced induced DNA damages and apoptosis of a spheroid culture of DU145 prostate cancer cells treated by a combination of radiofrequency hyperthermia (RF HT) with radiation treatment (RT) from an external radiotherapy machine compared to RT alone. MATERIALS AND METHODS: In this experimental study, DU145 cells were cultured as spheroids until they reached 300 µm in diameter. We exposed these cultures to either: RF HT for 90 minutes at 43˚C originated from a Celsius TCS system, RF HT followed by RT at doses of 2 Gy or 4 Gy (15 MV energy) with 15-minute interval, or RT alone at the above mentioned doses. The trypan blue exclusion assay, alkaline comet assay, and annexin V/PI flow cytometry were performed to measure cell viability, the amount of DNA damage in an individual cell as the tail moment, and percentage of induced cell apoptosis in response to treatments explained. RESULTS: We calculated the thermal enhancement factor (TEF) for the combined treatment regime. RF HT followed by the 4 Gy dose of RT resulted in minimum viability (85.33 ± 1.30%), the highest tail moment (1.98 ± 0.18), and highest percentage of apoptotic cells (64.48 ± 3.40%) compared to the other treatments. The results of the TEF assay were 2.54 from the comet assay and 2.33 according to flow cytometry. CONCLUSION: The present data suggest that combined treatment of mega voltage X-rays and RF HT can result in significant radiosensitization of prostate cancer cells.

Measurements of nanoparticle-enhanced heating from 1MHz ultrasound in solution and in mice bearing CT26 colon tumors.

Hyperthermia is considered as a new approach for cancer therapy. Non-selectivity of tissue heating in conventional hyperthermia methods results in collateral damages to healthy tissues and this is the greatest obstacle against hyperthermia in clinic. Herein, to promote the efficiency of conventional hyperthermia methods, nanoparticle-enhanced heating from 1MHz ultrasound was investigated in vitro and in vivo. The experiments were conducted on two mediums; (1) various colloidal nano-solutions (in vitro section) and (2) CT26 mouse colon carcinoma tumor loaded by various nanoparticles (in vivo section). Experiments in this study were designed to evaluate and compare the sonosensitizing potentials of gold nanoparticles (AuNPs), iron oxide nanoparticles (IONPs), and nano-graphene oxide (NGO) in enhancement of ultrasound-induced heat generation. The temperature profile of the solutions and the animal tumors containing nanoparticles were recorded during sonication. An increased heating rate during sonication was observed for both in vitro and in vivo mediums when the nanoparticles were present. Our in vitro experiments revealed that percentages of increases in temperature elevation rates were 12.5%, 20.4%, and 37.5% for IONPs, NGO, and AuNPs, respectively. Compared to the nanoparticles-free tumors, direct injection of AuNPs, NGO and IONPs into the tumors and subsequent sonication for 10min caused an increased temperature elevation rate of 37.5%, 24.1% and 16.1%, respectively. AuNPs, IONPs and NGO are proposed as ultrasound responsive nanomaterials with the potential of focusing the energy of acoustic waves on the tumor and inducing localized hyperthermia.

Combination of ultrasound and newly synthesized magnetic nanocapsules affects the temperature profile of CT26 tumors in BALB/c mice.

PURPOSE: To investigate the effects of a combination of 3-MHz ultrasound waves with a new magnetic nanocapsule containing 5-fluorouracil (5-Fu) on the temperature profile of a mouse colon tumor (CT26) in BALB/c mice. METHODS: Firstly, 5-Fu-loaded magnetic nanocapsules were synthesized using a multiple emulsion solvent evaporation procedure. Magnetic resonance imaging (MRI) was performed to evaluate the efficiency of nanocapsule localization in the tumor during magnetic drug targeting (MDT). Tumors were separately exposed to 3-MHz ultrasound waves at the intensities of 0.1, 0.3, 0.5, and 1 W/cm(2) for 10 min in the absence and presence of nanocapsules. The temperature of the tumor was recorded at 1-min intervals. RESULTS: The effective diameter of the nanocapsules was approximately 70 nm, and it was demonstrated that magnetic nanoparticles were well dispersed inside the nanocapsules. MRI confirmed that the magnetic nanocapsules were successfully targeted to the tumor after accomplishing MDT. Temperature change due to sonication of the tumor was strongly intensity dependent. Moreover, temperature-time curves revealed that the magnetic nanocapsules significantly affected the temperature rise profile of a sonicated tumor. CONCLUSION: Data presented in this study would be helpful to develop an ultrasound-mediated MDT procedure so that temperature changes of the tumor and its surrounding normal tissues may be controllable.

Synergistic effects of magnetic drug targeting using a newly developed nanocapsule and tumor irradiation by ultrasound on CT26 tumors in BALB/c mice.

The aim of the current study was to magnetically target the 5-fluorouracil (5-Fu) loaded magnetic poly lactic-co-glycolic acid (PLGA) nanocapsules towards CT26 colon tumor model in BALB/c mice. In addition, we ultrasonicated the tumors impregnated by nanocapsules with the goal of aiding them in magnetic drug targeting (MDT) procedure. Newly synthesized 5-Fu-loaded PLGA magnetic nanocapsules were characterized. Various treatment modalities with the use of nanocapsules, magnetic fields, and ultrasound were applied to the tumors and appropriate controls were considered. Magnetic resonance imaging (MRI) and Prussian blue (PB) staining were performed to analyze the distribution of nanocapsules within the CT26 tumor. Finally, anti-tumor and pro-apoptotic effects of each treatment modality on CT26 tumors were investigated. The effective diameter of nanocapsules was approximately 70 nm. The histological staining of the tumor tissue with PB as well as MRI revealed a broad distribution of magnetic nanocapsules within the tumor and confirmed the targeting of nanocapsules to the tumors. Anti-tumor studies demonstrated that the combination of nanocapsules-MDT-ultrasound effectively inhibits the growth of CT26 tumors compared with injection of 5-Fu alone (P < 0.01). The present study exhibits potentials of the newly synthesized magnetic nanocapsule and suggests that the combination of MDT and ultrasound might help this new nanotechnology-based cancer chemotherapy agent in vivo.

A new magnetic nanocapsule containing 5-fluorouracil: in vivo drug release, anti-tumor, and pro-apoptotic effects on CT26 cells allograft model.

The purpose of this study was to create an optimized method for preparation of 5-fluorouracil-loaded magnetic poly lactic-co-glycolic acid nanocapsules and to investigate its potential as multifunctional carriers to deliver therapeutic agents for tumor-targeted therapies. The in vitro release of the newly synthesized 5-fluorouracil-loaded poly lactic-co-glycolic acid magnetic nanocapsules was investigated in phosphate-buffered saline medium using the dialysis method. In vivo release studies of the magnetic nanocapsules were performed in rabbits. Finally, the targeting properties, anti-tumor, and pro-apoptotic effects of this new magnetic nanocapsule on CT26 cells allograft model were studied. The effective diameter of nanocapsules was 67.2 nm. In vivo release investigations showed that 5-fluorouracil has a sustained release profile, prolonged lifetime in the rabbit plasma, and increased tissue appetency when loaded into the magnetic nanocapsule. Magnetic resonance imaging confirmed that the magnetic nanocapsules were successfully targeted to the tumor. Additionally, the anti-tumor studies revealed that the targeted therapy with magnetic nanocapsules containing 5-fluorouracil effectively inhibits the growth of tumors compared with 5-fluorouracil alone (P < 0.01). The present study demonstrates that this new magnetic nanocapsule can be considered a new nanotechnology-based cancer chemotherapy agent in vivo.

Derivation of attenuation map for attenuation correction of PET data in the presence of nanoparticulate contrast agents using spectral CT imaging.

OBJECTIVE: Uptake value in quantitative PET imaging is biased due to the presence of CT contrast agents when using CT-based attenuation correction. Our aim was to examine spectral CT imaging to suppress inaccuracy of 511 keV attenuation map in the presence of multiple nanoparticulate contrast agents. METHODS: Using a simulation study we examined an image-based K-edge ratio method, in which two images acquired from energy windows located above and below the K-edge energy are divided by one another, to identify the exact location of all contrast agents. Multiple computerized phantom studies were conducted using a variety of NP contrast agents with different concentrations. The performance of the proposed methodology was compared to conventional single-kVp and dual-kVp methods using wide range of contrast agents with varying concentrations. RESULTS: The results demonstrate that both single-kVp and dual-kVp energy mapping approaches produce inaccurate attenuation maps at 511 keV in the presence of multiple simultaneous contrast agents. In contrast, the proposed method is capable of handling multiple simultaneous contrast agents, thus allowing suppression of 511 keV attenuation map inaccuracy. CONCLUSION: Attenuation map produced by spectral CT clearly outperforms conventional single-kVp and dual-kVp approaches in the generation of accurate attenuation maps in the presence of multiple contrast agents.

Optimizing a novel method for low intensity ultrasound in chondrogenesis induction.

BACKGROUND: Hyaline cartilage tissue of joints is susceptible to injuries due to avascularity. Mesenchymal stem cells (MSCs) are used for cartilage tissue engineering. Among MSCs, adipose stem cells (ASCs) are attractive because of accessibility, their large number, and rapid growth. Common in vitro protocols successfully induce chondrogenic differentiation by expression of multiple cartilage-specific molecules. However, transforming growth factor ß (TGFß) promotes chondrogenesis to terminal stages. Despite much attention being given to the influences of biochemical factors on chondrogenesis of MSCs, few studies have examined the chondrogenic effect of mechanical factors such as ultrasound as a feasible tool. MATERIALS AND METHODS: In this study, we focused on inducing chondrogenesis in the early stages of differentiation by using low-intensity ultrasound (LIUS). Four groups of ASC pellets (control, ultrasound, TGFß, and ultrasound/TGF) were cultured under chondrogenic (10 ng/ml of TGFß3) and ultrasound conditions (200 mW/cm(2), 10 min/day). After 2 weeks, differentiation was evaluated by histology, quantitative gene expression analysis, and immunohistochemistry. RESULTS: Our data demonstrated that ultrasound differentiated pellets showed increased expression of early chondrogenesis marker, Col2A, than those in TGFß groups (P < 0.001), and Col2B and Col10 expression were more prominent in TGFß groups. Immunostaining of sections showed Col2 fibrils around lacuna in LIUS and TGFß treated groups. CONCLUSION: Using LIUS resulted in early chondrogenesis in comparison with terminally differentiated chondrocytes by TGFß. Therefore, LIUS might provide an applicable, safe, efficient, and cheap tool for chondrogenic differentiation of ASCs in cartilage tissue engineering.