Weighted Magnetic Resonance Imaging Research Articles

Development and validation of cardiac diffusion weighted magnetic resonance imaging for the diagnosis of myocardial injury in small animal models

Cardiac diffusion weighted-magnetic resonance imaging (DWI) has slowly developed due to its technical difficulties. However, this limitation could be overcome by advanced techniques, including a stimulated echo technique and a gradient moment nulling technique. This study aimed to develop and validate a high-order DWI sequence, using echo-planar imaging (EPI) and second-order motion-compensated (M012) diffusion gradient applied to cardiac imaging in small-sized animals with fast heart and respiratory rates, and to investigate the feasibility of cardiac DWI, diagnosing acute myocardial injury in isoproterenol-induced myocardial injury rat models. The M012 diffusion gradient sequence was designed for diffusion tensor imaging of the rat myocardium and validated in the polyvinylpyrrolidone phantom. Following sequence optimization, 23 rats with isoproterenol-induced acute myocardial injury and five healthy control rats underwent cardiac MRI, including cine imaging, T1 mapping, and DWI. Diffusion gradient was applied using a 9.4-T MRI scanner (Bruker, BioSpec 94/20, gradient amplitude = 440 mT/m, maximum slew rate = 3440 T/m/s) with double gating (electrocardiogram and respiratory gating). Troponin I was used as a serum biomarker for myocardial injury. Histopathologic examination of the heart was subsequently performed. The developed DWI sequence using EPI and M012 provided the interpretable images of rat hearts. The apparent diffusion coefficient (ADC) values were significantly higher in rats with acute myocardial injury than in the control group (1.847 ± 0.326 * 10–3 mm2/s vs. 1.578 ± 0.144 * 10–3 mm2/s, P < 0.001). Troponin I levels were increased in the blood samples of rats with acute myocardial injury (P < 0.001). Histopathologic examinations detected myocardial damage and subendocardial fibrosis in rats with acute myocardial injury. The newly developed DWI technique has the ability to detect myocardial injury in small animal models, representing high ADC values on the myocardium with isoproterenol-induced injury.

ADSCs labeled with SPIONs tracked in corpus cavernosum of rat and miniature pig by MR imaging and histological examination

Adipose tissue-derived stem cells (ADSCs) have been shown to improve erectile function in animal models of erectile dysfunction. However, few studies have been carried out using a reliable in vivo imaging method to trace transplanted cells in real time, which is necessary for systematic investigation of cell therapy. The study aims to explore the feasibility of non-invasively monitoring intracavernous injection of ADSCs in rat and miniature pig corpus cavernosum using in vivo magnetic resonance (MR) imaging. Thirty-six male Sprague Dawley rats (10 weeks old) and six healthy, sexually mature male miniature pigs (20 kg weight) were obtained. ADSCs were isolated from paratesticular fat of donor rats and cultured. Then ADSCs were labeled with superparamagnetic iron oxide nanoparticles (SPIONs), a type of MR imaging contrast agent, before transplantation into rats and pigs. After intracavernous injection, all rats and pigs underwent and were analyzed by MR imaging at the day of ADSC transplantation and follow-up at 1, 2 and 4 weeks after transplantation. In addition, penile histological examination was performed on all rats and pigs before (n = 6) and at 1 day (n = 6), 1 week (n = 6), 2 weeks (n = 6) or 4 weeks (n = 12) after ADSC transplantation. SPION-labeled ADSCs demonstrated a strong decreased signal intensity compared with distilled water, unlabeled ADSCs or agarose gel. SPION-labeled ADSCs showed a hypointense signal at all concentrations, and the greatest hypointense signal was observed at the concentration of 1 × 106. MR images of the corpus cavernosum showed a hypointense signal located at the injection site. T2*-weighted signal intensity increased over the course of 1 week after ADSCs transplantation, and demonstrated a similar MR signal with that before ADSCs transplantation. After SPION-labeled ADSC injection, T2*-weighted MR imaging clearly demonstrated a marked hypointense signal in pig corpus cavernosum. The T2*-weighted signal faded over time, similar to the MR imaging results in rats. Obvious acute inflammatory exudation was induced by intracavernous injection, and the T2*-weighted signal intensity of these exudation was higher than that of the injection site. The presence of iron was detected by Prussian blue staining, which demonstrated ADSC retention in rat corpus cavernosum. Lack of cellular infiltrations were demonstrated by H&E staining before and 4 weeks after transplantation, which indicated no negative immune response by rats. Prussian blue staining was positive for iron oxide nanoparticles at 2 weeks after transplantation. SPION-labeled ADSCs showed a clear hypointense signal on T2-weight MRI in vitro and in vivo. The MR signal intensity in the corpus cavernosum of the rats and miniature pigs faded and disappeared over time after ADSC transplantation. These findings suggested that MR imaging could trace transplanted ADSCs in the short term in the corpus cavernosum of animals.

The Role of 3 Tesla Diffusion Weighted-Magnetic Resonance Imaging and Apparent Diffusion Coefficient Mapping with Aging and Gendering in Primary Parotid Tumors: Preoperative Foresight of Histopathological Subtypes

The Role of 3 Tesla Diffusion Weighted-Magnetic Resonance Imaging and Apparent Diffusion Coefficient Mapping with Aging and Gendering in Primary Parotid Tumors: Preoperative Foresight of Histopathological Subtypes

Abstract 13412: Updated Meta-Analysis on Safety and Efficacy of Cerebral Embolic Protection Devices Among Patients Undergoing Transcatheter Aortic Valve Replacement

Introduction: Cerebral embolic protection devices (CEP) have been introduced to capture embolic debris and reduce the risk of stroke during Transcatheter Aortic Valve Replacement (TAVR). Available evidence regarding the safety and efficacy of CEP is inconclusive. Therefore, we aimed to determine the safety and efficacy of CEP use during TAVR. Methods: Major electronic databases were searched for the relevant articles with appropriate search terms. All relevant data from 17 studies were extracted into a standardized form. Statistical analyses were performed using Revman 5.4. Odds Ratio (OR) or mean differences (MD) were used to estimate the desired outcome with a 95% confidence interval (CI). Results: A total of 17 studies involving 204,875 patients (15,880 in the CEP arm and 188,995 in the non-CEP arm) were included. No significant difference in 30-day stroke was observed with the use of CEP between the two groups (OR 0.75, 95% CI 0.55 to 1.03). The use of CEP was associated with a lower odds of 30-day mortality by 39% (OR 0.61, 95% CI 0.53 to 0.70). Based on diffusion weighted-magnetic resonance imaging (DW-MRI), there were no differences in the occurrence of new lesions, the total volume of lesions, and the number of new lesions. In addition, the use of CEP in patients undergoing TAVR was associated with a reduction in major or life-threatening bleeding events (OR 0.89, 95% CI 0.81 to 0.98). No differences were observed in the outcomes of acute kidney injury and major vascular complications between both arms. Conclusion: No significant difference in 30-day stroke was observed with the use of CEP in TAVR patients. The use of CEP was associated with significantly lower odds of 30-day mortality and lower rates of major or life-threatening bleeding compared with no CEP in patients undergoing TAVR. Further studies are needed to confirm current findings

Clinical and radiomics prediction of complete response in rectal cancer pre-chemoradiotherapy.

Patients with rectal cancer could avoid major surgery if they achieve clinical complete response (cCR) post neoadjuvant treatment. Therefore, prediction of treatment outcomes before treatment has become necessary to select the best neo-adjuvant treatment option. This study investigates clinical and radiomics variables' ability to predict cCR in patients pre chemoradiotherapy. Using the OnCoRe database, we recruited a matched cohort of 304 patients (152 with cCR; 152 without cCR) deriving training (N=200) and validation (N=104) sets. We collected pre-treatment MR (magnetic resonance) images, demographics and blood parameters (haemoglobin, neutrophil, lymphocyte, alkaline phosphate and albumin). We segmented the gross tumour volume on T2 Weighted MR Images and extracted 1430 stable radiomics features per patient. We used principal component analysis (PCA) and receiver operating characteristic area under the curve (ROC AUC) to reduce dimensionality and evaluate the models produced. Using Logistic regression analysis, PCA-derived combined model (radiomics plus clinical variables) gave a ROC AUC of 0.76 (95% CI: 0.69-0.83) in the training set and 0.68 (95% CI 0.57-0.79) in the validation set. The clinical only model achieved an AUC of 0.73 (95% CI 0.66-0.80) and 0.62 (95% CI 0.51-0.74) in the training and validation set, respectively. The radiomics model had an AUC of 0.68 (95% CI 0.61-0.75) and 0.66 (95% CI 0.56-0.77) in the training and validation sets. The predictive characteristics of both clinical and radiomics variables for clinical complete response remain modest but radiomics predictability is improved with addition of clinical variables.

Duodenum edema due to reduced lymphatic drainage leads to increased inflammation in a porcine endotoxemic model

BackgroundInterventions, such as mechanical ventilation with high positive end-expiratory pressure (PEEP), increase inflammation in abdominal organs. This effect could be due to reduced venous return and impaired splanchnic perfusion, or intestinal edema by reduced lymphatic drainage. However, it is not clear whether abdominal edema per se leads to increased intestinal inflammation when perfusion is normal. The aim of the presented study was to investigate if an impaired thoracic duct function can induce edema of the abdominal organs and if it is associated to increase inflammation when perfusion is maintained normal. In a porcine model, endotoxin was used to induce systemic inflammation. In the Edema group (n = 6) the abdominal portion of the thoracic duct was ligated, while in the Control group (7 animals) it was maintained intact. Half of the animals underwent a diffusion weighted-magnetic resonance imaging (DW-MRI) at the end of the 6-h observation period to determine the abdominal organ perfusion. Edema in abdominal organs was assessed using wet–dry weight and with MRI. Inflammation was assessed by measuring cytokine concentrations in abdominal organs and blood as well as histopathological analysis of the abdominal organs.ResultsOrgan perfusion was similar in both groups, but the Edema group had more intestinal (duodenum) edema, ascites, higher intra-abdominal pressure (IAP) at the end of observation time, and higher cytokine concentration in the small intestine. Systemic cytokines (from blood samples) correlated with IAP.ConclusionsIn this experimental endotoxemic porcine model, the thoracic duct’s ligation enhanced edema formation in the duodenum, and it was associated with increased inflammation.

Poly(4-Styrenesulfonic Acid-co-maleic Anhydride)-Coated NaGdF4:Yb,Tb,Nd Nanoparticles with Luminescence and Magnetic Properties for Imaging of Pancreatic Islets and β-Cells.

Novel Yb,Tb,Nd-doped GdF3 and NaGdF4 nanoparticles were synthesized by a coprecipitation method in ethylene glycol (EG) in the presence of the poly(4-styrenesulfonic acid-co-maleic anhydride) stabilizer. The particle size and morphology, crystal structure, and phase change were controlled by adjusting the PSSMA concentration and source of fluoride anions in the reaction. Doping of Yb3+, Tb3+, and Nd3+ ions in the NaGdF4 host nanoparticles induced luminescence under ultraviolet and near-infrared excitation and high relaxivity in magnetic resonance (MR) imaging (MRI). In vitro toxicity of the nanoparticles and their cellular uptake efficiency were determined in model rat pancreatic β-cells (INS-1E). As the NaGdF4:Yb,Tb,Nd@PSSMA-EG nanoparticles were non-toxic and possessed good luminescence and magnetic properties, they were applicable for in vitro optical and MRI of isolated pancreatic islets in phantoms. The superior contrast was achieved for in vivo T2*-weighted MR images of the islets transplanted under the kidney capsule to mice in preclinical trials.

Design and evaluation of a modular multimodality imaging phantom to simulate heterogeneous uptake and enhancement patterns for radiomic quantification in hybrid imaging: A feasibility study.

BackgroundAccuracy and precision assessment in radiomic features is important for the determination of their potential to characterize cancer lesions. In this regard, simulation of different imaging conditions using specialized phantoms is increasingly being investigated. In this study, the design and evaluation of a modular multimodality imaging phantom to simulate heterogeneous uptake and enhancement patterns for radiomics quantification in hybrid imaging is presented.MethodsA modular multimodality imaging phantom was constructed that could simulate different patterns of heterogeneous uptake and enhancement patterns in positron emission tomography (PET), single‐photon emission computed tomography (SPECT), computed tomography (CT), and magnetic resonance (MR) imaging. The phantom was designed to be used as an insert in the standard NEMA‐NU2 IEC body phantom casing. The entire phantom insert is composed of three segments, each containing three separately fillable compartments. The fillable compartments between segments had different sizes in order to simulate heterogeneous patterns at different spatial scales. The compartments were separately filled with different ratios of 99mTc‐pertechnetate, 18F‐fluorodeoxyglucose ([18F]FDG), iodine‐ and gadolinium‐based contrast agents for SPECT, PET, CT, and T1‐weighted MR imaging respectively. Image acquisition was performed using standard oncological protocols on all modalities and repeated five times for repeatability assessment. A total of 93 radiomic features were calculated. Variability was assessed by determining the coefficient of quartile variation (CQV) of the features. Comparison of feature repeatability at different modalities and spatial scales was performed using Kruskal‐Wallis‐, Mann‐Whitney U‐, one‐way ANOVA‐ and independent t‐tests.ResultsHeterogeneous uptake and enhancement could be simulated on all four imaging modalities. Radiomic features in SPECT were significantly less stable than in all other modalities. Features in PET were significantly less stable than in MR and CT. A total of 20 features, particularly in the gray‐level co‐occurrence matrix (GLCM) and gray‐level run‐length matrix (GLRLM) class, were found to be relatively stable in all four modalities for all three spatial scales of heterogeneous patterns (with CQV < 10%).ConclusionThe phantom was suitable for simulating heterogeneous uptake and enhancement patterns in [18F]FDG‐PET, 99mTc‐SPECT, CT, and T1‐weighted MR images. The results of this work indicate that the phantom might be useful for the further development and optimization of imaging protocols for radiomic quantification in hybrid imaging modalities.

Low muscle volume of the anal sphincter complex: A novel prognostic factor in children with anorectal malformations?

Background/PurposeThe anal sphincter complex (ASC) plays a key role in continence and is often dysfunctional in infants born with anorectal malformations (ARM). The ASC is well depicted by magnetic resonance (MR) imaging but volumetric reference data are lacking in infants. Thus, we tested the feasibility of MR based ASC volumetry, collected reference data, and compared them with cases of favorableprognosis and unfavorable prognosis (as defined by the type of ARM). MethodsWe determined ASC volume on T2 weighted MR images of seventy six infants (ARM n = 33; controls n = 43) by manual segmentation. Inter operator agreement was assessed by intraclass correlation coefficient. Linear regression was used to establish weight dependent reference data. Observed to expected ASC volumes of patients with unfavorable and favorable prognosis were compared (unpaired t test). ResultsASC volumetry was feasible in all cases. Patients with ARM had low ‘observed to expected’ ASC volume ( 18.1%; p = 0.006). ‘Observed to expected’ ASC volume differed significantly between patients with favorableand unfavorable prognosis (p < 0.001). ConclusionWe confirmed the feasibility of MRI based ASC volumetry and provided initial reference data for infants. Although ASC volumes were lowest in infants with ARM of unfavorable prognosis for fecal continence, the value of ASC volume as prognostic parameter remains to be determined.

FDG-PET/CT and MR imaging for target volume delineation in rectal cancer radiotherapy treatment planning: a systematic review

AbstractAim:The aim of this systematic review was to synthesise and summarise evidence surrounding the clinical use of fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT) and magnetic resonance imaging (MRI) for target volume delineation (TVD) in rectal cancer radiotherapy planning.Methods:PubMed, EMBASE, Cochrane library, CINAHL, Web of Science and Scopus databases and other sources were systematically queried using keywords and relevant synonyms. Eligible full-text studies were assessed for methodological quality using the QUADAS-2 tool.Results:Eight of the 1448 studies identified met the inclusion criteria. Findings showed that MRI significantly delineate larger tumour volumes (TVs) than FDG-PET/CT while diffusion-weighted magnetic resonance imaging (DW-MRI) defined smaller gross tumour volumes (GTVs) compared to T2 weighted-Magnetic Resonance Image. CT-based GTVs were found to be larger compared to FDG-PET/CT. FDG-PET/CT also identified new lesions in 15–17% patients and TVs extending outside the routinely used clinical standard CT TV in 29–83% patients. Between observers, delineated volumes were similar and consistent between MRI sequences, whereas interobserver agreement was significantly improved with FDG-PET/CT than CT.Conclusion:FDG-PET/CT and DW-MRI appear to delineate smaller rectal TVs and show improved interobserver variability. Overall, this study provides valuable insights into the amount of attention in the research literature that has been paid to imaging for TVD in rectal cancer.

Correlation of quantitative diffusion weighted MR imaging between benign, malignant chondrogenic and malignant non-chondrogenic bone tumors with histopathologic type

ObjectivesThis study aims to determine the diffusion on weighted imaging which may help in providing characterization of Apparent Diffusion Coefficient (ADC) values in benign, malignant chondrogenic and malignant non-chondrogenic bone tumors. Material and methodsA retrospective study with 84 samples was conducted from October 2017 to December 2019. The samples consisted of 44 males and 40 females; the age range of 10–73 years (mean age of 32.7 years old). A Diffusion-weighted Magnetic Resonance (MR) utilizes a single-shot echo-planar imaging sequence technique with the 3T MR Scanner. We classified the types of tumors into benign, malignant chondrogenic and malignant non-chondrogenic bone tumors. The mean of ADC values from the area with lowest ADC values was selected for statistical analysis. ADC values were compared between benign, malignant chondrogenic and malignant non-chondrogenic bone tumors. Therefore, Receiver Operating Curve (ROC) analysis was done to determine optimal cut-off values. The correlation of ADC values between benign, malignant chondrogenic and malignant non-chondrogenic bone tumor with histopathologic type was also evaluated. ResultsThe mean of ADC values from the area of benign, malignant chondrogenic and malignant non-chondrogenic bone tumor were 1.55 × 10−3 mm2/s, 1.84 × 10−3 mm2/s and 1.12 × 10−3 mm2/s respectively. As a matter of fact, there was a significant difference between benign and malignant bone tumor with cut-off value of 1.15 × 10−3 mm2/s and had a sensitivity of 82%, and a specificity of 92.3%. Moreover, a significant correlation was also found between ADC values with the histopathology type of bone tumors. ConclusionThe ADC values of benign and malignant (chondrogenic and non-chondrogenic groups) bone tumors are different. Thus, the measurement of ADC values improves the accuracy of the diagnosis of bone tumors.

Ultrasound-enhanced precision tumor theranostics using cell membrane-coated and pH-responsive nanoclusters assembled from ultrasmall iron oxide nanoparticles

Design of novel theranostic nanoplatforms integrating precision dynamic imaging modalities, tumor targeting ligands and therapeutic components with enhanced tumor accumulation still remains to be challenging. Here we report a facile strategy to prepare cell membrane (CM)-coated nanoclusters assembled from ultrasmall iron oxide nanoparticles (USIO NPs) with pH-responsiveness as a nanocarrier to load anti-cancer drug doxorubicin (DOX). Citric-stabilized USIO NPs with a size of 3.2 nm were synthesized, modified to have surface amine groups, and crosslinked to obtain pH-responsive nanoclusters (NCs). Then, the formed USIO NCs were loaded with DOX, and coated with cancer CMs to render them with resistance to macrophage cellular uptake and homologous cancer cell targeting specificity. Within the acidic tumor microenvironment, the pH-responsive USIO NCs/DOX@CM with dominant T2 magnetic resonance (MR) imaging performance can be dissociated to form single USIO NPs with T1 MR imaging ability, and simultaneously rapidly release DOX, thereby enabling dynamic T2/T1-weighted MR imaging and chemotherapy of tumors. Further, through the ultrasound-induced sonoporation effect, the dynamic MR imaging and tumor chemotherapy can be further enhanced. The designed USIO NCs/DOX@CM may be developed as a versatile theranostic platform for ultrasound-enhanced targeted precision theranostics of different cancer types.

Ultrasmall Ternary FePtMn Nanocrystals with Acidity-Triggered Dual-Ions Release and Hypoxia Relief for Multimodal Synergistic Chemodynamic/Photodynamic/Photothermal Cancer Therapy.

Multimodal imaging-guided synergistic anticancer strategies have attracted increasing attention for efficient diagnosis and therapy of cancer. Herein, a multifunctional nanotheranostic agent FePtMn-Ce6/FA (FPMCF NPs) is constructed by covalently anchoring photosensitizer chlorin e6 (Ce6) and targeting molecule folic acid (FA) on ultrasmall homogeneous ternary FePtMn nanocrystals. Response to tumor microenvironment (TME), FPMCF NPs can release Fe2+ to catalyze H2 O2 into •OH by Fenton reaction and simultaneously catalyze hydrogen peroxide (H2 O2 ) into O2 to overcome the tumor hypoxia barrier. Released O2 is further catalyzed into 1 O2 under 660 nm laser irradiation with Ce6. Thus, the FPMCF NPs exhibit superior dual-ROS oxidization capability including ferroptosis chemodynamic oxidization and 1 O2 -based photodynamic oxidization. Interestingly, FPMCF NPs reveal strong photothermal conversion efficiency exposed to an 808 nm laser, which can assist dual-ROS oxidization to suppress solid tumor remarkably. Additionally, Mn2+ can be released from FPMCF NPs to enhance longitudinal relaxivity (T1 -weighted magnetic resonance (MR) imaging) and Fe-synergistic transverse relaxivity (T2 -weighted MR imaging), which is convenient for diagnosis of solid tumors. Meanwhile, the fluorescent/photothermal (FL/PT) imaging function of FPMCF NPs can also accurately monitor tumor location. Therefore, FPMCF NPs with multimodal MR/FL/PT imaging-guided synergistic chemodynamic/photodynamic/photothermal cancer therapy capability have potential bioapplication in bionanomedicine field.

Cerebral Embolism After Transcarotid Transcatheter Aortic Valve Replacement: Factors Associated With Ipsilateral Ischemic Burden

Transcarotid transcatheter aortic valve replacement (TAVR) recipients may be exposed to a higher ipsilateral subclinical cerebral ischemic burden compared with the contralateral hemisphere. We sought (1) to compare the cerebral ischemic burden of the 2 hemispheres after transcarotid TAVR, as evaluated by diffusion weighted-magnetic resonance imaging (DW-MRI), and (2) to identify the factors associated with ipsilateral ischemic burden. This prospective study included 52 patients undergoing transcarotid TAVR, followed by a DW-MRI examination. All DW-MRIs were analyzed offline by a radiologist blinded to the clinical data. TAVR was performed through the left (n= 50) or right (n= 2) carotid artery. Procedural success was achieved in all patients, carotid dissection requiring patch closure occurred in 1 patient, and there were no periprocedural stroke events. At least 1 cerebral ischemic lesion was identified in the ipsilateral and contralateral hemisphere in 84.6% and 63.5% of patients, respectively (P= .005), and the number of ischemic lesions per patient was higher in the ipsilateral vs the contralateral hemisphere (2 [interquartile range, 1-5] vs 1 [interquartile range, 0-3], P= .005). The lesion volume (per lesion) and the average lesion volume (per patient) did not differ between the 2 hemispheres. A larger sheath/catheter size (≥18F vs ≤16F) was associated with a higher ipsilateral ischemic burden (P= .026). Carotid artery access for TAVR was associated with a higher number of cerebral ischemic lesions in the ipsilateral (vs contralateral) cerebral hemisphere. The use of a larger sheath/delivery system (≥18F) was associated with an increased ipsilateral ischemic burden.

Natural polymeric nanoparticles as a non-invasive probe for mesenchymal stem cell labelling

Non-invasive tracking of stem cells after transplant is necessary for cell therapy and tissue engineering field. Herein, we introduce natural and biodegradable nanoparticle to develop a highly efficient nanoprobe with the ability to penetrate the stem cell for tracking. Based on the use of (Gd3+) to label stem cells for magnetic resonance imaging (MRI) we synthesized nanoparticle-containing Gd3+. Gd3+ could be used as t 1-weighted MRI contrast agents. In this study, chitosan-alginate nanoparticles were synthesized as a clinical Dotarem® carrier for decreased t 1-weighted. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), and Fourier-transform infrared spectroscopy (FTIR) were utilized for nanoprobe characterization and ICP analysis was performed for Gd3+ concentration measurement. The results illustrate that nanoprobes with spherical shape and with a size of 80 nm without any aggregation were obtained. Relaxivity results suggest that r 1 in the phantom was 12.8 mM−1s−1 per Gd3+ ion, which is 3.5 times larger than that for Dotarem® (r 1 ∼3.6 mM−1s−1 per Gd3+ ion) and this result for synthesized nanoprobe in stem cells 3.56 mM−1s−1 per Gd3+ ion with 2.16 times larger than that for Dotarem® was reported and also enhanced signal in in-vivo imaging was observed. Chitosan-alginate nanoparticles as a novel biocompatible probe for stem cell tracking can be utilized in tissue engineering approach.

Multifunctional imaging of amyloid-beta peptides with a new gadolinium-based contrast agent in Alzheimer’s disease

Multifunctional imaging of the deposition of amyloid-beta (Aβ) aggregates in the brain is of great importance in diagnosing Alzheimer’s disease. Herein, we report a multifunctional Aβ-targeting small-molecular-weight gadolinium (Gd)-based contrast agent (CA), Gd-DO3A-Chal (a new Gd-chelate conjugated with chalcone), that showed 8 times higher binding affinity to Aβ aggregates than a previously reported Gd-chelate conjugated with Pittsburgh compound B. Gd-DO3A-Chal showed multimodal imaging capability. As a new fluorescence imaging probe, Gd-DO3A-Chal showed a good match with immunostained images using 6E10 monoclonal antibodies for the detection of Aβ aggregates in 5XFAD transgenic mouse brain sections. For in vivo magnetic resonance (MR) imaging without blood-brain barrier disruption, longitudinal relaxation time (T1)-weighted MR images after intravenous administration of Gd-DO3A-Chal showed signal enhancement of the Aβ distribution in living 5XFAD transgenic mouse brain. Therefore, in vivo MR images for Aβ detection in addition to fluorescent optical images of Aβ aggregates with high specificity and sensitivity using this new multifunctional Aβ-targeting CA were successfully demonstrated.

Monitoring Physiological Changes in Neutron-Exposed Normal Mouse Brain Using FDG-PET and DW-MRI.

We monitored a physiological response in a neutron-exposed normal mouse brain using two imaging tools, [18F]fluro-deoxy-D-glucose positron emission tomography ([18F]FDG-PET) and diffusion weighted-magnetic resonance imaging (DW-MRI), as an imaging biomarker. We measured the apparent diffusion coefficient (ADC) of DW-MRI and standardized uptake value (SUV) of [18F]FDG-PET, which indicated changes in the cellular environment for neutron irradiation. This approach was sensitive enough to detect cell changes that were not confirmed in hematoxylin and eosin (H&E) results. Glucose transporters (GLUT) 1 and 3, indicators of the GLUT capacity of the brain, were significantly decreased after neutron irradiation, demonstrating that the change in blood-brain-barrier (BBB) permeability affects the GLUT, with changes in both SUV and ADC values. These results demonstrate that combined imaging of the same object can be used as a quantitative indicator for in vivo pathological changes. In particular, the radiation exposure assessment of combined imaging, with specific integrated functions of [18F]FDG-PET and MRI, can be employed repeatedly for noninvasive analysis performed in clinical practice. Additionally, this study demonstrated a novel approach to assess the extent of damage to normal tissues as well as therapeutic effects on tumors.

Preoperative evaluation of histologic grade in invasive breast cancer with T2W-MRI based radiomics signature

To develop and validate a fat-suppressed (T2 weighted-magnetic resonance imaging, T2W-MRI) based radiomics signature to preoperatively evaluate the histologic grade (grade I/II VS. grade III) of invasive breast cancer. Methods: A total of 202 patients with MRI examination and pathologically confirmed invasive breast cancer from June 2011 to February 2017 were retrospectively enrolled. After retrieving fat-suppressed T2W images and tumor segmentation, radiomics features were extracted and valuable features were selected to build a radiomic signature with the least absolute shrinkage and selection operator (LASSO) method. Mann-Whitney U test was used to explore the correlation between radiomics signature and histologic grade. Receiver operating characteristics (ROC) curve was applied to determine the discriminative performance of the radiomics signature [area under curre (AUC), sensitivity, specificity, and accuracy]. An independent validation dataset was used to confirm the discriminatory power of radiomics signature. Results: Eight radiomics features were selected to build a radiomics signature, which showed good performance for preoperatively evaluating histologic grade of invasive breast cancer, with an AUC of 0.802 (95% CI 0.729 to 0.875), sensitivity of 78.7%, specificity of 70.3% and accuracy of 73.7% in training dataset and AUC of 0.812 (95% CI 0.686 to 0.938), sensitivity of 80.0%, specificity of 73.3% and accuracy of 76.0% in the validation dataset. Conclusion: The fat-suppressed T2W-MRI based radiomics signature can be used to preoperatively evaluate the histologic grade of invasive breast cancer, which may assist clinical decision-maker.

Upconversion-mediated ZnFe2O4 nanoplatform for NIR-enhanced chemodynamic and photodynamic therapy.

ZnFe2O4, a semiconductor catalyst with high photocatalytic activity, is ultrasensitive to ultraviolet (UV) light and tumor H2O2 for producing reactive oxygen species (ROS). Thereby, ZnFe2O4 can be used for photodynamic therapy (PDT) from direct electron transfer and the newly defined chemodynamic therapy (CDT) from the Fenton reaction. However, UV light has confined applicability because of its high phototoxicity, low penetration, and speedy attenuation in the biotissue. Herein, an upconversion-mediated nanoplatform with a mesoporous ZnFe2O4 shell was developed for near-infrared (NIR) light enhanced CDT and PDT. The nanoplatform (denoted as Y-UCSZ) was comprised of upconversion nanoparticles (UCNPs), silica shell, and mesoporous ZnFe2O4 shell and was synthesized through a facile hydrothermal method. The UCNPs can efficiently transfer penetrable NIR photons to UV light, which can activate ZnFe2O4 for producing singlet oxygen thus promoting the Fenton reaction for ROS generation. Besides, Y-UCSZ possesses enormous internal space, which is highly beneficial for housing DOX (doxorubicin, a chemotherapeutic agent) to realize chemotherapy. Moreover, the T 2-weighted magnetic resonance imaging (MRI) effect from Fe3+ and Gd3+ ions in combination with the inherent upconversion luminescence (UCL) imaging and computed tomography (CT) from the UCNPs makes an all-in-one diagnosis and treatment system. Importantly, in vitro and in vivo assays authenticated excellent biocompatibility of the PEGylated Y-UCSZ (PEG/Y-UCSZ) and high anticancer effectiveness of the DOX loaded PEG/Y-UCSZ (PEG/Y-UCSZ&DOX), indicating its potential application in the cancer treatment field.

Ultrasensitive magnetic resonance imaging of systemic reactive oxygen species in vivo for early diagnosis of sepsis using activatable nanoprobes.

Current diagnostic methods for sepsis lack required speed or precision, often failing to make timely accurate diagnosis for early medical treatment. The systemic excess generation of reactive oxygen species (ROS) during sepsis has been considered as an early indicator of sepsis. Herein, we present the rational design of novel activatable nanoprobes (ROS CAs) composed of a clinically approved iron oxide core, Gd-DTPA, and hyaluronic acid (HA) that can image ROS down to sub-micromolar concentrations via magnetic resonance imaging (MRI), and use them as sensitive contrast agents for sepsis evaluation. Such a well-defined nanostructure allows them to undergo ROS-triggered degradation and release Gd-DTPA in the presence of ROS, leading to the recovery of the quenched T 1-weighted MRI signal with fast response. With outstanding sensitivity and unlimited tissue penetration depth, ROS CAs are capable of imaging systemic ROS overproduction in mice with early sepsis. Moreover, by using these well-prepared ROS CAs, the severity of the sepsis can be rapidly evaluated by monitoring the systemic ROS levels in vivo. Overall, the present study will not only provide a new strategy to aid in the early diagnosis and risk assessment of sepsis, but also offer valuable insight for the study of sepsis and ROS biology.