MRI Contrast Research Articles

Up-converting β-NaY0.8[Yb0.18Er0.02]F4 nanoparticles coated by superparamagnetic γ-Fe2O3 nanosatellites: elaboration, characterization and in vitro cytotoxicity.

Current biomedical imaging techniques are vital for the diagnosis of various diseases. They are related to the development of multimodal probes encompassing all the functionalities required for comprehensive imaging. In this context, we applied a simple and reproducible wet synthesis route to produce such probes. This method allowed us to prepare about 100 nm sized lanthanide-doped yttrium fluoride nanoparticles β-NaY0.8[Yb0.18Er0.02]F4, coated with about 10 nm sized iron oxide γ-Fe2O3 nanocrystals. By this way, the built granular hetero-nanostructures combine desirable up-converting photoluminescence (the core) and superparamagnetic properties (the satellites), enabling dual optical and magnetic resonance imaging applications. Through citrate ligand grafting, the designed core-satellite particles formed stable aqueous colloids, which are valuable for biomedical applications. Optical spectroscopy and confocal microscopy revealed their capability for sustained visible light emission (predominantly green) upon near-infrared excitation (980 nm). Additionally, based on XTT assays, when incubated for 24 hours with mammalian healthy or cancer cells, even at doses as high as 0.1 mg mL-1 (milligrams of particles), they did not induce significant cytotoxicity. The measured body temperature magnetization of the engineered nanoconstructs was found to be about 10 emu g-1 (grams of particles) at 1.5 T, which is high enough to use them as positive or negative contrast magnetic resonance agents in the clinic, as confirmed by relaxometry measurements in Milli-Q water. This result underscores their promising biomedical utility as bimodal probes for optical and magnetic imaging.

Cyclodextrin-conjugated low-molecular-weight polyethyleneimine as a macromolecular contrast agent for tumor-targeted magnetic resonance imaging.

Macromolecular contrast agents (CAs) usually possess excellent contrast ability and tumor-targeting ability in comparison with small-molecule CAs, especially for early tumor detection. Herein, cyclodextrin-conjugated low-molecular-weight polyethyleneimine was synthesized as a macromolecular backbone. Afterward, a linear polymer with adamantane terminal and Gd chelates was synthesized, followed by conjugating with the backbone via host-guest interaction. Finally, folic acid was conjugated onto the as-prepared CAs through bioorthogonal chemistry, which endowed the CAs with the capability to accumulate into the tumor region. Compared to Magnevist (r1 = 4.25 mM-1 s-1) used in clinic, the PC/Ad-PEG2000-PLL(DTPA-Gd)-FA exhibited higher longitudinal relaxivity (r1 = 11.62 mM-1 s-1) with excellent biocompatibility. Furthermore, in vivo experiments demonstrated that PC/Ad-PEG2000-PLL(DTPA-Gd)-FA could effectively accumulate in the tumor region and produce a brighter image than that of Magnevist. The H&E staining and metabolic data further illustrated that this CA possessed excellent biocompatibility in vivo. Finally, these results above suggest that this macromolecular CA could be a potential candidate as a MRI CA for tumor-targeted diagnosis.

Ion carrier modulated MRI contrast.

An ion-responsive MRI contrast agent based on a POPC liposomal scaffold is generated that displays a large amplitude relaxivity switch. Entrapment of MR active Gd-DOTA within cholesterol-doped, i.e., membrane rigidified, liposomes dampens the MR response through diminished water exchange across the lipid bilayer. Relaxivity is re-established by integration of ion carriers in the liposome membrane to mediate solvated ion flux.

A Targeted Multi-Crystalline Manganese Oxide as a Tumor-Selective Nano-Sized MRI Contrast Agent for Early and Accurate Diagnosis of Tumors.

Magnetic resonance imaging (MRI) is an important tool for the accurate diagnosis of malignant tumors in clinical settings. However, the lack of tumor-specific MRI contrast agents limits diagnostic accuracy. Herein, we developed αvintegrin receptor-targeting multi-crystalline manganese oxide (MCMO) as a novel MRI contrast agent for accurate diagnosis of tumors by coupling iRGD cyclopeptide PEGylation polymer onto the surface of MCMO (iRGD-pMCMO). The MCMO consisted of numerous small crystals and exhibited an oval structure of 200 nm in size. The iRGD-pMCMO actively recognizes tumor cells and effectively accumulates at the tumor site, consequently releasing abundant Mn2+ ions in a weakly acidic and high-GSH-expressing tumor microenvironment. Subsequently, Mn2+ ions interact with cellular GSH to form Mn-GSH chelates, enabling efficient T1-weighted MR contrast imaging. In vivo experiments indicated that iRGD-pMCMO significantly improved T1-weighted images, achieving an accurate diagnosis of subcutaneous and orthotopic tumors. The results verified that the T1 contrast effect of iRGD-pMCMO was closely associated with the expression of GSH in tumor cells. Altogether, the novel tumor-targeting, highly sensitive MRI contrast agent developed in this study can improve the accuracy of MRI for tumor diagnosis.

Safety of Administering Intravenous CT Contrast Agents Repeatedly or Using Both CT and MRI Contrast Agents on the Same Day: An Animal Study.

To investigate molecular and functional consequences of additional exposures to iodine- or gadolinium-based contrast agents within 24 hours from the initial intravenous administration of iodine-based contrast agents through an animal study. Fifty-six Sprague-Dawley male rats were equally divided into eight groups: negative control, positive control (PC) with single-dose administration of CT contrast agent, and additional administration of either CT or MR contrast agents 2, 4, or 24 hours from initial CT contrast agent injection. A 12 µL/g of iodinated contrast agent or a 0.47 µL/g of gadolinium-based contrast agent were injected into the tail vein. Serum levels of blood urea nitrogen, creatinine, cystatin C (Cys C), and malondialdehyde (MDA) were measured. mRNA and protein levels of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) were evaluated. Levels of serum creatinine (SCr) were significantly higher in repeated CT contrast agent injection groups than in PC (0.21 ± 0.02 mg/dL for PC; 0.40 ± 0.02, 0.34 ± 0.03, and 0.41 ± 0.10 mg/dL for 2-, 4-, and 24-hour interval groups, respectively; P < 0.001). There was no significant difference in the average Cys C and MDA levels between PC and repeated CT contrast agent injection groups (Cys C, P = 0.256-0.362; MDA, P > 0.99). Additional doses of MR contrast agent did not make significant changes compared to PC in SCr (P > 0.99), Cys C (P = 0.262), and MDA (P = 0.139-0.771) levels. mRNA and protein levels of KIM-1 and NGAL were not significantly different among additional CT or MR contrast agent groups (P > 0.05). A sufficient time interval, probably more than 24 hours, between repeated contrast-enhanced CT examinations may be necessary to avoid deterioration in renal function. However, conducting contrast-enhanced MRI on the same day as contrast-enhanced CT may not induce clinically significant kidney injury.

Four-dimensional flow MRI for quantitative assessment of cerebrospinal fluid dynamics: Status and opportunities.

Neurological disorders can manifest with altered neurofluid dynamics in different compartments of the central nervous system. These include alterations in cerebral blood flow, cerebrospinal fluid (CSF) flow, and tissue biomechanics. Noninvasive quantitative assessment of neurofluid flow and tissue motion is feasible with phase contrast magnetic resonance imaging (PC MRI). While two-dimensional (2D) PC MRI is routinely utilized in research and clinical settings to assess flow dynamics through a single imaging slice, comprehensive neurofluid dynamic assessment can be limited or impractical. Recently, four-dimensional (4D) flow MRI (or time-resolved three-dimensional PC with three-directional velocity encoding) has emerged as a powerful extension of 2D PC, allowing for large volumetric coverage of fluid velocities at high spatiotemporal resolution within clinically reasonable scan times. Yet, most 4D flow studies have focused on blood flow imaging. Characterizing CSF flow dynamics with 4D flow (i.e., 4D CSF flow) is of high interest to understand normal brain and spine physiology, but also to study neurological disorders such as dysfunctional brain metabolite waste clearance, where CSF dynamics appear to play an important role. However, 4D CSF flow imaging is challenged by the long T1 time of CSF and slower velocities compared with blood flow, which can result in longer scan times from low flip angles and extended motion-sensitive gradients, hindering clinical adoption. In this work, we review the state of 4D CSF flow MRI including challenges, novel solutions from current research and ongoing needs, examples of clinical and research applications, and discuss an outlook on the future of 4D CSF flow.

Corrections for Rabi oscillations in cardiac chemical exchange saturation transfer MRI under the influence of very short preparation pulses.

Very short chemical exchange saturation transfer (CEST) pulses are beneficial in cardiac continuous wave (cw) CEST MRI, especially in small animals because of their rapid heartbeat; however, they result in signal modulations caused by Rabi oscillations. Therefore, we implemented two different filter techniques, DOwnsampling by SEparation of CEST spectrum into two parts (DOSE) and time domain (TD)-based filtering, to correct for these signal corruptions, allowing a reliable quantification of glucose-weighted CEST (glucoCEST) MRI contrast. In our study, cw CEST measurements were performed on a 9.4-T small animal BioSpec system using CEST pulses in the range of 10 to 200 ms. Experimental dependencies of Rabi oscillations on key MRI parameters were validated by Bloch-McConnell (BM) simulations. Filter efficiency was explored in a glucose concentration series as well as in the myocardium of healthy mice (n = 8), and glucoCEST contrast was subsequently quantified. The experimental results showed that the impact of Rabi oscillations on CEST spectra increased with decreasing CEST pulse length, optimized B0 homogeneity, and shorter T2 relaxation time, in accordance with results from BM simulations. Both investigated filter techniques reduced these signal modulations significantly, with DOSE filtering preserving the amplitude and TD filtering the spectral information of CEST data more accurately. Upon filter application, a significant decrease in glucoCEST contrast in the myocardium of healthy mice was observed after glucose infusion (pTD = 0.0079, pDOSE = 0.0044). To conclude, this study offers comprehensive experimental insights into Rabi oscillations within CEST MRI data along with methodological considerations that could be further advanced into a robust and precise cardiac cw CEST protocol by integrating DOSE and TD filtering into the standard CEST analysis pipeline.

Shaped Magnetogel Microparticles for Multispectral Magnetic Resonance Contrast and Sensing.

Multispectral magnetic resonance imaging (MRI) contrast agents are microfabricated three-dimensional magnetic structures that encode nearby water protons with discrete frequencies. The agents have a unique radiofrequency (RF) resonance that can be tuned by engineering the geometric parameters of these microstructures. Multispectral contrast agents can be used as sensors by incorporating a stimulus-driven shape-changing response into their structure. These geometrically encoded magnetic sensors (GEMS) enable MRI-based sensing via environmentally induced changes to their geometry and their corresponding RF resonance. Previously, GEMS have been made using thin-film lithography techniques in a cleanroom environment. While these approaches offer precise control of the microstructure, they can be a limitation for researchers who do not have cleanroom access or microfabrication expertise. Here, an alternative approach for GEMS fabrication based on soft lithography is introduced. The fabrication scheme uses cheap, accessible materials and simple chemistry to produce shaped magnetic hydrogel microparticles with multispectral MRI contrast properties. The microparticles can be used as sensors by fabricating them out of shape-reconfigurable, "smart" hydrogels. The change in shape causes a corresponding shift in the resonance of the GEMS, producing an MRI-addressable readout of the microenvironment. Proof-of-principle experiments showing a multispectral response to pH change with cylindrical shell-shaped magnetogel GEMS are presented.

Non-invasive differentiation of hepatic steatosis and steatohepatitis in a mouse model using nitroxyl radical as an MRI-contrast agent

Drug-induced steatohepatitis is considered more serious than drug-induced hepatic steatosis, so that differentiating between the two is crucial in drug development. In addition, early detection of drug-induced steatohepatitis is considered important since recovery is possible with drug withdrawal. However, no method has been established to differentiate between the two. In the development of drug-induced steatohepatitis, reactive oxygen species (ROS) is excessively generated in the liver. It has been reported that ROS can be monitored with electron spin resonance (ESR) and dynamic nuclear polarization-magnetic resonance imaging (DNP-MRI) by using nitroxyl radicals, which are known to participate in various in vivo redox reactions. The decay/reduction rate, which is an index for monitoring nitroxyl radicals, has been reported to be increased in tissues with excessive ROS levels other than liver, but decreased in methionine choline deficient (MCD) diet-induced steatohepatitis with excess ROS. Therefore, looking to differentiate between drug-induced hepatic steatosis and steatohepatitis, we examined whether the reduction rate decreases in steatohepatitis other than the MCD-diet induced disease and whether the decrease could be detected by MRI. We used STAM™ mice in which hepatic steatosis and steatohepatitis developed sequentially under diabetic conditions. 3-carbamoyl-PROXYL (CmP), one of the nitroxyl radicals, was injected intravenously during the MRI procedure and the reduction rate was calculated. The reduction rate was significantly higher in early steatohepatitis than in hepatic steatosis and the control. Excess ROS in early steatohepatitis was detected by an immunohistochemical marker for ROS. Therefore, it was indicated that the increase or decrease in the reduction rate in steatohepatitis differs depending on the model, and early steatohepatitis could be noninvasively differentiated from hepatic steatosis using CmP in MRI. Since the change in direction of the reduction rate in steatohepatitis in clinical studies could be predicted by confirming the reduction rate in preclinical studies, the present method, which can be used consistently in clinical and preclinical studies, warrants consideration as a candidate monitoring method for differentiating between early drug-induced steatohepatitis and hepatic steatosis in drug development.

Epidural Spinal Cord Compression by an Abscess from a Dumbbell Extension of a Non-Osseous Soft Tissue Paravertebral Hydatid Cyst in the Dorsal Region

Background and objectives: Human being may become infested with Echinococcus granulosus, as an intermediate host, ending with the formation of hydatid cyst. Hydatidosis, affecting various parts of human body and should be considered in the differential diagnosis of any cystic mass lesion. Osseous Hydatid cyst is rare; however, it involves the spinal column in half of the cases. In the current study, the epidural hydatid cyst had presented with spinal cord compression due to the formation of an epidural abscess formation. Methods: A young adult housewife lady who had been affected by the parasite, primary paravertebral hydatid cyst, between the seventh and ninth dorsal vertebral levels, presented with spinal cord compression due to epidural abscess lesion. Ultrasound, the contrast magnetic resonance, and computed tomography imaging are standard tests in the diagnostic work-up of the lesion and follow-up of the patient. Appropriate dorsal laminectomy, removal of the hydatid cyst, and the inflammatory epidural cystic compressing tissues were done. Results: Operative intervention had resulted in a dramatic improvement in the patient's condition and reversal of her neurological deficit back to normal; the paravertebral ectocyst size had eventually shrunken and there was no recurrence. The excised tissues that were compressing the dorsal spinal cord proved, Histopathologically, to be inflammatory in its microscopical appearance. Conclusions: Hydatid cyst epidural dumbbell extension may rupture and lead to the formation of an abscess, giving enhancement on contrast magnetic resonance and computed tomography scan studies. To our knowledge, this is the first case to be reported in the literature specifying spinal cord compression by an epidural abscess formation from a paraspinal dumbbell extension of hydatid cyst.

Locus coeruleus MRI contrast is associated with Complement factor C3b in cerebrospinal fluid

AbstractBackgroundDegeneration of the Locus coeruleus (LC) is associated with Alzheimer’s disease (AD) pathology and cognitive decline. Recent evidence from animal models indicates that this relationship may be mediated by neuroinflammation. Here we examined how LC MRI contrast is related to CSF biomarkers of neuroinflammation in humans.MethodThe LC as well as the Substantia nigra (SN) were visualized and segmented using neuromelanin‐sensitive T1‐weighted FLASH‐MRI images acquired at 3T and MRI contrast values were calculated as previously described (Betts et al., 2019b). A cohort of 65 participants with MRI contrast and CSF data from the DZNE longitudinal cognitive impairment and dementia (DELCODE) study (20 HC, 22 SCD, 16 MCI, 7 AD dementia; 53.8% female) were included in the analyses. We performed correlational analyses to test for associations between LC and SN contrast with a panel of 4 Principal Components (PC) created from a Principial Component Analysis on 16 individual inflammation‐related CSF biomarkers (Fig. 1). Both bivariate and partial correlation analyses were performed between PCs and MRI contrast values using sex, age, site and CSF levels of AD pathology, namely Aß42/40‐ratio and phosphorylated tau, as covariates (see Fig. 2).ResultWe found a significant positive association between LC MRI contrast and the inflammatory component PC4 including the proinflammatory complement factors C3 and C3b across the entire sample (r = 0.365, p = 0.003). Additional post‐hoc correlational analyses showed this association with LC MRI contrast was mainly due to a correlation with C3b (r = 0.349, p = 0.004). A significant positive association was still observed (r = 0.347, p = 0.008) in a subgroup of individuals comprising healthy older adults and individuals with a risk of AD dementia (HC, SCD and MCI) as shown in Fig. 2. In contrast, no significant associations between SN MRI contrast and any neurodegenerative or inflammatory measure were observed indicating effects were specific to the LC.ConclusionThe results demonstrate LC MRI contrast is associated with complement factors in CSF, in particular complement factor C3b in healthy older adults and individuals with a risk of AD dementia. Further analyses are required to determine if elevated complement factors may predict degeneration of the LC and subsequent cognitive decline.

Gd-doped Cerium Oxide Nanoparticles as a New MRI Contrast Agent: Analysis of Properties and Biocompatibility

Gd-doped Cerium Oxide Nanoparticles as a New MRI Contrast Agent: Analysis of Properties and Biocompatibility

Magnet-responsive choline carbomer ionogels as a versatile and recyclable catalyst for one-pot synthesis of benzopyran in water

Ionogels are gaining popularity as a potential replacement for volatile organic solvents in various processes, such as catalysts, electrochemistry, spectroscopy, and medicinal chemistry, due to their low toxicity, high thermal stability, and good solubility. Magnet-responsive ion gels with high magnetic susceptibility are promising and can be used as catalysts, sensors, and MRI contrast agents. Herein, we fabricated simple and novel magnet choline carbomer ionogels using a precipitation-deposition method with carbomers and choline hydroxide. The morphology and structure of the resulting ionogels were analyzed using various characterization techniques, including FTIR, EDX, TGA, and SEM spectroscopy. These magnet ionogels were effective catalysts for a one-pot, three-component synthesis of benzopyran derivatives, providing mild reaction conditions, environmental friendliness, and good to excellent (78–96%) yields within a short reaction time (1–2 h). Additionally, the magnet ionogels were easily recyclable, and they could be reused up to five times without catalytic deactivation.

MRI of Neuroinflammation Using a Folate Receptor β‐Targeted Nanoparticle Contrast Agent

AbstractBackgroundNeuroinflammation plays an important role in Alzheimer’s disease (AD) pathogenesis and disease progression leading to cognitive decline. Current efforts for non‐invasive imaging of neuroinflammation are based on using PET radiotracers. An MRI‐based contrast agent for imaging of neuroinflammation would be highly desirable due to widespread use of MRI in imaging of neurological disorders. Folate receptor β, a marker of pro‐inflammatory phenotype, is expressed in microglia. In this work, we investigated a folate‐targeted liposomal‐Gd contrast agent for molecular MRI of neuroinflammation in mouse models of AD.Method In vivo studies were performed in APP/PSEN1 mice, a model of amyloid pathology, and P301S mice, a model of tau pathology. Transgenic mice and wild‐type (WT) littermates (n = 6/genotype, 24 total) underwent pre‐contrast MRI using T1‐weighted spin echo sequences with 160 µm in‐plane resolution and 1.2 mm slice thickness. Delayed MRI was performed 4 days after systemic administration of a high T1 relaxivity liposomal‐Gd contrast agent bearing folic acid molecules. Animals were euthanized after the final imaging session for microscopic analysis of brain. Signal changes between pre‐contrast and post‐contrast MRI were determined in target regions of the brain.ResultTransgenic APP/PSEN1 and P301S mice demonstrated signal enhancement in post‐contrast T1w‐MRI compared to pre‐contrast MRI. In comparison, WT control mice did not show signal enhancement in post‐contrast MRI. APP/PSEN1 transgenic mice exhibited greater relative enhancement (+5.9%, p&lt;0.005) and lower inter‐subject variance than P301S mice (3.9%, p&lt;0.05). Immunofluorescence analysis demonstrated higher burden of activated microglia in brains of transgenic mice compared to WT control mice.ConclusionA folate receptor β‐targeted liposomal‐Gd contrast agent enables in vivo MRI of neuroinflammation in mouse models of Alzheimer’s disease. Such imaging agents could play an important role in monitoring of Alzheimer’s disease progression leading to cognitive decline and evaluation of therapies that target neuroinflammation.

Evaluation of locus coeruleus changes during aging by post‐mortem brain MRI contrast

AbstractBackgroundNeuropathological studies have pointed to the importance of neurodegeneration in the locus coeruleus (LC) as a possible early biomarker of Alzheimer’s Disease (AD). The aim of this study is to explore a non‐invasive MRI technique to evaluate normal and pathological changes in the LC during aging.MethodsSubjects were recruited from our Capital’s Death Verification Service. After obtaining written consent from family members, 24 individuals (55‐94 yrs) were submitted for post‐mortem brain in situ MRI with a 7T scanner. Post‐mortem interval ranged from 7 to 20 hours and body temperature varied from 14.8°C to 26°C. MRI protocol included acquisition of multi‐echo gradient‐echo axial images with 2 mm thickness and 0.4 mm in‐plane resolution. LC signal intensity was evaluated from a single gradient‐echo image presenting the brightest signal for the LC. In the same slice normalized values for the left and right LC were quantified (LNV and RNV) by selecting a ROI on the brightest spot of the LC (one‐pixel sized) and dividing it by the signal intensity measured in the left and right pons, respectively (ROI of approx. 50mm2) (Figure1). Subject’s Clinical Dementia Rating (CDR) was obtained by interviewing a close family member. A two‐tailed paired t‐test was performed between the RNV and the LNV, and dependence with age was analyzed by Pearson correlation.ResultsCDR was 0 (n = 17); 0,5 (n = 2); 1 (n = 1), 2 (n = 1), and 3 (n = 3). LNV was higher than RNV (t(23) = 3.9; p&lt; 0.001 (Figure2). The mean of LNV and RNV (MNV) was higher in individuals with CDR = 0 than in subjects with CDR &gt;0, but subjects with CDR&gt;0 were also significantly elder, and there was a significant effect of age on the MNV (r = ‐ 0,49, p = 0,015), Figure 3.ConclusionMRI LC contrast was able to depict LC changes as a function of age, whereby subjects with symptons seemed to present lower LC intensity. The left LC was consistently brighter than the right LC endorsing results observed in other studies (Betts et al.2019 https://doi.org/10.1016/j.dadm.2019.02.001). Future histopathological analysis will help to elucidate the origin for this signal difference.

Evaluation of the MRI contrast of locus coeruleus in patients with neurodegenerative diseases

Evaluation of the MRI contrast of locus coeruleus in patients with neurodegenerative diseases

Advanced cerebrospinal fluid flow MRI findings of aqueductal stenosis caused by web.

The aqueductal web (AW) is one of the causes of aqueductus stenosis (AS). Recent advances in Magnetic resonance (MR) imaging have enabled us to better reveal the cerebrospinal fluid (CSF) flow dynamics and aqueductal anatomy. The aim of this study is to evaluate the CSF flow dynamics of patients with AW with phase contrast Magnetic resonance imaging (MRI) and compare them with the imaging findings. We evaluated 23 patients under 65-year-old age. On constructive interference in steady-state (T2 CISS) images, the width of prepontine cistern (PPC) and the width of Sylvian aqueduct (SA) were measured. Localization and number of webs were evaluated. The existence of flow at the aqueduct and the presence of spontaneous third ventriculostomy (STV) were evaluated on sagittal Sampling Perfection with Application optimized Contrast (SPACE) sequences. Of the 23 patients included in the study, 11 were male and 12 were female. The mean age was 34.02 (0.5-64). A total of 31 AWs were detected in 23 patients. Six of 23 patients (26.1%) had STV and 17 of those not. Four of 23 patients (17.4%) had aqueductal flow on SPACE sequences. The PPC distance was significantly wider in patients with STV (median: 6.7-4.5, interquartile range (IQR): 1.35, p = 0.004). In the cases where artifact secondary to flow is observed in SPACE sequences in aqueduct, the Evan index (EI) was significantly lower (median: 0.2955-0.3900, IQR: 0.03-0.14, p < 0.001). In patients with a low EI, there may be flow in the SA even if there is a web. In patients with a wide PPC distance, it is necessary to consider the presence of STV and evaluate the presence of flow with the SPACE sequences.

AIEgens Cross‐linked Iron Oxide Nanoparticles Synchronously Amplify Bimodal Imaging Signals in Situ by Tumor Acidity‐Mediated Click Reaction

AbstractActivatable dual‐modal molecular imaging probes present a promising tool for the diagnosis of malignant tumors. However, synchronously enhancing dual‐modal imaging signals under a single stimulus is challenging. Herein, we propose an activatable bimodal probe that integrates aggregation‐induced emission luminogens (AIEgens) and iron oxide nanoparticles (IOs) to synergistically enhance near‐infrared fluorescence (NIRF) intensity and magnetic resonance (MR) contrast through a tumor acidity‐mediated click reaction. Tumor acidity‐responsive IOs containing dibenzocyclooctyne groups (termed cDIOs) and AIEgens containing azide groups (termed AATs) can be covalently cross‐linked in response to tumor acidity, which leads to a simultaneous enhancement in NIRF intensity (≈12.4‐fold) and r2 relaxivity (≈2.8‐fold). cDIOs and AATs were effectively activated in mice orthotropic breast tumor, and the cross‐linking prolonged their retention in tumor, further augmenting the bimodal signals and expanding imaging time frame. This facile strategy leverages the inherent properties of probes themselves and demonstrates promise in future translational studies.

AIEgens Cross-linked Iron Oxide Nanoparticles Synchronously Amplify Bimodal Imaging Signals in Situ by Tumor Acidity-Mediated Click Reaction.

Activatable dual-modal molecular imaging probes present a promising tool for the diagnosis of malignant tumors. However, synchronously enhancing dual-modal imaging signals under a single stimulus is challenging. Herein, we propose an activatable bimodal probe that integrates aggregation-induced emission luminogens (AIEgens) and iron oxide nanoparticles (IOs) to synergistically enhance near-infrared fluorescence (NIRF) intensity and magnetic resonance (MR) contrast through a tumor acidity-mediated click reaction. Tumor acidity-responsive IOs containing dibenzocyclooctyne groups (termed cDIOs) and AIEgens containing azide groups (termed AATs) can be covalently cross-linked in response to tumor acidity, which leads to a simultaneous enhancement in NIRF intensity (≈12.4-fold) and r2 relaxivity (≈2.8-fold). cDIOs and AATs were effectively activated in mice orthotropic breast tumor, and the cross-linking prolonged their retention in tumor, further augmenting the bimodal signals and expanding imaging time frame. This facile strategy leverages the inherent properties of probes themselves and demonstrates promise in future translational studies.

Evaluation of Dynamic Contrast-Enhanced and Oxygen-Enhanced Functional Lung Magnetic Resonance Imaging in Chronic Obstructive Pulmonary Disease Patients

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory condition characterized by obstruction of airways and emphysematous lung tissue damage, with associated hypoxic vasoconstriction in the affected lung parenchyma. In our study, we evaluate the role of oxygen-enhanced (OE) MRI and dynamic contrast enhanced (DCE)-MRI in COPD patients for assessment of ventilation and perfusion defects and compared their severity with clinical severity. A total of 60 patients with COPD (diagnosed based on clinical and spirometry findings) and 2 controls with normal spirometry and no history of COPD were enrolled. All patients underwent MRI within 1 month of spirometry. OE-MRI was performed by administering oxygen at 12 L/min for 4 min to look for ventilation defects. DCE-MRI was performed by injecting intravenous gadolinium contrast, and perfusion abnormalities were detected by subtracting the non-enhanced areas from the first pass perfusion contrast images. A total of 87% of the subjects demonstrated ventilation and perfusion abnormalities on MRI independently. The lobe-wise distribution of ventilation and perfusion abnormalities correlated well with each other and was statistically significant in all lobes (p &lt; 0.05). The severity of ventilation-perfusion defects also correlated well with clinical severity, as their median value (calculated using a Likert rating scale) was significantly lower in patients in the Global initiative for chronic Obstructive Lung Disease (GOLD) I/II group (3.25) compared to the GOLD III/IV group (7.25). OE- and DCE-MRI provide functional information about ventilation-perfusion defects and their regional distribution, which correlates well with clinical severity in patients with COPD.