Precise diagnosis and effective treatment of gliomas still remain a huge challenge. Photoacoustic-guided photothermal therapy (PTT) has unique advantages over conventional techniques for brain tumor ...theranostics, but existing nanoagents for photoacoustic imaging (PAI)-guided PTT are mainly organic small molecules or inorganic nanoparticles, which have the limitations of poor photostability and biocompatibility. Besides, the restricted absorption in the first near-infrared window (NIR-I) of the most existing nanoagents compromises their effectiveness for deep tissue PAI and PTT. We herein develop novel semiconducting polymer nanoparticles (SPNs) that are strongly absorptive in the second NIR window (NIR-II) to alleviate these problems. With the merits of excellent photoacoustic and photothermal performance, high photostability, proper size, and low toxicity, SPNs not only show efficient cellular uptake for PAI and PTT toward U87 glioma cells but also demonstrate effective accumulation in both subcutaneous tumors and brain tumors upon intravenous injection, thereby realizing efficient PAI-guided PTT toward gliomas under NIR-II light irradiation.
Phosphocreatine (PCr) plays a vital role in neuron and myocyte energy homeostasis. Currently, there are no routine diagnostic tests to noninvasively map PCr distribution with clinically relevant ...spatial resolution and scan time. Here, we demonstrate that artificial neural network-based chemical exchange saturation transfer (ANNCEST) can be used to rapidly quantify PCr concentration with robust immunity to commonly seen MRI interferences. High-quality PCr mapping of human skeletal muscle, as well as the information of exchange rate, magnetic field and radio-frequency transmission inhomogeneities, can be obtained within 1.5 min on a 3 T standard MRI scanner using ANNCEST. For further validation, we apply ANNCEST to measure the PCr concentrations in exercised skeletal muscle. The ANNCEST outcomes strongly correlate with those from
P magnetic resonance spectroscopy (R = 0.813, p < 0.001, t test). These results suggest that ANNCEST has potential as a cost-effective and widely available method for measuring PCr and diagnosing related diseases.
The goal of this study was to develop a molecular biomarker for the detection of protein aggregation involved in Alzheimer's disease (AD) by exploiting the features of the water saturation transfer ...spectrum (Z-spectrum), the CEST signal of which is sensitive to the molecular configuration of proteins. A radial-sampling steady-state sequence based ultrashort echo time (UTE) readout was implemented to image the Z-spectrum in the mouse brain, especially the contributions from mobile proteins at the frequency offsets for the composite protein amide proton (+3.6 ppm) and aliphatic proton (−3.6 ppm) signals. Using a relatively weak radiofrequency (RF) saturation amplitude, contributions due to strong magnetization transfer contrast (MTC) from solid-like macromolecules and direct water saturation (DS) were minimized. For practical measure of the changes in the mobile protein configuration, we defined a saturation transfer difference (ΔST) by subtracting the Z-spectral signals at ±3.6 ppm from a control signal at 8 ppm. Phantom studies of glutamate solution, protein (egg white) and hair conditioner show the capability of the proposed scheme to minimize the contributions from amine protons, DS, and MTC, respectively. The ST signal at ±3.6 ppm of the cross-linked bovine serum albumin (BSA) solutions demonstrated that the ΔST signal can be used to monitor the aggregation process of the mobile proteins. High-resolution ΔST images of AD mouse brains at ±3.6 ppm of mouse brains showed significantly reduced ΔST (-3.6) signal compared to the age-matched wild-type (WT) mice. Thus, this signal has potential to serve as a molecular biomarker for monitoring protein aggregation in AD.
•A low-B1 radial-sampling steady-state MRI acquisition scheme was developed to acquire high-resolution saturation transfer difference (ΔST) maps.•Low B1 was used to focus on the chemical exchange saturation transfer from mobile proteins and minimize the direct water saturation and the magnetization transfer effects in tissue.•ΔST maps at offset frequencies of ±3.6 ppm from water reflected changes in protein aggregation, providing a novel imaging biomarker.•Detection of protein aggregation associated with Alzheimer's disease using a mouse model by a UTE-CEST sequence.
Purpose
To examine the detection sensitivity for the rapidly exchanging hydroxyl protons of D‐glucose using the recently developed on‐resonance variable delay multi‐pulse (onVDMP) chemical exchange ...saturation transfer (CEST) technique.
Methods
The onVDMP method was applied for the detection of water signal changes upon venous D‐glucose infusion in mice with 9L glioma xenografts. The effect size of onVDMP MRI during infusion was compared with that of conventional continuous wave (CW) CEST MRI.
Results
Both methods highlighted the tumor and the blood vessels on D‐glucose infusion. In interleaved studies, the mean signal changes detected by onVDMP were found to be 1.8 times higher than those by CW‐CEST, attributed to its high labeling efficiency for fast exchanging protons and the labeling of the OH protons over a larger frequency range.
Conclusions
The onVDMP method is a more sensitive technique for the detection of exogenous CEST agents with fast‐exchanging protons compared to CW‐CEST MRI.
Biocompatible nanomaterials and hydrogels have become an important tool for improving cell-based therapies by promoting cell survival and protecting cell transplants from immune rejection. Although ...their potential benefit has been widely evaluated, at present it is not possible to determine, in vivo, if and how long cells remain viable following their administration without the use of a reporter gene. Here, we report a pH-nanosensor-based magnetic resonance imaging (MRI) technique that can monitor cell death in vivo non-invasively. We demonstrate that specific MRI parameters that change on cell death of microencapsulated hepatocytes are associated with the measured bioluminescence imaging radiance. Moreover, the readout from this pH-sensitive nanosensor can be directly co-registered with high-resolution anatomical images. All of the components of these nanosensors are clinical grade and hence this approach should be a translatable and universal modification of hydrogels.
Purpose
To develop a steady‐state saturation with radial readout chemical exchange saturation transfer (starCEST) for acquiring CEST images at 3 Tesla (T). The polynomial Lorentzian line‐shape ...fitting approach was further developed for extracting amideCEST intensities at this field.
Method
StarCEST MRI using periodically rotated overlapping parallel lines with enhanced reconstruction‐based spatial sampling was implemented to acquire Z‐spectra that are robust to brain motion. Multi‐linear singular value decomposition postprocessing was applied to enhance the CEST SNR. The egg white phantom studies were performed at 3T to reveal the contributions to the 3.5 ppm CEST signal. Based on the phantom validation, the amideCEST peak was quantified using the polynomial Lorentzian line‐shape fitting, which exploits the inverse relationship between Z‐spectral intensity and the longitudinal relaxation rate in the rotating frame. The 3D turbo spin echo CEST was also performed to compare with the starCEST method.
Results
The amideCEST peak showed a negligible peak B1 dependence between 1.2 µT and 2.4 µT. The amideCEST images acquired with starCEST showed much improved image quality, SNR, and motion robustness compared to the conventional 3D turbo spin echo CEST method with the same scan time. The amideCEST contrast extracted by the polynomial Lorentzian line‐shape fitting method trended toward a stronger gray matter signal (1.32% ± 0.30%) than white matter (0.92% ± 0.08%; P = .02, n = 5). When calculating the magnetization transfer contrast and T1‐corrected rotating frame relaxation rate maps, amideCEST again was not significantly different for white matter and gray matter.
Conclusion
Rapid multi‐slice amideCEST mapping can be achieved by the starCEST method (< 5 min) at 3T by combing with the polynomial Lorentzian line‐shape fitting method.
Roles of Cytokines in Alzheimer’s Disease Chen, Zilin; Balachandran, Yekkuni L; Chong, Wai Po ...
International journal of molecular sciences,
06/2024, Volume:
25, Issue:
11
Journal Article
Peer reviewed
Open access
The neuroimmune system is a collection of immune cells, cytokines, and the glymphatic system that plays a pivotal role in the pathogenesis and progression of Alzheimer’s disease (AD). Of particular ...focus are cytokines, a group of immune signaling molecules that facilitate communication among immune cells and contribute to inflammation in AD. Extensive research has shown that the dysregulated secretion of certain cytokines (IL-1β, IL-17, IL-12, IL-23, IL-6, and TNF-α) promotes neuroinflammation and exacerbates neuronal damage in AD. However, anti-inflammatory cytokines (IL-2, IL-3, IL-33, and IL-35) are also secreted during AD onset and progression, thereby preventing neuroinflammation. This review summarizes the involvement of pro- and anti-inflammatory cytokines in AD pathology and discusses their therapeutic potential.
PDF
