Search Results (70)

Background/Objectives: This study aimed to examine the changes in brain metabolites and water molecule diffusion using chemical exchange saturation transfer (CEST) imaging and diffusion-weighted imaging (DWI) after 15 Gy of X-ray irradiation in a rat model of glioma. Methods: The glioma-derived cell line, C6, was implanted into the striatum of the right brain of 7-week-old male Wistar rats. CEST imaging and DWI were performed on days 8, 10, and 17 after implantation using a 7T-magnetic resonance imaging. X-ray irradiation (15 Gy) was performed on day 9. Magnetization transfer ratio (MTR) and apparent diffusion coefficient (ADC) values were calculated for CEST and DWI, respectively. Results: On day 17, the MTR values at 1.2 ppm, 1.5 ppm, 1.8 ppm, 2.1 ppm, and 2.4 ppm in the irradiated group decreased significantly compared with those of the control group. The standard deviation for the ADC values on a pixel-by-pixel basis increased from day 8 to day 17 (0.6 ± 0.06 → 0.8 ± 0.17 (×10⁻³ mm²/s)) in the control group, whereas it remained nearly unchanged (0.6 ± 0.06 → 0.8 ± 0.11 (×10⁻³ mm²/s)) in the irradiated group. Conclusions: This study revealed the effects of 15 Gy X-ray irradiation in a rat model of glioma using CEST imaging and DWI. Full article

Introduction: Sepsis-associated encephalopathy (SAE) is an acute brain dysfunction secondary to systemic infection, occurring without direct central nervous system involvement. Despite its clinical relevance, reliable biomarkers for diagnosing SAE and assessing its severity remain limited. This study aimed to evaluate the feasibility of amide proton transfer-weighted (APTw) chemical exchange saturation transfer (CEST) MRI as a non-invasive molecular imaging technique for detecting metabolic alterations related to neuroinflammation in SAE. Using a lipopolysaccharide (LPS)-induced rat model, we focused on hippocampal changes associated with neuronal inflammation. Materials and Methods: Twenty-one Sprague–Dawley rats (8 weeks old, male) were divided into three groups: control (CTRL, n = 7), LPS-induced sepsis at 5 mg/kg (LPS05, n = 7), and 10 mg/kg (LPS10, n = 7). Sepsis was induced via a single intraperitoneal injection of LPS. APTw imaging was performed using a 7 T preclinical MRI system, and signal quantification in the hippocampus was conducted using the magnetization transfer ratio asymmetry analysis. Results and Discussion: APTw imaging at 7 T demonstrated significantly elevated hippocampal APTw signals in SAE model rats (LPS05 and LPS10) compared to the control (CTRL) group: CTRL (−1.940 ± 0.207%) vs. LPS05 (−0.472 ± 0.485%) (p < 0.001) and CTRL vs. LPS10 (−0.491 ± 0.279%) (p < 0.001). However, no statistically significant difference was observed between the LPS05 and LPS10 groups (p = 0.994). These results suggest that APTw imaging can effectively detect neuroinflammation-related metabolic alterations in the hippocampus. Conclusion: Our findings support the feasibility of APTw CEST imaging as a non-invasive molecular MRI technique for SAE, with potential applications in diagnosis, disease monitoring, and therapeutic evaluation. Full article

Chemical exchange saturation transfer (CEST) MRI is a novel technique that allows for the specific imaging of certain molecules that contain exchangeable protons. Neuroimaging is a major contributor to diagnosing and monitoring infections of the central nervous system (CNS). This review focuses on summarizing the current literature surrounding the use of CEST MRI imaging in diagnosing, monitoring, and treating CNS infections. BacCEST is a new technique to detect bacterial infection in organs at profound levels. This technique allows for the specific pathogen causing the infection to be understood, allowing for tailored antibiotic therapies. The bacCEST signal is also directly proportional to the number of bacterial cells; this means it can be used over periods to track response to treatment via cell numbers. The results show that most of the research in this area has focused on infections of the brain parenchyma (e.g., encephalitis) and that most studies investigate the use of CEST in animal models, with a minority exploring the application of CEST to human participants. The common neuroinfectious disease presentations relevant to clinical medicine are also briefly described, as well as the traditional and modern imaging techniques used to visualize them. Full article

Carbon dots (CDs) are metal-free carbon-based nanoparticles. They possess excellent photoluminescent properties, various physical properties, good chemical stability, high water solubility, high biocompatibility, and tunable surface functionalities, suitable for biomedical applications. Their properties are subject to synthetic conditions such as pH, reaction time, temperature, precursor, and solvent. Until now, a large number of articles on the synthesis and biomedical applications of CDs using their photoluminescent properties have been reported. However, their research on magnetic properties and especially, diamagnetic chemical exchange saturation transfer (diaCEST) in magnetic resonance imaging (MRI) is very poor. The diaCEST MRI contrast agents are based on exchangeable protons of materials with bulk water protons and thus, different from conventional MRI contrast agents, which are based on enhancements of proton spin relaxations of bulk water and tissue. In this review, various syntheses, characterizations, magnetic properties, and potential applications of CDs as diaCEST MRI contrast agents are reviewed. Finally, future perspectives of CDs as the next-generation diaCEST MRI contrast agents are discussed. Full article

Amide Proton Transfer-weighted (APTw) imaging is a molecular MRI technique used to quantify protein concentrations in gliomas, which have heterogeneous components with varying cellularity and metabolic activity. This study aimed to assess the correlation between the component-specific APT signal of the neoplasm and WHO grade, molecular profile and survival status. Sixty-one patients with adult-type diffuse gliomas were retrospectively analyzed. APT values were semi-automatically extracted from tumor solid and, whenever present, necrotic components. APT values were compared between groups stratified by WHO grade, IDH-mutation, MGMT promoter methylation and 1- and 2-year survival status using Wilcoxon rank-sum test, adjusting for multiple comparisons. Overall survival (OS) was analyzed in the subgroup of 48 patients with grade 4 tumors using Cox proportional-hazards models. Random-effects models were used to assess inter-subject heterogeneity of the mean APT values in each tumor component. APT values of the solid component significantly differed between patients with grades 2–3 and 4 tumors (mean 1.58 ± 0.50 vs. 2.04 ± 0.56, p = 0.028) and correlated with OS after 1 year (1.81 ± 0.58 in survivors vs. 2.17 ± 0.51 in deceased patients, p = 0.030). APT values did not differ by IDH-mutation, MGMT methylation, and 2-year survival status. Within grade 4 glioma patients, higher APT kurtosis of the solid component was a negative prognostic factor (hazard ratio = 1.60, p = 0.040). Mean APT values of the necrosis showed high inter-subject variability, although most necrotic tumors were grade 4 and IDH wildtype. In conclusion, APTw imaging in the solid component provided metrics associated with glioma grade and survival status but showed weak correlation with IDH-mutation and MGMT promoter methylation status, in contrast to previous works. Further research is needed to understand APT signal variability within the necrotic component of high-grade gliomas. Full article

Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) is a novel MRI technology to image certain compounds at extremely low concentrations. Long acquisition time to measure signals at a set of offset frequencies of the Z-spectra and to repeat measurements to reduce noise pose significant challenges to its applications. This study explores correlations of CEST MR images along the spatial and Z-spectral dimensions to improve MR image quality and robustness of magnetization transfer ratio (MTR) asymmetry estimation via a joint k-$\omega$ reconstruction model. The model was formulated as an optimization problem with respect to MR images at all frequencies $\omega$, while incorporating regularizations along the spatial and spectral dimensions. The solution was subject to a self-consistency condition that the Z-spectrum of each pixel follows a multi-peak data fitting model corresponding to different CEST pools. The optimization problem was solved using the alternating direction method of multipliers. The proposed joint reconstruction method was evaluated on a simulated CEST MRI phantom and semi-experimentally on choline and iopamidol phantoms with added Gaussian noise of various levels. Results demonstrated that the joint reconstruction method was more tolerable to noise and reduction in number of offset frequencies by improving signal-to-noise ratio (SNR) of the reconstructed images and reducing uncertainty in MTR asymmetry estimation. In the choline and iopamidol phantom cases with 10.5% noise in the measurement data, our method achieved an averaged SNR of 31.0 dB and 32.2 dB compared to the SNR of 24.7 dB and 24.4 dB in the conventional reconstruction approach. It reduced uncertainty of the MTR asymmetry estimation over all regions of interest by 54.4% and 43.7%, from 1.71 and 2.38 to 0.78 and 1.71, respectively. Full article

CEST-MRI is an emerging imaging technique suitable for various in vivo applications, including the quantification of tumor acidosis. Traditionally, CEST contrast is calculated by asymmetry analysis, but the presence of fat signals leads to wrong contrast quantification and hence to inaccurate pH measurements. In this study, we investigated four post-processing approaches to overcome fat signal influences and enable correct CEST contrast calculations and tumor pH measurements using iopamidol. The proposed methods involve replacing the Z-spectrum region affected by fat peaks by (i) using a linear interpolation of the fat frequencies, (ii) applying water pool Lorentzian fitting, (iii) considering only the positive part of the Z-spectrum, or (iv) calculating a correction factor for the ratiometric value. In vitro and in vivo studies demonstrated the possibility of using these approaches to calculate CEST contrast and then to measure tumor pH, even in the presence of moderate to high fat fraction values. However, only the method based on the water pool Lorentzian fitting produced highly accurate results in terms of pH measurement in tumor-bearing mice with low and high fat contents. Full article

Acidosis is an important immunosuppressive mechanism that leads to tumor growth. Therefore, we investigated the neutralization of tumor acidity to improve immunotherapy response. L-DOS47, a new targeted urease immunoconjugate designed to neutralize tumor acidity, has been well tolerated in phase I/IIa trials. L-DOS47 binds to CEACAM6, a cell-surface protein that is highly expressed in gastrointestinal cancers, allowing urease to cleave endogenous urea into two NH4+ and one CO₂, thereby raising local pH. To test the synergetic effect of neutralizing tumor acidity with immunotherapy, we developed a pancreatic orthotopic murine tumor model (KPC961) expressing human CEACAM6. Using chemical exchange saturation transfer–magnetic resonance imaging (CEST-MRI) to measure the tumor extracellular pH (pHe), we confirmed that L-DOS47 raises the tumor pHe from 4 h to 96 h post injection in acidic tumors (average increase of 0.13 units). Additional studies showed that combining L-DOS47 with anti-PD1 significantly increases the efficacy of the anti-PD1 monotherapy, reducing tumor growth for up to 4 weeks. Full article

Chemical exchange saturation transfer with glutamate (GluCEST) imaging is a novel technique for the non-invasive detection and quantification of cerebral Glu levels in neuromolecular processes. Here we used GluCEST imaging and ¹H magnetic resonance spectroscopy (¹H MRS) to assess in vivo changes in Glu signals within the hippocampus in a rat model of depression induced by a forced swim test. The forced swimming test (FST) group exhibited markedly reduced GluCEST-weighted levels and Glu concentrations when examined using ¹H MRS in the hippocampal region compared to the control group (GluCEST-weighted levels: 3.67 ± 0.81% vs. 5.02 ± 0.44%, p < 0.001; and Glu concentrations: 6.560 ± 0.292 μmol/g vs. 7.133 ± 0.397 μmol/g, p = 0.001). Our results indicate that GluCEST imaging is a distinctive approach to detecting and monitoring Glu levels in a rat model of depression. Furthermore, the application of GluCEST imaging may provide a deeper insight into the neurochemical involvement of glutamate in various psychiatric disorders. Full article

Molecular magnetic resonance imaging (MRI) is an emerging field that is set to revolutionize our perspective of disease diagnosis, treatment efficacy monitoring, and precision medicine in full concordance with personalized medicine. A wide range of hyperpolarized (HP) ¹²⁹Xe biosensors have been recently developed, demonstrating their potential applications in molecular settings, and achieving notable success within in vitro studies. The favorable nuclear magnetic resonance properties of ¹²⁹Xe, coupled with its non-toxic nature, high solubility in biological tissues, and capacity to dissolve in blood and diffuse across membranes, highlight its superior role for applications in molecular MRI settings. The incorporation of reporters that combine signal enhancement from both hyperpolarized ¹²⁹Xe and chemical exchange saturation transfer holds the potential to address the primary limitation of low sensitivity observed in conventional MRI. This review provides a summary of the various applications of HP ¹²⁹Xe biosensors developed over the last decade, specifically highlighting their use in MRI. Moreover, this paper addresses the evolution of in vivo applications of HP ¹²⁹Xe, discussing its potential transition into clinical settings. Full article

Treating glioblastoma and monitoring treatment response non-invasively remain challenging. Here, we developed a robust approach using a drug-loaded liposomal hydrogel that is mechanically compatible with the brain, and, simultaneously, we successfully monitored early tumor response using Chemical Exchange Saturation Transfer (CEST) MRI. This CEST-detectable liposomal hydrogel was optimized based on a sustainable drug release and a soft hydrogel for the brain tumor, which is unfavorable for tumor cell proliferation. After injecting the hydrogel next to the tumor, three distinctive CEST contrasts enabled the monitoring of tumor response and drug release longitudinally at 3T. As a result, a continuous tumor volume decrease was observed in the treatment group along with a significant decrease in CEST contrasts relating to the tumor response at 3.5 ppm (Amide Proton Transfer; APT) and at −3.5 ppm (relayed Nuclear Overhauser Effect; rNOE) when compared to the control group (p < 0.05). Interestingly, the molecular change at 3.5 ppm on day 3 (p < 0.05) was found to be prior to the significant decrease in tumor volume on day 5. An APT signal also showed a strong correlation with the number of proliferating cells in the tumors. This demonstrated that APT detected a distinctive decrease in mobile proteins and peptides in tumors before the change in tumor morphology. Moreover, the APT signal showed a regional response to the treatment, associated with proliferating and apoptotic cells, which allowed an in-depth evaluation and prediction of the tumor treatment response. This newly developed liposomal hydrogel allows image-guided brain tumor treatment to address clinical needs using CEST MRI. Full article

Given that cancer mortality is usually due to a late diagnosis, early detection is crucial to improve the patient’s results and prevent cancer-related death. Imaging technology based on novel nanomaterials has attracted much attention for early-stage cancer diagnosis. In this study, a new block copolymer, poly(ethylene glycol)-poly(l-lactide) diblock copolymer (PEG-PLLA), was synthesized by the ring-opening polymerization method and thoroughly characterized using Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance spectroscopy (H-NMR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The obtained PEG-PLLA was used to prepare nanoparticles encapsulated with perfluoropentane and salicylic acid by the emulsion-solvent evaporation method, resulting in a new dual-mode nano-image probe (PEG-PLLA@SA·PFP). The zeta potential and mean diameter of the obtained nanoparticles were measured using dynamic light scattering (DLS) with a Malvern Zetersizer Nano. The in vitro biocompatibility of the PEG-PLLA nanoparticles was evaluated with cell migration, hemolysis, and cytotoxicity assays. Ultrasonic imaging was performed using an ultrasonic imaging apparatus, and chemical exchange saturation transfer (CEST) MRI was conducted on a 7.0 T animal scanner. The results of IR and NMR confirmed that the PEG-PLLA was successfully synthesized. The particle size and negative charge of the nanoparticles were 223.8 ± 2.5 nm and −39.6 ± 1.9 mV, respectively. The polydispersity of the diameter was 0.153 ± 0.020. These nanoparticles possessed good stability at 4 °C for about one month. The results of cytotoxicity, cell migration, and hemolysis assays showed that the carrier material was biocompatible. Finally, PEG-PLLA nanoparticles were able to significantly enhance the imaging effect of tumors by the irradiation of ultrasound and saturation by a radiofrequency pulse, respectively. In conclusion, these nanoparticles exhibit promising dual-mode capabilities for US/CEST MR imaging. Full article

Proton transporters play a key role in maintaining the acidic tumor microenvironment; hence, their inhibition has been proposed as a new therapeutic treatment, although few methods can accurately assess their effect in vivo. In this study, we investigated whether MRI-CEST (Magnetic Resonance Imaging—Chemical Exchange Saturation Transfer) tumor pH imaging can be a useful tool to evaluate in vivo the therapeutic efficacy of several Proton Pump Inhibitors (PPIs) in breast cancer. Cell viability and extracellular pH assays were carried out in breast cancer cells cultured at physiological pH (7.4) or acid-adapted (pH of 6.5 and 6.8) following the exposure to inhibitors of V-ATPase (Lansoprazole, Esomeprazole) or NHE1 (Amiloride, Cariporide) at several concentrations. Next, triple-negative breast cancer 4T1 tumor-bearing mice were treated with Lansoprazole or Amiloride and MRI-CEST tumor pH imaging was utilized to assess the in vivo efficacy. Only Lansoprazole induced, in addition to breast cancer cell toxicity, a significant inhibition of proton extrusion. A significant reduction in tumor volume, prolonged survival, and increase in extracellular tumor pH after 1 and 2 weeks were observed after Lansoprazole treatment, whereas no significant changes were detected upon Amiloride treatment. Our results suggested that MRI-CEST tumor pH imaging can monitor the therapeutic efficacy of PPIs in breast cancer murine models. Full article

Chemical Exchange Saturation Transfer (CEST) magnetic resonance imaging (MRI) provides a novel method for analyzing biomolecule concentrations in tissues without exogenous contrast agents. Despite its potential, achieving a high signal-to-noise ratio (SNR) is imperative for detecting small CEST effects. Traditional metrics such as Magnetization Transfer Ratio Asymmetry (MTR_asym) and Lorentzian analyses are vulnerable to image noise, hampering their precision in quantitative concentration estimations. Recent noise-reduction algorithms like principal component analysis (PCA), nonlocal mean filtering (NLM), and block matching combined with 3D filtering (BM3D) have shown promise, as there is a burgeoning interest in the utilization of neural networks (NNs), particularly autoencoders, for imaging denoising. This study uses the Bloch–McConnell equations, which allow for the synthetic generation of CEST images and explores NNs efficacy in denoising these images. Using synthetically generated phantoms, autoencoders were created, and their performance was compared with traditional denoising methods using various datasets. The results underscored the superior performance of NNs, notably the ResUNet architectures, in noise identification and abatement compared to analytical approaches across a wide noise gamut. This superiority was particularly pronounced at elevated noise intensities in the in vitro data. Notably, the neural architectures significantly improved the PSNR values, achieving up to 35.0, while some traditional methods struggled, especially in low-noise reduction scenarios. However, the application to the in vivo data presented challenges due to varying noise profiles. This study accentuates the potential of NNs as robust denoising tools, but their translation to clinical settings warrants further investigation. Full article

(1) Background: Natalizumab dramatically reduces relapses and MRI inflammatory activity (new lesions and enhancing lesions) in multiple sclerosis (MS). Chemical exchange saturation transfer (CEST) MRI can explore brain tissue in vivo with high resolution and sensitivity. We investigated if natalizumab can prevent microstructural tissue damage progression measured with MRI at ultra-high field (7 Tesla) over the first year of treatment. (2) Methods: In this one-year prospective longitudinal study, patients with active relapsing–remitting MS were assessed clinically and scanned at ultra-high-field MRI at the time of their first natalizumab infusion, at 6 and 12 months, with quantitative imaging aimed to detect microstructural changes in the normal-appearing white matter (NAWM), including sequences sensitive to magnetisation transfer (MT) effects from amide proton transfer (MTRAPT) and the nuclear Overhauser effect (MTRNOE). (3) Results: 12 patients were recruited, and 10 patients completed the study. The difference in the T1 relaxation times at month 6 and month 12 of natalizumab treatment was not significant, suggesting the lack of accumulation of tissue damage, while improvements were seen in MTR (MTRAPT and MTRNOE measures) at month 12, suggesting a tissue repair effect. This paralleled the expected lack of clinical and radiological worsening of conventional MRI measures of disease activity (new lesions or gadolinium-enhancing lesions). (4) Conclusion: Natalizumab prevents microstructural brain damage and has effects suggesting an improved white matter microstructure measured at ultra-high field during the first year of treatment. Full article