Chemical Exchange Saturation Transfer Imaging Research Articles

Relationship between multi-pool model-based chemical exchange saturation transfer imaging, intravoxel incoherent motion MRI, and 11C-methionine uptake on PET/CT in patients with gliomas

PurposeMagnetization transfer ratio asymmetry (MTRasym) analysis is used for chemical exchange saturation transfer (CEST) in patients with gliomas; however, this approach has limitations. CEST imaging using a multi-pool model (MPM) may allow a more detailed assessment of gliomas; however, its mechanism remains unknown. This study aimed to assess the relationship between CEST imaging by MPM, intravoxel incoherent motion (IVIM), and 11C-methionine (11C-MET) uptake on positron emission tomography/computed tomography (PET/CT) to clarify the clinical significance of CEST imaging using MPM in gliomas. MethodsThis retrospective study included 17 patients with gliomas who underwent 11C-MET PET/CT at our institution between January 2020 and January 2022. Two-dimensional axial CEST imaging was conducted using single-shot fast-spin echo acquisition at 3 T. The apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient (D*), f, MTRasym (3.5 ppm), parameters of MPM-based CEST imaging, and tumor-to-contralateral normal brain tissue (T/N) ratio were calculated using a region-of-interest analysis. Shapiro–Wilk test, weighted kappa coefficient, and Spearman's rank correlation coefficients were used for statistical analysis. ResultsSignificant correlations were found between APT_T1 and T/N ratio (ρ = 0.87, p < 0.001), APT_T2 and T/N ratio (ρ = 0.47, p < 0.05), MTRasym and T/N ratio (ρ = 0.55, p < 0.01), and T2/T1 and T/N ratio (ρ = −0.36, p < 0.05). Furthermore, significant correlations were observed between APT_T1 and ADC (ρ = −0.67, p < 0.001), APT_T1 and D (ρ = −0.70, p < 0.001), APT_T2 and D* (ρ = −0.45, p < 0.05), and T2/T1 and D (ρ = 0.39, p < 0.05). ConclusionThese preliminary findings indicate that MPM-based CEST imaging parameters correlate with IVIM and 11C-MET uptake on PET/CT in patients with gliomas. In particular, the new parameter APT_T1 correlated more strongly with 11C-MET uptake compared to the traditional CEST parameter MTRasym.

Amide proton transfer-weighted imaging with a short acquisition time based on a self B0 correction using the turbo spin echo-Dixon method: A phantom study

PurposeConventional amide proton transfer (APT)-weighted imaging requires a chemical exchange saturation transfer (CEST) sequence with multiple saturation frequency offsets and a B0 correction sequence, plus a long acquisition time that can be reduced by applying the conventional method using CEST images with seven radiation pulses (i.e., the seven-points method). For a further reduction of acquisition times, we propose fast two-dimensional (2D) APT-weighted imaging based on a self B0 correction using the turbo spin echo (TSE)-Dixon method. We conducted a phantom study to investigate the accuracy of TSE-Dixon APT-weighted imaging. MethodsWe prepared two types of phantoms with six samples for a concentrationdependent evaluation and a pH-dependent evaluation. APT-weighted images were acquired by the conventional, seven-points, and TSE-Dixon methods. Linear regression analyses assessed the dependence between each method's APT signal intensities (SIs) and the concentration or pH. We performed a one-way analysis of variance with Tukey's honestly significant difference post hoc test to compare the APT SIs among the three methods. The agreement of the APT SIs between the conventional and seven-points or TSE-Dixon methods was assessed by a Bland- Altman plot analysis. ResultsThe APT SIs of all three acquisition methods showed positive concentration dependence and pH dependence. No significant differences were observed in the APT SIs between the conventional and TSE-Dixon methods at each concentration. The Bland-Altman plot analyses showed that the APT SIs measured with the seven-points method resulted in 0.42% bias and narrow 95% limits of agreement (LOA) (0.93%–0.09%) compared to the conventional method. The APT SIs measured using the TSE-Dixon method showed 0.14% bias and similar 95% LOA (−0.33% to 0.61%) compared with the seven-points method. The APT SIs of all three methods showed positive pH dependence. At each pH, no significant differences in the APT SIs were observed among the methods. Bland-Altman plot analyses showed that the APT SIs measured with the seven-points method resulted in low bias (0.03%) and narrow 95% LOA (−0.30% to 0.36%) compared to the conventional method. The APT SIs measured by the TSE-Dixon method showed slightly larger bias (0.29%) and similar 95% LOA (from −0.15% to 0.72%) compared to those measured by the seven-points method. ConclusionThese results demonstrated that our proposed method has the same concentration dependence and pH dependence as the conventional method and the seven-points method. We thus expect that APT-weighted imaging with less influence of motion can be obtained in clinical examinations.

Activatable near-infrared fluorescence and chemical exchange saturation transfer MRI multimodal imaging probe for tumor detection in vitro and in vivo

Multimodal imaging has emerged as a powerful tool in biomedical research and clinical diagnostics. Ideally, it combines multiple imaging techniques to provide complementary anatomical and molecular information in living subjects. Particularly desirable are multimodal imaging probes capable of providing differential diagnostic signals upon interaction with specific molecular targets. Hydrogen peroxide (H2O2) is a key target in this regard, since it is typically overexpressed in cancer cells. In this study, we present a small-molecule probe that not only selectively detects endogenous H2O2 through multimodal imaging, with a significant H2O2-triggered 15-fold fluorescence enhancement but also turns “on” a chemical exchange saturation transfer (CEST) magnetic resonance (MR) response with 60-fold signal enhancement at pH 7.4. Excellent selectivity against various other biologically relevant species is seen. Using this probe, we observed 3.4–4.5-fold and 2.8–5.8-fold higher H2O2 levels in cancerous cell lines and tumor tissues compared to normal cell lines and tissues, respectively. Time-dependent in vivo fluorescence and CEST imaging in a HeLa (Henrietta Lacks) tumor xenograft mouse model revealed probe-dependent tumor detection by fluorescence and CEST MRI contrast in the tumor area. These observations are attributed to the relatively high endogenous H2O2 levels produced during mitosis. This newly developed probe holds promise for advancing our understanding of H2O2-related biology and for cancer detection both in vitro and in vivo.

Ultrahigh Bifunctional Photocatalytic CO2 Reduction and H2 Evolution by Synergistic Interaction of Heteroatomic Pt-Ru Dimerization Sites.

Diatomic-site catalysts (DASCs) inherit the excellent performance of single-atom catalysts (SACs) by utilizing two adjacent atomic metal species to achieve functional complementarity and synergistic effects that improve the carbon dioxide reduction reaction (CO2RR) and H2 evolution reaction (HER) kinetics. Herein, we report a method to further improve the catalytic efficiency of Pt by using Pt and Ru single atoms randomly anchored on a g-C3N4 surface, yielding partial Pt-Ru dimers. The synthesized catalyst exhibits extraordinary photocatalytic activity and stability in both the CO2RR and HER processes. In-depth experimentation, the pH-dependent chemical exchange saturation transfer (CEST) imaging nuclear magnetic resonance (NMR) method, and theoretical analyses reveal that the excellent performance is attributed to orbital coupling between the Pt atoms and the neighboring Ru atoms (mainly dxy and dxz), which decreases the orbital energy levels and weakens the bond strength with intermediates, resulting in improved CO2RR and HER performance. This study successfully applies the pH-dependent CEST imaging NMR method to catalytic reactions, and CO2 adsorption is directly observed using CEST 2D imaging maps. This work presents significant potential for a variety of catalytic reaction applications by systematically designing bimetallic dimers with higher activity and stability.

Free-breathing abdominal chemical exchange saturation transfer imaging using water presaturation and respiratory gating at 3.0 T.

Free-breathing abdominal chemical exchange saturation transfer (CEST) has great potential for clinical application, but its technical implementation remains challenging. This study aimed to propose and evaluate a free-breathing abdominal CEST sequence. The proposed sequence employed respiratory gating (ResGat) to synchronize the data acquisition with respiratory motion and performed a water presaturation module before the CEST saturation to abolish the influence of respiration-induced repetition time variation. In vivo experiments were performed to compare different respiratory motion-control strategies and B0 offset correction methods, and to evaluate the effectiveness and necessity of the quasi-steady-state (QUASS) approach for correcting the influence of the water presaturation module on CEST signal. ResGat with a target expiratory phase of 0.5 resulted in a higher structural similarity index and a lower coefficient of variation on consecutively acquired CEST S0 images than breath-holding (BH) and respiratory triggering (all p < 0.05). B0 maps derived from the abdominal CEST dataset itself were more stable for B0 correction, compared with the separately acquired B0 maps by a dual-echo time scan and B0 maps derived from the water saturation shift referencing approach. Compared with BH, ResGat yielded more homogeneous magnetization transfer ratio asymmetry maps at 3.5 ppm (standard deviation: 3.96% vs. 3.19%, p = 0.036) and a lower mean squared difference between scan and rescan (27.52‱ vs. 16.82‱, p = 0.004). The QUASS approach could correct the water presaturation-induced CEST signal change, but its necessity for in vivo scanning needs further verification. The proposed free-breathing abdominal CEST sequence using ResGat had an acquisition efficiency of approximately four times that using BH. In conclusion, the proposed free-breathing abdominal CEST sequence using ResGat and water presaturation has a higher acquisition efficiency and image quality than abdominal CEST using BH.

Application of glutamate weighted CEST in brain imaging of nicotine dependent participants in vivo at 7T.

With nicotine dependence being a significant healthcare issue worldwide there is a growing interest in developing novel therapies and diagnostic aids to assist in treating nicotine addiction. Glutamate (Glu) plays an important role in cognitive function regulation in a wide range of conditions including traumatic brain injury, aging, and addiction. Chemical exchange saturation transfer (CEST) imaging via ultra-high field MRI can image the exchange of certain saturated labile protons with the surrounding bulk water pool, making the technique a novel tool to investigate glutamate in the context of addiction. The aim of this work was to apply glutamate weighted CEST (GluCEST) imaging to study the dorsal anterior cingulate cortex (dACC) in a small population of smokers and non-smokers to determine its effectiveness as a biomarker of nicotine use. 2D GluCEST images were acquired on 20 healthy participants: 10 smokers (ages 29-50) and 10 non-smokers (ages 25-69), using a 7T MRI system. T1-weighted images were used to segment the GluCEST images into white and gray matter tissue and further into seven gray matter regions. Wilcoxon rank-sum tests were performed, comparing mean GluCEST contrast between smokers and non-smokers across brain regions. GluCEST levels were similar between smokers and non-smokers; however, there was a moderate negative age dependence (R2 = 0.531) in smokers within the cingulate gyrus. Feasibility of GluCEST imaging was demonstrated for in vivo investigation of smokers and non-smokers to assess glutamate contrast differences as a potential biomarker with a moderate negative age correlation in the cingulate gyrus suggesting reward network involvement.

Abstract WMP61: Assessment of Carotid Artery Plaques With Chemical Exchange Saturation Transfer Imaging

Background: Assessing carotid artery plaques in stenosis is crucial for treatment strategies and safety. Chemical exchange saturation transfer (CEST)-MRI, particularly Amide proton transfer (APT) imaging, shows promise in molecular imaging. This study explores the correlation between APT imaging and histopathological findings of carotid artery plaques in 34 consecutive patients who had carotid endarterectomy. We investigated the utility of CEST-MRI as a preoperative plaque diagnostic tool. Methods: APT imaging evaluated plaques prior to the procedures. APT signal values were derived from concentration maps. Plaques were categorized into Group A (APT signal values ≥ 1.90 E-04) and Group B (APT signal values &lt; 1.90 E-04). Postoperative histopathological assessments were conducted on the excised plaques. Histology slides were categorized following AHA’s classification, distinguishing type VI lesions with intraplaque hemorrhage from non-type VI lesions. Results: Type VI lesions accounted for 64.7% (22 cases), while non-type VI lesions were 35.3% (12 cases). Type VI group showed significantly higher mean APT signal values (2.72 ± 1.96 E-04) compared to non-type VI group (0.70 ± 0.59 E-04) (p &lt; 0.001). Pathologically, Group A had a significantly higher proportion of Type VI lesions (100%) than Group B (45%) (p &lt; 0.01). Symptomatic patients or patients with worsening stenosis rates were significantly higher in Group A (75%) than Group B (36%) (p &lt; 0.01). Conclusion: Elevated APT signals were observed in unstable plaques with intraplaque hemorrhage and in plaques of symptomatic or progressive stenosis patients. CEST-MRI evaluation is valuable for assessing plaque characteristics and activity.

PH Mapping of Gliomas Using Quantitative Chemical Exchange Saturation Transfer MRI: Quasi-Steady-State, Spillover-, and MT-Corrected Omega Plot Analysis.

Quantitative in-situ pH mapping of gliomas is important for therapeutic interventions, given its significant association with tumor progression, invasion, and metastasis. Although chemical exchange saturation transfer (CEST) offers a noninvasive way for pH imaging based on the pH-dependent exchange rate (ksw ), the reliable quantification of ksw in glioma remains constrained due to technical challenges. To quantify the pH of gliomas by measuring the proton exchange rate through optimized omega plot analysis. Prospective. Creatine and murine brain lysates phantoms, six rats with glioma xenograft model, and three patients with World Health Organization grade 2-4 gliomas. 11.7 T, 7.0 T, CEST imaging, T2 -weighted (T2 W) imaging, and T1 -mapping. Omega plot analysis, quasi-steady-state (QUASS) analysis, multi-pool Lorentzian fitting, amine and amide concentration-independent detection, pH enhanced method with the combination of amide and guanidyl (pHenh ), and magnetization transfer ratio (MTR) were utilized for pH metric quantification. The clinical outcomes were determined through radiologic follow-up and histopathological analysis. Mann-Whitney U test was performed to compare glioma with normal tissue, and Pearson's correlation analysis was used to assess the relationship between ksw and other parameters. In vitro experiments reveal that the determined ksw at 2 ppm increases exponentially with pH (creatine phantoms: ksw = 106 + 0.147 × 10(pH-4.198) ; lysates: ksw = 185.1 + 0.101 × 10(pH-3.914) ). Omega plot analysis exhibits a linear correlation between 1/MTRRex and 1/ω1 2 in the glioma xenografts (R2 > 0.98) and glioma patients (R2 > 0.99). The exchange rate in the rat glioma decreases compared to the contralateral normal tissue (349.46 ± 30.40 s-1 vs. 403.54 ± 51.01 s-1 , P = 0.025), while keeping independence from changes in concentration (r = 0.5037, P = 0.095). Similar pattern was observed in human data. Utilizing QUASS-based, spillover-, and MT-corrected omega plot analysis for the measurement of exchange rates, offers a feasible method for quantifying pH within glioma. NA TECHNICAL EFFICACY: Stage 1.

3.0 T multi-parametric MRI reveals metabolic and microstructural abnormalities in the posterior visual pathways in patients with thyroid eye disease.

We aim to explore the microstructural and metabolic changes in visual pathways in patients with thyroid eye disease (TED) using 3T multi-parametric MRI. Thirty-four TED patients (inactive group = 20; active group = 14; acute group = 18; chronic group = 16) and 12 healthy controls (HC) were recruited from November 2020 to July 2021. Proton magnetic resonance spectroscopy (1H-MRS), glutamate chemical exchange saturation transfer (GluCEST) and diffusion kurtosis imaging (DKI) were performed on 3.0T MR scanner. Data analysis and group comparisons were performed after MR data processing. As compare to HC group, the levels of total choline (tCh) in optic radiation (OR) in active group ([1.404 ± 0.560] vs. [1.022 ± 0.260]; p < 0.05), together with tCh ([1.415 ± 0.507] vs. [1.022 ± 0.260]; p < 0.05) in OR in acute group were significantly increased. Glutamine (Gln) levels were higher in OR in the chronic group than those in HCs and were positively correlated with the levels of thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), free triiodothyronine (FT3) and FT4 in chronic group. Glutamate (Glu) levels by 1H-MRS did not show significant differences between any two groups. Interestingly, MTRasym (3.0 ppm) was higher in OL in inactive group, active group, acute group and chronic group than those in HCs, and was positively correlated with Glu levels in OL in 1H-MRS. Fractional anisotropy (FA) values from DKI in OR in acute group were significantly lower than those in HCs. Our initial study demonstrate that GluCEST performs better than 1H-MRS to monitor Glu alterations in visual pathway in TED patients. Changes of brain glutamine levels in TED patients are closely related to their associated hormones alterations, indicating that disease injury status could be reflected through non-invasive metabolites detection by brain 1H-MRS. FA is the most sensitive DKI index to reveal the visual pathway impairment in TED patients. Altogether, our study revealed that 3T multiparametric MR techniques are useful to demonstrate metabolic and microstructural alterations in visual pathways in TED patients. We found that damage to visual pathways occurs in mild TED cases, which not only offers a new approach to the diagnosis of dysthyroid optic neuropathy, but also demonstrates neuropathy in TED is a gradual and continuous spatio-emporal progression.

Deep learning for dense Z-spectra reconstruction from CEST images at sparse frequency offsets.

A direct way to reduce scan time for chemical exchange saturation transfer (CEST)-magnetic resonance imaging (MRI) is to reduce the number of CEST images acquired in experiments. In some scenarios, a sufficient number of CEST images acquired in experiments was needed to estimate parameters for quantitative analysis, and this prolonged the scan time. For that, we aim to develop a general deep-learning framework to reconstruct dense CEST Z-spectra from experimentally acquired images at sparse frequency offsets so as to reduce the number of experimentally acquired CEST images and achieve scan time reduction. The main innovation works are outlined as follows: (1) a general sequence-to-sequence (seq2seq) framework is proposed to reconstruct dense CEST Z-spectra from experimentally acquired images at sparse frequency offsets; (2) we create a training set from wide-ranging simulated Z-spectra instead of experimentally acquired CEST data, overcoming the limitation of the time and labor consumption in manual annotation; (3) a new seq2seq network that is capable of utilizing information from both short-range and long-range is developed to improve reconstruction ability. One of our intentions is to establish a simple and efficient framework, i.e., traditional seq2seq can solve the reconstruction task and obtain satisfactory results. In addition, we propose a new seq2seq network that includes the short- and long-range ability to boost dense CEST Z-spectra reconstruction. The experimental results demonstrate that the considered seq2seq models can accurately reconstruct dense CEST images from experimentally acquired images at 11 frequency offsets so as to reduce the scan time by at least 2/3, and our new seq2seq network contributes to competitive advantage.

Carbon nitride nanosheet-supported CuO for efficient photocatalytic CO2 reduction with 100% CO selectivity.

The optimal ratio of reaction solutions resulted in excellent performance and product selectivity of CuO/g-C3N4 composites in the photocatalytic CO2 reduction reaction. A pH-dependent chemical exchange saturation transfer (CEST) imaging nuclear magnetic resonance (NMR) method was used to confirm that CuO modification improves the adsorption capacity of CO2.

A rapid method for phosphocreatine-weighted imaging in muscle using double saturation power-chemical exchange saturation transfer.

Monitoring the variation in phosphocreatine (PCr) levels following exercise provides valuable insights into muscle function. Chemical exchange saturation transfer (CEST) has emerged as a sensitive method with which to measure PCr levels in muscle, surpassing conventional MR spectroscopy. However, existing approaches for quantifying PCr CEST signals rely on time-consuming fitting methods that require the acquisition of the entire or a section of the CEST Z-spectrum. Additionally, traditional fitting methods often necessitate clear CEST peaks, which may be challenging to obtain at low magnetic fields. This paper evaluated the application of a new model-free method using double saturation power (DSP), termed DSP-CEST, to estimate the PCr CEST signal in muscle. The DSP-CEST method requires the acquisition of only two or a few CEST signals at the PCr frequency offset with two different saturation powers, enabling rapid dynamic imaging. Additionally, the DSP-CEST approach inherently eliminates confounding signals, offering enhanced robustness compared with fitting methods. Furthermore, DSP-CEST does not demand clear CEST peaks, making it suitable for low-field applications. We evaluated the capability of DSP-CEST to enhance the specificity of PCr CEST imaging through simulations and experiments on muscle tissue phantoms at 4.7 T. Furthermore, we applied DSP-CEST to animal leg muscle both before and after euthanasia and observed successful reduction of confounding signals. The DSP-CEST signal still has contaminations from a residual magnetization transfer (MT) effect and an aromatic nuclear Overhauser enhancement effect, and thus only provides a PCr-weighted imaging. The residual MT effect can be reduced by a subtraction of DSP-CEST signals at 2.6 and 5 ppm. Results show that the residual MT-corrected DSP-CEST signal at 2.6 ppm has significant variation in postmortem tissues. By contrast, both the CEST signal at 2.6 ppm and a conventional Lorentzian difference analysis of CEST signal at 2.6 ppm demonstrate no significant variation in postmortem tissues.

Improved postprocessing of dynamic glucose-enhanced CEST MRI for imaging brain metastases at 3 T

BackgroundDynamic glucose-enhanced (DGE) chemical exchange saturation transfer (CEST) has the potential to characterize glucose metabolism in brain metastases. Since the effect size of DGE CEST is small at 3 T (< 1%), measurements of signal-to-noise ratios are challenging. To improve DGE detection, we developed an acquisition pipeline and extended image analysis for DGE CEST on a hybrid 3-T positron emission tomography/magnetic resonance imaging system.MethodsThis cross-sectional study was conducted after local ethical approval. Static Z-spectra (from -100 to 100 ppm) were acquired to compare the use of 1.2 versus 2 ppm to calculate static glucose-enhanced (glucoCEST) maps in 10 healthy volunteers before and after glucose infusion. Dynamic CEST images were acquired during glucose infusion. Image analysis was optimized using motion correction, dynamic B0 correction, and principal component analysis (PCA) to improve the detection of DGE CEST in the sagittal sinus, cerebrospinal fluid, and grey and white matter. The developed DGE CEST pipeline was applied to four patients diagnosed with brain metastases.ResultsGlucoCEST was strongest in healthy tissues at 2 ppm. Correcting for motion, B0, and use of PCA locally improved DGE maps. A larger contrast between healthy tissues and enhancing regions in brain metastases was found when dynamic B0 correction and PCA denoising were applied.ConclusionWe demonstrated the feasibility of DGE CEST with our developed acquisition and analysis pipeline at 3 T in patients with brain metastases. This work enables a direct comparison of DGE CEST to 18F-fluoro-deoxy-D-glucose positron emission tomography of glucose metabolism in patients with brain metastases.Relevance statementContrast between brain metastasis and healthy brain tissue in DGE CEST MR images is improved by including principle component analysis and dynamic magnetic field correction during postprocessing. This approach enables the detection of increased DGE CEST signal in brain metastasis, if present.Key points• Despite the low signal-to-noise ratio, dynamic glucose-enhanced CEST MRI is feasible at 3 T.• Principal component analyses and dynamic magnetic field correction improve DGE CEST MRI.• DGE CEST MRI does not consequently show changes in brain metastases compared to healthy brain tissue.• Increased DGE CEST MRI in brain metastases, if present, shows overlap with contrast enhancement on T1-weighted images.Graphical

Deep Learning-Based Denoising of CEST MR Data: A Feasibility Study on Applying Synthetic Phantoms in Medical Imaging.

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 (MTRasym) 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.

Reproducibility of APT-weighted CEST-MRI at 3T in healthy brain and tumor across sessions and scanners

Amide proton transfer (APT)-weighted chemical exchange saturation transfer (CEST) imaging is a recent MRI technique making its way into clinical application. In this work, we investigated whether APT-weighted CEST imaging can provide reproducible measurements across scan sessions and scanners. Within-session, between-session and between scanner reproducibility was calculated for 19 healthy volunteers and 7 patients with a brain tumor on two 3T MRI scanners. The APT-weighted CEST effect was evaluated by calculating the Lorentzian Difference (LD), magnetization transfer ratio asymmetry (MTRasym), and relaxation-compensated inverse magnetization transfer ratio (MTRREX) averaged in whole brain white matter (WM), enhancing tumor and necrosis. Within subject coefficient of variation (COV) calculations, Bland–Altman plots and mixed effect modeling were performed to assess the repeatability and reproducibility of averaged values. The group median COVs of LD APT were 0.56% (N = 19), 0.84% (N = 6), 0.80% (N = 9) in WM within-session, between-session and between-scanner respectively. The between-session COV of LD APT in enhancing tumor (N = 6) and necrotic core (N = 3) were 4.57% and 5.67%, respectively. There were no significant differences in within session, between session and between scanner comparisons of the APT effect. The COVs of LD and MTRREX were consistently lower than MTRasym in all experiments, both in healthy tissues and tumor. The repeatability and reproducibility of APT-weighted CEST was clinically acceptable across scan sessions and scanners. Although MTRasym is simple to acquire and compute and sufficient to provide robust measurement, it is beneficial to include LD and MTRREX to obtain higher reproducibility for detecting minor signal difference in different tissue types.

Boosting quantification accuracy of chemical exchange saturation transfer MRI with a spatial-spectral redundancy-based denoising method.

Chemical exchange saturation transfer (CEST) is a versatile technique that enables noninvasive detections of endogenous metabolites present in low concentrations in living tissue. However, CEST imaging suffers from an inherently low signal-to-noise ratio (SNR) due to the decreased water signal caused by the transfer of saturated spins. This limitation challenges the accuracy and reliability of quantification in CEST imaging. In this study, a novel spatial-spectral denoising method, called BOOST (suBspace denoising with nOnlocal lOw-rank constraint and Spectral local-smooThness regularization), was proposed to enhance the SNR of CEST images and boost quantification accuracy. More precisely, our method initially decomposes the noisy CEST images into a low-dimensional subspace by leveraging the global spectral low-rank prior. Subsequently, a spatial nonlocal self-similarity prior is applied to the subspace-based images. Simultaneously, the spectral local-smoothness property of Z-spectra is incorporated by imposing a weighted spectral total variation constraint. The efficiency and robustness of BOOST were validated in various scenarios, including numerical simulations and preclinical and clinical conditions, spanning magnetic field strengths from 3.0 to 11.7 T. The results demonstrated that BOOST outperforms state-of-the-art algorithms in terms of noise elimination. As a cost-effective and widely available post-processing method, BOOST can be easily integrated into existing CEST protocols, consequently promoting accuracy and reliability in detecting subtle CEST effects.

BEVACIZUMAB FOR SYMPTOMATIC RADIATION NECROSIS IN BRAIN METASTASES: OUTCOMES FROM A SINGLE-CENTER RETROSPECTIVE ANALYSIS

Abstract Radiation necrosis is a late complication after radiotherapy and can be treated with bevacizumab, however predictors of response are not well established. We performed a single-institution retrospective chart review of patients with previously irradiated brain metastases who developed radiation necrosis and were treated with bevacizumab. 19 patients (86% female, median age of 62 years) were included. 50% had metastatic lung cancer, 37% had breast cancer and 11 % had melanoma. 18 had perfusion imaging, 9 had chemical exchange saturation transfer (CEST) imaging to increase diagnostic confidence. 6 cases were tissue-confirmed, 3 before treatment, and 3 upon recurrence after bevacizumab. All patients received a dose of 7.5 mg/kg per infusion every 3 weeks and 63% received 4 infusions. All were symptomatic before treatment. Clinical response was seen in 89% while radiographic response was achieved in 95% of patients. Dexamethasone was successfully discontinued in 71% of steroid-dependent patients. The median duration of response (interval between first infusion and recurrence) was 7.2 months (range: 2.3 to 43.2). Of the nine diagnosed using perfusion and CEST imaging, 89% had clinical response, 100% had a reduction in T2/FLAIR volume and 89% in T1 post-gadolinium enhancement, 83% discontinued dexamethasone. Grade 1/2 adverse events occurred in 8 patients (hypertension, fatigue, rash, joint pain, intracranial hemorrhage). One patient developed a grade 3 bowel perforation requiring surgery. Bevacizumab resulted in significant and prolonged clinical and radiographic improvement in a series of carefully selected patients. CEST imaging helped select responders to bevacizumab in our cohort.

Hierarchical K-means clustering method for accelerated Lorentzian estimation (KALE) in chemical exchange saturation transfer-magnetic resonance imaging quantification.

Quantification of in vivo chemical exchange saturation transfer (CEST) magnetic resonance signals is challenging due to contamination from coexisting effects, including the direct water effect and asymmetric magnetization transfer. Fitting-based analysis allows the calculation of multiple types of signals from the line shape of Z-spectra. However, the conventional voxelwise method has several drawbacks, including its long computation time and its susceptibility to image noise and Z-spectra oscillations, and it is difficult to determine the initial fitting parameters. Herein, we propose a K-means clustering method for accelerated Lorentzian estimation (KALE) in CEST quantification. Briefly, voxels in CEST images are clustered into K groups according to their Z-spectra characteristics. A 'groupwise' fitting process is then performed with preset initial values, yielding a set of fitted spectra and fitted parameters for each group. With the updated initial values, each group is further clustered into subgroups, and groupwise fitting is performed again. This hierarchical K-means clustering and parameter updating process continues until the pixel number or intensity error meets the termination criteria. Voxelwise fitting could be further conducted to improve the quantification images (termed voxel-K) by utilizing the previous groupwise KALE results as the initial values (termed group-K). Incorporated with Lorentzian difference (LD) quantification, KALE was first optimized and evaluated on 5 healthy human brain datasets at 3 Tesla. Compared with traditional voxel-by-voxel LD quantification, the computation times of group-K and voxel-K were significantly reduced by ~85% and ~70%, respectively (P<0.001). Furthermore, the group-K images exhibited better denoising performance than traditional LD and voxel-K. KALE was further validated on six ischemic rat brains acquired at 7 Tesla, with both LD_group-K and LD_voxel-K displaying almost identical contrast maps with traditional voxelwise maps. When incorporated with the five-pool Lorentzian fitting (LF), KALE exhibited an improved contrast-to-noise ratio (CNR) for amplitude maps of each pool [P=0.003, 0.015, 0.047, and 0.047 for amide, nuclear Overhauser effect (NOE), magnetic transfer (MT) and guanidine amine, respectively] and improved fitting goodness (P=0.033). KALE quantification provides comparable or even superior contrast maps to traditional voxelwise fitting, with significantly reduced computation time. The 'smart' and hierarchical voxel-clustering and parameter updating process of KALE may facilitate more preclinical and clinical CEST applications.

Concurrent Dual-Contrast Enhancement Using Fe3O4 Nanoparticles to Achieve a CEST Signal Controllability.

Traditional T2 magnetic resonance imaging (MRI) contrast agents have defects inherent to negative contrast agents, while chemical exchange saturation transfer (CEST) contrast agents can quantify substances at trace concentrations. After reaching a certain concentration, iron-based contrast agents can "shut down" CEST signals. The application range of T2 contrast agents can be widened through a combination of CEST and T2 contrast agents, which has promising application prospects. The purpose of this study is to develop a T2 MRI negative contrast agent with a controllable size and to explore the feasibility of dual contrast enhancement by combining T2 with CEST contrast agents. The study was carried out in vitro with HCT-116 human colon cancer cells. A GE SIGNA Pioneer 3.0 T medical MRI scanner was used to acquire CEST images with different saturation radio-frequency powers (1.25/2.5/3.75/5 μT) by 2D spin echo-echo planar imaging (SE-EPI). Magnetic resonance image compilation (MAGiC) was acquired by a multidynamic multiecho 2D fast spin-echo sequence. The feasibility of this dual-contrast enhancement method was assessed by scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, dynamic light scattering, ζ potential analysis, inductively coupled plasma, X-ray photoelectron spectroscopy, X-ray powder diffraction, vibrating-sample magnetometry, MRI, and a Cell Counting Kit-8 assay. The association between the transverse relaxation rate r2 and the pH of the iron-based contrast agents was analyzed by linear fitting, and the linear relationship between the CEST effect in different B1 fields and pH was analyzed by the ratio method. Fe3O4 nanoparticles (NPs) with a mean particle size of 82.6 ± 22.4 nm were prepared by a classical process, and their surface was successfully modified with -OH active functional groups. They exhibited self-aggregation in an acidic environment. The CEST effect was enhanced as the B1 field increased, and an in vitro pH map was successfully plotted using the ratio method. Fe3O4 NPs could stably serve as reference agents at different pH values. At a concentration of 30 μg/mL, Fe3O4 NPs "shut down" the CEST signals, but when the concentration of Fe3O4 NPs was less than 10 μg/mL, the two contrast agents coexisted. The prepared Fe3O4 NPs had almost no toxicity, and when their concentration rose to 200 μg/mL at pH 6.5 or 7.4, they did not reach the half-maximum inhibitory concentration (IC50). Fe3O4 magnetic NPs with a controllable size and no toxicity were successfully synthesized. By combining Fe3O4 NPs with a CEST contrast agent, the two contrast agents could be imaged simultaneously; at higher concentrations, the iron-based contrast agent "shut down" the CEST signal. An in vitro pH map was successfully plotted by the ratio method. CEST signal inhibition can be used to realize the pH mapping of solid tumors and the identification of tumor active components, thus providing a new imaging method for tumor efficacy evaluation.

Role of Imaging Modalities and N-Acetylcysteine Treatment in Sepsis-Associated Encephalopathy.

Sepsis-associated encephalopathy is a severe systemic infection complication. Although early stages involve pathophysiological changes, detection using conventional imaging is challenging. Glutamate chemical exchange saturation transfer and diffusion kurtosis imaging can noninvasively investigate cellular and molecular events in early disease stages using magnetic resonance imaging (MRI). N-Acetylcysteine, an antioxidant and precursor of glutathione, regulates neurotransmitter glutamate metabolism and participates in neuroinflammation. We investigated the protective role of n-acetylcysteine in sepsis-associated encephalopathy using a rat model and monitored changes in brain using magnetic resonance (MR) molecular imaging. Bacterial lipopolysaccharide was injected intraperitoneally to induce a sepsis-associated encephalopathy model. Behavioral performance was assessed using the open-field test. Tumor necrosis factor α and glutathione levels were detected biochemically. Imaging was performed using a 7.0-T MRI scanner. Protein expression, cellular damage, and changes in blood-brain barrier permeability were assessed using western blotting, pathological staining, and Evans blue staining, respectively. Lipopolysaccharide-induced rats showed reduced anxiety and depression after treatment with n-acetylcysteine. MR molecular imaging can identify pathological processes at different disease stages. Furthermore, rats treated with n-acetylcysteine showed increased glutathione levels and decreased tumor necrosis factor α, suggesting enhanced antioxidant capacity and inhibition of inflammatory processes, respectively. Western blot analysis showed reduced expression of nuclear factor kappa B (p50) protein after treatment, suggesting that n-acetylcysteine inhibits inflammation via this signaling pathway. Finally, n-acetylcysteine-treated rats showed reduced cellular damage by pathology and reduced extravasation of their blood-brain barrier by Evans Blue staining. Thus, n-acetylcysteine might be a therapeutic option for sepsis-associated encephalopathy and other neuroinflammatory diseases. Furthermore, noninvasive "dynamic visual monitoring" of physiological and pathological changes related to sepsis-associated encephalopathy was achieved using MR molecular imaging for the first time, providing a more sensitive imaging basis for early diagnosis, identification, and prognosis.