Chemical Exchange Saturation Transfer Imaging Research Articles

Chemical Exchange Saturation Transfer MRI Signal Loss of the Substantia Nigra as an Imaging Biomarker to Evaluate the Diagnosis and Severity of Parkinson's Disease.

The early diagnosis of Parkinson's disease (PD) and the accurate evaluation of disease severity are crucial for intervention and treatment in PD patients. In this study, we applied chemical exchange saturation transfer (CEST) imaging to patients at different stages of PD and explored the clinical value of the CEST signal loss of the substantia nigra as an imaging biomarker of PD. The measured CEST signal intensities (including amide proton transfer-weighted or APTw, and total CEST or CESTtotal) of the substantia nigra in PD patients showed a significantly decreased tendency with PD progression. Compared to normal controls, the APTw and CESTtotal intensities of PD patients significantly decreased at both the early and advanced or late stages. These APTw and CESTtotal values of the substantia nigra were also significantly lower in advanced or late stage PD patients than in early stage PD patients. For PD patients with unilateral symptoms, the APTw and CESTtotal values in the substantia nigra on the affected side were significantly lower than those in normal controls. Both the APTw and CESTtotal values of PD were significantly correlated with the severity of disease and disease duration. Our findings suggest that the CEST MRI signal of the substantia nigra is a potential imaging biomarker for the diagnosis and monitoring of the severity of PD.

Chemical exchange saturation transfer imaging: Advances and applications. Edited by M. T.McMahonA. A.GiladJ. W. M.BulteP. C. M.vanZijl, Pan Stanford Publishing Pte. Ltd., Singapore, 2017, $179.95 (Hardcover) and $125.97 (E‐book), pp. 496

Chemical exchange saturation transfer imaging: Advances and applications. Edited by M. T.McMahonA. A.GiladJ. W. M.BulteP. C. M.vanZijl, Pan Stanford Publishing Pte. Ltd., Singapore, 2017, $179.95 (Hardcover) and $125.97 (E‐book), pp. 496

Differentiation between Radiation Necrosis and Tumor Progression Using Chemical Exchange Saturation Transfer.

Purpose: Stereotactic radiosurgery (SRS) is a common treatment used in patients with brain metastases and is associated with high rates of local control, however, at the risk of radiation necrosis. It is difficult to differentiate radiation necrosis from tumor progression using conventional MRI, making it a major diagnostic dilemma for practitioners. This prospective study investigated whether chemical exchange saturation transfer (CEST) was able to differentiate these two conditions.Experimental Design: Sixteen patients with brain metastases who had been previously treated with SRS were included. Average time between SRS and evaluation was 12.6 months. Lesion type was determined by pathology in 9 patients and the other 7 were clinically followed. CEST imaging was performed on a 3T Philips scanner and the following CEST metrics were measured: amide proton transfer (APT), magnetization transfer (MT), magnetization transfer ratio (MTR), and area under the curve for CEST peaks corresponding to amide and nuclear Overhauser effect (NOE).Results: Five lesions were classified as progressing tumor and 11 were classified as radiation necrosis (using histopathologic confirmation and radiographic follow-up). The best separation was obtained by NOEMTR (NOEMTR,necrosis = 8.9 ± 0.9%, NOEMTR,progression = 12.6 ± 1.6%, P < 0.0001) and AmideMTR (AmideMTR,necrosis = 8.2 ± 1.0%, AmideMTR,progression = 12.0 ± 1.9%, P < 0.0001). MT (MTnecrosis = 4.7 ± 1.0%, MTprogression = 6.7 ± 1.7%, P = 0.009) and NOEAUC (NOEAUC,necrosis = 4.3 ± 2.0% Hz, NOEAUC,progression = 7.2 ± 1.9% Hz, P = 0.019) provided statistically significant separation but with higher P values.Conclusions: CEST was capable of differentiating radiation necrosis from tumor progression in brain metastases. Both NOEMTR and AmideMTR provided statistically significant separation of the two cohorts. However, APT was unable to differentiate the two groups. Clin Cancer Res; 23(14); 3667-75. ©2017 AACR.

Abstract SY02-03: Imaging cancer metabolism in patients: FDG PET and beyond

Abstract The identification of altered energy metabolism as a hallmark of cancer (1) leads to opportunities to exploit cancer metabolism as a target for diagnosis. This has been most widely exploited using the elevated rate of glycolysis observed in most tumors as a target for imaging (2)–in particular, positron emission tomography (PET) imaging of the glucose analog 18F-fluorodeoxyglucose (FDG). FDG PET, now combined with anatomic imaging in the form of PET/CT, has become an important tool for cancer detection, staging, and response assessment, widely used in oncologic clinical practices around the world (3,4). Clinical use of FDG PET has increased our appreciation of aberrant glycolysis as a feature of more aggressive, less differentiated tumors (5,6). At the same time, the variability of tumor FDG uptake seen in clinical imaging has highlighted some of the limitations of imaging tumor glycolysis and has spurred the development of new imaging probes and novel imaging modalities designed to image other facets of cancer energy metabolism. In addition, the use of therapeutics that are targeted to and/or influenced by cancer metabolic phenotype (7) drives applications of cancer metabolic imaging to clinical challenges beyond detection to predicting and and monitoring response to targeted therapy (8). This talk highlights current uses of FDG PET/CT for cancer staging and response evaluation, as well as alternative PET probes targeted to other metabolic substrates such as amino acids, lipids, and TCA intermediates (9). It also highlights other methods for imaging cancer metabolism in patients, including magnetic resonance spectroscopy, optical imaging, chemical exchange saturation transfer (CEST), MR metabolomics, and MR imaging of hyperpolarized 13C-labeled metabolic substrates such as pyruvate (10-14). Unique features and advantages of each modality are highlighted, as are approaches to image analysis common across modalities, including quantitative imaging and kinetic analysis. Finally, the talk emphasizes the benefit of multimodality imaging as an approach to fully characterize cancer metabolism, using glutaminolysis imaging as an example of active investigation. Supported in part by Komen SAC130060, DOE DE-SE0012476, NIH P30-CA016520, and NIH R01-CA211337.

Book Review: Chemical Exchange Saturation Transfer Imaging: Advances and Applications

Book Review: Chemical Exchange Saturation Transfer Imaging: Advances and Applications

Chemical exchange rotation transfer imaging of intermediate-exchanging amines at 2ppm.

Chemical exchange saturation transfer (CEST) imaging of amine protons exchanging at intermediate rates and whose chemical shift is around 2ppm may provide a means of mapping creatine. However, the quantification of this effect may be compromised by the influence of overlapping CEST signals from fast-exchanging amines and hydroxyls. We aimed to investigate the exchange rate filtering effect of a variation of CEST, named chemical exchange rotation transfer (CERT), as a means of isolating creatine contributions at around 2ppm from other overlapping signals. Simulations were performed to study the filtering effects of CERT for the selection of transfer effects from protons of specific exchange rates. Control samples containing the main metabolites in brain, bovine serum albumin (BSA) and egg white albumen (EWA) at their physiological concentrations and pH were used to study the ability of CERT to isolate molecules with amines at 2ppm that exchange at intermediate rates, and corresponding methods were used for in vivo rat brain imaging. Simulations showed that exchange rate filtering can be combined with conventional filtering based on chemical shift. Studies on samples showed that signal contributions from creatine can be separated from those of other metabolites using this combined filter, but contributions from protein amines may still be significant. This exchange filtering can also be used for in vivo imaging. CERT provides more specific quantification of amines at 2ppm that exchange at intermediate rates compared with conventional CEST imaging.

B1 Power Optimization for Chemical Exchange Saturation Transfer Imaging: A Phantom Study Using Egg White for Amide Proton Transfer Imaging Applications in the Human Brain.

The chemical exchange saturation transfer (CEST) effect on an egg white (EW) suspension was investigated for optimization of magnetization transfer (MT) power (B1,rms) and pH dependency with the addition of lactic acid. Applying a higher MT pulse, B1,rms, Z-spectrum shows higher asymmetry and the magnetisation transfer ratio (MTR)asym signal increases to around 1–3.5 ppm, indicating a higher CEST effect. Amide proton transfer (APT) at 3.5 ppm shows a signal elevation in MTRasym with the application of higher B1,rms power and high pH. In addition, the hydroxyl proton signal in MTRasym increases as pH is reduced by lactic acid. In Z-spectrum of B1,rms at 1.0 μT and 2.0 μT, the dependence on CEST effect of amide proton and hydroxyl proton could be observed by using an EW suspension phantom. The CEST MT power was optimized on the EW suspension phantom with pH dependency and further confirmed on volunteers. In addition, APT imaging at 3.5 ppm using B1,rms at 1.0 μT performed on two human brains with different pathophysiological conditions indicated appropriate ATP effect.

Measurement of APT using a combined CERT-AREX approach with varying duty cycles

The goal is to develop an imaging method where contrast reflects amide-water magnetization exchange, with minimal signal contributions from other sources. Conventional chemical exchange saturation transfer (CEST) imaging of amides (often called amide proton transfer, or APT, and quantified by the metric MTRasym) is confounded by several factors unrelated to amides, such as aliphatic protons, water relaxation, and macromolecular magnetization transfer. In this work, we examined the effects of combining our previous chemical exchange rotation (CERT) approach with the non-linear AREX method while using different duty cycles (DC) for the label and reference scans. The dependencies of this approach, named AREXdouble,vdc, on tissue parameters, including T1, T2, semi-solid component concentration (fm), relayed nuclear Overhauser enhancement (rNOE), and nearby amines, were studied through numerical simulations and control sample experiments at 9.4T and 1μT irradiation. Simulations and experiments show that AREXdouble,vdc is sensitive to amide-water exchange effects, but is relatively insensitive to T1, T2, fm, nearby amine, and distant aliphatic protons, while the conventional metric MTRasym, as well as several other APT imaging methods, are significantly affected by at least some of these confounding factors.

Evaluating the cartilage adjacent to the site of repair surgery with glycosaminoglycan-specific magnetic resonance imaging

The glycosaminoglycan (GAG) chemical exchange saturation transfer (CEST) imaging method (gagCEST) makes it possible to assess and quantify the GAG concentration in human cartilage. This biochemical imaging technique facilitates detection of the loss of GAG in the course of osteoarthritis. The gagCEST technique was used to analyse the perilesional zone (PLZ) adjacent to repair tissue after cartilage repair surgery, to determine whether there are biochemical changes present in the sense of degeneration. Asymmetries in the PLZ of cartilage defects in 11 patients, who had been treated by microfracturing or matrix-associated autologous chondrocyte transplantation (MACT), were measured by gagCEST on a 7-T whole-body system. These results were correlated with gagCEST asymmetries of healthy reference cartilage (RC), measured anterior and posterior to the PLZ and to the repair tissue (RT). The mean gagCEST asymmetry for the anterior PLZ was 4.8% (±4.4), for the posterior PLZ 5.4% (±2.3), for the anterior RC 6.6% (±3.5) and 7.2% (±3.3) for the posterior RC and 4.5% (±2.3) for the RT. The difference between the anterior PLZ and the anterior RC (p = 0.019), the posterior PLZ and the posterior RC (p = 0.005), and the mean RC and the RT (p = 0.021) were all statistically significant. The measurements between RT and mean PLZ did not reveal significant results (p = 0.398). The gagCEST method provides a potentially useful biomarker for the loss of GAGs, indicating cartilage degeneration in the PLZ. Pre-operative and post-operative monitoring of the biomechanical state of the cartilage might influence intra-operative decision-making concerning the extent of cartilage resection or might give information of the success of the treatment post-operatively.

CEST imaging of fast exchanging amine pools with corrections for competing effects at 9.4T.

Chemical exchange saturation transfer (CEST) imaging of fast exchanging amine protons at 3ppm offset from the water resonant frequency is of practical interest, but quantification of fast exchanging pools by CEST is challenging. To effectively saturate fast exchanging protons, high irradiation powers need to be applied, but these may cause significant direct water saturation as well as non-specific semi-solid magnetization transfer (MT) effects, and thus decrease the specificity of the measured signal. In addition, the CEST signal may depend on the water longitudinal relaxation time (T1w ), which likely varies between tissues and with pathology, further reducing specificity. Previously, an analysis of the asymmetry of saturation effects (MTRasym ) has been commonly used to quantify fast exchanging amine CEST signals. However, our results show that MTRasym is greatly affected by the above factors, as well as asymmetric MT and nuclear Overhauser enhancement (NOE) effects. Here, we instead applied a relatively more specific inverse analysis method, named AREX (apparent exchange-dependent relaxation), that has previously been applied only to slow and intermediate exchanging solutes. Numerical simulations and controlled phantom experiments show that, although MTRasym depends on T1w and semi-solid content, AREX acquired in steady state does not, which suggests that AREX is more specific than MTRasym . By combining with a fitting approach instead of using the asymmetric analysis to obtain reference signals, AREX can also avoid contaminations from asymmetric MT and NOE effects. Animal experiments show that these two quantification methods produce differing contrasts between tumors and contralateral normal tissues in rat brain tumor models, suggesting that conventional MTRasym applied in vivo may be influenced by variations in T1w , semi-solid content, or NOE effect. Thus, the use of MTRasym may lead to misinterpretation, while AREX with corrections for competing effects likely enhances the specificity and accuracy of quantification to fast exchanging pools.

Quantitative chemical exchange saturation transfer (CEST) MRI of glioma using Image Downsampling Expedited Adaptive Least-squares (IDEAL) fitting

Chemical Exchange Saturation Transfer (CEST) MRI is sensitive to dilute metabolites with exchangeable protons, allowing tissue characterization in diseases such as acute stroke and tumor. CEST quantification using multi-pool Lorentzian fitting is challenging due to its strong dependence on image signal-to-noise ratio (SNR), initial values and boundaries. Herein we proposed an Image Downsampling Expedited Adaptive Least-squares (IDEAL) fitting algorithm that quantifies CEST images based on initial values from multi-pool Lorentzian fitting of iteratively less downsampled images until the original resolution. The IDEAL fitting in phantom data with superimposed noise provided smaller coefficient of variation and higher contrast-to-noise ratio at a faster fitting speed compared to conventional fitting. We further applied the IDEAL fitting to quantify CEST MRI in rat gliomas and confirmed its advantage for in vivo CEST quantification. In addition to significant changes in amide proton transfer and semisolid macromolecular magnetization transfer effects, the IDEAL fitting revealed pronounced negative contrasts of tumors in the fitted CEST maps at 2 ppm and −1.6 ppm, likely arising from changes in creatine level and nuclear overhauser effects, which were not found using conventional method. It is anticipated that the proposed method can be generalized to quantify MRI data where SNR is suboptimal.

Chemical-exchange-saturation-transfer magnetic resonance imaging to map gamma-aminobutyric acid, glutamate, myoinositol, glycine, and asparagine: Phantom experiments

The physical and technical development of chemical-exchange-saturation-transfer (CEST) magnetic resonance imaging (MRI) using clinical 3 T MRI was explored with the goal of mapping asparagine (Asn), gamma-aminobutyric acid (GABA), glutamate (Glu), glycine (Gly), and myoinositol (MI), which exist in the brain. Phantoms with nine different conditions at concentrations of 10, 30, and 50 mM and pH values of 5.6, 6.2, and 7.4 were prepared for the five target molecules to evaluate the dependence of the CEST effect in the concentration, the pH, and the amplitude of the applied radiofrequency field B1. CEST images in the offset frequency range of ±6 parts per million (ppm) were acquired using a pulsed radio-frequency saturation scheme with a clinical 3 T MRI system. A voxel-based main magnetic field B0 inhomogeneity correction, where B0 is the center frequency offset at zero ppm, was performed by using the spline interpolation method to fit the full Z-spectrum to estimate the center frequency. A voxel-based CEST asymmetry map was calculated to evaluate amide (-NH), amine (-NH2), and hydroxyl (-OH) groups for the five target molecules. The CEST effect for Glu, GABA, and Gly clearly increased with increasing concentrations. The CEST effect for MI was minimal, with no noticeable differences at different concentrations. The CEST effect for Glu and Gly increased with increasing acidity. The highest CEST asymmetry for GABA was observed at pH 6.2. The CEST effect for Glu, GABA, and Gly increased with increasing B1 amplitude. For all target molecules, the CEST effect for the human 3 T MRI system increased with increasing concentration and B1 amplitude, but varied with pH, depending on the characteristics of the molecules. The CEST effect for MI may be not suitable with clinical MRI systems. These results show that CEST imaging in the brain with the amine protons by using 3 T MRI is possible for several neuronal diseases.

B1+ inhomogeneity mitigation in CEST using parallel transmission.

In order to benefit from the increased spectral bandwidth at ultrahigh field (UHF), the use of parallel transmission (pTx) to mitigate flip-angle inhomogeneity in chemical exchange saturation transfer (CEST) imaging is investigated. A pTx basis pulse is homogenised by magnitude least-squares (MLS) optimization and expanded to form a frequency-selective saturation pulse for CEST. The pTx saturation pulse was simulated with a three-pool Bloch-McConnell equation to evaluate the impact of pTx on CEST contrast. In vivo CEST imaging performance (7 T) of the pTx saturation pulse and the standard Gaussian saturation in circularly polarized mode were compared. Two-spokes pTx homogeneous excitation was used in all in vivo experiments to ensure fair comparison of the two saturation pulses. Magnetization transfer ratio and inverse Z-spectrum analyses were used as metrics in evaluating the data from 3 healthy volunteers. Bloch-McConnell simulations showed that side bands of the pTx saturation pulse at ±20 ppm did not affect any CEST contrast. Improved homogeneity in contrasts and relaxation-compensated CEST metrics were observed in our in vivo data when the pTx saturation pulse was used. A pTx-based pulsed CEST presaturation scheme is proposed and validated by simulations and 7T in vivo imaging. Magn Reson Med 78:2216-2225, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Advanced MRI for Pediatric Brain Tumors with Emphasis on Clinical Benefits.

Conventional anatomic brain MRI is often limited in evaluating pediatric brain tumors, the most common solid tumors and a leading cause of death in children. Advanced brain MRI techniques have great potential to improve diagnostic performance in children with brain tumors and overcome diagnostic pitfalls resulting from diverse tumor pathologies as well as nonspecific or overlapped imaging findings. Advanced MRI techniques used for evaluating pediatric brain tumors include diffusion-weighted imaging, diffusion tensor imaging, functional MRI, perfusion imaging, spectroscopy, susceptibility-weighted imaging, and chemical exchange saturation transfer imaging. Because pediatric brain tumors differ from adult counterparts in various aspects, MRI protocols should be designed to achieve maximal clinical benefits in pediatric brain tumors. In this study, we review advanced MRI techniques and interpretation algorithms for pediatric brain tumors.

Physical Modeling of Chemical Exchange Saturation Transfer Imaging

Physical Modeling of Chemical Exchange Saturation Transfer Imaging

Balanced Steady-State Free Precession (bSSFP) from an effective field perspective: Application to the detection of chemical exchange (bSSFPX)

Chemical exchange saturation transfer (CEST) is a novel contrast mechanism and it is gaining increasing popularity as many promising applications have been proposed and investigated. Fast and quantitative CEST imaging techniques are further needed in order to increase the applicability of CEST for clinical use as well as to derive quantitative physiological and biological information. Steady-state methods for fast CEST imaging have been reported recently. Here, we observe that an extreme case of these methods is a balanced steady-state free precession (bSSFP) sequence. The bSSFP in itself is sensitive to the exchange processes; hence, no additional saturation or preparation is needed for CEST-like data acquisition. The bSSFP experiment can be regarded as observation during saturation, without separate saturation and acquisition modules as used in standard CEST and similar experiments. One of the differences from standard CEST methods is that the bSSFP spectrum is an XY-spectrum not a Z-spectrum. As the first proof-of-principle step, we have implemented the steady-state bSSFP sequence for chemical exchange detection (bSSFPX) and verified its feasibility in phantom studies. These studies have shown that bSSFPX can achieve exchange-mediated contrast comparable to the standard CEST experiment. Therefore, the bSSFPX method has a potential for fast and quantitative CEST data acquisition.

In Vivo Imaging of Tumor Metabolism and Acidosis by Combining PET and MRI-CEST pH Imaging.

The vast majority of cancers exhibit increased glucose uptake and glycolysis regardless of oxygen availability. This metabolic shift leads to an enhanced production of lactic acid that decreases extracellular pH (pHe), a hallmark of the tumor microenvironment. In this way, dysregulated tumor pHe and upregulated glucose metabolism are linked tightly and their relative assessment may be useful to gain understanding of the underlying biology. Here we investigated noninvasively the in vivo correlation between tumor 18F-FDG uptake and extracellular pH values in a murine model of HER2+ breast cancer. Tumor extracellular pH and perfusion were assessed by acquiring MRI-CEST (chemical exchange saturation transfer) images on a 3T scanner after intravenous administration of a pH-responsive contrast agent (iopamidol). Static PET images were recorded immediately after MRI acquisitions to quantify the extent of 18F-FDG uptake. We demonstrated the occurrence of tumor pHe changes that report on acidification of the interstitial fluid caused by an accelerated glycolysis. Combined PET and MRI-CEST images reported complementary spatial information of the altered glucose metabolism. Notably, a significant inverse correlation was found between extracellular tumor pH and 18F-FDG uptake, as a high 18F-FDG uptake corresponds to lower extracellular pH values. These results show how merging the information from 18F-FDG-uptake and extracellular pH measurements can improve characterization of the tumor microenvironment. Cancer Res; 76(22); 6463-70. ©2016 AACR.

Aggregation‐induced changes in the chemical exchange saturation transfer (CEST) signals of proteins

Chemical exchange saturation transfer (CEST) is an MRI technique that allows mapping of biomolecules (small metabolites, proteins) with nearly the sensitivity of conventional water proton MRI. In living organisms, several tissue-specific CEST effects have been observed and successfully applied to diagnostic imaging. In these studies, particularly the signals of proteins showed a distinct correlation with pathological changes. However, as CEST effects depend on various properties that determine and affect the chemical exchange processes, the origins of the observed signal changes remain to be understood. In this study, protein aggregation was identified as an additional process that is encoded in the CEST signals of proteins. Investigation of distinct proteins that are involved in pathological disorders, namely amyloid beta and huntingtin, revealed a significant decrease of all protein CEST signals upon controlled aggregation. This finding is of particular interest with regard to diagnostic imaging of patients with neurodegenerative diseases that involve amyloidogenesis, such as Alzheimer's or Huntington's disease. To investigate whether the observed CEST signal decrease also occurs in heterogeneous mixtures of aggregated cellular proteins, and thus prospectively in tissue, heat-shocked yeast cell lysates were employed. Additionally, investigation of different cell compartments verified the assignment of the protein CEST signals to the soluble part of the proteome. The results of in vitro experiments demonstrate that aggregation affects the CEST signals of proteins. This observation can enable hypotheses for CEST imaging as a non-invasive diagnostic tool for monitoring pathological alterations of the proteome in vivo.

The potential of multiparametric MRI of the breast.

MRI is an essential tool in breast imaging, with multiple established indications. Dynamic contrast-enhanced MRI (DCE-MRI) is the backbone of any breast MRI protocol and has an excellent sensitivity and good specificity for breast cancer diagnosis. DCE-MRI provides high-resolution morphological information, as well as some functional information about neoangiogenesis as a tumour-specific feature. To overcome limitations in specificity, several other functional MRI parameters have been investigated and the application of these combined parameters is defined as multiparametric MRI (mpMRI) of the breast. MpMRI of the breast can be performed at different field strengths (1.5-7 T) and includes both established (diffusion-weighted imaging, MR spectroscopic imaging) and novel MRI parameters (sodium imaging, chemical exchange saturation transfer imaging, blood oxygen level-dependent MRI), as well as hybrid imaging with positron emission tomography (PET)/MRI and different radiotracers. Available data suggest that multiparametric imaging using different functional MRI and PET parameters can provide detailed information about the underlying oncogenic processes of cancer development and progression and can provide additional specificity. This article will review the current and emerging functional parameters for mpMRI of the breast for improved diagnostic accuracy in breast cancer.

Diamagnetic chemical exchange saturation transfer (diaCEST) affords magnetic resonance imaging of extracellular matrix hydrogel implantation in a rat model of stroke.

Extracellular matrix (ECM) is widely used as an inductive biological scaffold to repair soft tissue after injury by promoting functional site-appropriate remodeling of the implanted material. However, there is a lack of non-invasive analysis methods to monitor the remodeling characteristics of the ECM material after implantation and its biodegradation over time. We describe the use of diamagnetic chemical exchange saturation transfer (CEST) magnetic resonance imaging to monitor the distribution of an ECM hydrogel after intracerebral implantation into a stroke cavity. Invitro imaging indicated a robust concentration-dependent detection of the ECM precursor and hydrogel at 1.8 and 3.6ppm, which broadly corresponded to chondroitin sulfate and fibronectin. This detection was robust to changes in pH and improved at 37°C. Invivo implantation of ECM hydrogel into the stroke cavity in a rat model corresponded macroscopically to the distribution of biomaterial as indicated by histology, but mismatches were also evident. Indeed, CEST imaging detected an endogenous "increased deposition". To account for this endogenous activity, pre-implantation images were subtracted from post-implantation images to yield a selective visualization of hydrogel distribution in the stroke cavity and its evolution over 7 days. The CEST detection of ECM returned to baseline within 3 days due to a decrease in fibronectin and chondroitin sulfate in the hydrogel. The distribution of ECM hydrogel within the stroke cavity is hence feasible invivo, but further advances are required to warrant a selective long-term monitoring in the context of biodegradation.