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 (CEST) MRI provides a sensitive detection mechanism for imaging dilute labile protons, complementing the routine radiological exams. Enormous progress has been ...achieved in CEST MRI and image analysis, from the mathematical modeling, CEST agent design, and most importantly, increasing adoption of CEST imaging in the clinical setting. Therefore, CEST imaging represents an emerging field that involves multiple disciplines and together made a remarkable transition from the simplistic CEST‐weighted MRI to quantitative CEST (qCEST) analysis. This review focuses on the recent advancements in CEST quantification techniques and findings of in vivo CEST imaging in representative disorders of ischemia, tumor, and epilepsy. In addition, limitations of current CEST methodologies are examined that should help guide future development of more sensitive and quantitative CEST imaging techniques and ultimately, facilitate their adoption in the clinical setting.
Liver fibrogenesis is accompanied by upregulation of lysyl oxidase enzymes, which catalyze oxidation of lysine ε-amino groups on the extracellular matrix proteins to form the aldehyde containing ...amino acid allysine (LysAld). Here, we describe the design and synthesis of novel manganese-based MRI probes with high signal amplification for imaging liver fibrogenesis. Rational design of a series of stable hydrazine-equipped manganese MRI probes gives Mn-2CHyd with the highest affinity and turn-on relaxivity (4-fold) upon reaction with LysAld. A dynamic PET-MRI study using 52 MnMn-2CHyd showed low liver uptake of the probe in healthy mice. The ability of the probe to detect liver fibrogenesis was then demonstrated in vivo in CCl4-injured mice. This study enables further development and application of manganese-based hydrazine-equipped probes for imaging liver fibrogenesis.
Imaging tools for kidney inflammation could improve care for patients suffering inflammatory kidney diseases by lessening reliance on percutaneous biopsy or biochemical tests alone. During kidney ...inflammation, infiltration of myeloid immune cells generates a kidney microenvironment that is oxidizing relative to normal kidney. Here, we evaluated whether magnetic resonance imaging (MRI) using the redox-active iron (Fe) complex Fe-PyC3A as an oxidatively activated probe could serve as a marker of kidney inflammation using mouse models of unilateral ischemia-reperfusion injury (IRI) and lupus nephritis (MRL-lpr mice). We imaged unilateral IRI in gp91phox knockout mice, which are deficient in the nicotinamide oxidase II (NOX2) enzyme required for myeloid oxidative burst, as loss of function control, and imaged MRL/MpJ mice as non-kidney involved lupus control. Gadoterate meglumine was used as a non-oxidatively activated control MRI probe. Fe-PyC3A safety was preliminarily examined following a single acute dose. FePyC3A generated significantly greater MRI signal enhancement in the IRI kidney compared to the contralateral kidney in wild-type mice, but the effect was not observed in the NOX2-deficient control. Fe-PyC3A also generated significantly greater kidney enhancement in MRL-lpr mice compared to MRL/MpJ control. Gadoterate meglumine did not differentially enhance the IRI kidney over the contralateral kidney and did not differentially enhance the kidneys of MRL-lpr over MRL/MpJ mice. Fe-PyC3A was well tolerated at the highest dose evaluated, which was a 40-fold greater than required for imaging. Thus, our data indicate that MRI using Fe-PyC3A is specific to an oxidizing kidney environment shaped by activity of myeloid immune cells and support further evaluation of Fe-PyC3A for imaging kidney inflammation.
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pH-sensitive amide proton transfer (APT) MRI provides a surrogate metabolic biomarker that complements the widely-used perfusion and diffusion imaging. However, the endogenous APT MRI is often ...calculated using the asymmetry analysis (MTRasym), which is susceptible to an inhomogeneous shift due to concomitant semisolid magnetization transfer (MT) and nuclear overhauser (NOE) effects. Although the intact brain tissue has little pH variation, white and gray matter appears distinct in the MTRasym image. Herein we showed that the heterogeneous MTRasym shift not related to pH highly correlates with MT ratio (MTR) and longitudinal relaxation rate (R1w), which can be reasonably corrected using the multiple regression analysis. Because there are relatively small MT and R1w changes during acute stroke, we postulate that magnetization transfer and relaxation-normalized APT (MRAPT) analysis increases MRI specificity to acidosis over the routine MTRasym image, hence facilitates ischemic lesion segmentation. We found significant differences in perfusion, pH and diffusion lesion volumes (P<0.001, ANOVA). Furthermore, MRAPT MRI depicted graded ischemic acidosis, with the most severe acidosis in the diffusion lesion (−1.05±0.29%/s), moderate acidification within the pH/diffusion mismatch (i.e., metabolic penumbra, −0.67±0.27%/s) and little pH change in the perfusion/pH mismatch (i.e., benign oligemia, −0.04±0.14%/s), providing refined stratification of ischemic tissue injury.
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•Magnetization transfer and relaxation-normalized APT (MRAPT) MRI is pH specific.•pH MRI shows graded metabolic disruption in acute ischemic tissue.•pH MRI delineates metabolic penumbra from benign oligemia.•pH MRI augments perfusion and diffusion imaging for refined tissue classification.
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