In vivo Magnetic Resonance Imaging of Tumor Protease Activity

Haris, Mohammad; Singh, Anup; Mohammed, Imran; Ittyerah, Ranjit; Nath, Kavindra; Nanga, Ravi Prakash Reddy; DeBrosse, Catherine; Kogan, Feliks; Cai, Kejia; Poptani, Harish; Reddy, D. R.; Hariharan, Hari; Reddy, Ravinder

doi:10.1038/srep06081

Cited by 58 publications

(42 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A variety of other CEST agents have been developed that detect enzyme activity using catalyCEST MRI or similar CEST MRI protocols. CatalyCEST agents have detected proteases such as cathepsins, caspases, matrix metalloproteases, urokinase plasminogen activator, kallikrein 6, and general protease activity . Other agents have cleaved substrates to detect glycoside hydrolases, sulfatases, esterases, and phosphatases .…”

Section: Catalycest Mrimentioning

confidence: 99%

Assessments of tumor metabolism with CEST MRI

Goldenberg

Pagel

2018

NMR in Biomedicine

View full text Add to dashboard Cite

Chemical exchange saturation transfer (CEST) is a relatively new contrast mechanism for MRI. CEST MRI exploits a specific MR frequency (chemical shift) of a molecule while generating an image with good spatial resolution using standard MRI techniques, combining the specificity of MRS with the spatial resolution of MRI. Many CEST MRI acquisition methods have been developed to improve analyses of tumor metabolism. GluCEST, CrCEST, and LATEST can map glutamate, creatine, and lactate, which are important metabolites involved in tumor metabolism. GlucoCEST MRI tracks the pharmacokinetics of glucose transport and cell internalization within tumors. CatalyCEST MRI detects enzyme catalysis that changes a substrate CEST agent. AcidoCEST MRI measures extracellular pH of the tumor microenvironment by exploiting a ratio of two pH-dependent CEST signals. This review describes each technique, the technical issues involved with CEST MRI and each specific technique, and the merits and challenges associated with applying each CEST MRI technique to study tumor metabolism.

show abstract

Section: Catalycest Mrimentioning

confidence: 99%

Assessments of tumor metabolism with CEST MRI

Goldenberg

Pagel

2018

NMR in Biomedicine

View full text Add to dashboard Cite

show abstract

“…The substantial sensitivity gain enables CEST MRI to map certain dilute metabolites (2)(3)(4)(5) and physiological properties such as pH (6)(7)(8). It has been applied to study acute stroke (9)(10)(11)(12), tumor (13)(14)(15)(16)(17), and epilepsy (18).…”

Section: Introductionmentioning

confidence: 99%

Direct saturation‐corrected chemical exchange saturation transfer MRI of glioma: Simplified decoupling of amide proton transfer and nuclear overhauser effect contrasts

Zhou

Wang

Cheung

et al. 2017

Magnetic Resonance in Med

View full text Add to dashboard Cite

Purpose Chemical exchange saturation transfer (CEST) MRI has shown promise in tissue characterization in diseases like stroke and tumor. However, in vivo CEST imaging such as amide proton transfer (APT) MRI is challenging due to concomitant factors such as direct water saturation, macromolecular magnetization transfer and nuclear overhauser effect (NOE), which leads to a complex contrast in the commonly-used asymmetry analysis (MTRasym). Herein we proposed a DIrect Saturation-Corrected CEST (DISC-CEST) analysis for simplified decoupling and quantification of in vivo CEST effects. Methods CEST MRI and relaxation measurements were performed on a classical 2-pool creatine-gel CEST phantom and normal rat brains (N=6) and a rat model of glioma (N=8) at 4.7T. The proposed DISC-CEST quantification was performed and compared with conventional MTRasym and the original three-offset method. Results We demonstrated the DISC-CEST contrast of the phantom had much stronger correlation with MTRasym than the three-offset method, which showed substantial underestimation. In normal rat brains, the DISC-CEST approach revealed significantly stronger APT effect in gray matter and higher NOE effect in white matter. Furthermore, the APT and NOE maps derived from DISC-CEST showed significantly higher APT effect in the tumors than contralateral normal tissue but no apparent difference in NOE. Conclusion The proposed DISC-CEST method, by correction of non-linear direct water saturation effect, serves as a promising alternative to both the commonly-used MTRasym and the simplistic three-offset analyses. It provides simple yet reliable in vivo CEST quantification such as APT and NOE mapping in brain tumor, which is promising for clinical translation.

show abstract

“…Chemical exchange saturation transfer (CEST) MRI is sensitive to the chemical exchange process between labile protons and bulk water signal, providing a contrast mechanism for imaging dilute CEST agents and microenvironment properties such as pH and temperature (1)(2)(3)(4)(5). Indeed, CEST-weighted MRI has found substantial interest in molecular imaging as well as in vivo applications such as acute stroke (6)(7)(8)(9)(10)(11)(12)(13)(14)(15), tumor (16)(17)(18)(19)(20)(21)(22)(23)(24) and epilepsy imaging (25). Whereas the CEST MRI measurement varies with experimental factors, particularly the RF irradiation level and duration, such dependence has been harnessed as a novel approach for quantitative CEST (qCEST) analysis, including omega plots and RF-power based ratiometric calculation (26)(27)(28)(29)(30)(31)(32)(33).…”

Section: Introductionmentioning

confidence: 99%

A theoretical analysis of chemical exchange saturation transfer echo planar imaging (CEST‐EPI) steady state solution and the CEST sensitivity efficiency‐based optimization approach

Jiang

Zhou

Wen

et al. 2016

Contrast Media & Molecular

View full text Add to dashboard Cite

Chemical exchange saturation transfer (CEST) MRI is sensitive to dilute labile protons and microenvironmental properties, augmenting routine relaxation-based MRI. Recent development of quantitative CEST (qCEST) analysis such as omega plot and RF-power based ratiometric calculation have extended our ability to elucidate the underlying CEST system beyond the simplistic apparent CEST measurement. CEST MRI strongly varies with experimental factors, including the RF irradiation level and duration as well as repetition time and flip angle. In addition, CEST MRI effect is typically small, and experimental optimization strategies have to be carefully evaluated in order to enhance the CEST imaging sensitivity. Although routine CEST MRI has been optimized largely based on maximizing the magnitude of the CEST effect, the CEST signal-to-noise (SNR) efficiency provides a more suitable optimization index, particularly when the scan time is constrained. Herein, we derived an analytical solution of the CEST effect that takes into account of key experimental parameters including repetition time, imaging flip angle and RF irradiation level, and solved its SNR efficiency. The solution expedites CEST imaging sensitivity calculation, substantially faster than Bloch-McConnell equations-based numerical simulation approach. In addition, the analytical solution-based SNR formula enables the exhaustive optimization of CEST MRI, which simultaneously predict multiple optimal parameters such as repetition time, flip angle and RF saturation level based on the chemical shift and exchange rate. The sensitivity efficiency-based optimization approach could simplify and guide imaging of CEST agents, including glycogen, glucose, creatine, gamma-aminobutyric acid and glutamate.

show abstract

In vivo Magnetic Resonance Imaging of Tumor Protease Activity

Cited by 58 publications

References 21 publications

Assessments of tumor metabolism with CEST MRI

Assessments of tumor metabolism with CEST MRI

Direct saturation‐corrected chemical exchange saturation transfer MRI of glioma: Simplified decoupling of amide proton transfer and nuclear overhauser effect contrasts

A theoretical analysis of chemical exchange saturation transfer echo planar imaging (CEST‐EPI) steady state solution and the CEST sensitivity efficiency‐based optimization approach

Contact Info

Product

Resources

About