Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) has been developed and employed in multiple clinical imaging research centers worldwide. Selective radiofrequency (RF) ...saturation pulses with standard 2D and 3D MRI acquisition schemes are now routinely performed, and CEST MRI can produce semiquantitative results using magnetization transfer ratio asymmetry (MTRasym) analysis while accounting for B0 inhomogeneity. Faster clinical CEST MRI acquisition methods and more quantitative acquisition and analysis routines are under development. Endogenous biomolecules with amide, amine, and hydroxyl groups have been detected during clinical CEST MRI studies, and exogenous CEST agents have also been administered to patients. These CEST MRI tools show promise for contributing to assessments of cerebral ischemia, neurological disorders, lymphedema, osteoarthritis, muscle physiology, and solid tumors. This review summarizes the salient features of clinical CEST MRI protocols and critically evaluates the utility of CEST MRI for these clinical imaging applications.
Level of Evidence: 5
Technical Efficacy: Stage 1
J. Magn. Reson. Imaging 2018;47:11–27.
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.
Machine learning applied to the entire CEST spectrum improved the classification of the three tumor models, relative to classifications that used % CEST values at single saturation frequencies. A similar improvement was not attained with machine learning applied to T1 relaxation times or DCE signal evolutions, relative to more simplistic analysis methods.
The tumor microenvironment (TME) evolves to support tumor progression. One marker of more aggressive malignancy is hyaluronan (HA) accumulation. Here, we characterize biological and physical changes ...associated with HA-accumulating (HA-high) tumors.
We used immunohistochemistry,
imaging of tumor pH, and microdialysis to characterize the TME of HA-high tumors, including tumor vascular structure, hypoxia, tumor perfusion by doxorubicin, pH, content of collagen. and smooth muscle actin (α-SMA). A novel method was developed to measure real-time tumor-associated soluble cytokines and growth factors. We also evaluated biopsies of murine and pancreatic cancer patients to investigate HA and collagen content, important contributors to drug resistance.
In immunodeficient and immunocompetent mice, increasing tumor HA content is accompanied by increasing collagen content, vascular collapse, hypoxia, and increased metastatic potential, as reflected by increased α-SMA.
treatment of HA-high tumors with PEGylated recombinant human hyaluronidase (PEGPH20) dramatically reversed these changes and depleted stores of VEGF-A165, suggesting that PEGPH20 may also diminish the angiogenic potential of the TME. Finally, we observed in xenografts and in pancreatic cancer patients a coordinated increase in HA and collagen tumor content.
The accumulation of HA in tumors is associated with high tIP, vascular collapse, hypoxia, and drug resistance. These findings may partially explain why more aggressive malignancy is observed in the HA-high phenotype. We have shown that degradation of HA by PEGPH20 partially reverses this phenotype and leads to depletion of tumor-associated VEGF-A165. These results encourage further clinical investigation of PEGPH20.
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Recent advances in magnetic resonance imaging (MRI) contrast agents have provided new capabilities for biomarker detection through molecular imaging. MRI contrast agents based on the T
2
exchange ...mechanism have more recently expanded the armamentarium of agents for molecular imaging. Compared with T
1
and T
2
* agents, T
2
exchange agents have a slower chemical exchange rate, which improves the ability to design these MRI contrast agents with greater specificity for detecting the intended biomarker. MRI contrast agents that are detected through chemical exchange saturation transfer (CEST) have even slower chemical exchange rates. Another emerging class of MRI contrast agents uses hyperpolarized
13
C to detect the agent with outstanding sensitivity. These hyperpolarized
13
C agents can be used to track metabolism and monitor characteristics of the tissue microenvironment. Together, these various MRI contrast agents provide excellent opportunities to develop molecular imaging for biomarker detection.
Modern ultrasound (US) imaging is increasing its clinical impact, particularly with the introduction of US-based quantitative imaging biomarkers. Continued development and validation of such novel ...imaging approaches requires imaging phantoms that recapitulate the underlying anatomy and pathology of interest. However, current US phantom designs are generally too simplistic to emulate the structure and variability of the human body. Therefore, there is a need to create a platform that is capable of generating well-characterized phantoms that can mimic the basic anatomical, functional, and mechanical properties of native tissues and pathologies. Using a 3D-printing technique based on stereolithography, we fabricated US phantoms using soft materials in a single fabrication session, without the need for material casting or back-filling. With this technique, we induced variable levels of stable US backscatter in our printed materials in anatomically relevant 3D patterns. Additionally, we controlled phantom stiffness from 7 to >120 kPa at the voxel level to generate isotropic and anisotropic phantoms for elasticity imaging. Lastly, we demonstrated the fabrication of channels with diameters as small as 60 micrometers and with complex geometry (e.g., tortuosity) capable of supporting blood-mimicking fluid flow. Collectively, these results show that projection-based stereolithography allows for customizable fabrication of complex US phantoms.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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