Analysis Protocol for the Quantification of Renal pH Using Chemical Exchange Saturation Transfer (CEST) MRI

Published on Jan 1, 2021in Methods of Molecular Biology
· DOI :10.1007/978-1-0716-0978-1_40
Hahnsung Kim1
Estimated H-index: 1
(Yerkes National Primate Research Center),
Yin Wu21
Estimated H-index: 21
(Harvard University)
+ 3 AuthorsPhillip Zhe Sun33
Estimated H-index: 33
(Yerkes National Primate Research Center)
The kidney plays a major role in maintaining body pH homeostasis. Renal pH, in particular, changes immediately following injuries such as intoxication and ischemia, making pH an early biomarker for kidney injury before the symptom onset and complementary to well-established laboratory tests. Because of this, it is imperative to develop minimally invasive renal pH imaging exams and test pH as a new diagnostic biomarker in animal models of kidney injury before clinical translation. Briefly, iodinated contrast agents approved by the US Food and Drug Administration (FDA) for computed tomography (CT) have demonstrated promise as novel chemical exchange saturation transfer (CEST) MRI agents for pH-sensitive imaging. The generalized ratiometric iopamidol CEST MRI analysis enables concentration-independent pH measurement, which simplifies in vivo renal pH mapping. This chapter describes quantitative CEST MRI analysis for preclinical renal pH mapping, and their application in rodents, including normal conditions and acute kidney injury.This publication is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This analysis protocol chapter is complemented by two separate chapters describing the basic concepts and experimental procedure.
📖 Papers frequently viewed together
5 Citations
16 Authors (Yanyan Tang, ..., Renhua Wu)
3 Citations
#1Kowsalya Devi Pavuluri (ICSCI: Kennedy Krieger Institute)H-Index: 2
#2Irini Manoli (NIH: National Institutes of Health)H-Index: 24
Last. Michael T. McMahon (ICSCI: Kennedy Krieger Institute)H-Index: 45
view all 7 authors...
Chronic Kidney Disease (CKD) is a cardinal feature of methylmalonic acidemia (MMA), a prototypic organic acidemia. Impaired growth, low activity, and protein restriction affect muscle mass and lower serum creatinine, which can delay diagnosis and management of renal disease. We have designed an alternative strategy for monitoring renal function based on administration of a pH sensitive MRI agent and assessed this in a mouse model. This protocol produced three metrics: kidney contrast, ~4% for se...
19 CitationsSource
#1Annasofia Anemone (UNITO: University of Turin)H-Index: 6
#2Lorena Consolino (UNITO: University of Turin)H-Index: 13
Last. Dario Livio Longo (UNITO: University of Turin)H-Index: 28
view all 5 authors...
Cancer cells are characterized by a metabolic shift in cellular energy production, orchestrated by the transcription factor HIF-1α, from mitochondrial oxidative phosphorylation to increased glycolysis, regardless of oxygen availability (Warburg effect). The constitutive upregulation of glycolysis leads to an overproduction of acidic metabolic products, resulting in enhanced acidification of the extracellular pH (pHe ~ 6.5), which is a salient feature of the tumor microenvironment. Despite the im...
51 CitationsSource
#1Enfeng Wang (Zhengzhou University)H-Index: 11
#2Yin Wu (CAS: Chinese Academy of Sciences)H-Index: 21
Last. Phillip Zhe Sun (Harvard University)H-Index: 33
view all 7 authors...
Abstract pH-weighted amide proton transfer (APT) MRI is sensitive to tissue pH change during acute ischemia, complementing conventional perfusion and diffusion stroke imaging. However, the currently used pH-weighted magnetization transfer (MT) ratio asymmetry (MTRasym) analysis is of limited pH specificity. To overcome this, MT and relaxation normalized APT (MRAPT) analysis has been developed that to homogenize the background signal, thus providing highly pH conspicuous measurement. Our study ai...
23 CitationsSource
#1Dong-Hoon Lee (USYD: University of Sydney)H-Index: 18
#2Do-Wan Lee (Asan Medical Center)H-Index: 5
Last. Dong-Cheol Woo (UOU: University of Ulsan)H-Index: 7
view all 10 authors...
Purpose To evaluate signal changes in the hippocampus of epileptic seizure rat models, based on quantified creatine chemical exchange saturation transfer (CrCEST) signals.
5 CitationsSource
#1Aaron Kujawa (UCL: University College London)H-Index: 3
#2Mina Kim (UCL: University College London)H-Index: 3
Last. Xavier Golay (UCL: University College London)H-Index: 5
view all 7 authors...
Abstract Fitting a model based on the Bloch-McConnell (BM) equations to Chemical Exchange Saturation Transfer (CEST) spectra allows for the quantification of metabolite concentration and exchange rate as well as simultaneous correction of field inhomogeneity, direct water saturation and magnetization transfer. Employing a Bayesian fitting approach permits the integration of prior information into the analysis to incorporate expected parameter distributions and to prevent over-fitting. However, t...
3 CitationsSource
#1Yin Wu (CAS: Chinese Academy of Sciences)H-Index: 21
#2Iris Yuwen Zhou (Harvard University)H-Index: 19
Last. Phillip Zhe Sun (Harvard University)H-Index: 33
view all 6 authors...
PURPOSE: To extend the pH detection range of iopamidol-based ratiometric chemical exchange saturation transfer (CEST) MRI at sub-high magnetic field and establish quantitative renal pH MRI. METHODS: Chemical exchange saturation transfer imaging was performed on iopamidol phantoms with pH of 5.5 to 8.0 and in vivo on rat kidneys (n = 5) during iopamidol administration at a 4.7 T. Iopamidol CEST effects were described using a multipool Lorentzian model. A generalized ratiometric analysis was condu...
33 CitationsSource
#1Francesca ArenaH-Index: 17
#2Pietro IrreraH-Index: 3
Last. Dario Livio LongoH-Index: 28
view all 6 authors...
Abstract Several molecules have been exploited for developing MRI pH sensors based on the chemical exchange saturation transfer (CEST) technique. A ratiometric approach, based on the saturation of two exchanging pools at the same saturation power, or by varying the saturation power levels on the same pool, is usually needed to rule out the concentration term from the pH measurement. However, all these methods have been demonstrated by using a continuous wave saturation scheme that limits its tra...
7 CitationsSource
#1Tao Jin (University of Pittsburgh)H-Index: 35
#2Ping Wang (University of Pittsburgh)H-Index: 18
Last. Seong-Gi Kim (SKKU: Sungkyunkwan University)H-Index: 85
view all 4 authors...
Abstract Amide-proton-transfer weighted (APTw) MRI has emerged as a non-invasive pH-weighted imaging technique for studies of several diseases such as ischemic stroke. However, its pH-sensitivity is relatively low, limiting its capability to detect small pH changes. In this work, computer simulations, protamine phantom experiments, and in vivo gas challenge and experimental stroke in rats showed that, with judicious selection of the saturation pulse power, the amide-CEST at 3.6 ppm and guanidyl-...
33 CitationsSource
#1Annasofia Anemone (UNITO: University of Turin)H-Index: 6
#2Lorena Consolino (UNITO: University of Turin)H-Index: 13
Last. Dario Livio Longo (National Research Council)H-Index: 28
view all 7 authors...
: Dichloroacetate (DCA) can reverse the glycolytic phenotype that is responsible of increased lactate production and extracellular pH acidification in cancer cells. Magnetic resonance imaging-chemical exchange saturation transfer (MRI-CEST) pH mapping is a novel non-invasive imaging approach that can measure in vivo extracellular tumour pH. We examined whether MRI-CEST pH mapping can monitor in vivo changes in tumour acidosis for assessing treatment response to DCA. Cell viability and extracellu...
32 CitationsSource
#1Dario Livio LongoH-Index: 28
#2Juan Carlos CutrinH-Index: 13
Last. Silvio AimeH-Index: 91
view all 5 authors...
: Acute kidney injury (AKI) in mice caused by sustained ischemia followed by reperfusion is associated with acute tubular necrosis and renal dysfunctional blood flow. Although the principal role of the kidney is the maintenance of acid-base balance, current imaging approaches are unable to assess this important parameter, and clinical biomarkers are not robust enough in evaluating the severity of kidney damage. Therefore, novel noninvasive imaging approaches are needed to assess the acid-base ho...
28 CitationsSource
Cited By1
Abstract Metabolism reveals pathways by which cells, in healthy and disease tissues, use nutrients to fuel their function and (re)growth. However, gene-centric views have dominated cancer hallmarks, relegating metabolic reprogramming that all cells in the tumor niche undergo as an incidental phenomenon. Aerobic glycolysis in cancer is well known, but recent evidence suggests that diverse symbolic traits of cancer cells are derived from oncogene-directed metabolism required for their sustenance a...