Brain pH Imaging and its Applications

Regulation of physiological pH is integral for proper whole-body and cellular function, and disruptions in pH homeostasis can be both a cause and effect of disease. In light of this, many methods have been developed to monitor pH in cells and animals. In this study, we report a chemiluminescence resonance energy transfer (CRET) probe Ratio-pHCL-1, comprised of an acrylamide 1,2-dioxetane chemiluminescent scaffold with an appended pH-sensitive carbofluorescein fluorophore. The probe provides an accurate measurement of pH between 6.8-8.4, making it viable tool for measuring pH in biological systems. Further, its ratiometric output is independent of confounding variables. Quantification of pH can be accomplished both using common fluorimetry and advanced optical imaging methods. Using an IVIS Spectrum, pH can be quantified through tissue with Ratio-pHCL-1, which has been shown in vitro and precisely calibrated in sacrificed mouse models. Initial studies showed that intraperitoneal injections of Ratio-pHCL-1 into sacrificed mice produce a photon flux of more than 10^10 photons per second, and showed a significant difference in ratio of emission intensities between pH 6.0, 7.0, and 8.0.

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Ratiometric MRI Sensors Based on Core-Shell Nanoparticles for Quantitative pH Imaging

Advanced Materials ◽

10.1002/adma.201305018 ◽

2014 ◽

Vol 26 (19) ◽

pp. 2989-2992 ◽

Cited By ~ 23

Author(s):

Satoshi Okada ◽

Shin Mizukami ◽

Takao Sakata ◽

Yutaka Matsumura ◽

Yoshichika Yoshioka ◽

...

Keyword(s):

Core Shell ◽

Shell Nanoparticles ◽

Ph Imaging ◽

Core Shell Nanoparticles

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Application of chemical imaging sensor to in-situ pH imaging in the vicinity of a corroding metal surface

Electrochimica Acta ◽

10.1016/j.electacta.2015.07.184 ◽

2015 ◽

Vol 183 ◽

pp. 137-142 ◽

Cited By ~ 12

Author(s):

Ko-ichiro Miyamoto ◽

Sakura Sakakita ◽

Torsten Wagner ◽

Michael J. Schöning ◽

Tatsuo Yoshinobu

Keyword(s):

Metal Surface ◽

Chemical Imaging ◽

Ph Imaging ◽

Imaging Sensor

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In vivo evaluation of tumour acidosis for assessing the early metabolic response and onset of resistance to dichloroacetate by using magnetic resonance pH imaging

International Journal of Oncology ◽

10.3892/ijo.2017.4029 ◽

2017 ◽

Vol 51 (2) ◽

pp. 498-506 ◽

Cited By ~ 20

Author(s):

Annasofia Anemone ◽

Lorena Consolino ◽

Laura Conti ◽

Francesca Reineri ◽

Federica Cavallo ◽

...

Keyword(s):

Magnetic Resonance ◽

Metabolic Response ◽

In Vivo Evaluation ◽

Ph Imaging ◽

Early Metabolic Response

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Bimodal MR-PET Agent for Quantitative pH Imaging

Angewandte Chemie ◽

10.1002/ange.201000075 ◽

2010 ◽

Vol 122 (13) ◽

pp. 2432-2434 ◽

Cited By ~ 21

Author(s):

Luca Frullano ◽

Ciprian Catana ◽

Thomas Benner ◽

A. Dean Sherry ◽

Peter Caravan

Keyword(s):

Ph Imaging

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Application of the pH-Imaging Sensor to Determining the Diffusion Coefficients of Ions in Electrolytic Solutions

Japanese Journal of Applied Physics ◽

10.1143/jjap.39.l318 ◽

2000 ◽

Vol 39 (Part 2, No. 4A) ◽

pp. L318-L320 ◽

Cited By ~ 20

Author(s):

Tatsuo Yoshinobu ◽

Tetsuro Harada ◽

Hiroshi Iwasaki

Keyword(s):

Diffusion Coefficients ◽

Ph Imaging ◽

Imaging Sensor

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Effect of hyperglycemia on brain pH levels in areas of focal incomplete cerebral ischemia in monkeys

Journal of Neurosurgery ◽

10.3171/jns.1986.65.5.0693 ◽

1986 ◽

Vol 65 (5) ◽

pp. 693-696 ◽

Cited By ~ 46

Author(s):

W. Richard Marsh ◽

Robert E. Anderson ◽

Thoralf M. Sundt

Keyword(s):

Adverse Effect ◽

Cerebral Ischemia ◽

Cell Damage ◽

Treated Group ◽

Squirrel Monkeys ◽

Control Group ◽

Content Type ◽

Brain Ph ◽

Fine Print ◽

Incomplete Ischemia

✓ The adverse effect of a minimal cerebral blood flow (CBF) in models of global ischemia has been noted by many investigators. One factor believed important in this situation is the level of blood glucose, since a continued supply of this metabolite results in increased tissue lactate, decreased brain pH, and increased cell damage. The authors have extended these observations to a model of focal incomplete ischemia. Brain pH was measured in fasted squirrel monkeys in regions of focal incomplete ischemia after transorbital occlusion of the middle cerebral artery (MCA). In both control and hyperglycemic animals, CBF was reduced to less than 30% of baseline. At 3 hours after MCA occlusion, brain pH in the control group was 6.66 ± 0.68 as compared to 6.27 ± 0.26 in the glucose-treated group. This difference was statistically significant by Student's unpaired t-test (p < 0.05). Thus, hyperglycemia results in decreased tissue pH in regions of focal incomplete cerebral ischemia in monkeys.

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Brain pH responses to sodium bicarbonate and Carbicarb during systemic acidosis

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1989.256.5.h1316 ◽

1989 ◽

Vol 256 (5) ◽

pp. H1316-H1321 ◽

Cited By ~ 7

Author(s):

J. I. Shapiro ◽

M. Whalen ◽

R. Kucera ◽

N. Kindig ◽

G. Filley ◽

...

Keyword(s):

Metabolic Acidosis ◽

Sodium Bicarbonate ◽

Ammonium Chloride ◽

Respiratory Acidosis ◽

Arterial Pco2 ◽

Bicarbonate Therapy ◽

Brain Ph ◽

Dose Dependent ◽

Intracellular Alkalinization

Rats subjected to ammonium chloride-induced metabolic acidosis or respiratory acidosis caused by hypercapnia were given alkalinization therapy with either sodium bicarbonate or Carbicarb. Ammonium chloride induced dose-dependent systemic acidosis but did not affect intracellular brain pH. Hypercapnia caused dose-dependent systemic acidosis as well as decreases in intracellular brain pH. Sodium bicarbonate treatment resulted in systemic alkalinization and increases in arterial PCO2 in both acidosis models, but it caused intracellular brain acidification in rats with ammonium chloride acidosis. Carbicarb therapy resulted in systemic alkalinization without major changes in arterial PCO2 and intracellular brain alkalinization in both acidosis models. These data demonstrate that bicarbonate therapy of systemic acidosis may be associated with "paradoxical" intracellular brain acidosis, whereas Carbicarb causes both systemic and intracellular alkalinization under conditions of fixed ventilation.

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