Multiparametric quantification of the heterogeneity of free Ca2+ concentration by 19F MR spectroscopy

Lutz, Norbert W.; Bernard, Monique

doi:10.1016/j.jmr.2018.10.009

Cited by 3 publications

(19 citation statements)

References 30 publications

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“…The use of 19 F MRS for measuring Na + concentrations is based on the dependence of the chemical shift, δ, of the [Na + ] i ‐sensitive 19 F resonance of the reporter molecule (FCrown‐1). The relationship between the measured chemical shift, δ mea , and [Na + ] is given by the following equations, in strict analogy with equations previously used for [Ca 2+ ] and [Mg 2+ ]:

([], {Na}^{+}) = K_{d}^{NaCro} ((), \frac{1}{Φ} - 1)

with normalΦ = \frac{{([], Cro)}_{normalf}}{{([], Cro)}_{tot}} = \frac{δ_{mea} - δ_{NaCro}}{δ_{Cro} - δ_{NaCro}}

with

K_{d}^{NaCro}

, dissociation constant of complex between Na + and the ligand, FCrown‐1; [Cro] f , concentration of free (uncomplexed) FCrown‐1; [FCro] tot , total concentration of FCrown‐1 (free and complexed with Na + ); δ Cro , meta ‐ 19 F chemical shift for free (uncomplexed) FCrown‐1; δ NaCro , meta ‐ 19 F chemical shift for FCrown‐1 complexed with Na + . Experimentally determined

K_{d}^{NaCro}

, δ Cro and δ NaCro values have been published previously .…”

Section: Methodsmentioning

confidence: 99%

“…[Na + ] curves are then used to calculate quantitative parameters characterizing the statistical distribution of [Na + ] values in a given volume. The algorithmic tools are similar to those presented by us previously for the evaluation of heterogeneity in other physical parameters; the resulting equations for [Na + ] heterogeneity analysis are presented in the supporting information. Briefly, the obtained [Na + ] curve is approximated as a histogram, and appropriate equations are used to extract a number of statistical descriptors of [Na + ] heterogeneity.…”

Section: Methodsmentioning

confidence: 99%

“…In addition, we subject in vitro spectra to our algorithms designed to extract statistical [Na + ] descriptors. Our mathematical and statistical equations are formally analogous to the equations presented previously for studying Ca 2+ or Mg 2+ concentrations based on 19 F or 31 P MRS, respectively . Therefore, the general mathematical validity of the transformation of appropriate NMR line shapes to ion concentration profiles, and the justification for deriving statistical parameters from these profiles are already documented; we now adjust the underlying equations to the case of [Na + ] analysis by way of FCrown‐1.…”

Section: Introductionmentioning

confidence: 92%

“…In many cases, the relative sizes of sample regions representing characteristic concentration ranges may also be calculated. The algorithms to be employed are similar to those previously introduced by us to analyze heterogeneity in Ca 2+ or Mg 2+ concentration (by 19 F or 31 P MRS, respectively), in pH (by 31 P MRS), or in temperature (by 1 H MRS) . In addition to the presentation of our algorithm, we provide the proof of principle for our method, both in silico and in vitro.…”

Section: Introductionmentioning

confidence: 99%

“…When combined with monovoxel 19 F NMR acquisition, our analysis will be fast and provide valuable statistical information that is complementary to the spatially resolved data obtainable by the Na + mapping techniques mentioned above. When used in multivoxel 19 F NMR experiments such as chemical‐shift imaging (CSI), our new method will be able to generate spatial and full statistical information on the distribution of [Na + ] i concentrations in one single experiment, akin to the analogous method for Ca 2+ . Once translated into the field of biomedicine, our multiparametric analysis can be expected to significantly enhance the analysis of free intracellular Na + concentrations in vivo by offering hitherto inaccessible quantitative characterization of tissue heterogeneity with respect to [Na + ] i , ie information that is complementary to 23 Na MRI.…”

Section: Introductionmentioning

confidence: 99%

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A method for multiparametric statistical quantification of the heterogeneity of free Na⁺concentration by¹⁹F MR spectroscopy: Proof of principlein silicoandin vitro

Lutz

Bernard

2019

NMR in Biomedicine

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Sodium(I) (Na+) is one of the most important cations in mammalian tissues. Since Na+ plays a key role in basic cell function, noninvasive methods for measuring intracellular concentrations of free sodium ions in biological tissue have been developed on the basis of 19F NMR spectroscopy. However, intracellular Na+ levels are often not uniform throughout a tissue volume (or voxel) being measured. In such cases, [Na+] heterogeneity is not reflected in results obtained by the classical technique, and may even result in biased average values. For this reason, we have designed an approach for quantifying [Na+] heterogeneity. First, the 19F MRS resonance from FCrown‐1 serving as a “Na+ probe” is transformed into a [Na+] curve. Then the digital points of the resulting [Na+] profile are used to construct a histogram with specially developed algorithms. From each [Na+] histogram, at least eight quantitative parameters describing the underlying statistical [Na+] distribution were computed: weighted median, weighted mean, standard deviation, range, mode(s), kurtosis, skewness, and entropy. In addition to our new paradigm, we present a first validation based on (i) computer simulations and (ii) experimentally obtained 19F MR spectra of model solutions. This basic proof of principle warrants future in vivo experiments, in particular because of its ability to provide quantitative information complementary to that made available by commonly used 23Na MRI: (i) multiparametric statistical characterization of [Na+] distributions; (ii) total [Na+] heterogeneity analysis not intrinsically limited by the size of any MRI voxels; and (iii) analysis of unequivocally intracellular [Na+], as opposed to measurement of a combination of intra‐ and extracellular [Na+].

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([], {Na}^{+}) = K_{d}^{NaCro} ((), \frac{1}{Φ} - 1)

with normalΦ = \frac{{([], Cro)}_{normalf}}{{([], Cro)}_{tot}} = \frac{δ_{mea} - δ_{NaCro}}{δ_{Cro} - δ_{NaCro}}

with

K_{d}^{NaCro}

K_{d}^{NaCro}

, δ Cro and δ NaCro values have been published previously .…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

A method for multiparametric statistical quantification of the heterogeneity of free Na⁺concentration by¹⁹F MR spectroscopy: Proof of principlein silicoandin vitro

Lutz

Bernard

2019

NMR in Biomedicine

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Multiparametric statistical quantification of pH heterogeneity by ¹H MRS and MRSI of extracellular pH markers: Proof of principle

Lutz

Bernard

2019

NMR in Biomedicine

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Acid production and transport in numerous biological tissues and medical conditions are active areas of research. Heterogeneity of pH within a given homogeneous‐appearing tissue volume has been reported, but none of the conventional methods currently available for measuring tissue pH provides quantitative parameters describing the frequency of occurrence of pH values within such a volume. We have previously presented a multiparametric noninvasive in vivo approach, providing at least 10 different statistical descriptors of pH heterogeneity based on a novel type of line shape analysis developed for pH‐sensitive 31P MRS resonances. However, this method suffers from lack of sensitivity, thus making rapid and spatially resolved measurements difficult. We present here the proof of principle of a new, more sensitive approach to statistical characterization of extracellular pH heterogeneity based on 1H MRS, with the potential of being combined with spatial resolution. We experimentally study a range of test solutions of a reporter molecule that has previously been shown to possess a 1H MRS resonance whose chemical shift varies with pH, including when injected intravenously into experimental animals (imidazole ethoxycarbonylpropionic acid, [IEPA]). Statistical pH heterogeneity descriptors are determined for phantoms mimicking tissue pH heterogeneity. To this end, the pH‐sensitive 1H MRS resonance is transformed into a pH curve. Subsequently, the digital points of this pH profile are used to build a histogram using dedicated algorithms. The following descriptors are computed from this histogram: weighted mean pH and median pH, pH standard deviation, pH range, pH mode(s), pH kurtosis, pH skewness and pH entropy. Our new method is also validated by analyzing previously published in vivo MRSI spectra. The proof of principle provided in this work should form the basis of further in vivo studies in physiology and medicine, eg in cancer research, but also in other fields such as kidney and muscle research.

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Contactless Thermometry by MRI and MRS: Advanced Methods for Thermotherapy and Biomaterials

Lutz¹,

Bernard²

2020

iScience

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Control of temperature variation is of primordial importance in particular areas of biomedicine. In this context, medical treatments such as hyperthermia and cryotherapy, but also the development and use of hydrogel-based biomaterials are of particular concern. To enable accurate temperature measurement without perturbing or even destroying the biological tissue or material to be monitored, contactless thermometry methods are preferred. Among these, the most suitable are based on magnetic resonance imaging and spectroscopy (MRI, MRS). Here, we address the latest developments in this field as well as their current and anticipated practical applications. We highlight recent progress aimed at rendering MR thermometry faster and more reproducible, versatile and sophisticated, and provide our perspective on how these new techniques broaden the range of applications in medical treatments and biomaterial development by enabling insight into finer details of thermal behavior. Thus, these methods facilitate optimization of clinical and industrial heating and cooling protocols.

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Multiparametric quantification of the heterogeneity of free Ca2+ concentration by 19F MR spectroscopy

Cited by 3 publications

References 30 publications

A method for multiparametric statistical quantification of the heterogeneity of free Na⁺concentration by¹⁹F MR spectroscopy: Proof of principlein silicoandin vitro

A method for multiparametric statistical quantification of the heterogeneity of free Na⁺concentration by¹⁹F MR spectroscopy: Proof of principlein silicoandin vitro

Multiparametric statistical quantification of pH heterogeneity by ¹H MRS and MRSI of extracellular pH markers: Proof of principle

Contactless Thermometry by MRI and MRS: Advanced Methods for Thermotherapy and Biomaterials

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Multiparametric quantification of the heterogeneity of free Ca2+ concentration by 19F MR spectroscopy

Cited by 3 publications

References 30 publications

A method for multiparametric statistical quantification of the heterogeneity of free Na+concentration by19F MR spectroscopy: Proof of principlein silicoandin vitro

A method for multiparametric statistical quantification of the heterogeneity of free Na+concentration by19F MR spectroscopy: Proof of principlein silicoandin vitro

Multiparametric statistical quantification of pH heterogeneity by 1H MRS and MRSI of extracellular pH markers: Proof of principle

Contactless Thermometry by MRI and MRS: Advanced Methods for Thermotherapy and Biomaterials

Contact Info

Product

Resources

About

A method for multiparametric statistical quantification of the heterogeneity of free Na⁺concentration by¹⁹F MR spectroscopy: Proof of principlein silicoandin vitro

A method for multiparametric statistical quantification of the heterogeneity of free Na⁺concentration by¹⁹F MR spectroscopy: Proof of principlein silicoandin vitro

Multiparametric statistical quantification of pH heterogeneity by ¹H MRS and MRSI of extracellular pH markers: Proof of principle