Intracellular pH measured by <sup>31</sup>P‐MR‐spectroscopy might predict site of progression in recurrent glioblastoma under antiangiogenic therapy

Wenger, Katharina; Hattingen, Elke; Franz, Kea; Steinbach, Joachim P.; Bähr, Oliver; Pilatus, Ulrich

doi:10.1002/jmri.25619

Cited by 38 publications

(45 citation statements)

References 47 publications

(55 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…4 Recent in vivo studies investigating pH i in patients with recurrent glioblastoma observed an increase of pH i in apparently unaffected tissue that could be attributed to tumor progression. 5 Therefore, pH i might be a sensitive marker to detect early tumor progression with the potential to investigate new therapeutic approaches.…”

Section: Introductionmentioning

confidence: 99%

The pH sensitivity of APT‐CEST using phosphorus spectroscopy as a reference method

et al. 2019

Self Cite

View full text Add to dashboard Cite

The pH value is a potential physiological marker for clinical diagnosis as it is altered in pathologies such as tumors. While intracellular pH can be measured noninvasively via phosphorus spectroscopy (31P MRSI), Amide Proton Transfer‐Chemical Exchange Saturation Transfer (APT‐CEST) MRI has been suggested as an alternative method for pH quantification. To assess the suitability of APT‐CEST contrast for pH quantification, two approaches (magnetization transfer ratio asymmetry [MTRasym] and Lorentzian difference analysis [LDA]) for analyzing the Z‐spectrum have been correlated with pH values obtained by 31P MRSI. Fourteen patients with glioblastoma and 12 healthy controls were included. In contrast to MTRasym, the LDA is modeling the direct water saturation and the semi‐solid magnetization transfer, allowing a separate evaluation of the aliphatic nuclear Overhauser effect and the APT‐CEST. The results of our study show that the pH values obtained by 31P MRSI correspond well with both methods describing the APT‐CEST contrast. Two‐sample t‐test showed significant differences in MTRasym, LDA and pH obtained by 31P MRSI for regions of interest in glioblastoma, contralateral control areas and normal appearing white matter (P < 0.001). A slightly improved correlation between the amide signal and pH was found after performing LDA (r = 0.78) compared with MTRasym (r = 0.70). While both methods can be used to monitor pH changes, the LDA approach appears to be better suited.

show abstract

Section: Introductionmentioning

confidence: 99%

The pH sensitivity of APT‐CEST using phosphorus spectroscopy as a reference method

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…Эти пики частично перекрываются. В некоторых работах [9,10] исследователи отдельно описывают метаболиты, составляющие основную часть пика РМЕ -фосфохолин (PCho) и фосфоэтаноламин (PEth) и пика PDE -глицерофосфоэтаноламин (GPE) и глицерофосфохолин (GPC). При исследовании добровольцев нам достоверно удалось дифференцировать только пики GPE и GPC, которые образуют общий пик PDE.…”

Section: Discussionunclassified

“…Полученное в нашем исследовании среднее значение рН является более низким по сравнению с таковым в работах D. Maintz и соавт., D. Ha и соавт., Wenger K. и соавт. [9,10,17], где значения рН составили 7,04±0,01, 7,07±0,1 и 7,017±0,026 соответственно. Однако их результаты соответствуют максимальным значениям рН, полученным нами.…”

Section: Discussionunclassified

“…Фосфорная МРС способна визуализировать патологические изменения в мозговой ткани, наступающие на самых ранних этапах структурной перестройки, которые позже можно визуализировать на структурных изображениях. Кроме того, важной составной частью фосфорной МРС является возможность проведения неинвазивной оценки рН мозгового вещества в норме и при опухолевой патологии [8][9][10].…”

Section: Pme -фосфомоноэфиры Pde -фосфодиэфирыunclassified

See 1 more Smart Citation

Phosphorus (P) magnetic resonance spectroscopy for evaluation of brain tissue metabolism and measuring non-invasive pH. A study involving 23 volunteers. Part I

Pronin¹,

Захарова²,

Podoprigora³

et al. 2019

Vopr. neirokhir.

View full text Add to dashboard Cite

“…Only recently has 31 P MRSI of GB patients been able to provide non‐invasive images of this slightly basic pHi in proliferating GB and its changes upon transient response to therapy or in relapse. Wenger et al used 31 P MRSI at 3 T to prove that good quality spectra can be obtained with this technique (Supplementary Figure 5) and pH i maps produced (Figure ). In these MRSI grids, it can be shown that untreated GB has a more basic pH i than contralateral brain (mean 7.110 for tumour and mean 7.017 for contralateral brain), but also that upon transiently successful antiangiogenic therapy (bevacizumab) pH i decreases (about 7.090 at best response time), and at relapse it slightly increases again.…”

Section: Mrs(i)‐detectable Metabolic Hallmarks Of Cancer: Applicationmentioning

confidence: 99%

Cancer metabolism in a snapshot: MRS(I)

2019

View full text Add to dashboard Cite

The contribution of MRS(I) to the in vivo evaluation of cancer-metabolism-derived metrics, mostly since 2016, is reviewed here. Increased carbon consumption by tumour cells, which are highly glycolytic, is now being sampled by 13 C magnetic resonance spectroscopic imaging (MRSI) following the injection of hyperpolarized [1-13 C] pyruvate (Pyr). Hot-spots of, mostly, increased lactate dehydrogenase activity or flow between Pyr and lactate (Lac) have been seen with cancer progression in prostate (preclinical and in humans), brain and pancreas (both preclinical) tumours. Therapy response is usually signalled by decreased Lac/Pyr 13 C-labelled ratio with respect to untreated or nonresponding tumour. For therapeutic agents inducing tumour hypoxia, the 13 C-labelled Lac/bicarbonate ratio may be a better metric than the Lac/Pyr ratio. 31 P MRSI may sample intracellular pH changes from brain tumours (acidification upon antiangiogenic treatment, basification at fast proliferation and relapse). The steady state tumour metabolome pattern is still in use for cancer evaluation. Metrics used for this range from quantification of single oncometabolites (such as 2-hydroxyglutarate in mutant IDH1 glial brain tumours) to selected metabolite ratios (such as total choline to N-acetylaspartate (plain ratio or CNI index)) or the whole 1 H MRSI(I) pattern through pattern recognition analysis. These approaches have been applied to address different questions such as tumour subtype definition, following/predicting the response to therapy or defining better resection or radiosurgery limits. KEYWORDSanimal model study, cancer, cellular and molecular cancer imaging, hyperpolarized C-13, MRS and MRSI methods, phosphorus MRS/MRSI | TEMPORAL AND THEMATIC BOUNDARIES OF THE TOPICS COVEREDThe authors of this review declare at the outset that there is no intention of being exhaustive or systematic. The temporal boundaries reviewed will be modest: only relevant literature since 2016, chosen according to our bias. Earlier work or reviews will only be referred to in order to put recent findings in due perspective. Authors hope that this summary will give readers a picture of how far cancer metabolism analysis with MRS(I) has advanced and, perhaps, why it is not advancing further.For quite a long time MRS, rather than MRI, has been the only approach able to evaluate cancer metabolism. Nevertheless, the MRI-derived information related to cancer metabolism should not be forgotten: consider for example the chemical exchange saturation transfer (CEST) effect caused by exchangeable protons in water-derived images of glucose uptake and metabolism in tumours. 1,2 However, apart from these CESTrelated studies, we should acknowledge that most information about cancer metabolism using MR still refers to MRS(I) acquisitions, which are the ones dealt with in our text.Supplementary Figure 1 shows a PUBMED search illustrating the different proportions of articles investigating several cancer types through MRS(I) approaches. The retrieved information can help unders...

show abstract

Intracellular pH measured by ³¹P‐MR‐spectroscopy might predict site of progression in recurrent glioblastoma under antiangiogenic therapy

Abstract: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1200-1208.

Cited by 38 publications

References 47 publications

The pH sensitivity of APT‐CEST using phosphorus spectroscopy as a reference method

The pH sensitivity of APT‐CEST using phosphorus spectroscopy as a reference method

Phosphorus (P) magnetic resonance spectroscopy for evaluation of brain tissue metabolism and measuring non-invasive pH. A study involving 23 volunteers. Part I

Cancer metabolism in a snapshot: MRS(I)

Contact Info

Product

Resources

About

Intracellular pH measured by 31P‐MR‐spectroscopy might predict site of progression in recurrent glioblastoma under antiangiogenic therapy

Abstract: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1200-1208.

Cited by 38 publications

References 47 publications

The pH sensitivity of APT‐CEST using phosphorus spectroscopy as a reference method

The pH sensitivity of APT‐CEST using phosphorus spectroscopy as a reference method

Phosphorus (P) magnetic resonance spectroscopy for evaluation of brain tissue metabolism and measuring non-invasive pH. A study involving 23 volunteers. Part I

Cancer metabolism in a snapshot: MRS(I)

Contact Info

Product

Resources

About

Intracellular pH measured by ³¹P‐MR‐spectroscopy might predict site of progression in recurrent glioblastoma under antiangiogenic therapy