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PDF file - 52K, Conversion of a 31P NMR spectrum of 3-APP into a pHe distribution curve.

PDF file - 69K, Statistical parameters characterizing pHe heterogeneities modeled by phantoms.

PDF file - 23K, Graphical presentation of a conventional histogram based on bins (buckets), and an analogous histogram derived from digital pH curve points.

PDF file - 34K, Gaussian curve fitting to 3-APP 31P NMR spectral regions of phantoms and mouse tumors for varying numbers and intensities of pHe modes.

PDF file - 120K

PDF file - 287K, Includes additional experimental procedures, algorithm and logarithm data, and equations used. Also includes supplementary references.

PDF file - 79K, Statistical parameters characterizing unimodal computer-simulated pH distributions.

PDF file - 53K, Scaling corrections.

PDF file - 91K, Flowchart presenting the step-by-step procedure for calculating multiple pH heterogeneity parameters from 31P NMR spectra.

Acid production and transport are currently being studied to identify new targets for efficient cancer treatment, as subpopulations of tumor cells frequently escape conventional therapy owing to their particularly acidic tumor microenvironment. Heterogeneity in intracellular and extracellular tumor pH (pHi, pHe) has been reported, but none of the methods currently available for measuring tissue pH provides quantitative parameters characterizing pH distribution profiles in tissues. To this intent, we present here a multiparametric, noninvasive approach based on in vivo 31P nuclear magnetic resonance (NMR) spectroscopy and its application to mouse tumor xenografts. First, localized 31P NMR spectrum signals of pHi and pHe reporter molecules [inorganic phosphate (Pi) and 3-aminopropylphosphonate (3-APP), respectively] were transformed into pH curves using established algorithms. Although Pi is an endogenous compound, 3-APP had to be injected intraperitoneally. Then, we developed algorithms for the calculation of six to eight quantitative pH parameters from the digital points of each pH curve obtained. For this purpose, each pH distribution profile was approximated as a histogram, and intensities were corrected for the nonlinearity between chemical-shift and pH. Cancer Res; 73(15); 4616–28. ©2013 AACR

PDF file - 77K, Statistical parameters characterizing bimodal computer-simulated pH distributions.

XLSX file - 8061K, Contains four numbered calculation sheets for calculations of pH heterogeneity parameters, and also as templates that can be used directly for new calculations.

PDF file - 29K, Simulation of bimodal pH distributions by addition of computer-generated Gaussian curves.

BackgroundHeart failure (HF) and diabetes epidemiologically share a bidirectional relationship, with each increasing the incidence and worsening the prognosis of the other. Global longitudinal strain (GLS) measured by feature tracking cardiovascular magnetic resonance (CMR) has prognostic value in HF. However, this has not been established in HF patients with diabetes.ObjectivesThis study aimed to assess the prognostic value of GLS in HF patients with diabetes.MethodsConsecutive patients (n=315) with HF from six tertiary cardiac centres in Singapore underwent CMR at 3T, including GLS, late gadolinium enhancement (LGE), native T1 mapping, and extracellular volume fraction (ECV) mapping. The primary outcome was a composite of all-cause mortality or HF hospitalisation.ResultsCompared to those without diabetes (n=156), the diabetes group (n=159) had a higher prevalence of LGE (76 vs 60%, pConclusionCompared to heart failure patients without diabetes, those with diabetes have worse CMR markers of fibrosis and adverse prognosis. GLS is a powerful and independent prognostic marker in heart failure patients with diabetes.

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