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Limits of a localized magnetic resonance spectroscopy assay for ex vivo myocardial triacylglycerol.

ABSTRACT: Localized magnetic resonance spectroscopy (LMRS) promises a powerful non-invasive means to determine myocardial triacylglycerol (TAG) in a clinical setting. Here, the linearity, specificity, robustness, precision, and accuracy of an ex vivo mouse-heart LMRS TAG assay are assessed by quantifying the spatial, spectral, and relaxation-induced uncertainties. The protocol, which is based on localization by adiabatic selective refocusing (LASER) using frequency offset corrected inversion (FOCI) pulses, alternating gradient polarity, and simple post-processing, is shown to have good characteristics. The presented protocol has a benchmark, phantom-based, accuracy of 3%, and when applied to ex vivo mouse hearts the accuracy is 6%, making the LMRS assay comparable to the typical destructive bioanalytical assay.

SUBMITTER: O'Connor RD

PROVIDER: S-EPMC2692310 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature

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Limits of a localized magnetic resonance spectroscopy assay for ex vivo myocardial triacylglycerol.

O'Connor Robert D RD Gropler Robert J RJ Peterson Linda L Schaffer Jean J Ackerman Joseph J H JJ

Journal of pharmaceutical and biomedical analysis 20070901 3

Localized magnetic resonance spectroscopy (LMRS) promises a powerful non-invasive means to determine myocardial triacylglycerol (TAG) in a clinical setting. Here, the linearity, specificity, robustness, precision, and accuracy of an ex vivo mouse-heart LMRS TAG assay are assessed by quantifying the spatial, spectral, and relaxation-induced uncertainties. The protocol, which is based on localization by adiabatic selective refocusing (LASER) using frequency offset corrected inversion (FOCI) pulses ...[more]

PMID: 17931816

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Project description:Medulloblastoma (MB) is the most common malignant brain tumor occurring in childhood and rarely found in adult. Based on transcriptome profile MB are currently classified into four major molecular groups reflecting a considerable biological heterogeneity: WNT-activated, SHH-activated, group 3 and group 4. Recently, DNA methylation profiling allowed the identification of additional subgroups within the four major molecular groups associated with different clinic-pathological and molecular features. Isocitrate Dehydrogenase-1 (IDH1) mutations have been described in several tumours, including gliomas, while in MB are exceptionally reported and not routinely investigated. By mean of magnetic resonance spectroscopy (MRS) we unequivocally assessed the presence the oncometabolite D-2-Hydroxyglutarate (2HG), a marker of IDH1 and IDH2 mutation, in a case of adult MB. Immunophenotypical work-up and methylation profiling assigned the diagnosis of MB, subclass SHH-A, and molecular testing revealed the presence of the non-canonical somatic IDH1(p.R132C) mutation and an additional GNAS mutation, also exceptionally described in MB. To our knowledge this is the first reported case of MB harboring both mutations together. Of note, tumour exhibited a heterogeneous phenotype with a tumour component displaying glial differentiation, with robust GFAP expression, and a component with conventional MB features and selective presence of GNAS mutation, suggesting coexistence of two different major tumour clones. These findings draw attention to the need of a deeper genetic characterization of MB in order to get insights into their biology and improve stratification and clinical management of the patients. Moreover, reported data underling the importance of performing MRS for the identification of IDH mutations in non-glial tumours. The use of throughput molecular profiling analysis and advanced medical imaging technology will certainly increase the frequency with which rare tumour entities will be identified. Whether they have any particular therapeutic implications or prognostic relevance requires further investigations.

Project description:BackgroundT2* cardiovascular magnetic resonance (CMR) is commonly used in the diagnosis of intramyocardial hemorrhage (IMH). For quantifying IMH with T2* CMR, despite the lack of consensus studies, two different methods [subject-specific T2* (ssT2*) and absolute T2* thresholding (aT2* < 20 ms)] are interchangeably used. We examined whether these approaches yield equivalent information.MethodsST elevation myocardial infarction (STEMI) patients (n = 70) were prospectively recruited for CMR at 4-7 days post revascularization and for 6-month follow up (n = 43). Canines studies were performed for validation purposes, where animals (n = 20) were subject to reperfused myocardial infarction (MI) and those surviving the MI (n = 16) underwent CMR at 7 days and 8 weeks and then euthanized. Both in patients and animals, T2* of IMH and volume of IMH were determined using ssT2* and aT2* < 20 ms. In animals, ex-vivo T2* CMR and mass spectrometry for iron concentration ([Fe]Hemo) were determined on excised myocardial sections. T2* values based on ssT2* and absolute T2* threshold approaches were independently regressed against [Fe]Hemo and compared. A range of T2* cut-offs were tested to determine the optimized conditions relative to ssT2*.ResultsWhile both approaches showed many similarities, there were also differences. Compared to ssT2*, aT2* < 20 ms showed lower T2* and volume of IMH in patients and animals independent of MI age (all p < 0.005). While T2* determined from both methods were highly correlated against [Fe]Hemo (R2 = 0.9 for both), the slope of the regression curve for ssT2* was significantly larger as compared to aT2* < 20 ms (0.46 vs. 0.32, p < 0.01). Further, slightly larger absolute T2* cut-offs (patients: 23 ms; animals: 25 ms) showed similar IMH characteristics compared to ssT2*.ConclusionCurrent quantification methods have excellent capacity to identify IMH, albeit the T2*of IMH and volume of IMH based on aT2* < 20 ms are smaller compared to ssT2*. Thus the method used to quantify IMH from T2* CMR may influence the diagnosis for IMH.

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Limits of a localized magnetic resonance spectroscopy assay for ex vivo myocardial triacylglycerol.

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Limits of a localized magnetic resonance spectroscopy assay for ex vivo myocardial triacylglycerol.

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