NMR in Biomedicine

Cover image for Vol. 26 Issue 1

January 2013

Volume 26, Issue 1

Pages i–ii, 1–114

  1. Issue information

    1. Top of page
    2. Issue information
    3. Editorial
    4. Research articles
    1. Issue Information (pages i–ii)

      Article first published online: 26 DEC 2012 | DOI: 10.1002/nbm.2854

  2. Editorial

    1. Top of page
    2. Issue information
    3. Editorial
    4. Research articles
  3. Research articles

    1. Top of page
    2. Issue information
    3. Editorial
    4. Research articles
    1. Noninvasive quantification of intracellular sodium in human brain using ultrahigh–field MRI (pages 9–19)

      Lazar Fleysher, Niels Oesingmann, Ryan Brown, Daniel K. Sodickson, Graham C. Wiggins and Matilde Inglese

      Article first published online: 20 JUN 2012 | DOI: 10.1002/nbm.2813

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      In this study, we report a non-invasive quantitative in vivo measurement of the intracellular sodium concentration and intracellular sodium volume fraction of a healthy human brain The method features the use of single-quantum and triple-quantum filtered imaging at 7 T to provide quantification of cell volume fraction, intracellular sodium concentration and intracellular sodium molar fraction. This method opens many possibilities for structural and functional metabolic studies in the healthy and diseased brain.

    2. NMR studies of preimplantation embryo metabolism in human assisted reproductive techniques: a new biomarker for assessment of embryo implantation potential (pages 20–27)

      Shivanand M. Pudakalakatti, Shubhashree Uppangala, Fiona D'Souza, Guruprasad Kalthur, Pratap Kumar, Satish Kumar Adiga and Hanudatta S. Atreya

      Article first published online: 19 JUN 2012 | DOI: 10.1002/nbm.2814

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      A new biomarker for assessing the potential of human embryos for successful implantation using NMR as a noninvasive tool was established. The biomarker involves the measurement of the ratio of two metabolites, pyruvate and alanine, in the growth medium ISM1 used for culturing embryos. The biomarker is easy to measure and in addition to morphological based methods, provides a rapid and sensitive means for assessing the quality of embryos prior to their transfer.

    3. Doubly selective multiple quantum chemical shift imaging and T1 relaxation time measurement of glutathione (GSH) in the human brain in vivo (pages 28–34)

      In-Young Choi and Phil Lee

      Article first published online: 22 JUN 2012 | DOI: 10.1002/nbm.2815

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      Mapping of a major antioxidant, glutathione (GSH), was achieved in the human brain in vivo using doubly-selective multiple quantum filtering based chemical shift imaging (CSI) of GSH at 3 T.

      GSH concentration in the fronto-parietal region was 1.20 ± 0.16 µmol/g (mean ± SD, n = 7). The T1 of GSH in the human brain was 397 ± 44 ms (mean ± SD, n = 5), which was substantially shorter than that of other metabolites.

    4. Lactate detection in inducible and orthotopic Her2/neu mammary gland tumours in mouse models (pages 35–42)

      S. Magnitsky, G. K. Belka, C. Sterner, S. Pickup, L. A. Chodosh and J. D. Glickson

      Article first published online: 5 JUL 2012 | DOI: 10.1002/nbm.2816

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      In this study, we performed lactate spectroscopy of inducible transgenic and orthotopic mouse models of breast cancer. Lactate was “NMR invisible” in vivo in inducible tumours but could be detected after PCA extraction and in vivo in orthotopic models. The most likely reason for this phenomenon is an interaction of lactate with high levels of adiposities present in inducible tumours but not as abundant in orthotopic models. This study suggests that the tumour lactate level measured by the HadSelMQC pulse sequence may be significantly underestimated in human breast cancer patients.

    5. An in vivo ultrahigh field 14.1 T 1H-MRS study on 6-OHDA and α-synuclein-based rat models of Parkinson's disease: GABA as an early disease marker (pages 43–50)

      P. G. Coune, M. Craveiro, M. N. Gaugler, V. Mlynárik, B. L. Schneider, P. Aebischer and R. Gruetter

      Article first published online: 18 JUN 2012 | DOI: 10.1002/nbm.2817

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      This study investigated the striatal metabolite levels in two Parkinson's disease rat models: 6-OHDA lesioned rats and a genetic model based on alpha-synuclein overexpression using proton magnetic resonance spectroscopy. The models respectively replicated a late and earlier stage of the disease. The results of this study showed that striatal GABA levels were significantly altered in conditions of early nigro-striatal defects, which suggests that they may be a sensitive biomarker of conditions found in presymptomatic Parkinson's disease.

    6. Feasibility of measuring prostate perfusion with Aparterial spin labeling (pages 51–57)

      Xiufeng Li and Gregory J. Metzger

      Article first published online: 7 JUN 2012 | DOI: 10.1002/nbm.2818

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      Prostate perfusion has the potential to become an important pathophysiological marker for the monitoring of disease progression or assessment of the therapeutic response of prostate cancer. The feasibility of arterial spin labeling (ASL) is demonstrated in the prostate for the first time with a whole-body transmit coil and an external receiver array at 3 T.

      Corrected by:

      Erratum: Feasibility of measuring prostate perfusion with arterial spin labeling

      Vol. 26, Issue 10, 1338, Article first published online: 26 APR 2013

    7. Structural and functional abnormalities in migraine patients without aura (pages 58–64)

      Chenwang Jin, Kai Yuan, Limei Zhao, Ling Zhao, Dahua Yu, Karen M. von Deneen, Ming Zhang, Wei Qin, Weixin Sun and Jie Tian

      Article first published online: 7 JUN 2012 | DOI: 10.1002/nbm.2819

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      By combining structural and functional data, we found that the left dorsal anterior cingulate cortex (dACC) showed decreased gray matter volume and increased resting-state functional connectivity with several other brain regions in migraine patients without aura when compared with controls. The structural and functional changes in the left dACC were correlated with the duration of disease in migraine patients.

    8. Pushing the limits of high-resolution functional MRI using a simple high-density multi-element coil design (pages 65–73)

      N. Petridou, M. Italiaander, B. L. van de Bank, J. C. W. Siero, P. R. Luijten and D. W. J. Klomp

      Article first published online: 7 JUN 2012 | DOI: 10.1002/nbm.2820

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      Human functional MRI studies at very high resolution are rare because of signal-to-noise ratio (SNR) limitations. A flexible surface coil array with ultra-small elements was developed that enhances SNR at 7 T, yielding blood oxygenation level-dependent (BOLD) sensitivity increases up to approximately six-fold for submillimeter three-dimensional echo planar imaging and up to approximately two-fold for 1-mm/0.4-s multi-slice echo planar imaging. BOLD signals could be detected at an isotropic resolution as high as 0.55 mm, close to the scale of the fundamental functional organization of the human cortex.

    9. Quantification issues of in vivo 1H NMR spectroscopy of the rat brain investigated at 16.4 T (pages 74–82)

      Sung-Tak Hong and Rolf Pohmann

      Article first published online: 19 JUN 2012 | DOI: 10.1002/nbm.2821

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      Monte-Carlo simulations were performed to investigate the effects of linewidth and signal-to-noise ratio (SNR) on the estimation of the concentrations of 20 metabolites by varying both factors based on high-quality in vivo data. Correlations between overlapping signals were shown to be insignificant. The influence of the accurate determination of macromolecular components was also studied by comparing the results produced by two different approaches: parameterization and regularized spline baseline.

    10. Multiexponential T2 analyses in a murine model of hepatic fibrosis at 11.7 T MRI (pages 83–90)

      Jonathan E. Scalera, Jorge A. Soto, Hernan Jara, Al Ozonoff, Michael O'Brien and Stephan W. Anderson

      Article first published online: 7 JUN 2012 | DOI: 10.1002/nbm.2822

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      This study evaluated the effects of hepatic fibrosis on the multiexponential T2 (MET2) relaxation of ex vivo murine liver specimens using 11.7 T MRI. Two peaks of the MET2 signal decay were identified in all liver specimens. Strong correlation was found between the degree of hepatic fibrosis and the amplitude of the short T2 component, as well as between hepatic fibrosis and the geometric mean T2 value of the long T2 component.

    11. Feasibility of noninvasive quantitative measurements of intrarenal R2′ in humans using an asymmetric spin echo echo planar imaging sequence (pages 91–97)

      Xiaodong Zhang, Yudong Zhang, Xuedong Yang, Xiaoying Wang, Hongyu An, Jue Zhang and Jing Fang

      Article first published online: 11 JUN 2012 | DOI: 10.1002/nbm.2823

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      Intrarenal R2′ provides critically important information to assess the intrarenal oxygen metabolism in both normal and disease states. An asymmetric spin echo (ASE) single-shot echo planar imaging (EPI) sequence can provide rapid measurements of R2′ in the human kidney. In addition, the proposed ASE R2′measurement is highly reproducible and is sensitive to renal oxygenation changes under pharmacological conditions.

    12. 31P and 1H MRS of DB-1 melanoma xenografts: lonidamine selectively decreases tumor intracellular pH and energy status and sensitizes tumors to melphalan (pages 98–105)

      Kavindra Nath, David S. Nelson, Andrew M. Ho, Seung-Cheol Lee, Moses M. Darpolor, Stephen Pickup, Rong Zhou, Daniel F. Heitjan, Dennis B. Leeper and Jerry D. Glickson

      Article first published online: 29 JUN 2012 | DOI: 10.1002/nbm.2824

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      In vivo 31P and 1H MRS demonstrates that lonidamine induces a significant decrease in intracellular pH (pHi) and bioenergetics (nucleoside triphosphate/inorganic phosphate, NTP/Pi) and an increase in steady-state lactate of melanoma xenografts. However, extracellular pH exhibits a minimal decrease. Noninvasive monitoring of brain and muscle showed no significant changes. However, liver showed a transient decrease in pHi after 20 min. The prolonged selective decrease in tumor pH and bioenergetics may be exploited for pH-dependent therapeutics, such as chemotherapy with alkylating agents or hyperthermia. Intracellular pH (A), extracellular pH (B), tumor lactate (C) and NTP/Pi (D) of human melanoma xenograft and normal tissues in mice after the administration of lonidamine (100 mg/kg intraperitoneally). (E) Growth delay experiments performed on DB-1 human melanoma xenografts in nude mice treated with 7.5 mg/kg melphalan.

    13. Decreased lactate concentration and glycolytic enzyme expression reflect inhibition of mTOR signal transduction pathway in B-cell lymphoma (pages 106–114)

      Seung-Cheol Lee, Michal Marzec, Xiaobin Liu, Suzanne Wehrli, Kanchan Kantekure, Puthiyaveettil N. Ragunath, David S. Nelson, Edward J. Delikatny, Jerry D. Glickson and Mariusz A. Wasik

      Article first published online: 18 JUN 2012 | DOI: 10.1002/nbm.2825

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      Using human B-cell lymphoma models and MRS, we demonstrated that rapamycin-mediated inhibition of the mTOR signaling pathway can be detected in malignant cells in vitro and noninvasively in vivo by measurement of the lactate levels. The rapamycin-induced inhibition of lactate synthesis correlated with the inhibition of expression of hexokinase II, the key enzyme in the glycolytic pathway (A). Rapamycin treatment for 2 and 4 days produced significant changes in lactic acid concentration in the xenotransplanted lymphoma tumors (B, C).

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