NMR in Biomedicine

Cover image for Vol. 28 Issue 7

Early View (Online Version of Record published before inclusion in an issue)

Impact Factor: 3.044

ISI Journal Citation Reports © Ranking: 2014: 9/44 (Spectroscopy); 24/125 (Radiology Nuclear Medicine & Medical Imaging); 27/73 (Biophysics)

Online ISSN: 1099-1492

Associated Title(s): Contrast Media & Molecular Imaging

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  1. 1 - 31
  1. Research articles

    1. Measurement of vascular water transport in human subjects using time-resolved pulsed arterial spin labelling

      Adnan Bibic, Linda Knutsson, Anders Schmidt, Erik Henningsson, Sven Månsson, Kasim Abul-Kasim, Jonas Åkeson, Matthias Gunther, Freddy Ståhlberg and Ronnie Wirestam

      Article first published online: 5 JUL 2015 | DOI: 10.1002/nbm.3344

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      In the applied model, the Brownian motion of labelled spins was described by a one-dimensional general Langevin equation as the starting point, and as a Fokker–Planck differential equation for the averaged distribution of labelled spins at the end point. The model allows the measurement of the transfer time of the labelled water as a result of bulk flow in the large vessels and dispersion caused by the pseudo-random nature of the microvasculature and transcapillary permeability.

    2. Viability and MR detectability of iron labeled mesenchymal stem cells used for endoscopic injection into the porcine urethral sphincter

      Susanne Will, Petros Martirosian, Frank Eibofner, Fritz Schick, Rüdiger Bantleon, Martin Vaegler, Gerd Grözinger, Claus D. Claussen, Ulrich Kramer and Jörg Schmehl

      Article first published online: 5 JUL 2015 | DOI: 10.1002/nbm.3339

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      To restore damaged porcine urethral sphincter function, therapeutic mesenchymal stem cells were injected into the muscle tissue. Evaluation with highly resolved MR data acquisition and comparison with histological staining allows sensitive cell tracking in the porcine urethral sphincter for up to six months. Labeling with superparamagnetic iron oxide particles has shown no significant undesired biological effects on mesenchymal stem cells.

    3. Direct dynamic measurement of intracellular and extracellular lactate in small-volume cell suspensions with 13C hyperpolarised NMR

      Vincent Breukels, Kees (C.) F. J. Jansen, Frits H. A. van Heijster, Andrea Capozzi, P. Jan M. van Bentum, Jack A. Schalken, Arnaud Comment and Tom W. J. Scheenen

      Article first published online: 30 JUN 2015 | DOI: 10.1002/nbm.3341

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      Hyperpolarised (HP) 13C NMR has been used to probe the conversion of [1-13C]pyruvate to [1-13C]lactate in live systems. We introduce a new set-up for HP 13C experiments in cell suspensions with increased spectral resolution, and reveal a 3-Hz chemical shift difference between intracellular and extracellular lactate. The dynamic and simultaneous detection of both lactate pools allows lactate transport to be measured directly in cell suspensions in addition to the pyruvate to lactate label conversion rate.

    4. 1H nuclear magnetic resonance (NMR) as a tool to measure dehydration in mice

      Matthew Li, Christophoros C. Vassiliou, Lina A. Colucci and Michael J. Cima

      Article first published online: 30 JUN 2015 | DOI: 10.1002/nbm.3334

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      Relaxometry analysis of live mice undergoing thermal dehydration demonstrated a linear correlation between signal amplitude and two clinical dehydration metrics: body weight changes and urine osmolality. Multi-exponential analysis revealed the best correlation between lean tissue and clinical metrics, while adipose tissue and free fluid correlations were weak. With appropriate hardware, such non-invasive NMR methods could one day be used for hydration state assessment and preclude clinical tools, such as MRI, that are often impractical for routine use.

    5. Robust hyperpolarized 13C metabolic imaging with selective non-excitation of pyruvate (SNEP)

      Way Cherng Chen, Xing Qi Teo, Man Ying Lee, George K. Radda and Philip Lee

      Article first published online: 28 JUN 2015 | DOI: 10.1002/nbm.3346

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      Selective Non-Excitation of Pyruvate (SNEP) is a novel RF excitation scheme for dynamic metabolic imaging using hyperpolarized [1-13C]pyruvate. Not exciting [1-13C]pyruvate eliminates the RF-induced decay of hyperpolarized substrate magnetization allowing transfer of more hyperpolarized magnetization to metabolites. Similar to multi-band (MB) excitation, SNEP improves SNR and signal decay rates compared to non-selective (NS). However, SNEP has added advantages over MB in terms of easy implementation, reduced gradient requirement, robustness to frequency drifts and easy quantification using [1-13C]pyruvate-hydrate as a proxy.

    6. Characterization of hepatic fatty acids in mice with reduced liver fat by ultra-short echo time 1H-MRS at 14.1 T in vivo

      Ana Francisca Soares, Hongxia Lei and Rolf Gruetter

      Article first published online: 28 JUN 2015 | DOI: 10.1002/nbm.3345

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      Fatty-acyl chains in hepatic lipids were characterized non-invasively by 1H-MRS in vivo in control and streptozotocin-induced diabetic mice using a validated ultra-short echo time STEAM at 14.1 T. Induction of diabetes decreased the hepatic lipid content while causing an increase in the contribution of saturated fatty acids to cytosolic lipids, which became dominated by shorter chains compared with the baseline assessment. Complementary NMR measurements performed in liver extracts mirrored the findings in vivo, pointing to concomitant alterations in membrane fatty acids.

    7. Rapid assessment of quantitative T1, T2 and T2* in lower extremity muscles in response to maximal treadmill exercise

      Juliet Varghese, Debbie Scandling, Rohit Joshi, Ashish Aneja, Jason Craft, Subha V. Raman, Sanjay Rajagopalan, Orlando P. Simonetti and Georgeta Mihai

      Article first published online: 28 JUN 2015 | DOI: 10.1002/nbm.3332

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      Quantitative T1, T2 and T2* maps of lower extremity skeletal muscles were sequentially acquired at rest and post-treadmill exercise in an integrated examination to non-invasively evaluate rest/recovery kinetics. Treadmill exercise caused differential increase in relaxometric measures in muscle groups, which subsequently recovered to resting values and were influenced by age and gender. Quantitative T1, T2 and T2* may provide rapid non-invasive measures of pathophysiology and functional impairment in characterizing disease severity.

  2. Special issue review articles

    1. Diffusion imaging of the vertebral bone marrow

      Olaf Dietrich, Tobias Geith, Maximilian F. Reiser and Andrea Baur-Melnyk

      Article first published online: 26 JUN 2015 | DOI: 10.1002/nbm.3333

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      Diffusion-weighted MRI (DWI) of the vertebral bone marrow is a clinically important tool for the characterization of bone-marrow pathologies and, in particular, for the differentiation of benign and malignant vertebral compression fractures. DWI of the vertebral bone marrow is, however, complicated by some unique MR and tissue properties of vertebral bone marrow. This review summarizes data from numerous studies in which diffusion measurements of normal vertebral bone marrow and of different vertebral bone-marrow lesions were performed.

    2. Sodium NMR/MRI for anisotropic systems

      U. Eliav and G. Navon

      Article first published online: 24 JUN 2015 | DOI: 10.1002/nbm.3331

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      Many biological tissues contain structures such as fibers and membranes that impose anisotropic translational and rotational motions on the sodium ions. Translational motion can be studied by diffusion measurements. Anisotropic rotational motion, resulting in non-degenerate ±1/2–±3/2 transitions, is best studied using multiple-quantum 23Na NMR and MRI (see the spectrum for the optic nerve). The current review covers various NMR techniques applied to 23Na in anisotropic compartments of cartilage, tendon, intervertebral discs, red blood cells, nervous system and muscles.

  3. Research articles

    1. Optimization of arterial spin labeling MRI for quantitative tumor perfusion in mouse xenograft model

      Reshmi Rajendran, Jieming Liang, Mei Yee Annie Tang, Brian Henry and Kai-Hsiang Chuang

      Article first published online: 24 JUN 2015 | DOI: 10.1002/nbm.3330

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      Flow-sensitive alternating inversion recovery (FAIR) ASL was optimized for low perfusion. The lumbar muscle was used as a reference region, where perfusion of 32.4 ± 4.8 (mean ± SD) ml/100g/min was measured in 20 min with a quantification error of 14.4 ± 9.1%. Applying the protocol to a xenograft tumor, heterogeneous perfusion from 49.5 to 211.2 ml/100g/min in renal carcinoma was observed. The results were compared with vessel density, apoptosis and hypoxia.

    2. Reproducibility and optimization of in  vivo human diffusion-weighted MRS of the corpus callosum at 3T and 7T

      Emily T. Wood, Ayse Ece Ercan, Francesca Branzoli, Andrew Webb, Pascal Sati, Daniel S. Reich and Itamar Ronen

      Article first published online: 18 JUN 2015 | DOI: 10.1002/nbm.3340

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      In this study, we show that the diffusion-weighted MRS (DWS) method is feasible for clinical studies. Our power calculations based on empirical and modeled total N-acetylaspartate (tNAA) diffusion measures show that a subtle difference of 10% can be detected when sample sizes of about 10 subjects per group are used in case–control studies. With the separate acquisition schemes suggested for 3T and 7T, robust DWS measures can be achieved within 10–13 min of scan time.

    3. Sodium MRI of the human heart at 7.0 T: preliminary results

      Andreas Graessl, Anjuli Ruehle, Helmar Waiczies, Ana Resetar, Stefan H. Hoffmann, Jan Rieger, Friedrich Wetterling, Lukas Winter, Armin M. Nagel and Thoralf Niendorf

      Article first published online: 17 JUN 2015 | DOI: 10.1002/nbm.3338

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      This pilot study demonstrated the feasibility of sodium MRI of the human heart at 7.0 T using a dedicated transceiver RF coil array. The proposed setup afforded the acquisition of sodium images with reasonable myocardial signal in clinically acceptable scan times. 3D density adapted radial acquisitions yielded a signal gain compared with Cartesian gradient echo acquisitions. This improvement supported whole heart, cine sodium imaging of the heart with an isotropic spatial resolution of 6 mm within approximately 19 min scan time.

    4. Monitoring dynamic alterations in calcium homeostasis by T1-mapping manganese-enhanced MRI (MEMRI) in the early stage of small intestinal ischemia–reperfusion injury

      Da-wei Zhao, Le-tian Zhang, Hai-yun Cheng, Yu-long Zhang, Jia-yan Min, Hua-liang Xiao and Yi Wang

      Article first published online: 17 JUN 2015 | DOI: 10.1002/nbm.3335

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      Manganese (Mn2+) acts as an excellent probe of calcium ion (Ca2+) influx for monitoring Ca2+-associated physiological activities in a Mn2+-enhanced MRI (MEMRI) study. In this study, we prospectively demonstrated that Mn2+-enhanced T1-map MRI has the sensitivity to monitor variations in Ca2+ homeostasis in vivo directly related to Ca2+ overload in the early stage of intestinal ischemia–reperfusion injury. MEMRI provides additional information in intestinal ischemia–reperfusion injury models used to monitor disease development.

    5. A multi-Gaussian model for apparent diffusion coefficient histogram analysis of Wilms’ tumour subtype and response to chemotherapy

      Patrick W. Hales, Øystein E. Olsen, Neil J. Sebire, Kathy Pritchard-Jones and Chris A. Clark

      Article first published online: 9 JUN 2015 | DOI: 10.1002/nbm.3337

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      A multi-Gaussian modelling approach for the analysis of apparent diffusion coefficient (ADC) histograms acquired in patients with Wilms’ tumour is presented. The model separates viable and non-viable tissue, and can be used to determine the predominant cellular subpopulation of viable tissue in the tumour. Comparison with histopathology in the same tumours shows that the ADC value in this subpopulation is lower in high-risk blastemal-type Wilms’ tumours compared with most other subtypes.

  4. Special issue research articles

    1. Quantitative sodium MRI of the human brain at 9.4 T provides assessment of tissue sodium concentration and cell volume fraction during normal aging

      Keith Thulborn, Elaine Lui, Jonathan Guntin, Saad Jamil, Ziqi Sun, Theodore C. Claiborne and Ian C. Atkinson

      Article first published online: 9 JUN 2015 | DOI: 10.1002/nbm.3312

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      Quantitative sodium MRI at 9.4 T performed on human brains shows that the tissue sodium concentration (TSC) and cell volume fraction remain constant during cognitively normal ageing, confirming a result previously available only from neuropathology. The figure shows TSC of the brain as a function of adult age. Representative images of TSC (top) and tissue cell volume fraction (bottom) are shown across the age scale for representative young and old individuals. Images were acquired at 9.4 T.

  5. Research articles

    1. Dynamic oxygen challenge evaluated by NMR T1 and T2* – insights into tumor oxygenation

      Dawen Zhao, Jesús Pacheco-Torres, Rami R. Hallac, Derek White, Peter Peschke, Sebastian Cerdán and Ralph P. Mason

      Article first published online: 8 JUN 2015 | DOI: 10.1002/nbm.3325

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      Blood oxygen level-dependent (BOLD) and tissue oxygen level-dependent (TOLD) measurements were compared in Dunning prostate R3327-AT1 and HI tumors with respect to carbogen breathing challenge. A strong correlation was observed between BOLD and TOLD signal responses, but ΔR2* and ΔR1 were only correlated for the HI tumors. The magnitude of BOLD and TOLD signal responses to carbogen breathing reflected expected hypoxic fractions and oxygen dynamics, suggesting potential value of this test as a prognostic biomarker of tumor hypoxia.

    2. Quantitative MRI in a non-surgical model of cervical spinal cord injury

      Wendy Oakden, Jacek M. Kwiecien, Meaghan A. O'Reilly, Wojciech Dabrowski, Cari Whyne, Joel Finkelstein, Kullervo Hynynen and Greg J. Stanisz

      Article first published online: 4 JUN 2015 | DOI: 10.1002/nbm.3326

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      MRI was performed in a non-surgical model of spinal cord injury, induced under MR guidance using focused ultrasound and microbubbles. Quantitative T2 revealed a large component with very short T2 of about 3 ms, highly correlated with hemorrhage (24 h) or hemosiderin (2 weeks) on histology. Intra/extracellular water T2 was elevated at 24 h and was correlated with vacuolation/edema, while a cystic water peak with T2 > 250 ms was correlated with the presence of cystic cavities.

  6. Review articles

    1. You have full text access to this OnlineOpen article
      Parallel transmission for ultrahigh-field imaging

      Francesco Padormo, Arian Beqiri, Joseph V. Hajnal and Shaihan J. Malik

      Article first published online: 19 MAY 2015 | DOI: 10.1002/nbm.3313

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      Ultrahigh-field MRI provides a powerful new investigational device for in vivo imaging, but is hindered by non-uniform and variable radiofrequency fields. Parallel transmission (PTx) promises to address these issues by providing more control over the fields. In this article, we review methods for exploiting the new degrees of freedom provided by PTx to improve image quality and to reduce the specific absorption rate (SAR).

  7. Special issue review articles

    1. The technological future of 7 T MRI hardware

      A. G. Webb and P. F. Van de Moortele

      Article first published online: 14 MAY 2015 | DOI: 10.1002/nbm.3315

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      In this article we present some projections for future hardware developments on human 7 T MRI scanners. Areas covered include magnet design, magnetic field gradients, RF coils, dynamic shimming, SAR estimation, and patient monitoring.

  8. Special issue research articles

    1. A simple approach to evaluate the kinetic rate constant for ATP synthesis in resting human skeletal muscle at 7 T

      Jimin Ren, A. Dean Sherry and Craig R. Malloy

      Article first published online: 6 MAY 2015 | DOI: 10.1002/nbm.3310

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      Extracting the ATP synthesis rate constant (kPi[RIGHTWARDS ARROW]γATP) from 31P inversion transfer measurements is generally complicated by the tangle of multiple spin relaxation and exchange parameters in the magnetization equations describing the exchange system. This problem can be avoided by using a simple alternative approach based on the Bloch–McConnell equation for inorganic phosphate Pi, which allows the evaluation of kPi[RIGHTWARDS ARROW]γATP by a linear plot of Pi magnetization rate (m˙Pi) against the magnetization difference between Pi and γ-ATP (mPi − mγATP) .

    2. You have full text access to this OnlineOpen article
      Assessment of blood flow velocity and pulsatility in cerebral perforating arteries with 7-T quantitative flow MRI

      W. H. Bouvy, L. J. Geurts, H. J. Kuijf, P. R. Luijten, L. J. Kappelle, G. J. Biessels and J. J. M. Zwanenburg

      Article first published online: 27 APR 2015 | DOI: 10.1002/nbm.3306

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      A two-dimensional, single-slice, quantitative flow (Qflow) sequence on a 7-T system yielded the first non-invasive in vivo measurements of blood flow velocity and pulsatility in cerebral perforating arteries in the basal ganglia (BG) and semioval centre (CSO), with the middle cerebral artery as reference. The precision of the velocity measurements in individual vessels and the pulsatility index per anatomical region was determined using Bland–Altman analysis. This sequence allows the study of the haemodynamics of cerebral perforating arteries and their association with, for example, vascular lesions.

    3. Enhancing the quantification of tissue sodium content by MRI: time-efficient sodium B1 mapping at clinical field strengths

      Jonathan Lommen, Simon Konstandin, Philipp Krämer and Lothar R. Schad

      Article first published online: 21 APR 2015 | DOI: 10.1002/nbm.3292

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      B1 mapping methods for tissue sodium content (TSC) quantification are evaluated. On this basis, a new protocol using the phase-sensitive (PS) method is developed, which allows for simultaneous B1 mapping and spin density-weighted imaging. The accuracy of TSC measurements is increased without the need for additional measurement time, which allows for a better incorporation of quantitative sodium imaging into clinics.

    4. Safety testing and operational procedures for self-developed radiofrequency coils

      Jens Hoffmann, Anke Henning, Ioannis A. Giapitzakis, Klaus Scheffler, G. Shajan, Rolf Pohmann and Nikolai I. Avdievich

      Article first published online: 6 APR 2015 | DOI: 10.1002/nbm.3290

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      Herein, a comprehensive guideline on electrical and mechanical safety tests, specific absorption rate (SAR) simulation, risk analysis and operational procedures for self-developed RF coils is described that helps to recognize and eliminate safety concerns during RF coil design and operation. Although the procedure is generally applicable to all field strengths, specific requirements with regard to SAR simulation and verification, as well as electrical safety and performance, at ultrahigh-field are considered.

  9. Special issue review articles

    1. Sodium MRI of multiple sclerosis

      Maria Petracca, Lazar Fleysher, Niels Oesingmann and Matilde Inglese

      Article first published online: 6 APR 2015 | DOI: 10.1002/nbm.3289

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      Sodium MRI is a topic of increasing interest in multiple sclerosis (MS) research as it allows the metabolic characterization of brain tissue in vivo, aiding in the exploration of pathogenetic mechanisms and possibly offering insights into disease progression and the monitoring of treatment outcomes. We present an up-to-date review of sodium MRI application in MS, organized into four main sections: biological and pathogenetic role of sodium; brief overview of sodium imaging techniques; results of sodium MRI application in clinical studies; and future perspectives.

    2. Evaluation of cartilage repair and osteoarthritis with sodium MRI

      Štefan Zbýň, Vladimír Mlynárik, Vladimir Juras, Pavol Szomolanyi and Siegfried Trattnig

      Article first published online: 23 MAR 2015 | DOI: 10.1002/nbm.3280

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      Sodium MRI is technologically a challenging yet sensitive method for the detection of even small changes in cartilage glycosaminoglycan content, which play a key role in homeostasis. Clinical applications of sodium imaging published over the past decade demonstrate its potential for the non-invasive evaluation of cartilage pathologies. In this review, we present basic information on cartilage composition and sodium imaging methodology, as well as an overview of clinical studies evaluating different cartilage repair techniques and osteoarthritis by sodium imaging.

    3. Recent applications of UHF-MRI in the study of human brain function and structure: a review

      Wietske van der Zwaag, Andreas Schäfer, José P. Marques, Robert Turner and Robert Trampel

      Article first published online: 12 MAR 2015 | DOI: 10.1002/nbm.3275

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      MRI at ultra-high field strength of 7 T and greater has made tremendous progress over the last decade and a half. This review discusses the rapidly expanding literature on UHF applications of BOLD fMRI and structural imaging in the brain, including relaxation-time-weighted imaging, phase imaging, and QSM; angiography and diffusion- and MT-weighted imaging.

    4. Clinical applications at ultrahigh field (7  T). Where does it make the difference?

      Siegfried Trattnig, Wolfgang Bogner, Stephan Gruber, Pavol Szomolanyi, Vladimir Juras, Simon Robinson, Štefan Zbýň and Stefan Haneder

      Article first published online: 12 MAR 2015 | DOI: 10.1002/nbm.3272

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      Although it will probably take some years before full whole-body investigations can be performed routinely with high quality at 7 T, many morphological applications, as well as metabolic and functional MRI applications, in neuroimaging, musculoskeletal and breast imaging have already been shown to be superior compared with the benchmark 3 T, which will further enhance the move to 7 T. The rapid increase in operating 7-T systems indicates the growing interest in ultrahigh-field MRI because of the improved clinical results with regard to morphological detail, as well as functional and metabolic imaging capabilities.

    5. Quantitative sodium MRI of kidney

      Frank G. Zöllner, Simon Konstandin, Jonathan Lommen, Johannes Budjan, Stefan O. Schoenberg, Lothar R. Schad and Stefan Haneder

      Article first published online: 27 FEB 2015 | DOI: 10.1002/nbm.3274

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      The human kidneys maintain the homeostasis of the body's fluid and electrolyte balance by filtration of the plasma and excretion of the end products, herein the regulation of extracellular sodium (23Na). Renal 23Na MRI can provide new insights into the physiological function and viability of tissues via the quantification of the tissue sodium concentration. Initial pre-clinical and clinical studies have already outlined the potential of this technique. Future studies must be extended to larger patient groups to demonstrate its diagnostic power. In conclusion, 23Na MRI is seen as a powerful technique with the option to establish a non-invasive renal biomarker for tissue viability, but is still a long way from real clinical implementation.

    6. W(h)ither human cardiac and body magnetic resonance at ultrahigh fields? technical advances, practical considerations, applications, and clinical opportunities

      Thoralf Niendorf, Katharina Paul, Celal Oezerdem, Andreas Graessl, Sabrina Klix, Till Huelnhagen, Fabian Hezel, Jan Rieger, Helmar Waiczies, Jens Frahm, Armin M. Nagel, Eva Oberacker and Lukas Winter

      Article first published online: 23 FEB 2015 | DOI: 10.1002/nbm.3268

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      This work documents and reviews advances and progress in cardiac and body MR technology at ultrahigh fields and its application in forefront research and in early clinical applications. The achievements of ultrahigh field cardiac and body MR are shown to be a powerful motivator and enabler, since the extra speed, signal and imaging capabilities may be invested to overcome the fundamental constraints that continue to hamper traditional cardiac and body MR applications at lower magnetic field strengths.

    7. Sodium MRI in human heart: a review

      Paul A. Bottomley

      Article first published online: 12 FEB 2015 | DOI: 10.1002/nbm.3265

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      The properties, methods and clinical potential of sodium MRI in human heart are reviewed. The myocardial sodium concentration is about 40 µmol/g wet weight, and its signal-to-noise ratio is about one-6000th of conventional proton MRI. Sodium's short multi-component relaxation behavior necessitates fast, ultra-short-echo MRI sequences, especially for quantification. Currently, intra- and extra-cellular sodium cannot be unambiguously resolved, but increased sodium, primarily attributable to sodium influx, is demonstrated in human myocardial infarction. The added value of cardiac 23Na MRI versus existing methods remains key.

  10. Special issue research articles

    1. Cortical phase changes measured using 7-T MRI in subjects with subjective cognitive impairment, and their association with cognitive function

      Sanneke van Rooden, Mathijs Buijs, Marjolein E. van Vliet, Maarten J. Versluis, Andrew G. Webb, Ania M. Oleksik, Lotte van de Wiel, Huub A. M. Middelkoop, Gerard Jan Blauw, Annelies W. E. Weverling-Rynsburger, Jeroen D. C. Goos, Wiesje M. van der Flier, Ted Koene, Philip Scheltens, Frederik Barkhof, Ondine van de Rest, P. Eline Slagboom, Mark A. van Buchem and Jeroen van der Grond

      Article first published online: 19 DEC 2014 | DOI: 10.1002/nbm.3248

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      In subjects with subjective cognitive impairment (SCI), Alzheimer's disease-like changes may occur in the brain. We investigated whether cortical phase shifts at 7 T in SCI can be detected, implicating the deposition of amyloid-beta (Aβ) plaques and associated iron, and which cognitive domains are associated with cortical phase shifts in SCI. In SCI, an increased cortical phase shift at high field is associated with a poorer memory performance, although no increased phase shift could be determined in subjects with SCI compared with controls.

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