Magn Reson Mater Phy (2014) 27:1–4 DOI 10.1007/s10334-013-0426-z
30 years of sodium/X-nuclei magnetic resonance imaging Simon Konstandin • Lothar R. Schad
Received: 8 October 2013 / Revised: 8 November 2013 / Accepted: 22 November 2013 / Published online: 22 January 2014 Ó ESMRMB 2014
Abstract In principle, all nuclei with nonzero spin can be employed for magnetic resonance imaging (MRI). Special scanner hardware and MR sequences are required to select the nucleus-specific frequency and to enable imaging with ‘‘sufficient’’ signal-to-noise ratio. This Special Issue starts with an overview of different nuclei that can be used for MRI today, followed by a review article about techniques required for imaging of quadrupolar nuclei with short relaxation times. Sequence developments to improve image quality and applications on different organs and diseases are presented for different nuclei (23Na, 35Cl, 17O, and 19F), with a focus on imaging at natural abundance. Keywords X-nuclei MRI Oxygen-17 Fluorine-19 Sodium-23 Chlorine-35
Besides conventional proton (1H) magnetic resonance imaging (MRI), there are many other X-nuclei that can be used in MRI. A prerequisite is a nonzero nuclear spin (i.e., an odd number of protons and/or neutrons) associated with a magnetic moment to generate signal in a receiver coil. Furthermore, high MR sensitivity—depending on the gyromagnetic ratio µ c3 and spin quantum number µ I (I ? 1)—and a ‘‘sufficient’’ number of nuclei must be present to achieve an adequate signal-to-noise ratio (SNR). This is the reason why most X-nuclei MR imaging studies are performed on sodium (23Na), measuring a mean intrinsic concentration of about 80 mmol/L [1] in the human body (up to *300 mM in intervertebral disks). S. Konstandin (&) L. R. Schad Computer Assisted Clinical Medicine, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany e-mail: [email protected]
Since the first in vivo sodium images were published 30 years ago by Hilal et al. [2], higher magnetic field strengths and improved gradient hardware and sequences have recently brought other X-nuclei (e.g., 17O, 35Cl, 39K) into focus. SNR-efficient acquisition techniques with short echo times [3, 4] and sampling density weighted apodization [5] for filtered acquisition lead to higher image quality, especially for quadrupolar nuclei (spin [ 1/2) that are subject to faster relaxation because of a nonspherical charge distribution and electric quadrupole moment. Administration of tracer compounds with an X-nucleus with good intrinsic SNR, such as fluorine (19F), which is not abundant in the human body, enables the backgroundfree observation of these compounds as specific tracers for biological processes. Ion fluxes in cells play an important role in many processes of cell activity. Several mechanisms maintain concentration gradients of different ions (e.g., 23Na, 39K, 35Cl) between the intracellular and extracellular space. The main part of the energy, stored in form of adenosine triphosphate (ATP), is invested in the sodium–potassium pump (Na?– K?-ATPase), which pumps three Na? ions out of the cell while two K? ions are pumped into the cell. This active transport mechanism is one factor to keep the resting membrane potential in cells at about -70 mV. Different ion-specific channels are able to transmit information via electrical signals by gating the flow of ions across the cell membrane. The pathological change in concentration gradients and the metabolism of intrinsic and external contrast agents can be visualized by X-nuclei MRI. There are many biomedical applications where imaging of nuclei other than protons can give additional functional information. Because of its favorable MR properties, 23Na was the first and is still the most imaged X-nucleus thus far, offering a unique tool for visualization of tissue viability non-invasively.
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In the beginning of sodium MRI, many organs such as brain [2], heart [6], and kidney [7] have been imaged despite low resolution and strong T2 weighting of spin echo sequences used. Imaging of large structures and fluid compartments was feasible, but quantification of sodium content was not possible. Measurement times were too long, so that sodium MRI had no clinical relevance at that time. The development of higher magnetic field strengths with faster gradient hardware and improved sequence acquisition schemes led to a revival of sodium imaging in the late 1990s. Many biomedical applications have emerged in the last few decades. MR studies on the temporal and spatial distribution of 23Na have been investigated in stroke [8, 9], tumor [10], heart [11, 12], kidney [13, 14], and prostate [15, 16]. The measurement of tissue sodium concentration and the distinction of intracellular and extracellular sodium content by administration of paramagnetic shift reagents [17] and multiple quantum filtering [18, 19] techniques give additional information on tissue viability and pathophysiological processes. Nowadays, sodium images with submillimeter in-plane resolution can be achieved, which brings imaging of thin structures like cartilage [20] and plaque burden in Alzheimer’s disease [21] and multiple sclerosis [22] into focus. This Special Issue of MAGMA contains two review articles and nine research papers. Most studies deal with 23Na-MRI but studies using 35Cl, 17O, and 19 F for imaging are also presented. The first contribution from Konstandin and Nagel [23] gives an overview of MR techniques used for imaging of fast relaxing nuclei (i.e., spin [ 1/2). The most important properties of these acquisition schemes are their ultra-short echo time (UTE) and high SNR efficiency. Different k-space trajectories are presented, possessing different behaviors regarding k-space coverage per projection, gradient hardware requirements, and SNR efficiency. Techniques for intrinsic filtering and anisotropic resolution to improve image quality of thin structures (e.g., cartilage) are shown. Different methods to put more weighting on either the intracellular or the extracellular signal are summarized. The major drawbacks of X-nuclei concentration quantification are the need for long repetition times and the difficulty to avoid T*2 weighting from the fast T2 component (T2f) of quadrupolar nuclei. Relaxation-weighted sodium MRI provides higher SNR and additional information besides density-weighted imaging. Stobbe and Beaulieu [24] investigated the use of gradient refocusing of the transverse magnetization in simulations and experiments. Short repetition times and relatively long radiofrequency excitation pulses lead to a contrast that is dependent on T2f and T1, which gives an enhanced contrast-to-noise ratio between gray and white matter in the human brain. This complementary contrast could provide a better differentiation for various diseases, and should be further explored in the future.
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Although UTE sequences are available at a few scanners, these sequences are designed for 1H-MRI and can be optimized for X-nuclei imaging. This includes uniform k-space sampling for optimal SNR efficiency and twisting k-space trajectories to shorten measurement times. Riemer et al. [25] give a comparison between two UTE sequences available on their clinical MRI system and an acquisition scheme that is based on three-dimensional (3D) cones established by Gurney et al. [26]. While these three different sequences provide similar SNR in human brain measurements, the latter gives a better reproducibility and a narrower point-spread function, due to uniform k-space sampling by gradient adaption during acquisition. The feasibility study by Haneder et al. [27] demonstrates the potential of sodium imaging for the non-invasive assessment of physiological changes in the kidney at clinical MRI scanners. They investigated the effect of desmopressin—a synthetic replacement for the hormone vasopressin (AVP)—on renal corticomedullary sodium concentration of patients with central diabetes insipidus (i.e., deficiency of AVP). This hormone regulates the body’s retention of water, and therefore, an overall mean decrease of 17 % could be observed after administration of desmopressin. Although conventional proton MRI is extremely sensitive in detecting multiple sclerosis (MS)-related abnormalities, it lacks specificity to clinical parameters such as relapse rate and neurological disability. Recently, an increase in sodium concentration could be detected inside white matter (WM) lesions, normal-appearing white matter (NAWM) and grey matter (GM) in relapsing-remitting multiple sclerosis patients [28]. The contribution by Maarouf et al. [29] investigates sodium accumulation in different tissues (WM T2 lesions, NAWM, GM) and brain areas and correlated with disability of primary-progressive and secondary-progressive MS. Two interesting applications of 35Cl-MRI are presented in this Special Issue. The study by Schepkin et al. [30] demonstrates the feasibility of chlorine and sodium quantification in rat at an ultra-high magnetic field of 21.1 Tesla. They measured T1 and T*2 relaxation times, and compared the increase in chlorine and sodium concentration between normal rat brain and rat with glioma using a volume RF coil. The contribution from Baier et al. [31] shows combined proton, sodium and chlorine measurements in a rat stroke model during the acute phase using a triple-resonant coil setup. Different rates of increase in sodium and chlorine signal could be detected with chemical shift imaging; this provides interesting data on cellular processes in stroke. The metabolism of oxygen plays an important role in aerobic respiration to produce energy-rich ATP. In this issue, an overview of 17O-MRI with its advantages and challenges is given by Gordji-Nejad et al. [32]. Different
Magn Reson Mater Phy (2014) 27:1–4
methods for determination of the cerebral metabolic rate of oxygen and clinical applications (e.g., Alzheimer’s disease, stroke, and tumor) are presented. A second contribution by Borowiak et al. [33] shows the feasibility of direct 17OMRI in the human brain and heart at a clinical whole-body 3T MR scanner. Three-dimensional UTE imaging of the human brain at nominal isotropic resolution of 5.6 mm could be acquired in a measurement time of 30 min using a single-loop surface coil. Another X-nucleus used for MRI is 19F, which possesses nearly the same sensitivity as the hydrogen nucleus. The lack of endogenous fluorine in the human body and the administration of non-toxic fluorinated molecules as MR contrast agent lead to a high degree of specificity. Perfluorocarbons (PFC) are molecules in which hydrogen atoms are replaced by fluorine. These agents are phagocytized by macrophages, and thus, in vivo tracking of them is useful to localize inflammation. The short communication by Jacoby et al. [34] demonstrates that nanoemulsions of PFCs can be used in 19F-MRI to detect myocarditis in a murine model at 9.4 Tesla. While 1H-MRI diagnosis of myocarditis is rather nonspecific, the presented method specifically visualizes the infiltration of immune cells into the myocardium. This contribution is followed by a pilot study from Terekhov et al. [35] that investigates the wash-in and wash-out kinetics of two different anesthetics in the pig brain using 19 F-MRI. A periodic administration of anesthetics shows a fast oscillatory response to concentration changes in the brain, while a slower accumulation without oscillations could be observed in fatty tissue. This method may help for better understanding of the spatial and temporal distribution of different fluorinated substances. We hope that the included articles are interesting for the reader, and that they will advance X-nuclei research to help for the diagnosis, prognosis, and treatment of diseases. This interdisciplinary field will gain from future development of ultra-high magnetic field MRI scanners. The area of applications needs the support of physicists, mathematicians, engineers and clinicians to improve the intrinsically low SNR of X-nuclei MRI and to bring this technique into the clinic. Contributions from various branches of science are still necessary to understand X-nuclei MRI signal variations in different diseases by a biological cell model— so let’s get started.
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References 19. 1. Haacke EM, Brown RW, Thompson MR, Venkatesan R (1999) Magnetic resonance imaging: physical principles and sequence design. Wiley, New York 2. Hilal SK, Maudsley AA, Simon HE, Perman WH, Bonn J, Mawad ME, Silver AJ, Ganti SR, Sane P, Chien IC (1983) In vivo
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NMR imaging of tissue sodium in the intact cat before and after acute cerebral stroke. AJNR Am J Neuroradiol 4(3):245–249 Boada FE, Gillen JS, Shen GX, Chang SY, Thulborn KR (1997) Fast three dimensional sodium imaging. Magn Reson Med 37(5):706–715 Nagel AM, Laun FB, Weber MA, Matthies C, Semmler W, Schad LR (2009) Sodium MRI using a density-adapted 3D radial acquisition technique. Magn Reson Med 62(6):1565–1573 Konstandin S, Nagel AM (2013) Performance of sampling density-weighted and postfiltered density-adapted projection reconstruction in sodium magnetic resonance imaging. Magn Reson Med 69(2):495–502 Maudsley AA, Hilal SK (1984) Biological aspects of sodium-23 imaging. Br Med Bull 40(2):165–166 Ra JB, Hilal SK, Oh CH, Mun IK (1988) In vivo magnetic resonance imaging of sodium in the human body. Magn Reson Med 7(1):11–22 Thulborn KR, Gindin TS, Davis D, Erb P (1999) Comprehensive MR imaging protocol for stroke management: tissue sodium concentration as a measure of tissue viability in nonhuman primate studies and in clinical studies. Radiology 213(1):156–166 Hussain MS, Stobbe RW, Bhagat YA, Emery D, Butcher KS, Manawadu D, Rizvi N, Maheshwari P, Scozzafava J, Shuaib A, Beaulieu C (2009) Sodium imaging intensity increases with time after human ischemic stroke. Ann Neurol 66(1):55–62 Ouwerkerk R, Bleich KB, Gillen JS, Pomper MG, Bottomley PA (2003) Tissue sodium concentration in human brain tumors as measured with 23Na MR imaging. Radiology 227(2):529–537 Sandstede JJ, Hillenbrand H, Beer M, Pabst T, Butter F, Machann W, Bauer W, Hahn D, Neubauer S (2004) Time course of 23Na signal intensity after myocardial infarction in humans. Magn Reson Med 52(3):545–551 Ouwerkerk R, Bottomley PA, Solaiyappan M, Spooner AE, Tomaselli GF, Wu KC, Weiss RG (2008) Tissue sodium concentration in myocardial infarction in humans: a quantitative 23Na MR imaging study. Radiology 248(1):88–96 Maril N, Rosen Y, Reynolds GH, Ivanishev A, Ngo L, Lenkinski RE (2006) Sodium MRI of the human kidney at 3 Tesla. Magn Reson Med 56(6):1229–1234 Haneder S, Konstandin S, Morelli JN, Nagel AM, Zoellner FG, Schad LR, Schoenberg SO, Michaely HJ (2011) Quantitative and qualitative (23)Na MR imaging of the human kidneys at 3 T: before and after a water load. Radiology 260(3):857–865 Near J, Bartha R (2010) Quantitative sodium MRI of the mouse prostate. Magn Reson Med 63(3):822–827 Hausmann D, Konstandin S, Wetterling F, Haneder S, Nagel AM, Dinter DJ, Schonberg SO, Zollner FG, Schad LR (2012) Apparent diffusion coefficient and sodium concentration measurements in human prostate tissue via hydrogen-1 and sodium23 magnetic resonance imaging in a clinical setting at 3T. Invest Radiol 47(12):677–682 Gupta RK, Gupta P (1982) Direct observation of resolved resonances from intra- and extracellular sodium-23 ions in NMR studies of intact cells and tissues using dysprosium(III)tripolyphosphate as paramagnetic shift reagent. J Magn Reson (1969) 47:344–350 Borthakur A, Hancu I, Boada FE, Shen GX, Shapiro EM, Reddy R (1999) In vivo triple quantum filtered twisted projection sodium MRI of human articular cartilage. J Magn Reson 141(2):286–290 Schepkin VD, Choy IO, Budinger TF, Obayashi DY, Taylor SE, DeCampli WM, Amartur SC, Young JN (1998) Sodium TQF NMR and intracellular sodium in isolated crystalloid perfused rat heart. Magn Reson Med 39(4):557–563 Madelin G, Babb J, Xia D, Chang G, Krasnokutsky S, Abramson SB, Jerschow A, Regatte RR (2013) Articular cartilage:
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Magn Reson Mater Phy (2014) 27:1–4 evaluation with fluid-suppressed 7.0-T sodium MR imaging in subjects with and subjects without osteoarthritis. Radiology 268(2):481–491 Mellon EA, Pilkinton DT, Clark CM, Elliott MA, Witschey WR 2nd, Borthakur A, Reddy R (2009) Sodium MR imaging detection of mild Alzheimer disease: preliminary study. AJNR Am J Neuroradiol 30(5):978–984 Zaaraoui W, Konstandin S, Audoin B, Nagel AM, Rico A, Malikova I, Soulier E, Viout P, Confort-Gouny S, Cozzone PJ, Pelletier J, Schad LR, Ranjeva JP (2012) Distribution of brain sodium accumulation correlates with disability in multiple sclerosis: a cross-sectional 23Na MR imaging study. Radiology 264(3):859–867 Konstandin S, Nagel AM (2014) Measurement techniques for magnetic resonance imaging of fast relaxing nuclei. Magn Reson Mater Phy 27(1):5–19 Stobbe RW, Beaulieu C (2014) Exploring and enhancing relaxation-based sodium MRI contrast. Magn Reson Mater Phy 27(1):21–33 Riemer F, Solanky BS, Stehning C, Clemence M, WheelerKingshott CA, Golay X (2014) Sodium (23Na) ultra-short echo time imaging in the human brain using a 3D-Cones trajectory. Magn Reson Mater Phy 27(1):35–46 Gurney PT, Hargreaves BA, Nishimura DG (2006) Design and analysis of a practical 3D cones trajectory. Magn Reson Med 55(3):575–582 Haneder S, Michaely HJ, Konstandin S, Schad LR, Morelli JN, Kra¨mer BK, Schoenberg SO, Lammert A (2014) 3T Renal 23NaMRI: effects of desmopressin in patients with central diabetes insipidus. Magn Reson Mater Phy 27(1):47–52 Inglese M, Madelin G, Oesingmann N, Babb JS, Wu W, Stoeckel B, Herbert J, Johnson G (2010) Brain tissue sodium concentration
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in multiple sclerosis: a sodium imaging study at 3 Tesla. Brain 133(Pt3):847–857 Maarouf A, Audoin B, Konstandin S, Rico A, Soulier E, Reuter F, Le Troter A, Confort-Gouny S, Cozzone PJ, Guye M, Schad LR, Pelletier J, Ranjeva JP, Zaaraoui W (2014) Topography of brain sodium accumulation in progressive multiple sclerosis. Magn Reson Mater Phy 27(1):53–62 Schepkin VD, Elumalai M, Kitchen JA, Qian C, Gor’kov PL, Brey WW (2014) In vivo chlorine and sodium MRI of rat brain at 21.1 T. Magn Reson Mater Phy 27(1):63–70 Baier S, Kra¨mer P, Grudzenski S, Fatar M, Kirsch S, Schad LR (2014) Chlorine and sodium chemical shift imaging during acute stroke in a rat model at 9.4 Tesla. Magn Reson Mater Phy 27(1):71–79 Gordji-Nejad A, Mo¨llenhoff K, Oros-Peusquens AM, Pillai DR, Shah NJ (2014) Characterizing cerebral oxygen metabolism employing oxygen-17 MRI/MRS at high fields. Magn Reson Mater Phy 27(1):81–93 Borowiak R, Groebner J, Haas M, Hennig J, Bock M (2014) Direct cerebral and cardiac 17O-MRI at 3 Tesla: initial results at natural abundance. Magn Reson Mater Phy 27(1):95–99 Jacoby C, Borg N, Heusch P, Sauter M, Bo¨nner F, Kandolf R, Klingel K, Schrader J, Flo¨gel U (2014) Visualization of immune cell infiltration in experimental viral myocarditis by 19F MRI in vivo. Magn Reson Mater Phy 27(1):101–106 Terekhov M, Scholz A, Schreiber LM (2014) Measurement of anesthetic uptake kinetics in the brain using 19F MRI and crosscorrelation analysis after pulsed application. Magn Reson Mater Phy 27(1):107–111
30 years of sodium/X-nuclei magnetic resonance imaging Simon Konstandin • Lothar R. Schad
Received: 8 October 2013 / Revised: 8 November 2013 / Accepted: 22 November 2013 / Published online: 22 January 2014 Ó ESMRMB 2014
Abstract In principle, all nuclei with nonzero spin can be employed for magnetic resonance imaging (MRI). Special scanner hardware and MR sequences are required to select the nucleus-specific frequency and to enable imaging with ‘‘sufficient’’ signal-to-noise ratio. This Special Issue starts with an overview of different nuclei that can be used for MRI today, followed by a review article about techniques required for imaging of quadrupolar nuclei with short relaxation times. Sequence developments to improve image quality and applications on different organs and diseases are presented for different nuclei (23Na, 35Cl, 17O, and 19F), with a focus on imaging at natural abundance. Keywords X-nuclei MRI Oxygen-17 Fluorine-19 Sodium-23 Chlorine-35
Besides conventional proton (1H) magnetic resonance imaging (MRI), there are many other X-nuclei that can be used in MRI. A prerequisite is a nonzero nuclear spin (i.e., an odd number of protons and/or neutrons) associated with a magnetic moment to generate signal in a receiver coil. Furthermore, high MR sensitivity—depending on the gyromagnetic ratio µ c3 and spin quantum number µ I (I ? 1)—and a ‘‘sufficient’’ number of nuclei must be present to achieve an adequate signal-to-noise ratio (SNR). This is the reason why most X-nuclei MR imaging studies are performed on sodium (23Na), measuring a mean intrinsic concentration of about 80 mmol/L [1] in the human body (up to *300 mM in intervertebral disks). S. Konstandin (&) L. R. Schad Computer Assisted Clinical Medicine, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany e-mail: [email protected]
Since the first in vivo sodium images were published 30 years ago by Hilal et al. [2], higher magnetic field strengths and improved gradient hardware and sequences have recently brought other X-nuclei (e.g., 17O, 35Cl, 39K) into focus. SNR-efficient acquisition techniques with short echo times [3, 4] and sampling density weighted apodization [5] for filtered acquisition lead to higher image quality, especially for quadrupolar nuclei (spin [ 1/2) that are subject to faster relaxation because of a nonspherical charge distribution and electric quadrupole moment. Administration of tracer compounds with an X-nucleus with good intrinsic SNR, such as fluorine (19F), which is not abundant in the human body, enables the backgroundfree observation of these compounds as specific tracers for biological processes. Ion fluxes in cells play an important role in many processes of cell activity. Several mechanisms maintain concentration gradients of different ions (e.g., 23Na, 39K, 35Cl) between the intracellular and extracellular space. The main part of the energy, stored in form of adenosine triphosphate (ATP), is invested in the sodium–potassium pump (Na?– K?-ATPase), which pumps three Na? ions out of the cell while two K? ions are pumped into the cell. This active transport mechanism is one factor to keep the resting membrane potential in cells at about -70 mV. Different ion-specific channels are able to transmit information via electrical signals by gating the flow of ions across the cell membrane. The pathological change in concentration gradients and the metabolism of intrinsic and external contrast agents can be visualized by X-nuclei MRI. There are many biomedical applications where imaging of nuclei other than protons can give additional functional information. Because of its favorable MR properties, 23Na was the first and is still the most imaged X-nucleus thus far, offering a unique tool for visualization of tissue viability non-invasively.
123
2
In the beginning of sodium MRI, many organs such as brain [2], heart [6], and kidney [7] have been imaged despite low resolution and strong T2 weighting of spin echo sequences used. Imaging of large structures and fluid compartments was feasible, but quantification of sodium content was not possible. Measurement times were too long, so that sodium MRI had no clinical relevance at that time. The development of higher magnetic field strengths with faster gradient hardware and improved sequence acquisition schemes led to a revival of sodium imaging in the late 1990s. Many biomedical applications have emerged in the last few decades. MR studies on the temporal and spatial distribution of 23Na have been investigated in stroke [8, 9], tumor [10], heart [11, 12], kidney [13, 14], and prostate [15, 16]. The measurement of tissue sodium concentration and the distinction of intracellular and extracellular sodium content by administration of paramagnetic shift reagents [17] and multiple quantum filtering [18, 19] techniques give additional information on tissue viability and pathophysiological processes. Nowadays, sodium images with submillimeter in-plane resolution can be achieved, which brings imaging of thin structures like cartilage [20] and plaque burden in Alzheimer’s disease [21] and multiple sclerosis [22] into focus. This Special Issue of MAGMA contains two review articles and nine research papers. Most studies deal with 23Na-MRI but studies using 35Cl, 17O, and 19 F for imaging are also presented. The first contribution from Konstandin and Nagel [23] gives an overview of MR techniques used for imaging of fast relaxing nuclei (i.e., spin [ 1/2). The most important properties of these acquisition schemes are their ultra-short echo time (UTE) and high SNR efficiency. Different k-space trajectories are presented, possessing different behaviors regarding k-space coverage per projection, gradient hardware requirements, and SNR efficiency. Techniques for intrinsic filtering and anisotropic resolution to improve image quality of thin structures (e.g., cartilage) are shown. Different methods to put more weighting on either the intracellular or the extracellular signal are summarized. The major drawbacks of X-nuclei concentration quantification are the need for long repetition times and the difficulty to avoid T*2 weighting from the fast T2 component (T2f) of quadrupolar nuclei. Relaxation-weighted sodium MRI provides higher SNR and additional information besides density-weighted imaging. Stobbe and Beaulieu [24] investigated the use of gradient refocusing of the transverse magnetization in simulations and experiments. Short repetition times and relatively long radiofrequency excitation pulses lead to a contrast that is dependent on T2f and T1, which gives an enhanced contrast-to-noise ratio between gray and white matter in the human brain. This complementary contrast could provide a better differentiation for various diseases, and should be further explored in the future.
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Although UTE sequences are available at a few scanners, these sequences are designed for 1H-MRI and can be optimized for X-nuclei imaging. This includes uniform k-space sampling for optimal SNR efficiency and twisting k-space trajectories to shorten measurement times. Riemer et al. [25] give a comparison between two UTE sequences available on their clinical MRI system and an acquisition scheme that is based on three-dimensional (3D) cones established by Gurney et al. [26]. While these three different sequences provide similar SNR in human brain measurements, the latter gives a better reproducibility and a narrower point-spread function, due to uniform k-space sampling by gradient adaption during acquisition. The feasibility study by Haneder et al. [27] demonstrates the potential of sodium imaging for the non-invasive assessment of physiological changes in the kidney at clinical MRI scanners. They investigated the effect of desmopressin—a synthetic replacement for the hormone vasopressin (AVP)—on renal corticomedullary sodium concentration of patients with central diabetes insipidus (i.e., deficiency of AVP). This hormone regulates the body’s retention of water, and therefore, an overall mean decrease of 17 % could be observed after administration of desmopressin. Although conventional proton MRI is extremely sensitive in detecting multiple sclerosis (MS)-related abnormalities, it lacks specificity to clinical parameters such as relapse rate and neurological disability. Recently, an increase in sodium concentration could be detected inside white matter (WM) lesions, normal-appearing white matter (NAWM) and grey matter (GM) in relapsing-remitting multiple sclerosis patients [28]. The contribution by Maarouf et al. [29] investigates sodium accumulation in different tissues (WM T2 lesions, NAWM, GM) and brain areas and correlated with disability of primary-progressive and secondary-progressive MS. Two interesting applications of 35Cl-MRI are presented in this Special Issue. The study by Schepkin et al. [30] demonstrates the feasibility of chlorine and sodium quantification in rat at an ultra-high magnetic field of 21.1 Tesla. They measured T1 and T*2 relaxation times, and compared the increase in chlorine and sodium concentration between normal rat brain and rat with glioma using a volume RF coil. The contribution from Baier et al. [31] shows combined proton, sodium and chlorine measurements in a rat stroke model during the acute phase using a triple-resonant coil setup. Different rates of increase in sodium and chlorine signal could be detected with chemical shift imaging; this provides interesting data on cellular processes in stroke. The metabolism of oxygen plays an important role in aerobic respiration to produce energy-rich ATP. In this issue, an overview of 17O-MRI with its advantages and challenges is given by Gordji-Nejad et al. [32]. Different
Magn Reson Mater Phy (2014) 27:1–4
methods for determination of the cerebral metabolic rate of oxygen and clinical applications (e.g., Alzheimer’s disease, stroke, and tumor) are presented. A second contribution by Borowiak et al. [33] shows the feasibility of direct 17OMRI in the human brain and heart at a clinical whole-body 3T MR scanner. Three-dimensional UTE imaging of the human brain at nominal isotropic resolution of 5.6 mm could be acquired in a measurement time of 30 min using a single-loop surface coil. Another X-nucleus used for MRI is 19F, which possesses nearly the same sensitivity as the hydrogen nucleus. The lack of endogenous fluorine in the human body and the administration of non-toxic fluorinated molecules as MR contrast agent lead to a high degree of specificity. Perfluorocarbons (PFC) are molecules in which hydrogen atoms are replaced by fluorine. These agents are phagocytized by macrophages, and thus, in vivo tracking of them is useful to localize inflammation. The short communication by Jacoby et al. [34] demonstrates that nanoemulsions of PFCs can be used in 19F-MRI to detect myocarditis in a murine model at 9.4 Tesla. While 1H-MRI diagnosis of myocarditis is rather nonspecific, the presented method specifically visualizes the infiltration of immune cells into the myocardium. This contribution is followed by a pilot study from Terekhov et al. [35] that investigates the wash-in and wash-out kinetics of two different anesthetics in the pig brain using 19 F-MRI. A periodic administration of anesthetics shows a fast oscillatory response to concentration changes in the brain, while a slower accumulation without oscillations could be observed in fatty tissue. This method may help for better understanding of the spatial and temporal distribution of different fluorinated substances. We hope that the included articles are interesting for the reader, and that they will advance X-nuclei research to help for the diagnosis, prognosis, and treatment of diseases. This interdisciplinary field will gain from future development of ultra-high magnetic field MRI scanners. The area of applications needs the support of physicists, mathematicians, engineers and clinicians to improve the intrinsically low SNR of X-nuclei MRI and to bring this technique into the clinic. Contributions from various branches of science are still necessary to understand X-nuclei MRI signal variations in different diseases by a biological cell model— so let’s get started.
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References 19. 1. Haacke EM, Brown RW, Thompson MR, Venkatesan R (1999) Magnetic resonance imaging: physical principles and sequence design. Wiley, New York 2. Hilal SK, Maudsley AA, Simon HE, Perman WH, Bonn J, Mawad ME, Silver AJ, Ganti SR, Sane P, Chien IC (1983) In vivo
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