On the extracellular contribution to multiple quantum filtered 23Na NMR of perfused rat heart

We investigated the contribution of extracellular Na⁺ to the multiple-quantum filtered ²³Na NMR signal of perfused rat hearts to determine if the presence of shift reagent Dy(PPPi)₂ and inorganic phosphate were somehow responsible for the generation of extracellular multiple quantum coherence. Neither phosphate nor shift reagent caused an increase in the total multiple-quantum filtered signal intensity or in the percent contribution from extracellular ions. On the contrary, addition of Dy(PPPi)₂ actually decreased the total signal intensity from intra- and extracellular ions. Further addition of 1.5 mM Gd(PPPi)₂ eliminated the extracellular contribution. These data indicate that the previously reported extracellular contribution in perfused hearts is a true contribution of extracellular ions, and not an artifact originating from their interaction with the shift reagent.     

Three-dimensional triple-quantum-filtered 23Na imaging of the dog head in vivo

Multiple-quantum (MQ)-filtered ²³Na NMR has been proposed as a means to partially discriminate between intracellular and extracellular sodium. However, low signal-to-noise ratio (SNR) has been a major obstacle to MQ-filtered ²³Na imaging becoming an important technique for biological and clinical applications. We compared the various MQ-filtered ²³Na imaging pulse sequences to select the optimum sequence that provides the best SNR. The results of phantom experiments show that the gradient-echo MQ-filtered ²³Na imaging sequence produces the best SNR. We also report, for the first time, three-dimensional single-quantum (SQ) and triple-quantum (TQ)-filtered ²³Na images of the live dog brain and demonstrate the sensitivity of these images to ischemia produced by euthanizing the animal. The SQ images showed a 10% to 15% decrease in signal intensity from the brain postmortem, whereas the TQ-filtered images showed a 40% to 50% increase. These changes in signal intensities are consistent with the influx of Na⁺ into the cells upon death. The feasibility of obtaining TQ-filtered ²³Na images of in situ dog brain encourages us to apply this technique to humans.     

Three-dimensional triple quantum-filtered 23na imaging of rabbit kidney with weighted signal averaging

Low signal-to-noise ratio (SNR) has been the main obstacle to multiple quantum-filtered ²³Na imaging becoming an important technique for biologic and clinical applications. Through computer simulations and phantom experiments, we show that the SNR in ²³Na imaging can be substantially improved by weighted signal averaging. Three-dimensional single quantum and triple quantum (TQ)-filtered ²³Na images of an externalized rabbit kidney were collected with this technique. The TQ-filtered image did not show any signal when the animal was alive. However, upon sacrificing the animal, the renal cortex became clearly visible without any significant increase in signal from the medullary region. This increase in TQ-flltered signal in the renal cortex may be caused by an increased concentration of intracellular Na⁺ in the large intracellular space present herein, compared with the medulla. To our knowledge, this study represents the first example of three-dimensional TQ-filtered ²³Na image of a biological sample.     

Sodium TQF NMR and intracellular sodium in isolated crystalloid perfused rat heart

The feasibility of monitoring intracellular sodium changes using Na triple quantum filtered NMR without a chemical shift reagent (SR) was investigated in an isolated rat heart during a variety of interventions for Ma, loading. Perfusion with 1 mM ouabain or without K⁺ present in the perfusate for 30 min produced a rise of the Na TQF signal with a plateau of -190% and ?228% relative to the preintervention level, respectively. Stop-flow ischemia for 30 min resulted in a TQF signal growth of ?147%. The maximal Na TQF signal increase of 460% was achieved by perfusion without K⁺/Ca²⁺, corresponding to an elimination of the Na transmembrane gradient. The observed values of Na NMR TQF growth in the physiological and pathological ranges are in agreement with reported data by other methods and have a linear correlation with intracellular sodium content as determined in this study by Co-EDTA method and by sucrose-histidine washout of the extracellular space. Our data indicate that the increase in Na TQF NMR signal is determined by the growth of Na_i, and the extracellular Na contribution to the total TQF signal is unchanged at ?64%. In conclusion, Na TQF NMR without using SR offers a unique and noninvasive opportunity to monitor alterations of intracellular sodium. It may provide valuable insights for developing car-dioprotective strategies and for observing the effects of pharmaceutical treatments on sodium homeostasis.     

39K NMR measurement of intracellular potassium during ischemia in the perfused guinea pig heart

The hyperfine shift reagent, TmDOTP^5?, was used to resolve the ³⁹K NMR resonances of intra- (K_i⁺) and extracellular (K_e⁺) potassium in isolated, perfused guinea pig hearts. [K_i⁺] as measured by ³⁹K NMR was 25.9 ± 10.3 mM, compared with 114.4 ± 10.8 mM as measured by atomic absorption spectros-copy (AAS) using TmD0TP^5- as a marker of extracellular space. Thus, only approximately 23% of intracellular potassium was detected by ³⁹K NMR using our experimental conditions. The area of the K_i⁺ signal increased during early ischemia then returned to baseline levels during reperfusion. In an effort to learn more about the K_i⁺ not detected by ³⁹K NMR, hearts were perfused with a Rb⁺-enriched, K⁺ -depleted buffer for an extended period. This resulted in loss of the entire ³⁹K NMR signal, and K_i⁺, as measured by AAS, decreased from ～60 to ～6 to 7 μmol/g wet weight. When K⁺-depleted hearts were subjected to global ischemia, a small ³⁹K NMR signal reappeared, suggesting that at least a portion of the nonexchangeable K_i⁺ becomes detectable by NMR during ischemia. This newly visible K⁺ signal subsequently dissipated during reperfusion of ischemic hearts. We conclude that ischemia induces changes in the NMR visibility of ³⁹K in perfused guinea pig hearts.     

Sequential changes of sodium magnetic resonance images after cerebral hemorrhage

Summary Four patients with cerebral hemorrhage were examined serially from the acute to chronic phase by¹H magnetic resonance imaging (MRI),²³Na MRI and computed tomography (CT). At 1–2 days after bleeding, the²³Na image revealed no visible signal change in the area of hemorrhage, although CT and¹H images clearly demonstrated the existence of a hematoma in the thalamus or putamen. At 4–7 days after the hemorrhage, the²³Na images began to exhibit a small increase in signal intensity at the hematoma site, while at 2–3 weeks, a marked increase in²³Na signal intensity was observed. These findings suggest that the hematoma consisted mainly of a corpuscular component, with a low Na⁺ concentration, with little serum component. Lack of signal from the corpuscular component on the²³Na image was confirmed by an in vitro study. In the late acute phase, Na⁺ accumulation may occur in the corpuscular component due to failure of the Na⁺ pump. The intracellular²³Na appears to be totally visible to MRI, resulting in an increase in signal intensity. In the subacute or chronic phase, the corpuscular component may be destroyed, leaving fluid in its place. A high Na⁺ concentration in this fluid may give markedly increased²³Na signal intensity on MRI.²³Na MRI appears to provide important information for understanding the evoluation of cerebral hemorrhage and for estimating the viability of cells, although its value for diagnosis may not be great.     

Sodium mapping in focal cerebral ischemia in the rat by quantitative 23Na MRI

Purpose

To validate ²³Na twisted projection magnetic resonance imaging (MRI) as a quantitative technique to assess local brain sodium concentration ([Na⁺]_br) during rat focal ischemia every 5.3 minutes.

Materials and Methods

The MRI protocol included an ultrashort echo‐time (0.4 msec), a correction of radiofrequency (RF) inhomogeneities by B₁ mapping, and the use of 0–154 mM NaCl calibration standards. To compare MRI [Na⁺]_br values with those obtained by emission flame photometry in precision‐punched brain samples of about 0.5 mm³ size, MR images were aligned with a histological three‐dimensional reconstruction of the punched brain and regions of interest (ROIs) were placed precisely over the punch voids.

Results

The Bland–Altman analysis of [Na⁺]_br in normal and ischemic cortex and caudate putamen of seven rats quantitated by ²³Na MRI and flame photometry yielded a mean bias and limits of agreement (at ±1.96 SD) of 2% and 43% of average, respectively. A linear increase in [Na⁺]_br was observed between 1 and 6 hours after middle cerebral artery occlusion.

Conclusion

²³Na MRI provides accurate and reliable results within the whole range of [Na⁺]_br in ischemia with a temporal resolution of 5.3 minutes and precisely targeted submicroliter ROIs in selected brain structures. J. Magn. Reson. Imaging 2009;29:962–966. © 2009 Wiley‐Liss, Inc.     

The role of Na+/K+ ATPase activity during low flow ischemia in preventing myocardial injury: A 31P, 23Na and 87Rb NMR spectroscopic study

An increase in intracellular Na⁺ during ischaemia has been associated with myocardial injury. In this study, we determined whether inhibition of Na⁺/K⁺ ATPase activity contributes to this increase and whether Na⁺/K⁺ ATPase activity can be maintained by provision of glucose to perfused rat hearts during low flow, 0.5 ml/min, ischemia. We used ³¹P NMR spectroscopy to determine changes in myocardial energetics and intracellular and extracellular volumes. ²³Na NMR spectroscopy, with DyTTHA^3- present as a shift reagent, was used to measure changes in intracellular Na⁺ and ⁸⁷Rb NMR spectroscopy was used to estimate Na⁺/K⁺ ATPase activity from Rb⁺ influx rates, Rb⁺ being an NMR-sensitive congener of K⁺. In hearts provided with 11 mM glucose throughout ischemia, glycolysis continued and ATP was twofold higher than in hearts without glucose. In the glucose-hearts, Rb⁺ influx rate was threefold higher, intracellular Na⁺ was fivefold lower at the end of ischemia and functional recovery during reperfusion was twofold higher. We propose that continuation of glycolysis throughout low flow ischemia allowed maintenance of sufficient Na⁺/K⁺ ATPase activity to prevent the increase in intracellular Na⁺ that would otherwise have led to myocardial injury.     

Determination of the intracellular sodium concentration in perfused mouse liver by 31P and 23Na magnetic resonance spectroscopy

A combination of ³¹P and ²³Na NMR spectroscopy has been used to quantify the concentration of intracellular sodium, [Na]_IC in the isolated and perfused mouse liver. The ³¹P resonances of dimethyl methylphosphonate and LaDOTP^5?, markers of total tissue space and extracellular space, respectively, were used to determine the intracellular liver volume. For a mean wet weight of 1.7 ± 0.3 g, the intracellular liver volume as measured by ³¹P NMR averaged 1.2 ± 0.2 ml. The amount of intracellular sodium was measured from the baseline-resolved intracellular ²³Na resonance during perfusion of the shift reagent, TmDOTP^5?. These two measurements resulted in an NMR-determined value for [Na]_IC of 29.0 ± 5.2 mM. Separate measurement of total tissue Tm and Na by atomic absorption spectroscopy on the same samples provided an AAS-determined value for [Na]_Ic of 32.1 ± 7.4 mM. These results indicate that intracellular sodium in the isolated, perfused liver is 100% visible by ²³Na NMR spectroscopy.     

Tmdotp5− as a 23na shift reagent for the in vivo rat kidney

Since transmembrane sodium gradient is essential to many cell functions, there is continuing interest in methods that differentiate intracellular and extracellular Na⁺. In the kidney, shift reagent (SR) aided ²³Na magnetic resonance spectros-copy (MRS) has been successfully used only in isolated cells, tubules, and the perfused organ. In this report, we demonstrate for the first time that TmDOTP^5? can be used to distinguish Na⁺ compartments in kidneys in vivo. Infusion of 80 mM TmDOTP^5? without added Ca²⁺ produced three resolved ²³Na resonances, which we have assigned to intracellular Na⁺, vascular Na⁺, and intraluminal Na⁺. In comparison, infusion of 400 mM DyTTHA^3? produced two broad and unresolved resonances. The ³¹P spectra of the cellular high energy phosphate metabolites indicate that TmDOTP^5? is safe for in vivo applications. Washout studies suggest that this SR displays renal clearance similar to that of MR imaging contrast agents. However, the glomerular filtration rate (GFR) in animals infused with TmDOTP^5? was reduced by 49% compared with the GFR in control animals, perhaps due to the hypotensive effects of the SR. We conclude that TmDOTP^5? is effectively cleared from the blood of live animals but that a different formulation will be required for clinical application.     

Inhomogeneous sodium accumulation in the ischemic core in rat focal cerebral ischemia by 23Na MRI

Purpose

To test the hypotheses that (i) the regional heterogeneity of brain sodium concentration ([Na⁺]_br) provides a parameter for ischemic progression not available from apparent diffusion coefficient (ADC) data, and (ii) [Na⁺]_br increases more in ischemic cortex than in the caudate putamen (CP) with its lesser collateral circulation after middle cerebral artery occlusion in the rat.

Materials and Methods

²³Na twisted projection MRI was performed at 3 Tesla. [Na⁺]_br was independently determined by flame photometry. The ischemic core was localized by ADC, by microtubule‐associated protein‐2 immunohistochemistry, and by changes in surface reflectivity.

Results

Within the ischemic core, the ADC ratio relative to the contralateral tissue was homogeneous (0.63 ± 0.07), whereas the rate of [Na⁺]_br increase (slope) was heterogeneous (P < 0.005): 22 ± 4%/h in the sites of maximum slope versus 14 ± 1%/h elsewhere (here 100% is [Na⁺]_br in the contralateral brain). Maximum slopes in the cortex were higher than in CP (P < 0.05). In the ischemic regions, there was no slope/ADC correlation between animals and within the same brain (P > 0.1). Maximum slope was located at the periphery of ischemic core in 8/10 animals.

Conclusion

Unlike ADC, ²³Na MRI detected within‐core ischemic lesion heterogeneity. J. Magn. Reson. Imaging 2009;30:18–24. © 2009 Wiley‐Liss, Inc.     

Improved assessment of cartilage repair tissue using fluid-suppressed 23Na inversion recovery MRI at 7 Tesla: preliminary results

Objectives

To evaluate cartilage repair and native tissue using a three-dimensional (3D), radial, ultra-short echo time (UTE) ²³Na MR sequence without and with an inversion recovery (IR) preparation pulse for fluid suppression at 7 Tesla (T).

Methods

This study had institutional review board approval. We recruited 11 consecutive patients (41.5 ± 11.8 years) from an orthopaedic surgery practice who had undergone a knee cartilage restoration procedure. The subjects were examined postoperatively (median = 26 weeks) with 7-T MRI using: proton-T2 (TR/TE = 3,000 ms/60 ms); sodium UTE (TR/TE = 100 ms/0.4 ms); fluid-suppressed, sodium UTE adiabatic IR. Cartilage sodium concentrations in repair tissue ([Na⁺]_R), adjacent native cartilage ([Na⁺]_N), and native cartilage within the opposite, non-surgical compartment ([Na⁺]_N2) were calculated using external NaCl phantoms.

Results

For conventional sodium imaging, mean [Na⁺]_R, [Na⁺]_N, [Na⁺]_N2 were 177.8 ± 54.1 mM, 170.1 ± 40.7 mM, 172.2 ± 30 mM respectively. Differences in [Na⁺]_R versus [Na⁺]_N (P = 0.59) and [Na⁺]_N versus [Na⁺]_N2 (P = 0.89) were not significant. For sodium IR imaging, mean [Na⁺]_R, [Na⁺]_N, [Na⁺]_N2 were 108.9 ± 29.8 mM, 204.6 ± 34.7 mM, 249.9 ± 44.6 mM respectively. Decreases in [Na⁺]_R versus [Na⁺]_N (P = 0.0.0000035) and [Na⁺]_N versus [Na⁺]_N2 (P = 0.015) were significant.

Conclusions

Sodium IR imaging at 7 T can suppress the signal from free sodium within synovial fluid. This may allow improved assessment of [Na⁺] within cartilage repair and native tissue.

Key Points

• NaIR magnetic resonance imaging can suppress signal from sodium within synovial fluid.

• NaIR MRI thus allows assessment of sodium concentration within cartilage tissue alone.

• This may facilitate more accurate assessment of repair tissue composition and quality.

     

31P NMR and triple quantum filtered 23Na NMR studies of the effects of inhibition of Na+/H+ exchange on intracellular sodium and pH in working and ischemic hearts

The triple quantum filtered ²³Na NMR method is applied here to measure the effects of EIPA, a specific inhibitor of the Na⁺/H⁺antiporter, on relative intracellular sodium concentrations in isolated working hearts at baseline, during ischemia, and at subsequent reperfusion. In analogy to the spectrophotometric isosbestic point, an approach is developed that defines a value of τ at which the effect of the relaxation times on the TQF signal intensities is minimized, and the signals are proportional to the sodium concentration for both ischemic and working hearts. EIPA at 1.5 μ significantly inhibited (P < 0.01) the influx of intracellular Na⁺ during 20 min of ischemia at 36.2°C in this rat heart model. In parallel³¹P NMR studies, EIPA had no effect on either the development of acidosis during ischemia or on the recovery of pH, during reperfusion despite its profound effect on intracellular Na⁺ influx. Thus, under our conditions the Na⁺/H⁺ antiporter did not play a critical role in the maintenance of intracellular pH. EIPA treatment resulted in improved recovery (P < 0.005) of mechanical function after 20 min of ischemia. [ATP] was higher in treated hearts during ischemia and reperfusion.     

Electrolyte analysis of pleural effusion for discrimination between seawater and freshwater drowning in decomposed bodies

ObjectiveThe diagnosis of drowning is an important issue in forensic investigations. Moreover, discriminating between seawater and freshwater drowning is crucial to identify where the drowning occurred. The present study aimed to investigate electrolyte concentrations in pleural fluid in decomposed bodies in late postmortem intervals and derive cut-off values for the diagnosis of seawater and freshwater drowning.Study designData were collected from 44 seawater drowning cases, 60 freshwater drowning cases, and 30 non-drowning cases with pleural effusion which served as controls. The levels of sodium ion (Na⁺), potassium ion (K⁺), and chloride ion (Cl⁻) of pleural fluid were measured, and two indices were calculated: summation of Na⁺ and K⁺ levels (SUM _Na + K), and summation of Na⁺, K⁺, and Cl⁻ levels (SUM _{Na + K + Cl}). The means of the three ion concentrations and two indices significantly differed between the three groups (p < 0.0001).ResultsThe receiver operating characteristic analysis revealed that the sensitivity and specificity were both 1.000 for SUM _{Na + K + Cl} of 288.3 mEq/L between the seawater and control groups. The Na⁺ value of 109.0 mEq/L also had a high sensitivity of 0.977 and a specificity of 0.933 in the seawater and control groups. The sensitivity and specificity were 0.967 and 1.000, respectively, for SUM _Na + K of 123.2 mEq/L between the freshwater and control groups.ConclusionThe electrolyte concentrations in pleural effusion may be useful for the diagnosis of drowning in decomposed bodies with a longer postmortem interval.     

Complete elimination of the extracellular 23Na NMR signal in triple quantum filtered spectra of rat hearts in the presence of shift reagents

A method is suggested whereby the shifted extracellular triple quantum filtered ²³Na signal of an isolated organ is completely eliminated. The method is based on the long relaxation time of the triple quantum coherence and on its fast evolution rate. When the carrier frequency is set on top of the intracellular sodium signal and the time interval between the last two pullses to (12 Δv)-l (Δv is the frequency difference between the intiracellular and the extracellular signals), a complete elimination of the extracellular ²³Na signal is achieved. The method is demonstrated for isolated rat hearts and the quantification of intracellular sodium using triple quantum filtered spectroscopy is discussed.     

Sequential changes on23Na MRI after cerebral infarction

²³Na MRI changes from the acute to chronic phase were investigated in seven patients with cerebral in-farcts. They showed no signal increase during the first 13 h after the stroke and revealed a definite signal increase thereafter. This reached a maximum 45–82 h after stroke and became slightly less marked in the subactue and chronic phases, probably as a result of disappearance of cerebral oedema. In the early acute phase of stroke,²³Na MRI appears to fail to demonstrate Na⁺ increases in the ischaemic area, due presumably to the invisibility on MRI of intracellular²³Na in the intact brain. The increase more than 13 h after stroke, during which ischaemic cells are likely to die, is presumably because of increased visibility of intracellular²³Na in the dead cells.²³Na MRI is apparently insensitive to early ischaemic changes, but may be useful for assessing the cell viability in the ischaemic brain.     

Na+/K+-ATPase,acetylcholinesterase and glutathione S-transferase activities as new markers of postmortem interval in Swiss mice

Determining precisely the postmortem interval (PMI) is a key parameter for forensic researches, given that various physical, biochemical and metabolic changes begin to occur in the body after death. In the present study, the Na⁺/K⁺-ATPase, glutathione S-transferase (GST) and acetylcholinesterase (AChE) activities were evaluated. For this, male adult Swiss mice were killed by isoflurane inhalation anesthesia and divided into four groups according to time of death (0, 6, 24 and 48 h). The brain, liver, kidney and skeletal muscle tissues were removed. Our results revealed that at the time of 6 h, there was a decrease on Na⁺/K⁺-ATPase and GST activities in the brain and liver tissues, respectively. In addition, at this time point, an increase on renal GST activity was verified. At the time of 24 h, an increase on the cerebral AChE and renal GST activities was observed, while the cerebral Na⁺/K⁺-ATPase activity was decreased. Forty-eight hours after death, cerebral Na⁺/K⁺-ATPase and renal GST activities remained decreased and increased, respectively. In addition, no alteration was observed on the GST activity in the skeletal muscle and brain (in PMIs evaluated). The present study revealed that the brain and kidney (at the times of 24 and 48 h) were the tissues that suffered the most changes in almost all the enzymes evaluated. Our results demonstrated that enzyme activity assessments are reliable, easy-to-perform and low-cost determinations, and could be promising postmortem markers.     

肝癌模型的23Na-MRI和1H扩散加权成像研究

目的 探讨应用无创23Na-MRI和1H-MRI监测大鼠原位肝癌的生长和结构与代谢转化过程的可行性.方法 大鼠肝脏种植N1S1细胞制备原位肝癌,应用动物专用MR机对肝脏在建模后7、14、21、28 d分别成像,DWI测量ADC值,单量子(SQ)23Na和三量子滤波(TQF)23Na-MRI分别测量组织Na+总含量和细胞内Na+含量,并与组织病理对照.采用方差分析比较肝脏、肿瘤、肿瘤/肝脏的ADC值、SQ和TQF 23Na信号强度组间差异,并进一步采用SNK法进行组内两两比较.结果 大鼠肝癌平均倍增时间为3.9 d.肿瘤生长的4个星期中,和周围肝组织的ADC比值保持为1.4～1.5;肝癌的SQ和TQF23Na信号强度在生长过程中都升高,而周围肝组织基本不变,4个时间点(N1S1细胞种植7 d、14 d、21 d和28 d)肝癌与周围肝组织SQ、TQF的信号强度比值分别为1.05±0.20、1.41±0.32、1.50±0.45、1.62±0.50(F=2.97,P＜0.05);1.32±0.11、1.54±0.18、2.38±0.22、2.39±0.16(F=11.18,P＜0.01).病理示肿瘤活细胞区相对细胞外间隙(ECS)为(9.7±1.8)%,肿瘤内炎症/坏死细胞区ECS为(12.7±1.7)%,较正常肝脏ECS(5.2±0.4)%增加(t值分别为5.55、11.36,P＜0.05),单位面积内肿瘤存活细胞区和炎症/坏死细胞数较周围正常肝组织细胞数增多(t值分别为14.9、26.51,P＜0.05),细胞/核比值从正常的4.0±0.3降低至肿瘤细胞的1.6±0.1(t=20.08,P＜0.05),反映出细胞内外间隙不同权重的复杂变化.结论 水ADC和SQ23Na-MRI反映ECS和组织总Na+的改变从而反映肿瘤组织的改变,TQF Na-MRI反映细胞内Na+的变化从而反映肝癌细胞生理和代谢的转化.在肝癌生长中组织总Na+和细胞内Na+都增高.     

23Na and 2H magnetic resonance studies of osteoarthritic and osteoporotic articular cartilage

In this study, the short component of the ²³Na T₂ (T_2f) and the ²³Na and ²H quadrupolar interactions (ν_Q) were measured in bone‐cartilage samples of osteoarthritic (OA) and osteoporotic (OP) patients. ²³Na ν_Q was found to increase in osteoarthritic articular cartilage relative to controls. Similar results were found in bovine cartilage following proteoglycan (PG) depletion, a condition that prevails in osteoarthritis. ²³Na ν_Q and 1/T_2f for articular cartilage obtained from osteoporotic patients were significantly larger than for control and osteoarthritic cartilage. Decalcification of both human and bovine articular cartilage resulted in an increase of ²³Na ν_Q and 1/T_2f, showing the same trend as the osteoporotic samples. Differences in the ratio of the intensity of the large ²H splitting to that of the small one in the calcified zone were also observed. In osteoporosis, this ratio was twice as large as that obtained for both control and osteoarthritic samples. The ²H and ²³Na results can be interpreted as due to sodium ions and water molecules filling the void created by the calcium depletion and to calcium ions being located in close association with the collagen fibers. To the best of our knowledge, this is the first study reporting differences of NMR parameters in cartilage of osteoporotic patients. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Shift reagent enhanced concurrent 23Na and 1H magnetic resonance spectroscopic studies of transcellular sodium distribution in the dog brain in vivo

The intracellular to extracellular sodium distribution is one of the primary determinants of action potentials necessary for the electrical function of organs such as brain, heart and skeletal muscle. The ability of shift reagent enhanced ²³Na MRS to directly measure the intracellular and extracellular sodium distribution in brain is controversial and centers on the relative contributions of bulk magnetic susceptibility and hyper-fine interactions to the observed chemical shifts. In this study, infusion of dysprosium (111) triethylenetetraminehexacetate (Dy(TTHA)⁻³), resulted in a ²³Na MRS spectrum of dog brain with two well resolved peaks at 9 and 0.4 ppm. The 9 ppm peak corresponded to the resonance seen in aspirated blood. After disruption of the blood brain barrier, the single peak at 0.4 ppm split into two peaks at 3 and 0 ppm. The ability of Dy-(lTHIA)⁻³ enhanced ²³Na MRS to follow global changes in brain sodium distribution was tested during cardiac arrest. The expected rapid Na influx into the intracellular space produced a marked decrease in the 3 ppm signal and a parallel increase in the 0 ppm peak. This is consistent with the assignment of the 3 ppm peak as interstitial sodium and the 0 ppm peak as intracellular sodium.