Dietary salt intake has been investigated in relation to hypertension since the early 20th century.1 Mendelian forms of hypertension have underscored the role of salt intake in the development of hypertension.2 Clinicians have advised patients in terms of their dietary intake and have relied on 24 hour urine collections to verify dietary compliance. 3 Nonetheless, the results have been suboptimal. Clinicians have been limited to measuring Na + in plasma and urine, and the relationship to these sources for determining salt-sensitivity has been disappointing. The issue is important, as salt-sensitivity portends an earlier death. 4 Na + is bound to negatively charged proteoglycans that are very abundant in the skin, the body's largest organ. 5 We showed recently that signaling mechanisms exist in skin that control skin electrolyte storage. 6 When these mechanisms are perturbed, salt-sensitive hypertension results. Translating such findings to humans has been challenging. For that reason, we implemented quantitative 23 Na magnetic resonance imaging ( 23 Na-MRI) to visualize Na + in skin and soft tissues. 7 We reported on rodents measured with 23 Na-MRI and with MR spectroscopy, a small number of normal subjects, and 5 patients with primary aldosteronism, who were studied before and after definitive treatment. We have now extended our observations to larger numbers of normal men and women, as well as to patients with essential hypertension. We believe that 23 Na-MRI shows promise to be of clinical utility in further defining the relationship between salt and hypertension. MethodsWe implemented 23 Na-MRI for quantitative analysis in men; the methods were recently published. 7 We measured Na + content in lower leg muscle and skin with a 23 Na knee-coil (Stark-Contrast, Erlangen, Germany) at 3.0 T with a MRI scanner (Magnetom-Trio, Siemens Healthcare, Erlangen, Germany) using a 2D-FLASH sequence (total acquisition time, TA=13.7 minutes; echo time, TE=2.07 ms; repetition time, TR=100 ms; flip angle, FA=90°; 128 averages, resolution:Abstract-High dietary salt intake is associated with hypertension; the prevalence of salt-sensitive hypertension increases with age. We hypothesized that tissue Na + might accumulate in hypertensive patients and that aging might be accompanied by Na + deposition in tissue. We implemented 23 Na magnetic resonance imaging to measure Na + content of soft tissues in vivo earlier, but had not studied essential hypertension. We report on a cohort of 56 healthy control men and women, and 57 men and women with essential hypertension. The ages ranged from 22 to 90 years.23 Na magnetic resonance imaging measurements were made at the level of the calf. We observed age-dependent increases in Na + content in muscle in men, whereas muscle Na + content did not change with age in women. We estimated water content with conventional MRI and found no age-related increases in muscle water in men, despite remarkable Na + accumulation, indicating water-free Na + storage in muscle. With increasing age, there was ...

Summary Immune cells regulate a hypertonic microenvironment in the skin; however, the biological advantage of increased skin Na+ concentrations is unknown. We found that Na+ accumulated at the site of bacterial skin infections in humans and in mice. We used the protozoan parasite Leishmania major as a model of skin-prone macrophage infection to test the hypothesis that skin-Na+ storage facilitates antimicrobial host defense. Activation of macrophages in the presence of high NaCl concentrations modified epigenetic markers and enhanced p38 mitogen-activated protein kinase (p38/MAPK)-dependent nuclear factor of activated T cells 5 (NFAT5) activation. This high-salt response resulted in elevated type-2 nitric oxide synthase (Nos2)-dependent NO production and improved Leishmania major control. Finally, we found that increasing Na+ content in the skin by a high-salt diet boosted activation of macrophages in an Nfat5-dependent manner and promoted cutaneous antimicrobial defense. We suggest that the hypertonic microenvironment could serve as a barrier to infection.

Hypertension is linked to disturbed total-body sodium (Na(+)) regulation; however, measuring Na(+) disposition in the body is difficult. We implemented (23)Na magnetic resonance spectroscopy ((23)Na-MR) and imaging technique ((23)Na-MRI) at 9.4T for animals and 3T for humans to quantify Na(+) content in skeletal muscle and skin. We compared (23)Na-MRI data with actual tissue Na(+) content measured by chemical analysis in animal and human tissue. We then quantified tissue Na(+) content in normal humans and in patients with primary aldosteronism. We found a 29% increase in muscle Na(+) content in patients with aldosteronism compared with normal women and men. This tissue Na(+) was mobilized after successful treatment without accompanying weight loss. We suggest that, after further refinements, this tool could facilitate understanding the relationships between Na(+) accumulation and hypertension. Furthermore, with additional technical advances, a future clinical use may be possible.

We have previously reported sodium is stored in skin and muscle. The amounts stored in hemodialysis (HD) patients are unknown. We determined whether 23Na magnetic resonance imaging (sodium-MRI) allows assessment of tissue sodium and its removal in 24 HD patients, and 27 age-matched healthy controls. We also studied 20 HD patients before and shortly after HD with a batch dialysis system with direct measurement of sodium in dialysate and ultrafiltrate. Age was associated with higher tissue sodium content in controls. This increase was paralleled by an age-dependent decrease of circulating levels of vascular endothelial growth factor-C (VEGF-C). Older (over 60 years) HD patients showed increased sodium and water in skin and muscle, and lower VEGF-C levels than age-matched controls. After HD, patients with low VEGF-C levels had significantly higher skin sodium content than patients with high VEGF-C levels (low VEGF-C: 2.3 ng/ml and skin sodium: 24.3 mmol/L; high VEGF-C: 4.1ng/ml and skin sodium: 18.2mmol/L). Thus, sodium-MRI quantitatively detects sodium stored in skin and muscle in humans and allows studying sodium storage reduction in ESRD patients. Age and VEGF-C-related local tissue-specific clearance mechanisms may determine the efficacy of tissue sodium removal with HD. Prospective trials on the relationship between tissue sodium content and hard endpoints could provide new insights into sodium homeostasis, and clarify whether increased sodium storage is a cardiovascular risk factor.

Ga-PSMA-11 PET/CT-derived metabolic tumor parameters showed promising results for evaluation of treatment response. Especially, TL-PSMA demonstrated higher agreement rates with biochemical response compared to SUVmax. Larger, ideally prospective trials are needed to help to reveal the full potential of metabolic parameters derived from PET imaging with Ga-PSMA-11.

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The combination of nelfinavir and chemoradiotherapy showed acceptable toxicity and promising activity in patients with pancreatic cancer.

ObjectiveNa+ can be stored in muscle and skin without commensurate water accumulation. The aim of this study was to assess Na+ and H2O in muscle and skin with MRI in acute heart failure patients before and after diuretic treatment and in a healthy cohort.MethodsNine patients (mean age 78 years; range 58–87) and nine age and gender-matched controls were studied. They underwent 23Na/1H-MRI at the calf with a custom-made knee coil. Patients were studied before and after diuretic therapy. 23Na-MRI gray-scale measurements of Na+-phantoms served to quantify Na+-concentrations. A fat-suppressed inversion recovery sequence was used to quantify H2O content.ResultsPlasma Na+-levels did not change during therapy. Mean Na+-concentrations in muscle and skin decreased after furosemide therapy (before therapy: 30.7±6.4 and 43.5±14.5 mmol/L; after therapy: 24.2±6.1 and 32.2±12.0 mmol/L; p˂0.05 and p˂0.01). Water content measurements did not differ significantly before and after furosemide therapy in muscle (p = 0.17) and only tended to be reduced in skin (p = 0.06). Na+-concentrations in calf muscle and skin of patients before and after diuretic therapy were significantly higher than in healthy subjects (18.3±2.5 and 21.1±2.3 mmol/L).Conclusions 23Na-MRI shows accumulation of Na+ in muscle and skin in patients with acute heart failure. Diuretic treatment can mobilize this Na+-deposition; however, contrary to expectations, water and Na+-mobilization are poorly correlated.