²³ Na Magnetic Resonance Imaging-Determined Tissue Sodium in Healthy Subjects and Hypertensive Patients

Abstract

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 ...

Acute changes in extracellular volume fraction in skeletal muscle monitored by23Na NMR spectroscopy

“…Not only patients with refractory hypertension have an increased tissue Na + which is detectable by 23 Na‐NMR (Kopp et al. 2013), but also dystrophic muscle fibers are characterized by an extensive imbalance in the sodium homeostasis (Weber et al. 2012; Jakob et al.…”

Role of the Vascular Wall in Sodium Homeostasis and Salt Sensitivity

“…16 The capacity for nonosmotic sodium storage has been shown for various tissues, such as skin, cartilage, bone, and muscle. 14,[17][18][19][20] Studies using 23 Na magnetic resonance imaging and conventional 1 H magnetic resonance imaging have revealed that, in both patients with primary hyperaldosteronism and patients with essential hypertension, considerable amounts of sodium are stored in muscle and skin without commensurate water retention. 19,20 Experiments in both mice and rats have identified that GAGs in the skin interstitium are responsible for sodium storage.…”

Skin sodium measured with 23Na MRI at 7.0 T

“…We have developed 23 Na-MRI as a method to non-invasively study the Na + skin depot in normal and hypertensive humans (12,13). We calibrated the method with human tissue that was then ashed and measured with atomic absorption spectrometry (12).…”

“…We calibrated the method with human tissue that was then ashed and measured with atomic absorption spectrometry (12). We have shown that the proposed 3.0 T approach has clinical utility (12)(13)(14).…”