Molecular mechanisms of brain water transport.

Our brains consist of 80% water, which is continuously shifted between different compartments and cell types during physiological and pathophysiological processes. Disturbances in brain water homeostasis occur with pathologies such as brain oedema and hydrocephalus, in which fluid accumulation leads to elevated intracranial pressure. Targeted pharmacological treatments do not exist for these conditions owing to our incomplete understanding of the molecular mechanisms governing brain water transport. Historically, the transmembrane movement of brain water was assumed to occur as passive movement of water along the osmotic gradient, greatly accelerated by water channels termed aquaporins. Although aquaporins govern the majority of fluid handling in the kidney, they do not suffice to explain the overall brain water movement: either they are not present in the membranes across which water flows or they appear not to be required for the observed flow of water. Notably, brain fluid can be secreted against an osmotic gradient, suggesting that conventional osmotic water flow may not describe all transmembrane fluid transport in the brain. The cotransport of water is an unconventional molecular mechanism that is introduced in this Review as a missing link to bridge the gap in our understanding of cellular and barrier brain water transport.

LRBA is essential for urinary concentration and body water homeostasis.

Protein kinase A (PKA) directly phosphorylates aquaporin-2 (AQP2) water channels in renal collecting ducts to reabsorb water from urine for the maintenance of systemic water homeostasis. More than 50 functionally distinct PKA-anchoring proteins (AKAPs) respectively create compartmentalized PKA signaling to determine the substrate specificity of PKA. Identification of an AKAP responsible for AQP2 phosphorylation is an essential step toward elucidating the molecular mechanisms of urinary concentration. PKA activation by several compounds is a novel screening strategy to uncover PKA substrates whose phosphorylation levels were nearly perfectly correlated with that of AQP2. The leading candidate in this assay proved to be an AKAP termed lipopolysaccharide-responsive and beige-like anchor protein (LRBA). We found that LRBA colocalized with AQP2 in vivo, and Lrba knockout mice displayed a polyuric phenotype with severely impaired AQP2 phosphorylation. Most of the PKA substrates other than AQP2 were adequately phosphorylated by PKA in the absence of LRBA, demonstrating that LRBA-anchored PKA preferentially phosphorylated AQP2 in renal collecting ducts. Furthermore, the LRBA-PKA interaction, rather than other AKAP-PKA interactions, was robustly dissociated by PKA activation. AKAP-PKA interaction inhibitors have attracted attention for their ability to directly phosphorylate AQP2. Therefore, the LRBA-PKA interaction is a promising drug target for the development of anti-aquaretics.

Frequency shifts of free water signals from compact bone: Simulations and measurements using a UTE-FID sequence.

PURPOSE: Free water in cortical bone is either contained in nearly cylindrical structures (mainly Haversian canals oriented parallel to the bone axis) or in more spherically shaped pores (lacunae). Those cavities have been reported to crucially influence bone quality and mechanical stability. Susceptibility differences between bone and water can lead to water frequency shifts dependent on the geometric characteristics. The purpose of this study is to calculate and measure the frequency distribution of the water signal in MRI in dependence of the microscopic bone geometry. METHODS: Finite element modeling and analytical approaches were performed to characterize the free water components of bone. The previously introduced UTE-FID technique providing spatially resolved FID-spectra was used to measure the frequency distribution pixel-wise for different orientations of the bone axis. RESULTS: The frequency difference between free water in spherical pores and in canals parallel to B0 amounts up to approximately 100 Hz at 3T. Simulated resonance frequencies showed good agreement with the findings in UTE-FID spectra. The intensity ratio of the two signal components (parallel canals and spherical pores) was found to vary between periosteal and endosteal regions. CONCLUSION: Spatially resolved UTE-FID examinations allow the determination of the frequency distribution of signals from free water in cortical bone. This frequency distribution indicates the composition of the signal contributions from nearly spherical cavities and cylindrical canals which allows for further characterization of bone structure and status.

Magnetic resonance fingerprinting-based myelin water fraction mapping for the assessment of white matter maturation and integrity in typical development and leukodystrophies.

A quantitative biomarker for myelination, such as myelin water fraction (MWF), would boost the understanding of normative and pathological neurodevelopment, improving patients' diagnosis and follow-up. We quantified the fraction of a rapidly relaxing pool identified as MW using multicomponent three-dimensional (3D) magnetic resonance fingerprinting (MRF) to evaluate white matter (WM) maturation in typically developing (TD) children and alterations in leukodystrophies (LDs). We acquired DTI and 3D MRF-based R1, R2 and MWF data of 15 TD children and 17 LD patients (9 months-12.5 years old) at 1.5 T. We computed normative maturation curves in corpus callosum and corona radiata and performed WM tract profile analysis, comparing MWF with R1, R2 and fractional anisotropy (FA). Normative maturation curves demonstrated a steep increase for all tissue parameters in the first 3 years of age, followed by slower growth for MWF while R1, R2R2 and FA reached a plateau. Unlike FA, MWF values were similar for regions of interest (ROIs) with different degrees of axonal packing, suggesting independence from fiber bundle macro-organization and higher myelin specificity. Tract profile analysis indicated a specific spatial pattern of myelination in the major fiber bundles, consistent across subjects. LD were better distinguished from TD by MWF rather than FA, showing reduced MWF with respect to age-matched controls in both ROI-based and tract analysis. In conclusion, MRF-based MWF provides myelin-specific WM maturation curves and is sensitive to alteration due to LDs, suggesting its potential as a biomarker for WM disorders. As MRF allows fast simultaneous acquisition of relaxometry and MWF, it can represent a valuable diagnostic tool to study and follow up developmental WM disorders in children.

The effect of aquaporin-4 inhibition on cerebrospinal fluid-tissue water exchange in mouse brain detected by magnetization transfer indirect spin labeling MRI.

The fluid transport of cerebrospinal fluid (CSF) and interstitial fluid in surrounding tissues plays an important role in the drainage pathway that facilitates waste clearance from the brain. This pathway is known as the glymphatic or perivascular system, and its functions are dependent on aquaporin-4 (AQP4). Recently, magnetization transfer indirect spin labeling (MISL) magnetic resonance imaging (MRI) has been proposed as a noninvasive and noncontrast-enhanced method for detecting water exchange between CSF and brain tissue. In this study, we first optimized the MISL sequence at preclinical 3 T MRI, and then studied the correlation of MISL in CSF with magnetization transfer (MT) in brain tissue, as well as the altered water exchange under AQP4 inhibition, using C57BL/6 mice. Results showed a strong correlation of MISL signal with MT signal. With the AQP4 inhibitor, we observed a significant decrease in MISL value (P < 0.05), suggesting that the hampered AQP4 activity led to decreased water exchange between CSF and brain tissue or the impairment of the glymphatic function. Overall, our findings demonstrate the potential application of MISL in assessing brain water exchange at 3 T MRI and its potential clinical translation.

Predictors of Water Turnover in Older Adults: A Doubly Labeled Water- and Triaxial Accelerometer-Based Study.

BACKGROUND: Water is one of the most essential nutrients for life. The water turnover (WT), total body water (TBW), and total energy expenditure (TEE) can be measured using the doubly labeled water (DLW) method. WT and TBW are lower in older adults than in young adults, and the former are susceptible to dehydration, necessitating to identify predictors of the WT in older adults. OBJECTIVES: The current study aimed to examine the association between WT and physical activity, physical function, and body composition in Japanese adults aged ≥65 y and identify predictors for WT in this population. METHODS: This study enrolled 133 older adults (women, n = 61; men, n = 72) aged 65-88 y. WT, TBW, TEE, fat-free mass (FFM), and percent body fat (%Fat) were determined using the DLW method. The fitness age score (FAS) was obtained from 5 physical fitness tests. Physical activity and the step count were assessed using a previously validated triaxial accelerometer. Multiple regression analyses were performed with WT as the dependent variable. RESULTS: WT was positively associated with weight, physical activity level (PAL), moderate-vigorous physical activity, and TEE, and negatively associated with sedentary behavior. We examined potential predictors for WT using age, sex, height, weight, FFM, %Fat, TEE, PAL, and FAS in older Japanese adults. CONCLUSIONS: Our results confirmed that age, sex, weight, FFM, TEE, and PAL are the potential predictors of WT in older Japanese adults aged ≥65 y.

H2OAthletes study protocol: effects of hydration changes on neuromuscular function in athletes.

We aim to understand the effects of hydration changes on athletes' neuromuscular performance, on body water compartments, fat-free mass hydration and hydration biomarkers and to test the effects of the intervention on the response of acute dehydration in the hydration indexes. The H2OAthletes study (clinicaltrials.gov ID: NCT05380089) is a randomised controlled trial in thirty-eight national/international athletes of both sexes with low total water intake (WI) (i.e. < 35·0 ml/kg/d). In the intervention, participants will be randomly assigned to the control (CG, n 19) or experimental group (EG, n 19). During the 4-day intervention, WI will be maintained in the CG and increased in the EG (i.e. > 45·0 ml/kg/d). Exercise-induced dehydration protocols with thermal stress will be performed before and after the intervention. Neuromuscular performance (knee extension/flexion with electromyography and handgrip), hydration indexes (serum, urine and saliva osmolality), body water compartments and water flux (dilution techniques, body composition (four-compartment model) and biochemical parameters (vasopressin and Na) will be evaluated. This trial will provide novel evidence about the effects of hydration changes on neuromuscular function and hydration status in athletes with low WI, providing useful information for athletes and sports-related professionals aiming to improve athletic performance.

Fluids and body composition during anesthesia in children and adolescents: A pilot study.

The purpose of this study is to evaluate the intracellular and extracellular volume before and after anesthesia in order to ascertain their variations and determine the potential utility of this information in optimizing intraoperative fluid administration practices. A bioimpedance spectroscopy device (body composition monitor, BCM) was used to measure total body fluid volume, extracellular volume, and intracellular volume. BCM measurements were performed before and after general anesthesia in unselected healthy children and adolescents visiting the Pediatric Institute of Southern Switzerland for low-risk surgical procedures hydrated with an isotonic solution. In 100 children and adolescents aged 7.0 (4.8-11) years (median and interquartile range), the average total body water increased perioperatively with a delta value of 182 (0-383) mL/m2 from pre- to postoperatively, as well as the extracellular water content, which had a similar increase with a delta value of 169 (19-307) mL/m2. The changes in total body water and extracellular water content significantly correlated with the amount of fluids administered. The intracellular water content did not significantly change.   Conclusion: Intraoperative administration of isotonic solutions results in a significant fluid accumulation in low-risk schoolchildren during general anesthesia. The results suggest that children without major health problems undergoing short procedures do not need any perioperative intravenous fluid therapy, because they are allowed to take clear fluids up to 1 h prior anesthesia. In future studies, the use of BCM measurements has the potential to be valuable in guiding intraoperative fluid therapy. What is Known: • Most children who undergo common surgical interventions or investigations requiring anesthesia are nowadays hydrated at a rate of 1700 mL/m2/day with an isotonic solution. • The use bioimpedance spectroscopy for the assessment of fluid status in healthy children has already been successfully validated. • The bioimpedance spectroscopy is already currently widely used in various nephrological settings to calculate fluid overload and determine patient's optimal fluid status. What is New: • Routine intraoperative fluid administration results in a significant fluid accumulation during general anesthesia in low-risk surgical procedures. • This observation might be relevant for children and adolescents with conditions predisposing to fluid retention. • In future studies, the use of BCM measurements has the potential to be valuable in guiding intraoperative fluid therapy.

Intra-day variations in volar forearm skin hydration.

BACKGROUND: Skin hydration (SKH) measurements are used for multiple purposes: to study skin physiology, to clinically investigate dermatological issues, and to assess localized skin water in pathologies like diabetes and lymphedema. Often the volar forearm is measured at various times of day (TOD). This report aims to characterize intra-day variations in volar forearm SKH to provide guidance on expected TOD dependence. MATERIALS AND METHODS: Forty medical students (20 male) self-measured tissue dielectric constant (TDC) on their non-dominant forearm in triplicate as an index of local skin tissue water every 2 h starting at 0800 and ending at 2400 h. All were trained and pre-certified in the procedure and had whole-body fat (FAT%) and water (H2O%) measured. Day average TDC (TDCAVG) was determined as the average of all time points expressed as mean ± SD. RESULTS: Males versus females had similar ages (25.1 ± 2.2 years vs. 25.1 ± 1.5 years), higher H2O% (56.6 ± 5.0 vs. 51.8 ± 5.7, p = 0.002), and higher TDCAVG (32.7 ± 4.1 vs. 28.5 ± 5.1, p = 0.008). TDC values were not significantly impacted by H2O% or FAT%. Female TDC exhibited a significant decreasing trend from morning to night (p = 0.004); male TDC showed no trend. CONCLUSION: Skin water assessed by TDC shows some intra-day variations for females and males but with quite different temporal patterns. Clinical relevance relates to the confidence level associated with skin hydration estimates when measured at different times of day during normal clinic hours which, based on the present data, is expected to be around 5% for both males and females.

Calculated plasma volume status in hemodialysis patients.

BACKGROUND: Plasma volume (PV) calculated from hematocrit and body weight has applications in cardiovascular disease. The current study investigated the validity of the calculated PV for predicting volume overload and its prognostic utility in patients undergoing hemodialysis (HD). PATIENTS AND METHODS: Fifty-four HD patients were prospectively enrolled, and their actual PV (aPV) and relative PV status (PVS) were calculated. Bioelectrical impedance analysis (BIA) with assessment of and total body water (TBW), intracellular water (ICW), extracellular water (ECW), and overhydration (OH) and routine blood examinations were performed before dialysis. A second cohort of 164 HD patients was retrospectively enrolled to evaluate the relationship between the calculated PVS and the outcome, with an endpoint of all-cause mortality. RESULTS: aPV was significantly associated with TBW, ICW, ECW, OH, and ECW/TBW (all p < 0.001), and most strongly with ECW (r = 0.83). aPV predicted the extent of volume overload with an AUC of 0.770 (p < 0.001), but PVS did not (AUC = 0.617, p = 0.091). Median follow-up time was 53 months, during the course of which 60 (36.58%) patients died. Values for PVS (12.94 ± 10.87% vs. 7.45 ± 5.90%, p = 0.024) and time-averaged PVS (12.83 ± 11.20 vs. 6.78 ± 6.22%, p < 0.001) were significantly increased in patients who died relative to those who survived. A value of time-averaged PVS >8.72% was significantly associated with an increased incidence of all-cause mortality (HR = 2.48, p = 0.0023). CONCLUSIONS: aPV was most strongly associated with ECW measured using BIA. HD patients with higher time-averaged PVS had a higher rate of all-cause mortality.

Impact of volume indices in bioelectrical impedance measurement on the assessment of cardiac function indices by echocardiography in hemodialysis patients.

INTRODUCTION: Cardiovascular events resulting from volume overload are a primary cause of mortality in hemodialysis patients. Bioelectrical impedance analysis (BIA) is significantly valuable for assessing the volume status of hemodialysis (HD) patients. In this article, we explore the correlation between the volume index measured by BIA and the cardiac function index assessed by echocardiography (ECG) in HD patients. METHODS: Between April and November 2018, we conducted a cross-sectional study involving randomly selected 126 maintenance HD patients. Comprehensive data on medical history and laboratory test results were collected. Subsequently, we investigated the correlation between volume indices measured by BIA and cardiac function parameters by ECG. RESULTS: We discovered a significant correlation between the volume indices measured by BIA and various parameter of cardiac function. The Left Ventricular Hypertrophy (LVH) group exhibited higher levels of the percentage of Extracellular Water (ECW%) and the percentage of Total Body Water (TBW%) compared to the Non-LVH group. Extracellular Water (ECW) and Third Interstitial Fluid Volume (TSFV) were identified as independent risk factors for Left Ventricular Mass (LVM), and both demonstrated a high predictive value for LVM. ECW% emerged as an independent risk factor for the Left Ventricular Mass Index (LVMI), with a high predictive value for LVMI. CONCLUSION: ECW and TSFV were found to be positively associated with cardiac function parameters in HD patients.

Multi-Modal Spectroscopic Assessment of Skin Hydration.

Human skin acts as a protective barrier, preserving bodily functions and regulating water loss. Disruption to the skin barrier can lead to skin conditions and diseases, emphasizing the need for skin hydration monitoring. The gold-standard sensing method for assessing skin hydration is the Corneometer, monitoring the skin's electrical properties. It relies on measuring capacitance and has the advantage of precisely detecting a wide range of hydration levels within the skin's superficial layer. However, measurement errors due to its front end requiring contact with the skin, combined with the bipolar configuration of the electrodes used and discrepancies due to variations in various interfering analytes, often result in significant inaccuracy and a need to perform measurements under controlled conditions. To overcome these issues, we explore the merits of a different approach to sensing electrical properties, namely, a tetrapolar bioimpedance sensing approach, with the merits of a novel optical sensing modality. Tetrapolar bioimpedance allows for the elimination of bipolar measurement errors, and optical spectroscopy allows for the identification of skin water absorption peaks at wavelengths of 970 nm and 1450 nm. Employing both electrical and optical sensing modalities through a multimodal approach enhances skin hydration measurement sensitivity and validity. This layered approach may be particularly beneficial for minimising errors, providing a more robust and comprehensive tool for skin hydration assessment. An ex vivo desorption experiment was carried out on fresh porcine skin, and an in vivo indicative case study was conducted utilising the developed optical and bioimpedance sensing devices. Expected outcomes were expressed from both techniques, with an increase in the output of the optical sensor voltage and a decrease in bioimpedance as skin hydration decreased. MLR models were employed, and the results presented strong correlations (R-squared = 0.996 and p-value = 6.45 × 10-21), with an enhanced outcome for hydration parameters when both modalities were combined as opposed to independently, highlighting the advantage of the multimodal sensing approach for skin hydration assessment.

Total body water percentage and 3rd space water are novel risk factors for training-related lower extremity muscle injuries in young males.

PURPOSE: To identify the risk factors for training-related lower extremity muscle injuries in young males by a non-invasive method of body composition analysis. METHODS: A total of 282 healthy young male volunteers aged 18 - 20 years participated in this cohort study. Injury location, degree, and injury rate were adjusted by a questionnaire based on the overuse injury assessment methods used in epidemiological studies of sports injuries. The occurrence of training injuries is monitored and diagnosed by physicians and treated accordingly. The body composition was measured using the BodyStat QuadScan 4000 multifrequency Bio-impedance system at 5, 50, 100 and 200 kHz to obtain 4 impedance values. The Shapiro-Wilk test was used to check whether the data conformed to a normal distribution. Data of normal distribution were shown as mean ± SD and analyzed by t-test, while those of non-normal distribution were shown as median (Q1, Q3) and analyzed by Wilcoxon rank sum test. The receiver operator characteristic curve and logistic regression analysis were performed to investigate risk factors for developing training-related lower extremity injuries and accuracy. RESULTS: Among the 282 subjects, 78 (27.7%) developed training injuries. Lower extremity training injuries revealed the highest incidence, accounting for 23.4% (66 cases). These patients showed higher percentages of lean body mass (p = 0.001), total body water (TBW, p = 0.006), extracellular water (p = 0.020) and intracellular water (p = 0.010) as well as a larger ratio of basal metabolic rate/total weight (p = 0.006), compared with those without lower extremity muscle injuries. On the contrary, the percentage of body fat (p = 0.001) and body fat mass index (p = 0.002) were lower. Logistic regression analysis showed that TBW percentage > 65.35% (p = 0.050, odds ratio = 3.114) and 3rd space water > 0.95% (p = 0.045, odds ratio = 2.342) were independent risk factors for lower extremity muscle injuries. CONCLUSION: TBW percentage and 3rd space water measured with bio-impedance method are potential risk factors for predicting the incidence of lower extremity muscle injuries in young males following training.

Cellular Exchange Imaging (CEXI): Evaluation of a diffusion model including water exchange in cells using numerical phantoms of permeable spheres.

PURPOSE: Biophysical models of diffusion MRI have been developed to characterize microstructure in various tissues, but existing models are not suitable for tissue composed of permeable spherical cells. In this study we introduce Cellular Exchange Imaging (CEXI), a model tailored for permeable spherical cells, and compares its performance to a related Ball & Sphere (BS) model that neglects permeability. METHODS: We generated DW-MRI signals using Monte-Carlo simulations with a PGSE sequence in numerical substrates made of spherical cells and their extracellular space for a range of membrane permeability. From these signals, the properties of the substrates were inferred using both BS and CEXI models. RESULTS: CEXI outperformed the impermeable model by providing more stable estimates cell size and intracellular volume fraction that were diffusion time-independent. Notably, CEXI accurately estimated the exchange time for low to moderate permeability levels previously reported in other studies ( κ < 25 µ m / s $$ \kappa <25\kern0.3em \mu \mathrm{m}/\mathrm{s} $$ ). However, in highly permeable substrates ( κ = 50 µ m / s $$ \kappa =50\kern0.3em \mu \mathrm{m}/\mathrm{s} $$ ), the estimated parameters were less stable, particularly the diffusion coefficients. CONCLUSION: This study highlights the importance of modeling the exchange time to accurately quantify microstructure properties in permeable cellular substrates. Future studies should evaluate CEXI in clinical applications such as lymph nodes, investigate exchange time as a potential biomarker of tumor severity, and develop more appropriate tissue models that account for anisotropic diffusion and highly permeable membranes.

Reducing the ambiguity of field inhomogeneity and chemical shift effect for fat-water separation by field factor.

PURPOSE: To reduce the ambiguity between chemical shift and field inhomogeneity with flexible TE combinations by introducing a variable (field factor). THEORY AND METHODS: The ambiguity between chemical shift and field inhomogeneity can be eliminated directly from the multiple in-phase images acquired at different TEs; however, it is only applicable to few echo combinations. In this study, we accommodated such an implementation in flexible TE combinations by introducing a new variable (field factor). The effects of the chemical shift were removed from the field inhomogeneity in the candidate solutions, thus reducing the ambiguity problem. To validate this concept, multi-echo MRI data acquired from various anatomies with different imaging parameters were tested. The derived fat and water images were compared with those of the state-of-the-art fat-water separation algorithms. RESULTS: Robust fat-water separation was achieved with the accurate solution of field inhomogeneity, and no apparent fat-water swap was observed. In addition to the good performance, the proposed method is applicable to various fat-water separation applications, including different sequence types and flexible TE choices. CONCLUSION: We propose an algorithm to reduce the ambiguity of chemical shift and field inhomogeneity and achieved robust fat-water separation in various applications.

A field map updating algorithm to improve fat-water spiral imaging.

PURPOSE: An accurate field map is essential to separate fat and water signals in a dual-echo chemical shift encoded spiral MRI scan. A rapid low-resolution B0 map prescan is usually performed before each exam. Occasional inaccuracy in these field map estimates can lead to misclassification of the water and fat signals as well as blurring artifacts in the reconstruction. The present work proposes a self-consistent model to evaluate residual field offsets according to the image data to improve the reconstruction quality and facilitate the scan efficiency. THEORY AND METHODS: The proposed method compares the phase differences of the two-echo data after correcting for fat frequency offsets. A more accurate field map is approximated according to the phase discrepancies and improved image quality. Experiments were conducted with simulated off-resonance on a numerical phantom, five volunteer head scans, and four volunteer abdominal scans for validation. RESULTS: The initial reconstruction of the demonstrated examples exhibit blurring artifacts and misregistration of fat and water because of the inaccuracy of the field map. The proposed method updates the field map to amend the fat and water estimation and improve image quality. CONCLUSIONS: This work presents a model to improve the quality of fat-water imaging of the spiral MRI by estimating a better field map from the acquired data. It allows reducing the field map pre-scans before each spiral scan under normal circumstances to increase scan efficiency.

Simultaneous estimation of the cellular water exchange rate, intracellular volume fraction, and longitudinal relaxation rate in cancer cells.

The purpose of the current study was to investigate the feasibility of simultaneously estimating the cellular water efflux rate ( k ie ), intracellular longitudinal relaxation rate ( R 10 i ), and intracellular volume fraction ( v i ) of a cell suspension using multiple samples with different gadolinium concentrations. Numerical simulation studies were conducted to assess the uncertainty in the estimation of k ie , R 10 i , and v i from saturation recovery data using single (SC) or multiple concentrations (MC) of gadolinium-based contrast agent (GBCA). In vitro experiments with 4 T1 murine breast cancer and SCCVII squamous cell cancer models were conducted at 11 T to compare parameter estimation using the SC protocol with that using the MC protocol. The cell lines were challenged with a Na+ /K+ -ATPase inhibitor, digoxin, to assess the treatment response in terms of k ie , R 10 i , and v i . Data analysis was conducted using the two-compartment exchange model for parameter estimation. The simulation study data demonstrate that the MC method, compared with the SC method, reduces the uncertainty of the estimated k ie by decreasing the interquartile ranges from 27.3% ± 3.7% to 18.8% ± 5.1% and the median differences from ground truth from 15.0% ± 6.3% to 7.2% ± 4.2%, while estimating R 10 i and v i simultaneously. In the cell studies, the MC method demonstrated reduced uncertainty in overall parameter estimation compared with the SC approach. MC method-measured parameter changes in cells treated with digoxin increased R 10 i by 11.7% (p = 0.218) and k ie by 5.9% (p = 0.234) for 4 T1 cells, respectively, and decreased R 10 i by 28.8% (p = 0.226) and k ie by 1.6% (p = 0.751) for SCCVII cells, respectively. v i did not change noticeably by the treatment. The results of this study substantiate the feasibility of using saturation recovery data of multiple samples with different GBCA concentrations for simultaneous measurement of the cellular water efflux rate, intracellular volume fraction, and intracellular longitudinal relaxation rate in cancer cells.

Anthropometry-Based Prediction Equation of Body Composition in a Population Aged 12-88 Years.

BACKGROUND: Direct anthropometric measurements to assess body composition have limited precision and/or specificity. OBJECTIVES: The study aimed to develop a prediction equation based on anthropometric measurements for estimating total body water (TBW) in a healthy population. METHODS: TBW was assessed using the deuterium dilution method in 398 Moroccan participants (235 women and 163 men) aged 11.6-88 y, then compared to the estimations made by previously published anthropometric equations. By sex, participants were randomly assigned into development (n = 199) and validation subgroups (n = 199). A new anthropometric equation was developed in the development subgroup from data obtained on body volume (BV), weight, and sex, where the BV was calculated from participants' height. Then the equation was validated in the validation subgroup using the Bland and Altman procedure, bias, and pure error. External validation was performed using a sample from Tunisia (n = 220, 51.8% female, 18-65 y). RESULTS: Bias in predicting TBW showed unacceptable value for all previously published equations as it was significantly overestimated. The following new equation using anthropometric measurements [TBW (kg) = -5.249 + 107.502 BV (L) + 0.289 weight (kg) + 2.015 sex (male: 1, female: 0); (R2 = 0.91, RMSE = 1.885 kg)] was developed, and its internal validation was confirmed. The generated bias and pure error values were 0.047 kg (95% CI: -0.235, 0.330) and 2.02 kg (95% CI: 1.73, 2.31), respectively. The external validation of the new TBW prediction equation on a Tunisian sample showed a bias and pure error values of 0.07 kg (95% CI: -0.289, 0.429) and 2.36 kg, respectively. CONCLUSIONS: The results indicate that the new anthropometric-based prediction equation provides a good estimation of TBW and other body composition compartments. It could be recommended as an alternative method to assess body composition for epidemiological and clinical studies.

Comparison of Bioelectrical Impedance Indices for Skeletal Muscle Mass and Intracellular Water Measurements of Physically Active Young Men and Athletes.

BACKGROUND: Bioelectrical impedance analysis (BIA) is a minimally invasive, safe, easy, and quick technology used to determine body composition. OBJECTIVES: We compared the relationship among impedance indices obtained using single-frequency BIA, multi-frequency BIA, bioelectrical impedance spectroscopy (BIS), and skeletal muscle mass (SMM) of physically active young men and athletes using the creatine (methyl-d3) dilution method. We also compared the SMM and intracellular water (ICW) of athletes and active young men measured using a reference stable isotope dilution and BIS method, respectively. METHODS: We analyzed data from 28 men (mean age, 20 ± 2 y) who exercised regularly. Single-frequency BIA at 5 kHz and 50 kHz (R5 and R50), multi-frequency BIA (R250-5), and BIS (RICW) methods of determining the SMM were compared. The deuterium and sodium bromide dilution methods of obtaining the total body water, ICW, and extracellular water measurements were also used, and the results were compared to those acquired using bioimpedance methods. RESULTS: The correlation coefficients between SMM and L2/R5, L2/R50, L2/R250-5, and L2/RICW were 0.738, 0.762, 0.790, and 0.790, respectively (P < 0.01). The correlation coefficients between ICW and L2/R5, L2/R50, L2/R250-5, and L2/RICW were 0.660, 0.687, 0.758, and 0.730, respectively (P < 0.001). However, the correlation coefficients of L2/R50, L2/R250-5, and L2/RICW for SMM and ICW were not significantly different. CONCLUSIONS: Our findings suggest that single-frequency BIA at L2/R50, multi-frequency BIA, and BIS are valid for assessing the SMM of athletes and active young men. Additionally, we confirmed that the SMM and ICW were correlated with single-frequency BIA, multi-frequency BIA, and BIS. Bioimpedance technologies may be dependable and practical means for assessing SMM and hydration compartment status of active young adult males; however, cross-validation is needed.

Estimation of Hydration and Density of Fat-Free Mass in Indian Children Using a 4-Compartment Model: Implications for the Estimation of Body Composition Using 2-Compartment Models.

BACKGROUND: Accurate methods are needed to measure body fat mass (FM), particularly in South Asian children who are thought to have greater adiposity for a given body size. The accuracy of simple 2-compartment (2C) models of measuring FM depends on the primary measurement of the fat free mass (FFM) and the validity of assumed constants for FFM hydration and density. These have not been measured in this particular ethnic group. OBJECTIVES: To measure FFM hydration and density in South Indian children using a 4-compartment (4C) model and to compare FM estimates from this 4C-model with 2C-model-based estimates from hydrometry and densitometry, using literature-reported FFM hydration and density in children. METHODS: This study included 299 children (45% boys), aged 6-16 y from Bengaluru, India. Total body water (TBW), bone mineral content (BMC), and body volume were measured using deuterium dilution, dual-energy X-ray absorptiometry, and air displacement plethysmography, respectively, to calculate the FFM hydration and density, and the FM using 4C and 2C models. The agreement between FM estimates from 2C and 4C models was also evaluated. RESULTS: Mean FFM hydration and density were 74.2% ± 2.1% and 71.4% ± 2.0% and 1.095 ± 0.008 kg/L and 1.105 ± 0.008 kg/L in boys and girls respectively, which were significantly different from published values. Using the presently estimated constants, the mean hydrometry-based FM (as % body weight) estimates decreased by 3.5% but increased by 5.2% for densitometry-based 2C methods. When 2C-FM (using previously reported FFM hydration and density) were compared with 4C-FM estimates, the mean difference was -1.1 ± 0.9 kg for hydrometry and 1.6 ± 1.1 kg for densitometry. CONCLUSIONS: Previously published constants of hydration and density of FFM may induce errors of -12% to +17% in FM (kg) when using different 2C models in comparison to the 4C models in Indian children. J Nutr 20xx;x:xx.