Assessment of compression-induced solid stress, fluid pressure and mechanopathological parameters in cancersin vivousing poroelastography.

Objective.Compression-induced solid stress (SSc) and fluid pressure (FPc) during ultrasound poroelastography (USPE) experiments are correlated with two markers of cancer growth and treatment effectiveness: growth-induced solid stress (SSg) and interstitial fluid pressure (IFP). The spatio-temporal distributions of SSg and IFP are determined by the transport properties of the vessels and interstitium in the tumor microenvironment.Approach.We propose a new USPE method for the non-invasive imaging of the local cancer mechanical parameters and dynamics of fluid flow. When performing poroelastography experiments, it may be difficult to implement a typical creep compression protocol, which requires to maintain a constant normally applied force. In this paper, we investigate the use of a stress relaxation protocol, which might be a more convenient choice for clinical poroelastography applications.Main results.Based on our finite element and ultrasound simulations study, we demonstrate that the SSc, FPc and their spatio-temporal distribution related parameters, interstitial permeability and vascular permeability, can be determined from stress relaxation experiments with errors below 10% as compared to the ground truth and accuracy similar to that of corresponding creep tests, respectively. We also demonstrate the feasibility of the new methodology forin vivoexperiments using a small animal cancer model.Significance.The proposed non-invasive USPE imaging methods may become an effective tool to assess local tumor pressure and mechanopathological parameters in cancers.

Controllable-Swelling Microneedle-Assisted Ultrasensitive Paper Sensing Platforms for Personal Health Monitoring.

Microneedle (MN) patches, which allow the extraction of skin interstitial fluid (ISF) without a pain sensation, are powerful tools for minimally invasive biofluid sampling. Herein, an MN-assisted paper-based sensing platform that enables rapid and painless biofluid analysis with ultrasensitive molecular recognition capacity is developed. First, a controllable-swelling MN patch is constructed through the engineering of a poly(ethylene glycol) diacrylate/methacrylated hyaluronic acid hydrogel; it combines rapid, sufficient extraction of ISF with excellent structural integrity. Notably, the analyte molecules in the needles can be recovered into a moist cellulose paper through spontaneous diffusion. More importantly, the paper can be functionalized with enzymatic colorimetric reagents or a plasmonic array, enabling a desired detection capacity-for example, the use of paper-based surface-enhanced Raman spectroscopy sensors leads to label-free, trace detection (sub-ppb level) of a diverse set of molecules (cefazolin, nicotine, paraquat, methylene blue). Finally, nicotine is selected as a model drug to evaluate the painless monitoring of three human volunteers. The changes in the nicotine levels can be tracked, with the levels varying significantly in response to the metabolism of drug in different volunteers. This as-designed minimally invasive sensing system should open up new opportunities for precision medicine, especially for personal healthcare monitoring.

Skin Interstitial Fluid and Plasma Multiplex Cytokine Analysis Reveals IFN-γ Signatures and Granzyme B as Useful Biomarker for Activity, Severity and Prognosis Assessment in Vitiligo.

Background: The course of vitiligo is unpredictable, with periods of disease flare-ups and prolonged recovery periods. It is essential to establish a biomarker profile as a substitute marker for disease activity to predict disease activity, severity, and prognosis prediction. The use of localized skin interstitial fluid as biomarkers has recently gained interest, but extensive studies of the association between skin interstitial fluid, plasma, and the disease course is lacking. This study aims to evaluate the cytokine expression profiles in the skin and plasma and the utility of the biomarker panel in assessing disease activity, severity, and prognosis in patients with vitiligo. Methods: In this prospective cohort study, 86 patients and 34 healthy controls were recruited from the outpatient department of a tertiary medical center from March 2019 to September 2021. All patients were of Asian ethnicity. Two independent investigators evaluated disease activity and severity with longitudinal follow-ups for treatment response for a-12 month period. Ultrasensitive multiplex cytokine panel and single-molecule counting technology immunoassays were used to study the cytokine expression in skin interstitial fluid and plasma. Results: IFN-γ and its' signature cytokines, including CXCL9, CXCL10, and GzmB, are most highly expressed in the vitiligo patients' lesion skin interstitial fluid and plasma compared to healthy control. By way of comparison, no significant changes in IL-1ß, IL-13, IL-15, IL-17A, IL-18 were observed. Receiver operating characteristic analysis revealed that IFN-γ is the most sensitive and specific marker in predicting disease activity, followed by CXCL10 and GzmB. CXCL-9 was sensitive and specific in diagnosing vitiligo disease severity. The decrease in IFN-γ expression level is positively correlated with the treatment response. Conclusion: IFN-γ, CXCL9, CXCL10, and GzmB are highly expressed in vitiligo patients' lesion skin and plasma and may serve as biomarkers for the clinical activity, severity, and prognosis prediction in vitiligo patients. Among all, IFN-γ exerts the highest predictive value in disease activity and treatment response, supporting the critical role of IFN-γ in the pathogenesis of vitiligo.

Costs Associated with Laser Interstitial Thermal Therapy Are Lower Than Anterior Temporal Lobectomy for Treatment of Temporal Lobe Epilepsy.

BACKGROUND: Laser interstitial thermal therapy (LITT) is a minimally invasive alternative to anterior temporal lobectomy (ATL) for treatment of temporal lobe epilepsy. It has gained popularity as familiarity with technique increases and outcomes are better characterized. There has been no direct cost comparison between the 2 techniques in literature to date. The current study directly compares hospital costs associated with LITT with those of ATL patients and analyzes the factors potentially responsible for those costs. METHODS: Patients who underwent ATL (27) and LITT (15) were retrospectively reviewed for total hospital costs along with demographic, surgical, and postoperative factors potentially affecting cost. T-tests were used to compare costs and independent linear regressions, and hierarchical regressions were used to examine predictors of cost for each procedure. RESULTS: Mean hospital costs of admission for single-trajectory LITT ($104,929.88) were significantly less than for ATL ($134,980.04) (P = 0.001). In addition, length of stay, anesthesia costs, operative room costs, and postoperative hospitalization costs were all significantly lower in LITT. CONCLUSIONS: Given the minimally invasive nature of LITT, it is associated with shorter length of stay and lower hospital costs than ATL in the first head-to-head comparison of procedural costs in literature to date. Long-term efficacy as it relates to these costs associated with LITT and ATL should be further investigated to better characterize the utility of LITT in temporal lobe epilepsy patients.

Fast uncertainty quantification of tracer distribution in the brain interstitial fluid with multilevel and quasi Monte Carlo.

Efficient uncertainty quantification algorithms are key to understand the propagation of uncertainty-from uncertain input parameters to uncertain output quantities-in high resolution mathematical models of brain physiology. Advanced Monte Carlo methods such as quasi Monte Carlo (QMC) and multilevel Monte Carlo (MLMC) have the potential to dramatically improve upon standard Monte Carlo (MC) methods, but their applicability and performance in biomedical applications is underexplored. In this paper, we design and apply QMC and MLMC methods to quantify uncertainty in a convection-diffusion model of tracer transport within the brain. We show that QMC outperforms standard MC simulations when the number of random inputs is small. MLMC considerably outperforms both QMC and standard MC methods and should therefore be preferred for brain transport models.

[Body composition assessment before and after weight loss following a Roux-en-Y gastric bypass. Are bioimpedanciometry estimations reliable?] / Evaluación de la composicion corporal antes y después de la reducción de peso con baipás gastrico en Y de Roux. ¿Son confiables las mediciones de la bioimpedanciometría?

INTRODUCTION: Introduction: in patients with severe and morbid obesity it has been observed that bioimpedance (BIA) assessment generates an underestimation of fat mass (FM) and weight loss as FM after bariatric surgery, overestimating the loss of fat-free mass (FFM) and muscle mass. Objective: to evaluate the reliability of bioelectrical impedance analysis (BIA) to estimate total body water (TBW), fat-free mass (FFM), fat mass (FM), and its changes after 6 months of a Roux-en-Y gastric bypass (RYGBP), in patients with severe and morbid obesity. Methods: thirty-six patients approved for RYGBP were prospectively studied. TBW was measured by deuterium (D), and FM and FFM were calculated. A dual-frequency BIA device (5 and 200 kHz) (Bodystat Dualscan®) was used to estimate FM, FFM, TBW, extracellular water (ECW), intracellular water (ICW), and ECW/ICW ratio. Results: before RYGBP, BIA overestimated TBW by 2.6 ± 4.3 L (p = 0.002) and FFM by 3.5 ± 5.7 kg (p = 0.002), and underestimated FM% by 2.98 ± 4.7% (p = 0.002). The ECW/ICW ratio showed a significant and positive correlation with the difference BIA-D for FFM (r = 0.49; p = 0.002). After surgery, the differences between BIA and D were not significant, and the estimation error of FFM did not correlate with the ECW/ICW ratio. Conclusions: BIA generates an underestimation of FM as reported in patients with severe and morbid obesity, which is attenuated after weight reduction, underestimating weight loss as FM and overestimating FFM loss. Future research may assess whether these errors are reproduced by other BIA devices.

INTRODUCCIÓN: Introducción: en pacientes con obesidad severa y mórbida se ha observado que la evaluación por bioimpedanciometría (BIA) genera una subestimación de la masa grasa (MG) y del peso perdido como MG después de la cirugía bariátrica, sobreestimándose la pérdida de masa libre de grasa (MLG) y la masa muscular. Objetivo: evaluar la confiabilidad de la BIA para estimar el agua corporal total (ACT), la MLG, la MG y sus cambios después de 6 meses de un baipás gástrico en Y de Roux (BPGYR) en pacientes con obesidad severa y mórbida. Métodos: 36 adultos con indicación de BPGYR se estudiaron prospectivamente. Se midió el ACT por deuterio (D) y se calcularon la MLG y MG. Con BIA de doble frecuencia (5 y 200 kHz) (Bodystat Dualscan®) se estimaron la MG, la MLG, el ACT, el agua extracelular (AEC), el agua intracelular (AIC) y la relación AEC/AIC. Resultados: antes del BPGYR, la BIA sobreestimó el ACT en 2,6 ± 4,3 L (p = 0,002) y la MLG en 3,5 ± 5,7 kg (p = 0,002), y subestimó el %MG en 2,98 ± 4,7% (p = 0,002). La relación AEC/AIC mostró una correlación positiva con la sobreestimación de la MLG por BIA (r = 0,49; p = 0,002). Después de la cirugía, las diferencias entre BIA y D no fueron significativas y el error de estimación de la MLG no se correlacionó con la relación AEC/AIC. Conclusiones: la BIA genera una subestimación de la MG como la reportada, la cual se atenúa después de la reducción de peso, subestimando el peso perdido como MG y sobreestimando la pérdida de MLG. Futuras investigaciones podrán evaluar si estos errores se reproducen con otros equipos de BIA.

An Initial Cost-Effectiveness Analysis of Magnetic Resonance-Guided Laser Interstitial Thermal Therapy in Pediatric Epilepsy Surgery.

INTRODUCTION: Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a new technology that provides a clinically efficacious and minimally invasive alternative to conventional microsurgical resection. However, little data exist on how costs compare to traditional open surgery. The goal of this paper is to investigate the cost-effectiveness of MRgLITT in the treatment of pediatric epilepsy. METHODS: We retrospectively analyzed the medical records of pediatric patients who underwent MRgLITT via the Visualase® thermal therapy system (Medtronic, Inc., Minneapolis, MN, USA) between December 2013 and September 2017. Direct costs associated with preoperative, operative, and follow-up care were extracted. Benefit was calculated in quality-adjusted life years (QALYs), and the cost-effectiveness was derived from the discounted total direct costs over QALY. Sensitivity analysis on 4 variables was utilized to assess the validity of our results. RESULTS: Twelve consecutive pediatric patients with medically refractory epilepsy underwent MRgLITT procedures. At the last postoperative follow-up, 8 patients were seizure free (Engel I, 66.7%), 2 demonstrated significant improvement (Engel II, 16.7%), and 2 patients showed worthwhile improvement (Engel III, 16.7%). The average cumulative discounted QALY was 2.11 over the lifetime of a patient. Adjusting for inflation, MRgLITT procedures had a cost-effectiveness of USD 22,211 per QALY. Our sensitivity analysis of cost variables is robust and supports the procedure to be cost--effective. CONCLUSION: Our data suggests that MRgLITT may be a cost-effective alternative to traditional surgical resection in pediatric epilepsy surgery.

Bioimpedance spectroscopy for fluid status assessment in patients with decompensated liver cirrhosis: Implications for peritoneal dialysis.

Bioimpedance spectroscopy (BIS) is routinely used in peritoneal dialysis patients and might aid fluid status assessment in patients with liver cirrhosis, but the effect of ascites volume removal on BIS-readings is unknown. Here we determined changes in BIS-derived parameters and clinical signs of fluid overload from before to after abdominal paracentesis. Per our pre-specified sample size calculation, we studied 31 cirrhotic patients, analyzing demographics, labs and clinical parameters along with BIS results. Mean volume of the abdominal paracentesis was 7.8 ± 2.6 L. From pre-to post-paracentesis, extracellular volume (ECV) decreased (20.2 ± 5.2 L to 19.0 ± 4.8 L), total body volume decreased (39.8 ± 9.8 L to 37.8 ± 8.5 L) and adipose tissue mass decreased (38.4 ± 16.0 kg to 29.9 ± 12.9 kg; all p < 0.002). Correlation of BIS-derived parameters from pre to post-paracentesis ranged from R² = 0.26 for body cell mass to R² = 0.99 for ECV. Edema did not correlate with BIS-derived fluid overload (FO ≥ 15% ECV), which occurred in 16 patients (51.6%). In conclusion, BIS-derived information on fluid status did not coincide with clinical judgement. The changes in adipose tissue mass support the BIS-model assumption that fluid in the peritoneal cavity is not detectable, suggesting that ascites (or peritoneal dialysis fluid) mass should be subtracted from adipose tissue if BIS is used in patients with a full peritoneal cavity.

Fluid assessment in dialysis patients by point-of-care magnetic relaxometry.

Magnetic resonance imaging (MRI) is a powerful diagnostic tool, but its use is restricted to the scanner suite. Here, we demonstrate that a bedside nuclear magnetic resonance (NMR) sensor can assess fluid status changes in individuals at a fraction of the time and cost compared to MRI. Our study recruited patients with end-stage renal disease (ESRD) who were regularly receiving hemodialysis treatments with intradialytic fluid removal as a model of volume overload and healthy controls as a model of euvolemia. Quantitative T 2 measurements of the lower leg of patients with ESRD immediately before and after dialysis were compared to those of euvolemic healthy controls using both a 0.28-T bedside single-voxel NMR sensor and a 1.5-T clinical MRI scanner. In the MRI data, we found that the first sign of fluid overload was an expanded muscle extracellular fluid (ECF) space, a finding undetectable at this stage using physical exam. A decrease in muscle ECF upon fluid removal was similarly detectable with both the bedside sensor and MRI. Bioimpedance measurements performed comparably to the bedside NMR sensor but were generally worse than MRI. These findings suggest that bedside NMR may be a useful method to identify fluid overload early in patients with ESRD and potentially other hypervolemic patient populations.

Estimated dietary sodium intake in peritoneal dialysis patients using food frequency questionnaires and total urinary and peritoneal sodium losses and assessment of extracellular volumes.

BACKGROUND: Peritoneal dialysis (PD) patients are advised to restrict sodium intake. For best use of resources, rapid screening tools are required for dietary assessments to allow for targeting of patients. We wished to evaluate the usefulness of food frequency questionnaires (FFQ) for estimating dietary sodium. METHODS: Sodium intake was estimated using the Derby Salt Questionnaire (DSQ), and Royal Free Sodium Questionnaire (RFSQ). Body composition was determined by bioimpedance. RESULTS: 90 peritoneal dialysis patients, 52 men (57.8%), mean age 62 ± 15.8 years, were asked to complete the DSQ and RFSQ questionnaires. 88 completed one or more questionnaire, with 87 completing the DSQ and 86 the RFSQ. The median estimated dietary sodium intake 104 (72-145) mmol/day (2.39 (1.64-3.34) g sodium/day) DSQ, and 92 (60-114) mmol/day (2.11 (1.38-2.62) g sodium/day) RFSQ. Younger patients, aged ≤52 years had greater dietary sodium intake compared to those ≥76 years (RFSQ 105.4 (73-129) vs 96 (71-116) mmol/day), p < 0.05. Extracellular water to total body water (ECW/TBW) was greater in those with higher DSQ estimated dietary sodium intake (0.40 ± 0.01 vs 0.39 ± 0.01, p < 0.05). A multivariable model showed that increased dietary sodium intake was independently associated with increased SMM (DSQ odds ratio (OR) 1.17 (95% confidence limits 1.05-1.32, RFSQ OR 1.15 (1.04-1.27, p < 0.05) and raised ECW/TBW (DSQ OR 1.88 (1.22-2.92) p = 0.004, and ECW/height (RFSQ OR 1.42 (1.02-1.98) p = 0.04. CONCLUSIONS: Both questionnaires were acceptable to patients, and the majority were found to be consuming more dietary sodium than recommended. Dietary sodium estimation was associated with SMM and increased ECW.

In vitro assessment of the differences in retinal ganglion cell responses to intra- and extracellular electrical stimulation.

OBJECTIVE: To compare responses of retinal ganglion cells (RGCs) to intracellular and extracellular electrical stimulation of varying frequency and amplitude. APPROACH: In vitro patch clamp was used to record the responses of RGCs to sinusoidal current stimulation of varying frequency and amplitude. The results were simulated using the Neuron software package. MAIN RESULTS: The stimulation frequency yielding the greatest response was higher for extracellular stimulation compared to intracellular stimulation in the same cells (256 Hz versus 64 Hz). In fact, at the high end of the frequency range, where extracellular stimulation was highly efficacious, no responses could be generated using intracellular stimulation. A region in the amplitude-frequency stimulation space was identified where OFF-RGCs could be preferentially stimulated over ON-RGCs. We found that the inability of RGCs to respond at high frequencies of intracellular stimulation is likely the result of the axon acting as a low pass filter. SIGNIFICANCE: There is no direct translation of the results obtained with intracellular stimulation to those that employ extracellular stimulation.

Assessment of Anticancer Drug Effects on Pancreatic Cancer Cells under Glucose-Depleted Conditions Using Intracellular and Extracellular Amino Acid Metabolomics.

Previously, we developed a method to evaluate states of cells treated with anticancer drugs via the comprehensive analysis of amino acids, termed amino acid metabolomics. In the present study, we evaluated the effects of the anticancer drugs, gemcitabine hydrochloride and pyrvinium pamoate, on the proliferation of a pancreatic cancer cell line (PANC-1) under hypoglycemic conditions using amino acid metabolomics. Intracellular and extracellular amino acid profiles of PANC-1 were determined by hydrophilic interaction chromatography-tandem mass spectrometry with simple pretreatment. Changes to the drugs' anticancer effects resulting from glucose starvation conditions were presented in score plots obtained from principal component analyses. In particular, the analysis of intracellular amino acids was found to be the superior approach because the results allowed a clearer assessment of the cell state. Further, orthogonal partial least squares discriminant analysis was performed to search for amino acid candidates that discriminate with anticancer drug-treated PANC-1 cells. We identified several amino acids that might be able to distinguish the drug-treated group from the control group. These results might provide a better understanding of the mechanisms underlying cell responses such as drug resistance or austerity. The present study is the first to evaluate the efficacy of anticancer drugs under glucose starvation based on the analysis of the variation of extracellular and intracellular amino acid profiles in vitro.

Comparative Assessment of Tedizolid Pharmacokinetics and Tissue Penetration between Diabetic Patients with Wound Infections and Healthy Volunteers via In Vivo Microdialysis.

Herein, we present pharmacokinetic and tissue penetration data for oral tedizolid in hospitalized patients with diabetic foot infections (DFI) compared with healthy volunteers. Participants received oral tedizolid phosphate 200 mg every 24 h for 3 doses to achieve steady state. A microdialysis catheter was inserted into the subcutaneous tissue near the margin of the wound for patients or into thigh tissue of volunteers. Following the third dose, 12 blood and 14 dialysate fluid samples were collected over 24 h to characterize tedizolid concentrations in plasma and interstitial extracellular fluid of soft tissue. Mean ± standard deviation (SD) tedizolid pharmacokinetic parameters in plasma for patients compared with volunteers, respectively, were as follows: maximum concentration (Cmax), 1.5 ± 0.5 versus 2.7 ± 1.1 mg/liter (P = 0.005); time to Cmax (Tmax) (median [range]), 5.9 (1.2 to 8.0) versus 2.5 (2.0 to 3.0 h) (P = 0.003); half-life (t1/2), 9.1 ± 3.6 versus 8.9 ± 2.2 h (P = 0.932); and plasma area under the concentration-time curve for the dosing interval (AUC p ), 18.5 ± 9.7 versus 28.7 ± 9.6 mg · h/liter (P = 0.004). The tissue area under the concentration-time curve (AUC t ) for the dosing interval was 3.4 ± 1.5 versus 5.2 ± 1.6 mg · h/liter (P = 0.075). Tissue penetration median (range) was 1.1 (0.3 to 1.6) versus 0.8 (0.7 to 1.0) (P = 0.351). Despite lower plasma Cmax and delayed Tmax values for patients with DFI relative to healthy volunteers, the penetration into and exposure to tissue were similar. Based on available pharmacodynamic thresholds for tedizolid, the plasma and tissue exposures using the oral 200 mg once-daily regimen are suitable for further study in treatment of DFI.

Quantitative Assessment of Drug Delivery to Tissues and Association with Phospholipidosis: A Case Study with Two Structurally Related Diamines in Development.

Drug induced phospholipidosis (PLD) may be observed in the preclinical phase of drug development and pose strategic questions. As lysosomes have a central role in pathogenesis of PLD, assessment of lysosomal concentrations is important for understanding the pharmacokinetic basis of PLD manifestation and forecast of potential clinical appearance. Herein we present a systematic approach to provide insight into tissue-specific PLD by evaluation of unbound intracellular and lysosomal (reflecting acidic organelles) concentrations of two structurally related diprotic amines, GRT1 and GRT2. Their intratissue distribution was assessed using brain and lung slice assays. GRT1 induced PLD both in vitro and in vivo. GRT1 showed a high intracellular accumulation that was more pronounced in the lung, but did not cause cerebral PLD due to its effective efflux at the blood-brain barrier. Compared to GRT1, GRT2 revealed higher interstitial fluid concentrations in lung and brain, but more than 30-fold lower lysosomal trapping capacity. No signs of PLD were seen with GRT2. The different profile of GRT2 relative to GRT1 is due to a structural change resulting in a reduced basicity of one amino group. Hence, by distinct chemical modifications, undesired lysosomal trapping can be separated from desired drug delivery into different organs. In summary, assessment of intracellular unbound concentrations was instrumental in delineating the intercompound and intertissue differences in PLD induction in vivo and could be applied for identification of potential lysosomotropic compounds in drug development.

The Value of Using a SkinFibroMeter for Diagnosis and Assessment of Secondary Lymphedema and Associated Fibrosis of Lower Limb Skin.

BACKGROUND: Skin fibrosis is a clinically serious pathological process of secondary lymphedema (SLE). The detection of latent or incipient skin fibrosis, including early tissue changes, using sensitive diagnostic equipment is essential. The SkinFibroMeter has been used in skin care; however, its ability to assess skin fibrosis in patients with SLE of the lower limb has not been explored. METHODS AND RESULTS: In this study, 45 female patients with secondary unilateral lower limb LE and 15 healthy female volunteers were enrolled. The skin stiffness values of affected and healthy limbs were measured by using the SkinFibroMeter, and skin samples were assayed by Masson staining. The circumference and interstitial fluid of limbs were also measured and analyzed. Increasing skin stiffness with increasing severity of SLE of the lower limb and skin stiffness significantly positively correlated with stage of lower limb SLE. CONCLUSIONS: Our results demonstrate that the SkinFibroMeter is very sensitive and accurate for detecting skin fibrosis of edematous limb. Therefore, this new instrument is a promising prospect for diagnosis and assessment of skin fibrosis in patients with lower limb SLE.

Ultrasound Strain Relaxation Time Ratio: A Quantitative Marker for the Assessment of Cortical Inflammation/Edema in Renal Allografts.

Purpose: To evaluate the ability of ultrasound strain relaxation time ratio to assess cortical inflammation/edema in renal allografts. Materials and Methods: We prospectively assessed renal allograft cortical inflammation/edema in 16 renal transplants using ultrasound elasticity imaging and correlated the findings with kidney biopsy. Strain relaxation times in the renal cortex and reference soft tissue were produced by free-hand compression with the ultrasound transducer and estimated with 2 D speckle tracking. Compression was performed in 3-second compression-relaxation cycles (push for 1 second, constant pressure for 1 second, and release for 1 second). We propose a strain relaxation time ratio (time of cortical strain to return to zero/time of the reference strain return to zero) to assess the relationship of compression-induced time-dependent strain relaxation in the cortex and reference tissue. 16 patients were divided into a group with ≤ 25 % (n = 8) and a group with > 26 % (n = 8) cortical inflammation/edema based on the Banff score. A t-test was used to examine the difference in the strain relaxation time ratio between the two groups. The diagnostic accuracy, inter-rater reliability, and reproducibility of this technique in discriminating between the groups were tested. Results: The strain relaxation time ratio of cortex/reference tissue was significantly higher in patients with > 26 % than in patients with ≤ 25 % cortical inflammation/edema (1.15 ±â€Š0.10 vs. 0.91 ±â€Š0.08, P = 0.0002). The strain relaxation time ratio has high reliability (Pearson correlation coefficient, R²â€Š= 0.93), reproducibility (intraclass correlation coefficient = 0.98, P = 0.000), and accuracy (area under curve = 1) in determining > 26 % renal cortical inflammation/edema. Conclusion: The strain relaxation time ratio of cortex/reference tissue can be used as a quantitative marker for the assessment of cortical inflammation/edema in renal allografts.

4D flow MRI and T1 -Mapping: Assessment of altered cardiac hemodynamics and extracellular volume fraction in hypertrophic cardiomyopathy.

PURPOSE: Hypertrophic cardiomyopathy (HCM) is associated with altered hemodynamics in the left ventricular outflow tract (LVOT) and myocardial tissue abnormalities such as fibrosis. The aim of this study was to quantify changes in LVOT 3D hemodynamics and myocardial extracellular volume fraction (ECV, measure of fibrosis) and to investigate relationships between elevated flow metrics and left ventricular (LV) tissue abnormalities. MATERIALS AND METHODS: Cardiac magnetic resonance imaging (MRI) including 4D flow (field strength = 1.5T, resolution = 2.1-4.0 × 2.1-4.0 × 2.5-3.2 mm(3) ; venc = 150-250 cm/s; TE/TR/FA = 2.2-2.5msec/4.6-4.9msec/15°) for the in vivo assessment of 3D blood flow velocities with full coverage of the LVOT was applied in 35 patients with HCM (54 ± 15 years) and 10 age-matched healthy controls (45 ± 14 years). In addition, pre- and postcontrast myocardial T1 -mapping (resolution = 2.3 × 1.8 mm, slice thickness = 8 mm, TE/TR-FA = 1.0-1.1msec/2.0-2.2msec/35°) of the LV (basal, mid-ventricular, apical short axis) was performed in a subgroup of 23 HCM patients. Analysis included the segmentation of the LVOT and quantification of peak systolic LVOT pressure gradients and rate of viscous energy loss EL ' as well as left ventricular ECV. RESULTS: HCM patients demonstrated significantly elevated peak systolic LVOT pressure gradients (21 ± 16 mmHg vs. 9 ± 2 mmHg) and energy loss EL ' (3.8 ± 2.5 mW vs. 1.5 ± 0.7 mW, P < 0.005) compared to controls. There was a significant relationship between increased LV fibrosis (ECV) with both elevated pressure gradients (R(2) = 0.44, P < 0.001) and energy loss EL ' (R(2) = 0.46, P < 0.001). CONCLUSIONS: The integration of 4D-flow and T1 -mapping-MRI allowed for the evaluation of tissue and flow abnormalities in HCM patients. Our findings suggest a mechanistic link between abnormal LVOT flow, increased LV loading, and adverse myocardial remodeling in HCM.

A Bioimpedance Analysis Platform for Amputee Residual Limb Assessment.

OBJECTIVE: The objective of this research was to develop a bioimpedance platform for monitoring fluid volume in residual limbs of people with trans-tibial limb loss using prostheses. METHODS: A customized multifrequency current stimulus profile was sent to thin flat electrodes positioned on the thigh and distal residual limb. The applied current signal and sensed voltage signals from four pairs of electrodes located on the anterior and posterior surfaces were demodulated into resistive and reactive components. An established electrical model (Cole) and segmental limb geometry model were used to convert results to extracellular and intracellular fluid volumes. Bench tests and testing on amputee participants were conducted to optimize the stimulus profile and electrode design and layout. RESULTS: The proximal current injection electrode needed to be at least 25 cm from the proximal voltage sensing electrode. A thin layer of hydrogel needed to be present during testing to ensure good electrical coupling. Using a burst duration of 2.0 ms, intermission interval of 100 µs, and sampling delay of 10 µs at each of 24 frequencies except 5 kHz, which required a 200-µs sampling delay, the system achieved a sampling rate of 19.7 Hz. CONCLUSION: The designed bioimpedance platform allowed system settings and electrode layouts and positions to be optimized for amputee limb fluid volume measurement. SIGNIFICANCE: The system will be useful toward identifying and ranking prosthetic design features and participant characteristics that impact residual limb fluid volume.

Quantitative Assessment of Fluid Accumulation Using Bioelectrical Impedance Analysis in Patients With Acute Decompensated Heart Failure.

BACKGROUND: Acute decompensated heart failure (ADHF) is generally considered to be a problem of fluid volume overload, therefore accurately quantifying the degree of fluid accumulation is of critical importance in assessing whether adequate decongestion has been achieved. The aim of this study was to develop and validate a method to quantify the degree of fluid accumulation in patients with ADHF. METHODS AND RESULTS: Using multi-frequency bioelectrical impedance analysis (BIA), we measured extracellular water (ECW) volume in 130 ADHF patients on admission and at discharge. We also predicted optimal ECW volume using original equations based on data from 60 control subjects without the signs of HF. Measured/predicted (M/P) ratio of ECW in ADHF patients was observed to decrease from 1.26±0.25 to 1.04±0.17 during hospitalization (P<0.001). The amount of ECW volume reduction was significantly correlated with reduction in body weight (r=0.766, P<0.001). On multivariate analysis, higher M/P ratio of ECW at discharge was associated with increased risk of ADHF readmission or cardiac death within 6 months after discharge. CONCLUSIONS: Multi-frequency BIA-measured ECW was found to offer valuable information for analyzing the pathophysiology of ADHF, and may be a useful guide in the management of this disease.

Glucose metabolism following human traumatic brain injury: methods of assessment and pathophysiological findings.

The pathophysiology of traumatic brain (TBI) injury involves changes to glucose uptake into the brain and its subsequent metabolism. We review the methods used to study cerebral glucose metabolism with a focus on those used in clinical TBI studies. Arterio-venous measurements provide a global measure of glucose uptake into the brain. Microdialysis allows the in vivo sampling of brain extracellular fluid and is well suited to the longitudinal assessment of metabolism after TBI in the clinical setting. A recent novel development is the use of microdialysis to deliver glucose and other energy substrates labelled with carbon-13, which allows the metabolism of glucose and other substrates to be tracked. Positron emission tomography and magnetic resonance spectroscopy allow regional differences in metabolism to be assessed. We summarise the data published from these techniques and review their potential uses in the clinical setting.