Lizette Warner

Noninvasive In vivo assessment of renal tissue elasticity during graded renal ischemia using MR elastography.

Objectives:Magnetic resonance elastography (MRE) allows noninvasive assessment of tissue stiffness in vivo. Renal arterial stenosis (RAS), a narrowing of the renal artery, promotes irreversible tissue fibrosis that threatens kidney viability and may elevate tissue stiffness. However, kidney stiffness may also be affected by hemodynamic factors. This study tested the hypothesis that renal blood flow (RBF) is an important determinant of renal stiffness as measured by MRE. Material and Methods:In 6 anesthetized pigs MRE studies were performed to determine cortical and medullary elasticity during acute graded decreases in RBF (by 20%, 40%, 60%, 80%, and 100% of baseline) achieved by a vascular occluder. Three sham-operated swine served as time control. Additional pigs were studied with MRE 6 weeks after induction of chronic unilateral RAS (n = 6) or control (n = 3). Kidney fibrosis was subsequently evaluated histologically by trichrome staining. Results:During acute RAS the stenotic cortex stiffness decreased (from 7.4 ± 0.3 to 4.8 ± 0.6 kPa, P = 0.02 vs. baseline) as RBF decreased. Furthermore, in pigs with chronic RAS (80% ± 5.4% stenosis) in which RBF was decreased by 60% ± 14% compared with controls, cortical stiffness was not significantly different from normal (7.4 ± 0.3 vs. 7.6 ± 0.3 kPa, P = 0.3), despite histologic evidence of renal tissue fibrosis. Conclusion:Hemodynamic variables modulate kidney stiffness measured by MRE and may mask the presence of fibrosis. These results suggest that kidney turgor should be considered during interpretation of elasticity assessments.

Determinations of renal cortical and medullary oxygenation using blood oxygen level-dependent magnetic resonance imaging and selective diuretics.

Objective:This study was undertaken to test the hypothesis that blood O2 level-dependent magnetic resonance imaging (BOLD MRI) can detect changes in cortical proximal tubule (PT) and medullary thick ascending limb of Henle (TAL) oxygenation consequent to successive administration of furosemide and acetazolamide (Az). Assessment of PT and TAL function could be useful to monitor renal disease states in vivo. Therefore, the adjunct use of diuretics that inhibit Na+ reabsorption selectively in PT and TAL, Az and furosemide, respectively, may help discern tubular function by using BOLD MRI to detect changes in tissue oxygenation. Material and Methods:BOLD MRI signal R2* (inversely related to oxygenation) and tissue oxygenation with intrarenal O2 probes were measured in pigs that received either furosemide (0.05 mg/kg) or Az (15 mg/kg) alone, Az sequentially after furosemide (n = 6 each, 15-minute intervals), or only saline vehicle (n = 3). Results:R2* decreased in the cortex of Az-treated and medulla of furosemide-treated kidneys, corresponding to an increase in their tissue O2 assessed with probes. However, BOLD MRI also showed decreased cortical R2* following furosemide that was additive to the Az-induced decrease. Az administration, both alone and after furosemide, also decreased renal blood flow (−26% ± 3.5% and −29.2% ± 3%, respectively, P < 0.01). Conclusion:These results suggest that an increase in medullary and cortical tissue O2 elicited by selective diuretics is detectable by BOLD MRI, but may be complicated by hemodynamic effects of the drugs. Therefore, the BOLD MRI signal may reflect functional changes additional to oxygenation, and needs to be interpreted cautiously.

Revascularization of swine renal artery stenosis improves renal function but not the changes in vascular structure

Renal revascularization by percutaneous transluminal angioplasty improves blood pressure and stenotic kidney function in selected groups of patients, but the reversibility of intrarenal and microvascular remodeling remains unknown. Here, we tested the hypothesis that renal angioplasty improves the function and structure of renal microcirculation in experimental chronic renal artery stenosis. Stenotic kidney function, hemodynamics, and endothelial function were assessed in vivo in pigs after 10 weeks of unilateral renal artery stenosis. Renal microvascular remodeling, angiogenic pathways, and fibrosis were measured ex vivo. Angioplasty and stenting carried out 4 weeks before measurement decreased blood pressure, improved glomerular filtration rate, and improved microvascular endothelial function. It also promoted the expression of angiogenic factors and decreased renal apoptosis due to stenosis, compared with a sham intervention. The spatial density of renal microvessels, however, was partially improved after angioplasty. Renal blood flow was incompletely restored compared with the kidneys of sham-treated animals, as was interstitial fibrosis. Renal microvascular media-to-lumen ratio remained unchanged by angioplasty. Thus, our study shows that revascularization of a stenotic renal artery restores the glomerular filtration rate and renal endothelial function 4 weeks later. Renal hemodynamics and structure, however, are incompletely resolved.

Increased hypoxia and reduced renal tubular response to furosemide detected by BOLD magnetic resonance imaging in swine renovascular hypertension

Oxygen consumption beyond the proximal tubule is mainly determined by active solute reabsorption, especially in the thick ascending limb of the Loop of Henle. Furosemide-induced suppression of oxygen consumption (FSOC) involves inhibition of sodium transport in this segment, which is normally accompanied by a marked decrease in the intrarenal deoxyhemoglobin detectable by blood oxygen level-dependent (BOLD)-magnetic resonance imaging (MRI). This study tested the hypothesis that the magnitude of BOLD-MRI signal change after furosemide is related to impaired renal function in renovascular hypertension. In 16 pigs with unilateral renal artery stenosis, renal hemodynamics, function, and tubular function (FSOC and fluid concentration capacity) were evaluated in both kidneys using MR and multidetector computerized tomography (MDCT) imaging. Animals with adequate FSOC (23.6 +/- 2.2%, P > 0.05 vs. baseline) exhibited a mean arterial pressure (MAP) of 113 +/- 7 mmHg, and relatively preserved glomerular filtration rate (GFR) of 60 +/- 4.5 ml/min, comparable to their contralateral kidney (66 +/- 4 ml/min, P > 0.05). In contrast, animals with low FSOC (3.1 +/- 2.1%, P = NS vs. baseline) had MAP of 124 +/- 9 mmHg and GFR (22 +/- 6 ml/min) significantly lower than the contralateral kidneys (66 +/- 4 ml/min, P < 0.05). The group with preserved GFR and FSOC showed an increase in intratubular fluid concentration as assessed by MDCT that was greater than that observed in the low GFR group, suggesting better preservation of tubular function in the former group. These results suggest that changes in BOLD-MRI after furosemide can differentiate between underperfused kidneys with preserved tubular function and those with tubular dysfunction. This approach may allow more detailed physiologic evaluation of poststenotic kidneys in renovascular hypertension than previously possible.

Regional Decreases in Renal Oxygenation during Graded Acute Renal Arterial Stenosis: A Case for Renal Ischemia

Ischemic nephropathy describes progressive renal failure, defined by significantly reduced glomerular filtration rate, and may be due to renal artery stenosis (RAS), a narrowing of the renal artery. It is unclear whether ischemia is present during RAS since a decrease in renal blood flow (RBF), O(2) delivery, and O(2) consumption occurs. The present study tests the hypothesis that despite proportional changes in whole kidney O(2) delivery and consumption, acute progressive RAS leads to decreases in regional renal tissue O(2). Unilateral acute RAS was induced in eight pigs with an extravascular cuff. RBF was measured with an ultrasound flow probe. Cortical and medullary tissue oxygen (P(t(O(2)))) of the stenotic kidney was measured continuously with sensors during baseline, three sequentially graded decreases in RBF, and recovery. O(2) consumption decreased proportionally to O(2) delivery during the graded stenosis (19 +/- 10.8, 48.2 +/- 9.1, 58.9 +/- 4.7 vs. 15.1 +/- 5, 35.4 +/- 3.5, 57 +/- 2.3%, respectively) while arterial venous O(2) differences were unchanged. Acute RAS produced a sharp reduction in O(2) efficiency for sodium reabsorption (P < 0.01). Cortical (P(t(O(2)))) decreases are exceeded by medullary decreases during stenosis (34.8 +/- 1.3%). Decreases in tissue oxygenation, more pronounced in the medulla than the cortex, occur despite proportional reductions in O(2) delivery and consumption. This demonstrates for the first time that hypoxia is present in the early stages of RAS and suggests a role for hypoxia in the pathophysiology of this disease. Furthermore, the notion that arteriovenous shunting and increased stoichiometric energy requirements are potential contributors toward ensuing hypoxia with graded and progressive acute RAS cannot be excluded.

In vitro renal cortex elasticity and viscosity measurements with shearwave dispersion ultrasound vibrometry (SDUV) on swine kidney

Shearwave dispersion ultrasound vibrometry (SDUV) is used to quantify both tissue shear elasticity and shear viscosity by evaluating dispersion of shear wave propagation speed over a certain bandwidth (50 to 500 Hz). The motivation for developing elasticity imaging techniques is the desire to diagnose disease processes. However, it is important to study the mechanical properties of healthy tissues; such data can enhance clinical knowledge and improve understanding of the mechanical properties of tissue. The purpose of this study is to evaluate the feasibility of using SDUV for in vitro measurements of renal cortex shear elasticity and shear viscosity in healthy swine kidneys. Eight excised kidneys from female pigs were used in these in vitro experiments and a battery of tests was performed to gain insight into the material proper ties of the renal cortex. In these 8 kidneys, the overall renal cortex elasticity and viscosity were 1.81 ± 0.17 kPa and 1.48 ± 0.49 Pa-s, respectively. In an analysis of the material properties over time after excision, there was not a statistically significant difference in shear elasticity over a 24-h period, but a statistically significant difference in shear viscosity was found. Homogeneity of the renal cortex was examined and it was found that shear elasticity and shear viscosity were statistically different within a kidney, suggesting global tissue inhomogeneity. In creases of more than 30% in shear elasticity and shear viscosity were observed after immersion in 10% formaldehyde. Finally, it was found that the renal cortex is rather anisotropic. Two values for shear elasticity and shear viscosity were measured depending on shear wave propagation direction. These various tests elucidated different aspects of the material properties and the structure of the ex vivo renal cortex.

Measurements of swine renal cortex shear elasticity and viscosity with Shearwave Dispersion Ultrasound Vibrometry (SDUV)

Fibrosis has been associated with altered tissue structure affecting the biomechanical properties of the organs, quantifiable as elasticity and viscosity. Renal fibrosis threatens kidney viability. Evaluation of renal fibrosis by conventional imaging modalities is difficult. Importantly, early detection of renal fibrosis may guide therapy and eliminate invasive biopsy procedures. A newly emerging method called Shearwave Dispersion Ultrasound Vibrometry (SDUV) offers a potential tool to determine renal elasticity and viscosity in vivo. SDUV quantifies both elasticity and viscosity by evaluating dispersion of shear wave propagation speed versus its frequency. The purpose of this study was to evaluate the feasibility of SDUV for in vitro measurements of renal cortex elasticity and viscosity in swine kidney.

Bayesian tracking of a nonlinear model of the capnogram.

Capnography, the monitoring of expired carbon dioxide (CO2 ) has been employed clinically as a non-invasive measure for the adequacy of ventilation of the alveoli of the lung. In combination with air flow measurements, the capnogram can be used to estimate the partial pressure of CO2 in the alveolar sacs. In addition, physiologically relevant parameters, such as the extent of CO2 rebreathing, the airway dead space, and the metabolic CO 2 production can be predicted. To calculate these parameters, mathematical models have been previously formulated and applied to experimental data using off-line optimization procedures. Unfortunately, this does not permit online identification of the capnogram to detect changes in the physiological model parameters. In the present study, a Bayesian method for breath-by-breath identification of the volumetric capnogram is presented. The method integrates a model of CO2 exchange in the lungs, which is nonlinear due to the nature of human tidal breathing, with a particle filtering algorithm for estimation of the model parameters and changes therein. In addition, this allowed for a dynamic prediction of the unmeasured alveolar CO2 tension. The method is demonstrated using simulations of the capnogram. The proposed method could aid the clinician in the interpretation of the capnogram

Calculating the Effect of Altered Respiratory Parameters on Capnographic Indices

Capnography, the monitoring of exhaled CO2, has been clinically utilized as a noninvasive measure of alveolar ventilation. The shape of the capnogram is significantly altered in patients with lung disease or hemodynamic instability. Shape indices obtained from the capnogram provide an indication of dead space ventilation, ventilation/perfusion status, and the extent of rebreathing. In this study, the quantitative relationship between physical respiratory parameters and capnographic shape indices was determined using a mathematical model of CO2 exchange in a tidally ventilated lung. This relationship may provide clinicians with guidance for physiological interpretation of capnograms.

Algorithm for real-time identification and order estimation of jump-linear systems

Abstract In this paper, we propose a novel method for the real-time identification and simultaneous order estimation of a class of piecewise linear systems, namely jump-linear systems. The parameters, orders and time instances of switching are identified, based on a recursive weighted least-squares scheme and pole-zero cancellations. Several examples demonstrate the effectiveness of the algorithm. The proposed real-time technique is promising for use in patient monitoring and feedback control systems.