US Time-Harmonic Elastography for the Early Detection of Glomerulonephritis.

Background Glomerulonephritis refers to renal diseases characterized by glomerular and tubulointerstitial fibrosis. Multifrequency US time-harmonic elastography enables the noninvasive quantification of tissue elasticity. Purpose To assess the diagnostic performance of US time-harmonic elastography for the early detection of glomerulonephritis. Materials and Methods From August 2016 through May 2017, study participants with biopsy-proven glomerulonephritis were prospectively examined with US time-harmonic elastography. Participants were subdivided according to chronic kidney disease (CKD) stage. All participants underwent elastography of both kidneys to generate full-field-of-view maps of renal shear wave speed (SWS). SWS was determined separately for the whole renal parenchyma, cortex, and medulla and was correlated with quantitative B-mode findings such as renal length and parenchymal thickness. Diagnostic performance of renal elastography was assessed with receiver operating characteristic curve analysis. Results Fifty-three participants with glomerulonephritis (mean age ± standard deviation, 49 years ± 14) and 30 healthy volunteers (mean age, 37 years ± 11) were evaluated. Age-adjusted renal SWS was lower in participants with glomerulonephritis than in healthy volunteers in the parenchyma, cortex, and medulla, with mean values of 1.55 m/sec (95% confidence interval [CI]: 1.51 m/sec, 1.59 m/sec) and 1.69 m/sec (95% CI: 1.64 m/sec, 1.74 m/sec; P < .001), respectively, in parenchyma, 1.80 m/sec (95% CI: 1.75 m/sec, 1.84 m/sec) and 2.08 m/sec (95% CI: 2.02 m/sec, 2.13 m/sec; P < .001) in cortex, and 1.25 m/sec (95% CI: 1.21 m/sec, 1.29 m/sec) and 1.33 (95% CI: 1.27 m/sec, 1.38 m/sec; P = .03) in medulla. Age-adjusted renal cortex SWS was lower in participants with glomerulonephritis and stage 1 CKD (preserved renal function) than in healthy volunteers (mean, 1.88 [95% CI: 1.81, 1.96] vs 2.08 [95% CI: 2.02, 2.13]; P < .001). In participants with CKD, renal cortex SWS values showed a positive association with estimated glomerular filtration rate (n = 39; r = 0.56; P < .001). Exploratory diagnostic performance of US time-harmonic elastography (area under the receiver operating characteristic curve [AUC], 0.89; 95% CI: 0.82, 0.97) outperformed that of B-mode parameters such as parenchymal thickness (AUC, 0.64; 95% CI: 0.51, 0.77; P < .001) and renal length (AUC, 0.55; 95% CI: 0.40, 0.68; P < .001) in identifying glomerulonephritis. Conclusion US time-harmonic elastography depicts abnormal renal stiffness in glomerulonephritis, particularly among patients with early disease and preserved renal function. Advanced chronic kidney disease is associated with further cortical softening. Time-harmonic elastography outperforms B-mode-based size quantification. © RSNA, 2019 Online supplemental material is available for this article.

Full-Field-of-View Time-Harmonic Elastography of the Native Kidney.

The purpose of this study was to analyze full-field-of-view maps of renal shear wave speed (SWS) measured by time-harmonic elastography (THE) in healthy volunteers in terms of reproducibility, regional variation and physiologic effects. The kidneys of 37 healthy volunteers were investigated by multifrequency THE. The complete renal parenchyma, as well as cortex and medulla, was analyzed. A subgroup was investigated to test reproducibility (n = 3). Significant differences between SWS in cortex, medulla and full parenchyma were observed (2.10 ± 0.17, 1.35 ± 0.11 and 1.71 ± 0.16 m/s, all p values < 0.001) with mean intra-volunteer standard deviations of repeated measurements of 0.04 m/s (1.6%), 0.06 m/s (4.0%) and 0.08 m/s (4.5%), respectively. No effects of kidney anatomy, age, body mass index, blood pressure and heart rate on SWS were observed. THE allows generation of full-field-of-view SWS maps of native kidneys with high reproducibility.

Two-Dimensional Time-Harmonic Elastography of the Human Liver and Spleen.

Measurement of shear wave speed of the liver and spleen by elastography is an established diagnostic procedure for the detection of hepatic fibrosis, portal hypertension and esophageal varices. However, current elastography systems are limited by the size and penetration depth of elastographic windows. In this study, 2D time-harmonic elastography is proposed for generating full field-of-view shear wave speed maps in great depth. Two-dimensional time-harmonic elastography uses external harmonic stimulation at multiple frequencies to create compound shear wave speed maps. The method is tested in a phantom with soft and stiff inclusions and used for elastography of the liver and spleen in 13 asymptomatic volunteers. Each volunteer was scanned twice to determine the sensitivity of the method to physiologic variations: first, after 2 h of fasting, and a second time, 15 min after drinking 1 L of water. The wave speed maps of the phantom clearly identified the soft and stiff inclusions, yielding values that were consistent with those from magnetic resonance elastography. In vivo wave speed values were 1.49 ± 0.11 m/s for the liver and 2.03 ± 0.15 m/s for the spleen in a lower-frequency band centered at 40 Hz and 3.15 ± 0.30 m/s for the spleen in a higher-frequency band centered at 120 Hz. After water intake, wave speed values increased by 6% in the liver (p = 0.002) and decreased in the spleen by 4% (p = 0.021, low-frequency band) and 6% (p = 0.0002, high-frequency band), suggesting the high sensitivity of the method to altered blood flow and perfusion pressure. Two-dimensional time-harmonic elastography of the liver and spleen is a promising method for measuring tissue stiffness at different states of blood flow and perfusion in a large tissue window and at great penetration depth.

Associating spontaneous with evoked activity in a neural mass model of visual cortex.

Spontaneous activity of the brain at rest frequently has been considered a mere backdrop to the salient activity evoked by external stimuli or tasks. However, the resting state of the brain consumes most of its energy budget, which suggests a far more important role. An intriguing hint comes from experimental observations of spontaneous activity patterns, which closely resemble those evoked by visual stimulation with oriented gratings, except that cortex appeared to cycle between different orientation maps. Moreover, patterns similar to those evoked by the behaviorally most relevant horizontal and vertical orientations occurred more often than those corresponding to oblique angles. We hypothesize that this kind of spontaneous activity develops at least to some degree autonomously, providing a dynamical reservoir of cortical states, which are then associated with visual stimuli through learning. To test this hypothesis, we use a biologically inspired neural mass model to simulate a patch of cat visual cortex. Spontaneous transitions between orientation states were induced by modest modifications of the neural connectivity, establishing a stable heteroclinic channel. Significantly, the experimentally observed greater frequency of states representing the behaviorally important horizontal and vertical orientations emerged spontaneously from these simulations. We then applied bar-shaped inputs to the model cortex and used Hebbian learning rules to modify the corresponding synaptic strengths. After unsupervised learning, different bar inputs reliably and exclusively evoked their associated orientation state; whereas in the absence of input, the model cortex resumed its spontaneous cycling. We conclude that the experimentally observed similarities between spontaneous and evoked activity in visual cortex can be explained as the outcome of a learning process that associates external stimuli with a preexisting reservoir of autonomous neural activity states. Our findings hence demonstrate how cortical connectivity can link the maintenance of spontaneous activity in the brain mechanistically to its core cognitive functions.