Knoll, Kate M

Key Points The kidney microvasculature was quantified reliably in human autosomal dominant polycystic kidney disease early on, using super-resolution ultrasound localization microscopy. Microvascular parameters correlated with structural and functional indices, constituting promising biomarkers to evaluate noncystic parenchyma. Microvascular parameters may serve to assess disease severity and monitor progression from the early stages of the disease. Background In vitro studies in individuals with autosomal dominant polycystic kidney disease (ADPKD) have shown extensive intrarenal microvascular remodeling. However, analyses have been limited to the time of kidney failure because of the invasive nature of current methodologies to assess the intrarenal microvasculature. We hypothesized that super-resolution ultrasound microvascular imaging, known as ultrasound localization microscopy, enabled by high-framerate ultrasound imaging and microbubble localization and tracking postprocessing techniques, would safely, reliably, and reproducibly assess the intrarenal microvasculature in individuals with ADPKD at an early stage of the disease. Methods We prospectively enrolled young (<40 years of age), well-characterized, early-stage (eGFR >90 ml/min per 1.73 m 2 ) individuals with ADPKD, and sex–age 1:1 matched controls ( n =17 each) and assessed the intrarenal microvasculature using ultrasound localization microscopy. We determined the intersonographer reliability, intraobserver repeatability, and interobserver reproducibility of microvascular parameters in both groups, and the day-to-day variability in the control group. Microvascular parameters were correlated with structural (total kidney volume) and functional (eGFR) markers in individuals with ADPKD. Results Ultrasound localization microscopy provided a super-resolved map of the intrarenal microvasculature in ADPKD and matched controls. Intrarenal microvascular parameters ( e.g ., vessel density) were quantified in a safe, reliable (intraclass correlation coefficients, 0.96; 95% confidence interval, 0.91 to 0.98), reproducible (intraclass correlation coefficient, 0.96; 95% confidence interval, 0.93 to 0.98), and repeatable (coefficient of variations, 3.6%) manner. In control individuals, the day-to-day variability of most parameters was low, with coefficient of variation ranging from 1.8% to 10.7%. Microvascular parameters differed in individuals with ADPKD compared with controls, despite preserved eGFR. Interestingly, cortical vessel density and its derived perfusion correlated directly with eGFR, whereas tortuosity indices presented an inverse correlation. Conclusions Ultrasound localization microscopy provided a safe and reliable in vivo assessment of the human intrarenal microvasculature.

ObjectivesMetabolic dysfunction‐associated steatotic liver disease (MASLD) is the most prevalent liver disorder in Western countries, with approximately 20%–30% of the MASLD patients progressing to severe stages. There is an urgent need for noninvasive, cost‐effective, widely accessible, and precise biomarkers to evaluate liver steatosis. This study aims to assess and compare the diagnostic performance of a novel reference frequency method‐based ultrasound attenuation coefficient estimation (ACE) in both fundamental (RFM‐ACE‐FI) and harmonic (RFM‐ACE‐HI) imaging for detecting and grading liver steatosis.MethodsAn Institutional Review Board‐approved prospective study was carried out between December 2018 and October 2022. A total number of 130 subjects were enrolled in the study. The correlation between RFM‐ACE‐HI values and magnetic resonance imaging proton density fat fraction (MRI‐PDFF), as well as between RFM‐ACE‐FI values and MRI‐PDFF were calculated. The diagnostic performance of RFM‐ACE‐FI and RFM‐ACE‐HI was evaluated using receiver operating characteristic (ROC) curve analysis, as compared to MRI‐PDFF. The reproducibility of RFM‐ACE‐HI was assessed by interobserver agreement between two sonographers.ResultsA strong correlation was observed between RFM‐ACE‐HI and MRI‐PDFF, with R = 0.88 (95% confidence interval [CI]: 0.83–0.92; P < .001), while the correlation between RFM‐ACE‐FI and MRI‐PDFF was R = 0.65 (95% CI: 0.50–0.76; P < .001). The area under the ROC (AUROC) curve for RFM‐ACE‐HI in staging liver steatosis grades of S ≥ 1 and S ≥ 2 was 0.97 (95% CI: 0.91–0.99; P < .001) and 0.98 (95% CI: 0.93–1.00; P < .001), respectively, and 0.76 (95% CI: 0.65–0.85) and 0.80 (95% CI: 0.70–0.88) for RFM‐ACE‐FI, respectively. Great reproducibility was achieved for RFM‐ACE‐HI, with an interobserver agreement of R = 0.97 (95% CI: 0.94–0.99; P < .001).ConclusionsThe novel RFM‐ACE‐HI method offered high liver steatosis diagnostic accuracy and reproducibility, which has important clinical implications for early disease intervention and treatment evaluation.

Recent advancements in ultrasound technologies, such as ultrasound localization microscopy and ultrafast ultrasound Doppler, have enabled high-definition imaging of microvasculature. However, detecting weak microbubble or blood flow signals amid strong background noise remains a challenge, particularly in deep tissues. This study aims to enhance the signal contrast of microbubble and blood flow by leveraging their distinct spatial-temporal coherence in comparison to undesired noise for robust microbubble detection and microvascular imaging. We propose to quantify the signal coherence based on similarity analysis of beamformed ultrasound microbubble/blood flow data within the plane wave imaging framework. A spatial pixel is considered more likely to be a true microbubble/blood flow signal with a higher level of similarity, which can be measured by either of the following methods: 1) spatially block-wise normalized cross-correlation between two compounded frames; 2) temporally normalized autocorrelation across multiple compounded frames; 3) normalized cross-correlation between two subsets of post-compounded frames; 4) normalized autocorrelation of the pre-compounded data across angular direction. The original microbubble/blood flow signal is then weighted by the similarity measurement on a pixel-by-pixel basis to generate images with an improved signal contrast. The robustness of the proposed methods was first demonstrated in both phantom experiments and in vivo microbubble data from kidney transplant. We further validated their feasibility in blood flow imaging without the use of microbubbles based on in vivo data of human liver and kidney. Significant contrast improvement was observed, facilitating better visualization and detection of both microbubble and noncontrast microflow signals, which indicates a great potential of the methods for improved microvascular imaging and widespread clinical translation.

The diaphragm muscle is important in both sustaining ventilation and performing higher-force behaviors necessary for maintaining airway patency. Ventilatory behaviors (i.e., eupnea and response to hypoxia-hypercapnia) require only ~20% of maximal force generation, whereas coughing requires forces ~60% of maximal. Existing techniques to measure the full range of forces generated by respiratory muscles are limited by their invasiveness (e.g., balloon manometry for transdiaphragmatic pressure (Pdi) measurements), requirements for training, supervision and subjectivity (e.g., maximal inspiratory and expiratory pressures). Ultrasound-based shear-wave elastography (SWE) assesses muscle stiffness and has shown promising results in being used as a surrogate for Pdi to evaluate diaphragm muscle force. Previous literature has demonstrated a correlation between diaphragm SWE and Pdi at lower force behaviors and the goal of the present study was to evaluate the efficacy of SWE-based measurements of the diaphragm in correlating with Pdi measurements across the range of forces generated by the diaphragm. In this pilot study, we recruited 6 male and 5 female healthy volunteers. Subjects were positioned in a seated position with their torso unsupported. Pdi was measured during graded inspiratory threshold loading trials using a POWERbreathe Plus commercial inspiratory loading device, as well as during maximal inspiratory pressure (MIP). Simultaneously, SWE was performed at the zone of apposition in the right anterior axillary line, and diaphragm Young’s modulus and shear wave speed were subsequently measured. The average Pdi during MIP testing was 149 ± 66 cm H2O. Pdi during inspiratory loading at a low resistance was 39 ± 14 cm H2O and at a high resistance was 78 ± 29 cm H2O. Subjects were able to generate an average Pdi range of 39 ± 19 cm H2O across the graded resistance levels, and the average percent of MIP obtained was 54 ± 13%. Average Young’s modulus as measured with SWE during inspiratory loading at a low resistance was 46 ± 19 kPa and at a high resistance was 104 ± 19 kPa. From low to high resistance, Pdi, Young’s modulus, and shear wave speed increased by an average of 100%, 126%, and 59%, respectively. Taken together, SWE is a promising method of non-invasive assessment of diaphragm muscle forces across a range of voluntary behaviors. Support from NIH grant R21 DA055848 and the Mayo Clinic. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.