Evaluation of Renal Fibrosis Using Magnetization Transfer Imaging at 1.5T and 3T in a Porcine Model of Renal Artery Stenosis.

Renal fibrosis is an important marker in the progression of chronic kidney disease, and renal biopsy is the current reference standard for detecting its presence. Currently, non-invasive methods have only been partially successful in detecting renal fibrosis. Magnetization transfer imaging (MTI) allows estimates of renal fibrosis but may vary with scanning conditions. We hypothesized that MTI-derived renal fibrosis would be reproducible at 1.5T and 3T MRI and over time in fibrotic kidneys. Fifteen pigs with unilateral renal artery stenosis (RAS, n = 9) or age-matched sham controls (n = 6) underwent MTI-MRI at both 1.5T and 3T 6 weeks post-surgery and again 4 weeks later. Magnetization transfer ratio (MTR) measurements of fibrosis in both kidneys were compared between 1.5T and 3T, and the reproducibility of MTI at the two timepoints was evaluated at 1.5T and 3T. MTR at 3T with 600 Hz offset frequency successfully distinguished between normal, stenotic, and contralateral kidneys. There was excellent reproducibility of MTI at 1.5T and 3T over the two timepoints and no significant differences between MTR measurements at 1.5T and 3T. Therefore, MTI is a highly reproducible technique which is sensitive to detect changes in fibrotic compared to normal kidneys in the RAS porcine model at 3T.

Predicting tracheal work of breathing in neonates based on radiological and pulmonary measurements.

Tracheomalacia is an airway condition in which the trachea excessively collapses during breathing. Neonates diagnosed with tracheomalacia require more energy to breathe, and the effect of tracheomalacia can be quantified by assessing flow-resistive work of breathing (WOB) in the trachea using computational fluid dynamics (CFD) modeling of the airway. However, CFD simulations are computationally expensive; the ability to instead predict WOB based on more straightforward measures would provide a clinically useful estimate of tracheal disease severity. The objective of this study is to quantify the WOB in the trachea using CFD and identify simple airway and/or clinical parameters that directly relate to WOB. This study included 30 neonatal intensive care unit subjects (15 with tracheomalacia and 15 without tracheomalacia). All subjects were imaged using ultrashort echo time (UTE) MRI. CFD simulations were performed using patient-specific data obtained from MRI (airway anatomy, dynamic motion, and airflow rates) to calculate the WOB in the trachea. Several airway and clinical measurements were obtained and compared with the tracheal resistive WOB. The maximum percent change in the tracheal cross-sectional area (ρ = 0.560, P = 0.001), average glottis cross-sectional area (ρ = -0.488, P = 0.006), minute ventilation (ρ = 0.613, P < 0.001), and lung tidal volume (ρ = 0.599, P < 0.001) had significant correlations with WOB. A multivariable regression model with three independent variables (minute ventilation, average glottis cross-sectional area, and minimum of the eccentricity index of the trachea) can be used to estimate WOB more accurately (R2 = 0.726). This statistical model may allow clinicians to estimate tracheal resistive WOB based on airway images and clinical data.NEW & NOTEWORTHY The work of breathing due to resistance in the trachea is an important metric for quantifying the effect of tracheal abnormalities such as tracheomalacia, but currently requires complex dynamic imaging and computational fluid dynamics simulation to calculate it. This study produces a method to predict the tracheal work of breathing based on readily available imaging and clinical metrics.

Multiparametric quantitative renal MRI in children and young adults: comparison between healthy individuals and patients with chronic kidney disease.

PURPOSE: Multiparametric quantitative renal MRI may provide noninvasive radiologic biomarkers of chronic kidney disease (CKD) based on investigations in animal models and adults. We aimed to (1) obtain normative multiparametric quantitative MRI data from the kidneys of healthy children and young adults, (2) compare MRI measurements between healthy control participants and patients with CKD, and (3) determine if MRI measurements correlate with clinical and laboratory data as well as histology. METHODS: This was a prospective, case-control study of 20 healthy controls and 12 CKD patients who underwent percutaneous renal biopsy ranging from 12 to 23 years of age between October 2018 and March 2020. Kidney function was documented and pathology assessed for fibrosis/inflammation. Utilizing a field strength of 1.5T, we examined renal T1, T2, and T2* relaxation mapping, MR elastography (MRE), and diffusion-weighted imaging (DWI). A single analyst made all manual measurements for quantitative MRI pulse sequences. Independent measurements from cortex, medulla, and whole kidney were obtained by drawing regions of interest on single slices from the upper, mid, and lower kidney. A weighted average was calculated for each kidney; if two kidneys, the right and left were averaged. Continuous variables were compared with Mann-Whitney U test; bivariate relationships were assessed using Spearman rank-order correlation. RESULTS: Median estimated glomerular filtration rate (eGFR) was 112.3 ml/min/1.73 m2 in controls (n = 20, 10 females) and 55.0 ml/min/m2 in CKD patients (n = 12, 2 females) (p < 0.0001). Whole kidney (1333 vs. 1291 ms; p = 0.018) and cortical (1212 vs 1137 ms; p < 0.0001) T1 values were higher in CKD patients. Cortical T1 values correlated with eGFR (rho = - 0.62; p = 0.0003) and cystatin C (rho = 0.58; p = 0.0007). Whole kidney (1.87 vs. 2.02 10-3 mm2/s; p = 0.007), cortical (1.89 vs. 2.04 10-3 mm2/s; p = 0.008), and medullary (1.87 vs. 1.98 10-3 mm2/s; p = 0.0095) DWI apparent diffusion coefficients (ADC) were lower in CKD patients. Whole kidney ADC correlated with eGFR (rho = 0.45; p = 0.012) and cystatin C (rho = - 0.46; p = 0.009). Cortical histologic inflammation correlated with DWI ADC (rho = - 0.71; p = 0.011). CONCLUSION: Renal T1 relaxation and DWI ADC measurements differ between pediatric healthy controls and CKD patients, correlate with laboratory markers of CKD, and may have histologic correlates.

Associations between MRI T1 mapping, liver stiffness, quantitative MRCP, and laboratory biomarkers in children and young adults with autoimmune liver disease.

PURPOSE: Define relationships between quantitative magnetic resonance imaging (MRI) metrics and clinical/laboratory data in a pediatric and young adult cohort with autoimmune liver disease (AILD). MATERIALS AND METHODS: This prospective, cross-sectional study was institutional review board-approved. Patients enrolled in an institutional AILD registry were divided into groups: (1) autoimmune hepatitis (AIH) or (2) primary sclerosing cholangitis (PSC)/autoimmune sclerosing cholangitis (ASC). Participants underwent serum liver biochemistry testing and research MRI examinations, including 3D magnetic resonance cholangiopancreatography (MRCP), magnetic resonance elastography (MRE), and iron-corrected T1 mapping (cT1). MRCP + and LiverMultiScan (Perspectum Ltd., Oxford, UK) were used to post-process 3D MRCP and cT1 data. Multiple linear regression models were used to assess relationships. RESULTS: 58 patients, 35 male, median age 16 years were included; 30 in the AIH group, 28 in the PSC/ASC group. After statistical adjustments for patient age, sex, presence of inflammatory bowel disease (IBD), specific diagnosis (PSC/ASC vs. AIH), and time from diagnosis to MRI examination, left hepatic bile duct maximum diameter was a statistically significant predictor of whole liver mean cT1, cT1 interquartile range (IQR), and MRE liver stiffness (p = 0.01-0.04). Seven laboratory values were significant predictors of whole liver cT1 IQR (p < 0.0001-0.04). Eight laboratory values and right hepatic bile duct median and maximum diameter were significant predictors of liver stiffness (p < 0.0001-0.03). CONCLUSIONS: Bile duct diameters and multiple laboratory biomarkers of liver disease are independent predictors of liver stiffness and cT1 IQR in pediatric patients with AILD.

Neonates With Tracheomalacia Generate Auto-Positive End-Expiratory Pressure via Glottis Closure.

BACKGROUND: In pediatrics, tracheomalacia is an airway condition that causes tracheal lumen collapse during breathing and may lead to the patient requiring respiratory support. Adult patients can narrow their glottis to self-generate positive end-expiratory pressure (PEEP) to raise the pressure in the trachea and prevent collapse. However, auto-PEEP has not been studied in newborns with tracheomalacia. The objective of this study was to measure the glottis cross-sectional area throughout the breathing cycle and to quantify total pressure difference through the glottis in patients with and without tracheomalacia. RESEARCH QUESTION: Do neonates with tracheomalacia narrow their glottises? How does the glottis narrowing affect the total pressure along the airway? STUDY DESIGN AND METHODS: Ultrashort echo time MRI was performed in 21 neonatal ICU patients (11 with tracheomalacia, 10 without tracheomalacia). MRI scans were reconstructed at four different phases of breathing. All patients were breathing room air or using noninvasive respiratory support at the time of MRI. Computational fluid dynamics simulations were performed on patient-specific virtual airway models with airway anatomic features and motion derived via MRI to quantify the total pressure difference through the glottis and trachea. RESULTS: The mean glottis cross-sectional area at peak expiration in the patients with tracheomalacia was less than half that in patients without tracheomalacia (4.0 ± 1.1 mm2 vs 10.3 ± 4.4 mm2; P = .002). The mean total pressure difference through the glottis at peak expiration was more than 10 times higher in patients with tracheomalacia compared with patients without tracheomalacia (2.88 ± 2.29 cm H2O vs 0.26 ± 0.16 cm H2O; P = .005). INTERPRETATION: Neonates with tracheomalacia narrow their glottises, which raises pressure in the trachea during expiration, thereby acting as auto-PEEP.

Quantitative Evaluation of Subglottic Stenosis Using Ultrashort Echo Time MRI in a Rabbit Model.

OBJECTIVE/HYPOTHESIS: To assess the ability of ultra-short echo time (UTE)-MRI to detect subglottic stenosis (SGS) and evaluate response to balloon dilation. To correlate measurements from UTE-MRI with endotracheal-tube (ETT)-sizing and to investigate whether SGS causes change in airway dynamics. STUDY DESIGN: Animal research study. METHODS: Eight adult New-Zealand white rabbits were used as they approximate neonatal airway-size. The airways were measured using ETT-sizing and 3D UTE-MRI at baseline, 2 weeks post-cauterization induced SGS injury, and post-balloon dilation treatment. UTE-MR images were acquired to determine airway anatomy and motion. Airways were segmented from MR images. Cross-sectional area (CSA), major and minor diameters (Dmajor and Dminor ), and eccentricity were measured. RESULTS: Post-injury CSA at SGS was significantly reduced (mean 38%) compared to baseline (P = .003) using UTE-MRI. ETT-sizing correlated significantly with MRI-measured CSA at the SGS location (r = 0.6; P < .01), particularly at the post-injury timepoint (r = 0.93; P < .01). Outer diameter from ETT-sizing (OD) correlated significantly with Dmajor (r = 0.63; P < .01) from UTE-MRI at the SGS location, especially for the post-injury timepoint (r = 0.91; P < .01). Mean CSA of upper trachea did not change significantly between end-expiration and end-inspiration at any timepoint (all P > .05). Eccentricity of the upper trachea increased significantly post-balloon dilation (P < .05). CONCLUSIONS: UTE-MRI successfully detected SGS and treatment response in the rabbit model, with good correlation to ETT-sizing. Balloon dilation increased CSA at SGS, but not to baseline values. SGS did not alter dynamic motion for the trachea in this rabbit model; however, tracheas were significantly eccentric post-balloon dilation. UTE-MRI can detect SGS without sedation or ionizing radiation and may be a non-invasive alternative to ETT-sizing. LEVEL OF EVIDENCE: NA Laryngoscope, 131:E1971-E1979, 2021.

Association between liver diffusion-weighted imaging apparent diffusion coefficient values and other measures of liver disease in pediatric autoimmune liver disease patients.

BACKGROUND: Multiple quantitative magnetic resonance imaging (MRI) methods have been described to noninvasively detect and characterize liver fibrosis, including diffusion-weighted imaging (DWI). PURPOSE: To evaluate associations between liver MRI DWI apparent diffusion coefficient (ADC) values and clinical factors and other quantitative liver MRI metrics in pediatric patients with autoimmune liver disease (AILD). MATERIALS AND METHODS: Fifty-seven research liver MRI examinations performed from January 2017 to August 2018 for pediatric AILD registry participants were evaluated. Liver DWI ADC values, liver and spleen stiffness (kPa), and iron-corrected T1 (cT1; Perspectum Diagnostics) were measured at four anatomic levels. Participant age, sex, and laboratory data (alanine aminotransferase [ALT], total bilirubin, alkaline phosphatase, gamma-glutamyl transferase [GGT]) were recorded. Spearman's rank-order correlation (rho) and multiple linear regression were used to evaluate the associations between liver ADC values and predictor variables. RESULTS: Mean (SD) participant age was 14.8 (4.0) years, 45.6% (26/57) were girls. Mean liver DWI ADC value was 1.34 (0.14 × 10-3) mm2/s. Liver ADC values showed weak to moderate correlations with liver stiffness (r = - 0.42, p = 0.001), spleen stiffness (r = - 0.34; p = 0.015), whole-liver mean cT1 (r = - 0.39; p = 0.007), ALT (r = - 0.50; p = 0.0001), and GGT (r = - 0.48; p = 0.0004). Multiple linear regression showed liver stiffness (p = 0.0009) and sex (p = 0.023) to be independent predictors of liver ADC values. CONCLUSION: Liver DWI ADC values are significantly associated with liver and spleen stiffnesses, liver cT1, ALT, GGT, and participant sex, with liver stiffness and sex remaining significant at multivariable regression. Liver ADC ultimately may play a role in multi-parametric prediction of chronic liver disease/fibrosis severity.

Increased Work of Breathing due to Tracheomalacia in Neonates.

Rationale: Dynamic collapse of the tracheal lumen (tracheomalacia) occurs frequently in premature neonates, particularly in those with common comorbidities such as bronchopulmonary dysplasia. The tracheal collapse increases the effort necessary to breathe (work of breathing [WOB]). However, quantifying the increased WOB related to tracheomalacia has previously not been possible. Therefore, it is also not currently possible to separate the impact of tracheomalacia on patient symptoms from parenchymal abnormalities.Objectives: To measure the increase in WOB due to airway motion in individual subjects with and without tracheomalacia and with different types of respiratory support.Methods: Fourteen neonatal intensive care unit subjects not using invasive mechanical ventilation were recruited. In eight, tracheomalacia was diagnosed via clinical bronchoscopy, and six did not have tracheomalacia. Self-gated three-dimensional ultrashort-echo-time magnetic resonance imaging (MRI) was performed on each subject with clinically indicated respiratory support to obtain cine images of tracheal anatomy and motion during the respiratory cycle. The component of WOB due to resistance within the trachea was then calculated via computational fluid dynamics (CFD) simulations of airflow on the basis of the subject's anatomy, motion, and respiratory airflow rates. A second CFD simulation was performed for each subject with the airway held static at its largest (i.e., most open) position to determine the increase in WOB due to airway motion and collapse.Results: The tracheal-resistive component of WOB was increased because of airway motion by an average of 337% ± 295% in subjects with tracheomalacia and 24% ± 14% in subjects without tracheomalacia (P < 0.02). In the tracheomalacia group, subjects who were treated with continuous positive airway pressure (CPAP) using a RAM cannula expended less energy for breathing compared with the subjects who were breathing room air or on a high-flow nasal cannula.Conclusions: Neonatal subjects with tracheomalacia have increased energy expenditure compared with neonates with normal airways, and CPAP may be able to attenuate the increase in respiratory work. Subjects with tracheomalacia expend more energy on the tracheal-resistive component of WOB alone than nontracheomalacia patients expend on the resistive WOB for the entire respiratory system, according to previously reported values. CFD may be able to provide an objective measure of treatment response for children with tracheomalacia.