Endometriosis is characterized by the presence of endometrial glands and stroma in extrauterine sites. Our objective was to determine whether endometriotic lesions (ELs) from women with endometriosis have altered retinoid levels compared with their eutopic endometrium, and to test the hypothesis that defects in all-trans retinoic acid (ATRA) biosynthesis in EL is related to reduced expression of cellular retinol-binding protein type 1 (RBP1). Retinoids were evaluated by liquid chromatography-tandem mass spectrometry and high-performance liquid chromatography in eutopic endometrial biopsies (EBs) and ELs from 42 patients with pathologically confirmed endometriosis. The ATRA levels were reduced, whereas the retinol and retinyl ester concentrations were elevated in EL compared with EB tissue. Similar results were found in a mouse model of endometriosis that used green fluorescent protein-positive endometrial tissue injected into the peritoneum of syngeneic hosts to mimic retrograde menses. The ATRA biosynthesis in vitro in retinol-treated primary human endometrial stromal cell (ESC) cultures derived from ELs was reduced compared with that of ESCs derived from patient-matched EBs. Correspondingly, RBP1 expression was reduced in tissue and ESCs derived from EL versus EB. Rbp1(-/-) mice showed reduced endometrial ATRA concentrations compared with wild type, associated with loss of tissue organization and hypercellularity. These findings provide the first quantitative measurements of ATRA in human endometrium and endometriosis, demonstrating reduced ATRA in ectopic tissue and corresponding ESC cultures. Quantitation of retinoids in murine endometriosis and in Rbp1(-/-) mice supports the contention that impaired ATRA synthesis caused by reduced RBP1 promotes an "endometriosis phenotype" that enables cells to implant and grow at ectopic sites.

Purpose: Examine the feasibility of characterizing the regulation of renal oxygenation using high-temporal-resolution monitoring of the T * 2 response to a step-like oxygenation stimulus. Methods: For T * 2 mapping, multi-echo gradient-echo imaging was used (temporal resolution = 9 seconds). A step-like renal oxygenation challenge was applied involving sequential exposure to hyperoxia (100% O 2), hypoxia (10% O 2 + 90% N 2), and hyperoxia (100% O 2). In vivo experiments were performed in healthy rats (N = 10) and in rats with bilateral ischemia-reperfusion injury (N = 4). To assess the step response of renal oxygenation, a second-order exponential model was used (model parameters: amplitude [A], time delay [Δt], damping constant [D], and period of the oscillation [T]) for renal cortex, outer stripe of the outer medulla, inner stripe of the outer medulla, and inner medulla. Results: The second-order exponential model permitted us to model the exponential T * 2 recovery and the superimposed T * 2 oscillation following renal oxygenation stimulus. The in vivo experiments revealed a difference in D outer medulla between healthy controls (D < 1, indicating oscillatory recovery) and ischemia-reperfusion injury (D > 1, reflecting aperiodic recovery). The increase in D outer medulla by a factor of 3.7 (outer stripe of the outer medulla) and 10.0 (inner stripe of the outer medulla) suggests that this parameter might be rather sensitive to (patho)physiological oxygenation changes. Conclusion: This study demonstrates the feasibility of monitoring the dynamic oxygenation response of renal tissues to a step-like oxygenation challenge using | 335 ZHAO et Al.

Background Non‐Gaussian diffusion models and T1rho quantification may reflect the changes in tissue heterogeneity in hepatic sinusoidal obstruction syndrome (SOS). Purpose To investigate the feasibility of diffusion kurtosis imaging (DKI), stretched exponential model (SEM), and T1rho quantification in detecting and staging SOS in a monocrotaline (MCT)‐induced rat model. Study Type Animal study. Population Thirty male Sprague–Dawley rats gavaged with MCT to induce hepatic SOS and six male rats without any intervention. Field Strength/Sequence 3.0T, DWI with five b‐values (0–2000 s/mm2) and T1rho with five spin lock times (1–60 msec). Assessment MRI was performed 1 day before and 1, 3, 5, 7, and 10 days after MCT administration. The corrected apparent diffusion coefficient (Dapp), kurtosis coefficient (Kapp), distributed diffusion coefficient (DDC), and intravoxel water molecular diffusion heterogeneity (α) were calculated from the corresponding non‐Gaussian diffusion model. The T1rho value was calculated using a monoexponential model. Specimens obtained from the six timepoints were categorized into normal liver (n = 6), early‐stage (n = 16), and late‐stage (n = 14) SOS in accordance with the pathological score. Statistical Tests Parametric statistical methods and receiver operating characteristic (ROC) curves were employed to determine diagnostic accuracy. Results The Dapp, Kapp, DDC, α, and T1rho values were correlated with pathological score with r values of −0.821, 0.726, −0.828, −0.739, and 0.714 (all P < 0.001), respectively. DKI (combined Dapp and Kapp) and SEM (combined DDC and α) were better than T1rho for staging SOS. The areas under the ROC curve of DKI, SEM, and T1rho for differentiating normal liver and early‐stage SOS were 0.97, 1.00, and 0.79, whereas those of DKI, SEM, and T1rho for differentiating early‐stage and late‐stage SOS were 1.00, 0.97, and 0.92, respectively. Data Conclusion DKI, SEM, and T1rho may be helpful in staging SOS. Level of Evidence 2 Technical Efficacy Stage 2 J. Magn. Reson. Imaging 2020;52:1110–1121.

Exposure to aristolochic acid (AA) is of increased concern due to carcinogenic and nephrotoxic effects, and incidence of aristolochic acid nephropathy (AAN) is increasing. This study characterizes renal alterations during the acute phase of AAN using parametric magnetic resonance imaging (MRI). An AAN and a control group of male Wistar rats received administration of aristolochic acid I (AAI) and polyethylene glycol (PEG), respectively, for six days. Both groups underwent MRI before and 2, 4 and 6 days after AAI or PEG administration. T2 relaxation times and apparent diffusion coefficients (ADCs) were determined for four renal layers. Serum creatinine levels (sCr) and blood urea nitrogen (BUN) were measured. Tubular injury scores (TIS) were evaluated based on histologic findings. Increased T2 values were detected since day 2 in the AAN group, but decreased ADCs and increased sCr levels and BUN were not detected until day 4. Significant linear correlations were observed between T2 of the cortex and the outer stripe of outer medulla and TIS. Our results demonstrate that parametric MRI facilitates early detection of renal injury induced by AAI in a rat model. T2 mapping may be a valuable tool for assessing kidney injury during the acute phase of AAN.