Experimental Study of Intravoxel Incoherent Motion Diffusion Imaging Combined with Ultrasound Renal Resistance Index in Contrast-Induced Nephropathy

Experimental Study of Intravoxel Incoherent Motion Diffusion Imaging Combined with Ultrasound Renal Resistance Index in Contrast-Induced Nephropathy | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Experimental Study of Intravoxel Incoherent Motion Diffusion Imaging Combined with Ultrasound Renal Resistance Index in Contrast-Induced Nephropathy Jinlong Chen, Xiaoyu Song, Zhao Wang, Zhiqiang Wang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5792456/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Jul, 2025 Read the published version in BMC Nephrology → Version 1 posted 7 You are reading this latest preprint version Abstract Objective This study explored the application of Intravoxel Incoherent Motion (IVIM) diffusion imaging combined with Ultrasound Renal Resistance Index (RRI) for monitoring the pathophysiological changes associated with early contrast-induced nephropathy (CIN). Methods In this study, forty-two male Sprague-Dawley (SD) rats were equally divided into two groups: a contrast media (CM) group and a control group, each containing 21 animals. The CM group was administered a tail vein injection of ioversol (370 mg I/ml, 1.5 ml/kg), while the control group received a saline solution in a similar volume. Assessments using IVIM-MRI and Doppler ultrasound were performed 24 hours before and at 1, 24, 48, and 72 hours post-injection. These assessments aimed to evaluate the true diffusion coefficient (D), pseudo-diffusion coefficient (D * ), perfusion fraction (f), apparent diffusion coefficient (ADC), and RRI. Concurrently, three rats from each group were sacrificed at these time points for renal histopathology, hypoxia-inducible factor-1α (HIF-1α) expression analysis, and the quantification of serum creatinine (SCr) and blood urea nitrogen (BUN) levels. Receiver operating characteristic (ROC) curves were plotted, and the area under the curve (AUC) was analyzed to evaluate the diagnostic performance of IVIM and RRI in predicting CIN. Results Post-ioversol administration, significant declines were noted in the D, D * , f, ADC across the renal cortex (CO), outer medulla (OM), and inner medulla (IM) from 1 to 48 hours (P < 0.05), with the lowest values observed at 48 hours. These parameters began to recover after 72 hours. Conversely, RRI values escalated from 1 to 48 hours, peaking at 48 hours (P < 0.05), and then diminished gradually after 72 hours. The control group showed no significant changes in these parameters. Furthermore, a negative correlation was observed between RRI, histopathological grades, HIF-1α expression levels, and the levels of SCr and BUN. In contrast, RRI exhibited a positive correlation with these pathological scores and the levels of SCr and BUN. ROC curve analysis revealed that the combined predictive performance of IVIM and RRI was superior to that of individual parameters. Conclusion The synergistic application of IVIM and RRI techniques offers a non-invasive approach for early detection of renal damage after ioversol exposure and is a potent method for observing the pathophysiological shifts associated with early-stage CIN. Contrast-induced nephropathy Intravoxel incoherent motion Renal resistance index Acute kidney injury Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Introduction CIN, also recognized as contrast-induced acute kidney injury (CI-AKI), is characterized by a swift decline in renal function that manifests within days after CM administration. It ranks as the third leading cause of hospital-acquired acute kidney injury (AKI), surpassed only by reduced renal perfusion and the impact of nephrotoxic agents [ 1 , 2 ]. CIN is identified by a rise in SCr of 25% or an increase of 0.5 mg/dL within 1 to 3 days following iodine CM exposure [ 2 , 3 ]. The underlying pathophysiological mechanisms of CIN are complex, involving altered renal hemodynamics, the production of oxygen free radicals, and direct cytotoxicity [ 4 ]. Despite CIN being typically reversible, the proliferation of interventional procedures has heightened its frequency, particularly among vulnerable groups such as individuals with diabetes, chronic kidney disease (CKD), the elderly, and those with cardiovascular conditions [ 5 ]. While CIN occurs in less than 5% of patients with intact renal function, its prevalence escalates to 12–27% among those with pre-existing renal impairments [ 6 ]. Traditional diagnostic approaches, predominantly based on SCr, are hindered by their delayed response and limited sensitivity and specificity [ 7 ], underscoring the need for more effective diagnostic methods such as the combined use of IVIM-MRI and RRI. Traditional ADC, calculated using a mono-exponential model Sb/S0 = exp (-b×ADC), is a composite parameter that does not differentiate molecular diffusion from microvascular perfusion[ 8 , 9 ]. In contrast, IVIM analysis employs a biexponential model with a piecewise fitting approach to assess diffusion signal decay. This method separately fits the signal intensities within manually delineated ROIs for low b-values (0-200 s/mm²) and high b-values (> 200 s/mm²), yielding three distinct parameters: D, D ∗ , and f. This approach effectively distinguishes water molecular diffusion from blood microcirculation flow-related information. The calculation formula is expressed as: Sb/S0 = (1 – f) × exp(–b × D) + f × exp (–b × D * ) Where S0​ and Sb​ represent the signal intensities at b = 0 and a given b-value, respectively [ 8 ].The b-value refers to the diffusion sensitivity coefficient, which is used in diffusion-weighted imaging (DWI) to quantify the degree of diffusion weighting, with its unit being s/mm². D reflects the restricted diffusion capacity of water molecules within and between cells. A reduction in D is closely associated with microstructural damage, such as cellular edema and fibrosis. D ∗ characterizes capillary segment length and mean blood flow velocity. Changes in D ∗ are sensitive indicators of vascular constriction or endothelial dysfunction. f represents the ratio of the total fluid volume in capillaries and renal tubules to the total fluid volume per unit of renal tissue. A decline in f suggests impaired microcirculatory perfusion [ 10 ]. IVIM enables non-contrast assessment of tissue microcirculation and water diffusion dynamics [ 11 ], offering a non-invasive method to evaluate renal blood flow, glomerular filtration rate, and cortical and medullary microcirculation [ 12 ]. Studies have shown that IVIM can detect early microenvironmental and tissue deterioration in CKD and monitor varying degrees of renal function during kidney transplant recovery [ 13 , 14 , 15 ]. Post-CM administration, IVIM has demonstrated the ability to precisely detail diffusion characteristics and microvascular flow-related changes in renal tissues, providing valuable insights into the pathophysiology of CIN [ 16 ]. RRI, a critical metric in ultrasound Doppler examinations, assesses changes in the blood flow patterns of renal arcuate or interlobar arteries, which is crucial for appraising renal blood flow dynamics. An increase in RRI typically indicates elevated renal vascular resistance and disrupted hemodynamics. Given its advantages—non-invasiveness, real-time capability, repeatability, and accuracy—RRI is essential in assessing renal perfusion [ 17 ] and predicting AKI [ 18 ] and mortality in critically ill patients [ 19 ]. In this study, HIF-1α is used as a primary immunohistochemical antibody to validate our findings. HIF-1α, a key oxygen-dependent nuclear transcription factor under hypoxic conditions, mediates diverse physiological processes, including erythropoiesis, iron metabolism, and energy homeostasis regulation. Under hypoxia, HIF-1α remains stable and translocates to the nucleus, facilitating prompt detection and management of hypoxia. It plays an integral role in modulating oxidative stress and inflammatory responses and is a significant biomarker in renal injury studies related to CM exposure [ 20 ]. This study utilizes IVIM imaging and RRI to non-invasively monitor water diffusion, microcirculation, and hemodynamic alterations in rat renal tissues post-CM injection at an early stage. By integrating histopathological examinations, HIF-1α expression levels, and serum biochemical markers, we aim to elucidate the diagnostic value of these techniques for early CIN diagnosis. We propose that IVIM parameters and RRI will provide comprehensive insights into renal diffusion, microcirculatory flow-related information, and hemodynamic shifts, advancing early detection and intervention for CIN. Materials and methods Forty-two male SD rats, aged 6–8 weeks and weighing 200-250g, were obtained from the Animal Experiment Center of Beihua University. The rats were housed in a controlled environment at 22 ± 2°C with 55 ± 5% relative humidity and a 12-hour light-dark cycle. They had unrestricted access to food and water. The study was approved by the Medical Research Ethics Committee at Beihua University (Approval Number: 2024112604) and followed the National Institute of Health's Guide for the Care and Use of Laboratory Animals. The 42 rats were randomly divided into two groups: the CM group and the control group, each consisting of 21 rats. In the CM group, a CIN model was induced by injecting ioversol (concentration: 370 mg I/ml, 1.5 mg I/kg)[ 21 ] via tail vein. Rats in the control group received an equivalent volume of physiological saline via tail vein injection. IVIM-MRI and Doppler ultrasound assessments were performed at baseline (24 hours prior to CM administration), and at 1 hour, 24 hours, 48 hours, and 72 hours post-injection. A flowchart depicting the experimental procedure for the CM group is shown in Fig. 1 . Magnetic resonance imaging IVIM-MRI was conducted using a 3.0T whole-body scanner (uMR790, United Imaging Healthcare Co., Ltd., Shanghai). The rats were fasted for 12 hours before the procedure and anesthetized with an intraperitoneal injection of 0.3% pentobarbital sodium (2 mL/kg). Once anesthetized, the rats were positioned prone in a dedicated rat coil with their heads placed first. To minimize motion artifacts due to respiration and gastrointestinal movements, gauze was used to stabilize the abdomen. A single-shot spin-echo diffusion-weighted echo-planar imaging sequence was applied with nine b-values: 0, 10, 30, 50, 100, 200, 400, 600, and 800 s/mm 2 . Coronal scanning was performed to capture images of the right kidney in the coronal plane with the following parameters: TR = 2808 ms, TE = 84 ms, number of slices = 5, slice thickness = 2.0 mm, interslice gap = 10 mm, FOV = 80 mm × 80 mm, and matrix size = 128 × 128. After scanning, the raw DICOM images were transferred to a post-processing workstation (uWS-MR, R005) for analysis. ROIs in the CO, OM, and IM were manually delineated by a senior radiologist using T2WI images for reference (Fig. 2 ). For cortical measurements, three ROIs were placed at the upper, middle, and lower poles of the kidney, and the average of these three values was used as the final result. The same methodology was applied to measure parameters in the inner and outer medulla. Doppler ultrasound examination Ultrasound examinations were performed using the EPIQ7 high-resolution diagnostic system (Philips, USA) with a 12 MHz high-frequency linear array transducer, modulation depth of 3 cm, and a sampling volume of 2–4 mm, positioned at an angle of less than 60°. The rats were placed in a left lateral recumbent position under anesthesia, and the renal area was exposed and coated with coupling gel. The transducer was adjusted to capture longitudinal images of the kidneys. Peak systolic velocity (PSV) and end-diastolic velocity (EDV) of the arcuate and interlobar arteries were recorded. RRI was calculated using the formula: RRI = (PSV − EDV)/PSV. Each rat underwent three independent RI measurements at the upper, middle, and lower poles of the right kidney, with the final RRI value being the average of these measurements. Histological analysis After IVIM and ultrasound assessments, euthanasia was performed on three rats from each group at each time point via intraperitoneal overdose of 0.3% pentobarbital sodium (10 mL/kg). The kidneys were harvested, and the capsules were removed. Each kidney was longitudinally sectioned and immediately placed in 10% neutral formalin for fixation for 24 hours. After fixation, the tissues were dehydrated, cleared, and paraffin-embedded using an automatic dehydrator following standard protocols. Continuous 4 µm thick sections were obtained using a microtome. The sections were stained with hematoxylin, treated with a bluing reagent, and then stained with eosin. The slides were dehydrated and mounted with neutral gum. A pathologist with over 10 years of clinical experience conducted the pathological assessment, evaluating the samples in a blinded manner. For each slide, five non-overlapping fields were randomly selected, and morphological changes in the renal tissues were observed under a light microscope at 200x magnification. Criteria for evaluation included vacuolar degeneration of renal tubular epithelial cells, tubular dilation, necrosis, cast formation, inflammatory cell infiltration, and interstitial fibrosis. Upon completion of the study, all remaining rats were euthanized with a lethal intraperitoneal dose of 0.3% pentobarbital sodium (10 mL/kg). Renal injury severity was classified on a scale from 0 to 4 based on the criteria established by Ulusoy et al. [ 22 ]: 0 (normal renal tissue), 1 (renal injury 75%). The sections were placed in an antigen retrieval buffer (Tris/EDTA pH 9) and heated at 97°C for 30 minutes. After cooling to room temperature, FLEX Peroxidase Block blocking solution was added and incubated at 37°C for 5 minutes. The primary antibody, HIF-1α monoclonal antibody (dilution 1:100) (JieHao Biotechnology, HM-0091, China), was applied at 150 µL per section and incubated for 35 minutes. After washing, a secondary antibody (FLEX/HRP horseradish peroxidase) was added at 150 µL per section and incubated at 37°C for 20 minutes. DAB chromogen (300 µL) was then applied and incubated at 37°C for 10 minutes. The sections were counterstained with hematoxylin, dehydrated, and mounted with neutral gum. The expression of HIF-1α was observed and recorded using an optical microscope. Biochemical marker testing Before euthanizing the rats, tail vein blood samples (0.5-1.0 mL) were collected and allowed to stand at room temperature for 30 minutes to facilitate coagulation. The samples were then centrifuged at 3000 rpm for 5 minutes to obtain serum, which was analyzed for SCr and BUN levels using a fully automated biochemical analyzer (BECKMAN AU5800). All tests were conducted according to the reagent kit instructions and standard operating procedures, with testing performed by trained technical personnel. Statistical analysis All data were analyzed using SPSS 27.0 software (SPSS Inc, Chicago, IL, USA). Continuous variables are expressed as mean ± standard deviation (mean ± SDs). Between-group comparisons were conducted using one-way analysis of variance (ANOVA), with post-hoc pairwise comparisons using the LSD test. Comparisons of different time points within groups were analyzed using repeated measures ANOVA. Correlation analyses were conducted using the Spearman rank correlation test to explore relationships between D, D * , f, and ADC with pathological injury scores and HIF-1α expression, as well as the correlation between RRI and pathological injury scores, HIF-1α expression, SCr, and BUN. ROC curves were plotted to assess the diagnostic efficacy of IVIM and RRI for CIN by analyzing the area under the curve. A p-value of < 0.05 was considered statistically significant. Results In this study, all rats successfully underwent IVIM and ultrasound examinations. The D, D * , f, and ADC parameter maps were obtained by fitting the acquired diffusion-weighted data to both the biexponential and monoexponential functions. The measured values for D, D * , f, and ADC were recorded in a standardized datasheet ( Figure 3, Table 1 ). Doppler ultrasound clearly captured longitudinal pulsed-wave spectral images of the kidneys, and RRI data were fully documented at all time points ( Figure 4, Table 2 ). Following CM administration, notable changes were observed in the IVIM parameters at various time points. Compared to baseline measurements, the values of D, D * , f, and ADC in the CO, OM, and IM showed significant reductions at 1, 24, and 48 hours (P < 0.05), reaching their lowest levels at 48 hours ( Figure 5 ). A slight recovery was detected at 72 hours, though values remained lower than baseline and those recorded 1 hour after contrast injection. In contrast, no significant changes were observed in the control group at any time point (P > 0.05). Ultrasound results demonstrated a gradual increase in RRI values following CM injection (P < 0.05), with a peak at 48 hours (maximum value of 0.66, Figure 6 ). At 72 hours, RRI values decreased but remained above baseline levels (P 0.05). Histological analysis To confirm the accuracy of the imaging results, histological examinations were conducted. Hematoxylin and eosin staining revealed no significant pathological changes at 1 hour post-CM injection. At 24 hours, renal tubular epithelial cell swelling and vacuolar degeneration were observed, along with mild tubular dilation. The most pronounced renal injury occurred at 48 hours, characterized by extensive dilation of renal tubular epithelial cells, some of which exhibited necrosis and sloughing. Inflammatory cell infiltration was observed in the interstitial tissue, accompanied by chronic hemorrhage and hemosiderin deposition. By 72 hours, the tubular dilation and vacuolation had significantly reduced, although complete recovery to normal structure had not been achieved ( Figure 7 ). The control group exhibited normal kidney tissue structure throughout the study. According to the scoring system established by Ulusoy et al. [19], the CM group showed the highest renal injury score at 48 hours (3.09 ± 0.18), which was statistically significant compared to baseline (P < 0.05) ( Table 3 ). Immunohistochemical staining revealed positive HIF-1α expression in the nuclei of renal tubular epithelial cells as early as 1 hour post-injection. The most significant expression was observed at 48 hours, where the staining intensity peaked ( Figure 8 ). By 72 hours, staining intensity decreased but remained above baseline levels. No significant changes in HIF-1α expression were noted at any time point in the control group (P > 0.05) ( Table 3 ). Biochemical analysis In the CM group, SCr levels peaked at 72 hours post-CM injection (P 0.05). BUN levels were significantly elevated at both 48 and 72 hours (P < 0.05 compared to baseline), with a peak at 48 hours and a slight reduction at 72 hours compared to 48 hours. No significant changes in SCr or BUN were detected at any time point in the control group (P > 0.05) ( Table 4 ). Correlation analysis of IVIM parameters with histopathology and HIF-1α expression The values of D, D * , f, and ADC for the CO, OM, and IM exhibited significant negative correlations with histopathological scores and HIF-1α expression levels ( Table 5 ). The correlation coefficients are as follows: For the CO, the correlations between D, D * , f, and ADC with histopathological scores were: (r = -0.755, -0.628, -0.787, -0.804, all p < 0.001). The correlation with HIF-1α scores was: (r = -0.774, -0.647, -0.786, -0.835, all p < 0.001). For the OM, the correlations with histopathological scores were: (r = -0.779, -0.822, -0.644, -0.771, all p < 0.001), and with HIF-1α scores: (r = -0.778, -0.818, -0.649, -0.754, all p < 0.001). For the IM, the correlations with histopathological scores were: (r = -0.734, -0.778, -0.804, -0.762, all p < 0.001), and with HIF-1α scores: (r = -0.769, -0.731, -0.803, -0.722, all p < 0.001). Correlation analysis of IVIM parameters with RRI and blood biomarkers The values of D, D * , f, and ADC for the CO, OM, and IM exhibited significant negative correlations with RRI (Figure 9) .The correlation coefficients are as follows: For the CO, the correlations between D, D * , f, and ADC with RRI were: (r = -0.729, -0.867, -0.816, -0.751, all p < 0.001). For the OM, the correlations between D, D * , f, and ADC with RRI were: (r = -0.824, -0.825, -0.823, -0.717, all p < 0.001). For the IM, the correlations between D, D * , f, and ADC with RRI were: (r = -0.778, -0.681, -0.744, -0.830, all p < 0.001). Correlation analysis of RRI with histopathology, HIF-1α scores, and biochemical indicators RRI demonstrated a strong positive correlation with histopathological scores, HIF-1α expression, SCr, and BUN, with correlation coefficients of (r = 0.739, p < 0.001), (r = 0.769, p < 0.001), (r = 0.665, p < 0.001), and (r = 0.646, p < 0.001), respectively ( Figure 10 ). Predictive value of IVIM parameters and RRI for CIN The ROC curve analysis revealed AUC values for IVIM and RRI of 0.820 and 0.825, respectively, in detecting CIN. The combined prediction model achieved an AUC of 0.915 (95% CI: 0.794–1.000), with a sensitivity of 90.00% and specificity of 90.00%, demonstrating superior diagnostic performance compared to individual parameters (Figure 11) . Discussion This study systematically examined the changes in IVIM parameters and RRI at various time points following CM injection, alongside correlation analyses with histological and biochemical markers. The results show that IVIM parameters and RRI can sensitively reflect pathophysiological changes in the kidneys, often earlier than traditional biochemical markers. These findings have significant clinical implications, offering a multidimensional experimental foundation for the early detection and accurate diagnosis of CIN. In this study, the IVIM parameters (D, D * , f) and ADC of the CO, OM, and IM in rats progressively decreased at different time points following CM injection, reaching their lowest values at 48 hours. This pattern suggests significant suppression of renal microcirculation flow-related information and the diffusion capacity of water molecules. Although partial recovery was observed after 72 hours, the parameters did not return to baseline, indicating that the tissue was in a partial repair phase but still showing potential damage. These results align with previous studies by Wang et al. [ 20 ] and Feng et al. [ 13 ]. The D parameter reflects the diffusion capacity of water molecules within tissue. In this study, D values in all anatomical regions began to decrease at 1 hour, likely due to the high viscosity and osmotic pressure of CM, which restrict water molecule diffusion and may cause epithelial cell edema and renal tubular damage [ 16 , 23 ]. Some studies have indicated that D is a reliable indicator for detecting AKI [ 24 ] and assessing CI-AKI [ 23 ]. D * and f represent quantitative parameters of tissue flow-related information. D * reflects the capillary segment length and average blood flow velocity within tissues, while f denotes the ratio of the total fluid volume in capillaries and renal tubules per unit volume to the total liquid content per unit volume of renal tissue. The reduction in D * and f values is associated with multiple pathophysiological cascades: 1. Hemodynamic impairment: The hyperosmolarity and viscous effects of CM induce renal tubular epithelial cell swelling and luminal dilation, reducing capillary blood flow velocity (manifested as decreased D * values) and causing regional hypoperfusion [ 13 , 20 ]. Compensatory vasodilation is triggered, but CM's direct cytotoxic effects through reactive oxygen species and apoptotic pathways [ 25 ] disrupt the balance of vasoactive mediators (endothelin, adenosine, and nitric oxide), leading to sustained renal vasoconstriction [ 16 ]. Although luminal dilation may transiently increase resting tubular fluid volume, the persistent vasoconstriction-induced reduction in effective blood flow is a critical factor in f value decline [ 13 ]. 2. Microstructural damage: Ischemia-reperfusion injury induces interstitial edema, compressing capillary beds, while tubular casts formed by necrotic debris obstruct fluid flow [ 23 ], further reducing the proportion of mobile fluid reflected by f values. The ischemic-hypoxic state activates the tubuloglomerular feedback mechanism, initiating a cycle of vasoconstriction → GFR reduction → aggravated ischemia → cellular damage [ 26 ], which exacerbates the decline in D * and f values. Our study confirmed significant reductions in D * and f values across all time points, corroborated by pathological findings. This study observed that the ADC value reached its lowest point at 48 hours post-contrast injection, which was closely related to reductions in D * , f, and D. As an imaging parameter reflecting both water molecular diffusion and microcirculatory flow-related information [ 9 ], the dynamic changes in ADC values suggest the following pathological mechanisms: 1. CM induces renal tubular epithelial cell edema and microstructural damage through its hyperosmolar properties and cytotoxicity, restricting water molecule diffusion. 2. Increased renal vascular resistance and hemodynamic disturbances, caused by afferent arteriole constriction and capillary blood flow deceleration, significantly reduce microcirculatory perfusion in the renal parenchyma [ 10 , 27 ]. Our findings revealed significantly lower ADC values in the OM and IM compared to CO, likely due to the medulla’s inherent low-perfusion characteristics and increased susceptibility to ischemic-hypoxic injury [ 28 ]. Pathological examinations showed characteristic changes, including tubular cell edema and inflammatory infiltration, further validating the correlation between ADC reduction and cellular edema/microcirculatory dysfunction. These findings align with Le et al.'s conclusions [ 9 ], which suggest that ADC dynamics reflect both cellular edema and ischemic injury severity, serving as biomarkers for renal injury progression and prognosis. Recent studies [ 29 ] also confirm that quantitative ADC analysis provides objective imaging evidence for evaluating renal tissue hypoxia and ischemia-reperfusion injury. Doppler ultrasound provides a practical, effective, safe, and accurate method for assessing renal blood flow perfusion. The RRI has significant clinical value in the early diagnosis and prognostic assessment of various renal diseases, including diabetic nephropathy [ 30 ], CKD [ 31 ], and kidney transplantation [ 32 ]. A study by Xu et al. [ 33 ] identified RRI as an independent predictor of CIN in patients undergoing percutaneous coronary intervention. Interestingly, in this study, the CM group of rats showed an increase in RRI values at 1 hour post-CM injection, peaking at 48 hours before slightly declining, yet remaining above baseline levels. This indicates that CM induced an increase in renal vascular resistance. The elevation of RRI may be attributed to several factors: first, the high viscosity and hyperosmolarity of CM can cause tubular damage and endothelial dysfunction, leading to increased renal arterial resistance [ 16 , 23 , 34 ]. Second, CM-induced excessive stimulation of the tubule-glomerular feedback mechanism may increase adenosine secretion, causing constriction of afferent arterioles and further contributing to the rise in renal vascular resistance [ 27 ]. This finding aligns with the trends observed in D * and f values. In our study, RRI showed a significant positive correlation with histopathological damage scores, HIF-1α expression levels, SCr, and BUN (r = 0.739, 0.769, 0.665, 0.646, p < 0.001). These results support the notion that RRI is an effective indicator for assessing hemodynamic changes in the kidneys following CM injection in rats. Wybraniec et al. [ 35 ] reported that the sensitivity of RRI for predicting CI-AKI at 48 hours was 78%, with specificity of 81% in patients undergoing coronary angiography or percutaneous coronary intervention, in univariate analysis, both RRI and the pulsatility index were identified as predictors of CI-AKI; however, in multivariate models, only RRI remained an independent predictor of CI-AKI incidence. RRI is a highly sensitive parameter for kidney disease, providing valuable insights into the pathophysiology of native or transplanted kidneys. It serves as an important metric for evaluating renal function status and reflects the pathological process of renal functional decline in patients with AKI [ 36 ]. It is noteworthy that in this study, early changes in IVIM parameters and RRI occurred significantly earlier than changes in SCr and BUN. SCr levels in the CM group of rats showed a significant increase at 72 hours post-CM injection, while BUN levels elevated significantly at 48 hours. This indicates that SCr and BUN have insufficient sensitivity for the early diagnosis of CIN. As a key indicator of kidney function, SCr is influenced not only by the secretion from renal tubular epithelial cells but also by various factors, such as individual muscle metabolism, body weight, ethnicity, age, and gender [ 37 ]. To comprehensively validate the scientific rigor and reliability of this research, HIF-1α was selected as a critical immunohistochemical marker. This study elucidated the mechanisms by which CM induces tubular injury and localized hypoxia, leading to high expression of HIF-1α in the context of CIN [ 38 ]. A significant upregulation of HIF-1α expression was observed following CM injection, peaking at 48 hours. This trend closely aligns with the dynamic changes observed in IVIM parameters and RRI, providing strong evidence for the scientific value of these imaging markers in accurately reflecting pathological changes in renal tissue. This study conducted a longitudinal analysis of changes in critical IVIM parameters and RRI across various anatomical regions of the kidneys before and after CM injection, integrating histological and biochemical indicators to evaluate the diagnostic value of these methods in CIN. Compared to single indicators, the combined application of multiple indicators provides a more comprehensive and accurate reflection of renal function changes. IVIM offers quantitative information on microcirculatory flow-related information and water molecule diffusion, while RRI enables real-time observation of renal hemodynamic changes. The complementary advantages of these methods provide a multidimensional view of renal function changes and their potential pathophysiological mechanisms following CM injection. Histopathological damage and HIF-1α expression serve as gold standards, further validating the reliability of these imaging markers in monitoring the pathophysiological changes associated with CIN. This innovative research is expected to contribute to the development of a precise, non-invasive imaging diagnostic method for clinical assessment and prediction of CIN. This study has certain limitations: Both IVIM and ultrasound images were susceptible to interference from rat respiratory movements. Although the abdomen was secured with gauze to minimize artifacts, residual effects still impacted image quality and parameter measurement accuracy. The experimental subjects were limited to rats, suggesting the need for future studies involving multiple species. Additionally, challenges such as low signal-to-noise ratio, insufficient low b-value acquisitions, and suboptimal fitting constraints may compromise the stability and reliability of IVIM parameter estimation and image quality. Conclusion The results of this study demonstrate that significant reductions in IVIM parameters and increases in RRI are observable as early as 1 hour after CM injection in the early stages of CIN, reaching peak levels at 48 hours. These changes are strongly correlated with histopathological damage, HIF-1α expression, and biochemical indicators. This suggests that IVIM and RRI are effective methods for monitoring the early pathophysiological changes associated with CIN. Abbreviations IVIM Intravoxel incoherent motion RRI Renal resistance index CIN DWI Contrast-induced nephropathy Diffusion-weighted imaging SD Sprague-Dawley CM Contrast media CO Cortex OM Outer medulla IM Inner medulla D Diffusion coefficient D * Pseudo-diffusion coefficien； f Perfusion fraction ADC Apparent diffusion coefficient HIF-1α Hypoxia-inducible factor-1α SCr Serum creatinine BUN Blood urea nitrogen AKI Acute kidney injury CI-AKI Contrast-induced acute kidney injury CKD Chronic kidney disease ROI Region of interest PSV Peak systolic velocity EDV End-diastolic velocity ROC AUC Receiver operating characteristic Area under the curve Declarations Authors’ contributions JLC and ZQW contributed to the conceptualization and methodology. JLC and XYS contributed to the data collection. ZQW and ZW contributed to the statistical analysis. JLC wrote the main manuscript text. ZQW and ZW made the first revision of the manuscript. All authors reviewed the manuscript. Funding No funding. Availability of data and materials The dataset supporting the conclusions of this article is included within the article (and its additional file) Competing interests The authors declare that they have no competing interests. Ethics approval and consent to participate No human samples or clinical data were included in this study，hence consent to participate is not applicable. All animal procedures were conducted according to the National Institute of Health Guide for the Care and Use of Laboratory Animals and approved by the University of Beihua Ethics Committee (approval number 2024112604). Consent for publication Not applicable. Author details 1 College of Clinical Medicine, Beihua University, Jilin, China. 2 Department of Ultrasound, Siping Central People’s Hospital, Siping, China. 3 Department of Radiology, Jilin Central Hospital, Jilin, China. 4 Department of Radiology, The Affiliated Hospital of BeiHua University, Jilin, China. 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The predictive value of the renal resistive index for contrast-induced nephropathy in patients with acute coronary syndrome. BMC Cardiovasc Disord. 2019;19(1):36. Published 2019 Feb 11. 10.1186/s12872-019-1017-3 Sendeski M, Patzak A, Persson PB. Constriction of the vasa recta, the vessels supplying the area at risk for acute kidney injury, by four different iodinated contrast media, evaluating ionic, nonionic, monomeric and dimeric agents. Invest Radiol. 2010;45(8):453–7. 10.1097/RLI.0b013e3181d77eed . Wybraniec MT, Chudek J, Bożentowicz-Wikarek M, Mizia-Stec K. Prediction of contrast-induced acute kidney injury by early post-procedural analysis of urinary biomarkers and intra-renal Doppler flow indices in patients undergoing coronary angiography. J Interv Cardiol. 2017;30(5):465–72. 10.1111/joic.12404 . Wang L, Wang X. Diagnostic value of multi-parameter ultrasound evaluation in sepsis complicated by acute kidney injury. Ren Fail. 2024;46(1):2313861. 10.1080/0886022X.2024.2313861 . Shams E, Mayrovitz HN, Contrast-Induced Nephropathy. A Review of Mechanisms and Risks. Cureus. 2021;13(5):e14842. 10.7759/cureus.14842 . Published 2021 May 4. Wang Y, Zhang X, Wang B, et al. Evaluation of Renal Pathophysiological Processes Induced by an Iodinated Contrast Agent in a Diabetic Rabbit Model Using Intravoxel Incoherent Motion and Blood Oxygenation Level-Dependent Magnetic Resonance Imaging. Korean J Radiol. 2019;20(5):830–43. 10.3348/kjr.2018.0757 . Tables Table 1. Average values of D(x10 -3 mm 2 /s)、D * (x10 -3 mm 2 /s)、f(%)、ADC(x10 -3 mm 2 /s) at different time points in the contrast media group Group Baseline 1h 24h 48h 72h D(x10 -3 mm 2 /s) CO 1.64±0.02 1.58±0.02 * 1.43±0.04 * 1.34±0.04 * 1.46±0.03 * OM 1.68±0.05 1.59±0.04 * 1.44±0.05 * 1.36±0.04 * 1.50±0.03 * IM 1.73±0.04 1.67±0.04 * 1.52±0.04 * 1.42±0.04 * 1.56±0.05 * D * (x10 -3 mm 2 /s) CO 8.98±0.52 7.10±0.37 * 5.89±0.50 * 4.44±0.61 * 6.54±0.42 * OM 9.05±0.50 6.87±0.42 * 5.70±0.40 * 4.27±0.51 * 6.36±0.45 * IM 8.34±0.23 7.18±0.64 * 5.95±0.58 * 4.60±0.52 * 6.63±0.70 * f(%) CO 29.87±0.72 25.67±1.23 * 22.57±0.52 * 19.34±0.78 * 24.26±0.48 * OM 28.63±0.73 25.37±1.04 * 21.89±1.56 * 19.43±1.11 * 23.88±0.93 * IM 28.34±0.88 25.47±1.39 * 22.81±0.91 * 20.02±1.15 * 24.43±0.90 * ADC(x10 -3 mm 2 /s) CO 1.68±0.05 1.61±0.04 * 1.50±0.08 * 1.37±0.07 * 1.53±0.07 * OM 1.72±0.03 1.65±0.03 * 1.50±0.06 * 1.34±0.05 * 1.55±0.06 * IM 1.66±0.05 1.57±0.06 * 1.44±0.08 * 1.30±0.05 * 1.51±0.07 * Note：CO=Cortex；OM=Outer medulla；IM=Inner medulla * Compared to baseline, P < 0.05. The inter-group and intra-group differences were analyzed using Analysis of Variance (ANOVA) and Repeated Measures ANOVA, respectively. Table 2. Average values of RRI at different time points in the contrast media group Group Baseline 1h 24h 48h 72h RRI 0.45±0.01 0.51±0.02 * 0.58±0.01 * 0.64±0.01 * 0.55±0.01 * Note：Compared to baseline, P < 0.05. The inter-group and intra-group differences were analyzed using Analysis of Variance (ANOVA) and Repeated Measures ANOVA, respectively. Table 3. Renal injury scores and HIF-1α expression scores at different time points before and after the injection of contrast media baseline 1h 24h 48h 72h Renal injury score 0.00±0.00 0.78±0.21 2.04±0.26 3.09±0.18 1.58±0.21 HIF-1α expression score 0.00±0.00 1.00±0.17 2.24±0.19 3.20±0.20 1.89±0.23 Table 4. Average values of SCr (mol/L) and BUN (µmol/L) at different time points in the contrast media group Group Baseline 1h 24h 48h 72h SCr（mol/L） 20.73±0.96 21.27±0.75 23.00±0.39 24.82±0.44 30.76±0.98 * BUN（umol/L） 3.94±0.09 4.09±0.13 4.32±0.07 4.95±0.07 * 4.72±0.09 * *Compared to baseline, P < 0.05. Table 5 ． Correlation analysis of IVIM parameters with renal injury scores and HIF-1α expression scores Renal injury score HIF-1α expression score Group r p r p D CO -0.755 <0.001 -0.774 <0.001 D * CO -0.628 <0.001 -0.647 <0.001 f CO -0.787 <0.001 -0.786 <0.001 ADC CO -0.804 <0.001 -0.835 <0.001 D OM -0.779 <0.001 -0.778 <0.001 D * OM -0.822 <0.001 -0.818 <0.001 f OM -0.644 <0.001 -0.649 <0.001 ADC OM -0.771 <0.001 -0.754 <0.001 D IM -0.743 <0.001 -0.769 <0.001 D * IM -0.778 <0.001 -0.731 <0.001 f IM -0.804 <0.001 -0.803 <0.001 ADC IM -0.762 <0.001 -0.722 <0.001 Note：CO=Cortex；OM=Outer medulla；IM=Inner medulla. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 18 Jul, 2025 Read the published version in BMC Nephrology → Version 1 posted Editorial decision: Revision requested 05 May, 2025 Reviews received at journal 01 May, 2025 Reviewers agreed at journal 25 Apr, 2025 Reviewers agreed at journal 24 Apr, 2025 Reviewers invited by journal 22 Apr, 2025 Submission checks completed at journal 22 Apr, 2025 First submitted to journal 16 Apr, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5792456","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":446576391,"identity":"c5468320-7a38-4a1b-94fd-fd2e584beb77","order_by":0,"name":"Jinlong Chen","email":"","orcid":"","institution":"Beihua University","correspondingAuthor":false,"prefix":"","firstName":"Jinlong","middleName":"","lastName":"Chen","suffix":""},{"id":446576398,"identity":"2d2075c1-b244-4b61-bec0-71938a856ade","order_by":1,"name":"Xiaoyu Song","email":"","orcid":"","institution":"Beihua University","correspondingAuthor":false,"prefix":"","firstName":"Xiaoyu","middleName":"","lastName":"Song","suffix":""},{"id":446576399,"identity":"94e3837d-66d8-42b5-a2bc-7ac60b863a5e","order_by":2,"name":"Zhao Wang","email":"","orcid":"","institution":"Siping Central People’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Zhao","middleName":"","lastName":"Wang","suffix":""},{"id":446576401,"identity":"057d279e-3004-414f-a08d-0767ecce5bed","order_by":3,"name":"Zhiqiang Wang","email":"data:image/png;base64,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","orcid":"","institution":"The Affiliated Hospital of BeiHua University","correspondingAuthor":true,"prefix":"","firstName":"Zhiqiang","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2025-01-09 02:08:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5792456/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5792456/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12882-025-04329-3","type":"published","date":"2025-07-18T15:57:30+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":81541143,"identity":"b5067b8c-3028-4604-8d4c-70fedb6ff918","added_by":"auto","created_at":"2025-04-28 11:14:08","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":105916,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of the contrast media group\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5792456/v1/256b1161413a416873255cc0.jpg"},{"id":81542694,"identity":"70e90c1b-5411-4745-80d5-0cb16512545b","added_by":"auto","created_at":"2025-04-28 11:22:08","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":135299,"visible":true,"origin":"","legend":"\u003cp\u003eRegions of interest images of rat kidneys：a. A representative T2-weighted image; b. An enlarged view of the right kidney T2-weighted image, showing three regions of interest (ROIs): the green dashed line indicates the cortex region of interest (CO-ROI), the blue dashed line indicates the outer medulla region of interest (OM-ROI), and the red dashed line indicates the inner medulla region of interest (IM-ROI); c. An anatomical diagram of the right kidney, showing the corresponding cortex, outer medulla, and inner medulla anatomical divisions\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5792456/v1/c7bc32f84310262c59493381.jpg"},{"id":81541149,"identity":"74c6fafd-56cb-409a-a8cc-b8ad01948d2b","added_by":"auto","created_at":"2025-04-28 11:14:08","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1296756,"visible":true,"origin":"","legend":"\u003cp\u003eCoronal cross-sectional parameter images of renal IVIM in the contrast media group of rats at baseline and at 1 hour, 24 hours, 48 hours, and 72 hours after contrast media injection.\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5792456/v1/48b29025e766a0240d21c779.jpg"},{"id":81541148,"identity":"43363e09-1e49-4b1c-80b9-e2a56745cda9","added_by":"auto","created_at":"2025-04-28 11:14:08","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":203193,"visible":true,"origin":"","legend":"\u003cp\u003eDoppler ultrasound images of blood flow signals in the contrast media group of rats, as well as renal resistance index value images at 1 hour, 24 hours, 48 hours, and 72 hours after contrast media injection. RRI =（peak-systolic velocity − end-diastolic velocity)/peak-systolic velocity\u003c/p\u003e","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5792456/v1/eba6e54237d8fc0d1fe0c7b7.jpg"},{"id":81541151,"identity":"90ac3612-9f29-442a-bfee-9478527ce9de","added_by":"auto","created_at":"2025-04-28 11:14:08","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":225502,"visible":true,"origin":"","legend":"\u003cp\u003eD, D\u003csup\u003e*\u003c/sup\u003e, f and ADC values in the cortex, outer medulla, and inner medulla at each time point for the contrast media group and the control group. The changes in IVIM parameters in the CM group were most significant at 48 hours. **P \u0026lt; 0.05\u003c/p\u003e","description":"","filename":"Figure5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5792456/v1/ba50ad6fe2ae602c0f4e78eb.jpg"},{"id":81541146,"identity":"9296e020-e67c-48b6-8d9d-2b2769e0aa05","added_by":"auto","created_at":"2025-04-28 11:14:08","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":60244,"visible":true,"origin":"","legend":"\u003cp\u003eThe RRI values at different time points for the contrast media group and the control group. The changes in RRI in the contrast media group were most significant at 48 hours. **P \u0026lt; 0.05\u003c/p\u003e","description":"","filename":"Figure6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5792456/v1/726bea4d74d6827f8ee2a224.jpg"},{"id":81541156,"identity":"12f5529c-356d-4c23-aeca-b0d98a94d094","added_by":"auto","created_at":"2025-04-28 11:14:08","extension":"jpg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":565789,"visible":true,"origin":"","legend":"\u003cp\u003eHematoxylin-eosin stain images of the renal cortex and medulla at different time points after contrast media injection. The main observations included vacuolar degeneration of tubular epithelial cells (black arrow), infiltration of inflammatory cells in the interstitium (green arrow), and proliferation of some capillary endothelial cells (blue arrow). The renal injury score was most pronounced at 48 hours\u003c/p\u003e","description":"","filename":"Figure7.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5792456/v1/5c63cd61f717c867ad54bbfa.jpg"},{"id":81541154,"identity":"b4db0c57-2dcb-4eb9-a6b5-68ff1d4a6628","added_by":"auto","created_at":"2025-04-28 11:14:08","extension":"jpg","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":379373,"visible":true,"origin":"","legend":"\u003cp\u003eAfter contrast media injection, the expression of HIF-1α in the cortex and medulla gradually increased, with the most significant nuclear staining observed at 48 hours (black arrow)\u003c/p\u003e","description":"","filename":"Figure8.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5792456/v1/5eb74ebbdcaaf8275e2fc28a.jpg"},{"id":81541157,"identity":"04e913bd-5cf7-434d-b241-151ad62fe7fc","added_by":"auto","created_at":"2025-04-28 11:14:08","extension":"jpg","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":185415,"visible":true,"origin":"","legend":"\u003cp\u003eThe IVIM parameters are significantly negatively correlated with RRI\u003c/p\u003e","description":"","filename":"Figure9.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5792456/v1/132f6de630d221a1f9ba124a.jpg"},{"id":81541160,"identity":"43f9f4a9-03ce-46f2-8813-552c7bc596b9","added_by":"auto","created_at":"2025-04-28 11:14:08","extension":"jpg","order_by":10,"title":"Figure 10","display":"","copyAsset":false,"role":"figure","size":95333,"visible":true,"origin":"","legend":"\u003cp\u003eRRI is significantly positively correlated with renal injury scores, HIF-1α expression, SCr, and BUN\u003c/p\u003e","description":"","filename":"Figure10.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5792456/v1/3025adcffc93068fc7dcea4c.jpg"},{"id":81542697,"identity":"63d32ed7-3b50-4fba-9809-8e4df442cfb7","added_by":"auto","created_at":"2025-04-28 11:22:08","extension":"jpg","order_by":11,"title":"Figure 11","display":"","copyAsset":false,"role":"figure","size":54321,"visible":true,"origin":"","legend":"\u003cp\u003eThe ROC curves of IVIM, RRI, SCr, and the combined IVIM and RRI index. The combined index shows higher efficacy in predicting CIN than individual indicators\u003c/p\u003e","description":"","filename":"Figure11.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5792456/v1/209a53049353f682dc9e2f22.jpg"},{"id":88505963,"identity":"b87f8534-e3d8-46fc-b475-462465f56b50","added_by":"auto","created_at":"2025-08-07 07:29:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4317831,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5792456/v1/6e234d05-99aa-4ee5-976d-b0dcf0948f76.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Experimental Study of Intravoxel Incoherent Motion Diffusion Imaging Combined with Ultrasound Renal Resistance Index in Contrast-Induced Nephropathy","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCIN, also recognized as contrast-induced acute kidney injury (CI-AKI), is characterized by a swift decline in renal function that manifests within days after CM administration. It ranks as the third leading cause of hospital-acquired acute kidney injury (AKI), surpassed only by reduced renal perfusion and the impact of nephrotoxic agents [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. CIN is identified by a rise in SCr of 25% or an increase of 0.5 mg/dL within 1 to 3 days following iodine CM exposure [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The underlying pathophysiological mechanisms of CIN are complex, involving altered renal hemodynamics, the production of oxygen free radicals, and direct cytotoxicity [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite CIN being typically reversible, the proliferation of interventional procedures has heightened its frequency, particularly among vulnerable groups such as individuals with diabetes, chronic kidney disease (CKD), the elderly, and those with cardiovascular conditions [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. While CIN occurs in less than 5% of patients with intact renal function, its prevalence escalates to 12\u0026ndash;27% among those with pre-existing renal impairments [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Traditional diagnostic approaches, predominantly based on SCr, are hindered by their delayed response and limited sensitivity and specificity [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], underscoring the need for more effective diagnostic methods such as the combined use of IVIM-MRI and RRI.\u003c/p\u003e \u003cp\u003eTraditional ADC, calculated using a mono-exponential model Sb/S0\u0026thinsp;=\u0026thinsp;exp (-b\u0026times;ADC), is a composite parameter that does not differentiate molecular diffusion from microvascular perfusion[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In contrast, IVIM analysis employs a biexponential model with a piecewise fitting approach to assess diffusion signal decay. This method separately fits the signal intensities within manually delineated ROIs for low b-values (0-200 s/mm\u0026sup2;) and high b-values (\u0026gt;\u0026thinsp;200 s/mm\u0026sup2;), yielding three distinct parameters: D, D\u003csup\u003e\u0026lowast;\u003c/sup\u003e, and f. This approach effectively distinguishes water molecular diffusion from blood microcirculation flow-related information. The calculation formula is expressed as:\u003c/p\u003e \u003cp\u003eSb/S0\u0026thinsp;=\u0026thinsp;(1 \u0026ndash; f) \u0026times; exp(\u0026ndash;b \u0026times; D)\u0026thinsp;+\u0026thinsp;f \u0026times; exp (\u0026ndash;b \u0026times; D\u003csup\u003e*\u003c/sup\u003e)\u003c/p\u003e \u003cp\u003eWhere S0​ and Sb​ represent the signal intensities at b\u0026thinsp;=\u0026thinsp;0 and a given b-value, respectively [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].The b-value refers to the diffusion sensitivity coefficient, which is used in diffusion-weighted imaging (DWI) to quantify the degree of diffusion weighting, with its unit being s/mm\u0026sup2;. D reflects the restricted diffusion capacity of water molecules within and between cells. A reduction in D is closely associated with microstructural damage, such as cellular edema and fibrosis. D\u003csup\u003e\u0026lowast;\u003c/sup\u003e characterizes capillary segment length and mean blood flow velocity. Changes in D\u003csup\u003e\u0026lowast;\u003c/sup\u003e are sensitive indicators of vascular constriction or endothelial dysfunction. f represents the ratio of the total fluid volume in capillaries and renal tubules to the total fluid volume per unit of renal tissue. A decline in f suggests impaired microcirculatory perfusion [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. IVIM enables non-contrast assessment of tissue microcirculation and water diffusion dynamics [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], offering a non-invasive method to evaluate renal blood flow, glomerular filtration rate, and cortical and medullary microcirculation [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eStudies have shown that IVIM can detect early microenvironmental and tissue deterioration in CKD and monitor varying degrees of renal function during kidney transplant recovery [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Post-CM administration, IVIM has demonstrated the ability to precisely detail diffusion characteristics and microvascular flow-related changes in renal tissues, providing valuable insights into the pathophysiology of CIN [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRRI, a critical metric in ultrasound Doppler examinations, assesses changes in the blood flow patterns of renal arcuate or interlobar arteries, which is crucial for appraising renal blood flow dynamics. An increase in RRI typically indicates elevated renal vascular resistance and disrupted hemodynamics. Given its advantages\u0026mdash;non-invasiveness, real-time capability, repeatability, and accuracy\u0026mdash;RRI is essential in assessing renal perfusion [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] and predicting AKI [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] and mortality in critically ill patients [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this study, HIF-1α is used as a primary immunohistochemical antibody to validate our findings. HIF-1α, a key oxygen-dependent nuclear transcription factor under hypoxic conditions, mediates diverse physiological processes, including erythropoiesis, iron metabolism, and energy homeostasis regulation. Under hypoxia, HIF-1α remains stable and translocates to the nucleus, facilitating prompt detection and management of hypoxia. It plays an integral role in modulating oxidative stress and inflammatory responses and is a significant biomarker in renal injury studies related to CM exposure [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study utilizes IVIM imaging and RRI to non-invasively monitor water diffusion, microcirculation, and hemodynamic alterations in rat renal tissues post-CM injection at an early stage. By integrating histopathological examinations, HIF-1α expression levels, and serum biochemical markers, we aim to elucidate the diagnostic value of these techniques for early CIN diagnosis. We propose that IVIM parameters and RRI will provide comprehensive insights into renal diffusion, microcirculatory flow-related information, and hemodynamic shifts, advancing early detection and intervention for CIN.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003eForty-two male SD rats, aged 6\u0026ndash;8 weeks and weighing 200-250g, were obtained from the Animal Experiment Center of Beihua University. The rats were housed in a controlled environment at 22\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u0026deg;C with 55\u0026thinsp;\u0026plusmn;\u0026thinsp;5% relative humidity and a 12-hour light-dark cycle. They had unrestricted access to food and water. The study was approved by the Medical Research Ethics Committee at Beihua University (Approval Number: 2024112604) and followed the National Institute of Health's Guide for the Care and Use of Laboratory Animals.\u003c/p\u003e \u003cp\u003eThe 42 rats were randomly divided into two groups: the CM group and the control group, each consisting of 21 rats. In the CM group, a CIN model was induced by injecting ioversol (concentration: 370 mg I/ml, 1.5 mg I/kg)[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] via tail vein. Rats in the control group received an equivalent volume of physiological saline via tail vein injection. IVIM-MRI and Doppler ultrasound assessments were performed at baseline (24 hours prior to CM administration), and at 1 hour, 24 hours, 48 hours, and 72 hours post-injection. A flowchart depicting the experimental procedure for the CM group is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eMagnetic resonance imaging\u003c/h2\u003e \u003cp\u003eIVIM-MRI was conducted using a 3.0T whole-body scanner (uMR790, United Imaging Healthcare Co., Ltd., Shanghai). The rats were fasted for 12 hours before the procedure and anesthetized with an intraperitoneal injection of 0.3% pentobarbital sodium (2 mL/kg). Once anesthetized, the rats were positioned prone in a dedicated rat coil with their heads placed first. To minimize motion artifacts due to respiration and gastrointestinal movements, gauze was used to stabilize the abdomen. A single-shot spin-echo diffusion-weighted echo-planar imaging sequence was applied with nine b-values: 0, 10, 30, 50, 100, 200, 400, 600, and 800 s/mm\u003csup\u003e2\u003c/sup\u003e. Coronal scanning was performed to capture images of the right kidney in the coronal plane with the following parameters: TR\u0026thinsp;=\u0026thinsp;2808 ms, TE\u0026thinsp;=\u0026thinsp;84 ms, number of slices\u0026thinsp;=\u0026thinsp;5, slice thickness\u0026thinsp;=\u0026thinsp;2.0 mm, interslice gap\u0026thinsp;=\u0026thinsp;10 mm, FOV\u0026thinsp;=\u0026thinsp;80 mm \u0026times; 80 mm, and matrix size\u0026thinsp;=\u0026thinsp;128 \u0026times; 128.\u003c/p\u003e \u003cp\u003eAfter scanning, the raw DICOM images were transferred to a post-processing workstation (uWS-MR, R005) for analysis. ROIs in the CO, OM, and IM were manually delineated by a senior radiologist using T2WI images for reference (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). For cortical measurements, three ROIs were placed at the upper, middle, and lower poles of the kidney, and the average of these three values was used as the final result. The same methodology was applied to measure parameters in the inner and outer medulla.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eDoppler ultrasound examination\u003c/h3\u003e\n\u003cp\u003eUltrasound examinations were performed using the EPIQ7 high-resolution diagnostic system (Philips, USA) with a 12 MHz high-frequency linear array transducer, modulation depth of 3 cm, and a sampling volume of 2\u0026ndash;4 mm, positioned at an angle of less than 60\u0026deg;. The rats were placed in a left lateral recumbent position under anesthesia, and the renal area was exposed and coated with coupling gel. The transducer was adjusted to capture longitudinal images of the kidneys. Peak systolic velocity (PSV) and end-diastolic velocity (EDV) of the arcuate and interlobar arteries were recorded. RRI was calculated using the formula: RRI = (PSV\u0026thinsp;\u0026minus;\u0026thinsp;EDV)/PSV. Each rat underwent three independent RI measurements at the upper, middle, and lower poles of the right kidney, with the final RRI value being the average of these measurements.\u003c/p\u003e\n\u003ch3\u003eHistological analysis\u003c/h3\u003e\n\u003cp\u003eAfter IVIM and ultrasound assessments, euthanasia was performed on three rats from each group at each time point via intraperitoneal overdose of 0.3% pentobarbital sodium (10 mL/kg). The kidneys were harvested, and the capsules were removed. Each kidney was longitudinally sectioned and immediately placed in 10% neutral formalin for fixation for 24 hours. After fixation, the tissues were dehydrated, cleared, and paraffin-embedded using an automatic dehydrator following standard protocols. Continuous 4 \u0026micro;m thick sections were obtained using a microtome. The sections were stained with hematoxylin, treated with a bluing reagent, and then stained with eosin. The slides were dehydrated and mounted with neutral gum. A pathologist with over 10 years of clinical experience conducted the pathological assessment, evaluating the samples in a blinded manner. For each slide, five non-overlapping fields were randomly selected, and morphological changes in the renal tissues were observed under a light microscope at 200x magnification. Criteria for evaluation included vacuolar degeneration of renal tubular epithelial cells, tubular dilation, necrosis, cast formation, inflammatory cell infiltration, and interstitial fibrosis. Upon completion of the study, all remaining rats were euthanized with a lethal intraperitoneal dose of 0.3% pentobarbital sodium (10 mL/kg). Renal injury severity was classified on a scale from 0 to 4 based on the criteria established by Ulusoy et al. [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]: 0 (normal renal tissue), 1 (renal injury\u0026thinsp;\u0026lt;\u0026thinsp;5%), 2 (renal injury 5\u0026ndash;25%), 3 (renal injury 25\u0026ndash;75%), and 4 (renal injury\u0026thinsp;\u0026gt;\u0026thinsp;75%).\u003c/p\u003e \u003cp\u003eThe sections were placed in an antigen retrieval buffer (Tris/EDTA pH 9) and heated at 97\u0026deg;C for 30 minutes. After cooling to room temperature, FLEX Peroxidase Block blocking solution was added and incubated at 37\u0026deg;C for 5 minutes. The primary antibody, HIF-1α monoclonal antibody (dilution 1:100) (JieHao Biotechnology, HM-0091, China), was applied at 150 \u0026micro;L per section and incubated for 35 minutes. After washing, a secondary antibody (FLEX/HRP horseradish peroxidase) was added at 150 \u0026micro;L per section and incubated at 37\u0026deg;C for 20 minutes. DAB chromogen (300 \u0026micro;L) was then applied and incubated at 37\u0026deg;C for 10 minutes. The sections were counterstained with hematoxylin, dehydrated, and mounted with neutral gum. The expression of HIF-1α was observed and recorded using an optical microscope.\u003c/p\u003e\n\u003ch3\u003eBiochemical marker testing\u003c/h3\u003e\n\u003cp\u003eBefore euthanizing the rats, tail vein blood samples (0.5-1.0 mL) were collected and allowed to stand at room temperature for 30 minutes to facilitate coagulation. The samples were then centrifuged at 3000 rpm for 5 minutes to obtain serum, which was analyzed for SCr and BUN levels using a fully automated biochemical analyzer (BECKMAN AU5800). All tests were conducted according to the reagent kit instructions and standard operating procedures, with testing performed by trained technical personnel.\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eAll data were analyzed using SPSS 27.0 software (SPSS Inc, Chicago, IL, USA). Continuous variables are expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SDs). Between-group comparisons were conducted using one-way analysis of variance (ANOVA), with post-hoc pairwise comparisons using the LSD test. Comparisons of different time points within groups were analyzed using repeated measures ANOVA. Correlation analyses were conducted using the Spearman rank correlation test to explore relationships between D, D\u003csup\u003e*\u003c/sup\u003e, f, and ADC with pathological injury scores and HIF-1α expression, as well as the correlation between RRI and pathological injury scores, HIF-1α expression, SCr, and BUN. ROC curves were plotted to assess the diagnostic efficacy of IVIM and RRI for CIN by analyzing the area under the curve. A p-value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eIn this study, all rats successfully underwent IVIM and ultrasound examinations. The D, D\u003csup\u003e*\u003c/sup\u003e, f, and ADC parameter maps were obtained by fitting the acquired diffusion-weighted data to both the biexponential and monoexponential functions. The measured values for D, D\u003csup\u003e*\u003c/sup\u003e, f, and ADC were recorded in a standardized datasheet (\u003cstrong\u003eFigure 3, Table 1\u003c/strong\u003e). Doppler ultrasound clearly captured longitudinal pulsed-wave spectral images of the kidneys, and RRI data were fully documented at all time points (\u003cstrong\u003eFigure 4, Table 2\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003eFollowing CM administration, notable changes were observed in the IVIM parameters at various time points. Compared to baseline measurements, the values of D, D\u003csup\u003e*\u003c/sup\u003e, f, and ADC in the CO, OM, and IM showed significant reductions at 1, 24, and 48 hours (P \u0026lt; 0.05), reaching their lowest levels at 48 hours (\u003cstrong\u003eFigure 5\u003c/strong\u003e). A slight recovery was detected at 72 hours, though values remained lower than baseline and those recorded 1 hour after contrast injection. In contrast, no significant changes were observed in the control group at any time point (P \u0026gt; 0.05).\u003c/p\u003e\n\u003cp\u003eUltrasound results demonstrated a gradual increase in RRI values following CM injection (P \u0026lt; 0.05), with a peak at 48 hours (maximum value of 0.66, \u003cstrong\u003eFigure 6\u003c/strong\u003e). At 72 hours, RRI values decreased but remained above baseline levels (P \u0026lt; 0.05). No significant changes in RRI were noted in the control group (P \u0026gt; 0.05).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHistological analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo confirm the accuracy of the imaging results, histological examinations were conducted. Hematoxylin and eosin staining revealed no significant pathological changes at 1 hour post-CM injection. At 24 hours, renal tubular epithelial cell swelling and vacuolar degeneration were observed, along with mild tubular dilation. The most pronounced renal injury occurred at 48 hours, characterized by extensive dilation of renal tubular epithelial cells, some of which exhibited necrosis and sloughing. Inflammatory cell infiltration was observed in the interstitial tissue, accompanied by chronic hemorrhage and hemosiderin deposition. By 72 hours, the tubular dilation and vacuolation had significantly reduced, although complete recovery to normal structure had not been achieved (\u003cstrong\u003eFigure 7\u003c/strong\u003e). The control group exhibited normal kidney tissue structure throughout the study. According to the scoring system established by Ulusoy et al. [19], the CM group showed the highest renal injury score at 48 hours (3.09 \u0026plusmn; 0.18), which was statistically significant compared to baseline (P \u0026lt; 0.05) (\u003cstrong\u003eTable 3\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003eImmunohistochemical staining revealed positive HIF-1\u0026alpha; expression in the nuclei of renal tubular epithelial cells as early as 1 hour post-injection. The most significant expression was observed at 48 hours, where the staining intensity peaked (\u003cstrong\u003eFigure 8\u003c/strong\u003e). By 72 hours, staining intensity decreased but remained above baseline levels. No significant changes in HIF-1\u0026alpha; expression were noted at any time point in the control group (P \u0026gt; 0.05) (\u003cstrong\u003eTable 3\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBiochemical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn the CM group, SCr levels peaked at 72 hours post-CM injection (P \u0026lt; 0.05 compared to baseline), while no significant changes were observed at other time points (P \u0026gt; 0.05). BUN levels were significantly elevated at both 48 and 72 hours (P \u0026lt; 0.05 compared to baseline), with a peak at 48 hours and a slight reduction at 72 hours compared to 48 hours. No significant changes in SCr or BUN were detected at any time point in the control group (P \u0026gt; 0.05) (\u003cstrong\u003eTable 4\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCorrelation analysis of IVIM parameters with histopathology and HIF-1\u0026alpha; expression\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe values of D, D\u003csup\u003e*\u003c/sup\u003e, f, and ADC for the CO, OM, and IM exhibited significant negative correlations with histopathological scores and HIF-1\u0026alpha; expression levels (\u003cstrong\u003eTable 5\u003c/strong\u003e). The correlation coefficients are as follows:\u003c/p\u003e\n\u003cp\u003eFor the CO, the correlations between D, D\u003csup\u003e*\u003c/sup\u003e, f, and ADC with histopathological scores were: (r = -0.755, -0.628, -0.787, -0.804, all p \u0026lt; 0.001). The correlation with HIF-1\u0026alpha; scores was: (r = -0.774, -0.647, -0.786, -0.835, all p \u0026lt; 0.001).\u003c/p\u003e\n\u003cp\u003eFor the OM, the correlations with histopathological scores were: (r = -0.779, -0.822, -0.644, -0.771, all p \u0026lt; 0.001), and with HIF-1\u0026alpha; scores: (r = -0.778, -0.818, -0.649, -0.754, all p \u0026lt; 0.001).\u003c/p\u003e\n\u003cp\u003eFor the IM, the correlations with histopathological scores were: (r = -0.734, -0.778, -0.804, -0.762, all p \u0026lt; 0.001), and with HIF-1\u0026alpha; scores: (r = -0.769, -0.731, -0.803, -0.722, all p \u0026lt; 0.001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCorrelation analysis of IVIM parameters with RRI and blood biomarkers\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe values of D, D\u003csup\u003e*\u003c/sup\u003e, f, and ADC for the CO, OM, and IM exhibited significant negative correlations with RRI\u003cstrong\u003e\u0026nbsp;(Figure 9)\u003c/strong\u003e.The correlation coefficients are as follows:\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; For the CO, the correlations between D, D\u003csup\u003e*\u003c/sup\u003e, f, and ADC with RRI were: (r = -0.729, -0.867, -0.816, -0.751, all p \u0026lt; 0.001).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; For the OM, the correlations between D, D\u003csup\u003e*\u003c/sup\u003e, f, and ADC with RRI were: (r = -0.824, -0.825, -0.823, -0.717, all p \u0026lt; 0.001).\u003c/p\u003e\n\u003cp\u003eFor the IM, the correlations between D, D\u003csup\u003e*\u003c/sup\u003e, f, and ADC with RRI were: (r = -0.778, -0.681, -0.744, -0.830, all p \u0026lt; 0.001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCorrelation analysis of RRI with histopathology, HIF-1\u0026alpha; scores, and biochemical indicators\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRRI demonstrated a strong positive correlation with histopathological scores, HIF-1\u0026alpha; expression, SCr, and BUN, with correlation coefficients of (r = 0.739, p \u0026lt; 0.001), (r = 0.769, p \u0026lt; 0.001), (r = 0.665, p \u0026lt; 0.001), and (r = 0.646, p \u0026lt; 0.001), respectively (\u003cstrong\u003eFigure 10\u003c/strong\u003e).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePredictive value of IVIM parameters and RRI for CIN\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe ROC curve analysis revealed AUC values for IVIM and RRI of 0.820 and 0.825, respectively, in detecting CIN. The combined prediction model achieved an AUC of 0.915 (95% CI: 0.794\u0026ndash;1.000), with a sensitivity of 90.00% and specificity of 90.00%, demonstrating superior diagnostic performance compared to individual parameters \u003cstrong\u003e(Figure 11)\u003c/strong\u003e.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study systematically examined the changes in IVIM parameters and RRI at various time points following CM injection, alongside correlation analyses with histological and biochemical markers. The results show that IVIM parameters and RRI can sensitively reflect pathophysiological changes in the kidneys, often earlier than traditional biochemical markers. These findings have significant clinical implications, offering a multidimensional experimental foundation for the early detection and accurate diagnosis of CIN.\u003c/p\u003e \u003cp\u003eIn this study, the IVIM parameters (D, D\u003csup\u003e*\u003c/sup\u003e, f) and ADC of the CO, OM, and IM in rats progressively decreased at different time points following CM injection, reaching their lowest values at 48 hours. This pattern suggests significant suppression of renal microcirculation flow-related information and the diffusion capacity of water molecules. Although partial recovery was observed after 72 hours, the parameters did not return to baseline, indicating that the tissue was in a partial repair phase but still showing potential damage. These results align with previous studies by Wang et al. [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] and Feng et al. [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The D parameter reflects the diffusion capacity of water molecules within tissue. In this study, D values in all anatomical regions began to decrease at 1 hour, likely due to the high viscosity and osmotic pressure of CM, which restrict water molecule diffusion and may cause epithelial cell edema and renal tubular damage [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Some studies have indicated that D is a reliable indicator for detecting AKI [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] and assessing CI-AKI [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eD\u003csup\u003e*\u003c/sup\u003e and f represent quantitative parameters of tissue flow-related information. D\u003csup\u003e*\u003c/sup\u003e reflects the capillary segment length and average blood flow velocity within tissues, while f denotes the ratio of the total fluid volume in capillaries and renal tubules per unit volume to the total liquid content per unit volume of renal tissue. The reduction in D\u003csup\u003e*\u003c/sup\u003e and f values is associated with multiple pathophysiological cascades: 1. Hemodynamic impairment: The hyperosmolarity and viscous effects of CM induce renal tubular epithelial cell swelling and luminal dilation, reducing capillary blood flow velocity (manifested as decreased D\u003csup\u003e*\u003c/sup\u003e values) and causing regional hypoperfusion [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Compensatory vasodilation is triggered, but CM's direct cytotoxic effects through reactive oxygen species and apoptotic pathways [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] disrupt the balance of vasoactive mediators (endothelin, adenosine, and nitric oxide), leading to sustained renal vasoconstriction [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Although luminal dilation may transiently increase resting tubular fluid volume, the persistent vasoconstriction-induced reduction in effective blood flow is a critical factor in f value decline [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. 2. Microstructural damage: Ischemia-reperfusion injury induces interstitial edema, compressing capillary beds, while tubular casts formed by necrotic debris obstruct fluid flow [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], further reducing the proportion of mobile fluid reflected by f values. The ischemic-hypoxic state activates the tubuloglomerular feedback mechanism, initiating a cycle of vasoconstriction \u0026rarr; GFR reduction \u0026rarr; aggravated ischemia \u0026rarr; cellular damage [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], which exacerbates the decline in D\u003csup\u003e*\u003c/sup\u003e and f values. Our study confirmed significant reductions in D\u003csup\u003e*\u003c/sup\u003e and f values across all time points, corroborated by pathological findings.\u003c/p\u003e \u003cp\u003eThis study observed that the ADC value reached its lowest point at 48 hours post-contrast injection, which was closely related to reductions in D\u003csup\u003e*\u003c/sup\u003e, f, and D. As an imaging parameter reflecting both water molecular diffusion and microcirculatory flow-related information [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], the dynamic changes in ADC values suggest the following pathological mechanisms: 1. CM induces renal tubular epithelial cell edema and microstructural damage through its hyperosmolar properties and cytotoxicity, restricting water molecule diffusion. 2. Increased renal vascular resistance and hemodynamic disturbances, caused by afferent arteriole constriction and capillary blood flow deceleration, significantly reduce microcirculatory perfusion in the renal parenchyma [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Our findings revealed significantly lower ADC values in the OM and IM compared to CO, likely due to the medulla\u0026rsquo;s inherent low-perfusion characteristics and increased susceptibility to ischemic-hypoxic injury [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Pathological examinations showed characteristic changes, including tubular cell edema and inflammatory infiltration, further validating the correlation between ADC reduction and cellular edema/microcirculatory dysfunction. These findings align with Le et al.'s conclusions [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], which suggest that ADC dynamics reflect both cellular edema and ischemic injury severity, serving as biomarkers for renal injury progression and prognosis. Recent studies [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] also confirm that quantitative ADC analysis provides objective imaging evidence for evaluating renal tissue hypoxia and ischemia-reperfusion injury.\u003c/p\u003e \u003cp\u003eDoppler ultrasound provides a practical, effective, safe, and accurate method for assessing renal blood flow perfusion. The RRI has significant clinical value in the early diagnosis and prognostic assessment of various renal diseases, including diabetic nephropathy [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e], CKD [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e], and kidney transplantation [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. A study by Xu et al. [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] identified RRI as an independent predictor of CIN in patients undergoing percutaneous coronary intervention. Interestingly, in this study, the CM group of rats showed an increase in RRI values at 1 hour post-CM injection, peaking at 48 hours before slightly declining, yet remaining above baseline levels. This indicates that CM induced an increase in renal vascular resistance. The elevation of RRI may be attributed to several factors: first, the high viscosity and hyperosmolarity of CM can cause tubular damage and endothelial dysfunction, leading to increased renal arterial resistance [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Second, CM-induced excessive stimulation of the tubule-glomerular feedback mechanism may increase adenosine secretion, causing constriction of afferent arterioles and further contributing to the rise in renal vascular resistance [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. This finding aligns with the trends observed in D\u003csup\u003e*\u003c/sup\u003e and f values.\u003c/p\u003e \u003cp\u003eIn our study, RRI showed a significant positive correlation with histopathological damage scores, HIF-1α expression levels, SCr, and BUN (r\u0026thinsp;=\u0026thinsp;0.739, 0.769, 0.665, 0.646, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). These results support the notion that RRI is an effective indicator for assessing hemodynamic changes in the kidneys following CM injection in rats. Wybraniec et al. [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e] reported that the sensitivity of RRI for predicting CI-AKI at 48 hours was 78%, with specificity of 81% in patients undergoing coronary angiography or percutaneous coronary intervention, in univariate analysis, both RRI and the pulsatility index were identified as predictors of CI-AKI; however, in multivariate models, only RRI remained an independent predictor of CI-AKI incidence. RRI is a highly sensitive parameter for kidney disease, providing valuable insights into the pathophysiology of native or transplanted kidneys. It serves as an important metric for evaluating renal function status and reflects the pathological process of renal functional decline in patients with AKI [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIt is noteworthy that in this study, early changes in IVIM parameters and RRI occurred significantly earlier than changes in SCr and BUN. SCr levels in the CM group of rats showed a significant increase at 72 hours post-CM injection, while BUN levels elevated significantly at 48 hours. This indicates that SCr and BUN have insufficient sensitivity for the early diagnosis of CIN. As a key indicator of kidney function, SCr is influenced not only by the secretion from renal tubular epithelial cells but also by various factors, such as individual muscle metabolism, body weight, ethnicity, age, and gender [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. To comprehensively validate the scientific rigor and reliability of this research, HIF-1α was selected as a critical immunohistochemical marker. This study elucidated the mechanisms by which CM induces tubular injury and localized hypoxia, leading to high expression of HIF-1α in the context of CIN [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. A significant upregulation of HIF-1α expression was observed following CM injection, peaking at 48 hours. This trend closely aligns with the dynamic changes observed in IVIM parameters and RRI, providing strong evidence for the scientific value of these imaging markers in accurately reflecting pathological changes in renal tissue.\u003c/p\u003e \u003cp\u003eThis study conducted a longitudinal analysis of changes in critical IVIM parameters and RRI across various anatomical regions of the kidneys before and after CM injection, integrating histological and biochemical indicators to evaluate the diagnostic value of these methods in CIN. Compared to single indicators, the combined application of multiple indicators provides a more comprehensive and accurate reflection of renal function changes. IVIM offers quantitative information on microcirculatory flow-related information and water molecule diffusion, while RRI enables real-time observation of renal hemodynamic changes. The complementary advantages of these methods provide a multidimensional view of renal function changes and their potential pathophysiological mechanisms following CM injection. Histopathological damage and HIF-1α expression serve as gold standards, further validating the reliability of these imaging markers in monitoring the pathophysiological changes associated with CIN. This innovative research is expected to contribute to the development of a precise, non-invasive imaging diagnostic method for clinical assessment and prediction of CIN.\u003c/p\u003e \u003cp\u003eThis study has certain limitations: Both IVIM and ultrasound images were susceptible to interference from rat respiratory movements. Although the abdomen was secured with gauze to minimize artifacts, residual effects still impacted image quality and parameter measurement accuracy. The experimental subjects were limited to rats, suggesting the need for future studies involving multiple species. Additionally, challenges such as low signal-to-noise ratio, insufficient low b-value acquisitions, and suboptimal fitting constraints may compromise the stability and reliability of IVIM parameter estimation and image quality.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe results of this study demonstrate that significant reductions in IVIM parameters and increases in RRI are observable as early as 1 hour after CM injection in the early stages of CIN, reaching peak levels at 48 hours. These changes are strongly correlated with histopathological damage, HIF-1α expression, and biochemical indicators. This suggests that IVIM and RRI are effective methods for monitoring the early pathophysiological changes associated with CIN.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 20.434%;\"\u003e\n \u003cp\u003eIVIM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79.566%;\"\u003e\n \u003cp\u003eIntravoxel incoherent motion\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 20.434%;\"\u003e\n \u003cp\u003eRRI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79.566%;\"\u003e\n \u003cp\u003eRenal resistance index\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 20.434%;\"\u003e\n \u003cp\u003eCIN\u003c/p\u003e\n \u003cp\u003eDWI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79.566%;\"\u003e\n \u003cp\u003eContrast-induced nephropathy\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eDiffusion-weighted imaging\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 20.434%;\"\u003e\n \u003cp\u003eSD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79.566%;\"\u003e\n \u003cp\u003eSprague-Dawley\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 20.434%;\"\u003e\n \u003cp\u003eCM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79.566%;\"\u003e\n \u003cp\u003eContrast media\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 20.434%;\"\u003e\n \u003cp\u003eCO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79.566%;\"\u003e\n \u003cp\u003eCortex\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 20.434%;\"\u003e\n \u003cp\u003eOM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79.566%;\"\u003e\n \u003cp\u003eOuter medulla\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 20.434%;\"\u003e\n \u003cp\u003eIM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79.566%;\"\u003e\n \u003cp\u003eInner medulla\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 20.434%;\"\u003e\n \u003cp\u003eD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79.566%;\"\u003e\n \u003cp\u003eDiffusion coefficient\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 20.434%;\"\u003e\n \u003cp\u003eD\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79.566%;\"\u003e\n \u003cp\u003ePseudo-diffusion coefficien；\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 20.434%;\"\u003e\n \u003cp\u003ef\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79.566%;\"\u003e\n \u003cp\u003ePerfusion fraction\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 20.434%;\"\u003e\n \u003cp\u003eADC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79.566%;\"\u003e\n \u003cp\u003eApparent diffusion coefficient\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 20.434%;\"\u003e\n \u003cp\u003eHIF-1\u0026alpha;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79.566%;\"\u003e\n \u003cp\u003eHypoxia-inducible factor-1\u0026alpha;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 20.434%;\"\u003e\n \u003cp\u003eSCr\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79.566%;\"\u003e\n \u003cp\u003eSerum creatinine\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 20.434%;\"\u003e\n \u003cp\u003eBUN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79.566%;\"\u003e\n \u003cp\u003eBlood urea nitrogen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 20.434%;\"\u003e\n \u003cp\u003eAKI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79.566%;\"\u003e\n \u003cp\u003eAcute kidney injury\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 20.434%;\"\u003e\n \u003cp\u003eCI-AKI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79.566%;\"\u003e\n \u003cp\u003eContrast-induced acute kidney injury\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 20.434%;\"\u003e\n \u003cp\u003eCKD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79.566%;\"\u003e\n \u003cp\u003eChronic kidney disease\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 20.434%;\"\u003e\n \u003cp\u003eROI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79.566%;\"\u003e\n \u003cp\u003eRegion of interest\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 20.434%;\"\u003e\n \u003cp\u003ePSV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79.566%;\"\u003e\n \u003cp\u003ePeak systolic velocity\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 20.434%;\"\u003e\n \u003cp\u003eEDV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79.566%;\"\u003e\n \u003cp\u003eEnd-diastolic velocity\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 20.434%;\"\u003e\n \u003cp\u003eROC\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eAUC\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79.566%;\"\u003e\n \u003cp\u003eReceiver operating characteristic\u003c/p\u003e\n \u003cp\u003eArea under the curve\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJLC and ZQW contributed to the conceptualization and methodology. JLC and XYS contributed to the data collection. ZQW and ZW contributed to the statistical analysis. JLC wrote the main manuscript text. ZQW and ZW made the first revision of the manuscript. All authors reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe dataset supporting the conclusions of this article is included within the article (and its additional file)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo human samples or clinical data were included in this study，hence consent to participate is not applicable. All animal procedures were conducted according to the National Institute of Health Guide for the Care and Use of Laboratory Animals and approved by the University of Beihua Ethics Committee (approval number 2024112604).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eCollege of Clinical Medicine, Beihua University, Jilin, China.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e2\u003c/sup\u003eDepartment of Ultrasound, Siping Central People\u0026rsquo;s Hospital, Siping, China.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e3\u003c/sup\u003eDepartment of Radiology, Jilin Central Hospital, Jilin, China.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e4\u003c/sup\u003eDepartment of Radiology, The Affiliated Hospital of BeiHua University, Jilin, China.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAhmed K, McVeigh T, Cerneviciute R et al. 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Korean J Radiol. 2019;20(5):830\u0026ndash;43. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3348/kjr.2018.0757\u003c/span\u003e\u003cspan address=\"10.3348/kjr.2018.0757\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eAverage values of D(x10\u003csup\u003e-3\u003c/sup\u003emm\u003csup\u003e2\u003c/sup\u003e/s)、D\u003csup\u003e*\u003c/sup\u003e(x10\u003csup\u003e-3\u003c/sup\u003emm\u003csup\u003e2\u003c/sup\u003e/s)、f(%)、ADC(x10\u003csup\u003e-3\u003c/sup\u003emm\u003csup\u003e2\u003c/sup\u003e/s) at different time points in the contrast media group\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 22.9167%;\"\u003e\n \u003cp\u003eGroup\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.5833%;\"\u003e\n \u003cp\u003eBaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e24h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e48h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e72h\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 22.9167%;\"\u003e\n \u003cp\u003eD(x10\u003csup\u003e-3\u003c/sup\u003emm\u003csup\u003e2\u003c/sup\u003e/s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.5833%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 22.9167%;\"\u003e\n \u003cp\u003eCO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.5833%;\"\u003e\n \u003cp\u003e1.64\u0026plusmn;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1.58\u0026plusmn;0.02\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1.43\u0026plusmn;0.04\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1.34\u0026plusmn;0.04\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1.46\u0026plusmn;0.03\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 22.9167%;\"\u003e\n \u003cp\u003eOM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.5833%;\"\u003e\n \u003cp\u003e1.68\u0026plusmn;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1.59\u0026plusmn;0.04\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1.44\u0026plusmn;0.05\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1.36\u0026plusmn;0.04\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1.50\u0026plusmn;0.03\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 22.9167%;\"\u003e\n \u003cp\u003eIM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.5833%;\"\u003e\n \u003cp\u003e1.73\u0026plusmn;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1.67\u0026plusmn;0.04\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1.52\u0026plusmn;0.04\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1.42\u0026plusmn;0.04\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1.56\u0026plusmn;0.05\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 22.9167%;\"\u003e\n \u003cp\u003eD\u003csup\u003e*\u003c/sup\u003e(x10\u003csup\u003e-3\u003c/sup\u003emm\u003csup\u003e2\u003c/sup\u003e/s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.5833%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 22.9167%;\"\u003e\n \u003cp\u003eCO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.5833%;\"\u003e\n \u003cp\u003e8.98\u0026plusmn;0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e7.10\u0026plusmn;0.37\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e5.89\u0026plusmn;0.50\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e4.44\u0026plusmn;0.61\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e6.54\u0026plusmn;0.42\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 22.9167%;\"\u003e\n \u003cp\u003eOM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.5833%;\"\u003e\n \u003cp\u003e9.05\u0026plusmn;0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e6.87\u0026plusmn;0.42\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e5.70\u0026plusmn;0.40\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e4.27\u0026plusmn;0.51\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e6.36\u0026plusmn;0.45\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 22.9167%;\"\u003e\n \u003cp\u003eIM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.5833%;\"\u003e\n \u003cp\u003e8.34\u0026plusmn;0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e7.18\u0026plusmn;0.64\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e5.95\u0026plusmn;0.58\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e4.60\u0026plusmn;0.52\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e6.63\u0026plusmn;0.70\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 22.9167%;\"\u003e\n \u003cp\u003ef(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.5833%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 22.9167%;\"\u003e\n \u003cp\u003eCO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.5833%;\"\u003e\n \u003cp\u003e29.87\u0026plusmn;0.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e25.67\u0026plusmn;1.23\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e22.57\u0026plusmn;0.52\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e19.34\u0026plusmn;0.78\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e24.26\u0026plusmn;0.48\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 22.9167%;\"\u003e\n \u003cp\u003eOM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.5833%;\"\u003e\n \u003cp\u003e28.63\u0026plusmn;0.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e25.37\u0026plusmn;1.04\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e21.89\u0026plusmn;1.56\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e19.43\u0026plusmn;1.11\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e23.88\u0026plusmn;0.93\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 22.9167%;\"\u003e\n \u003cp\u003eIM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.5833%;\"\u003e\n \u003cp\u003e28.34\u0026plusmn;0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e25.47\u0026plusmn;1.39\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e22.81\u0026plusmn;0.91\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e20.02\u0026plusmn;1.15\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e24.43\u0026plusmn;0.90\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 22.9167%;\"\u003e\n \u003cp\u003eADC(x10\u003csup\u003e-3\u003c/sup\u003emm\u003csup\u003e2\u003c/sup\u003e/s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.5833%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 22.9167%;\"\u003e\n \u003cp\u003eCO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.5833%;\"\u003e\n \u003cp\u003e1.68\u0026plusmn;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1.61\u0026plusmn;0.04\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1.50\u0026plusmn;0.08\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1.37\u0026plusmn;0.07\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1.53\u0026plusmn;0.07\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 22.9167%;\"\u003e\n \u003cp\u003eOM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.5833%;\"\u003e\n \u003cp\u003e1.72\u0026plusmn;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1.65\u0026plusmn;0.03\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1.50\u0026plusmn;0.06\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1.34\u0026plusmn;0.05\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1.55\u0026plusmn;0.06\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 22.9167%;\"\u003e\n \u003cp\u003eIM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.5833%;\"\u003e\n \u003cp\u003e1.66\u0026plusmn;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1.57\u0026plusmn;0.06\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1.44\u0026plusmn;0.08\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1.30\u0026plusmn;0.05\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1.51\u0026plusmn;0.07\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNote：CO=Cortex；OM=Outer medulla；IM=Inner medulla\u003c/p\u003e\n\u003cp\u003e* Compared to baseline, P \u0026lt; 0.05.\u003c/p\u003e\n\u003cp\u003eThe inter-group and intra-group differences were analyzed using Analysis of Variance (ANOVA) and Repeated Measures ANOVA, respectively.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eAverage values of RRI at different time points in the contrast media group\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 22.9167%;\"\u003e\n \u003cp\u003eGroup\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.5833%;\"\u003e\n \u003cp\u003eBaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e24h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e48h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e72h\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 22.9167%;\"\u003e\n \u003cp\u003eRRI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.5833%;\"\u003e\n \u003cp\u003e0.45\u0026plusmn;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e0.51\u0026plusmn;0.02\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e0.58\u0026plusmn;0.01\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e0.64\u0026plusmn;0.01\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e0.55\u0026plusmn;0.01\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNote：Compared to baseline, P \u0026lt; 0.05.\u003c/p\u003e\n\u003cp\u003eThe inter-group and intra-group differences were analyzed using Analysis of Variance (ANOVA) and Repeated Measures ANOVA, respectively.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3.\u003c/strong\u003e Renal injury scores and HIF-1\u0026alpha; expression scores at different time points before and after the injection of contrast media\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\u003ctd\u003e\u003c/td\u003e\n \u003ctd style=\"width: 13.8298%;\"\u003e\n \u003cp\u003ebaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8298%;\"\u003e\n \u003cp\u003e1h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8298%;\"\u003e\n \u003cp\u003e24h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8298%;\"\u003e\n \u003cp\u003e48h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8298%;\"\u003e\n \u003cp\u003e72h\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 25.5319%;\"\u003e\n \u003cp\u003eRenal injury score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8298%;\"\u003e\n \u003cp\u003e0.00\u0026plusmn;0.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8298%;\"\u003e\n \u003cp\u003e0.78\u0026plusmn;0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8298%;\"\u003e\n \u003cp\u003e2.04\u0026plusmn;0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8298%;\"\u003e\n \u003cp\u003e3.09\u0026plusmn;0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8298%;\"\u003e\n \u003cp\u003e1.58\u0026plusmn;0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"1\" style=\"width: 28.7234%;\"\u003e\n \u003cp\u003eHIF-1\u0026alpha; expression score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8298%;\"\u003e\n \u003cp\u003e0.00\u0026plusmn;0.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8298%;\"\u003e\n \u003cp\u003e1.00\u0026plusmn;0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8298%;\"\u003e\n \u003cp\u003e2.24\u0026plusmn;0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8298%;\"\u003e\n \u003cp\u003e3.20\u0026plusmn;0.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8298%;\"\u003e\n \u003cp\u003e1.89\u0026plusmn;0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4.\u0026nbsp;\u003c/strong\u003eAverage values of SCr (mol/L) and BUN (\u0026micro;mol/L) at different time points in the contrast media group\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20.6186%;\"\u003e\n \u003cp\u003eGroup\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4948%;\"\u003e\n \u003cp\u003eBaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.4639%;\"\u003e\n \u003cp\u003e1h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.4639%;\"\u003e\n \u003cp\u003e24h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.4639%;\"\u003e\n \u003cp\u003e48h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4948%;\"\u003e\n \u003cp\u003e72h\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20.6186%;\"\u003e\n \u003cp\u003eSCr（mol/L）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4948%;\"\u003e\n \u003cp\u003e20.73\u0026plusmn;0.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.4639%;\"\u003e\n \u003cp\u003e21.27\u0026plusmn;0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.4639%;\"\u003e\n \u003cp\u003e23.00\u0026plusmn;0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.4639%;\"\u003e\n \u003cp\u003e24.82\u0026plusmn;0.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4948%;\"\u003e\n \u003cp\u003e30.76\u0026plusmn;0.98\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20.6186%;\"\u003e\n \u003cp\u003eBUN（umol/L）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4948%;\"\u003e\n \u003cp\u003e3.94\u0026plusmn;0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.4639%;\"\u003e\n \u003cp\u003e4.09\u0026plusmn;0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.4639%;\"\u003e\n \u003cp\u003e4.32\u0026plusmn;0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.4639%;\"\u003e\n \u003cp\u003e4.95\u0026plusmn;0.07\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4948%;\"\u003e\n \u003cp\u003e4.72\u0026plusmn;0.09\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*Compared to baseline, P \u0026lt; 0.05.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5\u003c/strong\u003e\u003cstrong\u003e．\u003c/strong\u003eCorrelation analysis of IVIM parameters with renal injury scores and HIF-1\u0026alpha; expression scores\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\u003ctd\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 38px;\"\u003e\n \u003cp\u003eRenal injury score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 38px;\"\u003e\n \u003cp\u003eHIF-1\u0026alpha; expression score\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eGroup\u003c/p\u003e\n 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\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eD\u003csup\u003e*\u003c/sup\u003e\u003csub\u003eCO\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e-0.628\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e-0.647\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003ef\u003csub\u003eCO\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e-0.787\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e-0.786\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eADC\u003csub\u003eCO\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e-0.804\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e-0.835\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eD\u003csub\u003eOM\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e-0.779\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e-0.778\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eD\u003csup\u003e*\u003c/sup\u003e\u003csub\u003eOM\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e-0.822\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e-0.818\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003ef\u003csub\u003eOM\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e-0.644\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;-0.649\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eADC\u003csub\u003eOM\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e-0.771\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e-0.754\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eD\u003csub\u003eIM\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e-0.743\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e-0.769\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eD\u003csup\u003e*\u003c/sup\u003e\u003csub\u003eIM\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e-0.778\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e-0.731\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003ef\u003csub\u003eIM\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e-0.804\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e-0.803\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eADC\u003csub\u003eIM\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e-0.762\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e-0.722\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNote：CO=Cortex；OM=Outer medulla；IM=Inner medulla.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnep","sideBox":"Learn more about [BMC Nephrology](http://bmcnephrol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bnep/default.aspx","title":"BMC Nephrology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Contrast-induced nephropathy, Intravoxel incoherent motion, Renal resistance index, Acute kidney injury","lastPublishedDoi":"10.21203/rs.3.rs-5792456/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5792456/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eThis study explored the application of Intravoxel Incoherent Motion (IVIM) diffusion imaging combined with Ultrasound Renal Resistance Index (RRI) for monitoring the pathophysiological changes associated with early contrast-induced nephropathy (CIN).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eIn this study, forty-two male Sprague-Dawley (SD) rats were equally divided into two groups: a contrast media (CM) group and a control group, each containing 21 animals. The CM group was administered a tail vein injection of ioversol (370 mg I/ml, 1.5 ml/kg), while the control group received a saline solution in a similar volume. Assessments using IVIM-MRI and Doppler ultrasound were performed 24 hours before and at 1, 24, 48, and 72 hours post-injection. These assessments aimed to evaluate the true diffusion coefficient (D), pseudo-diffusion coefficient (D\u003csup\u003e*\u003c/sup\u003e), perfusion fraction (f), apparent diffusion coefficient (ADC), and RRI. Concurrently, three rats from each group were sacrificed at these time points for renal histopathology, hypoxia-inducible factor-1α (HIF-1α) expression analysis, and the quantification of serum creatinine (SCr) and blood urea nitrogen (BUN) levels. Receiver operating characteristic (ROC) curves were plotted, and the area under the curve (AUC) was analyzed to evaluate the diagnostic performance of IVIM and RRI in predicting CIN.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003ePost-ioversol administration, significant declines were noted in the D, D\u003csup\u003e*\u003c/sup\u003e, f, ADC across the renal cortex (CO), outer medulla (OM), and inner medulla (IM) from 1 to 48 hours (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), with the lowest values observed at 48 hours. These parameters began to recover after 72 hours. Conversely, RRI values escalated from 1 to 48 hours, peaking at 48 hours (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), and then diminished gradually after 72 hours. The control group showed no significant changes in these parameters. Furthermore, a negative correlation was observed between RRI, histopathological grades, HIF-1α expression levels, and the levels of SCr and BUN. In contrast, RRI exhibited a positive correlation with these pathological scores and the levels of SCr and BUN. ROC curve analysis revealed that the combined predictive performance of IVIM and RRI was superior to that of individual parameters.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe synergistic application of IVIM and RRI techniques offers a non-invasive approach for early detection of renal damage after ioversol exposure and is a potent method for observing the pathophysiological shifts associated with early-stage CIN.\u003c/p\u003e","manuscriptTitle":"Experimental Study of Intravoxel Incoherent Motion Diffusion Imaging Combined with Ultrasound Renal Resistance Index in Contrast-Induced Nephropathy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-28 11:14:03","doi":"10.21203/rs.3.rs-5792456/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-05-05T15:03:40+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-01T21:22:54+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"200457597520896028116976796578205199228","date":"2025-04-25T13:23:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"114150196952845015700947325726147467377","date":"2025-04-24T14:35:37+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-22T17:03:47+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-22T07:53:43+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Nephrology","date":"2025-04-16T05:06:25+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnep","sideBox":"Learn more about [BMC Nephrology](http://bmcnephrol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bnep/default.aspx","title":"BMC Nephrology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b78527b3-ecd2-400e-b126-ae7a106d1861","owner":[],"postedDate":"April 28th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-08-07T07:11:01+00:00","versionOfRecord":{"articleIdentity":"rs-5792456","link":"https://doi.org/10.1186/s12882-025-04329-3","journal":{"identity":"bmc-nephrology","isVorOnly":false,"title":"BMC Nephrology"},"publishedOn":"2025-07-18 15:57:30","publishedOnDateReadable":"July 18th, 2025"},"versionCreatedAt":"2025-04-28 11:14:03","video":"","vorDoi":"10.1186/s12882-025-04329-3","vorDoiUrl":"https://doi.org/10.1186/s12882-025-04329-3","workflowStages":[]},"version":"v1","identity":"rs-5792456","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5792456","identity":"rs-5792456","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}