Evaluation of renal tubular function by multiparametric functional MRI in early diabetes.

Purpose To evaluate the tubular function in an alloxan-induced type 1 diabetes mellitus (DM) rabbit model measured by renal oxygenation (R2*), oxygen extraction fraction (OEF), and renal blood flow (RBF) using blood oxygenation level dependent, asymmetric spin echo, and arterial spin labeling MRI. Methods Twenty-six rabbits were randomized into the 3-day DM group (n = 13) and the 7-day DM group (n = 13). We performed pairs of multiparametric MRIs (before and after furosemide injection) at baseline and 3/7 days post-DM, and scored pathological kidney injury. We performed statistical analyses using non-parametric, chi-square, and Spearman correlation tests. Results At baseline, medullary R2* significantly decreased by 24.97% and 16.74% in the outer and inner stripes of the outer medulla (OS and IS, p = 0.006 and 0.003, respectively) after furosemide administration. While the corresponding OEF decreased by 15.91% for OS and 16.67% for IS (both p = 0.003), and no significant change in medullary RBF was observed (p > 0.05). In the 3-day DM group, the decrease of medullary R2* and OEF post-furosemide became unremarkable, suggesting tubular dysfunction. We noticed similar changes in the 7-day DM group. Correlation analysis showed pathological tubular injury score significantly correlated with medullary ∆R2* (post-furosemide - pre-furosemide difference, r = 0.82 for OS and 0.82 for IS) and ∆OEF (r = 0.82 for OS and 0.82 for IS) (p < 0.001, respectively). Conclusion: The combination of medullary OEF and R2* in response to furosemide could detect renal tubular dysfunction in early DM.

An initial study on the comparison of diagnostic performance of 18F-FDG PET/MR and 18F-FDG PET/CT for thoracic staging of non-small cell lung cancer: Focus on pleural invasion.

OBJECTIVE: To compare the diagnostic performance of 18F-FDG PET/MR and PET/CT preliminarily for the thoracic staging of non-small cell lung cancer (NSCLC) with a special focus on pleural invasion evaluation. METHODS: 52 patients with pathologically confirmed NSCLC were included and followed for another year. Whole-body 18F-FDG PET/CT and subsequent thoracic PET/MR were performed for initial thoracic staging. Thoracic (simultaneous) PET/MR acquired PET images and MRI sequences including T2 weighted imaging, with and without fat saturation, T1 weighted imaging, and diffusion weighted imaging (DWI). Two radiologists independently assessed the thoracic T, N staging and pleural involvement. The McNemar Chi-square test was used to compare the differences between PET/CT and PET/MR in the criteria. The area under the receiver-operating-characteristic curves (AUC) was calculated. RESULTS: Compared to PET/CT, PET/MR exhibited higher sensitivity, specificity in the detection of pleural invasion; 82 % vs. 64% (p = 0.625), 98 % vs. 95% (p = 1.000), PET/MR to PET/CT respectively. The receiver-operating-characteristic analysis results of PET/CT vs PET/MR for the pleural invasion were as follow: AUCPET/CT = 0.79, AUCPET/MR = 0.90, p = 0.21. Both T staging results and N staging results were approximately identical in PET/CT and PET/MR. Differences between PET/CT and PET/MR in T staging, N staging as well as pleural invasion accuracy were not statistically significant (p > 0.05, each). CONCLUSION: PET/MR and PET/CT demonstrated equivalent performance about the evaluation of preoperative thoracic staging of NSCLC patients. PET/MR may have greater potential in pleural invasion evaluation for NSCLC, especially for solid nodules, crucial to clinical decision-making, though our results did not demonstrate statistical significance.

Predictive Value of 18 F-FDG PET/MRI for Pleural Invasion in Solid and Subsolid Lung Adenocarcinomas Smaller Than 3 cm.

BACKGROUND: Positron emission tomography (PET)/MRI combines the characteristics of metabolism imaging and high soft tissue resolution, and could provide high diagnostic efficacy for assessment of pleural invasion (PI) of lung cancer. PURPOSE: To investigate the application of 18 F-fluorodeoxyglucose (FDG) PET/MRI for predicting PI of lung cancer with the maximum diameter ≤3 cm. STUDY TYPE: Prospective. POPULATION: A total of 44 patients with non-small cell lung cancer (NSCLC), age from 39 to 79 years old, including 19 (56.82%) females. FIELD STRENGTH/SEQUENCE: A 3-T, hybrid PET/MRI including axial fast spin echo respiratory-triggered T2 fat-suppressed imaging (T2FS) and echo planar imaging diffusion-weighted imaging (DWI). ASSESSMENT: The maximum standardized uptake value (SUVmax) of all lesions was measured on PET images. Localized effusion outside the contact between the nodules and the pleura on T2FS and signal at the contact between the nodules and the pleura on DWI were evaluated by experienced physicians through visual assessment of the MRI sequences. STATISTICAL TESTS: Three models (models 1-3) were developed, incorporating CT, CT and PET, PET and MRI features, and Lasso regression was used in feature selection. The receiver operating characteristic (ROC) curve for PI diagnosis was visualized for each model, and the area under the curve (AUC) was calculated. The DeLong test was used to compare the different AUCs. A P value < 0.05 was considered statistically significant. RESULTS: The AUC of models 1-3 was 0.762, 0.829, and 0.915, respectively. The DeLong test showed a statistically significant difference between the AUCs of model 1 vs. model 3, while the differences between the AUCs of model 1 vs. model 2 (P = 0.253) and model 2 vs. model 3 (P = 0.075) were not statistically significant. DATA CONCLUSION: 18 F-FDG PET/MRI might show high predictive value for lung adenocarcinoma smaller than 3 cm with PI. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Value of 18F-FDG PET/MRI in the Preoperative Assessment of Resectable Esophageal Squamous Cell Carcinoma: A Comparison With 18F-FDG PET/CT, MRI, and Contrast-Enhanced CT.

Objectives: To investigate the value of 18F-FDG PET/MRI in the preoperative assessment of esophageal squamous cell carcinoma (ESCC) and compare it with 18F-FDG PET/CT, MRI, and CECT. Methods: Thirty-five patients with resectable ESCC were prospectively enrolled and underwent PET/MRI, PET/CT, and CECT before surgery. The primary tumor and regional lymph nodes were assessed by PET/MRI, PET/CT, MRI, and CECT, respectively, and the diagnostic efficiencies were determined with postoperative pathology as a reference standard. The predictive role of imaging and clinical parameters on pathological staging was analyzed. Results: For primary tumor staging, the accuracy of PET/MRI, MRI, and CECT was 85.7%, 77.1%, and 51.4%, respectively. For lymph node assessment, the accuracy of PET/MRI, PET/CT, MRI, and CECT was 96.2%, 92.0%, 86.8%, and 86.3%, respectively, and the AUCs were 0.883, 0.745, 0.697, and 0.580, respectively. PET/MRI diagnosed 13, 7, and 6 more stations of lymph node metastases than CECT, MRI, and PET/CT, respectively. There was a significant difference in SUVmax, TLG, and tumor wall thickness between T1-2 and T3 tumors (p = 0.004, 0.024, and < 0.001, respectively). Multivariate analysis showed that thicker tumor wall thickness was a predictor of a higher T stage (p = 0.040, OR = 1.6). Conclusions: 18F-FDG PET/MRI has advantages over 18F-FDG PET/CT, MRI, and CECT in the preoperative assessment of primary tumors and regional lymph nodes of ESCC. 18F-FDG PET/MRI may be a potential supplement or alternative imaging method for preoperative staging of ESCC.

Content-Noise Complementary Learning for Medical Image Denoising.

Medical imaging denoising faces great challenges, yet is in great demand. With its distinctive characteristics, medical imaging denoising in the image domain requires innovative deep learning strategies. In this study, we propose a simple yet effective strategy, the content-noise complementary learning (CNCL) strategy, in which two deep learning predictors are used to learn the respective content and noise of the image dataset complementarily. A medical image denoising pipeline based on the CNCL strategy is presented, and is implemented as a generative adversarial network, where various representative networks (including U-Net, DnCNN, and SRDenseNet) are investigated as the predictors. The performance of these implemented models has been validated on medical imaging datasets including CT, MR, and PET. The results show that this strategy outperforms state-of-the-art denoising algorithms in terms of visual quality and quantitative metrics, and the strategy demonstrates a robust generalization capability. These findings validate that this simple yet effective strategy demonstrates promising potential for medical image denoising tasks, which could exert a clinical impact in the future. Code is available at: https://github.com/gengmufeng/CNCL-denoising.

Catalytic core-shell nanoparticles with self-supplied calcium and H2O2 to enable combinational tumor inhibition.

Nanoparticles, presenting catalytic activity to induce intracellular oxidative species, have been extensively explored for tumor treatment, but suffer daunting challenges in the limited intracellular H2O2 and thus suppressed therapeutic efficacy. Here in this study, a type of composite nanoparticles, consisting CaO2 core and Co-ferrocene shell, is designed and synthesized for combinational tumor treatment. The findings indicate that CaO2 core can be hydrolyzed to produce large amounts of H2O2 and calcium ions at the acidic tumor sites. Meanwhile, Co-ferrocene shell acts as an excellent Fenton catalyst, inducing considerable ROS generation following its reaction with H2O2. Excessive cellular oxidative stress triggers agitated calcium accumulation in addition to the calcium ions released from the particles. The combined effect of intracellular ROS and calcium overload causes significant tumor inhibition both in vitro and in vivo.

Cu-Ferrocene-Functionalized CaO2 Nanoparticles to Enable Tumor-Specific Synergistic Therapy with GSH Depletion and Calcium Overload.

The conversion of endogenous H2 O2 into toxic hydroxyl radical (• OH) via catalytic nanoparticles is explored for tumor therapy and received considerable success. The intrinsic characteristics of microenvironment in tumor cells, such as limited H2 O2 and overexpressed glutathione (GSH), hinder the intracellular • OH accumulation and thus weaken therapeutic efficacy considerably. In this study, fine CaO2 nanoparticles with Cu-ferrocene molecules at the surface (CaO2 /Cu-ferrocene) are successfully designed and synthesized. Under an acidic condition, the particles release Ca2+ ions and H2 O2 in a rapid fashion, while they can remain stable in neutral. In addition, agitated production of • OH occurs following the Fenton reaction of H2 O2 and ferrocene molecules, and GSH is consumed by Cu2+ ions to avoid the potential • OH consumption. More interestingly, in addition to the exogenous Ca2+ released by the particles, the enhanced • OH production facilitates intracellular calcium accumulation by regulating Ca2+ channels and pumps of tumor cells. It turns out that promoted • OH induction and intracellular calcium overload enable significant in vitro and in vivo antitumor phenomena.

Dynamic R2' Imaging can Be a Biomarker for Diagnosing and Staging Early Acute Kidney Injury in Animals.

Background: Early diagnosis of acute kidney injury (AKI) is essential in clinical settings. None of the current biomarkers are widely applied. The combination of pulse-shifting multi-echo asymmetric spin-echo sequence (psMASE) and a modified hemodynamic response imaging (HRI) technique is promising. The purpose of this study was to evaluate the feasibility of psMASE combined with HRI in detecting early ischemic AKI in animal models of different severities. Methods: Twenty rabbits were divided into four groups (mild, moderate, and severe AKI and control groups). Transarterial embolization with different doses of microspheres was performed to establish AKI animal models of different severities. The 3T psMASE and HRI scans of kidneys were conducted. The R2*, R2, and R2' during room air and gas stimulation were acquired and the difference of R2' (dR2') was evaluated in different AKI groups. Results: The values were not different in R2* and R2 during room air and in R2* and R2, and R2' during gas stimulation. The value of R2' was significantly different during room air (P = 0.014), but the difference was only found between control and moderate/severe AKI groups (P = 0.032 and 0.022). The values of dR2' were different among groups (P < 0.0001) and differences between every two groups except comparison of moderate and severe AKI groups were significant (P < 0.01). Conclusion: The dR2' imaging acquired by a combination of renal psMASE and HRI technique can serve as a potential quantitative biomarker for early detection and staging of AKI.

Feasibility of MRI based oxygenation imaging for the assessment of acute limb ischemia.

BACKGROUND: Acute limb ischemia (ALI) can lead to death and amputation. Evaluating the severity of ischemia is important but difficult, through current methods of examination. The purpose of this research was to demonstrate the feasibility of magnetic resonance imaging (MRI) susceptibility-based imaging techniques for use in assessing muscle oxygenation alterations in ALI. METHODS: ALI animal models were established in 11 rabbits. Their left iliac arteries were embolized by microspheres. MRI scans were conducted 24 hours before (Pre) and 1 hour (Post 1) and 3 hours (Post 2) after the procedure. A susceptibility model was used to calculate skeletal muscle oxygenation extraction fraction (SMOEF) and relaxation rate (R2'). T2 weighted (T2w) imaging and diffusion-weighted (DW) imaging were performed. RESULTS: The average calf muscle SMOEF in the embolized hindlimbs increased from 0.43±0.02 (Pre) to 0.48±0.02 (Post 1) and 0.50±0.02 (Post 2), both P<0.05. The R2' value increased from 13.01±2.31 s-1 (Pre) to 16.78±2.28 s-1 (Post 1) and 17.90±3.29 s-1 (Post 2), both P<0.05. No significant changes of SMOEF and R2' were found after embolization in the contralateral hindlimbs. Apparent diffusion coefficient (ADC) values derived from DW imaging remained unchanged at different stages compared to before the procedures (all P>0.05). No abnormal signals were observed in the anatomical T2w images at Post 1 and Post 2. CONCLUSIONS: This study demonstrates the feasibility of using SMOEF for the assessment of oxygenation alterations in ALI models. SMOEF is more sensitive than T2w and DW imaging in detecting acute muscle ischemia at an early stage.

Quantitative renal function assessment of atheroembolic renal disease using view-shared compressed sensing based dynamic-contrast enhanced MR imaging: An in vivo study.

Atheroembolic renal disease (AERD) is the major cause of renal insufficiency in the elderly, and particularly, the diagnose of AERD is often delayed and even missed due to its nonspecific presentation and the sudden occurrence of an embolic event. To investigate the feasibility of the view-shared compressed sensing (VCS) based dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in the assessment of AERD in animal models. The reproducibility of VCS DCE-MRI based glomerular filtration rate (GFR) estimation was first evaluated using the three healthy rabbits. Animal models of unilateral AERD were then conducted. All the rabbits underwent VCS DCE-MRI and the GFR maps were estimated by a commonly used cortical-compartment model. The whole kidney and suspicious lesion region GFR values of embolized kidneys were then compared with the corresponding values of normal kidneys. Finally, the suspicious lesion regions were confirmed by the corresponding renal specimens and histological findings. The reproducibility of GFR measurements was analyzed using the coefficient of variation and Bland-Altman analysis. The GFR values of normal and embolized kidneys were compared using the Student t-test. Contrast-enhanced images with sufficient diagnostic quality and reduced motion artifacts are obtained at a temporal resolution of 2.5 s. The Bland-Altman plot indicated close agreement between the GFR values estimated from between-day scans in healthy rabbits. Besides, there existed significant differences between the pixel-wise GFR values of normal and AERD kidneys in region-based comparison(P < 0.0001). The suspicious lesions are consistent well with the renal specimen and histological findings. The preliminary animal study verified the feasibility of VCS DCE-MRI for renal function evaluation, and the strategy could potentially provide a valuable tool to identify AERD.

A feasibility study of using noninvasive renal oxygenation imaging for the early assessment of ischemic acute kidney injury in an embolization model.

PURPOSE: To investigate the feasibility of using MRI based oxygenation imaging for early assessment of ischemic acute kidney injury (AKI) in an embolization model. METHODS: Ischemic AKI model was induced in 40 rabbits by injection of microspheres into the right renal arteries. Animals were grouped according to the dose of microspheres: Severe AKI group, 2.0 mg (N = 10); Moderate AKI group, 1.0 mg (N = 10); Mild AKI group, 0.5 mg (N = 10); Control group, saline without microspheres (N = 10). A serial MRI examination was performed at intervals of 1 h, 1 day, 1 week and 4 weeks to evaluate the deterioration of renal function. A multi-echo ASE sequence was implemented for renal oxygenation measurement 1 h after surgery. Pathological examinations were performed 4 weeks after the surgery. RESULTS: In renal cortex, renal oxygen extraction fraction (OEF) raised significantly after embolization procedures in all experimental groups (severe AKI: 0.39 ±â€¯0.05, P < 0.05; moderate AKI: 0.36 ±â€¯0.03, P < 0.05; mild AKI: 0.34 ±â€¯0.02, P < 0.05) compared to the control group (0.29 ±â€¯0.02). In outer medulla, significant difference was observed between control group (0.29 ±â€¯0.03) and severe AKI group (0.35 ±â€¯0.03, P < 0.05), and between control group and moderate AKI group (0.34 ±â€¯0.04, P < 0.05). Corresponding lesions were found in pathological examinations 4 weeks after the procedure. CONCLUSION: This study demonstrates the feasibility of using oxygenation imaging to assess the embolization induced ischemic AKI at an early stage.

Comparison of blood oxygen level-dependent imaging and diffusion-weighted imaging in early diagnosis of acute kidney injury in animal models.

BACKGROUND: Early diagnosis of acute kidney injury (AKI) has clinical importance. Current methods are neither adequately sensitive nor specific. Blood oxygen level-dependent (BOLD) imaging and diffusion-weighted imaging (DWI) may help to assess AKI in the early phase. PURPOSE: To investigate the feasibility of BOLD imaging and DWI in the assessment of AKI and compare the sensitivities of both techniques in early detection of renal damage. STUDY TYPE: Prospective animal study. ANIMAL MODEL: Thirty New Zealand white rabbits. FIELD STRENGTH/SEQUENCE: 3 T clinical MRI/BOLD and DWI. ASSESSMENT: Thirty rabbits were divided into three groups (severe AKI group, mild AKI group, and control group). Transarterial renal embolization with different doses of microspheres was performed to create severe and mild AKI disease models. All the MRI scans of kidneys were conducted within 2 hours after the embolization procedure. Histological examinations with hematoxylin and eosin staining were performed to validate renal damage. STATISTICAL TESTS: Analysis of variance (ANOVA) for comparisons between groups, and paired t-test for tests within the same group. P < 0.05 was considered statistically significant. RESULTS: Both R2* and apparent diffusion coefficient (ADC) showed significant differences between the severe AKI group (56.34 ± 3.45 s-1 for R2*, 1.14 ± 0.23 mm2 /s for ADC) and the control group (28.24 ± 2.26 s-1 for R2*, 1.94 ± 0.33 mm2 /s for ADC, both P < 0.01). However, the ADC values did not show significant differences (P = 0.41) between mild AKI group (1.88 ± 0.31 mm2 /s for ADC) and the control group (1.94 ± 0.33 mm2 /s for ADC), while R2* was still useful in differentiating the two groups (52.32 ± 4.1 s-1 vs. 28.24 ± 2.26 s-1 for R2*, P < 0.01). The histopathologic results were found to be correlated with MRI findings. DATA CONCLUSION: BOLD contrast and DW images are both effective in detecting AKI noninvasively, but BOLD imaging is more sensitive in early detection of mild ischemia than DWI. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:719-724.

Early assessment of acute kidney injury using targeted field of view diffusion-weighted imaging: An in vivo study.

Acute kidney injury (AKI) is a common complication in various clinical settings. In recent years, AKI diagnostics have been investigated intensively showing the emerging need for early characterization of this disease. To verify whether targeted field-of-view diffusion-weighted imaging (tFOV-DWI) is feasible to significantly improve the performance of traditional full field-of-view diffusion-weighted imaging (fFOV-DWI) in the early assessment of AKI. 14 rabbits with unilateral AKI were induced by injection of microspheres under the guidance of digital subtraction angiography (DSA). All rabbits underwent tFOV-DWI and fFOV-DWI immediately after the surgery. Artifacts, distortion and lesion identification were graded by two experienced radiologists, and the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were measured. Apparent diffusion coefficient (ADC) maps were then derived. Blood samples were collected pre- and post-surgery and serum creatinine weres measured. Renal specimen and biopsy were performed as the reference standard. Student t-test was used to ascertain statistical significance between the above parameters for tFOV-DWI and fFOV-DWI. The interobserver agreement and ADC measurements agreement were assessed. A higher percentage of renal lesions (17 out of 19) were detected in tFOV-DWI compared with fFOV-DWI (14 out of 19). Significant differences were observed in ADC value for both techniques between the lesion regions and normal tissues (p < 0.001). Histological findings were inversely correlated with ADC values of tFOV-DWI (r = -0.97, P < 0.001 for cortex; r = -0.98, P < 0.001 for medulla) and fFOV-DWI sequences (r = -0.95, P < 0.001 for cortex; r = -0.98, P < 0.001 for medulla). Those tFOV-DW images rated by the radiologists exhibit superior performance in terms of all assessed measures (P < 0.05), and interobserver agreement was excellent (ICC, 0.78 to 0.92). Besides, the ADC values derived from tFOV-DWI had a satisfactory agreement with those estimated by fFOV-DWI. The animal study demonstrates that the tFOV-DWI strategy provided visually better image quality and lesion depiction than conventional fFOV-DWI for early assessment of AKI.

Compressed sensing based simultaneous black- and gray-blood carotid vessel wall MR imaging.

OBJECTIVE: In this study, we sought to demonstrate the blood suppression performance, image quality and morphological measurements for compressed sensing (CS) based simultaneous 3D black- and gray-blood imaging sequence (CS-siBLAG) in carotid vessel wall MR imaging. MATERIALS AND METHODS: Seven healthy volunteers and five patients were recruited. Healthy subjects underwent five CS-siBLAG scans with 1, 2, 3, 4 and 5-fold accelerations. Signal-to-tissue ratio (STR) and contrast-to-tissue ratio (CTR) were computed as the measures of flowing signal suppression performance and the image quality for black-blood imaging of the technique. Vessel lumen area (LA) and wall area (WA) were compared between fully sampled acquisition and each accelerated acquisition. Patients underwent three CS-siBLAG scans with 1, 3 and 5-fold accelerations as well as a 3D time of flight (3D TOF) scan. Two radiologists reviewed the under-sampled black- and gray-blood image quality. RESULTS: STR and CTR values obtained with 2 to 5-fold accelerations were not significantly different from those with full acquisition. LA and WA measured at 2×, 3×, 4× and 5× were all highly correlated to the corresponding values at 1×. For patients imaging, two radiologists both found that the dual-contrast images at 3× acceleration exhibited comparable image quality to that of the fully sampled acquisition, and that the images at 5× exhibited slightly blurred vessel wall and outer vessel wall boundaries. CONCLUSION: By combining the CS under-sampling pattern and reconstruction, pseudo-centric phase encoding order and dual blood contrast sequences, this technique provides spatially registered black- and gray-blood images and excellent visualization for vessel wall imaging and gray-blood imaging in a short scan time.