1.Evaluation of non-contrast magnetic resonance imaging as an imaging surveillance tool for hepatocellular carcinoma in at-risk patients.
Jing Kai Joel LIU ; Chau Hung LEE ; Cher Heng TAN
Singapore medical journal 2022;63(4):203-208
INTRODUCTION:
This study aimed to evaluate the potential of non-contrast-enhanced magnetic resonance (MR) imaging as an imaging surveillance tool for detection of hepatocellular carcinoma (HCC) in at-risk patients and to compare the performance of non-contrast MR imaging with ultrasonography (US) as a screening modality for the same.
METHODS:
In this retrospective study, patients diagnosed with HCC between 1 January 2010 and 31 December 2015 were selected from our institution's cancer registry. Patients who underwent MR imaging and had US performed within three months of the MR imaging were included. For each MR imaging, two non-contrast MR imaging sequences - T2-weighted fat-saturated (T2-W FS) sequence and diffusion-weighted imaging (DWI) - were reviewed for the presence of suspicious lesions. A non-contrast MR image was considered positive if the lesion was seen on both sequences. The performance of non-contrast MR imaging was compared to that of hepatobiliary US for the detection of HCC.
RESULTS:
A total of 73 patients with 108 HCCs were evaluated. Sensitivity of non-contrast MR imaging for the detection of HCC using T2-W FS and DWI was 93.2%, which was significantly higher than that of US, which was 79.5% (p = 0.02). In a subgroup of 55 patients with imaging features of liver cirrhosis, the sensitivity of non-contrast MR imaging was 90.9%, which was also significantly higher than that of US, which was 74.5% (p = 0.02).
CONCLUSION
Our pilot study showed that non-contrast MR imaging, using a combination of T2-W FS and DWI, is a potential alternative to US as a screening tool for surveillance of patients at risk for HCC.
Carcinoma, Hepatocellular/pathology*
;
Contrast Media
;
Diffusion Magnetic Resonance Imaging/methods*
;
Gadolinium DTPA
;
Humans
;
Liver Neoplasms/pathology*
;
Magnetic Resonance Imaging/methods*
;
Pilot Projects
;
Retrospective Studies
;
Sensitivity and Specificity
2.Epidural photobiomodulation accelerates the drainage of brain interstitial fluid and its mechanism.
Ying CAI ; Qiao Qin WAN ; Xian Jie CAI ; Ya Juan GAO ; Hong Bin HAN
Journal of Peking University(Health Sciences) 2022;54(5):1000-1005
OBJECTIVE:
To evaluate the effect of photobiomodulation (PBM) on the drainage of brain interstitial fluid (ISF) and to investigate the possible mechanism of the positive effect of PBM on Alzheimer's disease (AD).
METHODS:
Twenty-four SD male rats were randomly divided into PBM group (n=12), sham PBM group (n=6), and negative control group (n=6). According to the injection site of tracer, the PBM group was further divided into PBM-ipsilateral traced group (n=6) and PBM-contralateral traced group (n=6). Rats in the PBM group and the sham PBM group were exposed to the dura minimally invasively on the skull corresponding to the frontal cortical area reached by ISF drainage from caudate nucleus region. The PBM group was irradiated by using 630 nm red light (5-6 mW/cm2), following an irradiation of 5 min with a 2 min pause, and a total of 5 times; the sham PBM group was kept in the same position for the same time using the light without power. The negative control group was kept without any measure. After PBM, tracer was injected into caudate nucleus of each group. The changes of ISF drainage in caudate nucleus were observed according to the diffusion and distribution of tracer molecule by tracer-based magnetic resonance imaging, and the structural changes of brain extracellular space (ECS) were analyzed by diffusion rate in ECS-mapping (DECS-mapping) technique. Finally, parameters reflecting the structure of brain ECS and the drainage of ISF were obtained: volume fraction (α), tortuo-sity (λ), half-life (T1/2), and DECS. The differences of parameters among different groups were compared to analyze the effect of PBM on brain ECS and ISF. One-Way ANOVA post hoc tests and independent sample t test were used for statistical analysis.
RESULTS:
The parameters including T1/2, DECS, and λ were significantly different among the PBM-ipsilateral traced group, the PBM-contralateral traced group, and the sham PBM group (F=79.286, P < 0.001; F=13.458, P < 0.001; F=10.948, P=0.001), while there was no difference in the parameter α of brain ECS among the three groups (F=1.217, P=0.324). Compared with the sham PBM group and the PBM-contralateral traced group, the PBM-ipsilateral traced group had a significant decrease in the parameter T1/2 [(45.45±6.76) min vs. (76.01±3.44) min, P < 0.001; (45.45±6.76) min vs. (78.07±4.27) min, P < 0.001], representing a significant acceleration of ISF drainage; the PBM-ipsilateral traced group had a significant increase in the parameter DECS [(4.51±0.77)×10-4 mm2/s vs. (3.15±0.44)×10-4 mm2/s, P < 0.001; (4.51±0.77)×10-4 mm2/s vs. (3.01±0.38)×10-4 mm2/s, P < 0.001], representing a significantly increased molecular diffusion rate of in the brain ECS; the PBM-ipsilateral traced group had a significant decrease in the parameter λ (1.51±0.21 vs. 1.85±0.12, P=0.001; 1.51±0.21 vs. 1.89±0.11, P=0.001), representing a significant decrease in the degree of tortuosity in the brain ECS.
CONCLUSION
PBM can regulate the brain ISF drainage actively, which may be one of the potential mechanisms of the effect of PBM therapy on AD. This study provides a new method for enhancing the brain function via ECS pathway.
Animals
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Male
;
Rats
;
Alzheimer Disease
;
Brain
;
Drainage
;
Extracellular Fluid
;
Gadolinium DTPA/metabolism*
;
Low-Level Light Therapy
;
Rats, Sprague-Dawley
3.Application Values of Gadolinium-ethoxybenzyl Diethylenetriaminepentaacetic Acid Enhanced Magnetic Resonance Imaging-based Radiomics in the Quantitative Assessment of Liver Reserve Function of Patients with Liver Cirrhosis.
Wei ZHOU ; Hong-Jie HU ; Bo SHEN ; Wei-Qiang SHEN ; Hao CHEN ; Xiao WU ; Qiang YAN ; Pei-Pei PANG
Acta Academiae Medicinae Sinicae 2020;42(4):459-467
To evaluate the correlation between the radiomics signature of hepatobiliary phase imaging of gadolinium-ethoxybenzyl diethylenetriaminepentaacetic acid(Gd-EOB-DTPA)enhanced magnetic resonance imaging(MRI)and Child-Pugh of liver cirrhosis,establish nomogram prediction model,and assess the predictive value of quantitative assessment of liver reserve function of patients with liver cirrhosis. One hundred patients with liver cirrhosis who met the inclusion criteria were divided into 52 patients with Child-Pugh grade A and 48 patients with Child-Pugh grade B+C according to Child-Pugh classification criteria,and were randomly divided into training set and test set at a proportion of 7∶3.The AK software was used to extract the imaging features of the Gd-EOB-DTPA-enhanced MRI hepatobiliary images of the patients in the training set,and the least absolute shrinkage and selection operator feature selection algorithm was used to reduce the dimension of the data,select the features,and construct the radiomics tags.According to the radiomics label Rad-score,a line chart(nomogram)prediction model was established to predict the Child-Pugh B+C level of liver reserve function.The model was applied to the training set and test set respectively,and the diagnostic efficiency was quantitatively evaluated by receiver operating characteristic(ROC)curve. After dimension reduction and screening of 396 texture feature parameters extracted by AK software,7 image feature parameters were obtained.According to the above characteristics,the radiomics tag Rad-score was constructed and the nomogram prediction model was created.The differences of Rad-score scores between Child-Pugh A and Child-Pugh B+C groups in training set and test set were statistically analyzed by Wilcoxon rank sum test(=0.000, =0.001).The diagnostic efficacy of nomogram prediction model for predicting Child-Pugh B+C grade of liver reserve function in the ROC curve of training set and test set was 0.88 and 0.86 respectively. The nomogram prediction model created according to the radiomics tag Rad-score of patients with liver cirrhosis with different liver reserve functions can be used as a more accurate and reliable auxiliary detection tool for liver reserve function.It provides a new means for clinicians to evaluate liver reserve function more accurately.
Contrast Media
;
Gadolinium DTPA
;
Humans
;
Liver Cirrhosis
;
Magnetic Resonance Imaging
4.Effect of convection enhanced delivery on the microstructure of brain extracellular space in aged rats.
Yu SONG ; Hong Bin HAN ; Jun YANG ; Ai Bo WANG ; Qing Yuan HE ; Yuan Yuan LI ; Guo Mei ZHAO ; Ya Juan GAO ; Rui WANG ; Yi Xing HAN ; Ai Lian LIU ; Qing Wei SONG
Journal of Peking University(Health Sciences) 2020;52(2):362-367
OBJECTIVE:
To compare the changes of extracellular space (ECS) structure and local drug distribution in adult brain and aged brain at different drug delivery rates in minimally invasive treatment of encephalopathy by convection enhanced delivery (CED) via ECS pathway.
METHODS:
Thirty-six SD male rats were divided into adult rats group (2-8 months, n=18) and aged rats group (18-24 months, n=18) according to the age of the month. According to the drug rates (0.1 μL/min, 0.2 μL/min, and 0.3 μL/min), they were randomly divided into 3 subgroups, 6 in each subgroup. Gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) with a concentration of 10 mmol/L were introduced into the caudate nucleus of each group of rats by stereotactic injection. Tracer-based magnetic resonance imaging (MRI) was used to dynamically monitor the diffusion and distribution images of the Gd-DTPA in the brain interstitial system (ISS). Using the self-developed MRI image measurement and analysis system software to process and analyze the obtained images, the diffusion coefficient, clearance rate, volume fraction, and half-life of each group of rats in the caudate nucleus ECS could be acquired. The effects and differences of drug clearance and ECS structural function in the brain of aged rats and adult rats were compared and analyzed at different drug delivery rates. Magnetic tracer DECS-mapping technique was used to observe the distribution and drainage of tracer in caudate nucleus.
RESULTS:
At the injection rate of 0.1 μL/min, the volume fraction in the aged rats was increased compared with that in the adult rats (18.20%±0.04% vs. 17.20%±0.03%, t=3.752, P=0.004), and the degree of tortuosity was decreased (1.63±0.04 vs. 1.78±0.09, t=-3.680, P=0.004), the drug clearance rate was decreased [(1.94±0.68) mm2/s vs. (3.25±0.43) mm2/s, t=-3.971, P=0.003], and the molecular diffusion in ECS was increased [(3.99±0.21)×10-4 mm2/s vs. (3.36±0.37)×10-4 mm2/s, t=3.663, P=0.004]. When the rate of injection increased to 0.2 μL/min, the drug clearance in ECS of the aged rats was slowed down [(2.53±0.45) mmol/L vs. (3.37±0.72) mmol/L, t=-1.828, P=0.021]. However, there were no significant differences in volume fraction, molecular diffusion in ECS and macroscopic drug metabolism parameters. When the rate of injection increased to 0.3 μL/min, the volume fraction in the aged rats was decreased (17.20%±0.03% vs. 18.20%±0.05%, t=-0.869, P=0.045), and the drug clearance rate in ECS was significantly accelerated [(4.04±0.76) mmol/L vs. (3.26±0.55) mmol/L, t=1.786, P=0.014], and there was no significant difference in tortuosity and the rate of molecular diffusion in the ECS.
CONCLUSION
The drug clearance and ECS structural parameters of brain ECS in aged brain with CED administration were changed at different rates, and it has the least effect on ECS in the aged brain at the injection rate of 0.2 μL/min. For the application of CED for the treatment of encephalopathy, we should consider the influence of factors such as age and injection rate, and provide reference for the development of individualized clinical treatment plan for minimally invasive treatment of encephalopathy via ECS pathway.
Animals
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Brain
;
Convection
;
Extracellular Space
;
Gadolinium DTPA
;
Magnetic Resonance Imaging
;
Male
;
Rats
;
Rats, Sprague-Dawley
5.Value of Texture Analysis on Gadoxetic Acid-enhanced MR for Detecting Liver Fibrosis in a Rat Model.
Jia XU ; Xuan WANG ; Zheng-Yu JIN ; Yan YOU ; Qin WANG ; Shi-Tian WANG ; Hua-Dan XUE
Chinese Medical Sciences Journal 2019;34(1):24-32
Objective To explore the ability of texture analysis of gadoxetic acid-enhanced magnetic resonance imaging (MRI) T1 mapping images, as well as T1-weighted (T1W), T2-weighted (T2W) and apparent diffusion coefficient (ADC) maps for distinguishing between varying degrees of hepatic fibrosis in an experimental rat model.Methods Liver fibrosis in rats was induced by carbon tetrachloride intraperitoneal injection for 4-12 weeks (n=30). In the control group (n=10) normal saline was applied. The MRI protocol contained T2W, diffusion weighted imaging, pre-and post-contrast image series of T1W and T1 mapping images. METAVIR score was used to grade liver fibrosis as normal (F0), mild fibrosis (F1-2), and advanced fibrosis (F3-4). Texture parameters including mean gray-level intensity (Mean), standard deviation (SD), Entropy, mean of positive pixels (MPP), Skewness, and Kurtosis were obtained. Nonparametric Mann-Whitney U test was used to compare the average value of each texture parameter in each sequence for assessing the difference between F0 and F≥1 as well as F0-2 and F3-4. Receiver operating characteristic (ROC) curves were obtained to assess the diagnosing accuracy of the parameters for differentiating no liver fibrosis from liver fibrosis and rats with liver fibrosis grading F0-2 from those with grading F3-4. The area under ROC curve (AUC) was calculated to evaluate the diagnostic efficiency of texture parameters.Results Finally, 20 rats completed MR T1 mapping image scan. The pathologic staging of these 20 rats was no fibrosis (F0, n=6), mild fibrosis (F1-2, n=5) and advanced fibrosis (F3-4, n=9). On pre-contrast T1 mapping image, Entropy was seen to be statistically significant higher in the F≥1 group than that in the F0 group at each spatial scaling factor (SSF) setting (P=0.015, 0.015, 0.015, 0.013, 0.015 and 0.018 respectively to SSF=0, 2, 3, 4, 5, 6), and Mean of the F≥1 rats was statistically significant higher than that of the F0 rats at SSF 4, 5, 6 (P=0.004, 0.006, and 0.013, respectively). Entropy and Mean showed a moderate diagnostic performance in most SSF settings of T1 mapping pre-contrast images for differentiation of normal liver from liver fibrosis.Conclusions Certain texture features of gadoxetic acid-enhanced MR images, especially the Entropy of non-contrast T1 mapping image, was found to be a useful biomarker for the diagnosis of liver fibrosis.
Animals
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Contrast Media
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pharmacology
;
Diffusion Magnetic Resonance Imaging
;
Disease Models, Animal
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Gadolinium DTPA
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pharmacology
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Liver Cirrhosis
;
diagnostic imaging
;
physiopathology
;
Male
;
Rats
;
Rats, Sprague-Dawley
6.Temporary acceleration of interstitial fluid drainage in excited brain region induced by movement.
Wei WANG ; Jin HOU ; Wen Qiang HUANG
Journal of Peking University(Health Sciences) 2019;51(2):206-209
OBJECTIVE:
To investigate the changes of brain interstitial fluid (ISF) induced by movement.
METHODS:
Twenty mature male Sprague-Dawley rats were randomly divided into two groups: control group and movement group. Electrophysiological neurons in caudate nuclear of additional five rats were recorded and the differences analyzed between under anesthesia and by movement. In the control group, the rats were anesthetized using isoflurane continuously during the experiment process. In the meantime the magnetic tracer was injected into the center of the caudate nucleus and multi-period magnetic resonance scanning was performed at several time points until high signal intensity invisible in the images. In the movement group, the rats were anesthetized for the injection of the tracer, and the first post-injection magnetic resonance scanning was performed. Then the rats were waken and allowed moving voluntarily for 20 minutes. The rats were anesthetized again and multi-period magnetic resonance scanning was performed until the experiment ended. NanoDetect system (Version 1.2, MRI lab, Beijing, China) was used to measure the parameters on ISF, which included the weighed signal intensity (weighed ΔSI) , the term predicting the amount of the tracer, and half-time of the tracer. In movement group, the weighed ΔSI at the time points of pre-movement and 10, 40, 70, 130, and 190 minutes after movement were calculated respectively. In control group, the weighed ΔSI at the same time points also were measured. The weighed ΔSI and half-time were compared between the two groups.
RESULTS:
The electrophysiological recording and data analysis showed significant difference in the local field potential of Caudate Nucleus between under anesthesia and by movement. The weighed ΔSI (unit: ΔSI×mm3) values of the two groups, presented by movement group vs. control group, were as followings, 60 257.1±23 069.2 vs. 61 072.0±19 547.3 at pre-move, 83 624.3±21 475.7 vs. 71 218.1±12 586.5 at 10 min after movement, 57 336.0±36 243.4 vs. 69 756.1±13 306.0 at 40 min after movement, 43 705.9±10 246.3 vs. 55 443.2±20 733.3 at 70 min after movement, 7 734.9±2 645.2 vs. 8 967.6±2 007.3 at 130 min after movement and 2 497.3±987.5 vs. 3 013.2±1 760.8 at 190 min after movement. Moreover, at 40 min after movement, the weighed ΔSI of movement group was significantly reduced compared with control group (P<0.05). The half-time was not significantly different [(104.3±54.1) min vs. (113.4±47.3) min, P>0.05].
CONCLUSION
ISF drainage of caudate nuclear can be acclerated temporarily by movement.
Animals
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Beijing
;
Brain
;
China
;
Drainage
;
Extracellular Fluid
;
Gadolinium DTPA
;
Male
;
Rats
;
Rats, Sprague-Dawley
7.Gadolinium Ethoxybenzyl Diethylene-triamine-pentaacetic-acid-enhanced Magnetic Resonance Imaging Perfusion and Multiple Hepatobiliary-phase Imaging for Quantitative Assessment of Liver Fibrosis in Rat Models.
Jia XU ; Xuan WANG ; Yan YOU ; Hua Dan XUE ; Qin WANG ; Shi Tian WANG ; Zheng Yu JIN
Acta Academiae Medicinae Sinicae 2018;40(6):809-816
Objective To investigate the value of gadolinium ethoxybenzyl diethylene-triamine-pentaacetic-acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) in detecting different stages of liver fibrosis in rats.Methods Rat models of liver fibrosis were induced by carbon tetrachloride intraperitoneal injection for 4 - 12 weeks (n=45). The control group was applied with 0.9% saline (n=15). The MRI protocol contained both dynamic contrast-enhanced sequence (60 continuous scans within 3 minutes,including three pre-contrast measurements) and multiple hepatobiliary-phase acquisitions (every 5 minutes after contrast injection,60 minutes in total). METAVIR score was used to grade liver fibrosis:normal (F0),mild fibrosis (F1 - F2),and advanced fibrosis (F3 - F4). Liver perfusion parameters [transfer constant (K ),extravascular extracellular volume fraction (V),initial area under curve (iAUC),maximum relative enhancement (RE),and time of maximum RE (T)] as well as hepatobiliary-phase parameters [RE at different time point,the decrease of RE (RE=RE - RE),and elimination half-life of RE (T)] were measured and compared with ANOVA analysis and Spearman rank correlation.Results Thirty-one rats completed MRI exams and were then divided into normal (n=10),mild fibrosis (n=10),and advanced fibrosis (n=11) groups. K ,V and iAUC decreased as liver fibrosis progressed (r=-0.631,P=0.002;r=-0.503,P=0.017;r=-0.446,P=0.037). K and V showed significant differences among three groups(F=7.011,P=0.005;F=4.656,P=0.023). K and V were significantly lower in advanced fibrosis group than in normal group (P=0.001,P=0.009). There were statistical significant differences of T,T and RE among groups(F=6.633,P=0.005;F=5.493,P=0.010;F=5.343,P=0.014). Compared to normal and mild fibrosis groups,advanced fibrosis group had significantly longer T and T (P=0.005,P=0.004;P=0.008,P=0.008)and significantly lower RE(P=0.007,P=0.012).Conclusion Perfusion and multi-hepatobiliary-phase parameters such as K ,V,T, T and RE obtained from Gd-EOB-DTPA-enhanced MRI,may be valuable for detecting and staging liver fibrosis.
Animals
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Contrast Media
;
chemistry
;
Gadolinium DTPA
;
chemistry
;
Liver
;
diagnostic imaging
;
pathology
;
Liver Cirrhosis
;
diagnostic imaging
;
Magnetic Resonance Imaging
;
Rats
8.Optimization of the Flip Angle and Scan Timing in Hepatobiliary Phase Imaging Using T1-Weighted, CAIPIRINHA GRE Imaging
Jeongjae KIM ; Bong Soo KIM ; Jeong Sub LEE ; Seung Tae WOO ; Guk Myung CHOI ; Seung Hyoung KIM ; Ho Kyu LEE ; Mu Sook LEE ; Kyung Ryeol LEE ; Joon Hyuk PARK
Investigative Magnetic Resonance Imaging 2018;22(1):1-9
PURPOSE: This study was designed to optimize the flip angle (FA) and scan timing of the hepatobiliary phase (HBP) using the 3D T1-weighted, gradient-echo (GRE) imaging with controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA) technique on gadoxetic acid-enhanced 3T liver MR imaging. MATERIALS AND METHODS: Sixty-two patients who underwent gadoxetic acid-enhanced 3T liver MR imaging were included in this study. Four 3D T1-weighted GRE imaging studies using the CAIPIRINHA technique and FAs of 9° and 13° were acquired during HBP at 15 and 20 min after intravenous injection of gadoxetic acid. Two abdominal radiologists, who were blinded to the FA and the timing of image acquisition, assessed the sharpness of liver edge, hepatic vessel clarity, lesion conspicuity, artifact severity, and overall image quality using a five-point scale. Quantitative analysis was performed by another radiologist to estimate the relative liver enhancement (RLE) and the signal-to-noise ratio (SNR). Statistical analyses were performed using the Wilcoxon signed rank test and one-way analysis of variance. RESULTS: The scores of the HBP with an FA of 13° during the same delayed time were significantly higher than those of the HBP with an FA of 9° in all the assessment items (P < 0.01). In terms of the delay time, images at the same FA obtained with a 20-min-HBP showed better quality than those obtained with a 15-min-HBP. There was no significant difference in qualitative scores between the 20-min-HBP and the 15-min-HBP images in the non-liver cirrhosis (LC) group except for the hepatic vessel clarity score with 9° FA. In the quantitative analysis, a statistically significant difference was found in the degree of RLE in the four HBP images (P = 0.012). However, in the subgroup analysis, no significant difference in RLE was found in the four HBP images in either the LC or the non-LC groups. The SNR did not differ significantly in the four HBP images. In the subgroup analysis, 20-min-HBP imaging with a 13° FA showed the highest SNR value in the LC-group, whereas 15-min-HBP imaging with a 13° FA showed the best value of SNR in the non-LC group. CONCLUSION: The use of a moderately high FA improves the image quality and lesion conspicuity on 3D, T1-weighted GRE imaging using the CAIPIRINHA technique on gadoxetic acid, 3T liver MR imaging. In patients with normal liver function, the 15-min-HBP with a 13° FA represents a feasible option without a significant decrease in image quality.
Acceleration
;
Artifacts
;
Breath Holding
;
Contrast Media
;
Fibrosis
;
Gadolinium DTPA
;
Humans
;
Injections, Intravenous
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Liver
;
Magnetic Resonance Imaging
;
Signal-To-Noise Ratio
9.Role of aquaporin-4 in the change of interstitial fluid drainage in Alzheimer's disease.
E LIU ; Yi Xuan ZHANG ; Lin Lin SUN ; Ze TENG ; Ai Bo WANG ; Hong Bin HAN ; Jun Hao YAN
Journal of Peking University(Health Sciences) 2018;50(2):203-206
OBJECTIVE:
To observe the characteristics of the interstitial fluid (ISF) drainage in the Alzheimer's disease (AD) rats through magnetic resonance imaging (MRI) tracer gadolinium-diethylene triamine pentacetic acid (Gd-DTPA)spread in the brain extracellular space (ECS) and to discuss the role of aquaporin-4 (Aqp4) in the AD.
METHODS:
Wild type SD rats (300-350 g) and Aqp4 gene knock out (Aqp4-/-) SD rats (300-350g) were divided into Sham group, AD group, Aqp4-/--Sham group and Aqp4-/--AD group. Sham group and Aqp4-/--Sham group were injected with saline by intraperitoneal each day for 6 weeks, and the AD group and Aqp4-/--AD group were injected with D-galactose by intraperitoneal each day for 6 weeks. MRI tracer Gd-DTPA (10 mmol/L, 2 μL) was injected into the hippocampus of the rats. MRI scan was performed at the end of 0.5 h, 1.5 h, 1 h, 2 h, and 3 h to observe the dynamic distribution of the Gd-DTPA in the hippocampus and the diffusion rate D*, clearance rate k' and half-life t1/2 measured.
RESULTS:
The diffusion rate D* in Sham group was (2.66±0.36)×10-6 mm2/s, the diffusion rate D* in AD group was (2.72±0.62)×10-6 mm2/s, the diffusion rate D* in Aqp4-/--Sham group was (2.75±0.47)×10-6 mm2/s, the diffusion rate D* in Aqp4-/--AD group was (2.802±0.55)×10-6 mm2/s, and there was no statistically significant difference in the four groups (One-Way ANOVA, P>0.05).The clearance rate k' in Sham group was (4.57±0.14)×10-4/s, the clearance rate k' in AD group was (3.68±0.22)×10-4/s, the clearance rate k' in Aqp4-/--Sham group was (3.17±0.16)×10-4/s, the clearance rate k' in Aqp4-/--AD group was (2.59±0.19)×10-4/s, and there was significant difference in the four groups (One-Way ANOVA, P<0.05). The half-life t1/2 in Sham group was (0.67±0.12) h, the half-life t1/2 in AD group was (0.88±0.08) h, the half-life t1/2 in Aqp4-/--Sham group was (1.12±0.15) h, the half-life t1/2 in Aqp4-/--AD group was (1.58±0.11) h, and there was significance difference in the four groups(one-way ANOVA,P<0.05).
CONCLUSION
The ISF drainage is slow after AD and the loss of Aqp4 in the AD makes the ISF drainage obviously slow down, Aqp4 plays an important role in AD to remove the metabolism of waste out of the brain.
Alzheimer Disease/physiopathology*
;
Animals
;
Aquaporin 4/genetics*
;
Brain/physiopathology*
;
Diffusion
;
Drainage
;
Extracellular Fluid
;
Extracellular Space
;
Gadolinium DTPA
;
Magnetic Resonance Imaging
;
Rats
;
Rats, Sprague-Dawley
10.Application of anoptomagnetic probe Gd-DO3A-EA-FITC in imaging and analyzing the brain interstitial space.
Yun Qian LI ; Hui SHENG ; Lei LIANG ; Yue ZHAO ; Huai Ye LI ; Ning BAI ; Tong WANG ; Lan YUAN ; Hong Bin HAN
Journal of Peking University(Health Sciences) 2018;50(2):221-225
OBJECTIVE:
To investigate the application of the optical magnetic bimodal molecular probe Gd-DO3A-ethylthiouret-fluorescein isothiocyanate (Gd -DO3A-EA-FITC) in brain tissue imaging and brain interstitial space (ISS).
METHODS:
In the study, 24 male SD rats were randomly divided into 3 groups, including magnetic probe group (n=6), optical probe group (n=6) and optical magnetic bimodal probe group (n=12), then the optical magnetic bimodal probe group was divided equally into magnetic probe subgroup (n=6) and optical probe subgroup (n=6). Referencing the brain stereotaxic atlas, the coronal globus pallidus as center level, the probes including gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA), fluorescein isothiocyanate (FITC) and Gd-DO3A-EA-FITC of 2 μL (10 mmol/L) were injected into the caudate nucleus respectively, magnetic resonance imaging (MRI) was performed in the magnetic probe group and magnetic probe subgroup to image the dynamic diffusion and distribution of the probes in the brain ISS, a self-developed brain ISS image processing system was used to measure the diffusion coefficient, clearance, volume fraction and half-time in these two groups. Laser scanning confocal microscope (LSCM) was performed in vitro in the optical probe group and optical probe subgroup for fluorescence imaging at the time points 2 hours after the injection of the probe, and the distribution in the oblique sagittal slice was compared with the result of the first two groups.
RESULTS:
For the magnetic probe group and magnetic probe subgroup, there were the same imaging results between the probes of Gd-DTPA and Gd-DO3A-EA-FITC. The diffusion parameters of Gd-DTPA and Gd-DO3A-EA-FITC were as follows: the average diffusion coefficients [(3.31±0.11)×10-4 mm2/s vs. (3.37±0.15)×10-4 mm2/s, t=0.942, P=0.360], the clearance [(3.04±0.37) mmol/L vs. (2.90±0.51) mmol/L, t=0.640, P=0.531], the volume fractions (17.18%±0.14% vs. 17.31%±0.15%, t=1.961, P=0.068), the half-time [(86.58±3.31) min vs. (84.61±2.38) min, t=1.412, P=0.177], the diffusion areas [(23.25±0.68) mm2 vs. (22.71±1.00) mm2, t=1.100, P=0.297]. The statistical analysis of each brain was made by t test, and the diffusion parameters were not statistically significant. Moreover, for the optical probe group and optical probe subgroup, the diffusion area of Gd-DO3A-EA-FITC [(22.61±1.16) mm2] was slightly larger than that of FITC [(22.10±1.29) mm2], the statistical analysis of each brain was made by t test, and the diffusion parameters were not statistically significant (t=0.713, P=0.492).
CONCLUSION
Gd-DO3A-EA-FITC shows the same imaging results as the traditional GD-DTPA, and it can be used in measuring brain ISS.
Animals
;
Brain/diagnostic imaging*
;
Caudate Nucleus
;
Contrast Media
;
Diffusion
;
Fluorescein-5-isothiocyanate
;
Fluorescence
;
Gadolinium DTPA
;
Imaging, Three-Dimensional
;
Magnetic Resonance Imaging
;
Male
;
Microscopy, Confocal
;
Molecular Probes
;
Rats
;
Rats, Sprague-Dawley

Result Analysis
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