3.0T MRI BOLD and ASL-fMRI imaging of the use of iodine contrast-enhanced renal damage

Title: 3.0T MRI BOLD and ASL-fMRI imaging of the use of iodine contrast-enhanced renal damage evaluation studies Author: Liu products Degree awarded by: Southern Medical University Keywords: 3.0T magnetic resonance imaging;; iodine contrast agent;; kidney damage;; blood oxygen level dependent;; arterial spin labeling proton Abstract:
Background and significance:
Iodine-containing contrast agent is mainly Neodymium Magnets excreted by the kidneys, in recent years, the renal function caused by iodine contrast agent
To damage caused wide attention and research scholars. Iodine contrast agent injected into the body after temporary renal function can even continue to lose, by the
Iodine contrast agent-induced renal damage is known as contrast-induced nephropathy. The current use of iodine contrast agent cause kidney damage is an iatrogenic acute renal
The third largest cause of failure, after surgery and hypotension; about all of iatrogenic acute renal failure 10%, significantly increased in patients
Mental and financial burden, but also significantly increase the social and economic burden. Therefore, the kidney damage caused by iodine contrast agents for early detection, early prevention,
Early treatment has important clinical significance. Currently, the most commonly used clinical method of detection for the measurement of renal function in patients with serum creatinine concentration
And changes. However, studies have shown that changes in serum creatinine concentration and renal damage in the early insensitive. Therefore, the search for new,
Sensitive and early detection, early diagnosis and early prevention of kidney damage due to iodine contrast agent methods in clinical significance.

Many studies have shown that renal medullary blood flow changes in the iodine contrast agents play an important role in kidney disease. Renal medullary blood flow changes, can cause marrow
Qualitative change in oxygen content. http://www.everbeenmagnet.com/en/products/110-sintered-neodymium-magnets So far, kidney blood flow in animals and oxygen content of the study, invasive methods are used. Traditionally, the measurement
Renal medullary blood flow by applying invasive laser Doppler probes. However, renal medullary blood flow in the body of the study, invasive monitoring
Measurement instruments difficult to implement. The ideal method is in the physiological state, the use of non-invasive means of monitoring renal medullary blood flow and oxygen content of iodine in the study
Contrast nephropathy is essential, but also the people committed to research focus.
With advances in magnetic resonance equipment, functional magnetic resonance imaging
For many diseases, early detection, early diagnosis provides a powerful means and methods. Some studies have shown that blood oxygen level-dependent magnetic
Resonance imaging (Blood Oxygen Level Dependent Function Magnetic Resonance Imaging, BOLD-
fMRI) technology can effectively monitor changes in oxygen metabolism in the kidney medulla. Arterial spin labeling magnetic resonance imaging (Arterial Spin
Labeling Function Magnetic Resonance Imaging, ASL-fMRI) without exogenous contrast agents, only the use of tissues and organs
Their perfusion, quantitative detection of tissue and organ perfusion. The two are often present functional magnetic resonance imaging methods.
Current interest
Using BOLD and ASL-fMRI imaging in hypertensive kidney disease, diabetes, kidney diseases such as atherosclerosis and kidney cancer research has made
Significant effect. Studies have shown that, BOLD and ASL-fMRI technique the measured data in a different observers and repeated the same observer has a good
Sex. Thus, most scholars believe that the BOLD and ASL-fMRI technology in the diagnosis and evaluation of kidney disease has a very large potential value
. But so far, the application of BOLD and ASL-fMRI using iodine contrast agent technology assessment of renal function damage of rare literature.

In this study, functional magnetic resonance imaging (Function Magnetic Resonance Imaging, fMRI) BOLD and ASL imaging technology supervisor
Injection of iodine contrast agent measured renal perfusion and oxygen metabolism changes in the physiological conditions of iodine contrast agent injected into the renal function changes after
Change, due to impaired renal function to evaluate the situation, and exploring non-invasive, simple, practical assessment of iodine contrast agent injected into the renal damage after
Method.
Objective:
1 of 3.0TMRI BOLD and ASL imaging experiments in normal rat kidney research

2 of 3.0TMRI-BOLD imaging in rats after iodine-contrast-enhanced experimental study of kidney damage
3, of
3.0TMRI-ASL imaging of iodine contrast agent enhancement in rats after experimental study of kidney damage
4, of 3.0TMRI-BOLD and
ASL imaging technology combined with the assessment of iodine contrast-enhanced rat renal damage value.
Materials and methods:
1, real
Animal testing and preparation
Purchase of 29 SD rats. Sex, weighing in 109.60g ± 14.26g. Each MRI scan before the fasting rat
Water deprivation 4 hours, 30 minutes after anesthesia for abdominal MRI scan.
2, MRI scan
2.1 MRI scan sequences and methods


① tri-plane orientation as: transverse, sagittal and coronal.
② conventional MRI sequences: T2WI axial, T2WI coronal,
Axial T1WI, using fast spin echo (fast spin echo, FSE) sequence
③ BOLD imaging sequences: coronal, several times
Fast gradient echo (multilple-fast gradientrecalled echo, MFGRE sequence
④ ASL, imaging sequences: coronal,
Flow-sensitive alternating inversion recovery technique (Flow SensitiveAltemating Inversion Recovery, FAIR), single-shot fast
Spin-echo sequence (Single-ShotFast Spin Echo, SSFSE) FAIR-SSFSE, sequence
2.2 MRI scan method in rats:

Equipment: The 3.0TMRI scanner, 50mmbirdcage animal experiments dedicated coil. Using the first advanced, supine position.
Method:
Injection of iodine contrast agent, respectively, before, after injection of iodine contrast agent 20 minutes, 24 hours, 48 ​​hours, 72 hours, respectively, for MRI scans. Injection
Iodine contrast agent as a control group before the scan sequence: T1WI, T2WI, BOLD, FSE-FAIR scan, scan time: about 14 minutes and 12 seconds; injection
After iodine contrast agent in 20 minutes, 24 hours, 48 ​​hours, 72 hours experimental group, at each time point scanning T2WI coronal, BOLD, FSE-FAIR
Sequence; were scanned four times, each scan time: 6 minutes 14 seconds.
3, MRI image analysis
3.1 Image Quality sub-
Analyze
Two experienced physicians, respectively, of MR analysis of the sequence of diagnostic image quality, including the image signal to noise ratio, contrast, resolution
Rate, artifacts and display of anatomical structures.
3.2 BOLD image T2 ~ * values ​​and R2 ~ * values ​​are measured
Each side of the kidney
Dirty sweep four, each received eight different TE times (2.2ms ~ 14.7ms) of T2 ~ * images, the resulting image, the workstation functool soft
Pieces of processing, to obtain T2 ~ * Map image, the image in T2 ~ * Map measuring T2 ~ * values. R2 ~ * values ​​according to the formula: R2 ~ *= 1/T2 ~ * available. With the mean
± standard deviation ((?)± s) said.
3.3 ASL ASL-RBF value image measurement
Kidney sweep four on each side, each was
Have 20 different images, the resulting image, the workstation software functool-fair treatment, access to renal perfusion images. Figure in renal perfusion
As measured cortex, outer medulla and inner medullary blood flow values, with mean ± standard deviation ((?)± s) said.
3.4 ROI measurement

Kidney on each side of the same subjects selected region of interest (ROI), each ROI size, shape, exactly the same. ROI size is 1.5mm ~ 2 ~ 2.5
mm ~ 2, ROI contains at least 5 pixels. Cortex measuring 6 to 10 ROI, outer medulla, inner medullary area measuring 6 to 10 ROI, with a mean ± standard deviation
((?)± S) said. Choose the level of measurement without distortion and artifacts, to avoid the naked eye can see large blood vessels and artifacts.
4, rat kidney disease
Management observation
Each time point to take three rats, after scanning, and immediately take the kidneys, to the capsule, coronal cut along the renal pedicle, and MRI
Coronal scan line. Placed immediately after the saline flush of 10% formalin solution, fixed. Kidney specimens into the testing procedures according to pathological
With conventional gradient alcohol dehydration, xylene, dipping wax, paraffin embedded, cut 3um thick slices for conventional pathological HE staining, were mounted, etc.
Were observed under optical microscope at 80,400.
5, statistical analysis
Application SPSS16.0 statistical package, data recorded
Entry and analysis; using mean ± standard deviation ((?)± s), groups were compared using t test, analysis of variance, before and after their own group compared with paired t
Test, missing the use of non-normal distribution or variance rank test, Person correlation analysis, changes in measured values ​​at different time points using a line chart
Show.
Result
1, the experimental results in rats
29 SD rats were prepared for the numbers 1-29, male or female. 1-3 rats
Pre-test and parameter optimization, no line of data recording and analysis. Included in the analysis of experimental rats were 26, including 12 males, 14 females
Only. During the experiment, rats out of accidental death due to anesthesia experiments, not included in the next experimental point in time. Or from low SNR images
, Influence the value of poor image quality were measured, excluding when the second experimental group. Ultimately, this study measured the number of cases in each group and the experimental analysis of patients about kidney
Number are different. The right kidney (before injection of iodine contrast agent) the control group, after injection of iodine contrast agent 20 minutes, 24 hours, 48 ​​and 72 hours
R2 ~ * measurement and analysis of the value of the number of cases were 23,22,21,11,6 cases; the right kidney (before injection of iodine contrast agent) the control group, injection of iodine contrast
Agent after 20 minutes, 24 hours, 48 ​​hours and 72 hours ASL-RBF measurement and analysis of the value of the number of cases, respectively, 23,22,20,12,7 cases. Left kidney
(Before injection of iodine contrast agent) the control group, injection of iodine contrast agent after 20 minutes, 24 hours, 48 ​​hours and 72 hours R2 ~ * measurement and analysis of the value of the number of cases
Were 22,22,20,11,6 cases; the left kidney (before injection of iodine contrast agent) the control group, after injection of iodine contrast agent 20 minutes, 24 hours,
48 hours and 72 hours ASL-RBF measurement and analysis of the value of the number of cases, respectively, 22,22,21,12,7 cases.
2, image quality analysis

Axial and coronal T2WI best image quality, very few artifacts, displays a clear organizational structure. ASL image quality is better, fewer artifacts, organizations
Structure shows clear; BOLD image artifacts more, lower signal to noise ratio and resolution, but does not affect the image analysis and the value of the measurement.

3, statistical analysis
SPSS16.0 statistical software used for statistical analysis. Calculate the frequency count data, constitute more than
; Measurement data describe the mean ± standard deviation ((?)± s), description of non-normal distribution the median, maximum, minimum, between the two groups using t
Test, compared among groups using single factor analysis of variance (One-way ANOVA), pairwise comparisons among groups using LSD method (Least-
significant Difference, least significant difference method), was used to compare before and after their paired t-test (Paired-Samples t
Test), missing the use of non-normal distribution or variance rank test, person-related analysis, the significance level α = 0.05. Measured at different time points
Change the value of using a line graph.
3.1 or so on both sides of the kidney cortex, outer medulla and inner medullary in the same experimental group between the two values ​​of R2 ~ *
Two more, using paired t test, the experimental group in about the same renal cortex, outer medulla and inner medullary R2 ~ * no significant difference between values ​​(P>
0.05).
3.2 or so on both sides of the kidney cortex, outer medulla and inner medullary in the same experimental group ASL-RBF pairwise comparison between the values, using with
On the t-test, the experimental group in about the same renal cortex, outer medulla and inner medullary ASL-RBF was no significant difference between values ​​(P> 0.05).

3.3 normal control rats the left renal cortex, outer medulla and inner medullary R2 ~ * values ​​were compared, indicating that the outer medullary R2 ~ * maximum value for the 32.774 ±
3.07second ~ (-1), pairwise comparisons among the three significant differences (F = 3.357, P = 0.041 <0.05), cortex and outer medulla, inner medullary no system
Statistically difference (P> 0.05), within the outer medulla were significantly different between (P = 0.014). Rat kidney cortex, outer medulla and inner medullary inter-R2 ~ * value, foreign
Medullary R2 ~ * value of up to 31.76 ± 2.73 second ~ (-1), pairwise comparisons are significantly different (F = 19.961, P = 0.000 <0.05).

3.4 in rat cortex and medulla R2 ~ * values ​​in each group using paired t test analysis: the left kidney cortex of rats injected with the control group at different times after iodine contrast agent
Cortex in each group the value of R2 ~ * no significant difference; left kidney inner medullary control group R2 ~ * value and 24-hour group R2 ~ * values ​​between the 24-hour group and 72 h
Values ​​between the groups R2 ~ * significant difference (P <0.05), between groups over the value of R2 ~ * no significant difference. Control group, the left kidney outer medulla and into the value of R2 ~ *
Iodine contrast agent at each time point in each group R2 ~ * values ​​were significantly different between (P <0.05); 48 小时 group and 72 h group R2 ~ * value without a statistical
Learn the difference (P = 0.055), and other groups were significantly different between (P <0.05); rat kidney cortex of control group R2 ~ * value and 20 minutes, 24
Hours and 48 hours of each group the value of cortical R2 ~ * significant difference between (P <0.05); 24 hours and 48 hours, 72 hours in each group cortex R2 ~ *
Value, 48 hours and 72 hours set the value of cortical R2 ~ * no significant difference (P> 0.05); kidney outer medulla control group and 20 minutes, 24 hours and 48
Hours of each group, medullary R2 ~ * values ​​significantly different between (P <0.05), the control group and 72 h values ​​between the groups R2 ~ * no significant difference
(P = 0.106); kidney inner medullary control group and 20 minutes, 24 hours group R2 ~ * values ​​significantly different (P <0.05), than among the groups was not significant
Differences.
3.5 The group paired t-test analysis of rat cortex and medulla ASL-RBF value comparison between groups: control group, the left kidney cortex of rats
Cortex at different time points with the ASL-RBF value was no significant difference (P> 0.05), left kidney and inner medullary control group after injection of iodine contrast agent 20 minutes
Minutes; 20 minutes group and the 24 and 48 hours group ASL-RBF values ​​were significantly difference (P <0.05), within each group than marrow ASL-RBF values ​​were not significantly
Differences; left kidney outer medulla and the control group after injection of iodine contrast agent 20 minutes, 48 ​​and 72 hours in all experimental groups ASL-RBF values ​​were significant between
Differences (P <0.05), 20 minutes and 24 hours group ASL-RBF was no significant difference between values ​​(P = 0.216> 0.05); kidney cortex control group
And after injection of iodine contrast agent between the ASL-RBF in each group no significant difference in the value of 20 minutes group and 24-hour group, 24-hour group and 72 h groups
ASL-RBF value was no significant difference (P> 0.05), right kidney inner medullary 20 minutes group and 24-hour group ASL-RBF values ​​are significantly different
(P = 0.003 <0.05), remaining in each group showed no significant difference (P> 0.05).
3.6 The parts of the ASL-RBF value was between the value of R2 ~ *
Negative correlation, in which the right kidney inner medullary 20 minutes between the two groups was statistically significant (γ =- 0.537, P = 0.010); left kidney marrow within 24 hours group
ASL-RBF value of R2 ~ * statistical significance between values ​​(γ =- 0.637, P = 0.003), remaining cortex and outer medulla of each group ASL-RBF value between the value of R2 ~ *
Were not statistically significant (P> 0.05).
4, pathology results
Injection of iodine contrast agent to take before and after 20 minutes, 24 hours, 48
Hours and 72 hours in rat kidneys at different time points pathological HE staining, light microscope at 80,400 times the observed:
(1) injection of iodine contrast
Agent 20 minutes see some areas were observed proximal tubule epithelial cells cloudy swelling, individual solution. Small part of the region distal convoluted tube cavity narrow, epithelial
Individual cells dissolved and disappeared, interstitial blood vessels to dilate, a small amount of congestion. As time goes by:
(2) injection of iodine contrast agent 24 hours
See the glomeruli were observed small cell swelling, no atrophy and fibrosis. Part of the region proximal tubule and distal convoluted tubule cells Cloud
Swelling, no fatty degeneration, hyaline degeneration and necrosis and other changes. Most blood vessels and interstitial telangiectasia, congestion, rupture.

(3) injection of iodine contrast agent 48 hours were observed see glomerular cell swelling, shrinking. Part of the region proximal tubule and distal convoluted tubule epithelial cells
Cells cloudy swelling, fatty degeneration occurs, hyalinization and necrosis changes. Most of the stroma vascular dilation, congestion, most of the expansion of capillary
And hemorrhage.
(4) injection of iodine contrast agent 72 hours were observed structure of glomerular fibrosis and atrophy. Part of the region proximal
Tubules and distal convoluted tubule cells cloudy swelling, no fatty degeneration, hyaline degeneration and necrosis and other changes. A small amount of interstitial blood vessels to dilate, filling
Blood. Capillary a small amount of expansion and hemorrhage.
Conclusion:
1,3.0 T MRI BOLD imaging in rat kidneys, R_2 ~ * values ​​can be quantitatively
Injection of iodine contrast agent reflects renal tissue oxygen changes;
2,3.0 T MRI imaging techniques in rat kidney ASL, ASL-RBF
Values ​​reflect the quantitative injection of iodine contrast agents iodine renal blood flow changes;
3,3.0 T MRI renal BOLD and ASL-fMRI imaging
Iodine contrast agent technology can be used as kidney damage
Evaluation tools
Innovations in this issue
First proposed by
3.0TMRI BOLD and ASL-fMRI functional imaging techniques to monitor iodine contrast agent injected into the renal blood flow and oxygen metabolism changes in circumstances, the research
Research results that, 3.0T MRI BOLD and ASL-fMRI imaging technology can be used as after injection of iodine contrast agent to monitor the kidney in physiological conditions
The feasibility of functional changes in the means. Degree Year: 2009