Original Paper Nephron Physiol 2014;128:47–54 DOI: 10.1159/000366448
Received: October 4, 2013 Accepted: August 4, 2014 Published online: November 27, 2014
Renal Oxygenation Characteristics in Healthy Native Kidneys: Assessment with Blood Oxygen Level-Dependent Magnetic Resonance Imaging Zhenfeng Zheng a Huilan Shi b Hui Ma b Fengtan Li b Jing Zhang b Yunting Zhang b a
Department of Nephrology, and b Department of Radiology, General Hospital of Tianjin Medical University, Tianjin, PR China
Key Words Renal cortex · Renal medulla · Blood oxygen level-dependent MRI · R2* value
Abstract Objective: To explore the characteristics of blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) in healthy native kidneys. Methods: Seventy-nine patients without chronic kidney disease underwent BOLD-MRI with T2* spoiled gradient recalled echo sequences. BOLD images were analyzed using R2*map software to produce an R2* pseudo-color map. Cortical and medullary R2* values were analyzed in both kidneys and in both sexes. Different regional R2* values in the cortex and medulla were also analyzed. Physiological indices including age, height, weight, body mass index, body surface area, and estimated glomerular filtration rate (eGFR) were recorded. Correlations between R2* value and physiological indices were determined. Results: Renal cortical R2* values were lower than values in the medulla (p < 0.001). Female and male cortical R2* values were also lower than the corresponding values in the medulla (p < 0.001). Renal medullary R2* values in the lower renal pole were lower than values in the middle and upper poles
© 2014 S. Karger AG, Basel 1660–2137/14/1284–0047$39.50/0 E-Mail [email protected] www.karger.com/nep
(p = 0.001). Age was positively correlated with R2* values in the medulla (r = 0.32, p = 0.004). eGFR was negatively correlated with both cortical R2* values (r = –0.26, p = 0.02) and medullary R2* values (r = –0.29, p = 0.009). Conclusions: BOLD-MRI can directly visualize renal oxygenation. There was variation in the oxygenation of different regions of the kidney. Renal cortical and medullary oxygenation in healthy kidneys decreased with patient age. eGFR also decreased with patient age. © 2014 S. Karger AG, Basel
Introduction
Modern functional magnetic resonance imaging (MRI) provides noninvasive insight into disease development and tissue physiology. Blood oxygen level-dependent MRI (BOLD-MRI) has primarily been used for assessing functional imaging of the brain. BOLD-MRI has more recently been used to detect renal disease or pathophysiological changes. These investigations reflect the progress of radiology from a primarily anatomic discipline to one that provides insight into tissue physiology. BOLD-MRI is a noninvasive tool used to assess reZhenfeng Zheng, MD Department of Nephrology, General Hospital of Tianjin Medical University No.154, Anshan Road, Heping District, Tianjin (PR China) E-Mail zhengzhenfeng @ vip.126.com
gional renal oxygenation using deoxyhemoglobin as an endogenous marker. This technique relies on the change in the magnetic properties of hemoglobin when it converts from the oxygenated to the deoxygenated form. This change influences the magnetic properties of neighboring water molecules to increase signal intensity. The R2* value is commonly used to quantitatively assess changes in oxygenation. R2*(= 1/T2*), the apparent spin-spin relaxation rate, is directly related to the tissue content of deoxyhemoglobin and can be estimated from signal intensity measurements made using different echo times (TEs). The intensity versus TE data are fit to a single exponential decay function to determine the rate constant R2*. Decreases in R2* values imply an increase in the oxygenation of hemoglobin and thus improved blood oxygenation [1]. Previous studies have documented intrarenal oxygenation changes with diuresis [2], nephrotoxic xenobiotic administration [3], allograft nephropathy [4, 5]. Recently, Michaely et al. [6] published a large-sample clinical study in order to explore the natural distribution of R2* with regard to patient’s age, sex, and particularly renal function. Despite the fact that the author analyzed patient subgroups according to Kidney Disease Outcomes Quality Initiative stage this study failed to discriminate patients with chronic kidney disease from patients with nonchronic kidney disease. Moreover, only less than 40% patients underwent BOLD-MRI examination at 3.0 T. Higher field strengths, such as 3.0 T, have higher inherent signal-to-noise ratios [7]. Large-sample studies evaluating renal BOLD-MRI using 3.0-T field strengths in patients with nonkidney disease are lacking. The aim of our study is to investigate renal cortical and medullary oxygen distribution in nonkidney disease patients with estimated glomerular filtration rate (eGFR) above 60 ml/ min/1.73 m2. This will provide a robust baseline for future studies.
Materials and Methods Study Protocol This study was designed as an observational, open study. Patients were accrued from July 2013 to September 2013. Seventynine patients underwent abdominal MR imaging using a 3.0-T field. Approval of the institutional Ethical Committee was obtained, and all participants gave informed consent before entering the study. Inclusion criteria included: (1) normal urinalysis, blood tests and medical imaging studies within the last 3 months; (2) eGFR of at least 60 ml/min/1.73 m2 within the last 3 months; (3) recruited patients under physiological conditions. Physiological conditions were defined as: (a) no medication administration (an-
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Nephron Physiol 2014;128:55–61 DOI: 10.1159/000366448
giotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel antagonists, diuretics, or vasodilators) that could impact renal function; (b) No suffering from diseases (chronic obstructive pulmonary diseases, bronchiectasis, allergic asthma, cardiac functional insufficiency, aplastic anemia, polycythemia vera, etc.) that could impact renal oxygenation; (c) recruited subjects have not been to high altitude localities or have not undergone heavy stress loading within one week. Blood products and medication that could increase oxygen supply and consume renal oxygen were not used for 2 weeks before the patients underwent BOLD-MRI imaging. Physical examination, including body height, weight, blood pressure, heart rate, serum creatinine, and urine tests were completed in all participants. The body mass index (BMI), body surface area (BSA) and eGFR were calculated. Serum creatinine levels were obtained within 14 days of MR imaging. The serum creatinine value was used to calculate the current eGFR with the Chronic Kidney Disease Epidemiology Collaboration formula [8]. MRI Techniques MRI was performed using a 3.0-T imager (GE Discovery 750 3.0T, General Electric, USA). The scanner had a maximum gradient strength of 50 mT/m and a slew rate of 200 mT/m/s. A Torsopa eight-channel body coil was used. Images were acquired for morphologic evaluation using a T1-weighted fat-suppressed sequence. Images were acquired with a T1 in-phase + fat sequence. The field of view was 380 × 380 mm, section thickness 7.0 mm, section width 1.0 mm, repetition time (TR)/TE 180/2.1. BOLDMRI was performed using a T2* spoiled gradient recalled echo sequence. The field of view was 380 × 380 mm, matrix 192 × 160, TR 100 ms, and TE 2.4, 6.2, 10.0, 13.8, 17.6, 21.4, 25.2, and 29.0 ms. Echo number was 8.00, flip angle 35°, bandwidth 19.23 kHz, section thickness 7.0 mm, section width 1.0, section number 8 and scan time 25 s. Image Analysis R2* maps were constructed on an ADW 4.5 Workstation using the FUNCTOOL program. Ellipsoid regions of interest (ROIs) covering at least 10 pixels each were drawn on the anatomic templates. ROIs were placed in the upper pole, middle pole, and lower pole of the cortex and medulla of the section that covered large parts of the kidney. R2* values were read off the corresponding maps. Single total ROIs were created separately for the cortex and the medulla by merging all individual ROIs, yielding two ROIs for each subsection. ROIs in the right and left kidneys were merged for each subject separately for the cortex and the medulla, after excluding significant right-left differences. If cortex and medulla could not be differentiated on the color-coded T2* parameter maps, the definition of cortex and medulla was performed using raw data. Increasing TE resulted in a better differentiation between cortex and medulla. The ROIs were then copied from these raw data onto the T2* parameter map. The reader was blinded to patient’s age, sex, and field strength. The order of patients was randomized. Statistical Analysis Statistical analysis was performed using SPSS version 17.0 software. All of the values were expressed as mean ± standard deviation. Cortical and medullary R2* values were averaged in those patients with two kidneys in order to facilitate further analysis.
Zheng/Shi/Ma/Li/Zhang/Zhang
Color version available online
a
c
b
Fig. 1. Anatomic and BOLD-MRI map of normal healthy kidneys. a T1 in-phase fat suppression background reference map. b T2* pseudo-color map. c R2* pseudo-color map.
Quantitative measures were displayed as mean ± standard deviation. A Kolmogorov-Smirnov test was used to test for normal data distribution. T test analyses were performed to detect statistically significant differences when the data revealed a normal distribution. A general linear model for factorial design variance analysis was performed using the Bonferroni method for multiple comparisons. Two sided p values
Received: October 4, 2013 Accepted: August 4, 2014 Published online: November 27, 2014
Renal Oxygenation Characteristics in Healthy Native Kidneys: Assessment with Blood Oxygen Level-Dependent Magnetic Resonance Imaging Zhenfeng Zheng a Huilan Shi b Hui Ma b Fengtan Li b Jing Zhang b Yunting Zhang b a
Department of Nephrology, and b Department of Radiology, General Hospital of Tianjin Medical University, Tianjin, PR China
Key Words Renal cortex · Renal medulla · Blood oxygen level-dependent MRI · R2* value
Abstract Objective: To explore the characteristics of blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) in healthy native kidneys. Methods: Seventy-nine patients without chronic kidney disease underwent BOLD-MRI with T2* spoiled gradient recalled echo sequences. BOLD images were analyzed using R2*map software to produce an R2* pseudo-color map. Cortical and medullary R2* values were analyzed in both kidneys and in both sexes. Different regional R2* values in the cortex and medulla were also analyzed. Physiological indices including age, height, weight, body mass index, body surface area, and estimated glomerular filtration rate (eGFR) were recorded. Correlations between R2* value and physiological indices were determined. Results: Renal cortical R2* values were lower than values in the medulla (p < 0.001). Female and male cortical R2* values were also lower than the corresponding values in the medulla (p < 0.001). Renal medullary R2* values in the lower renal pole were lower than values in the middle and upper poles
© 2014 S. Karger AG, Basel 1660–2137/14/1284–0047$39.50/0 E-Mail [email protected] www.karger.com/nep
(p = 0.001). Age was positively correlated with R2* values in the medulla (r = 0.32, p = 0.004). eGFR was negatively correlated with both cortical R2* values (r = –0.26, p = 0.02) and medullary R2* values (r = –0.29, p = 0.009). Conclusions: BOLD-MRI can directly visualize renal oxygenation. There was variation in the oxygenation of different regions of the kidney. Renal cortical and medullary oxygenation in healthy kidneys decreased with patient age. eGFR also decreased with patient age. © 2014 S. Karger AG, Basel
Introduction
Modern functional magnetic resonance imaging (MRI) provides noninvasive insight into disease development and tissue physiology. Blood oxygen level-dependent MRI (BOLD-MRI) has primarily been used for assessing functional imaging of the brain. BOLD-MRI has more recently been used to detect renal disease or pathophysiological changes. These investigations reflect the progress of radiology from a primarily anatomic discipline to one that provides insight into tissue physiology. BOLD-MRI is a noninvasive tool used to assess reZhenfeng Zheng, MD Department of Nephrology, General Hospital of Tianjin Medical University No.154, Anshan Road, Heping District, Tianjin (PR China) E-Mail zhengzhenfeng @ vip.126.com
gional renal oxygenation using deoxyhemoglobin as an endogenous marker. This technique relies on the change in the magnetic properties of hemoglobin when it converts from the oxygenated to the deoxygenated form. This change influences the magnetic properties of neighboring water molecules to increase signal intensity. The R2* value is commonly used to quantitatively assess changes in oxygenation. R2*(= 1/T2*), the apparent spin-spin relaxation rate, is directly related to the tissue content of deoxyhemoglobin and can be estimated from signal intensity measurements made using different echo times (TEs). The intensity versus TE data are fit to a single exponential decay function to determine the rate constant R2*. Decreases in R2* values imply an increase in the oxygenation of hemoglobin and thus improved blood oxygenation [1]. Previous studies have documented intrarenal oxygenation changes with diuresis [2], nephrotoxic xenobiotic administration [3], allograft nephropathy [4, 5]. Recently, Michaely et al. [6] published a large-sample clinical study in order to explore the natural distribution of R2* with regard to patient’s age, sex, and particularly renal function. Despite the fact that the author analyzed patient subgroups according to Kidney Disease Outcomes Quality Initiative stage this study failed to discriminate patients with chronic kidney disease from patients with nonchronic kidney disease. Moreover, only less than 40% patients underwent BOLD-MRI examination at 3.0 T. Higher field strengths, such as 3.0 T, have higher inherent signal-to-noise ratios [7]. Large-sample studies evaluating renal BOLD-MRI using 3.0-T field strengths in patients with nonkidney disease are lacking. The aim of our study is to investigate renal cortical and medullary oxygen distribution in nonkidney disease patients with estimated glomerular filtration rate (eGFR) above 60 ml/ min/1.73 m2. This will provide a robust baseline for future studies.
Materials and Methods Study Protocol This study was designed as an observational, open study. Patients were accrued from July 2013 to September 2013. Seventynine patients underwent abdominal MR imaging using a 3.0-T field. Approval of the institutional Ethical Committee was obtained, and all participants gave informed consent before entering the study. Inclusion criteria included: (1) normal urinalysis, blood tests and medical imaging studies within the last 3 months; (2) eGFR of at least 60 ml/min/1.73 m2 within the last 3 months; (3) recruited patients under physiological conditions. Physiological conditions were defined as: (a) no medication administration (an-
48
Nephron Physiol 2014;128:55–61 DOI: 10.1159/000366448
giotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel antagonists, diuretics, or vasodilators) that could impact renal function; (b) No suffering from diseases (chronic obstructive pulmonary diseases, bronchiectasis, allergic asthma, cardiac functional insufficiency, aplastic anemia, polycythemia vera, etc.) that could impact renal oxygenation; (c) recruited subjects have not been to high altitude localities or have not undergone heavy stress loading within one week. Blood products and medication that could increase oxygen supply and consume renal oxygen were not used for 2 weeks before the patients underwent BOLD-MRI imaging. Physical examination, including body height, weight, blood pressure, heart rate, serum creatinine, and urine tests were completed in all participants. The body mass index (BMI), body surface area (BSA) and eGFR were calculated. Serum creatinine levels were obtained within 14 days of MR imaging. The serum creatinine value was used to calculate the current eGFR with the Chronic Kidney Disease Epidemiology Collaboration formula [8]. MRI Techniques MRI was performed using a 3.0-T imager (GE Discovery 750 3.0T, General Electric, USA). The scanner had a maximum gradient strength of 50 mT/m and a slew rate of 200 mT/m/s. A Torsopa eight-channel body coil was used. Images were acquired for morphologic evaluation using a T1-weighted fat-suppressed sequence. Images were acquired with a T1 in-phase + fat sequence. The field of view was 380 × 380 mm, section thickness 7.0 mm, section width 1.0 mm, repetition time (TR)/TE 180/2.1. BOLDMRI was performed using a T2* spoiled gradient recalled echo sequence. The field of view was 380 × 380 mm, matrix 192 × 160, TR 100 ms, and TE 2.4, 6.2, 10.0, 13.8, 17.6, 21.4, 25.2, and 29.0 ms. Echo number was 8.00, flip angle 35°, bandwidth 19.23 kHz, section thickness 7.0 mm, section width 1.0, section number 8 and scan time 25 s. Image Analysis R2* maps were constructed on an ADW 4.5 Workstation using the FUNCTOOL program. Ellipsoid regions of interest (ROIs) covering at least 10 pixels each were drawn on the anatomic templates. ROIs were placed in the upper pole, middle pole, and lower pole of the cortex and medulla of the section that covered large parts of the kidney. R2* values were read off the corresponding maps. Single total ROIs were created separately for the cortex and the medulla by merging all individual ROIs, yielding two ROIs for each subsection. ROIs in the right and left kidneys were merged for each subject separately for the cortex and the medulla, after excluding significant right-left differences. If cortex and medulla could not be differentiated on the color-coded T2* parameter maps, the definition of cortex and medulla was performed using raw data. Increasing TE resulted in a better differentiation between cortex and medulla. The ROIs were then copied from these raw data onto the T2* parameter map. The reader was blinded to patient’s age, sex, and field strength. The order of patients was randomized. Statistical Analysis Statistical analysis was performed using SPSS version 17.0 software. All of the values were expressed as mean ± standard deviation. Cortical and medullary R2* values were averaged in those patients with two kidneys in order to facilitate further analysis.
Zheng/Shi/Ma/Li/Zhang/Zhang
Color version available online
a
c
b
Fig. 1. Anatomic and BOLD-MRI map of normal healthy kidneys. a T1 in-phase fat suppression background reference map. b T2* pseudo-color map. c R2* pseudo-color map.
Quantitative measures were displayed as mean ± standard deviation. A Kolmogorov-Smirnov test was used to test for normal data distribution. T test analyses were performed to detect statistically significant differences when the data revealed a normal distribution. A general linear model for factorial design variance analysis was performed using the Bonferroni method for multiple comparisons. Two sided p values
