Alomary Mahfooz-Naef，Vikash，Wang Qiu-xia，Zhang Jin-hua，Hu Dao-yu

Kidney function is commonly evaluated by creatinine clearance，glomerular filtration rate and protein levels in urine，but these common laboratory tests cannot determine the unilateral（individual）kidney function.Noninvasive evaluation of kidney function on the regional basis is an useful clinical method.Evaluation of individual kidney function is crucial before kidney surgery and transplantation.For individual kidney function evaluation，the nuclear imaging of renal scan is the first choice of imaging modalities available，but the disadvantages of it in renal scan includes inability to assess the morphology and anatomy of the kidneys，radioactive cellular damage，higher cost compared to other investigative techniques，time commitment and the inconvenience for the practitioner[1].Nowadays，CT is being used as a primary choice in diagnosis of renal disease and evaluation of kidney function[2].The development of helical CT scan technology resulted in a high spatial resolution imaging，which allowed us for better assessment of anatomical parameters of the kidney[3].Lots of studies have presented a definite role of using CT as an estimator of renal perfusion and glomerular filtration rate（GFR）[4].Many previous studies showed that helical CT angiography can be a valid replacement of excretory urography and renal angiography in the evaluation of potential kidney donors[5-11].

At present，MDCT contrast enhanced scan is the latest technique to evaluate individual kidney function.MDCT allows for a clearer assessment of morphology and anatomy of the kidneys.MDCT can both show changes in renal morphology and detect blood flow perfusion providing a better evaluation of kidney function as well.MDCT imaging is a higher resolution modality with less radioactive damage at less cost.It permits us to depict the kidneys accurately through thinner section imaging，faster scanning，and higher longitudinal spatial resolution，which results in better quality of reformatted coronal images.With ongoing developmental techniques in CT technology，kidney function evaluation of individual kidney with MDCT will be more matured.

The purpose of this study is to explore the correlation among abdominal aorta CT value，renal artery CT value and renal cortex thickness with renal cortex CT value on contrast enhancement 64-MDCT，and then to determine the potential ability of MDCT to individual kidney function.

Materials and Methods

In this study all patients signed written informed consent before evaluation of kidney function with contrast enhancement MDCT.During the consecutive period of 4months，96patients（50men，46women；Mean age，50years；range，16to 74years）from July to October in 2013were evaluated in this study.All patients with normal kidney function confirmed clinically by kidney function test were subjected to the contrast enhanced MDCT；patients with renal diseases confirmed by CT diagnosis were excluded.The body weight（kg）of each patient was recorded by the time of physical examination.

Iopamidol（370mg I／mL）（Ultravist，Bayer Schering Pharma，Guangzhou，China），a nonionic iodinated contrast agent was used in this study.All patients were given intravenous（IV）injection with dose of 1mL／kg during the duration of 20s.

All patients were examined in the supine position using a 64MDCT（High Discovery CT750，GE Healthcare），scan parameters were 120kV，200mA，0.5s／r，detector coverage 40mm，pitch 0.984and slice thickness 5.0mm.

Scan protocols：all patients were scanned three times respectively in arterial，venous and delayed phases.The arterial phase scan started automatically 5.5s（diagnostic delay）after the contrast enhancement reached the threshold of 120HU in the abdominal aorta.Venous phase began automatically 15seconds after arterial phase while the 3min delayed phase was adjusted at 180seconds after injection of contrast.

All original data were transferred to the workstation（GE ADW 4.5）for post-processing.The renal cortex thickness was measured at the same level at three different areas in arterial phase.The attenuation measurements of the renal artery were performed by drawing an elliptical area（5.2mm2）and the average CT values of arterial phase was documented（Figure 1）.The attenuation measurements of abdominal aorta were taken at five different levels starting from the level of celiac trunk down to the level of abdominal aorta bifurcation by drawing an elliptical area（49.2mm2）and the average CT values of all three phases were recorded（Figure 2）.

The attenuation measurements of renal cortex were taken at five levels from the upper pole to lower pole of the kidney by drawing an elliptical area（18 mm2）and the average CT values of three phases was documented（Figure 3）.

Figure 1 58-years-old male，with the history of subtotal gastrectomy.Denoting renal artery（arrow）on contrast enhanced abdomen CT in the arterial phase.

Figure 2 58-years-old male，with the history of subtotal gastrectomy.Demarcating abdominal aorta（arrow）on contrast enhanced abdomen CT in the arterial phase.

Figure 3 20-years-old female，with the history of abdominal pain 3months ago.On contrast enhanced abdomen CT in arterial phase，denoting right renal cortex，liver hypodense area（arrow）and ascites.

All statistical analyses were performed by using IBM SPSS 20.0.Graphs were generated using Graph Pad Prism 5software.Quantitative data were presented as mean±standard deviation，while qualitative data were presented as frequency（%）.Pairedttest was used to test the statistical significance of mean differ-ences between renal cortex and abdominal aorta CT values on three different phases.ANOVA was used for repeated measures to test the statistical significance of difference in mean CT values of arterial，venous and delayed phases.Pearson＇s correlation was used to assess the correlation between renal cortex CT value and both renal cortex thickness and renal artery CT value.P＜0.05was considered to be statistically significant.

Results

This study involved 96patients with normal kidney function（92cases bilateral and 4unilateral），a total of 188kidneys（92left and 96right）.Renal cortex thickness and renal artery CT values were measured on arterial phase while renal cortex CT values and abdominal aorta CT values were measured in arterial，venous and 3min delayed phases（Table 1、2）.The mean renal cortex thickness was（5.19±0.81）mm in all kidneys（almost equal on both sides）.While，the mean renal artery CT values was（201.1±43.0）HU.Left kidneys have slightly higher CT values than right ones.

Table 1 Renal cortex thickness and renal artery CT values in arterial phase

Table 2 CT values of renal cortex and abdominal aorta in the 3phases

A positive correlation with statistical significance between renal cortex CT value and aorta CT value was shown（r＝0.584，P＜0.001）in arterial phase（Figure 4）；the mean CT value ratio of renal cortex to abdominal aorta in arterial phase was 0.5051，its 95%CI was 0.3679～0.6423（Table 2）.

Table 2 Ratio of renal cortex CT value to abdominal aorta CT value in arterial phase （HU）

Between renal cortex CT values and renal cortex thickness，a statistically significant correlation（r＝0.533，P＜0.0001）were demonstrated（Figure 5）.Likewise，there was a positive correlation between renal cortex and renal artery CT values（r＝0.43，P＜0.001，F(xiàn)igure 6）.

A statistically significant positive correlation between renal artery CT values and abdominal aorta CT values was shown（r＝0.526，P＜0.001）in the arterial phase（Figure 7）；the mean CT value ratio of abdominal aorta to renal artery was 1.511，its 95%CI was 1.471～1.550.

Mean CT values of renal cortex and abdominal aorta showed a statistically significant difference in the three phases（P＜0.001）.Renal cortex CT values increased in the venous phase，followed by a decrement in the 3min delayed phase.However，mean CT values of abdominal aorta showed significant decrement in both venous and delayed phases（Figure 8）.

The mean CT values of renal cortex was significantly higher than that of abdominal aorta in the venous and delayed phases（ΔCT＝21.6and 36.8HU，respectively），while it was significantly lower than abdominal aorta CT values in the arterial phase（-148.6HU）.

Discussion

Recently the MDCT has been used instead of helical computed tomography due to its effect of changing the trend of imaging modalities used in the urinary system evaluation.With these advantages，MDCT has been largely used clinically for better assessment and evaluation of kidney function[12].Since the technological advancements of MDCT systems and the common use of its commercial software，perfusion CT offers a wide array of clinical and research applications.The measurable enhancement of tissues relies on the iodine concentration deposition and is an indirect reflection of tissue vascularity and vascular physiology[13].

Figure 4 Correlation between renal cortex CT values and abdominal aorta CT values was detected by Pearson′s correlation coefficient（r＝0.584，P＜0.001）.

Figure 5 Correlation between Renal cortex CT values and renal cortex thickness was detected by Pearson′s correlation coefficient（r＝0.533，P＜0.0001）.

Figure 6 Correlation between renal cortex CT values and renal artery CT values was detected by Pearson′s correlation coefficient（r＝0.428，P＜0.001）.

Figure 7 Correlation between abdominal aorta CT values and renal artery CT values was detected by Pearson′s correlation coefficient（r＝0.526，P＜0.001）.

Figure 8 Differences of renal cortex and abdominal aorta mean CT values in the 3phases.

The method of how contrast agent passes through the vascular system is dependent on its perfusion of the venous system and its passage into the arterial system.Contrast agent is not metabolized in the body and is completely excreted by the kidney into urine in its original form，thus allowing it to be used as a reflection of the measurement of the GFR.Once it arrives at the kidneys，it flows through the renal arteries into the renal cortex and glomeruli where it reaches the outer and inner medulla at the junction the tubular capillary bed.This in turn，allows us to measure the amount and concentration of contrast that transits through the tissues of the kidneys at a particular rate.Therefore，by measuring the density of the contrast-infused tissue at different parts of the kidneys，the contrast concentration can be estimated.

Previous published studies used human and animal subjects to calculate the GFR at different time intervals[14-15].Due to the relationship between iodine concentration and tissue enhancement，a higher concentration of contrast medium is ideal，preferably a concentration of 370mg／mL[16].The limitations of contrast MDCT are contraindication in patient with abnormal kidney function and allergy to iodine contrast media.

Many factors affect contrast concentration in enhancement CT，but the major determining factors are patients particulars，contrast medium and CT scan[17-21].Regarding the patient＇s factors，the most important one is body weight[22-23].More weight means more blood volume so the contrast medium is diluted，which in turn reduces the iodine concentration in the blood[24].Other related factors of patients are such as age，BMI，cardiac output，heart diseases and vascular diseases[25-28].

The CT measurements of kidney function were well documented in animal studies，but the extension to humans clinical trials is less certain due to concerns about toxicity caused by ionizing radiation and iodinated contrast agents[29-33].In the previous studies，MDCT used to assess the renal cortex thickness and its correlation with the glomerular filtration rate（GFR）has been mentioned[34].The renal cortex and medulla varies greatly with regard to the amount of blood flow.Approximately，90%of the total blood flow passes through the renal cortex compared to 10%through the medulla[4.7mL／（min·mL）and 1.1mL／（min·mL），respectively][35].The nephron glomerulus constitutes the main architecture of the renal cortex and is responsible for renal excretory function.The number and functional status of glomerulus determines the absolute function of the kidney.

All pre-aortic factors affecting the contrast concentration in blood were excluded.In arterial（cortico-medullary）phase，i.e.，the phase of perfusion time to renal cortex，and the phase of enhanced cortex and unenhanced medulla，we found a significant fixed correlation between renal cortex and abdominal aorta CT values（r＝0.584，P＜0.001）.This fixed and positive correlation（ratio of renal cortex CT value to abdominal aortic CT value，mean value was 0.5051）might bring up a new and non-invasive method to evaluate kidney function in an individual kidney.

The concentration of contrast in renal cortex depends on the concentration in abdominal aorta，renal artery and the thickness of cortex in the normal kidney.The greater the concentrations of the contrast in the abdominal aorta，the greater it is in renal cortex showing direct correlation.In this study，the kidney function of individual kidney can be directly estimated from the abdominal aorta when pre-aortic factors affecting the contrast concentration were excluded.

Limitations of this study are contraindications in patient with abnormal kidney function and hypersensitivity to iodine contrast media.

In conclusion，the results of this study might bring a new method that can be used in the future to evaluate individual kidney function in enhancement MDCT through correlation of renal cortex CT value with abdominal aorta CT value，renal artery CT value and renal cortex thickness in individual kidney.Acknowledgements：We authors thank Xiaoyan Meng，Hao Tang，F(xiàn)iras Haj Kheder Mulla Issa，Kelash Rai and Sandeep whose important contributions to this study were indispensable for completion of this project and its success.Finally，the Authors would like to extend their love and gratitude for their families and friends for their unconditional love，motivation and support.

[1]Morrisroe SN，Su RR，Bae KT，et al.Differential kidney function estimation using computerized tomography based renal parenchymal volume measurement[J].J Urol，2010，183（6）：2289-2293.

[2]Hackstein N，Bauer J，Hauck EW，et al.Measuring single-kidney glomerular filtration rate on single-detector helical CT using a two-point Patlak plot technique in patients with increased interstitial space[J].AJR，2003，181（1）：147-156.

[3]Daghini E，Juillard L，Haas JA，et al.Comparison of mathematic models for assessment of glomerular filtration rate with electronbeam CT in pigs[J].Radiology，2007，242（2）：417-424.

[4]O＇Dell-Anderson KJ，Twardock R，Grimm JB，et al.Determination of glomerular filtration rate in dogs using contrast-enhanced computed tomography[J].Vet Radiol Ultrasound，2006，47（2）：127-135.

[5]Rubin GD，Alfrey EJ，Dake MD，et al.Assessment of living renal donors with spiral CT[J].Radiology，1995，195（2）：457-462.

[6]Cochran ST，Krasny RM，Danovitch GM，et al.Helical CT angiography for examination of living renal donors[J].AJR，1997，168（6）：1569-1573.

[7]Platt JF，Ellis JH，Korobkin M，et al.Helical CT evaluation of potential kidney donors：findings in 154subjects[J].AJR，1997，169（5）：1325-1330.

[8]Smith PA，Ratner LE，Lynch FC，et al.Role of CT angiography in the preoperative evaluation for laparoscopic nephrectomy[J].Radiographics，1998，18（6）：589-601.

[9]Pozniak MA，Balison DJ，Lee Jr FT，et al.CT angiography of potential renal transplant donors[J].Radiographics，1998，18（3）：565-587.

[10]Del Pizzo JJ，Sklar GN，You-Cheong JW，et al.Helical computerized tomography arteriography for evaluation of live renal donors undergoing laparoscopic nephrectomy[J].J Urol，1999，162（1）：31-34.

[11]Patil UD，Ragavan A，Nadaraj，et al.Helical CT angiography in evaluation of live kidney donors[J].Nephrol Dial Transplant，2001，16（9）：1900-1904.

[12]Shin HS，Chung BH，Lee SE，et al.Measurement of kidney volume with multi-detector computed tomography scanning in young Korean[J].J Yonsei Med，2009，50（2）：262-265.

[13]Miles KA，Griffiths MR.Perfusion CT：a worthwhile enhancement[J].Br J Radiol，2003，76（904）：220-231.

[14]Gaspari F，Perico N，Ruggenenti P，et al.Plasma clearance of non-radioactive Iohexol as a measure of GFR[J].J Am Soc Nephrol，1995，6（2）：257-263.

[15]Flavio G，Guerini E，Perico N，et al.Glomerular filtration rate determine from a single plasma sample after intravenous Iohexol injection：is it reliable[J].J Am Soc Nephrol，1996，12（1）：2689-2693.

[16]Miles KA.Functional computed tomography in oncology[J].Eur J Cancer，2002，38（16）：2079-2084.

[17]Bae KT，Heiken JP，Brink JA.Aortic and hepatic contrast medium enhancement at CT part II，effect of reduced cardiac output in aporcine model[J].Radiology，1998，207（3）：657-662.

[18]Berland LL.Slip-ring and conventional dynamic hepatic CT：contrast material and timing considerations[J].Radiology，1995，195（1）：1-8.

[19]Cademartiri F，van der Lugt，Luccichenti G，et al.Parameters affecting bolus geometry in CTA：a review[J].J Comput Assist Tomogr，2002，26（4）：598-607.

[20]Han JK，Kim AY，Lee KY，et al.Factors influencing vascular and hepatic enhancement at CT：experimental study on injection protocol using a canine model[J].J Comput Assist Tomogr，2000，24（3）：400-406.

[21]Bae KT.Intravenous contrast medium administration and scan timing at CT：considerations and approaches[J].Radiology，2010，256（1）：32-61.

[22]Bae KT.Peak contrast enhancement in CT and MR angiography：when does it occur and why？pharmacokinetic study in a porcine model[J].Radiology，2003，227（3）：809-816.

[23]Han JK，Choi BI，Kim AY，et al.Contrast media in abdominal computed tomography：optimization of delivery methods[J].Kor J Radiol，2001，2（1）：28-36.

[24]Bae KT.Intravenous contrast medium administration and scan timing at CT：considerations and approaches[J].Radiology，2010，256（1）：32-61，

[24]Glassock RJ，Rule AD.The implications of anatomical and functional changes of the aging kidney：with an emphasis on the glomeruli[J].Kidney Int，2012，82（3）：270-277.

[25]Emamian SA，Nielsen MB，Pedersen JF，et al.Kidney dimensions at sonography：correlation with age，sex and habitus in 665adult volunteers[J].AJR，1993，160（1）：83-86.

[26]Glodny B，Unterholzner V，Taferner B，et al.Normal kidney size and its influencing factors：a 64-slice MDCT study of 1，040asymptomatic patients[J].BMC Urol，2009，23（9）：19-？.

[27]Muto NS，Kamishima T，Harris AA，et al.Renal cortical volume measured using automatic contouring software for computed tomography and its relationship with BMI，age and kidney function[J].Eur J Radiol，2011，78（1）：151-156.

[28]Itano NB，Sherrill LE，Lerman LO，et al.Electron beam computerized tomography assessment of in vivo single kidney glomerular filtration rate and tubular dynamics during chronic partial unilateral ureteral obstruction in the pig[J].J Urol，2001，166（6）：2530-2535.

[29]Lerman LO，Bentley MD，Bell MR，et al.Quantitation of the in vivo kidney volume with cine computed tomography[J].Invest Radiol，1990，25（11）：1206-1211.

[30]Alexander K，Del Castillo JRE，Ybarra N，et al.Single-slice dynamic computed tomographic determination of glomerular filtration rate by use of Patlak plot analysis in anesthetized pigs[J].Am J Vet Res，2007，68（3）：297-304.

[31]Chang J，Kim S，Jung J，et al.Evaluation of the effects of thiopental，propofol，and etomidate on glomerular filtration rate measured by the use of dynamic computed tomography in dogs[J].Am J Vet Res，2011，72（1）：146-151.

[32]Dell-Anderson KJ，Twardock R，Grimm JB，et al.Determination of glomerular filtration rate in dogs using contrast-enhanced computed tomography[J].Vet Radiol Ultras，2006，47（2）：127-135.

[33]Gourtsoyiannis N，Prassopoulos P，Cavouras D，et al.The thickness of the renal parenchyma decreases with age：a CT study of 360patients[J].AJR，1990，155（3）：541-544.

[34]Mile KA，Hayball MP，Dixoz AK.Functional imaging of changes in human intrarenal perfusion using quantitative dynamic computed tomography[J].Invest Radiol，1994，29（10）：911-914.