DOI: 10.1148/radiol.2432060655
(Radiology 2007;243:405-412.)
© RSNA, 2007
Assessment of Renal Hemodynamics and Function in Pigs with 64-Section Multidetector CT: Comparison with Electron-Beam CT1
Elena Daghini, MD,
Andrew N. Primak, PhD,
Alejandro R. Chade, MD,
James D. Krier, MS,
Xiang-Yang Zhu, MD,
Erik L. Ritman, MD, PhD,
Cynthia H. McCollough, PhD, and
Lilach O. Lerman, MD, PhD
1 From the Department of Medicine, Divisions of Nephrology and Hypertension (E.D., A.R.C., J.D.K., X.Y.Z., L.O.L.) and Cardiovascular Diseases (L.O.L.), Department of Radiology (A.N.P., C.H.M.), and Department of Physiology and Biomedical Engineering (E.L.R.), Mayo Clinic College of Medicine, 200 First St SW, Rochester, MN 55905. From the 2005 RSNA Annual Meeting. Received April 13, 2006; revision requested June 21; revision received July 1; accepted August 2; final version accepted October 16. Supported in part by National Institutes of Health grants DK-73608, HL-77131, and HL-72255; American Heart Association; an Award for Research in Cardiology (ARC) from the Division of Cardiovascular Disease, Mayo Clinic College of Medicine; and University of Study of Pisa, Italy. C.H.M., A.N.P. supported in part by grants from Siemens Medical Solutions. C.H.M. and A.N.P. supported in part by a grant from GE Healthcare.
Address correspondence to L.O.L. (e-mail: lerman.lilach{at}mayo.edu).
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ABSTRACT
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Purpose: To prospectively evaluate the feasibility of obtaining reliable measurements of renal hemodynamics and function by using 64-section multidetector CT.
Materials and Methods: This study was approved by the Institutional Animal Care and Use Committee. Eight pigs (two with induced unilateral renal artery stenosis) were studied with both electron-beam CT and 64-section multidetector CT at 1-week intervals in randomized order. Both kidneys were scanned repeatedly, without table movement, for about 3 minutes after intravenous (IV) administration of a bolus of contrast medium and again during vasodilator challenge (acetylcholine). Images were reconstructed on each CT console but were analyzed on the same independent workstation. Attenuation changes in the kidneys were plotted as function of time, and time-attenuation curves (TACs) were subsequently analyzed to determine regional perfusion and volume, glomerular filtration rate (GFR), and renal blood flow (RBF). Statistical analysis utilized Student t test, analysis of variance (ANOVA), linear regression, and Bland-Altman analysis.
Results: TACs obtained with multidetector CT were qualitatively similar to those obtained with electron-beam CT, as were the quantitative values of renal perfusion and function. RBF correlated significantly between the two techniques (RBFMD = 0.96 · RBFEB mL/min; R = 0.77, P < .01). GFRMD was also similar to GFREB (77.6 ± 8.3 vs 79.8 ± 8.8 mL/min, p > .05). Bland-Altman plots showed good agreement between the two techniques. Both techniques similarly detected the differences between stenotic and contralateral kidneys.
Conclusion: The clinical multidetector CT scanner provides reliable measurements of single-kidney hemodynamics and function, which are similar to those obtained with previously validated electron-beam CT.
© RSNA, 2007
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INTRODUCTION
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Agrowing body of evidence indicates that computed tomography (CT) can be applied for quantitative noninvasive evaluation of hemodynamics and function of the kidney (14). Quantification of individual kidney hemodynamics and function could play a fundamental role in the evaluation of the onset and progression of asymmetric renal disease, such as unilateral renal artery stenosis (57) or ureteral obstruction (8), and may offer adequate sensitivity for assessment of mild changes in renal function (9,10). However, early regional structural and functional alterations in the kidneys may remain undetected (9,11), partly because of difficulties in estimating single-kidney or regional renal function (12).
Electron-beam CT provides reliable and reproducible estimates of renal hemodynamics and function (1,3,8,13) in a range of physiologic and pathophysiologic conditions and during pharmacologic challenge (2,6,10,14). The high temporal resolution of electron-beam CT allows detection of dynamic changes in tissue attenuation occurring during the transit of contrast media and thereby enables calculations of vascular and tubular flow. However, the applicability of these measurements has remained rather limited, partly because electron-beam CT scanners are not widely available.
The advent of increasingly faster multidetector helical CT scanners offering high spatial and temporal resolution, versatile scanning sequences, and extensive availability, may allow clinical adoption of these quantitative measures of single-kidney function. However, despite the clear advantages of these technologies, their capability for dynamic studies has not been fully established.
Therefore, the aim of this study was to prospectively evaluate the feasibility of obtaining reliable data for renal hemodynamics and function by using 64-section multidetector helical CT.
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MATERIALS AND METHODS
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This study was approved by the Institutional Animal Care and Use Committee of the Mayo Clinic College of Medicine, Rochester, Minn. Authors who received research funding from GE Healthcare (C.H.M.) and Siemens Medical Solutions (A.N.P., C.H.M.) were blinded to all data generated during the study. The remaining authors (E.D., A.R.C., J.D.K., X.Y.Z., E.L.R., L.O.L.) had sole control of the data generated by this experiment.
Eight female domestic crossbred pigs (4555 kg) were studied by using both electron-beam CT (C-150; Imatron, South San Francisco, Calif) and multidetector CT (Somatom Sensation 64; Siemens Medical Solutions, Forchheim, Germany) in randomized order at 1-week intervals. To increase the range of flow values, unilateral renal artery stenosis (causing renovascular hypertension) had been induced (J.D.K., A.R.C.) in two animals (5,6,10,14).
Induction of Renal Artery Stenosis
Six weeks before the CT studies, two animals were anesthetized with intramuscular ketamine (20 mg/kg; Fort Dodge Animal Health, Fort Dodge, Iowa) and xylazine (2 mg/kg; VET TEK, Blue Springs, Mo), intubated, and mechanically ventilated with room air. Anesthesia was maintained with constant infusion of ketamine (0.2 [mg · kg1]/min) and xylazine (0.03 [mg · kg1]/min), which have minimal effects on renal hemodynamics in animal models (1517). An intravenous bolus of heparin (5000 U) was followed by continuous infusion (1000 U/h). With fluoroscopic guidance, a percutaneous transluminal balloon 7.0 mm in diameter (Cordis, Miami, Fla) wrapped with a copper coil (made in house from 23-gauge copper wire) was advanced through the femoral artery into the proximal middle section of the single left renal artery. The balloon was inflated twice to high pressure, deflated, and removed, leaving the local-irritant copper coil embedded in the vascular wall. Selective renal angiography was used to confirm vessel patency and coil location. It has been demonstrated that placement of such a copper stent in the renal artery leads to a gradual and progressive luminal narrowing (average, 65%75%) within 10 days, associated with an increase in blood pressure values (5,6,10,14).
Experimental Protocol
Each CT study was performed to assess cortical and medullary perfusion, renal blood flow (RBF), glomerular filtration rate (GFR), and tubular function in the different nephron segments (proximal tubule, Henle loop, and distal tubule) (2,3). Studies were performed under basal conditions and were repeated after vasodilation with acetylcholine, to assess the ability of the 64-section multidetector CT to demonstrate functional changes in response to a pharmacologic challenge.
For each CT study, the animals were anesthetized as described above. With fluoroscopic guidance, a 7-F arterial guide (Cordis) was introduced from one carotid artery to the abdominal aorta for blood pressure monitoring. A tracker catheter (Prowler Microcatheter, Cordis) was placed above the level of both renal arteries for infusion of saline or acetylcholine. A pigtail catheter (Super Torque, Cordis) was advanced through one jugular vein into the right atrium for contrast medium injections (J.D.K., A.R.C., E.D.). Electrocardiograph leads were used to monitor heart rate. The presence of the stenosis in the two animals was angiographically confirmed.
The animal was then positioned supine in the electron-beam CT or multidetector CT scanning gantry and was allowed a 30-minute recovery, with a continuous infusion of saline (0.51 mL/min). All the pigs were studied by using both electron-beam CT and 64-section multidetector CT at 1-week intervals in randomized order.
Electron-Beam CT Scanning Sequence
Abdominal multisection CT scans served to localize the kidneys, and two contiguous anatomic levels through the hilar regions of both kidneys were selected (18).
For the study of renal perfusion and tubular flow, the kidneys were scanned with the multisection, standard-resolution (50 msec per scan) flow mode to obtain two parallel 7-mm-thick sections. The table position was fixed, so that repeated images of the same two levels were obtained over time. Electron-beam CT was performed at 130 kV and 630 mA with a field of view of 26 cm and a matrix of 360 x 360 pixels, resulting in a CT image pixel size of 0.72 mm2 (E.D., A.R.C., J.D.K., X.Y.Z.). One to 2 seconds before scanning (determined on the basis of preliminary studies and on swine circulation time), a bolus of the nonionic low-osmolar contrast medium iopamidol (Isovue-370, 0.5 mL/kg over 2 seconds; Bracco Diagnostics, Princeton, NJ) was injected into the right atrium by using a power injector connected to the catheter via a 36-inch contrast mediumfilled tube (13,1921).
Forty consecutive scans were obtained over the two preselected levels for about 3 minutes at variable time intervals (1921). To study the attenuation changes during the rapid intravascular phase, the first 20 scans were acquired during suspension of respiration at end expiration, every 0.62.5 seconds (two scans per second, eight scans every 0.6 second, two scans every 1 second, four scans every 2 seconds, and four scans every 2.5 seconds), for a total of 20 scans over 26.8 seconds. The animals then received assisted ventilation during the next 20 scans, performed at a rate of one scan every 6 seconds for 60 seconds and one scan every 8 seconds for 80 seconds, to follow intratubular attenuation changes (21). This protocol was designed to account for the swine cardiovascular and renal physiology (6,12) and the contrast material distribution pattern and excretion time (
2 minutes) (2225).
Fifteen minutes after the baseline flow study, a 20-minute infusion of acetylcholine (4.5 [µg · kg1]/min) was initiated, and the electron-beam CT study was repeated.
After a 15-minute recovery, scanning was performed in the continuous volume mode during short injection of iopamidol (0.5 mL/kg over 56 seconds) into the right atrium, to sustain corticomedullary differentiation (vascular phase) throughout the volume scan. Timing for initiation of scanning was predetermined from the preceding flow study to correspond to bolus arrival in the kidney. In this mode, one 6-mm image is obtained per 100-msec exposure as the patient table is moved through the scan plane. CT images (6-mm-thick) were obtained by scanning the kidneys from pole to pole during peak enhancement, for measurement of cortical, medullary, and total kidney volume (26).
Multidetector CT Scanning Sequence
A similar protocol was applied for multidetector CT. After CT examination of the kidneys, a bolus of iopamidol (0.5 mL/kg over 2 seconds) was followed by a flow study performed at a field of view of 25 cm and matrix of 512 x 512 pixels (CT image pixel size of 0.488 mm2). The perfusion scans were performed at 80 kV and 160 mA in sequential mode, with 20 x 1.2 collimation and 0-mm table feed (E.D., A.N.P., C.H.M.). By using a 0.5-second gantry rotation time and a 0.36-second partial reconstruction, 90 multiscan exposures were acquired during a 0.5-second cycle, followed by 70 scans during a 2-second cycle, bringing the total scanning time to about 3 minutes. For each exposure, four contiguous 6-mm images were acquired and reconstructed by using a B35 kernel. Respiration was suspended at end expiration for the first 90 scans, and assisted ventilation was provided between scans during the last 70 scans. After a 15-minute rest, studies were repeated during acetylcholine-induced (4.5 [µg · kg1]/min) vasodilation.
A renal volume study was performed in the helical mode (240 mAs, 120 kV, pitch of 1.2, and B40 medium kernel) to obtain contiguous 5-mm-thick levels for measurements of cortical, medullary, and total kidney volume. The timing was designed by following the same criteria used for the electron-beam CT study.
Image Analysis
Images were reconstructed on each CT console by using a filtered back-projection algorithm and were transferred to the same workstation (Sun Microsystems, Santa Clara, CA) for display and analysis with the software package ANALYZE (Biomedical Imaging Resource, Mayo Clinic, Rochester, Minn).
Regions of interest in the kidney were manually traced on the cross-sectional images (Fig 1) from the aorta, bilateral renal cortex, and medulla (J.D.K., 9 years of experience). Average tissue attenuation in each ROI in each image was automatically calculated, and the changes of attenuation over time were plotted in time-attenuation curves (TACs). These TACs were fitted by using extended gamma-variate curve-fitting algorithms and the curve-fitting parameters used to obtain measures of renal function (3,5,10,14).

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Figure 1a: Representative renal CT images and corresponding TACs obtained from one pig by using electron-beam CT and 64-section multidetector CT. (a, b) Transverse CT images of hilar region of both kidneys, obtained with (a) multidetector CT and (b) electron-beam CT 1 week apart show manually traced region of interest in the renal cortex (white arrow) and medulla (black arrow). (cf) Representative cortical and medullary TACs obtained with (c, e) multidetector CT and (d, f) electron-beam CT.
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Figure 1b: Representative renal CT images and corresponding TACs obtained from one pig by using electron-beam CT and 64-section multidetector CT. (a, b) Transverse CT images of hilar region of both kidneys, obtained with (a) multidetector CT and (b) electron-beam CT 1 week apart show manually traced region of interest in the renal cortex (white arrow) and medulla (black arrow). (cf) Representative cortical and medullary TACs obtained with (c, e) multidetector CT and (d, f) electron-beam CT.
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Figure 1c: Representative renal CT images and corresponding TACs obtained from one pig by using electron-beam CT and 64-section multidetector CT. (a, b) Transverse CT images of hilar region of both kidneys, obtained with (a) multidetector CT and (b) electron-beam CT 1 week apart show manually traced region of interest in the renal cortex (white arrow) and medulla (black arrow). (cf) Representative cortical and medullary TACs obtained with (c, e) multidetector CT and (d, f) electron-beam CT.
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Figure 1d: Representative renal CT images and corresponding TACs obtained from one pig by using electron-beam CT and 64-section multidetector CT. (a, b) Transverse CT images of hilar region of both kidneys, obtained with (a) multidetector CT and (b) electron-beam CT 1 week apart show manually traced region of interest in the renal cortex (white arrow) and medulla (black arrow). (cf) Representative cortical and medullary TACs obtained with (c, e) multidetector CT and (d, f) electron-beam CT.
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Figure 1e: Representative renal CT images and corresponding TACs obtained from one pig by using electron-beam CT and 64-section multidetector CT. (a, b) Transverse CT images of hilar region of both kidneys, obtained with (a) multidetector CT and (b) electron-beam CT 1 week apart show manually traced region of interest in the renal cortex (white arrow) and medulla (black arrow). (cf) Representative cortical and medullary TACs obtained with (c, e) multidetector CT and (d, f) electron-beam CT.
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Figure 1f: Representative renal CT images and corresponding TACs obtained from one pig by using electron-beam CT and 64-section multidetector CT. (a, b) Transverse CT images of hilar region of both kidneys, obtained with (a) multidetector CT and (b) electron-beam CT 1 week apart show manually traced region of interest in the renal cortex (white arrow) and medulla (black arrow). (cf) Representative cortical and medullary TACs obtained with (c, e) multidetector CT and (d, f) electron-beam CT.
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The parameters obtained from the vascular curve in each region of the kidney (Fig 1) were used to calculate regional perfusion, whereas parameters obtained from all subsequent peaks were used to calculate tubular dynamics. For each peak observed in the ROI, the area under the curve and its first moment were calculated.
Blood volume (BV) was subsequently calculated as the area under tissue vascular curve divided by the area under aorta curve. The first moment of the curve was assumed to represent mean transit time (MTT in seconds) starting at contrast material appearance in the kidney. Regional perfusion (milliliters per minute per cubic centimeter of tissue) was then calculated as BV/MTT (3,19). Intratubular concentration (ITC) was calculated for each nephron segment (Fig 1) as the ratio of the area under each tubular curve to that of the cortical vascular curve, divided by normalized GFR (3,9,21).
After identification of the renal cortex and medulla on each tomographic level obtained in the volume study, volumes were calculated by using a statistical point-counting volume estimation program (13,19,20) implemented with ANALYZE (Biomedical Imaging Resource).
RBF (milliliters per minute) was subsequently calculated as the sum of cortical and medullary blood flows obtained from each cortex and medulla as the product of its perfusion and volume. GFR (milliliters per minute) was calculated from the right and left cortical TAC by utilizing the slope of the proximal tubular curve (3).
Statistical Analysis
Results are expressed as means ± standard error of the mean. Statistical comparisons between experimental periods within techniques were performed by using a paired Student t test and among techniques by using analysis of variance and an unpaired Student t test, performed with StatView 5.1 (SAS Institute, Cary, NC). Correlation coefficients and least-squares regressions (forced through zero) were calculated to assess the relationship between electron-beam CT and multidetector CT assessments. Statistical significance for all tests was judged at P < .05. Bland-Altman analysis (27) was also applied to evaluate the agreement between the two techniques.
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RESULTS
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Systemic hemodynamic characteristics of the pigs (eg, blood pressure, heart rate) on the day of the first study remained unaltered during the second CT study 1 week later. In the two pigs with induced unilateral renal artery stenosis (70% and 75% stenosis at angiography), systemic hemodynamics were similar to those of the other six pigs, except for a markedly higher mean arterial pressure (163 mm Hg ± 7 vs 102.2 mm Hg ± 16.1).
The images obtained with multidetector CT were of better quality than those obtained with electron-beam CT (Fig 1). In the renal cortical TAC, three sequential peaks represented displacement of the contrast material bolus along the cortical vascular compartment, proximal tubule, and distal tubule (Fig 1c, 1d), as inferred from the timing, sequence, and location of the peaks. The medullary TAC (Fig 1e, 1f) exhibited two peaks, corresponding to the transit of the contrast medium in the vascular compartment, followed by tubular fluid arrival via the loop of Henle (2,3,6).
TACs obtained with the two techniques were qualitatively similar in shape but better defined with multidetector CT than with electron-beam CT, owing to the larger number of time points with multidetector CT (160 vs 40, Fig 1).
Renal Hemodynamics
The quantitative values of single-kidney perfusion, RBF, and GFR obtained with electron-beam CT and multidetector CT were similar (Table 1, P > .05 for all), while cortical and medullary volumes were slightly but significantly lower with electron-beam CT compared with multidetector CT (P < .05, Table 1). Acetylcholine induced a significant increase in cortical and medullary perfusion, RBF, and GFR, also similarly detected with both techniques (Table 1).
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Table 1. Swine Renal Hemodynamics and Function Obtained with Electron-Beam CT and 64-Section Multidetector CT before and after Vasodilation with Acetylcholine
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RBF and GFR values obtained with electron-beam CT and multidetector CT were correlated significantly (R = 0.77 and R = 0.87, respectively; P < .01 for both), as were cortical and medullary perfusion (Fig 2). Bland-Altman plots showed good agreement between electron-beam CT and multidetector CT (Fig 2) for all the parameters.
Both techniques were able to depict the lower basal cortical perfusion in the stenotic compared with the contralateral kidneys (Table 1). The lower baseline RBF and GFR in the stenotic kidneys, as well as their blunted response to acetylcholine, were consistent between electron-beam CT and multidetector CT (Fig 3).
Tubular Function
ITC obtained with the two techniques in the proximal tubule, Henle loop, and distal tubule were not significantly different (P > .05 for all regions, Table 2). The significant decrease in proximal tubular ITC in response to acetylcholine was detected with both electron-beam CT and multidetector CT, as was a tendency toward decrease in distal tubular ITC (P = .083 and P = .080, respectively).
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Table 2. Swine ITCs Obtained in Vivo in Eight Pigs by using Electron-Beam CT and 64-Section Multidetector CT in the Different Nephron Segments
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DISCUSSION
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Our study demonstrates the feasibility of obtaining minimally invasive quantifications of in vivo renal hemodynamics and function by using the clinically available 64-section multidetector CT scanner.
CT combines minimal invasiveness with tomographic capability that enables study of both single-kidney and regional renal function. Of importance, the progressive increase in temporal resolution to scan times under 500 msec enables the study of dynamic processes like flow phenomena.
The high temporal resolution of electron-beam CT (50 msec per scan in the standard-spatial-resolution mode) confers an advantage for following dynamic processes. Indeed, the accuracy and reproducibility of electron-beam CT measurements of renal perfusion and tubular function have been demonstrated in both animals and humans and have been validated against simultaneously employed reference standard techniques such as electromagnetic flow probe, intravascular Doppler wire, mercaptoacetyltriglycine renal scintigraphy, and inulin clearance (3,8,13,19). However, the wider availability, technical flexibility, and superior spatial resolution of new-generation helical scanners encouraged us to adapt the well-validated electron-beam CT methods and evaluate the potential for obtaining similar measurements by using multidetector CT. Our study demonstrated the feasibility of this approach.
Owing to lower noise and higher spatial resolution (pixel size of 0.48 vs 0.72 mm), renal images obtained with multidetector CT were of better quality than those obtained with electron-beam CT. Moreover, the higher number of sequential images that can be acquired with multidetector CT (the electron-beam CT flow mode is limited to up to 40 consecutive images) resulted in TACs that were similar in shape to those obtained with electron-beam CT but better defined and potentially more reliably fitted by the mathematic models used to calculate renal hemodynamic and functional parameters.
We observed that cortical perfusion assessments obtained with multidetector CT were similar to those obtained with electron-beam CT, both under baseline conditions and during vasodilation, and the two correlated significantly. Medullary perfusion assessments were also not different between multidetector CT and electron-beam CT, and their correlation was significant, although modest. Notably, the reproducibility of medullary perfusion assessed with electron-beam CT on consecutive days is moderate, possibly owing to greater temporal variation in medullary blood flow (13). Hence, the slight difference between medullary perfusion measurements obtained with electron-beam CT and multidetector CT may be due to intrinsic and physiologic, rather than technical, factors. Similarly, the small differences between electron-beam CT and multidetector CT in RBF and GFR may be attributed to amplified physiologic variability and the 1-week interval between the studies. Nevertheless, there was generally good agreement between the two methods. The slightly greater cortical and medullary volume estimated with multidetector CT likely resulted from its higher spatial resolution, which may have allowed better detection of both the external border of the cortex and the corticomedullary junction. Hence, a small but significant difference between the volumes obtained with the two techniques is likely ascribed to underestimation with electron-beam CT.
The use of contrast material and prolonged scanning time also allowed for study of tubular function in the intact kidney. The mean transit times and ITC in the different nephron segments at baseline and in response to acetylcholine were also consistent between the two techniques. Moreover, we observed that multidetector CT was able to help confirm worsening in the basal hemodynamics and function of the stenotic kidneys (5,10), as well as their impaired response to an endothelium-dependent challenge.
Our study had limitations: In our study, 64-section multidetector CT was not independently validated against reference standards but rather was compared with previously validated electron-beam CT criteria.
Several factors potentially hinder derivation of renal functional parameters with both CT scanners. The need to discern physiologic processes occurring in different renal compartments can be addressed by deriving separate ROIs from the cortex, medulla, and papilla. Although this process results in smaller ROIs and greater dependence on subtle boundary definition, this allows, for example, more accurate GFR estimates (since filtration occurs almost exclusively in the cortex) or ITC in each tubular segment. Nevertheless, other compartments (eg, interstitial or intracellular) remain indistinguishable. For example, undetectable leakage of contrast medium into the interstitium may account for the slight difference observed in the CT evaluation of GFR using electron-beam CT, compared with inulin clearance (3).
Moreover, our study was performed in a small sample size of pigs. The results are encouraging, but additional studies are needed to establish the accuracy of multidetector CT under pathologic conditions, as well as in humans.
In summary, 64-section multidetector CT provides reliable assessments of regional renal perfusion, tubular dynamics, and GFR and shows good agreement with the previously validated electron-beam CT measurements. Such measurements could potentially be obtained in conjunction with other CT studies, such as conventional abdominal CT or CT angiography. The minimal invasiveness and growing availability make multidetector CT a powerful tool to study the kidney under physiologic and pathologic conditions.
Practical application: The ability to add functional studies to derive quantitative assessments during the same examination could potentially reduce the number and overall cost of diagnostic procedures. Nevertheless, application of our technique in humans is still limited by the need for contrast medium and by the radiation burden. The radiation burden with multidetector CT is decreased by adjusting exposure to body thickness and can be further reduced by development of protocols that allow data acquisition at variable intervals, thereby decreasing the number of acquired images.
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ADVANCE IN KNOWLEDGE
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- Sixty-four-section multidetector CT provides reliable assessments of regional renal perfusion, tubular dynamics, and glomerular flow rate and shows good agreement with the previously validated electron-beam CT.
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ACKNOWLEDGMENTS
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The authors are grateful to Diane R. Eaker, BS, for her invaluable help handling CT images, and to the electron-beam CT and multidetector CT staff for technical assistance in performance of experiments. Siemens Medical Solutions provided an equipment grant.
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FOOTNOTES
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Abbreviations: GFR = glomerular filtration rate ITC = intratubular concentration RBF = renal blood flow TAC = time-attenuation curve
See Materials and Methods for pertinent disclosures.
Author contributions: Guarantor of integrity of entire study, L.O.L.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors; literature research, E.D., E.L.R., C.H.M., L.O.L.; experimental studies, E.D., A.N.P., A.R.C., J.D.K., X.Y.Z., C.H.M., L.O.L.; statistical analysis, E.D., J.D.K.; and manuscript editing, E.D., A.N.P., A.R.C., J.D.K., E.L.R., C.H.M., L.O.L.
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