functional mri

Functional MRI:Evaluation of Chronic Kidney Disease with Perfusion Imaging1

Xin-Long Pei, MD, Jing-Xia Xie, MD

Rationale and Objectives. To evaluate the functional alterations of chronic kidney disease (CKD) with magnetic reso-nance dynamic perfusion imaging.

Materials and Methods. Twenty-one healthy subjects (42 kidneys) and 20 CKD patients (40 kidneys) underwent routinescans with fat-saturated T1-weighted fast low angle shot (FLASH) and true-fast imaging with steady-state precession(FISP) sequences followed by dynamic perfusion scans using a turbo-FLASH T1-weighted sequence. Signal intensity (SI)of the cortex and medulla on images was measured and plotted as a function of time. Peak height (P) and time to peak(T) of the cortex and medulla SI were estimated, and P/T ratio and the area under the time-intensity curves were calcu-lated. We also tested the correlation between these data and serum creatinine (sCr) levels in patients.

Results. P, P/T ratio, and the area under the curve of patients’ cortex and medulla were significantly decreased comparedto control subjects, and T was delayed. In patients, P and P/T ratio of the cortex and P of the medulla were negativelycorrelated with sCr levels (r � �0.469, r � �0.419, and r � �0.423, respectively; P � 0.01).

Conclusion. Renal dysfunction in CKD can be evaluated by magnetic resonance dynamic perfusion imaging.

Key Words. Chronic kidney disease (CKD); magnetic resonance imaging (MRI); perfusion.

© AUR, 2009

Magnetic resonance imaging (MRI) has several distinctadvantages in the kidney compared to other imagingmethods. Ultrasound scanning (US) is suitable for mor-phologic evaluation but does not supply information aboutrenal function. Intravenous urography (IVU) allows visu-alization of general morphology and simple functionalevaluation of the kidney. Contrast-enhanced computedtomography (CT) has excellent spatial and temporal reso-lution, but the contrast used during IVU and CT is neph-rotoxic and unfit for patients with renal dysfunction. Al-

Acad Radiol 2009; 16:88–95

1 From the Department of Radiology, Peking University Third Hospital, 49North Garden Road, Haidian District, Beijing, 100083, China. ReceivedMarch 10, 2008; revised June 12, 2008; accepted July 10, 2008. This workwas supported by the the Department of Radiology, Peking University ThirdHospital, Beijing, China. Address correspondence to: J.-X.X. e-mail: [email protected].

©
AUR, 2009doi:10.1016/j.acra.2008.07.002
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though nuclear medicine has provided reliable functionaldata, inability to visualize the kidney and lack of spatialresolution limit morphologic evaluation.

Dynamic contrast-enhanced MRI has great potential inproviding both morphologic and functional information inthe kidney (1–12). Dynamic T1 contrast-enhancement is acommonly used MRI technique. T1 (longitudinal relax-ation time) is shortened because of the dipole–dipole in-teraction of the contrast agent, which corresponds to in-creased signal intensity (SI) in T1-weighted imaging. Acommon contrast agent, gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) is not contraindicated in pa-tients with impaired renal function (13), and it is thereforepossible to study renal perfusion and excretion in patientswith chronic renal dysfunction using dynamic MRI.

During the first pass of Gd-DTPA in the tissue, thebolus is predominantly in the intravascular space, whichresults in a large gradient of concentration across the in-
terface of capillary walls. Perfusion information can be
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1. C

Academic Radiology, Vol 16, No 1, January 2009 EVALUATION OF CHRONIC KIDNEY DISEASE

gathered through monitoring SI changes over the courseof passage of the contrast without diffusion (1,14–16).Because Gd-DTPA is concentrated in the renal tubulesafter being filtered at Bowman’s capsule, and it is neithersecreted nor reabsorbed, the concentrating and dilutingfunction of the renal tubules is reflected (9,17–24). Reno-

Figure 1. Dynamic perfusion images from a hemally followed by enhancement of medulla. Corkidneys were equally enhanced. The images induring dynamic perfusion imaging, with uniform

Figure 2. Dynamic perfusion images from a CKand medulla were subdued, compared with Figure

grams measuring SI in the cortex and medulla can quanti-

fiably evaluate renal function, analogous to scintigraphy(25–27). It is therefore possible to evaluate kidney tissueperfusion and nephron function by measuring SI duringthe first pass of Gd-DTPA.

Frank et al. (19) previously reported that when usingdynamic contrast-enhanced MRI, that 20% of the contrast

subject. Enhancement of the cortex was nor-edullary differentiation was preserved. Both

es 1–3 were chosen at the same time pointh and level.

ient (sCr 191 �mol/L). Enhancement of cortexorticomedullary differentiation was preserved.

althyticomFigur

D pat

agent entering into the kidney was filtered by the glomer-

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smal

PEI AND XIE Academic Radiology, Vol 16, No 1, January 2009

ulus during the first pass, resulting in an initial increase inregional SI corresponding to T1-shortening of contrastagent in the ultrafiltrate. As the agent passes through theBowman membrane and moves through the proximal con-voluted tubule and down the descending limb of the loopof Henle (LOH), water is reabsorbed and the concentra-tion of contrast agent increases, leading to T1 and T2shortening as well as susceptibility-induced intravoxelspin dephasing (19).

Although Gd-DTPA always shortens both T1 and T2,at lower concentrations, T1 shortening predominates, re-sulting in tissue enhancement on T1-weighted images. Athigher concentrations, the effect of a short T1 is maximal,and T2 shortening is the dominant effect, resulting in de-creased SI of tissue on T1-weighted images (3,19). SI ispositively correlated with Gd-DTPA concentration beforethe inflection point (17), allowing renal perfusion to beevaluated by measuring SI.

With the development of MRI equipment and rapid

Figure 3. Dynamic perfusion images from a Ctex and medulla were distinctly delayed and sublary differentiation was decreased. There was a

Table 1Statistical Results in CKD Patients and Controls

Healthy Controls

CortexTime to peak (Tc) 25.8 � 3.0Peak height (Pc) 57.0 � 12.2Pc/Tc 2.2 � 0.5

MedullaTime to peak (Tm) 85.5 � 15.8Peak height (Pm) 55.9 � 10.7Pm/Tm 0.67 � 0.15

imaging techniques, temporal resolution has improved

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greatly. However, data are still scarce about chronic kid-ney disease (CKD) in this field, and further studies arestill necessary (5). This work describes our initial experi-ence of applying fast imaging techniques to characterizerenal perfusion in normal kidneys, and demonstrateschanges in renal perfusion in CKD. The correlation be-tween perfusion data and serum creatinine (sCr) levelswas also analyzed.

MATERIALS AND METHODS

SubjectsMRI studies were performed in 20 CKD patients (clin-

ically diagnosed, 12 men and 8 women; 16–69 years old;mean, 40.1). Controls consisted of 21 healthy volunteers(9 men and 12 women; 26–59 years old; mean, 39.6).Their sCr level and their appearance at MRI were normal.

atient (sCr 295 �mol/L). Enhancement of cor-, especially in the left kidney. Corticomedul-

l cyst at the inferior pole of the right kidney.

CKD Patients t P Value

31.4 � 8.1 4.230 �.0149.6 � 13.1 2.642 �.05

1.7 � 0.7 3.919 �.01

96.1 � 28.0 2.111 �.0545.9 � 13.0 3.818 �.010.50 � 0.19 4.486 �.01

KD pdued

Informed consent was obtained from all patients and con-


trols. The study was performed with the approval of thelocal ethical committee.

MRIIn our investigation, hydration was standardized and

fluid intake was restricted for at least 6 hours prior toimaging, so that Gd-DTPA enhancement would not beinfluenced by total body fluid content and would mainlyreflect differences in renal function (17,28). sCr was mea-sured before MRI examination. MRI was performed on a1.5-T superconducting system (Siemens Sonata, Erlangen,Germany). An 8-channel phased array body coil was used.The examination was performed with routine pre-contrastcoronal and transverse T1-weighted fat-saturated flashsequences (repetition time/echo time � 184 ms/4.76 ms,20 slices, intersection gap � 1.8 mm, section thickness �6.0 mm, with one signal averaged, and a 256 � 179 ma-trix), followed by transverse T2-weighted true-fasting im-aging with steady-state precession (FISP) sequence (repe-tition time/echo time � 4.30 ms/2.15 ms, 20 slices, inter-section gap � 1.8 mm, section thickness � 6.0 mm, withone signal averaged, and a 256 � 220 matrix), with afield of view of 320 � 240 mm. After these sequenceswere performed, the coronal planes through the hilar ves-sels were selected for dynamic perfusion imaging with aT1-weighted gradient-echo sequence (turbo-flash, repeti-tion time/echo time � 382 ms/1.34 ms, inversion time �230 ms, field of view � 340 � 255 mm, number ofaverage � 2, number of slices � 3, section thickness �6 mm, intersection gap � 1.5 mm, flip angle � 10°, andacquisition matrix � 256 � 128). The sequence wasmeasured 70 times, and the measurement time was 2.4seconds.

At the beginning of the fourth measurement, 0.1mmol/kg Gd-DTPA was injected (3 ml/s, total 20 ml)with a power injector via a cubital vein, followed by20-ml saline at the same rate. This dose of Gd-DTPA isthe standard clinical dose. The total dynamic sequenceconsisted of 70 successive images in every slice. The ab-domen was bound tightly with a cummerbund to restrainmovement. Patients were not restricted from breathing.

PathologyOf 20 patients, 17 kidneys were punctured under direc-

tion of an ultrasound the day after MRI examination. Theobtained tissues underwent periodic acid silver-methena-mine (PASM) stain and Masson stain for pathologic ex-amination. The examination was conducted by two expe-
rienced pathologists.
Data AnalysisRegions of interest (ROIs) of five pixels each were

selected in the upper, middle, and lower parts of the cor-tex and the medulla of both kidneys through the hilar ves-sels. Measurements were made of ROIs delineating partof the image. Despite the fact that the abdomen was re-

Figure 4. (a, b) Perfusion curve of a healthy subject and of apatient (sCr 295 �mol/L). In the patient, peak height and the areaunder the curve of the cortex and medulla were decreased andtime to peak of the cortex and medulla were delayed comparedwith the control subject. Focal proliferative sclerosing glomerulo-nephritis with ischemic injury was confirmed pathologically.

stricted by a cummerbund during scanning, some motion

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interfered with accurate positioning of ROIs in the cortexand medulla. When images were scrolled, ROIs were in-dividually modified to place over the cortex and medullafor frames in which they were improperly placed.

SI values were measured and mean SI of the cortex ormedulla was calculated through the values of the three ROIs.SI was plotted as a function of time with commerciallyavailable software (Mean Curve, Siemens Medical System) onthe MRI unit. Peak height and time to peak of cortex (Pc andTc, respectively) and peak height and time to peak of medulla

Figure 5. (a, b) The same patient as Figure 3. Peak height of cortexand medulla of the left kidney were distinctly lower than the right kidney.

(Pm and Tm, respectively) were measured and the mean values

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for each kidney were calculated. P/T ratio and the area underthe time-intensity curves were calculated. Statistical significancewas calculated using the independent-sample t-test (P � .05).The correlations between these three parameters (P, T, and P/T)and sCr level in patients were also evaluated (P � .05).

RESULTS

For control subjects, three phases were defined usingdynamic contrast-enhanced MRI during the passage ofcontrast agent through the kidney: the cortex phase, corti-comedullary differentiation phase, and medulla phase.Clear corticomedullary differentiation was seen in thesecond phase (Fig 1). For CKD patients, enhancement ofthe cortex and medulla tended to decline, and corticomedul-lary differentiation became blurry or lost (Figures 2 and 3).

In the normal kidney, SI in the cortex increased rap-idly during the first pass of Gd-DTPA. At 25.8 � 3.0seconds, Pc was reached (57.0 � 12.2). An appreciabledecrease in signal was observed after Pc, but SI thenrose continuously until the end of the examination. SIin the medulla increased more slowly than that of cor-tex during the first pass of Gd-DTPA. At 85.5 � 15.8seconds, Pm was reached (55.9 � 10.7), followed by acontinuous increase in SI until the end of the examina-tion. No decrease in the curve appeared. Tc and Tmwere significantly longer in those with CKD thanhealthy controls (P � .01). Pc, Pm, and the Pc/Tc andPm/Tm ratios in CKD patients were statistically re-duced compared to healthy controls (P � .05). Dataare shown in Table 1 and Figures 4 and 5.

The sCr levels of the 21 healthy controls ranged from70 to 124 �mol/L (mean 86.5). In contrast, sCr in the 20

Table 2Correlation Between sCr and P, T, and P/T of Cortex andMedulla in CKD Patients

r P Value

CortexTime to peak (Tc) 0.127 �.05Peak height (Pc) �0.469 �.01Pc/Tc �0.419 �.01

MedullaTime to peak (Tm) �0.059 �.05Peak height (Pm) �0.423 �.01Pm/Tm �0.298 �.05

patients ranged from 61 to 393 �mol/L (mean 171.5).


Table 2 presents the correlations between P, T, and P/Tof the cortex and medulla and the sCr values in patients.Significant negative correlations were found between Pc,Pc/Tc, and Pm and sCr (P � .01; Fig 6). The area underthe time-intensity curves for the cortex and medulla inCKD patients was statistically reduced (P � 0.01) com-pared to healthy controls. The data are shown in Table 3.

In the 17 cases that underwent pathologic examination,results were approved as glomerulonephritis or ischemic

Figure 6. With increased serum creatinine (sCr) level, (a) peak heheight of medulla (Pm) of kidneys reduced gradually in patients.

renal injury. Glomerular sclerosis or crescent formation,

proliferation of mesangial cells and the extracellular ma-trix, denaturalization or atrophy of renal tubules or pro-tein casts, interstitium fibrosis, and thickening of the arte-riolar walls were seen (Fig 7).

DISCUSSION

In this study, we used an ultrafast gradient sequence

f cortex (Pc), (b) Pc/time to peak of cortex (Tc), and (c) peak
ight o
(turbo-Flash) to improve temporal resolution of MRI of

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kidney function and morphology and to evaluate its use inthe examination of CKD. Compared to scintigraphy, MRperfusion can differentiate the cortex and medulla andevaluate their respective functions; however, previousstudies were restricted by long scan times (5). We usedan ultrafast gradient echo sequence that provided bettertemporal resolution of the time-intensity curves, and ameasurement was finished in about 2 seconds. At thesame time, an 8-channel phased-array coil was used,which provided better image quality. However, if corticalsegments or individual pyramids are analyzed, motionproblems are of concern.

In CKD patients, we found Tc delay and Pc and Pc/Tcdecreases, suggesting that pathologic changes in glomeruliresulted in decline of filtering function. In contrast, thereis a known positive correlation between the area underthe time-intensity curve and blood volume (22,29). Thearea under the time-intensity curve of the cortex amongpatients was less than that of healthy controls, whichshowed that renal blood volume was reduced. We alsofound Tm delay, Pm and Pm/Tm decline, and decreasedarea under the time-intensity curve of the medulla. Theresults demonstrate that the concentrating function of thekidney was weakened due to lesions of tubules and thatcontrast entering tubules decreased because of reductionin renal blood volume.

In our study, significant correlations were found be-tween Pc, Pc/Tc, and Pm and sCr. SCr level was a goodclinical index for evaluating renal function. These find-ings confirm that these functional indexes obtainedthrough MRI vary consistently with the degree of renalinsufficiency and reflect renal function.

Few previous investigations have been based on patho-logic diagnosis (5). According to our results, there may be adirect relationship between time-intensity curves and patho-logic results. Glomerular sclerosis, crescent formation, andproliferation of the mesangial cells and the extracellular ma-trix contributed to renal blood flow block and the glomerularfiltration rate decrease. Denaturalization or atrophy of renal

Table 3The Area Under the Time-intensity Curves in CKD Patientsand Controls

HealthyControls

CKDPatients t P Value

Cortex 132.6 � 27.6 105.6 � 30.3 3.951 �.01Medulla 116.6 � 22.5 90.6 � 22.1 4.892 �.01

tubules, protein casts, and interstitium fibrosis weakened

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renal concentrating function. Thickening of the arteriolarwalls also influenced blood flow perfusion (30).

During the respiratory cycle, the kidneys slide alongthe surface of the psoas muscle in a cranial-dorsal to cau-dal-ventral direction, and rotate around the hilar vessels.The result is a complicated, three-dimensional motion (3).Although movement of the abdomen in our study wasrestrained by tight binding with a cummerbund instead ofby instructing participants to hold their breath, the qualityof images acquired was comparable to images describedin previous reports (3,4). Motion artifacts were avoided

Figure 7. Immunoglobulin A (IgA) glomerulonephritis with isch-emic injury at 20� magnification. (a) PASM stain. (b) Massonstain. Note the sclerosing glomerulus, crescents, and extensiveproliferation of the mesangial cells and extracellular matrix. Atro-phy of renal tubules, monocyte and fibrosis in interstitium, andlight thickening of arteriolar walls were observed.

and image quality was not influenced.


Some limitations in the study should be mentioned.Cases of severe renal insufficiency were lacking, andmore data are needed to further define the functional be-havior of MRI in these kidney diseases.

SummaryWe may make several conclusions based on the results

of this study. First, our method of binding the abdomen torestrain movement was comparable to previously usedmethods. Phased-array coils and ultrafast sequences pro-vided reliable image quality and good temporal resolutionof the time-intensity curves. P, P/T, and the area underthe curve of CKD patients’ cortex and medulla were de-creased and T was delayed relative to controls. Pc, Pc/Tc,and Pm were negatively correlated with sCr levels. Thesedata indicate decline in the filtering and concentratingfunctions of the kidney and were associated with patho-logic changes of the nephron in the CKD patients. In con-clusion, this study demonstrates that renal dysfunction inCKD can be evaluated with MR dynamic perfusion imag-ing, which is a promising method for clinical use.

ACKNOWLEDGMENT

We are grateful to Professor Song Wang Professor HuiXu , and Xue-Hui Yao for their assistance.

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