H. J. Michaely, MD
Department of Clinical Radiology, University Hospitals – Gross hadern, Ludwig Maximilian University of Munich, Marchioni nistr. 15, 81377 Munich, Germany
N. Oesingmann, PhD
Siemens Medical Solutions USA, Inc., MR R&D Collaboration, NYU CBI, 660 First Avenue, New York, NY 10016, USA
C O N T E N T S
39.1 Introduction 441
39.2 Arterial Spin-Labeling Perfusion
Measurements 442
39.3 First-Pass Perfusion 442
References 447
Imaging of Renal Perfusion 39
Henrik J. Michaely and Niels Oesingmann
39.1
Introduction
In the past years, the focus of MR imaging of the kidneys has changed from pure visualization of renal (vessel) morphology and the grading of renal- artery stenosis (RAS) by MR angiography (MRA) (Schoenberg et al. 2003; Shetty et al. 2000; Tan et al. 2002; Prince 1998) to more comprehensive approaches. These include MR fl ow measurements to evaluate the hemodynamic signifi cance of a RAS (de Haan et al. 2000; de Haan et al. 2003; Schoen- berg et al. 2000) and more recently also renal per- fusion measurements (Michaely et al. 2006a; Lee et al. 2001; Gandy et al. 2003; Montet et al. 2003; Lee et al. 2003; Karger et al. 2000; Michaely et al. 2004;
Michaely et al. 2005a). While the MRA and MR fl ow measurements can characterize the renal macrovas- culature, perfusion is intended to display the renal microvasculature. Hence, perfusion measurements
aim at demonstrating the capillary blood fl ow in the renal parenchyma, and especially in the highly vascu- larized renal cortex. The literature presents multiple concepts for renal perfusion imaging (Michaely et al. 2006a; Lee et al. 2001; Gandy et al. 2003; Lee et al. 2003; Karger et al. 2000; Michaely et al. 2004;
Aumann et al. 2003; Berr et al. 1999; Bjornerud et al.
2002; Ichikawa et al. 1997; Laissy et al. 1994; Prasad et al. 1999; Roberts et al. 1995; Schoenberg et al.
2003; Trillaud et al. 1993; Vallee et al. 2000; Wil- liams et al. 1994; Michaely et al. 2005b). In general, three different methods for MR perfusion imaging of the kidney have been described for renal artery steno- sis, namely qualitative assessment of renal perfusion with arterial spin-labeling (ASL) techniques without contrast agents, semi-quantitative perfusion meas- urements with extracellular gadolinium chelates, and quantitative assessment of renal perfusion with intra- vascular contrast agents with absolute parameters of regional renal perfusion (Michaely et al. 2006a;
Aumann et al. 2003; Prasad et al. 1999). Even though they are all subsumed under renal perfusion, they use different techniques and thus have different aims.
Contrast-enhanced (CE) fi rst-pass perfusion studies mainly aim at assessing the impact of renal artery stenosis or renal parenchymal disease on the paren- chymal perfusion or aim at assessing the patency of a renal artery stent (Gandy et al. 2003; Michaely et al. 2005a; Vallee et al. 2000).
An approach completely different from the CE techniques is arterial spin labeling where blood is used as endogenous contrast agent (Karger et al.
2000; Michaely et al. 2004; De Bazelaire et al.
2005; Gunther et al. 2001; Martirosian et al. 2004).
Depending on the specifi c technique used, ASL tech- niques may be able to yield only perfusion-weighted images (Michaely et al. 2004) or to exactly calculate the renal perfusion (Martirosian et al. 2004).
The clinical relevance of perfusion measurements
is underlined by publications showing that reduced
renal perfusion is associated with increased rates of
morbidity and mortality in different settings (Fan et
al. 1990; Hillege et al. 2000). Interestingly, decreased fi rst-pass perfusion parameters were also found in hypertensive rats without renal artery stenosis and were found to improve under therapy (Lenhard et al. 2003). This may indicate that fi rst-pass perfusion could also be applied to the detection and monitoring of chronic renal failure in the future.
39.2
Arterial Spin-Labeling Perfusion Measurements
ASL techniques are attractive in that they are non- invasive and do not require the administration of contrast agents (Michaely et al. 2004). In addition, many ASL sequences can be acquired within a single breath-hold. Different techniques have been pro- posed so far in the literature, however mainly animal studies or volunteer studies have been performed (Karger et al. 2000; Roberts et al. 1995; Williams et al. 1994; Wang et al. 1998). The basic idea of ASL is to acquire two images that are post-processed to obtain a perfusion-weighted image without the use of contrast agents. In one image, in-fl owing blood is labeled with an RF pulse, while a control image without blood labeling is acquired for subtraction to suppress signal from stationary tissue.
A commonly used technique is the so-called fl ow- sensitive alternating inversion-recovery method (FAIR) (Michaely et al. 2004). In this technique, fi rst a non-selective global inversion is applied for the labeling image, whereas the control image is acquired with selective inversion only. The stationary tissue is inverted in both images and thus disappears with the subtraction. This completely symmetric inversion scheme has the advantage of reducing magnetization transfer effects. However, no image information is sampled during the delay time, so that FAIR measure- ments are relatively ineffi cient and time-consuming.
To overcome this problem a Look-Locker acquisi- tion has been proposed (Gunther et al. 2001) that samples a series of images after each labeling pulse instead of just one image. This technique also over- comes the limitation of many ASL sequences to gener- ate only a single perfusion-weighted slice without the temporal perfusion information and thereby possibly offers quantifi cation of perfusion. Other approaches for ASL perfusion include STAR and EPISTAR tech- niques (Prasad et al. 1997) with an EPI readout
module being implemented into the latter. However, one disadvantage of STAR is the induction of magneti- zation-transfer contrast (MTC) caused by the specifi c labeling technique used. Recently, a steady-state free precession TrueFISP-readout for ASL sequences has been presented to increase the signal-to-noise ratio (SNR) and to decrease the susceptibility for artefacts (Martirosian et al. 2004), which allowed absolute quantifi cation of the perfusion.
One major disadvantage of using arterial spin labeling techniques for renal perfusion imaging is the poor signal-to-noise ratio of this approach at 1.5 T. This makes the calculation of semi-quantita- tive or quantitative parameters of renal perfusion diffi cult and unreliable, although some authors have presented absolute values of renal perfusion with modifi ed ASL techniques and acceptable reproduc- ibility (Karger et al. 2000). Newer approaches used a FAIR-TrueFISP readout (Martirosian et al. 2004) to yield a higher SNR than with the conventionally used FAIR-HASTE (Michaely et al. 2004) or FAIR-EPI (Gunther et al. 2001) readouts. Also, the transition to higher fi eld strength will surely be benefi cial for ASL measurements, as with the longer T1 relaxation times at higher fi eld strength the magnetic labeling will decay more slowly (Michaely et al. 2004; Thul- born 1999). Another major drawback associated with the low inherent SNR of ASL measurements is the sensitivity to susceptibility artefacts. While the application of parallel imaging would be disadvanta- geous in terms of SNR, it will be helpful in avoiding or reducing susceptibility artefacts, particularly with EPI readouts. Since suffi cient SNR for the application of parallel imaging is only available at higher fi eld strengths, ASL will surely profi t from the increasing number of high-fi eld scanners. However, no reports on the combination of parallel imaging and ASL exist so far for abdominal applications. In brain perfusion, the feasibility of ASL with parallel imaging has been proven (Wang et al. 2005).
39.3
First-Pass Perfusion
In contrast to the ASL techniques, CE MR perfusion
techniques do not suffer from SNR limitations. A bolus
of paramagnetic contrast agent such as Gd-DTPA or
Gd-BOPTA is administered at a high fl ow rate of 3 to
4 ml/s to obtain a well-defi ned bolus. Different reports
have been published about the ideal amount of con- trast agent raging from a 2 ml fl at dose (Lee et al. 2001) to 0.1 mmol/kg body weight (Michaely et al. 2006a).
The fi rst pass of the contrast-agent bolus is imaged with a high temporal resolution to fi nally obtain a signal-intensity-versus-time curve. Depending on the approach used, a semi-quantitative or quantitative measurement of the perfusion can be achieved with standard, extracellular contrast agents. The applied sequence techniques are characterized by a high tem- poral resolution, which is required to sample enough data points of the contrast agent bolus passing through the kidneys. In the literature VIBE (Gandy et al. 2003) sequences, TurboFLASH sequences (Michaely et al.
2006a; Trillaud et al. 1993) and fast gradient-echo (GRE) sequences without magnetization preparation (Vallee et al. 2000) are used to visualize the signal increase with standard contrast agents. With the application of intravascular contrast agents, such as investigational drugs including NC 100150 (Nycomed, Oslo, Norway), T2*-based techniques can be applied (Aumann et al. 2003; Schoenberg et al. 2003;
Trillaud et al. 1993). Recently approved strongly pro- tein-binding gadolinium chelates with semi-intravas- cular properties allow the absolute quantifi cation of renal perfusion with T1-weighted saturation-recovery GRE techniques (Prasad et al. 1999).
Perfusion data require intensive postprocessing to determine either semiquantitative parameters such as the mean transit time and the maximum upslope of the signal-intensity-versus-time curve (Fig. 39.1) (Michaely et al. 2006a; Gandy et al. 2003) or abso- lute parameters of renal perfusion such as blood fl ow per minute and 100 g of renal tissue. While semi- quantitative approaches are more robust, but some- what limited in their information, absolute quantifi - cation requires correction of the data by the arterial input function. For patients with renal artery stenosis (Fig. 39.2) the semiquantitavtive approach revealed signifi cant differences in the mean transit time and the maximal upslope of the signal-intensity-versus- time curve between patients with high-grade renal artery stenosis (>75% diameter) and healthy patients (Michaely et al. 2006a). In a study by Vallee et al.
(2000), a signifi cantly decreased absolute renal blood fl ow in patients with renal artery stenosis or renal fail- ure of 0.51 ml/min/g compared to 2.54 ml/min/g in healthy kidneys was found. Apart from this approach in which the signal intensity was converted into the concentration of the contrast agent, other approaches with deconvolution algorithms for quantifi cation of renal perfusion (Aumann et al. 2003; Dujardin et al.
2004; Johansson et al. 2003) have been published as well. However, none of these techniques have found widespread acceptance as major technical hurdles for fast and reliable deconvolution techniques have to be overcome in the future.
Initial results using parallel imaging for semi- quantitative assessment of kidneys were presented by Michaely et al. Hereby, the number of slices, which can be measured during the fi rst pass of the contrast agent bolus, could be increased from four to six. The applied TurboFLASH sequence used the GRAPPA algorithm, which led to some increased background noise. However, in an intraindividual comparison study of TurboFLASH without parallel imaging versus TurboFLASH with parallel imaging, the semiquantitative parameters were found to be statistically not different. While at 1.5 T the noise is signifi cantly increased with parallel imaging, imag- ing at 3.0 T offers suffi cient SNR for fast imaging with the application of parallel-imaging techniques.
Initial results of perfusion imaging at 3.0 T found superior image quality with a 60% increase in SNR even with the application of parallel-imaging tech- niques. The semiquantitative perfusion parameters were not statistically signifi cant to 1.5 T again (sub- mitted data). An example for 3.0-T perfusion can be found in Fig. 39.3.
A different methodological approach for the depic- tion of the renal perfusion is time-resolved MRA tech-
Fig. 39.1. This scheme demonstrates how the perfusion pa-
rameters maximal signal intensity (1), maximal upslope (2),
mean transit time (3) and the time-to-peak signal intensity
are derived based on a Gamma-variate fi t from the fi rst pass
part of the signal-intensity-versus-time curve. Reprinted with
permission from (Michaely et al. 2006b)
Fig. 39.2. a Thin MIP of an MRA of a patient without renal artery stenosis demonstrating a healthy renal artery. b The signal- intensity-versus-time curve of this patient reveals a regular curve with a steep upslope and a marked peak. c Thin MIP of a patient with high-grade renal artery stenosis (arrow) at the ostium of the renal artery. d The signal-intensity versus time curve of this patient demonstrates a markedly slower upslope of the perfusion curve with a less pointed peak (compare to b). Reprinted with permission from (Michaely et al. 2006b)
Fig. 39.3. a Exemplary images of a TurboFLASH perfusion measurement in a 29-year-old healthy volunteer. This sequence was acquired without parallel imaging, which allowed acquiring four slices per second. In this early arterial phase, there is marked enhancement in the aorta and the renal cortices. b Exemplary images of a TurboFLASH perfusion measurement in the same 29-year-old healthy volunteer as shown in a. This sequence was acquired with parallel imaging, which allowed acquiring six slices per second. In this early arterial phase, there is equal enhancement in the aorta and the renal cortices as compared to the images without parallel imaging.
Also, the visual assessment does not reveal a lower SNR of the TurboFLASH sequence with parallel imaging. c Comparison of the signal-intensity-versus-time curves of the two TurboFLASH sequences of the above volunteer. The curves reveal that using parallel a
a c
b d
컄컄
