Functional Renal Imaging: New Trends in Radiology and Nuclear Medicine

Functional Renal Imaging: New Trends in Radiology and Nuclear Medicine Emmanuel Durand, MD, PhD,* Philippe Chaumet-Riffaud, MD, PhD,* and Nicolas Grenier, MD† The objective of this work is to compare the characteristics of various techniques for functional renal imaging, with a focus on nuclear medicine and magnetic resonance imaging. Even with low spatial resolution and rather poor signal-to-noise ratio, classical nuclear medicine has the advantage of linearity and good sensitivity. It remains the gold standard technique for renal relative functional assessment. Technetium-99m (99mTc)- labeled diethylenetriamine penta-acetate remains the reference glomerular tracer. Tu- bular tracers have been improved: 123I- or 131I-hippuran, 99mTc-MAG3 and, recently, 99mTc-nitrilotriacetic acid. However, advancement in molecular imaging has not pro- duced a groundbreaking tracer. Renal magnetic resonance imaging with classical gadolinated tracers probably has potential in this domain but has a lack of linearity and, therefore, its value still needs evaluation. Moreover, the advent of nephrogenic sys- temic fibrosis has delayed its expansion. Other developments, such as diffusion or blood oxygen level-dependent imaging, may have a role in the future. The other modalities have a limited role in clinical practice for functional renal imaging. Semin Nucl Med 41:61-72 © 2011 Elsevier Inc. All rights reserved. he main function of the kidneys is to maintain the injection of a diagnostic agent, but physical labeling, such Thomeostasis of extracellular content. Imaging tech- as tagging or arterial spin labeling in magnetic resonance niques can indirectly explore this function by showing imaging (MRI), also may be used. Therefore, when com- processes that are used for this purpose: perfusion, filtra- paring different techniques for functional imaging, 2 as- tion, secretion, concentration, and drainage. Unlike ana- pects must be addressed: general image characteristics tomic imaging, functional imaging aims at showing dy- linked to the imaging technique and tracer characteristics. namic processes, ie, evolution over time. Some functional processes can be visualized by their motion (eg, the heart beating), but most are stationary, which makes them more Imaging difficult to visualize: for example, every water molecule leaving the organ is replaced by another water molecule. Medical imaging encompasses 4 main techniques: radiol- Major functional processes are occurring at a microscopic ogy (including computed tomography [CT]), nuclear scale, but macroscopic parameters do not change over medicine (NM), including positron emission tomography time. In these conditions, visualizing functional processes (PET), ultrasound (US), and MRI. In addition, optical im- requires some kind of labeling to interfere with the steady aging (OI) can be considered for small animal imaging. In state. Most of the time, this labeling is performed by the practice, renal functional imaging needs close follow-up over time with sequential imaging. Because of limitations attributable to radiation burden, this makes radiological techniques hardly suited to functional renal imaging. Con- *Biophysics and Nuclear Medicine, Univ. Paris Sud, Le Kremlin-Bicêtre Cedex, France. trast media (CM) suited to US techniques are mostly vas- †Service d’Imagerie Diagnostique et Interventionnelle de l’Adulte, Groupe cular, which makes them inappropriate for renal func- Hospitalier Pellegrin, Bordeaux-Cedex, France. tional imaging beyond mere perfusion studies. Therefore, Address reprint requests to Emmanuel Durand, MD, PhD, Biophysics and this review focuses on NM and MRI. A specific article in this Nuclear Medicine, Univ. Paris Sud, F94275, 78 Rue du Général Leclerc, 1 F94275 Le Kremlin-Bicêtre Cedex, France. E-mail: emmanuel.durand@ issue of the journal addresses renal PET; therefore, the present u-psud.fr article will focus on gamma-emitters. 0001-2998/11/$-see front matter © 2011 Elsevier Inc. All rights reserved. 61 doi:10.1053/j.semnuclmed.2010.08.003 62 E. Durand, P. Chaumet-Riffaud, and N. Grenier Physical Principles position of other structures over kidneys; however, this su- MR shows the signal that hydrogen nuclei emit after proper perimposition is addressed with signal processing and back- excitation when they are set in a strong magnetic field. This ground removal (or more sophisticated techniques, such as 2,3 signal comes from the magnetic moment of hydrogen nuclei. Patlak-Rutland technique ). Images can thus be acquired even without any diagnostic agent: Distinction between the parenchyma and cavities can be diagnostic agents act as contrast agents (CAs) (they modify the done with MRI but not in NM on 2D-projections because of image). NM uses injected tracers that emit gamma-rays parenchyma and cavity superimposition. Distinction be- (positrons for PET), which are localized to make an image. tween cortex and medulla can be done in MRI, provided the Therefore, injection of a diagnostic agent is mandatory to obtain region of interest is drawn with caution, but not in NM. Of any image. An advantage of classical NM over PET is that it is course, microstructures, such as nephrons or small vessels, possible to use radionuclides that emit photons with different are not distinguishable when any of these techniques are energy levels. Thus, several biomarkers can potentially be dis- used. Finally, delimitation of large vascular structures, such tinguished at the same time, as opposed to PET radionuclides, as aorta, to obtain arterial input function is quite easily which all emit the same energy photons (511 keV). achieved with MRI but is more difficult with NM. To summarize, the main issue in functional imaging is the Spatial Resolution separation between right and left kidney, which both modalities Imaging is localizing information. The localizing technique de- perform well. Better arterial input functions and separation in pends on the imaging modality. Electromagnetic waves can be duplicate kidneys are an advantage for MRI. The projection im- localized, at best, with a precision of one-half their wavelength. age for NM seems to be a drawback but it has also its advantage: For high-energy physics (gamma photons), wavelengths are a the whole kidney is seen in a single image (MR usually samples few picometers. For MR, radiofrequency waves are used, with function on a few slices) and the time taken to draw regions of wavelength of several meters. This would suggest a much better interest is much less for NM. resolution for NM. In fact, it is the opposite: spatial localiza- Kidneys are located under the diaphragm and experience tion in MRI is achieved through magnetic field gradients, movements caused by ventilation motion. Usually, MRI uses which theoretically enable localization at a micrometer scale, registration techniques to compensate the motion, which although signal-to-noise ratio usually limits it to a millimeter takes time. NM techniques usually skip this step, and motion scale. In contrast, gamma rays cannot be focused with lenses, blurring is not even considered in NM because one does not so lead collimators are used and effective resolving power is usually make it out from poor spatial resolution. This is a approximately 1 cm in humans (a slightly better resolution strong limitation for cortex versus medulla separation. Gated can be obtained with dedicated small animal imaging). imaging is possible in NM, but it lengthens the time for data In practice, in dynamic renal imaging, MRI typically pro- acquisition. vides multiple slices of approximately 1-cm slice thickness and 2-mm in-plane resolution, whereas NM provides 2-di- Temporal Resolution mensional (2D) projections with approximately a 10-mm Temporal resolution is not an intrinsic physical limitation: in in-plane resolution (Table 1). It may be sensible to look into theory, images could be obtained in a fraction of a second for the requirements in resolution for renal functional imaging. all techniques. It is rather a matter of trade-off between sig- The first aim of spatial resolution is to separate right from left nal-to-noise ratio, image quality, and spatial resolution. Both kidney: both NM and MRI perform well in this respect. An- NM and MRI can reach image cadence of a few seconds per other point is to separate upper from lower parts of the kid- image, which is enough for perfusion (vascular transit time is ney for duplicate systems; this can be done easily in MRI but approximately 5 s), renal uptake (peak usually obtained in a it is more tricky for NM, both because the 2 are not necessar- few minutes), drainage, and even to correct for breathing ily well-separated on 2D projection images. Separation be- artifacts. Cardiac motion is not really an issue but could even tween kidneys and other organs is easily attained in MRI and be corrected for with electrocardiogram gating. To summa- only indirectly in NM because 2D projection yields superim- rize, temporal resolution is not an issue. Synchronization Table 1 Typical Imaging Parameters for Human Dynamic Renal Imaging (These Values Vary Greatly According to Imager Performances and Settings) MRI NM PET CT US Spatial resolution Type Multiple 2D slices 2D projections 3D Multiple 2D slices Single 2D slices Slice thickness 10 mm N/A 5 mm 1 mm 5-10 mm In-plane 2 mm 10 mm 5 mm 1 mm 1 mm Temporal resolution 3 s 1-20 s 10 s* <1s† <1s Tracer sensitivity ␮mol-mmol pmol pmol 100 mmol NA *For list mode. †Cannot be repeated as fast because of radiation burden. Functional renal imaging 63 Figure 1 Example of relationship between CM concentration and signal; the first part of the curve is reasonably linear after correction for baseline. The first part of the curve is mostly attributable to longitudinal relaxation (signal increase); the second part is mostly attributable to transversal relaxation (signal decay). This curve is a simulation with TR ϭ 17 ϭ ϭ ϭ ϭ Ϫ1 Ϫ1 ϭ ϫ Ϫ1 Ϫ1 ms, TE 4 ms, flip angle 90°, T1 1100 ms, T2 76 ms, r1 3 L · mmol ·s and r2 4L mmol ·s .

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