Radionuclide Imaging . An Update on the Use of Dynamic Renal Scintigraphy

Renal scintigraphy is a nuclear medicine technique that uses medical radioactive isotopes for the evaluation of the renal function. Functional data complete clinical and anatomical data obtained through other imaging techniques and can assist the clinician in the diagnostic and management of various renal disorders. Radionuclide imaging provides important functional informations which complement anatomic evaluation performed by morphologic techniques – intravenous urography, ultrasound imaging, computerized tomography (CT) or magnetic resonance imaging (MRI). It also have the advantage of evaluating the functional status of each kidney – information that cannot be obtained through biochemical assessment of serum creatinine and blood urea nytrogen (BUN). The current work will focus on the dynamic scintigraphy, protocol of examination, quantitative parameters and current indications, with emphasize on the obstructive renal disease.


INTRODUCTION
Renal scintigraphy is a nuclear medicine technique that uses medical radioactive isotopes for the evaluation of the renal function.Functional data complete clinical and anatomical data obtained through other imaging techniques and can assist the clinician in the diagnostic and management of various renal disorders.
Th e most widely used radioactive isotope for medical imaging is Technetium-99m.In renal scintigraphy 99m-Tc is coupled to a substance that is eliminated predominantely by glomerular fi ltration (DTPA)  or tubular excretion (MAG3) or which is attached to tubular proteins (DMSA).DTPA and MAG3 allow a dynamic study which result in the generation of a nephrographic curve for each kidney and the calculation of clearance parameters -ie glomerular fi ltration rate (GFR) or the eff ective renal plasma fl ow (ERPF), respectively.
Usual biochemical tests as determination of serum creatinine and blood urea nytrogen (BUN) -are both useful tools for the evaluation of total renal function.However, these blood parameters cannot evaluate each kidney individually.Moreover, relevant changes in blood levels of serum creatinine or BUN arise late in the evolution of renal disease, usually when renal function is already severely impaired.
Radionuclide imaging is functional imaging.It usually complete the anatomic evaluation performed by morphologic techniques -intravenous urography, ultrasound imaging, computerized tomography (CT) or magnetic resonance imaging (MRI).

PURPOSE
Th e purpose of this paper is to review the literature and present a useful but defi nitely underutilized imaging technique -dynamic renal scintigraphy.Th is paper is aimed to allow a better understanding of clinical applications of dynamic renal scintigraphy with emphasis on obstructive renal disease, to realize an overview of technique protocol, interpretation and clinical use.

Indications
Current indications of renal scintigraphy are listed in table 1.

Radiopharmaceuticals
Th ere are several radiopharmaceutical that can be used for the evaluation of renal function.Two radiopharmaceuticals are currently available worldwide for performing a dynamic renal imaging study: Tc-99mdiethylene triaminepentaaceticacid (DTPA) and Tc-99m-mercaptoacetyltriglycine (MAG3).Tc-99m-dimercaptosuccinic acid (DMSA) is a cortical agent used for the so-called static radionuclide imaging.Th ere are also radiopharmaceuticals used in the non-imaging assesment of GFR: 51Cr-Ethylenediaminetetraacetic acid (EDTA) and 125I-Iothalamate (Glomerular Filtration).Th ese radiopharmaceuticals allows GFR assessment through a method that uses plasma samples.
Tc-99m-diethylene triaminepentaaceticacid (DTPA) is mainly eliminated by glomerular fi ltration.It can be therefore used for a very accurate measurement of the fi ltration rate.Th e extraction fraction is about 20% in normal patients 2,3 .In patient with severely reduced renal function this extraction fraction can result in a lower sensitivity of the study 4 .
Tc-99m-mercaptoacetyltriglycine (MAG3) is cleared mainly by tubular secretion and has a higher extraction fraction than DTPA 5,6 .For this reason this is the preferred radiopharmaceutical for renal scans in most of the nuclear medicine centers worldwide, especially those in the USA 6 .Th e 99mTc-MAG3 clearance is described as the tubular extraction rate and can be considered as independent measure of renal function 3,7 .
Tc-99m-dimercaptosuccinic acid (DMSA) is used for renal static studies with assessment of relative function in pyelonephritis and renal scar 8 .DMSA is bound to proximal tubular cellular proteins.Many centers uses this radiotracer for pediatric evaluation of renal pathology.Due to the fact that in Romania the only available radiotracer at the time of submitting this paper is 99m-Tc-DTPA -the current work will focus on the dynamic DTPA studies, protocol of examination and current indications, with emphasize on the obstructive renal disease.

Patient preparation
Patient should drink 0.5 l of water 30 minutes before the examination -because some renal functional parameters may change in the presence of dehydration.Good hydration is also important in minimizing the absorbed radiation dose of the bladder.
According to some researchers medication with anti-infl ammatory drugs should be discontinued prior to procedure because they have the potential of infl uencing parameters of the renogram 9 .If the study is performed for suspected renovascular hypertension, special preparation is required, with good hydration, use of diuretic medication, discontinuing angiotensinconverting enzyme inhibitors prior to the basal study 10 .

Protocol of investigation
TTh e radiopharmaceutical is administered intravenously, with the patient already in the supine positioned on the gamma camera table.Dynamic acquisition of images begins immediately.Th e administered dose is 10-15 mCi (370 -555 MBq).Th is dosage is required for obtaining enough counts for calculating fl ow parameters.Many authors shown that fl ow studies result in essential information in the evaluation of renal transplant 11,12 but is of less importance in all other indications, including renovascular hypertension.Th erefore according to some authors -an administered dose of 37 -185 MBq is appropriate for the great majority of indications 3 .
Th e entire procedure takes 20-30 minutes.Acquisition is made with the dynamic protocol with serial images initially acquired rapidly at every 1-3s for the fl ow study, followed by sequential with 10s to 20s per frame for the renal function.Displayed images correspond to the radioactive bolus passing through aorta to renal arteries in the fl ow study, followed by the passage of the radioactivity through the kidneys.

RESULTS
After the acquisition image will be checked in order to assess if the examination was properly performed.After visual inspection region of interest (ROIs) will be placed over each kidney and time-activity curve will be generated (renogram).Th is represents a graphic illus-tration of the uptake and excretion of the radiotracer through the kidney.Normal renogram (Figure 1) has 3 parts: 1. Initial rapid ascendant segment -due to the vascular supply to the kidney.Th is phase refl ects the bolus of radioactivity that arrives via the renal artery to the kidney.2. Ascendant segment corresponding to the accumulation of the tracer in the kidney up to a peak activity.Th is peak is the point at which the extraction and accumulation trend is reversed to the evacuation process.Two factors are currently infl uencing the rate at which the renogam rises over this ascendant segment: the blood concentration of tracer and function of the kidney (individual kidney GFR for Tc-99m-DTPA) 13 .3. Descendent segment -refl ects the excretion of the radiotracer from the kidney.In this phase the gradient of the renogram depends on the rate at which the radiotracer is eliminated.In obstructive renal disease the curve generated from the ROI placed on the aff ected kidney has a typical appearance -slow continuous accumulation of tracer in the collecting system, a slow increasing ascending curve with no downslope.In contrast, a normal kidney will show a good uptake and excretion, and a normal three part TAC 14,15 .
Diuretic renography may be indicated in order to diff erentiate between obstructive and nonobstructed dilated urinary tract.Th e technique consists of the administration of a diuretic agent (furosemid) after the 20 min dynamic renal study and imaging 10 to 30 min more with the same dynamic protocol.If no obstructi- on is present -the renogram will show a rapid drainage of the radioactivity through the collecting system.If mechanical obstruction is present -the radiotracer will accumulate and excretion phase of the renogram will show ascendant slope 10,15 .

Quantitative analyze
Processing of the renal dynamic scintigraphy usually result in some quantitative parameters and indices that will be reported.Th is ability to perform quantitation is one of the most important advantage of functional techniques, not only because it helps documenting some pathologic condition but also because it allows follow up.
Here are some quantitative parameters usually calculated during the dynamic renal scan: Relative perfusion -this is the fl ow phase, which is important for the evaluation of renal number anomalies and renal transplant 3,16 most radionuclide renal studies are conducted at institutions that perform fewer than 3 studies per week, and a large percentage of studies are interpreted by physicians with limited training in nuclear medicine.Ten panelists were asked to categorize specifi c reporting elements as essential, recommended, optional (without suffi cient data to support a higher ranking.It represents the transit of radioactive bolus through abdominal aorta to renal arteries.Asymmetries or delays in perfusion may suggest abnormal perfusion.Delay in renal visualization can sometimes suggest suboptimal injection technique.
Relative Function represents the relative uptake of the radiopharmaceutical and quantifi es the diff erential renal function.Th is "split" or "diff erential" function is particularly useful because estimated GFR and/or serum creatinine may not identify unilateral lesions 1 .In normal patients this split function ranges from 42% to 58% 6 .
T max (Time to peak) -time interval between injection and the peak of the renogram curve.Normal Tmax ranges from 3 min to 5 min for DTPA and MAG3 3,17,18 .
Th e T½ -time interval in which radioactivity in the kidney decreases 50% of the maximum value (T max).Normal T1/2 should be less than 20 min.T1/2 is of very important value in diuretic renography in suspected obstructive disease 10,18 .
Th e 20-min/maximum count ratio represents the ratio between total kidney counts at 20 min to the total number of kidney counts at peak (maximum counts); it practically off er a measurement of parenchymal functi- or background corrections 20 .Camera-based clearances are reproducible and superior to creatinine clearance for monitoring changes in renal function 3,21 .

CONCLUSION
Renal radionuclide studies are reliable procedures that provide essential information about renal function, not available with other anatomical imaging technique.Th ese informations have the ability to complete clinical and morphologic evaluation performed by other imaging modalities for an effi cient diagnostic process.Th e possibility of quantifi cation allows measurement of various parameters which can be useful not only in diagnostic but also for monitoring treatment response.Radionuclide techniques are defi nitely underutilized in Romania.Eff orts should be made in order to increase logistic capacity at least at hospital level, in order to open the access to high quality diagnostic capabilities to a larger number of medical professionals and patients.on and transit time; for normal subject and for MAG3 renogram -total 20 min/max count ratio is 0.19 6 ; this parameter is useful in monitoring patients with suspected urinary tract obstruction and for detecting renovascular hypertension 3,17,18 .
Clearance measurement -can be acquired using plasma samples or camera-based algorithms.Plasma sample techniques allows estimation of clearance from the dose injected and the measured radioactivity in a blood sample 45 min after injection 1,14,19 .
Th is technique is reliable and accurate but requires experienced and properly trained operator and can be aff ected if there is no normal volume (ascites, large edemas, etc) 3 .
Camera based algorithms for DTPA and MAG3 are easy to perform, highly reproducible, do not require blood samples and can be used at the time of renal dynamic scan.At present software delivered with gamma camera equipments provide accurate estimation of GFR for DTPA (or clearance, ERPF for MAG3), with automatically correction for renal depth

1 Blood flow abnormalities 2
Function quantifi cation -Differential function, Glomerular fi ltration rate (GFR), effective renal plasma flow (EPRF) 3 Differentiation between a mass lesion and a column of Bertin 4 In infants with abnormalities of the urinary tract to study the urinary flow 5 Obstruction: ureteropelvic junction, ureteral obstruction 6 Pyelonephritis 7 Renal failure: acute and chronic 8 Renal artery stenosis with/without renovascular hypertension 9 Renal vein thrombosis 10 Renal transplant evaluation -transplant rejection, transplant anastomosis assessment

Figure 1 .
Figure 1.Time activity curve in a normal kidney (adapted from EANM: Dynamic renal imaging in obstructive renal pathology.A Tech nologist's Guide) 15 .

Figure 2 .
Figure 2. Right kidney with normal renogram.Left kidney obstruction with renogram showing ascendant excretory segment.

Table 1 .
Current indications of renal scintigraphy -adapted from Harvey A Ziessman et al.Nuclear Medicine: The Requisites, 4 th ed): 1