Nuclear Medicine Genitourinary Imaging in Native Kidneys

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Similar to other facets of nuclear medicine, scintigraphic imaging of the genitourinary system emphasizes physiology over anatomy, which is typically evaluated with either ultrasound, computed tomography, or MRI. Nuclear medicine studies catered toward the genitourinary system in nontransplant patients assess renal blood flow, evaluate renal function, identify mechanical or functional obstruction, evaluate for renovascular hypertension, and assess vesicoureteral reflux. This article will review the most common radiopharmaceuticals and their clinical applications in evaluating the genitourinary system in native, nontransplant kidneys.

The kidneys filter the systemic blood supply by two mechanisms: passive filtration through the glomerulus and active tubular secretion. Approximately 20% of renal plasma flow is filtered and 80% is secreted. The glomerulus primarily filters larger compounds out of the urine, although some larger proteins are excreted into the urine by active secretion from the tubules.

Radiopharmaceuticals

While many radiopharmaceuticals have been used for renal imaging, the most common in clinical practice include technetium-99m (Tc-99m) mercaptoacetyltriglycerine (MAG3), Tc-99m dimercaptosuccinic acid (DMSA), Tc-99m diethylenetriaminepentaacetic acid (DTPA), and Tc-99m sulfur colloid. Tc-99m MAG3 is the most frequently used renal radiopharmaceutical in the United States (approximately 70% of cases) and is almost completely cleared by tubular secretion.1 Tc-99m MAG3 clearance correlates well with effective renal plasma flow and can be used as an independent measure of renal function. Tc-99m DMSA is the radiopharmaceutical of choice for renal cortical imaging, since it binds to sulfhydryl groups on the proximal convoluted tubule, allowing for minimal cortical transit. Tc-99m DTPA is a heavy metal chelator that is cleared by glomerular filtration. Tc-99 DTPA is used primarily for glomerular filtration rate (GFR) analysis, but may also be used in evaluation for renovascular hypertension.2 Tc-99m sulfur colloid is the preferred radiopharmaceutical in the evaluation for vesicoureteral reflux.

Dynamic Renography

Dynamic renography can be used to assess overall and differential renal function. In terms of patient preparation, patients should be instructed to drink plenty of water prior to the examination, as dehydration can affect the results.2 It is also recommended that patients void immediately following the procedure to reduce radiation exposure to the pelvic structures.2

After Tc-99m MAG3 is administered intravenously, posterior dynamic images are obtained for a total of approximately 30 minutes. Images are acquired every 1 to 5 seconds for the first minute to assess renal perfusion. One-minute images are then obtained for the remainder of the exam to evaluate cortical uptake and transit, as well as excretion.

Regions of interest (ROIs) are placed over each kidney and the aorta, with additional background ROIs inferior to each kidney, allowing for creation of time-activity curves (TACs) (Figure 1). The TACs allow for quantitative analysis of renal perfusion and function with regard to radiopharmaceutical uptake and excretion. Separate TACs can be created using ROIs encompassing the entire kidney, just the renal cortex, or the collecting system. Adjusting the ROIs may be necessary for accurate interpretation, especially in cases with collecting system retention (Figure 2).1

Renal uptake should occur around the same time as visualization of the aortic bifurcation on the initial dynamic images, with peak renal activity equal to or exceeding the aorta. The kidneys should also demonstrate symmetric activity/flow.4 A delay in visualization of the kidneys or decreased peak activity suggests abnormal perfusion. If both the renal and aortic flow curves demonstrate a slow rather than rapid rise, it is likely due to a poor injection bolus (Figure 3).5

Peak cortical activity should occur within 3 to 5 minutes, with half of the peak activity (T1/2) cleared from the kidney at 8 to 12 minutes. Less than 30% of peak activity should remain within the renal cortex at 20 minutes (Figure 4).2 A delay in cortical time to peak, prolonged cortical transit, or increased 20-minute cortical residual are nonspecific indicators of nephron dysfunction from acute or chronic renal disease (Figure 5).

Excretion is evaluated by determining the washout half-time (T1/2), which refers to the time from either peak activity to one-half peak activity, or with diuretic renography (discussed below) from the activity at the time of furosemide injection to one-half of that activity. T1/2 is considered normal if it is < 10 minutes.6

Differential function is usually calculated using the counts obtained between 2 and 3 minutes from the whole kidney ROIs. This should prevent inclusion of any significant collecting system activity. Differential function should be approximately equal between the kidneys with an acceptable range of a few percentage points to allow for differences in overlying attenuation. We use 45% to 55% as normal at our institution. No significant difference in differential function has been demonstrated between men and women.7

Diuretic Renography

While anatomic imaging can demonstrate dilation of the genitourinary collecting system, it is less reliable in delineating between obstructive and nonobstructive causes in the absence of a visualized source of obstruction. A patulous system with decreased peristalsis can result in dilation of the renal collecting system in the absence of a mechanical obstruction in a variety of clinical settings, to include vesicoureteral reflux (VUR), megaureter, and prior mechanical obstruction or infection.4 Diuretic renography can be helpful in these clinical scenarios.

Diuretic renography involves the addition of intravenous (IV) furosemide, a loop diuretic, to the dynamic renography study. It is important to first verify whether the patient is allergic to sulfa medications, as there is some degree of cross-reactivity with furosemide.8 Diuretic renography may be performed in one of three ways based on the timing of furosemide injection. The first option is to administer roughly 40 mg of IV furosemide (with dose adjusted for renal function and weight) at the same time as the radiopharmaceutical (MAG3) using the same imaging parameters discussed above under dynamic renography. This is referred to as the F+0 protocol. The second option is to perform the dynamic renography protocol as above and assess the need for furosemide administration at the 20-minute mark. If the examination is normal up to that point, then the study is complete without the need for diuretic administration. If the study is abnormal based on the parameters above, then the diuretic is administered at this point with continued imaging over the next 30 minutes. This is referred to as the F+20 protocol. The third option involves injecting the diuretic 15 minutes prior to radiopharmaceutical administration and then completing dynamic renography as described previously. Referred to as the F-15 protocol, this decreases the likelihood of a false positive exam by delaying imaging until after the peak effect of furosemide is reached.9

If collecting system dilation is due to a mechanical obstruction (eg, stone, stricture or mass), delayed washout of collecting system activity will be seen even after the administration of IV furosemide (Figure 6). If the dilation is not the result of an underlying mechanical obstruction, the increased urine production after diuretic administration will increase hydrostatic pressure enough to wash out the patulous system and T1/2 will normalize on dynamic renography (Figure 7).10 This process requires functioning renal tissue for the diuretic effect and can be negated by dehydration. T1/2 washout is considered normal if it occurs < 10 minutes after diuretic administration and abnormal if it is > 20 minutes.6 The 10 to 20 minute timeframe is less specific. At our institution, values of 10 to 15 minutes are generally deemed likely not obstructed, and values of 15 to 20 minutes are deemed likely obstructed.

Washout parameters from dynamic renography for patients with a dilated but not obstructed system will be normal if the diuretic is administered at the same time as (F+0 protocol), or prior to (F-15 protocol) administration of the radiopharmaceutical (Figure 8).

Renal Cortical Imaging

Renal cortical imaging with Tc-99m DMSA is useful in evaluating focal cortical abnormalities, such as pyelonephritis, space-occupying lesions, columns of Bertin (functional pseudotumors), and parenchymal scarring.11

Pyelonephritis refers to an infection involving the kidneys and has a variety of imaging appearances to include single or multiple cortical defects, and localized or diffuse decreased activity in one or both kidneys.12 Scintigraphy is sensitive for pyelonephritis and is especially useful in excluding pyelonephritis (with a normal study) in pediatric patients who often present with more challenging clinical symptoms. The primary limitation is the lack of specificity for an underlying infectious process.

For the imaging protocol, a weight-based dose of Tc-99m DMSA is administered, typically with a minimum of 500 µCi. Posterior and oblique images of the kidneys are obtained. Single-photon emission computed tomography (SPECT) images are also frequently obtained and often helpful.13 Normal kidneys will show homogenous uptake throughout the renal cortex; minimal heterogeneity secondary to renal cortical columns may be seen if a high-resolution collimator is used. In the acute phase of pyelonephritis, the defects are likely attributable to edema and relative ischemia of the renal parenchyma.14 These defects may resolve over time. However, if there is permanent scarring, cortical defects can develop with associated renal volume loss (Figure 9).15

Tc-99m DMSA scanning can also be used to assess renal masses to differentiate functional renal parenchyma from a space-occupying lesion. Space-occupying lesions, such as cysts, neoplasms, hematomas, abscesses, infarcts, and regions of scarring, will have focal decreased activity when compared to the adjacent renal parenchyma.11 Although a focal region of decreased activity is not specific to a particular pathologic process, it excludes normal renal tissue that may mimic a mass on other imaging modalities. Examples of normal variant and functional renal tissue that may mimic a mass include prominent columns of Bertin, fetal lobulation, and dromedary humps, all of which demonstrate normal radiopharmaceutical activity.4

Angiotensin-converting Enzyme Inhibitor (ACEI) Renography

Renal artery stenosis (RAS), usually due to atherosclerosis or fibromuscular dysplasia, is a relatively uncommon but important cause of hypertension. The associated hypertension is a result of the normal physiologic mechanisms designed to maintain glomerular filtration pressure. When there is decreased renal perfusion pressure secondary to RAS, renin is released by the juxtaglomerular apparatus (JGA). Renin is converted to angiotensin I (ATI) by angiotensinogen in the liver, which, in turn, is converted by ACE in the lungs to angiotensin II (ATII). ATII is vasoactive and results in vasoconstriction of the efferent arteriole, thus increasing pressure across the glomerulus.

Dynamic renography utilizing ACEI administration can help diagnose renovascular hypertension in at-risk patients, as there are no discriminatory clinical findings.16 The ACEI works by preventing the conversion of ATI to ATII in the lungs, thus preventing the compensatory renal vasoconstriction of the efferent arteriole. At-risk patients include those who initially present with hypertension before 30 or after 55 years of age; have severe or accelerated hypertension refractory to medical management; experience new difficulty with medical management; have evidence of occlusive vascular disease on other imaging modalities; have decreased renal function with recent hypertension; and/or exhibit abdominal pain or bruits auscultated over the flanks.17 The primary goal of ACEI renography is to identify patients who would benefit from correction of the underlying renal artery stenosis.

Prior to ACEI renography, patients should discontinue captopril 48 hours, and lisinorpil or enalapril 1 week, prior to the exam. They are also encouraged to be well-hydrated and to fast prior to the exam to improve the absorption of oral captopril administered as part of the study.18 Calcium channel blockers should also be discontinued as they have been shown to result in a false positive exam with bilateral decreased renal function.19

Protocols for ACEI renography generally involve a one- or two-day study. With a two-day protocol, an ACEI study is initially performed. If the study is normal, no further imaging is necessary. If abnormal, the patient returns on day two for a baseline study. The one-day protocol involves obtaining a baseline study with a low dose of radiopharmaceutical several hours prior to the ACEI study. Furosemide may be administered to clear the renal collection system.20 An ACEI study is performed approximately one hour following the oral administration of 25-50 mg of captopril or 15 minutes after 0.04mg/kg of IV enalapril.17 Ten mCi of Tc-99m MAG3 or DTPA is administered intravenously and renal scintigraphy is performed.

An ACEI study is abnormal when the renogram is asymmetric or becomes more abnormal when compared to the baseline renogram due to a drop in GFR caused by ACEI administration. When DTPA is used, a patient with renovascular hypertension will show diminished uptake and excretion on the ACEI study.18 When MAG3 is administered, an abnormal study will show increased cortical retention as tubular secretion is not affected, but the drop in GFR prevents washout of the tubular activity (Figure 10).18

Diagnostic criteria for RAS on a Tc-99m MAG 3 study include < 40% renal uptake at 2 to 3 minutes, retained cortical activity at 20 minutes that is > 20% asymmetric compared to the contralateral normal side or increased ≥ 15% from baseline (ipsilateral), or a delay in the time to peak activity > 2 minutes compared to baseline.21 Quantitative abnormalities should be confirmed on the qualitative data. Maintaining hydration throughout the exam is paramount, as both hypotension and dehydration can affect the renograms.5

In terms of reporting, a normal study or an abnormal baseline study that improves with ACEI is considered low probability (< 10%) for renovascular hypertension. If the baseline study is abnormal but is unchanged with ACEI, then it is considered intermediate probability for renovascular hypertension. High probability (> 90%) is reported when detrimental changes from baseline are seen after ACEI administration.21

Radionuclide Cystography (RNC)

While vesicoureteral reflux (VUR) is typically evaluated with a fluoroscopic voiding cystourethrogram (VCUG) initially, it is often followed up with radionuclide cystography (RNC). RNC may also be used in evaluating siblings of patients diagnosed with VUR.20 While RNC does not present the same level of detailed anatomic evaluation of VUR and cannot diagnose posterior urethral valves in a boy, it does prove a useful tool to confirm persistence or resolution of VUR. The benefits of RNC over VCUG include likely decreased radiation dose and increased sensitivity for small volume and intermittent reflux.22

RNC is performed by injecting a mixture of 0.5 to 1 mCi of Tc-99m sulfur colloid and saline through a bladder catheter, injecting enough volume to adequately fill the urinary bladder. Dynamic posterior images are obtained through at least one filling and voiding cycle. In a normal study, no radiopharmaceutical is visualized outside of the bladder. If reflux does occur, it may be seen during initial filling of the bladder, as the patient voids, or even on postvoid imaging. While reflux evaluated by fluoroscopic VCUG is categorized into one of five types based on varying severity, it is characterized as one of three variants (minimal, moderate, or severe) with radionuclide imaging. Minimal reflux is defined as radiopharmaceutical contained within the ureter(s), moderate if counts reach the pelvicalyceal system, and severe if the involved pelvicalyceal system appears dilated or the ureter is tortuous (Figure 11).4

The postvoid residual bladder volume can also be calculated by using the bladder counts before and after voiding. This quantitative assessment may be inaccurate in the setting of significant reflux, as the activity in the collecting system re-enters the bladder postvoid.23

Summary

Scintigraphy plays an important role in the evaluation of a variety of genitourinary pathologies. Its ability to assess renal function complements other cross-sectional modalities that rely more on anatomic assessment. Having a fundamental knowledge of the radiopharmaceuticals, clinical applications, and common pathologies is essential for those involved with interpretation of genitourinary nuclear medicine studies.

References

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Disclaimer: The views expressed in this article are those of the author and do not necessarily reflect the official policy or position of the Department of the Air Force, Department of Defense, or the U.S. Government.

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McQuillan BF, Zelasko S, Wolin EA.  Nuclear Medicine Genitourinary Imaging in Native Kidneys.  J Am Osteopath Coll Radiol.  2016;5(3):14-20.

About the Author

Brian F. McQuillan, M.D., Scott Zelasko, M.D., Ely A. Wolin, M.D.

Brian F. McQuillan, M.D., Scott Zelasko, M.D., Ely A. Wolin, M.D.

Drs. McQuillan, Zelasko, and Wolin are with the Department of Radiology, David Grant USAF Medical Center, Travis AFB, CA.


 

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