Nuclear Medicine Resources Manual

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CHAPTER 5. GUIDELINES FOR GENERAL IMAGING

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(d) Detection of associated abnormalities: abnormal duplex kidneys, small

kidneys, dysplastic kidneys and horseshoe kidneys;

(e) Distinguishing pseudotumours from tumours;

(f) Ectopic kidneys;

(g) Allergy to iodine contrast agents precluding radiological investigations.

5.4.2.3. Radiopharmaceuticals

Technetium-99m DMSA should be reconstituted with

99m

Tc-pertech-

netate and used within 30 min. Oxidation of the product reduces tubular

reabsorption and increases urinary excretion, so care should be taken to

prevent oxidation. As renal function becomes more impaired, increasing liver

uptake of DMSA occurs. The agent should be prepared according to the

manufacturer’s instructions for kidney studies.

5.4.2.4. Equipment

A single- or double-headed gamma camera is required with a low energy,

high resolution (LEHR) parallel hole collimator, or a pinhole collimator for

infants. SPECT is unnecessary for routine work but can be done as a

complement. Data should be recorded in a 256 × 256 matrix into a computer

for subsequent analysis. Alternatively the electronic zoom (factor 2) can be

used for recording in a 128 × 128 matrix.

5.4.2.5. Patient preparation

An explanation to the patient and/or the child’s parents should be given

before the start of the study. For adults, no preparation is necessary. Infants

should be fed before imaging. Anaesthetic skin preparation before an injection

is advised for children. An intravenous injection of 80–100 MBq (2–2.5 mCi) of

99m

Tc-DMSA is given for adults. For children and infants, the dose is scaled

down according to the body surface area; however, a minimum of 15 MBq

(0.4

mCi) should be administered.

Imaging is performed between 2 and 4 hours after injection. A child

should be cushioned comfortably against the camera face, and in an inclined or

supine position. An infant should be cushioned and supported in place with

Velcro strapping, lying supine on the face of the camera, which has been

covered by a protective sheet.

In adults, the acquisition of 500 000 counts each of the posterior, anterior,

left and right posterior oblique views is recommended. Additional oblique

images are recommended for scan evaluation only. In children, a posterior

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231

300 000 count acquisition is considered sufficient and the anterior view is

needed only if one or both kidneys are displaced. A pelvic view is obtained if

one or both kidneys are not seen.

5.4.2.6. Measurement

Relative function is determined from the background subtracted renal

activities in the posterior view according to right or left/(right + left). In the

case of displaced kidneys, the geometric mean of the background subtracted

renal activities in the posterior and anterior views is used. The relative function

may be inaccurate if there is pelvic retention of activity. Absolute uptake may

be used as an indication of renal growth.

5.4.2.7. Interpretation

Normally the kidney contours are smooth and rounded with a contrast

between the outer cortical part and the less active medial portion of the

kidneys. A smearing of the uptake and ‘soft’ kidney contours may indicate

patient motion during acquisition.

(a) The normal image variants are:

— A contour can be flattened without suggesting a lesion; this is particu-

larly the case for the upper lateral aspect of the left kidney (splenic

impression).

— In young children, the kidney may have a triangular shape, with

flattened external sides.

— A ‘slender’ kidney, characterized by a short transverse axis in the

posterior view, is usually normal and corresponds to a rotated kidney.

— The transverse axis is sometimes shorter at one pole (upper or lower),

giving the kidney a pear shaped appearance.

— The poles, and particularly the upper pole, may appear diffusely

hypoactive simply because of the contrast with the hyperactive

columns of Bertin below the pole or because of respiratory movement

of the kidneys.

— The number and size of the columns of Bertin differ from patient to

patient.

(b) Abnormal DMSA scintigraphy:

— The relative function is outside the normal range of 45–55%.

— Areas of reduced uptake, without cortical defects, are relatively

common. These kinds of defect are seen in acute pyelonephritis and

may either heal or develop into permanent lesions. Dilated calyces

CHAPTER 5. GUIDELINES FOR GENERAL IMAGING

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may cause parenchymal defects, as do cysts and space occupying

lesions.

— The diagnosis of a ‘scar’ requires both a cortical defect and a subjacent

parenchymal uptake defect for interpretation. The number and sites of

defects should be recorded.

— The timing of imaging is important. Imaging at the time of urinary

tract infection may show defects due to renal infection. Imaging three,

or preferably six, months later will show whether these defects have

healed or left scars. Scarring may be found without demonstrable

vesicoureteric reflux, and reflux may be present without demonstrable

scarring.

— Poor renal function leads to hepatic uptake.

— A suspected space occupying lesion on intravenous urography that

shows normal DMSA uptake at that site is called a pseudotumour.

5.4.2.8. Pitfalls

In the case of a unilateral duplex kidney with normal parenchyma, the

duplicated kidney may correspond to more than 55% of the total function. The

single moiety kidney may then be erroneously classified as abnormal. Bilateral

small kidneys may be overlooked.

Pelvic retention, in the case of hydronephrosis, may cause an artefactually

high differential function. Imaging after 24 hours will give the true relative

function.

5.4.3. Dynamic renal radionuclide studies

This procedure is also called renography for convenience, although

modern gamma camera studies include much more than simply recording

time–activity curves from the various regions of the kidneys.

5.4.3.1. Principle

The uptake by the kidneys of a tracer substance, its transit through the

nephrons and its excretion into the pelvis and then through the urethers into

the bladder are evaluated. The tracer should be non-reabsorbable and can be

filtered by the glomeruli, excreted by the renal tubules or a combination of

both. The amount filtered depends on the degree of protein binding of the

agent in the plasma. The amount secreted depends on the affinity of the

transport sites in the proximal tubules for the agent.

5.4. NEPHROLOGY AND UROLOGY

233

Changes of kidney activity with time are recorded and time–activity

curves from the kidney regions are created (renograms). On the basis of

renographic curves, descriptive indices or measurements related to renal

physiology may be obtained (e.g. uptake function, transit time and outflow

efficiency).

5.4.3.2. Clinical indications

Renography can be used for any of the following purposes:

(a) Measurement of the contribution of each kidney to global renal function.

(b) Evaluation of obstructive nephropathy and obstructing uropathy (for

definitions see Section 5.4.5).

hypertension.

(d) Evaluation of renal transplantation.

(e) Use prior to indirect radionuclide cystography (IRC).

(f) Investigation of lumbar pain.

(g) Investigation of acute or chronic renal failure.

(h) Investigation of renal disorder in patients who are allergic to contrast

media.

(i) Renal trauma.

5.4.3.3. Radiopharmaceuticals

(a) Technetium-99m DTPA

This agent may be used as a marker of the GFR after injection into the

plasma as it shows almost no protein binding and blood clearance takes place

only by filtration. Technetium-99m DTPA is no longer the agent of choice for

renal radionuclide studies except when GFR measurements are required,

although it is low cost and readily available. It should be prepared according to

the manufacturer’s instructions.

(b) Technetium-99m MAG3

This is currently the radiopharmaceutical of choice for radionuclide

renography. It is strongly protein bound and less than 2% of it is filtered by the

glomeruli. It is tubularly excreted with about 65% of the efficiency of

123

ortho-iodohippurate (

123

I-OIH (Hippuran)). It should be prepared according

to the manufacturer’s recommendations. Some preparations have lipophilic

CHAPTER 5. GUIDELINES FOR GENERAL IMAGING

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contaminants that are taken up and excreted by the liver, which increase with

temperature and exposure to light after preparation. Thus, liver uptake is not

dependent on renal function but on the impurities contained. These can be

minimized by dividing the preparation after the boiling and cooling step into

between two to five syringes, which are capped and kept in the refrigerator at

4°C for use as required.

This is an effective renal pharmaceutical which is rarely used now because

of expense and reduced availability. It is actively excreted by the tubules and

weakly protein bound with approximately 6% glomerular filtration.

(d) Iodine-131 OIH

This is no longer recommended for renal radionuclide studies, since

131

I is

both a beta emitter and a gamma emitter with an energy unsuitable for gamma

camera imaging. It requires a medium energy collimator and gives a high

radiation dose to the kidneys in the case of obstruction.

(e) Technetium-99m EC

Technetium-99m ethylene di-cysteine (EC) is tubularly secreted to a

greater extent than

99m

Tc-MAG3 and does not require a boiling step. It is less

strongly protein bound than

99m

Tc-MAG3. It is also recommended as an agent

of choice but is less easily available commercially.

5.4.3.4. Equipment

A large FOV gamma camera is required so that the left ventricle of the

heart, the kidneys, the pelvis and the proximal ureters are in the FOV. A low

energy, parallel hole collimator with high resolution is preferred for the most

widely used

99m

Tc agents. The data are transferred to a computer on-line in a

128 × 128 or 64 × 64 matrix. Electronic zoom should be used for small children.

5.4.3.5. Procedure

The procedure should be explained to the patient or parents before

entering the gamma camera room. An anaesthetic cream can be applied to

relieve discomfort of the venipuncture. The patient should be hydrated before

the study. Normally, 500 mL of water is given to the patient half an hour before

5.4. NEPHROLOGY AND UROLOGY

235

the procedure so that the patient is hydrated or slightly overhydrated.

Parenteral hydration can also be used. The bladder should be emptied before

entering the camera room and the time should be noted. In infants unable to

void on demand, bladder emptying will be spontaneous so catheterization is

not usually needed.

The patient should void again at the end of the test, and the volume and

time noted to give a measure of the urine flow. Diuresis should ideally be in the

range of 1–3 mL min

–1

The patient should lie in the supine position on the couch with a camera

positioned below or preferably reclining against the camera face, which is set

15° off the vertical so that the kidneys drop back. This is the most comfortable

position and allows free gravitational drainage of the pelvis and easy

observation of any tendency for the kidneys to descend. In children, the study

is performed more easily if the patient is lying in the supine position on the

couch. Velcro straps, sandbags or an inflatable cushion can be used to reduce

movements. The bladder should be in the FOV whenever possible, particularly

in the case of children. An image of the pelvis and bladder before and after

micturition and/or after five minutes in the upright position to ensure gravita

tional drainage is recommended in the event of pelvic retention at the end of

the study.

The injection consists of 200 MBq (5 mCi)

99m

Tc-DTPA, 100 MBq

(2.5

mCi)

99m

Tc-MAG3, 100 MBq (2.5 mCi)

99m

Tc-EC or 80 MBq (2 mCi)

123

I-

Hippuran. It should be given as a bolus. For children, the adult dose is scaled

down on a surface area basis, with a minimum of 20 MBq (0.5 mCi) for

99m

Tc-

DTPA and 15 MBq (0.4 mCi) for

99m

Tc-MAG3.

The arm should be abducted and a deep antecubical vein chosen for

puncture. The injection should be less than 1 mL in volume and either given

rapidly or pushed by a bolus of saline through a three way stopcock. The

injection should be given in one single continuous movement of the syringe

plunger.

Acquisition should last for a minimum of 30 min.

A flow study is not generally useful unless vascular problems are

suspected. If it is performed, one frame per 2 s for the first 60 s is suggested.

The rest of the study should be recorded at one frame per 10 s.

The use of frame times greater than 15 s reduces the temporal resolution

of the study so that the sharpness of the peak of the renogram and the quality

of the analysis can be impaired.

At completion, the study should be reviewed in cine-mode and

background corrected time–activity curves generated from kidney ROIs.

CHAPTER 5. GUIDELINES FOR GENERAL IMAGING

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5.4.3.6. Interpretation

A holistic approach to interpretation should be made combining images,

renograms, numerical results and interventions (see below).

A report should contain the demographic data, the name of the test, type

and activity of the injected radiopharmaceutical, any interventions and any

patient reactions (e.g. fainting). It should also include a description of the

images and curves, the numerical data, a separate conclusion and a separate

recommendation or clinical advice when appropriate.

A description of the images should consider relative renal size, cortical or

parenchymal defects and retention of activity in the parenchyma or pelvis.

Unusual anatomy features such as an ectopic, duplex or horseshoe kidney

should be recorded.

Normal renogram curves are symmetric in shape and height, and three

phases can be identified: an uptake phase with rapid upslope, a parenchymal

transit phase with less pronounced upslope ending in a peak of maximum

activity, and an excretion phase.

The background subtracted renograms should be described in terms of:

—The characteristics of the uptake and parenchymal phases;

—The presence and sharpness of the peaks;

—Whether the peaks occur at the same time (time to maximum activity);

—The shape of the third phases, or the continuing rise of the curve with no

excretion phase.

The relative function considering the normal range of 43–57% for each

kidney should be noted. If there is a duplex kidney, the relative function of the

upper and lower portions should also be given. The report should also note the

peak time and the difference in peak time.

There are various measurements that can be made from the time–activity

curve to characterize its shape, typically ratios of one point on the second phase

or peak activity time and one point on the third phase. These may be helpful in

straightforward cases but give disappointing results when renal function is poor

or in more complex cases.

Besides relative function, there are other physiological measurements

that can be done. Firstly, there are the times for the tracer to reach the

nephrons, cortex and pelvis. These are measured as transit time indices, for

example whole kidney transit time, mean parenchymal transit time (MPTT),

pelvic transit time, parenchymal transit time index (PTTI) and minimum transit

time. A whole kidney transit time index (WKTTI), which is the combination of

PTTI and pelvic transit time, may also be stated. Secondly, there is outflow

5.4. NEPHROLOGY AND UROLOGY

237

efficiency, which compares the cumulative output and input of the kidneys. The

value is given as a percentage for a specified time, usually 30 min, and has the

merit of being independent of the level of renal function.

Excretory indices (time to half-peak of the third phase and the ratio of

peak time to time of injection (T) plus 20 min) take no account of the level of

renal function, and NORA (the ratio of the 2 min value to the 20 min value)

should be used with caution. The following are normal values:

Peak time: 2.5–5 min depending on hydration

Whole kidney transit time: 2.5–5 min

MPTT: <240 s

PTTI: <156 s

Pelvic transit time: 20–75 s

WKTTI: <170 s.

Outflow efficiency is calculated as the percentage of the activity entering

the kidney that is discharged in 30 min. The normal value is above 78%. It is

independent of the level of renal function but is affected when MPTT is very

prolonged.

5.4.4. Interventions — renovascular disorder

5.4.4.1. Principle

Renovascular hypertension (RVH) is the name given to hypertension

caused by renovascular disorders. Correction of this disorder in one kidney

leads to a normalization of blood pressure, provided the other kidney is

functioning normally. This can be determined by a renal radionuclide study.

Renovascular disorders may be symmetrical when caused by systemic

pathology such as glomerulonephritis, diabetes, autoimmune diseases and

accelerated hypertension. It may be asymmetrical when caused by small vessel

disease such as in pyelonephritis, tuberculosis, endarteritis, amyloid or renal

vein thrombosis and large vessel disease, for example unilateral or bilateral

renal artery stenosis or fibromuscular hyperplasia, or in association with a

resistance to outflow. The features of renovascular disorder are a reduced

relative function, an impaired second phase of the renogram, a delayed peak of

over 60 s compared with the contralateral kidney and a prolonged mean

parenchymal transit time of over 240 s. These abnormalities may be revealed or

enhanced by the use of Captopril.

CHAPTER 5. GUIDELINES FOR GENERAL IMAGING

238

5.4.4.2. Captopril intervention

Captopril is an angiotensin II converting enzyme (ACE) inhibitor that

can be used as a stressor to the kidneys, exaggerating or producing renal

dysfunction in the case of renovascular disease but not in essential

hypertension.

Essential hypertension is associated with increased vasoconstriction of

the afferent arterioles of cortical nephrons, which is partly under angiotensin II

control. Captopril inhibits this vasoconstriction and increases the blood flow in

essential hypertension, thereby improving the uptake function, reducing peak

time, restoring a normal MPTT and improving the shape of the renogram.

Renovascular disorders are made worse with Captopril. There is no action

on the afferent arterioles, which are maximally dilated through autoregulation

in response to the renovascular disorder. It has a major effect on circulating

Angiotensin II, inhibiting its vasoconstrictor action on the efferent arterioles of

primarily juxtamedullary nephrons, which are thickly muscled, whereas those

of the cortical nephrons have almost no muscular layer in humans. Captopril of

25 mg strength given orally is appropriate. Blood pressure is monitored before

and at 5 min intervals after the oral administration of Captopril. If the diastolic

pressure falls by 10 mmHg or more during the subsequent hour, this is an

indication that Captopril has been absorbed and the test may be started. If this

is not the case, the test is started after one hour. It is sometimes recommended

that the patient fasts for at least four hours before the Captopril test, during

which time a normal amount of fluid is given to assure hydration. Infusion of

saline during the study is not necessary unless it is known or suspected that the

patient is salt depleted, in which case a severe hypotensive response may be

observed. Intravenous Enalapril (2.5 mg) can also be used.

5.4.4.3. Patient preparation

The patient should be taken off ACE inhibitors for at least seven days,

and angiotensin II inhibitors and diuretics for at least two days, in order to

reduce the likelihood of salt depletion. Other hypotensive therapy needs no

interruption.

5.4.4.4. Interpretation

The images may show parenchymal retention of activity at the side of the

renovascular disorder, persisting longer after use of Captopril compared with a

baseline study because the absence of filtration fluid precludes washout of the

tubulary secreted agents. With DTPA, however, since it is filtrated by the

5.4. NEPHROLOGY AND UROLOGY

239

glomerulus, disappearance of the affected kidney or a significant decrease in

uptake may be noted. Numerical indices such as the corticopelvic transfer time

(measuring the time of first appearance of activity in the kidneys and the first

appearance of activity in the pelvis) may be recorded and compared between

baseline and Captopril values.

The time–activity curve should deteriorate in shape in comparison with

the baseline; in particular there should be impairment of the second phase,

further prolongation of the peak time and deterioration or absence of the third

phase. The relative function should usually fall by 5%, although some authors

require a 10% fall for a positive diagnosis of RVH.

MPTT should increase to over 240 s, or 60 s more than the baseline value.

If unilateral renovascular disorder is suspected, the contralateral kidney should

show a normal renogram and indices.

5.4.4.5. Clinical indications

Renovascular disorder may be suspected in the following situations:

(a) Hypertension that becomes more difficult to control or resistant to

medical therapy;

(b) Hypertension occurring before the age of 35;

(d) Accelerated hypertension;

(e) Deteriorating renal function of no obvious cause;

(f) Evidence of vascular disease in other organs;

(g) Renal artery narrowing shown incidentally by angiography done for

another reason;

(h) Abdominal bruit.

It should be recognized that renal artery stenosis, common in the elderly

as a result of atheroma, might co-exist with essential hypertension, which is also

very common in this population. This does not mean that renal artery

narrowing, as seen on renal artery angiography, is the cause of renovascular

disorder or hypertension. Only renal radionuclide studies can distinguish

whether narrowing of a renal artery is functionally significant.

A baseline study may be conducted in patients on regular ACE inhibitor

medication, but if it is abnormal a true baseline study should be performed

once the patient has been taken off ACE inhibitors for one week. An

improvement in the result would indicate that ACE inhibitors are having a

detrimental effect on kidney function, pointing to the presence of renovascular