Nuclear Medicine Resources Manual

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CHAPTER 5. GUIDELINES FOR GENERAL IMAGING

260

5.5. RESPIRATORY SYSTEM

5.5.1. Introduction

Radionuclide methods are available for the study of lung ventilation and

perfusion. The main indication for lung scintigraphy is suspected pulmonary

embolism. Other indications are for assessment of residual lung function if

surgery is planned for lung tumours, ventilation scans to assess alveolar

capillary permeability in smoke inhalation injuries and studies of mucociliary

clearance (tracheobronchial clearance).

5.5.2. Pulmonary scintigraphy

5.5.2.1. Principle

(a) Airways

The airway runs from: trachea Æ main stem bronchi Æ segmental

bronchi

Æ bronchioles Æ terminal bronchioles Æ alveolar ducts Æ alveolar

sacs

Æ alveoli.

Ventilation or inhalation studies are performed using radioactive gases

(

133

Xe,

127

Xe and

81m

Kr) or submicronic (particle size less than 2 mm) radioaer-

osols (

99m

Tc-DTPA or colloid). Technegas, a vaporized

99m

Tc-carbide from a

special device, has a particle size of less than 0.02 mm, which avoids bronchial

trapping and is suitable but still expensive. The images obtained show the

distribution of gases or radioaerosols in the lungs. Using a positive pressure,

larger aerosol particulates such as

99m

Tc human serum albumin (HSA) can be

used and tracheobronchial epithelial function can be studied.

(b) Vascular system

The lungs are divided into lobes and discrete bronchopulmonary

segments, each with its own artery, vein and bronchus. In adults, there are

approximately 280 billion pulmonary arterioles small enough to trap the 20–

mm particles used for perfusion scanning.

Perfusion lung imaging permits an evaluation of the pulmonary arterial

blood flow. Usually

99m

Tc macroaggregated albumin (MAA) is employed, with

a particle size of 10–40 mm; given intravenously, the labelled particles lodge in

the pulmonary arterioles in proportion to the regional blood flow, giving a map

of the pulmonary functional circulation.

5.5. RESPIRATORY SYSTEM

261

5.5.2.2. Clinical indications

The most common indication for lung scintigraphy is to confirm or

exclude pulmonary embolism. Thrombi, usually from the deep venous system

of the lower extremities, and globules of fat and particulate amniotic fluid can

embolize the pulmonary arteries and produce acute pulmonary hypertension.

A ventilation study, performed in conjunction with the lung perfusion images,

improves the sensitivity of the lung perfusion image up to 90%. As a general

rule, normal ventilation is found in regions of pulmonary embolization.

Clinical suspicion of pulmonary embolism should lead to immediate

heparinization (unless there is a contraindication), with a lung study conducted

at the same time or on the following day in order to confirm or exclude

pulmonary embolism. Alternatively, spiral X ray CT may be considered.

Less common indications include the evaluation of lung function pre-

operatively, alveolar capillary permeability after smoke inhalation injury,

mucociliary function and lung transplant evaluation. Lung perfusion imaging in

conjunction with ventilation imaging has added a non-invasive component to

the proper evaluation of patients with bronchitis or obstructive forms of

chronic pulmonary disease.

Bronchogenic carcinoma, the most common form of lung carcinoma,

causes a decrease or absence of pulmonary blood flow to the affected bronchial

segment. Lung perfusion images can provide a direct quantitative estimate of

the amount of perfusion remaining in the total lung field, to enable a prediction

as to whether or not the patient will become respiratorily disabled if the

portion of the lung involved in the malignant process is surgically removed.

5.5.2.3. Radiopharmaceuticals

(a) Perfusion agents: Technetium-99m labelled MAA

Most of the MAA particles are 10–40 mm in size, with a biological half-life

of 2–9 hours. Albumin microspheres, although less available, give a more

homogeneous particle size. The minimum number of particles necessary to

obtain an even distribution of radioactivity in the vascular bed is 60 000; hence

it is reasonable to use about 100 000 particles, which will transiently occlude

one in 1500 arterioles of the lung. The usual adult administered activity is 40–

150 MBq (1–4 mCi). The usual paediatric administered activity is 0.5–2.0 MBq/

kg (20–80 mCi/kg), with a minimum of 7–8 MBq (»200 mCi).

Vials should be agitated prior to withdrawing a dose since labelled MAA

particles will settle in the vial with time; the syringe should be inverted prior to

injection.

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(b) Ventilation agents: Aerosols

Technetium-99m DTPA is the preferred radiopharmaceutical.

The usual administered activity of

99m

Tc-DTPA is 900–1300 MBq (25–

mCi) in the nebulizer, from which approximately 20–40 MBq (0.5–1.0 mCi)

reach the patient’s lungs.

Aerosol imaging is usually performed before perfusion imaging because

it is more difficult to deliver a larger dose of the

99m

Tc aerosol than to deliver a

larger dose of

99m

Tc-MAA. Since both agents are labelled with

99m

Tc, it is

extremely important for the count rate of the second study to be at least four

times that of the first study.

The radioactive gases

133

Xe or

81m

Kr are unavailable in many countries so

that radioaerosols are preferred.

5.5.2.4. Equipment

The following equipment is useful for pulmonary scintigraphy studies:

(a) Large FOV gamma cameras with low energy, general purpose (LEGP)

collimators or LEHR collimators.

(b) Large FOV gamma cameras with a rotation capability, as well as a

computer with appropriate software, for SPECT imaging. An LEGP

collimator is recommended for SPECT in order to minimize acquisition

time.

5.5.2.5. Preparation and procedure

(a) Patient preparation

A chest radiograph in both the anterior–posterior position and with

lateral projections should be obtained before lung scintigraphy for pulmonary

embolism. A portable anterior–posterior chest radiograph is acceptable only if

the patient cannot tolerate a routine upright examination. In patients who have

no changes in signs or symptoms, a chest radiograph within one day of scinti

graphy is adequate. A more recent radiograph (preferably within 1 hour) is

necessary in patients with evolving clinical status.

Before intravenous administration of the pulmonary perfusion radio-

pharmaceutical, the patient should be instructed to cough and to take several

deep breaths. The patient should be in a supine position during injection or, in

the case of a patient with orthopnea, as close to the supine position as possible,

since particle distribution is affected by gravity.

5.5. RESPIRATORY SYSTEM

263

In women of childbearing age, pregnancy and lactation status should be

noted and the procedure performed in such a manner as to minimize radiation

exposure. For example, half the usual activity may be used for the perfusion

study and the ventilation study is omitted if possible.

The pertinent clinical history should include details on:

—Right-to-left shunt(s);

—Severe pulmonary hypertension;

—Chest pain;

—Dyspnea;

—Haemoptysis;

—Syncope;

—Symptoms of deep venous thrombosis;

—Oral contraceptive use;

—Recent surgery;

—Prior pulmonary embolism(s);

—Cancer;

—Congestive heart failure;

—Underlying or previous diseases;

—Smoking;

—Intravenous drug abuse;

—Long air flights.

Other factors may also be relevant; a physical examination includes vital

signs, chest cardiac examination and leg findings, among other aspects.

(b) Review of prior lung scintigraphy

Pertinent chest radiographic findings include, but are not limited to,

consolidation, atelectasis, effusions, masses, cardiomegaly and decreased

pulmonary vasculature. The chest radiograph may be normal in patients with

pulmonary embolism. Treatment with anticoagulants or thrombolytic therapy

should be noted, as should the results of tests for deep venous thrombosis, for

example compression ultrasonography.

The referring physician’s estimate of the prior probability of pulmonary

embolism may be helpful, or may be assessed from a properly completed

request form.

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Reduced numbers of MAA particles should be considered for patients

with pulmonary hypertension or right-to-left shunting, and for infants and

children. In adults, the number may be reduced to between 100 000 and 200 000

particles without significantly altering the quality of the images for detection of

perfusion defects. Inhomogeneous distribution of activity may result from a

reduction in the number of particles to below 100 000 in adults.

(d) Procedure

A chest radiograph should be obtained and reviewed before lung scinti-

graphy. When

99m

Tc labelled aerosol imaging is performed before

99m

Tc-MAA

perfusion imaging, smaller amounts (40 MBq (1.0 mCi)) of activity should be

administered to the lungs.

In aerosol ventilation imaging, the aerosol is administered through a

mouthpiece with the nose occluded and the patient performing tidal breathing.

An advantage of aerosols is that images can be obtained in multiple projections

to match those obtained for perfusion.

It is preferable to have the patient inhale the aerosol in the upright

position, although the supine position can be used if necessary. Aerosol

ventilation imaging can be performed at the bedside.

In perfusion imaging the patient is asked to cough and take several deep

breaths. Technetium-99m MAA is then injected slowly during 3–5 respiratory

cycles, with the patient in the supine position.

A well flushed indwelling line can be used if venous access is difficult. The

physician should not administer the radiotracer in the distal port of a Swan–

Ganz catheter or any indwelling line or port that contains a filter, for example a

chemotherapy line.

Imaging is preferably performed in the upright position to increase chest

cavity size and minimize diaphragmatic motion. If necessary, images can be

obtained in the supine or decubitus position.

Planar images should be obtained in multiple projections including

anterior, posterior, both posterior oblique, both anterior oblique and both

lateral projections. The anterior oblique or the lateral projections may be

omitted. In some patients only a limited number of views are possible. A

minimum of six views, each of ventilation and perfusion, are required for

reliable interpretation.

5.5. RESPIRATORY SYSTEM

265

5.5.2.6. Interpretation

(a) Criteria for prospective investigation of pulmonary embolism diagnosis

(PIOPED) and modified PIOPED

These criteria are derived for interpretation but lead to a high indeter-

minate rate because they are based on limited ventilation scan views. Interpre-

tation is improved with six perfusion and ventilation images:

(1) High probability (>80%, in the absence of conditions known to mimic

pulmonary embolism):

— At least two large mismatched segmental perfusion defects or the

arithmetic equivalent in moderate or large and moderate defects;

—Two large mismatched segmental perfusion defects, or the arithmetic

equivalent.

(2) Moderate probability (70–80%):

—One large to two moderate mismatched perfusion defects or the

arithmetic equivalent in moderate or large and moderate defects.

(3) Low probability (<20%):

—Single matched ventilation–perfusion defects with clear chest

radiograph or very extensive matched defects;

—Non-segmental perfusion defects (e.g. cardiomegaly, enlarged aorta,

enlarged hila or elevated diaphragm);

—Any perfusion defects with a substantially larger ventilation defect or

chest radiographic abnormality;

—Perfusion defects matched by ventilation abnormality provided that

there are:

● a clear chest radiograph,

● some areas of normal perfusion in the lungs;

—Any number of small perfusion defects with a normal chest

radiograph.

(4) Indeterminate probability:

—Those that cannot be categorized as low, moderate or high probability.

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(5) Normal perfusion:

— No perfusion defects or perfusion exactly outlining the shape of the

lungs seen on the chest radiograph (note that hilar and aortic

impressions may be seen and the chest radiograph–ventilation study

may be abnormal).

(b) Further interpretive considerations

Ventilation–perfusion mismatch can result from any cause of pulmonary

arterial blood flow obstruction. Although a very long list of differential

diagnoses exists for ventilation–perfusion mismatch findings, the most common

causes include only a few:

—Acute pulmonary embolism;

—Old pulmonary embolism (without reperfusion);

—Obstruction of a pulmonary vessel by a tumour;

—Previous radiation therapy to the thorax.

On perfusion scintigraphy, extrapulmonary activity (which may be seen at

the edges of lung images in the thyroid or kidneys) may be due to right-to-left

shunt, free

99m

Tc-pertechnetate or reduced technetium compounds, or a recent

nuclear medicine procedure. An image of the head can be used to differentiate

free pertechnetate or reduced technetium from a shunt.

The stripe sign (activity at the periphery of a perfusion defect) lowers the

chance of pulmonary embolism in the zone of the perfusion defect that shows

the stripe.

Perfusion images can show hot spots in the lung if clotting of blood occurs

in the syringe during injection, or if the injection is made through an indwelling

catheter that is not well flushed.

Ventilation scintigraphy is obtained at a different point in time than

perfusion scintigraphy. In the intervening time, there can be changes in

ventilation and perfusion. Similarly, ventilation scintigraphy may be obtained

in an upright position and perfusion scintigraphy injected in the supine

position. These changes in position may also affect the comparability of the two

scintigrams.

Injection of

99m

Tc-MAA through a central line can result in inadequate

mixing of activity in the pulmonary artery. This inadequate distribution of

5.6. LIVER AND GASTROINTESTINAL SYSTEM

267

activity is especially common if the activity is injected through a pulmonary

artery line.

(d) Communication

Any urgent lung scan results should be discussed with the referring

physician or her/his representative.

BIBLIOGRAPHY TO SECTION 5.5

PARKER, J.A., COLEMAN, R.E., SIEGEL, B.A., SOSTMAN, H.D., McKUSICK,

K.A., Procedure guideline for lung scintigraphy, J. Nucl. Med. 37 (1996) 1906–1910.

THE PIOPED INVESTIGATORS, Value of the ventilation/perfusion scan in acute

pulmonary embolism: Results of the prospective investigation of pulmonary embolism

diagnosis (PIOPED), J. Am. Med. Assoc. 263 (1990) 2753–2759.

WAGNER, H.N., Jr., “Regional ventilation and perfusion”, Principles of Nuclear

Medicine, 2nd edn (WAGNER, H.N., SZABO, Z., BUCHANAN, J.W., Eds), Saunders,

Philadelphia, PA (1995).

5.6. LIVER AND GASTROINTESTINAL SYSTEM

5.6.1. Liver and spleen imaging

These procedures are used less often nowadays, having largely been

replaced by ultrasound, CT and MRI. However, some techniques remain

effective for specific clinical indications.

5.6.1.1. Principle

Liver–spleen imaging is performed following the injection of a

99m

labelled colloid, which is rapidly phagocytized by the reticuloendothelial cells

of the liver, spleen and bone marrow.

Liver blood pool imaging is performed following the injection of

99m

labelled RBCs for the detection of cavernous hemangiomas of the liver.

Hepatic perfusion studies are performed following the injection of

99m

Tc-

MAA through a hepatic artery catheter to determine whether intra-arterially

administered chemotherapeutic agents are being optimally delivered.

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Splenic imaging is performed following the injection of

99m

Tc labelled

heat damaged RBCs. Damaged RBCs are selectively taken up by functioning

splenic tissue.

5.6.1.2. Clinical indications

(a) Liver–spleen imaging

These studies can be used for determining the size and shape of the liver

and spleen as well as for detecting functional abnormalities of the reticulo

endothelial cells of these organs. Specifically, these studies are occasionally

performed for:

(1) Suspected focal nodular hyperplasia of the liver. These lesions often have

normal or increased uptake on sulphur colloid imaging.

(2) Assessment of reticuloendothelial system (RES) function in patients with

suspected liver disease. The decision to perform a liver biopsy or to

continue treatment with a hepatotoxic agent may be influenced by the

severity of the liver disease that is seen on liver–spleen imaging as a

complement to blood tests.

(b) Liver blood pool imaging

This procedure is highly specific for the diagnosis of cavernous

hemangiomas of the liver. The sensitivity for detecting large lesions (more than

2–3 cm) is very high, but hemangiomas as small as 0.5 cm may be detected with

SPECT.

These studies are useful for demonstrating that hepatic artery catheters

used to infuse chemotherapeutic agents are optimally positioned to perfuse

liver tumours and to avoid drug delivery to normal extrahepatic tissues (e.g. the

stomach).

(d) Splenic imaging

These studies are used for detecting functional splenic tissue. They are

often performed:

—In children, to rule out congenital asplenia or polysplenia;

5.6. LIVER AND GASTROINTESTINAL SYSTEM

269

—In adults with recurrent thrombocytopenia previously treated by

splenectomy;

—For characterizing an incidentally noted mass as functional splenic tissue;

—For the evaluation of abdominal trauma with suspected splenic rupture;

—For viability assessment of splenic grafts.

5.6.1.3. Radiopharmaceuticals and doses

(a) Liver–spleen imaging

Technetium-99m sulphur colloid (SC) is preferred for liver–spleen

imaging because the biodistribution and biokinetics of this agent are more

reproducible than those of

99m

Tc-albumin colloid (AC). Adult doses should be

in the range of 110–220 MBq (3–6 mCi) and those in children should be

properly adjusted.

(b) Liver blood pool imaging

Technetium-99m labelled RBCs can be labelled using in vitro, in vitro and

in vivo, or in vivo methods. Methods with higher labelling efficiency (in vitro

and in vivo, or in vitro) may improve the results of imaging. Recommended

adult doses are 370–1110 MBq (10–30 mCi) according to body weight. Large

doses allow better delayed images.

Technetium-99m MAA is used, with doses in the range of 110–220 MBq

(3–6 mCi).

(d) Splenic imaging

Technetium-99m heat damaged RBCs are used.

5.6.1.4. Equipment

A large FOV gamma camera equipped with a low energy, all purpose or

high resolution collimator is usually used. For a small FOV gamma camera, a

diverging collimator may be needed.