Nuclear Medicine Resources Manual

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CHAPTER 5. GUIDELINES FOR GENERAL IMAGING

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5.6.1.5. Preparation

(a) Patient preparation

No special patient preparation is required.

(b) Information pertinent to performing the procedure

The following information should be collected:

—Relevant history and results of physical examination;

—Results of other relevant imaging studies;

—Results of liver function tests;

—For splenic imaging, the results of a complete blood count with platelet

count;

—For hepatic perfusion studies, the position of the hepatic artery catheter.

When RBCs are labelled, it is essential to adhere to a strict procedure

designed to maintain sterility and prevent the administration of one patient’s

labelled RBCs to other patients. Appropriate procedures and quality assurance

for the correct identification of patients and the handling of blood products are

imperative.

5.6.1.6. Procedures

(a) Image acquisition

(1) Liver–spleen imaging

Imaging is begun 10–15 min or longer after the intravenous adminis-

tration of

99m

Tc-colloid. Anterior, posterior, right lateral, right anterior oblique

and right posterior oblique images of the liver are commonly obtained. Left

posterior oblique and left lateral views are added to evaluate the spleen.

For small FOV gamma cameras and standard amounts of administered

activity, images are usually collected for 300

000–500 000 counts. For large FOV

gamma cameras, an anterior image is usually acquired for 500

000–1 000 000

counts. Subsequent images are then obtained for the same length of time as for

the anterior image. SPECT imaging may be helpful, particularly if focal disease

is suspected or if organ volume determinations are needed.

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Views taken with the patient holding their breath may sometimes help

clarify ambiguous findings by eliminating image degradation due to respiratory

motion. A size marker and a costal margin marker are needed for measuring

liver and spleen size and for identifying anatomical landmarks.

(2) Hepatic blood pool imaging

A rapid sequence of images (1 frame per 2–3 s for 60 s) immediately

following injection may reveal useful information about regional variations in

blood flow. Such dynamic studies should be performed in the view that is most

likely to show the lesion. This view should be selected on the basis of the

location of the lesion of interest, which has usually been documented in a

previous imaging study (i.e. CT, ultrasound or MRI). Immediate blood pool

images should be obtained in the view most likely to show the lesion, as well as

in anterior, posterior and right lateral views. These views are generally acquired

for 1 000 000–2 000 000 counts each.

Delayed (45–180 min post-injection) blood pool images are obtained in

the anterior, posterior and right lateral views for 1

000 000–2 000 000 counts

each. When the lesion is small (less than 2–3 cm), or if there are multiple

lesions, SPECT imaging is preferred. If a high quality delayed SPECT study is

obtained, planar images are then optional. SPECT facilitates comparison with

CT and MRI, and permits calculation of liver–spleen absolute volumes.

A hepatic perfusion index, comparing the hepatic artery and portal

counts to total blood flow, may also be obtained from the dynamic flow study

and the corresponding hepatic time–activity curve. This index can aid in the

characterization of focal lesions.

(3) Hepatic perfusion imaging

The radiopharmaceutical

99m

Tc-MAA should be infused very slowly at a

measured rate through the hepatic catheter to demonstrate the tissue perfused

by the catheter. Imaging is performed immediately after the infusion of the

agent. Anterior, posterior and right lateral images of the liver containing

500

000–1 000 000 counts are typically acquired. Images of the lung are

required to identify intrahepatic arteriovenous fistulas.

(4) Splenic imaging

Imaging may commence 30–120 min after the injection of the heat

damaged labelled RBCs. Anterior, posterior and posterior oblique images of

the expected location of the spleen should be acquired for 300

000–750 000

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counts. If ectopic splenic tissue is a concern, the entire abdomen should be

imaged. If the patient has had prior trauma that may have resulted in a

diaphragmatic rupture, the chest should also be imaged. SPECT imaging

facilitates comparison with CT and MRI.

(b) Interpretation

(1) Liver–spleen imaging

Most focal lesions in the liver will have less activity than the normal

tissue. Focal nodular hyperplasia may have activity equal to, or greater than,

the surrounding liver in about 50% of patients. Normal activity or increased

activity found in a lesion is very specific to focal nodular hyperplasia. Visuali

zation of the caudate lobe only (with splenic enlargement) is typical of the

Budd–Chiari syndrome due to hepatic vein thrombosis.

A relative radiocolloid ‘shift’ (increased radionuclide deposition in the

spleen and bone marrow relative to the liver) may occur in liver cirrhosis but

also in any diffuse form of hepatic dysfunction, portal hypertension, hyper

splenism and marrow-active anaemia as a response to chemotherapy, as well as

in some patients with malignant melanoma. In patients with diffuse

parenchymal disease, serial studies can document the progression and severity

of the disease.

(2) Hepatic blood pool imaging

The finding of markedly increased blood pool activity within a liver lesion

is pathognomonic of a cavernous hemangioma. Hemangiomas typically have

reduced or normal initial blood flow with increased activity on delayed images.

Other tumours of the liver (e.g. angiosarcomas) have rarely been reported to

have an increased blood pool on delayed images; however, they can usually be

distinguished from cavernous hemangiomas by an increased blood flow in

dynamic studies.

Cavernous hemangiomas that are 3 cm or greater in size almost always

demonstrate a markedly increased blood pool even on planar images. The

sensitivity for detection of lesions smaller than 3 cm is improved by the use of

SPECT imaging. SPECT imaging is also helpful when there are multiple lesions

in the liver, and facilitates comparison with CT and MRI. A hepatoma usually

shows increased early perfusion followed by a defect, whereas abscesses and

cystic lesions are hypoactive in all phases of the study.

5.6. LIVER AND GASTROINTESTINAL SYSTEM

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(3) Hepatic perfusion imaging

The images should be assessed for the presence of extrahepatic accumu-

lation of activity (e.g. in the stomach and pancreas). Some activity in the lungs

may be seen with a properly positioned catheter due to arteriovenous fistulas in

the liver resulting in trapping of the radiolabelled MAA in the pulmonary

circulation. The presence of extrahepatic subdiaphragmatic activity indicates

that the catheter is not optimally positioned.

(4) Splenic imaging

Functional splenic tissue is preferentially visualized when heat damaged

blood cells are used. Hepatic activity is present but usually with less intensity

than splenic tissue.

(1) Liver–spleen imaging

The size and shape of the liver and spleen, and the relative amount of

activity in the liver, spleen and bone marrow, should be noted. Focal lesions

should be described. It is not always necessary to include absolute measure

ments of liver and spleen size, although volume measurements are feasible with

SPECT and appropriate computer software.

(2) Hepatic blood pool imaging

Lesion location, approximate size and uptake characteristics should be

described. The report should include the results of other imaging studies where

available. When multiple lesions have been noted in other imaging studies, the

presence or absence of an increased blood pool should be reported on a lesion-

by-lesion basis when possible.

(3) Hepatic perfusion imaging

The approximate rate (mL/min) of the injection of the radiopharmaceu-

tical should be included in the report. The presence of any extrahepatic activity

should be noted.

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(4) Splenic imaging

The time between injection and imaging should be reported as well as the

number, approximate size and location of any focal areas of uptake.

BIBLIOGRAPHY TO SECTION 5.6.1

BEKERMAN, C., GOTTSCHALK, A., Diagnostic significance of the relative uptake

of liver compared with spleen in Tc-99m sulfur colloid scintiphotography, J. Nucl. Med.

12 (1971) 237–240.

MOINUDDIN, M., et al., Scintigraphic diagnosis of hepatic hemangioma: Its role in the

management of hepatic mass lesions, Am. J. Roentgenol. 145 (1985) 223–228.

ROYAL, H.D., et al., Procedure guideline for hepatic and splenic imaging 2.0, Society

of nuclear medicine, J. Nucl. Med. 39 (1998) 1114–1116.

5.6.2. Hepatobiliary scintigraphy

5.6.2.1. Principle

Hepatobiliary scintigraphy is a diagnostic imaging study that evaluates

hepatocellular function and patency of the biliary system by tracing the

production and flow of bile from the liver through the biliary system into the

small intestine. Sequential images of the liver, biliary tree and intestinal tract

are obtained. Computer acquisition and analysis as well as pharmacological

interventions are frequently employed.

5.6.2.2. Clinical indications

(a) Functional assessment of the hepatobiliary system.

(b) Evaluation of integrity of the hepatobiliary tree.

These two categories include investigation of:

—Suspected acute cholecystitis;

—Suspected chronic biliary tract disorders;

—Common bile duct obstruction;

—Bile extravasation;

—Atresia of the biliary tree (differential diagnosis in neonatal jaundice);

5.6. LIVER AND GASTROINTESTINAL SYSTEM

275

—Patency of bilio-enteric surgical anastomosis;

—Enterogastric reflux.

5.6.2.3. Radiopharmaceuticals

Technetium-99m labelled disofenin (2,6-diisopropylacetanilido imino-

diacetic acid (DISIDA)) or mebrofenin (bromo-2,4,6-trimethylacetanilido

iminodiacetic acid (BRIDA)) is administered intravenously in activities of 50–

200

MBq (1.5–5 mCi) for adults; higher doses may be required in hyperbili-

rubinaemia with activities of 100–370 MBq (3–10 mCi). Mebrofenin may be

selected instead of disofenin in moderate to severe hyperbilirubinaemia due to

its higher hepatic extraction. For infants and children, the administered activity

is 2–7 MBq/kg (0.05–0.2 mCi/kg), with a minimum of 15–20 MBq (0.3–0.5

mCi).

5.6.2.4. Equipment

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

high resolution collimator is generally used. For a smaller FOV gamma camera,

a diverging collimator may be needed. Whenever possible, continuous

computer acquisition should be performed (1 frame/min for 30–60 min).

5.6.2.5. Patient preparation

To permit gall bladder visualization, the patient must have fasted for a

minimum of two and preferably four hours prior to administration of the

radiopharmaceutical. If the patient has fasted for longer than 24 hours or is on

total parenteral nutrition, a false positive study for cholecystitis may occur. In

those cases, especially with parenteral nutrition, the patient may be pre-treated

with sincalide (Section 5.5.2.7).

(a) Information pertinent to performing the procedure

The physician should review all the pertinent clinical, laboratory and

radiographic information available prior to the study for the patient.

Additional information specifically related to hepatobiliary scintigraphy

includes:

—History of previous surgeries, especially biliary and gastrointestinal

surgery;

—Time of most recent meal;

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—Current medications, including the time of their most recent adminis-

tration (with particular attention to opioid compounds);

—Results for bilirubin and liver enzyme levels;

—Results of ultrasound investigations.

(b) Precautions

The test should be performed under the optimal state of fasting to avoid a

false positive result. Interference by opioids can be minimized by delaying the

study for four hours after the last dose.

The protocol should be adjusted to the clinical situation, but normally

imaging should commence at injection and continue serially for 60 min or until

activity is seen in both the gall bladder (which confirms the patency of the cystic

duct) and the small bowel (which confirms the patency of the common bile

duct). Additional views (e.g. right lateral, left or right anterior oblique) may be

obtained as needed to clarify the anatomy. The digital data can be reformatted

to 5–15 min images for display and hard copying. Cinematic display of the data

may reveal additional information not readily apparent on the film.

When acute cholecystitis is suspected and the gall bladder is not seen

within 40–60 min, 3–4 hour delayed images should be obtained, or morphine

augmentation may be employed in lieu of delayed imaging. Delayed imaging at

18–24 hours may be necessary in some cases (e.g. patients who are seriously ill

and those with suspected common bile duct obstruction or suspected biliary

atresia). If the patient is being studied for a biliary leak, imaging delayed by 3–

4 hours and patient positioning manoeuvers (e.g. decubitus views) may be

helpful.

5.6.2.6. Interventions

A variety of pharmacological or physiological interventions may enhance

the diagnostic value of the examination. Appropriate precautions should be

taken to promptly detect and treat any adverse reactions caused by these

manoeuvres.

(a) Sincalide pretreatment

Sincalide, a synthetic C-terminal octapeptide of cholecystokinin (CCK), in

doses of 0.01–0.02

g/kg, may be given intravenously 30–60 min prior to the

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hepatobiliary tracer injection to minimize the potential for a false positive study

in acute cholecystitis. This may occur in patients who have fasted longer than 24

hours, are on parenteral hyperalimentation or have a severe intercurrent illness.

Sincalide should be administered slowly (over 3–5 min) to prevent biliary spasm

and abdominal cramps. An even slower infusion may also be used.

(b) Morphine sulphate

When acute cholecystitis is suspected and the gall bladder is not seen by

40–60 min, morphine sulphate, 0.04–0.1 mg/kg, may be administered intrave

nously over 2–3 min. If the cystic duct is patent, the flow of bile into the gall

bladder will be facilitated by morphine induced temporary spasm of the

sphincter of Oddi. The intrahepatic biliary tree and common bile duct (CBD)

must contain radioactive bile, and tracer activity should be present in the small

bowel at the time of morphine injection. A second injection of radiopharma

ceutical (a booster dose of approximately 1 mCi) may be necessary prior to

morphine injection if the remaining liver and/or biliary tree activity appears

insufficient to permit gall bladder visualization. Imaging is usually continued

for another 30 min following morphine administration but may be extended if

desired. Contraindications to the use of morphine include respiratory

depression in non-ventilated patients (absolute), morphine allergy (absolute)

and acute pancreatitis (relative).

Gall bladder contractility may be evaluated by determining the gall

bladder ejection fraction (GBEF) response to sincalide. The study involves a

min intravenous injection or a 15–45 min infusion of 0.01–0.04 mg/kg sincalide

after the gall bladder has been maximally filled with radiopharmaceutical

(usually 60 min after the injection) and there is minimal remnant activity in the

liver. Computer acquisition (1–2 frames/min) then continues for 20 to 30 min.

Numerous protocols can be employed, but when performing and interpreting

this procedure, the physician must adhere to a specific technique (i.e. dosage

and duration of infusion) and normal values must be validated, preferably at

the local institution.

(d) Fatty meal stimulation

Measurement of gall bladder ejection fraction using a fatty meal

challenge instead of sincalide has also been described. If visual assessment of

gall bladder emptying is adequate, a fatty snack may be used.

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(e) Phenobarbital

In jaundiced infants in whom biliary atresia is suspected, pretreatment

with phenobarbital, 5 mg/(kg

· day), may be given orally in two divided doses

daily for a minimum of 3–5 days prior to the hepatobiliary imaging study, to

enhance the biliary excretion of the radiotracer and increase the specificity of

the test. Mebrofenin may be preferred to Disofenin in suspected biliary atresia.

5.6.2.7. Processing

(a) Gall bladder ejection fraction

Using the immediate pre-sincalide and the post-sincalide data, ROIs are

drawn around the gall bladder (taking into account patient motion) and

adjacent liver (background) using any standard nuclear medicine software

package. The liver background ROI is selected taking care to exclude ductal

activity. GBEF is calculated from the gall bladder time–activity curve as:

where GB stands for gall bladder.

(b) Hepatic extraction fraction (HEF)

This index of hepatocellular function can be obtained by deconvolution

analysis of curves derived from ROIs over the liver and heart.

5.6.2.8. Interpretation

(a) Normal

A normal hepatobiliary scan is characterized by immediate demon-

stration of hepatic parenchyma, followed sequentially by activity in the intra-

extrahepatic biliary ductal system, gall bladder and upper small bowel. All

these structures should be evident within one hour. Gall bladder visualization

implies a patent cystic duct and excludes acute cholecystitis with a high degree

of accuracy. Some renal excretion of the tracer may be seen, and bladder

activity should not be regarded as pathological.

GBEF (%) =

(net GB counts ) (net GB counts ) 100

(net

max min

– ¥

GB counts)

max

5.6. LIVER AND GASTROINTESTINAL SYSTEM

279

(b) Acute cholecystitis

The hallmark of acute cholecystitis (acalculous as well as calculous) is

persistent gall bladder non-visualization 30 min post-morphine or on the 3–4 hour

delayed image. A pericholecystic hepatic band of increased activity (the rim

sign) is often associated with severe phlegmonous and/or gangrenous acute

cholecystitis, and constitutes a surgical emergency.

Chronic cholecystitis and clinical settings associated with physiological

failure of the gall bladder to fill with radiotracer (e.g. after prolonged fasting

for more than 24–48 hours, or in severely ill or post-operative hospitalized

patients) may result in gall bladder non-visualization within the first hour, but

may be distinguished from acute cholecystitis using low dose intravenous

morphine (see above) or delayed imaging. In chronic cholecystitis, the gall

bladder will usually be seen within 30 min of morphine administration or on 3–

4 hour delayed images, while true cystic duct obstruction (acute cholecystitis)

will result in persistent gall bladder non-visualization. Visualization of the gall

bladder after activity in the bowel has been observed has a significant

correlation with chronic cholecystitis. Further evaluation with ejection fraction

determination may be useful. Severely ill patients and those on total parenteral

nutrition will have a high incidence of gall bladder non-visualization even after

morphine despite a patent cystic duct, and a larger dose of morphine (0.1 mg/

kg) may be necessary to reduce the false positive rate of the study.

(d) Reduced gall bladder ejection fraction

Reduced gall bladder ejection fraction in response to sincalide may be

indicative of chronic cholecystitis, gall bladder dyskinesia or the cystic duct

syndrome.

(e) Common bile duct obstruction

Delayed biliary-to-bowel transit beyond 60 min raises the suspicion of

partial CBD obstruction, although it may constitute a normal variant found in

up to 20% of individuals. Conversely, activity in the small bowel observed

within 60 min does not exclude partial CBD obstruction. High grade CBD

obstruction should be suspected when neither the gall bladder nor the small

bowel are found within 18–24 hours after tracer injection. Severe hepatocel

lular dysfunction may appear similar but is associated with persistently high