Nuclear Medicine Resources Manual

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CHAPTER 5. GUIDELINES FOR GENERAL IMAGING

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and spurring, ‘sausage digit’, whiskering of the iliac crest, ischiopubic bone and

trochanter, and paravertebral enthesitis. Conspicuous involvement of entheses

in this syndrome sharply contrasts with the dominant involvement of the

synovium in rheumatoid arthritis. Bone scintigraphy appears to be the

diagnostic method of choice. The whole body scan can panoramically reveal

characteristic asymmetrical pauciarticular involvement of the spine and appen

dicular bones and joints. Pinhole scintigraphy often detects characteristic

enthesopathy in the pre-radiographic stage, especially in the heel and knee. In

addition, pinhole scintigraphy can show specific signs of Reiter’s syndrome,

namely the ‘knuckle bone’ sign of the sausage digit, the ‘teardrop’ sign of

paravertebral enthesopathy and the ‘whisker’ sign of periarticular hyperostosis.

(11) Reflex sympathetic dystrophy syndrome

Reflex sympathetic dystrophy syndrome (RSDS) is a rather common

condition. It is a rheumatic disorder of clinical importance and academic

interest, often related to previous trauma. The involvement is usually diffuse

but can be segmental. The pathogenesis has not yet been clarified, although the

theory of the internuncial pool is widely accepted. The identification of the

‘sympathetic vasoactive intestinal peptide-containing nerve fibres’ at the

cortical bone and the bone–periosteal junction has provided a biochemical

basis for the theory. Vasoactive intestinal peptides released from sympathetic

nerve fibres have been shown to cause hyperaemia and bone resorption, as

seen in RSDS. Three phase scintigraphy is useful, revealing increased blood

flow and blood pooling, which denotes hyperperfusion. Pinhole scintigraphy

and pinhole SPECT show mottled and band-like areas of tracer uptake in the

bone peripheries or cortical bones. Involvement of periarticular structures of

one or more joints of a limb is characteristic.

(12) Avascular necrosis of bone

Avascular necrosis of bone, or osteonecrosis, results from deprivation of

blood flow. The common causes include trauma, embolism, thrombosis,

elevated bone marrow pressure, irradiation and vasculitis. Scintigraphically,

avascular necrosis presents as a hot area on the planar image, especially in

small bones. However, when magnified using pinhole scintigraphy, a

photopenic area can be detected within the hot area. Typical examples are

avascular osteonecrosis of the femoral head and of the internal femoral condile

of the knee.

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331

(13) Osteochondroses

Contrary to the broadly accepted unitary concept of primary avascular

osteonecrosis, osteochondroses are now recognized as a group of heteroge

neous pathological entities. Common clinical features include a predilection for

actively growing bone, chronic exposure to trauma and local pain, and

tenderness.

Osteochondroses affect the capital femoral epiphysis (Legg–Calvé–

Perthes disease), the tarsal navicular bone (Koehler’s disease), the metatarsal

head (Freiberg’s disease), the medial clavicular end (Friedrich’s disease), the

secondary ossification centres of the vertebrae (Scheuermann’s disease) and

the tibial tubercle (Osgood–Schlatter’s disease). Bone scintigraphic findings

differ according to the type of underlying pathology. Large avascular

osteonecrosis produces cold areas, whereas microfractures or bone infraction

are represented by hot lesions. Scintigraphy can provide information regarding

the size, shape, location, texture and osteochondral junction pattern, frequently

leading to specific diagnosis.

(14) Traumatic and sports injuries of bone

Bone scintigraphy is the imaging procedure of choice in the diagnosis of

traumatic and sports injuries. In elderly patients, it is useful for the study of

contusion and fracture in osteoporotic ribs and spine. Bone scintigraphy is

valuable for the detection and differential diagnosis of shin splints and stress

fractures. It can be used for the classification of stress fractures, showing the

characteristic tracer uptake in the absence of radiographic alteration. Usually, a

planar whole body scan and spot images are sufficient for the diagnosis of a

fracture. Occasionally, however, magnification is needed for accurate locali

zation of the fracture, differential diagnosis between bruise and fracture, and

detection of an occult fracture. The posterior aspect of the cortical tibia is very

often affected.

(15) Periarticular rheumatism syndromes

Diseases in this category include bursitis, tenosynovitis and enthesitis.

Bone scintigraphy reinforced with pinhole magnification can portray tracer

accumulation in sites specific to the individual diseases. For example, in

Achilles tendinitis the tracer accumulates in the upper retrocalcaneal surface.

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(16) Muscular and musculotendinous rheumatism syndromes

These syndromes include myositis ossificans, rhabdomyolysis and

musculotendinous unit injuries. Bone scintigraphy is useful for the demon

stration of bone tracer accumulation in denatured or calcified muscle fibres and

musculotendinous units. Bone scintigraphy aided by pinhole magnification is

useful to delineate the individual structures affected.

(17) Metabolic diseases of bone

Metabolic bone diseases may be caused by a number of conditions,

including vitamin deficiency or excess, undernourishment, endocrine disorders,

renal failure, and disturbed calcium and phosphorus metabolisms. Clinical

entities are diverse and manifestations are complex. This presentation

describes involutional osteoporosis, osteomalacia, rickets and renal osteodys

trophy, all of which can be diagnosed by scintigraphy.

(a) Involutional osteoporosis

Involutional osteoporosis includes senile osteoporosis and post-

menopausal osteoporosis. Osteoporosis causes bone mass reduction, which

makes bones brittle and fragile. In post-menopausal osteoporosis, trabecular

bone mass is disproportionately reduced in comparison with cortical bone

mass. On the other hand, senile osteoporosis is characterized by the propor

tionate loss of cortical and trabecular bone. Frequent complications are

fracture of the spine and Colles’s fracture. Other common fracture sites are the

femoral neck, proximal humerus, tibia and pelvis. Women suffer twice as

frequently as men. The aetiology has not been established, but a generalized

decrease in metabolism may be responsible. Bone scintigraphy may show a

generalized decrease in tracer uptake. Pinhole scintigraphy reveals character

istic thinning of the cortices of the long bones or sparse end-plates of the

vertebrae. When porotic vertebral end-plates are fractured they display an

intense concentration of tracer. Compressed porotic end-plates give rise to the

‘fish vertebra’ appearance.

(b) Hyperparathyroidism

Hyperparathyroidism is either primary, secondary or tertiary and is

associated with increased parathormone production with consequent excessive

bone calcium mobilization. Scintigraphically, diffusely increased tracer uptake

can be observed in the calvarium, mandible, sternum and shoulder bones.

5.8. MUSCULOSKELETAL SYSTEM

333

Pinhole scintigraphy can portray linear tracer uptake in the subperiosteal bone

resorption in the phalangeal shafts and acrolysis of the tufts. In the calvarium,

pinhole scintigraphy shows a ‘salt and pepper’ pattern of diffusely increased

tracer uptake.

Renal osteodystrophy is caused by hyperparathyroidism secondary to

chronic renal insufficiency. The bone scintigraphic features of renal osteodys

trophy include the ‘tie sternum’ sign, ‘striped tie’ sign and costochondral

beading or ‘rosary’ sign. The so-called ‘hot patella’ sign is not specific for

metabolic bone diseases since it is also observed in chondromalacia patellae,

metastases and disuse osteoporosis or as a normal variant. Pinhole scintigraphy

is useful in the study and documentation of stimulated bone turnover, either

focally in Looser’s infraction or diffusely in the malacic skeleton. It can also be

used for the detection of subperiosteal bone resorption, cystic change and

osteosclerosis in renal osteodystrophy.

(d) Rickets and osteomalacia

Rickets and osteomalacia are characterized by deficient mineralization of

the osteoid. The basic difference between the two conditions is that the former

disease occurs in actively growing bones and the latter in mature bones. The

aetiology includes a deficiency of vitamin D and its active hormonal form (1,25-

dihydroxyvitamin D3) and a disturbed calcium–phosphorus metabolism. The

scintigraphic manifestations of rickets and osteomalacia can be divided into

systemic and local. For the study of systemic changes a whole body bone scan is

advantageous, and for the portrayal of local changes pinhole scintigraphy is

suitable. Whole body scintigraphy may show a generalized increase in tracer

uptake in the entire skeleton, producing a ‘superscan’ sign. The phenomenon

occurs more typically in the osteomalacia related to renal osteodystrophy.

Small, spotty, hot areas in cortical bones of the skeleton with a ‘superscan’

represent infractions, a pathognomonic sign of osteomalacia. Such hot spots are

mostly found in the lower rib cage, pubic bone and proximal femur, which are

easily subjected to external trauma or stress. In rickets, pinhole scintigraphy

may show very intense tracer uptake in the flared metaphyses and ossification

centres of the long bones, creating the ‘chicken bone’ sign. The joint spaces

appear spuriously widened as a result of small dystrophic ossification centres

and the bulky cartilaginous zone.

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(18) Benign and primary malignant bone tumours

Planar bone scintigraphy is less specific than radiography in the diagnosis

of primary bone tumours. The use of pinhole scintigraphy, however, is changing

that perception. With magnification, bone scintigraphy is capable of making an

accurate diagnosis of many tumours and tumorous conditions of the bone such

as bone cysts, giant cell tumours, osteochondroma, osteoid osteoma, Paget’s

bone disease, fibrous dysplasia and primary malignant bone tumours such as

osteosarcoma. It can also be used for the detection of soft tissue invasion of

osteosarcoma and bone-to-bone metastasis. Bone scintigraphy is particularly

helpful in the diagnosis of pathological fractures.

(19) Metastatic bone tumours

Evaluation of malignant bone metastases is one of the most widely

accepted indications for bone scintigraphy. It facilitates the early detection and

assessment of disseminated areas of metastasis, provides assistance about

future therapy and is useful for prognosis. Nonetheless, there are still

unanswered questions concerning the appropriate use of bone scintigraphy in

staging of the disease.

Bone scintigraphy can detect metastases weeks, and often months, before

radiography. The large majority of metastases are multiple, with only about 7%

presenting as a solitary lesion. Breast and prostatic cancers tend to spread to

the spine through the vertebral veins, while lung cancer spreads haemato

genously to random sites in the skeleton. Metastases from renal and thyroid

cancers are often photopenic. The incidence of photopenic metastasis has been

reported to be 2%. Extensive metastases to the axial skeleton may produce the

‘superscan’ sign. Approximately 5% of metastases with radiographically visible

osteolysis may not be visible on a bone scan. Certain scintigraphic features are

helpful in distinguishing metastases from benign lesions. Transaxial hot areas in

the ribs generally indicate fractures, while longitudinal hot areas are usually

metastases. A solitary hot area in the rib is malignant only in 1.4% of cases,

90% being related to a benign aetiology such as trauma or irradiation. In

contrast, 68% of solitary lesions in the axial bone are malignant. A solitary hot

area in the sternum in patients with known primary cancer indicates metastasis

if trauma is excluded. Segmental or spotty hot areas in the vertebral end-plates

and diffuse tracer uptake in the vertebral body usually indicate metastases,

while tracer uptake involving the whole length of an end-plate is characteristic

of compression fracture.

5.8. MUSCULOSKELETAL SYSTEM

335

(20) Tumorous conditions of bone

(a) Paget’s disease

Paget’s disease is relatively common in elderly Caucasians. It was

considered rare in Asians but appears to be increasing slowly. The main clinical

symptoms are local bone pain and tenderness with bone deformity but these

symptoms often represent an incidental finding. Common sites of involvement

are the skull, vertebrae, thoracic cage and long bones. Planar bone scintigraphy

characteristically shows bone growth with diffuse, intense tracer uptake.

Pinhole magnification is useful to delineate the characteristic tracer accumu

lation pattern in the cortex and peripheries of the skull, vertebrae, sacrum and

long bones. Polyostotic Paget’s disease can be mistaken for metastasis, although

both may coexist.

(b) Fibrous dysplasia

Fibrous dysplasia is an uncommon hamartomatous disease of the bone.

Its histology is characterized by metaplastic production of benign fibrous tissue

stroma and curled spicules of woven bone formed therefrom. The involvement

may be either monostotic or polyostotic and the lesion is a frequent site of

pathological fracture. Whole body bone scintigraphy is suitable for the

detection and mapping of fibrous dysplasia. Pinhole magnification is used to

differentiate between a fibrous and an osseous focus of the disease. In general,

an osseous focus is characterized by an intense concentration of tracer

compared with the poor concentration in a fibrous focus. When fractured,

lesions accumulate tracer very intensely.

BIBLIOGRAPHY TO SECTION 5.8

BAHK, Y.W., KIM, S.H., CHUNG, S.K., KIM, J.H., Dual-head pinhole bone scinti-

graphy, J. Nucl. Med. 39 (1998) 1444–1446.

BAHK, Y.W., et al., Pinhole SPECT in normal and morbid ankles, J. Nucl. Med. 39

(1998) 130–139.

CONNOLLY, L.P., TREVES, S.T., DAVIS, R.T., ZIMMERMAN, R.E., Paediatric

applications of pinhole magnification imaging, J. Nucl. Med. 40 (1999) 1896–1901.

DAVIS, M.A., JONES, A.G., Comparison of Tc-99m labelled phosphate and

phosphonate agents for skeletal imaging, Semin. Nucl. Med. 6 (1976) 19–31.

CHAPTER 5. GUIDELINES FOR GENERAL IMAGING

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DONOHOE, K.J., et al., Procedure guideline for bone scintigraphy 1.0, J. Nucl. Med. 37

(1998) 1903–1906.

PAEDIATRIC TASK GROUP OF THE EANM MEMBERS, A radiopharmaceutical

schedule for imaging in paediatrics, Eur. J. Nucl. Med. 17 (1990) 127–129.

TREVES, S.T., et al., “Bone”, Pediatric Nuclear Medicine, 2nd edn (TREVES, S.T.,

Ed.), Springer-Verlag, Berlin (1995) 233–301.

5.9. SPECIAL PROCEDURES IN ONCOLOGY

5.9.1. Gallium-67 citrate imaging

5.9.1.1. Principle

Gallium-67 citrate was one of the earliest radionuclides used in nuclear

medicine. Over the years, with the increased use of X rays, CT and MRI in

morphological imaging as well as the advent of other specific and non-specific

radiopharmaceuticals in tumour and infection imaging, the use of

Ga-citrate

for tumour imaging has become very limited. However, it still plays an

important role in malignant lymphoma but is likely to be eclipsed in the near

future by the broad use of

F-FDG PET technology, especially following the

introduction of dual head gamma camera coincidence imaging. Other

indications for

Ga include the localization of acute infections, the evaluation

of the extent or severity of certain benign diseases such as sarcoidosis and inter

stitial pulmonary fibrosis, and monitoring the response to therapy. Gallium-67

has also been used in tuberculosis, although clinical and laboratory findings are

more cost effective in developing countries, where the incidence of tuberculosis

is higher than in industrialized countries.

Gallium-67 has a physical half-life of almost 73 hours, which allows its

delivery worldwide, limited shelf-storage and easy scheduling. These character

istics have enabled its price to fall to a reasonable level in most parts of the

world. Gallium-67 decays by emission of four gamma rays at 93, 184, 296 and

388 keV; the first three peaks being used for imaging.

5.9.1.2. Clinical indications

(a) Oncological applications

5.9. SPECIAL PROCEDURES IN ONCOLOGY

337

There are applications to the following malignant conditions:

(1) Malignant lymphomas:

— At the time of diagnosis before commencing treatment, in order to

determine whether the tumour is gallium-avid. Gallium-67 citrate imaging

can then be used to evaluate treatment response. However, it cannot be

used to accurately assess the stage of the disease.

— After two or more cycles of chemotherapy in order to determine response

and prognosis.

— At the end of treatment, to identify residual disease and characterize the

nature of any residual mass revealed by X rays or CT scans in the

mediastinum or abdomen.

— Whenever early recurrence is suspected.

(2) Lung carcinomas:

— Evaluation of mediastinal nodal enlargement (if the scan is positive bilat-

erally, mediastinoscopy could be avoided).

— Evaluation of residual disease in collapsed lungs after radiotherapy, partic-

ularly in patients who have previously undergone a lobectomy.

(3) Bone and soft tissue sarcomas:

— Evaluation of pre-operative chemotherapy response, although

201

Tl-

chloride or

F-FDG are more appropriate, as is probably

99m

Tc-sestamibi.

(b) Benign applications

There are applications to the following benign conditions:

(1) Infection localization:

— In patients with fever of unknown origin or sepsis, gallium is preferred in

the chronic phase when the WBC count is not increased. In the acute

phase, where there is an increase in the WBC count, it is preferable to use

infection localizing radiopharmaceuticals such as

111

In- or

99m

Tc-HMPAO

WBCs.

(2) Sarcoidosis:

— Evaluation of the extent of the disease at the time of initial diagnosis.

— To assess the response to treatment.

(3) Idiopathic interstitial lung disease:

— At the time of the initial diagnosis.

— To verify the presence of disease.

— To establish the severity of lymphocytic infiltration.

— To monitor the response to treatment.

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5.9.1.3. Patient preparation

The following procedure should be followed:

(a) Before injection of radiopharmaceuticals:

—A full clinical examination and the information gathered from

laboratory tests and other sources of morphological imaging are

needed. There should be a valid justification for the test.

—For patients who are receiving chemotherapy, treatment should have

been stopped for at least ten days.

— Radiotherapy should cease for a period of two to four weeks before

the

Ga injection depending on the dose of radiation given, the length

of time and the volume irradiated. Steroids should be stopped for at

least one week. Patients should not have a gadolinium enhanced MRI

for several hours before a

Ga injection;

—Patients who have received blood transfusions or had a haemolytic

crisis requiring parenteral iron therapy will have saturated transferrin

binding sites. In such cases, gallium will be mainly taken up by the bone

marrow, with less uptake in the liver and pathological sites; the

sensitivity of the test will be low.

—If the gallium scan is requested in order to localize acute infection,

111

In-WBCs are preferred if there is leucocytosis and the duration of

fever is less than two weeks.

(b) After injection of the radiopharmaceutical:

—Bowel activity presents a problem for the recognition of abnormal

abdominal areas. Bowel cleansing with a mild laxative such as

magnesia milk or a washing enema is recommended. When imaging

malignant diseases, the problem of bowel activity can be resolved by

delayed imaging up to seven days following intravenous injection.

5.9.1.4. Doses and time of imaging

(a) Dose and route of injection

The following doses should be given:

(1) For tumour imaging:

—296–370 MBq (8–10 mCi) intravenously for adult doses.

—(5–7 MBq)/(kg body weight) ((0.15–0.16 mCi)/kg), with a mini-

mum of 74 MBq (2 mCi) in paediatrics.

5.9. SPECIAL PROCEDURES IN ONCOLOGY

339

(2) To localize infection:

—185–296 MBq (5–8 mCi) intravenously for adult doses.

—(3–5 MBq)/(kg body weight) ((0.07–0.15 mCi)/kg)), with a mini-

mum of 54 MBq (1.5 mCi) in paediatrics.

(b) Time of imaging

Images should be taken at the following times:

—

For acute infections: anterior images of the ROI at 4 hours post-injection using

a large FOV gamma camera for 2 million counts with a 128

128 matrix.

—For infection localization: a planar whole body image at 24–48 hours, and

SPECT if required for the chest and/or abdomen.

—For other benign applications: a planar whole body image at 48 hours, and

SPECT if needed for the chest and/or abdomen.

—For oncological applications: a planar whole body image at 48–72 hours,

and SPECT if needed for the chest and/or abdomen. Imaging should be

delayed 7–10 days if the result is equivocal.

The study may be repeated at variable times, in accordance with

department protocol, if there is bowel activity.

5.9.1.5. Procedure and equipment

The following procedures and items of equipment are required:

(a) A medium energy, parallel hole collimator (high energy collimators are

also used).

(b) Data acquisition:

(1) Planar acquisition should either be:

—Total body scanning on a 256 ¥ 1024 matrix for at least 40 min with

anterior and posterior projections from the head to below the

knees (approximately 4 million counts in total).

—Static planar images acquired on a 128 ¥ 128 matrix for:

● 500 000 for head and neck (anterior and posterior);

● 1 000 000 for chest, abdomen, pelvis and upper thighs (anterior

and posterior);

● 500 000 for thighs and knees (anterior only, posterior if needed).

—Occasionally lateral views for the axilla of 500 000 counts are

needed.

—Arms should be raised above the head when imaging the chest.