Nuclear Medicine Resources Manual

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CHAPTER 5. GUIDELINES FOR GENERAL IMAGING

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5.3.2.9. Reporting

The report should describe the location, extent and severity of defects,

their correlation with morphological and clinical abnormalities and, when

relevant, a differential diagnosis and/or statement of the significance of the

abnormalities. The report should include the radiopharmaceutical used, the

dose injected, the delay period post-injection, the type of equipment used for

acquisition of the data, as well as any interventional medication used and any

side effects noted. The report should also state whether the eyes were open or

closed at injection, and whether the patient is right or left handed.

There should be an assessment of the technical quality of the scan (good,

adequate, poor, including presence of patient motion and deviations from the

usual protocols, if relevant). There should also be a description of abnormal

ities (including the criteria for definition of abnormal, i.e. visual inspection

criteria, ROIs and comparison with the database).

5.3.2.10. Interpretation and conclusions

The referring physician must be given an answer to the reason for the

referral of the patient when feasible. The physician should relate the findings of

the SPECT studies to the patient’s condition.

The scan is to be interpreted in the context of known clinical history,

associated co-morbid conditions, medication and other diagnostic studies (CT,

MRI and EEG). There is a limitation regarding differential diagnosis if

relevant clinical data are not available, and additional tests may be recom

mended.

BIBLIOGRAPHY TO SECTION 5.3.2

DEVOUS, M.D., Sr., “SPECT functional brain imaging”, Clinical SPECT Imaging

(KRAMER, E.L., SANGER, J., Eds), Raven Press, New York (1995) 97–128.

FAYAD, P.B., BRASS, L.M., Single photon emission computed tomography in

cerebrovascular disease, Stroke 22 (1991) 950–954.

HOLMAN, B.L., DEVOUS, M.D., Sr., Functional brain SPECT: The emergence of a

powerful clinical method, J. Nucl. Med. 33 (1992) 1888–1904.

HOLMAN, B.L., et al., The scintigraphic appearance of Alzheimer’s disease: A

prospective study using technetium-99m-HMPAO SPECT, J. Nucl. Med. 33 (1992)

181

185.

5.3. CENTRAL NERVOUS SYSTEM

211

JUNI, J.E., Taking brain SPECT seriously: Reflections on recent clinical reports in the

Journal of Nuclear Medicine, J. Nucl. Med. 35 (1994) 1891–1895.

JUNI, J.E., et al., Society of Nuclear Medicine Procedure Guideline for Brain Perfusion

Single Photon Computed Tomography (SPECT) Using Tc-99m Radiopharmaceuticals,

Society of Nuclear Medicine, Reston, VA (1999).

MAYBERG, H.S., The ethical clinical practice of functional brain imaging, J. Nucl. Med.

37 (1996) 1256–1259.

VAN HEERTUM, R.L., MILLER, S.H., MOSESSON, R.E., SPECT brain imaging in

neurologic disease, Radiol. Clin. North Am. 31 (1993) 881–907.

VAN HEERTUM, R.L., TIKOFSKY, R.S. (Eds), Cerebral brain SPECT Imaging, 2nd

edn, Raven Press, New York (1995).

5.3.3. Brain tumour imaging

5.3.3.1. Principle

Current literature on the clinical use of

201

Tl chloride or

99m

Tc-sestamibi

supports their usefulness for tumour localization in general and for intracranial

lesions in particular.

The purpose of this guideline is to assist nuclear medicine practitioners in

recommending, performing, interpreting and reporting the results of brain

201

chloride or

99m

Tc-sestamibi studies for the purpose of CNS tumour evaluation.

5.3.3.2. Clinical indications

Imaging is required for the following purposes:

(a) Differentiation of tumour recurrence from oedema, fibrosis or necrosis

post-treatment;

(b) Evaluation of tumour response to various kinds of treatment;

malignant intracranial lesions in both immunosuppressed and

non-immunosuppressed patients.

5.3.3.3. Radiopharmaceuticals

The following doses of radiopharmaceuticals should be used:

CHAPTER 5. GUIDELINES FOR GENERAL IMAGING

212

(a) Thallium-201 chloride

The dose for an adult is 111–148 MBq (3–4 mCi), or 1.5–5.0 MBq (0.04–

0.05 mCi)/kg body weight, intravenously injected, with a minimum dose of

MBq (1 mCi).

(b) Technetium-99m-sestamibi

The dose for an adult is 555–740 MBq (15–20 mCi), or 7.5–12 MBq (0.2–

0.3 mCi)/kg body weight, intravenously injected. Use of

99m

Tc-sestamibi is

encouraged in paediatric patients because of higher injected dose, less

radiation burden and better physical characteristics. In paraventricular lesions,

201

Tl chloride is preferred because of physiological choroid plexus and pituitary

uptake with

99m

Tc-sestamibi.

5.3.3.4. Protocols

The following protocols should be made:

(a) Patient preparation

(i) No special recommendation such as fasting or stopping medications

is needed. Studies can be performed after a few days of chemo

therapy or radiotherapy but are not advisable in the immediate post-

operative period. Waiting for a few weeks is advisable in the post-

operative period. In AIDS patients with suspicion of intracranial

lymphoma versus toxoplasmosis, the study should be performed

before the patient has started medical treatment for toxoplasmosis.

Patients having antibiotic treatment for toxoplasmosis might give a

false positive.

(ii) Pre-injection preparation includes:

—Explaining to the patient the procedure, the time needed for it and

the need for their cooperation;

—Obtaining an informed written consent;

—If sedation is needed, giving this just before starting acquisition of

the study and minimizing the sedation period to the shortest time

possible.

5.3. CENTRAL NERVOUS SYSTEM

213

(b) Information pertinent to performing the procedure

A full clinical history, a clinical examination of the patient and the

findings of other morphological imaging modalities are essential for the proper

interpretation of a study. Previous radiation therapy, chemotherapy or surgery,

and the time period from the current study should be specifically mentioned.

Any previous studies should be made available for comparison.

5.3.3.5. Image acquisition

Attention should be paid to the following points:

(a) Waiting time after injection

Imaging can start at any time after a 15 min waiting period from

intravenous injection of either

201

Tl or

99m

Tc-sestamibi.

In the case of differentiation of post-operative changes, oedema or

inflammation, from residual tumour or recurrence, delayed images after a

minimum of two hours from the time of injection of the radiopharmaceuticals

are essential.

(b) Acquisition parameters

The following points should be noted:

—Multiple head gamma camera systems are preferable for the purpose of

shortening the time of study and acquiring higher counts for better

resolution. However, single head systems can be used with high levels of

confidence.

—The patient should be positioned for maximum comfort for the whole

period of the study. Preferably the patient should void before positioning

on the table.

—The patient’s head should be lightly restrained so as to minimize motion

during acquisition. It is not possible to rigidly bind the head in place. If

the patient’s cooperation is unsatisfactory, sedation may be used

according to the previous guidelines.

—The smallest radius of rotation possible is used with appropriate patient

safeguards. The maximum radius allowed is about 14 cm.

—General purpose collimators can be used for both radiopharmaceuticals;

however, for

99m

Tc-sestamibi it is possible to use high resolution colli-

mators.

CHAPTER 5. GUIDELINES FOR GENERAL IMAGING

214

—A matrix size of 64 ¥ 64 is adequate.

—Angular sampling: 3–6º is satisfactory (60–120 projections for a 360º

rotation).

—Time per projection: 40 s for Tl and a minimum of 20 s for sestamibi.

—Zooming is necessary in order to obtain the whole brain within

approximately a 25 cm FOV. The zoom factor will vary according to

different gamma cameras.

—Step and shoot or continuous acquisition mode can be used, either with

elliptical or circular obits.

5.3.3.6. Data processing

Filter all studies in three dimensions (x, y and z). This can be achieved

either by two dimensionally prefiltering the projection data or by applying a

3-D post-filter to the reconstructed data.

Low pass (e.g. Butterworth) filters should generally be used. Resolution

recovery or spatially varying filters should be used with caution, as they

may produce artefacts. It is highly recommended to reconstruct the whole

brain. Iterative reconstruction methods, available in modern systems, are

preferred.

Reconstruct data at one pixel resolution. If slices are to be summed,

this should be done after reconstruction and oblique orientation (if

performed).

Attenuation correction is encouraged especially in paraventricular

lesions and in the presence of low-grade lesion uptake.

Each institution should develop its own technique for calculating the

lesion-to-background ratio.

5.3.3.7. Image interpretation

Interpretation should be performed in conjunction with X ray CT, MRI,

full history and clinical data.

There is a higher confidence in the interpretation of CT and MRI images

of solid lesions than in those of necrotic lesions. The same is true for large

lesions.

Paraventricular small lesions (especially with

99m

Tc-sestamibi) must be

interpreted with caution, as well as lesions close to the calvarium, the petrous

bone, the temporal bone, the cribriform plate in the base of the anterior cranial

fossa and near the orbits.

Benign lesions such as tuberculosis, histiocytosis, sarcoidosis and brain

abscesses may produce high intensity uptakes. It is not the purpose of such

5.3. CENTRAL NERVOUS SYSTEM

215

studies to avoid biopsy of intracranial lesions. Low grade gliomas can show no

uptake of either radiopharmaceutical and be the cause of false negatives.

In post-operative studies, interpretation can be improved by taking into

consideration the site, extent, intensity and location of the abnormal uptake,

and also by comparing the early (if available) and delayed images.

A negative study following recent treatment does not indicate that a

disease has been cured. It only indicates a good response and does not exclude

microscopic residual disease.

If the studies are performed for the purpose of differentiation of intra-

cranial toxoplasmosis from lymphoma in the immunosuppressed patient,

recent treatment for toxoplasmosis might produce a false positive uptake.

5.3.3.8. Reporting

The report should include the radiopharmaceutical used, dose, route of

injection, waiting period, clinical history and the reason for referring the

patient for the study. If sedation has been given it should be mentioned, as well

as any adverse reactions.

The report should include and mention the findings of other morpho-

logical imaging modalities and their correlation with the nuclear medicine

procedure.

The intensity of uptake should be graded as low, medium or high,

together with the size of the lesion as accurately as possible, and its location. A

tumour-to-background ratio calculation might be useful.

Comparison with previous studies, if they have been done, is very

important.

BIBLIOGRAPHY TO SECTION 5.3.3

ABDEL-DAYEM, H.M., et al., “Role of thallium-201 chloride and Tc-99m sestamibi in

tumour imaging”, Nuclear Medicine Annual 1994 (FREEMAN, L.M., Ed.), Raven

Press, New York (1994) 181–234.

O’CONNOR, M.K., Mayo Clinic Manual of Nuclear Medicine, Churchill–Livingstone,

New York (1996).

CHAPTER 5. GUIDELINES FOR GENERAL IMAGING

216

5.3.4. Cerebral metabolic imaging

5.3.4.1. Principle

The trinity of metabolism–function–blood-flow of the brain are closely

interrelated. An abnormality in one aspect will be reflected in the other two.

Brain function can be studied with PET and SPECT through imaging radio

labelled substrates or RCBF markers. With PET, regional cerebral perfusion

can be imaged repeatedly at short intervals using

O-water. The RCBF images

reflect neuronal activities, which are used for the localization of activated areas

of brain after specific stimulation or performance of tasks. The subtraction of

rest images from activated images enables a clearer identification of activated

regions of the brain. Activation paradigms include visual, audio and finger

motion stimulations as well as speech and thinking. Activation studies may

elucidate higher brain functions in healthy volunteers and neuropsychiatry

patients.

5.3.4.2. Clinical indications

The indications are the same as those for the cerebral perfusion studies

(Section 5.3.2).

5.3.4.3. Radiopharmaceuticals

Positron emitting radiopharmaceuticals are used for metabolic imaging.

Three aspects of cerebral metabolism are of interest clinically, namely glucose

and oxygen utilization and protein synthesis. Oxygen-15-O

F-FDG and

C-

methionine, used to study these activities, require there to be a cyclotron in

close proximity for their production. Oxygen-15-O

can be continuously

inhaled, with little dissolved in plasma and most bound to haemoglobin. It is

the bound portion of

O that is transported to, and utilized by, the brain.

Fluorine-18-FDG is transported to the brain and taken up by cells as glucose

but cannot be metabolized any further. It reflects the regional glucose

utilization of tissue. Carbon-11-methionine shows protein synthesis and is used

mainly for brain tumour imaging.

5.3.4.4. Protocols

Patient preparation and pre-test precautions are similar to those

described for perfusion. Data acquisition is performed with either dedicated

PET or other forms of positron imaging devices. The start of the acquisition

5.3. CENTRAL NERVOUS SYSTEM

217

depends on the radiopharmaceutical selected, for example by 10–20 min when

using

C compounds, 40–90 min using

F compounds and immediately using

O compounds. Because of the very short half-life of radionuclides, brain

metabolic imaging may be repeated at short intervals to facilitate assessment of

different brain states. It is important to maintain very strict protocols and stable

test conditions.

5.3.4.5. Acquisition setting

The procedure is best performed with PET dedicated systems.

Acquisition is usually accompanied by a transmission session for attenuation

correction. If a kinetics analysis is required, dynamic or fast repeated acquisi

tions are needed.

5.3.4.6. Data processing and interpretation

Cerebral metabolic images are similar to those of cerebral perfusion.

Usually the metabolic and perfusion images are similar in pattern under

normal circumstances. Metabolic images should be interpreted with the

structural data available, and co-registration techniques are of great value.

BIBLIOGRAPHY TO SECTION 5.3.4

HERSCOVITCH, P., MARKHAM, J., RAICHLE, M.E., Brain blood flow measured

with intravenous H

O: Theory and error analysis, J. Nucl. Med. 24 (1982) 782–789.

PAWLIK, G., HEISS, W.D., “Position emission tomography and neuropsychological

function”, Neuropsychological Function and Brain Imaging (BIGLER, E.D., YEO,

R.A., TURKHEIMER, E., Eds), Plenum Press, New York and London (1989) 65–138.

HERSCOVITCH, P., “Functional mapping of the human brain”, Principles of Nuclear

Medicine (WAGNER, H.N., Jr., SZABO, Z., BUCHANAU, J.W., Eds), W.B. Saunders,

Philadelphia, PA (1995) 514–531.

5.3.5. Brain receptor imaging

5.3.5.1. Principle

Neuroreceptors can be altered in a variety of clinical settings. Characteri-

zation of neuroreceptor and neurotransporter activities has a more specific

impact on the diagnosis of many neurodegenerative and neuropsychiatric

CHAPTER 5. GUIDELINES FOR GENERAL IMAGING

218

disorders than do CT or MTI studies. Most brain functions are linked to certain

neurotransmitters or receptors.

5.3.5.2. Clinical indications

Most receptor–transporter studies have been performed to evaluate

movement disorders, epilepsy and psychiatric illnesses, but clinical indications

are still investigational.

5.3.5.3. Radiopharmaceuticals

The radiotracers used in the functional imaging of the brain are listed in

Table 5.15.

TABLE 5.15. RADIOPHARMACEUTICALS FOR NEURORECEPTOR

IMAGING

PET SPECT

Dopamine receptors

C-11, 3-N-methylspiperone (NMSP) I-123, Iodobenzamide (IBZM)

F-18, Fluoroethylspiperone I-123, Iodobenzofuran (IBF)

F-18, Fluoropropylspiperone I-123, Epidepride

C-11, Raclopride I-123, Lisuride

C-11, YM-09151-2 I-123, 2-Iodospiperone

C-11, FLB457 I-123, SCH23982

Benzodiazepine receptors

C-11, Flumazenil I-123, Iomazenil (IMZ)

C-11, Suriclone

C-11, Diazepam

Opiate receptors

C-11, Carfentanil

C-11, Diprenorphine

F-18, Acetylcyclofoxy

Muscarinic acetylcholine receptors

C-11, Nicotine I-123, Iododexetimide (IDEX)

C-11, Dexetimide I-123, (R)-3-quinuclidinyl-4-

iodobenzilate (QNB)

5.3. CENTRAL NERVOUS SYSTEM

219

5.3.5.4. Protocol

Preparation, basic requirements and operational procedures are almost

identical to those used in perfusion and metabolic studies. Intervention, for

example audiovisual stimulation, task performance tests and complicated

conditioning, are more widely used in neuroreceptor studies.

5.3.5.5. Acquisition setting

The same setting is used as for metabolic imaging.

Serotonin receptors

F-18, Setoperone

Dopa metabolism

F-18, 6-fluorodopa

Monoamine oxidase enzyme activity

C-11, Clorgyline

C-11, Deprenyl

C-11, Dimethylphenylethylamine

Acetylcholine enzyme activity

C-11, MP4A

Neurotransporter

C-11, Cocaine Tc-99m, TRODAT

F-18, CFT (WIN 35,428) I-123, Iodobenzovesamicol (IBVM)

F-18, N-3-fluoropropyl-2-β-

carbomethoxy-3-β-(4-

iodophenyl) nortropan

I-123, N-α-fluoropropyl-2β-

carbomethoxy-3β-

(4-iodophenyl) tropan

(FP-CIT)

I-123, β-Carbomethoxy-3β-(4-

iodophenyl) tropan (β-CIT)

TABLE 5.15. RADIOPHARMACEUTICALS FOR NEURORECEPTOR

IMAGING (cont.)

PET SPECT