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Imaging the Central Nervous System

© 2013 Omnipath, Inc. All rights reserved.

IMAGING THE CENTRAL NERVOUS

SYSTEM

OBJECTIVES

Upon completion of this course, participant will be able to do the following:

• Describe basic brain anatomy.

• Contrast the commercially available brain imaging agents and their mechanism of localization.

• Explain the role of acetazolamide as an interventional agent in assessing vascular reserve.

• Identify the clinical indications for cortical cerebral imaging.

• Describe the basic flow dynamics of cerebrospinal fluid.

• Identify the only FDA-approved radiopharmaceutical for a cisternography study and its

mechanism of localization.

• Define the clinical applications of a cisternography agent.

INTRODUCTION

Nuclear medicine studies of the central nervous system have been conducted for decades. The first

generation technetium-99m (99m

Tc) agents gave way to computed tomography (CT) and magnetic resonance

imaging (MRI) although the first generation agents do have a role in aiding in the diagnosis of brain death.

The development of the second generation 99m

Tc brain imaging agents expanded the role for nuclear

medicine in the evaluation of regional cerebral blood flow. Positron emission tomography (PET) with 18

F-

fludeoxyglucose (18

F-FDG) depicts the regional glucose metabolism within the brain. Nuclear medicine

cisternography studies have continued to play an important role in the assessment of cerebrospinal fluid

(CSF) dynamics throughout the decades.

ANATOMY

The anatomy of the central nervous system can be broadly divided into the brain and spinal cord. The brain

consists of cerebrum, cerebellum, diencephalon, and the brain stem (midbrain, pons, and medulla).



The cerebrum’s surface, or cortex, is made up of gray matter which for the most part contains the neurons.

Underlying this is a layer of white matter containing nerve tracts.1

The cerebral cortex is characterized by a succession of furrows that substantially increases its total area. A

sulcus is a single furrow and a gyrus is the ridge separating neighboring sulci.2

There are two cerebral hemispheres and the cerebrum can be further divided into 4 lobes or regions:

frontal, occipital, temporal, and parietal.1,3

Within the brain are the ventricles which are filled with cerebrospinal fluid.1

Ventricular choroid plexus secrete the cerebral spinal fluid (CSF) for the most part; however, there are

extraventricular sites of production that play a smaller role. Once the CSF leaves the ventricular system, it

goes into the subarachnoid space surrounding the brain and spinal cord.3

In addition to delivering nutrients and removing wastes from the brain and spinal cord, the CSF also

provides a protective cushion to the brain from shocks.1,4



Another protection for the brain is the blood-brain barrier (BBB). It protects the brain from potentially toxic

substances entering the brain, but it also maintains the ionic concentration of the fluid bathing the brain.4

The transport of substances across the BBB is under the control of active transport or by the extent of the

substance’s lipophilicity (affinity for fat).1

Molecules that are uncharged and lipophilic can cross the brain endothelium. However, a few substances,

that are both lipophilic and water soluble,can diffuse across the BBB.and these substances are oxygen,

carbon dioxide, alcohol, and fatty acids.5



RADIOPHARMACEUTICALS

FIRST GENERATION 9 9M

TC AGENTS

The first generation 99m

Tc radiopharmaceuticals are nondiffusible agents that are prevented from entering

the normal brain by an intact BBB. These tracers are ionized hydrophilic (water soluble) pharmaceuticals

possessing nonspecific mechanisms of localization within brain lesions.

When there is an alteration in the BBB due to brain pathology (e.g., stroke, tumor or trauma), these

radiopharmaceuticals exit the vascular space and localize in the brain lesions.

Sodium 99m

Tc-pertechnetate was the first radiopharmaceutical for brain imaging, and it has normal

accumulation in the choroid plexus and salivary glands.

In order to prevent a false positive study, potassium perchlorate was administered with this agent to

prevent this normal accumulation.

Due to the slow clearance from the blood pool, a considerable time delay was necessary between the flow

study and the static imaging.

Other first generation agents include 99m

Tc-pentetate and 99m

Tc-gluceptate.

These latter 2 agents do not have normal accumulation in the choroid plexus and the salivary glands, and

static imaging can be conducted sooner than with 99m

Tc-pertechnetate.

These agents fell out of favor for the detection of anatomic brain lesions due to the superiority of CT and

MRI in the evaluation of these lesions. However, 99m

Tc-pentetate is still used in the evaluation of brain

death.

There is no additional preparation for the use of 99m

Tc-pertechnetate in brain imaging, but it must satisfy the

radionuclidic and radiochemical standards before it can be administered.

Gluceptate was withdrawn from the U.S. market in 2008 by the commercial manufacturer because of low

sales.

Preparation of 99m

Tc-pentetate requires the aseptic addition of 99m

Tc-pertechnetate to a sterile, reaction vial

containing pentetate without the addition of air. Any saline used in the dilution of the product must not

contain any bacteriostatic agents.

Also, in withdrawing doses from a 99m

Tc-pentetatevial, the introduction of air should be avoided in order to

maintain the radiochemical integrity.

Before 99m

Tc-pertechnetate can be administered or used in the preparation of radiopharmaceuticals, it must

satisfy the radionuclidic requirement that a patient will not receive more than 0.15 microcurie of 99

Mo per

one millicurie of 99m

Tc.



Radiochemical purity of 99m

Tc-pertechnetate is determined using ascending paper chromatographyas the

stationary phase and acetone as the mobile phase. The minimum acceptable radiochemical purity for this

agent is 95%.

For the determination of radiochemical purity of 99m

Tc-pentetate, it is necessary to use two systems: one to

determine the percent free 99m

Tc-pertechnetate and another to determine the percent hydrolyzed-reduced

(HR)species.

Both the free 99m

Tc-pertechnetate and the 99m

Tc-HR are radiochemical impurities. Once these are

determined and added together, this value can be subtracted from 100% to determine the percent

radiolabeled compound. 99m

Tc-pentetate must have a minimal radiochemical purity of 90% to meet the USP

radiochemical purity standard.6

RADIOIODINATED AMINE COMPOUNDS

Two radioiodinated amine compounds, 123

I-Iofetamine (123

I-IMP) and 123

I-HIPDM, were introduced for brain

imaging in the early 1980s. Only 123

I-IMP received FDA approval, and this was in 1988. It is no longer

commercially available because the manufacturer ultimately pulled it from the market because of low

sales.5

99mTc-exametazime and

99mTc-bicisate have replaced it because these radiopharmaceuticals have superior

dosimetry and imaging characteristics.3Since

99mTc is a generator product, it does not have the cyclotron

produced product logistics of 123

I.

SECOND GENERATION99MTC AGENTS

The second generation of 99m

Tc agents are neutral lipophilic compounds, thus, they can passively diffuse

through an intact BBB and localize within the brain. 99m

Tc-exametazime and 99m

Tc-bicisate are the two

radiopharmaceuticals in this category. Please refer to Table 1.

Table 1:

DIFFUSIBLE BRAIN RADIOPHARMACEUTICALS

Brand Names Generic Names, Abbreviations or Alternate Names

CeretecTM

Exametazime, (HMPAO)

Neurolite® Biscisate, (ECD)



These agents diffuse into normal brain tissue in proportion to the regional cerebral blood flow (rCBF).5

Both

of these radiopharmaceuticals have high first-pass extraction across the BBB, but at high flow rates they

both slightly underestimate the true rCBF.

The delayed imaging of these 99m

Tc radiopharmaceuticals depicts the perfusion pattern at injection time,

and both are retained a sufficient amount of time to permit SPECT imaging.3,5

The development of these radiopharmaceuticals brought new life to nuclear medicine brain imaging by

providing functional information. This type of information complements what can be acquired with CT or

MRI studies.5

Both of these agents have their own unique characteristics.

9 9MTC-EXAMETAZIME

Upon intravenous administration of 99m

Tc-exametazime, the mean first pass extraction is 72%.5 Within one

minute post injection, the range of the injected dose localizing in the brain is 3.5 to 7.0%.3

Once the radiopharmaceutical has crossed the BBB, brain retention is the result of a glutathione-mediated

conversion of the lipophilic complex to a polar hydrophilic form that is not able to diffuse out of the brain.3,5

It should be noted that some of the 99m

Tc-exametazimemay exist in different isomeric forms which can

diffuse out of the brain. It has been reported that up to 15% of the injected dose diffuses out within the

first 2 minutes, however, there is minimal loss over the next 24 hours.5

With 99m

Tc-exametazimethere is more accumulation in the frontal lobes, thalamus, and cerebellum in

contrast to 99m

Tc-bicisate. At one hour post-injection, there is in excess of 12% of the activity remaining in

the blood.3

The excretion pattern is 40% via the kidneys and 15% by the gastrointestinal route.5

The package insert indication for imaging with 99m

Tc-exametazimeis as an adjunct in the detection of altered

cerebral perfusion in a stroke patient.

The recommended adult dosage is 10 to 20 mCi (370 to 740 MBq). According to the package insert, the

organ receiving the highest radiation dose is the lachrymal glands (5.16 rads/20 mCi).7

However, this value has been challenged, and it has been reported to be considerably lower.5

The whole body radiation dose for 20 mCi (740 MBq) of this radiopharmaceuticals is 0.26 rads (2.66 mGy).7

99mTc-exametazime may be prepared either with a stabilizer or without; however, the stabilized product has

a shelf life of 4 hours whereas the product prepared without the stabilizer only has a shelf life of 30 minutes.

Reconstitution of 99m

Tc-exametazime requires the aseptic addition of 99m

Tc-pertechnetate to a sterile,

reaction vial containing exametzime without the addition of air. Any saline used in the dilution of the

product must not contain any bacteriostatic agents.



Also, in withdrawing doses from a vial of 99m

Tc-exametazimethe introduction of air should be avoided in

order to maintain the radiochemical integrity. If the product is to be stabilized, the methylene blue

stabilizing solution must be added to the radiolabled vial within 2 minutes of reconstitution.

The package insert states to use only 99m

Tceluate from a generator that has been eluted within 24 hours and

the highest radiochemical purity results when freshly eluted 99m

Tcpertechnetate is used in the

reconstitution. With the stabilizing protocol the eluate should not be older than 30 minutes.7

An acceptable 99m

Tc-exametazimeproduct must have a radiochemical purity greater than 80%. The package

insert describes a radiochemical procedure that requires a 3 solvent system and requires approximately 15

minutes to complete.7

The literature has described a method which requires only 1 solvent system that is much easier to perform

but is also reliable.6

9 9MTC- BISCISATE

The first-pass extraction of 99m

Tc-bicisate ranges from 47% to 70% and the peak brain uptake in 5 minutes is

6.5% of the administered activity.3,5

At one hour post-injection, the blood contains 5% or less of the

administered activity.3,8

As compared to 99m

Tc-exametazime, 99m

Tc-bicisate has a faster blood clearance, thus yielding better brain-

to-background ratios.3By 4hours the brain retention has dropped to 3.8% of the injected activity.

5

The retention of 99m

Tc-bicisate inside the brain cell depends on metabolism by endogenous enzymes.3Upon

background clearance, brain images can be acquired from 10 minutes to 6 hours post-injection.8

As with 99m

Tc-exametazime, imaging with 99m

Tc-bicisate demonstrates the perfusion pattern at the time of

injection. With 99m

Tc-bicisate there is higher accumulation in the occipital and parietal lobes as compared to 99m

Tc-exametazime.

At 15 to 30 minutes post-injection, the brain images may be superior to 99m

Tc-exametazime; however, if

imaging is delayed to 4 hours, 99m

Tc-bicisate may be suboptimal.3

99mTc-bicisate undergoes both renal and fecal excretion. By 24 hours, 74% of the injected activity appears in

the urine; by 48 hours, 12.5% of the administered activity is excreted via the fecal route.8

In contrast, approximately 40% of the 99m

Tc-exametazimedose is eliminated by renal route in 48 hours and

about 15% is excreted by the intestinal tract in this same time period.5

The package insert lists the indication of this agent as an adjunct to conventional CT or MRI studies in the

localization of stroke in patients already diagnosed with stroke. The recommended adult dosage is 10 to 30

mCi (370 – 1110 MBq).

The organ receiving the greatest radiation burden is the urinary bladder wall. The radiation burden is shown

here (5.4 rads/20 mCi or 54.02 mGy/740 MBq with a 4.8 hour void).

The total body dose for 20 mCi (740 MBq) is 0.22 rads (2.14 MGy) when there is a 4.8 hour void.8



Preparation of radiolabeled bicisate requires 2 vials of the kit, 0.9% sodium chloride Injection, and up to 100

mCi of sterile, bacteriostatic-free sodium pertechnetate99m

Tc.

Aseptically add 2 mL of 99m

Tc sodium pertechnetate to vial B and swirl. Three milliliters of 0.9% sodium

chloride Injection are added to vial A and mixed well. Immediately withdraw 1 mL from vial A and add to

vial B.

After swirling the contents of vial B for a few seconds, let the vial stand for 30 minutes at room

temperature. All manipulations must be performed using aseptic technique. According to the package

insert, the product should be used within 6 hours of preparing it.8

Before using the product, radiochemical purity should be determined, and the acceptable radiochemical is

90% or greater.6,8

Radiochemical purity can be determined by thin layer chromatography utilizing Baker-Flex silica gel IB-F, and

ethyl acetate as the solvent.8

An alternative method for determining radiochemical purity involves the use of Whatman 17 paper as the

stationary phase and ethyl acetate as the solvent.6

1 8F-FLURODEOXYGLUCOSE (

1 8F-FDG)

18F-FDG is an analogue of glucose. and glucose is the brain’s primary energy substrate. The brain cortex

demonstrates a high uptake of this PET biomarker and an accurate assessment of regional glucose

metabolism can be determined.3,5

18F-FDG crosses the BBB using the same transporter system as glucose. and inside the brain cell FDG

undergoes phosphorylation as glucose does. However, FDG becomes metabolically trapped within the cell

at this point, and it cannot proceed any further along the pathway of glucose metabolism. The brain

localizes approximately 4% of this injected PET biomarker. 95% of peak uptake is obtained by 35 minutes

post-injection.3

At approximately 90 minutes post-injection, a plateau is reached in the gray and white matter.It has been

reported that the average brain FDG clearance half-time is 9.1 hours.The primary elimination route is renal,

with 20% of the injected activity excreted 2 hours post-injection. 5

Besides reflecting the regional cerebral blood flow as an indicator of glucose metabolism, 18

F-FDG can be

used to determine the viability of tumors. The resolution of 18

F-FDG PET is 4 to 5 mm which is superior to

SPECT’s resolution of 7mm.3

The usual adult dosage of this agent for brain imaging is 6 to 15 mCi (222 to 555 MBq). After a delay of 45 to

60 minutes post 18

F-FDG administration, brain imaging typically starts.

The urinary bladder wall is the critical organ; and, based on a 4.8 hour voiding interval, it receives a radiation

absorbed dose of 7 rad/10 mCi. 5

Because 18

F has a physical half-life of 110 minutes, an onsite cyclotron is not necessary. It can be prepared

at a centralized location and delivered to many different nuclear medicine departments several miles away.



A cyclotron is necessary for the production of 18

F and labeling 18

F to FDG requires sophisticated chemistry.

There are FDG synthesis modules available for the preparation of 18

F-FDG.

Once the biomarker is prepared, it must undergo extensive quality control testing before it is released.

Included in this testing is chemical, radionuclidic, radiochemical, and bacterial endotoxin testing (BET).

Sterility testing is performed although it is not completed prior to the release of the biomarker because

sterility testing requires 14 days. However, it is permissible to dispense 18

F-FDG prior to the completion of

sterility testing if the PET agent has been prepared using a validated aseptic process.6

1 11IN-PENETATE (

11 1IN-DTPA)

111In-pentetate is commercially available as a sterile, pyrogen-free, aqueous solution in a single use vial for

cisternography studies. 111

In has a physical half-life of 67.9 hours and decays by electron capture, emitting

two gamma photons (171 keV and 245 keV). 9

It is injected intrathecally into the lumbar subarachnoid space, and it follows the CSF flow without changing

the CSF dynamics.3

Once the radiopharmaceutical reaches the arachnoid villi, it is cleared into the blood stream.3,9

Within 24

hours of administration in a normal study, about 65% of the injected dose is excreted renally.9

A radionuclide cisternogram demonstrates CSF flow so it can be used to evaluate hydrocephalus and shunt

patency as well as demonstrate CSF leaks.10

According to the package insert, the maximum recommended adult dosage is 0.5 mCi (18.5 MBq), and the

organ receiving the greatest radiation burden is the surface of the spinal cord (5 rads/0.5 mCi).9

CLINICAL APPLICATIONS

CEREBRAL PERFUSION IMAGING

Cerebral perfusion imaging is useful in aiding in the activities listed here:

• Diagnosis of brain death,

• Assessment of patients with cerebrovascular disease,

• Locating a seizure focus,

• Detection of recurrent brain tumors,

• Grading of primary brain tumors,

• Evaluation of movement disorders, and

• Evaluation of dementia.3

BRAIN DEATH



The determination of brain death is primarily a clinical decision and no single test should be utilized to make

the diagnosis of brain death.3,10

An electroencephalogram (EEG) is used to confirm the diagnosis; however, an EEG can frequently be

equivocal.10

When the EEG and clinical criteria are equivocal, a radiopharmaceutical brain death study is usually

conducted. Diagnostic finding of brain death on a nuclear medicine study is the lack of blood flow. 3

Shown here in Figure 1 is an example of a normal CBF study.

Figure 1

99mTc-pentetate brain flow study for the evaluation for brain death.

Interpretation: Normal CBF



Shown here in Figure 2 for an example of brain death study.

Figure 2

Sodium 99m

TcO4CBF study for evaluation of brain death

Interpretation: CBF study appears to be compatible with diagnosis of brain death.

Radionuclide brain death studies can be performed with either the first or second generation 99m

Tc brain

imaging agents. With 99m

Tc-pertechnetate and99m

Tc-pentetate, a flow study is acquired after a bolus

injection to establish whether or not normal cerebral blood flow exists.10

Because 99m

Tc-pentetate rapidly clears from the blood, it has often been used since a repeat study can be

performed when necessary. When the diffusible radiopharmaceuticals (99m

Tc-exametazimeand 99m

Tc-

bicisate) are used, the delayed images show whether or not there is radiopharmaceutical brain uptake.

These lipophilic radiopharmaceuticals provide parenchymal imaging of both the brain and brain stem.11



In order for there to be a fixed presence in the brain of radioactivity, there must be blood flow to the brain.

Thus, without cerebral blood flow, there is a lack of cerebral uptake. The angiographic flow phase is

optional. Planar images are acceptable for the diagnosis of brain death.3

Since blood flow is necessary to provide substrates to living tissue, the continued lack of blood flow has

been regarded as a dependable indicator of brain death, thus generating a position for blood flow studies in

the evaluation of brain death.

The opposite is not necessarily correct, in that existence of blood flow does not inevitably mean the

existence of function. If this is received as fact, then the presence of brain dysfunction on physical

examination, indicating brain death, and radiopharmaceutical regional perfusion can exist simultaneously.

Using this approach, blood flow examinations are regarded as specific however not sensitive for brain

death.11

STROKE AND CEREBROVASCULAR DISEASE

CT and MRI are well accepted as the principal modalities for the diagnosis of stroke; however, PET and

SPECT (99m


Tc-bicisate) can be useful in the determination of the function of

therapeutic intervention.

Because PET and SPECT are functional imaging modalities, they allow the quantification of regional cerebral

blood flow and regional cerebral glucose metabolism. This provides information not observed with

structural imaging.

With the functional imaging modalities, it is possible to determine those patients at risk for stroke and

which patients would probably benefit from intervention.These modalities can even be used in the

prediction of stroke recovery.3

SPECT with 99m


Tc-bicisate can aid in the assessment of patients with suspected

ischemia, in the assessment of stroke risk in patients with transient ischemic attacks, and in the assessment

of vascular diseases.3

Acetazolamide can be used as an interventional agent with nuclear brain imaging when evaluating the

physiologic importance of an anatomic vascular lesion (e.g., carotid artery stenosis). Acetazolamide is a

carbonic anhydrase inhibitor which produces vasodilation of the cerebral vessels, thus increasing cerebral

blood flow.

Twenty minutes after 1 g of acetazolamide is injected, the radiopharmaceutical is administered. SPECT

imaging is conducted in the usual fashion. There are different protocols for this procedure; the baseline

study can be conducted either the day before the acetazolamide study or the day after.

If the acetazolamide study is normal, then there is no need for the baseline study. Stenotic vessels cannot

dilate, thus, after administration of acetazolamide, there will be no increase in flow to vascular territory

supplied by the stenotic vessel. Vascular territory supplied by the stenotic vessel will appear hypoperfused

in comparison to territories supplied by normal vessels.10



EPILEPSY

Epilepsy is characterized by abnormally synchronized electrical discharges from cerebral neurons, either

localized or widely distributed, with the result being recurring seizure episodes.3,12

Approximately 10% of epilepsy patients have seizures that do not respond to medical therapy, and surgery

has the potential to be of benefit to this group of patients.13

There are various methods to locate the seizure focus preoperatively, such as scalp EEG, MRI,

magnetoencephalography, SPECT, and PET; oftentimes, a combination of these methods are necessary to

locate the epileptogenic focus.3

When an epileptic seizure occurs (ictal), there is an increase in the neuronal activity of the brain

involved.13

Associated with this event is enhanced local blood flow and metabolism of glucose in the

activated foci.3,13

In contrast, imaging between seizures (interictical) demonstrates hypoperfusion or normal

radiopharmaceutical uptake. Radiopharmaceutical uptake is changing following a seizure, and there may be

areas of decreased and increased uptake.3

The studies that are more sensitive for localization of the epileptogenic focus are those that are ictal studies,

and these studies involve SPECT and the diffusible radiopharmaceuticals (99m


Tc-

bicisate).3

With ictalr CBF SPECT studies, the radiopharmaceutical is injected during, or shortly after a seizure. Imaging

can be conducted a few hours after radiopharmaceutical injection because the radiopharmaceutical

becomes fixed at the time of injection.13

Due to the physical half-life of 18

F, PET studies with 18

F-FDG are conducted interictally and are useful in the

presurgical epilepsy evaluation.3,12

Even though interictal studies are not as sensitive as ictal studies, it is

thought that interictal PET studies are superior to interictal SPECT studies.3

In temproral lobe epilepsy, nuclear medicine studies have a sensitivity ranging from about 85% to 90% in

locating the epileptogenic focus; however they are not always indicated clinically since other diagnostic

modalities may be successful in detection of the epileptogenic focus. When the MRI is negative or when the

MRI and EEG are discordant, nuclear medicine examination is important.14

BRAIN TUMORS

The anatomic imaging modalities of MRI and CT are crucial procedures for the assessment of brain tumors.

Since SPECT and PET provide functional information, they can provide critical information in the diagnostic

workup of a brain malignancy, in early evaluation of therapy, and in the long-term follow-up.



The information gained from anatomical imaging and functional imaging can be combined by means of

image fusion. Even though the applications of PET and PET/CT are increasing, SPECT studies still play a

significant role in the assessment of brain tumor patients.

There have been continuous instrumentation advances in SPECT technology, including the newly developed

integrated hybrid SPECT/CT instrumentation which could further enhance diagnostic accuracy.15

Both 99m


Tc-bicisate usually demonstrate normal or decreased uptake in the

evaluation of intracranial lesions.3 However, both agents may occasionally show uptake in brain tumors.

3,16

Thallium-201 (201

Tl) and 99m

Tc-sestamibi, cardiac imaging radiopharmaceuticals, demonstrate uptake in

several intracranial tumors. Some uptake of 99m

Tc-sestamibi in the choroid plexus can hinder the usefulness

of this agent in various tumors.

The SPECT tumor imaging procedure is conducted 20 to 30 minutes post-injection of 2 to 4 mCi (74 to 148

MBq) of 201

Tl or 20 mCi (740 MBq) of 99m

Tc-sestamibi. In some cases a 2-hour delayed image acquisition

with 201

Tl is necessary to improve sensitivity.3

Since the degree of malignancy does not correlate well with blood volume and cerebral blood flow,

metabolic studies are more desirable.1

Brain imaging with 18

F-FDG usually begins 45 to 60 minutes after the intravenous administration of 6 to 15

mCi (222 to 555 MBq). PET brain tumor imaging is not always ideal due to the fact that the brain is highly

metabolic.5

Glucose metabolism is enhanced with more aggressive tumors due to their greater metabolic activity. Thus,

the tumor grade is reflected by the degree of 18

F-FDG uptake. PET can be useful in grading tumors and

directing biopsy sites.3

There should be minimal or no uptake of 18

F-FDG in radiation necrosis.10

PET imaging with 18

F-FDG after

treatment provides information useful in determining tumor persistence, degree of malignancy, tumor

progression, and in differentiating between recurrence and necrosis. With this information, the physician

can better determine the patient’s prognosis.5

MOVEMENT DISORDERS

A wide variety of diseases areclassified as movement disorders, some exhibit diminished movement

conditions while others exhibit excessive movement states. Parkinson’s disease, characterized by

diminished movement, is the most familiar movement disorder.3

Brain perfusion SPECT studies have yielded mixed results.10

F-18-fluorodopa PET studies have been largely

used as a research modality in movement disorders; however, it is not ideal.

New agents have been developed which may be able to identify preclinical disease as well as differentiate

between Parkinson’s disease and non-Parkinson’s tremor.3



Dementia

Dementias may be categorized into those that respond to specific medical means and those that can only be

treated with supportive care.1

Both PET and SPECT have proved useful in aiding in the determination of the cause of dementia by the

assessment of metabolic abnormalities and regional blood flow in the brain.5

Even though the pattern for dementias is similar with both PET and SPECT, PET has greater definition and

sensitivity.10

In dementia it is usual to have symmetric perfusion to the cerebral hemispheres.

Although in Alzheimer’s disease the characteristic distribution is reduced perfusion and metabolism in the

temporoparietal regions of the brain. Decreased metabolism in the frontal lobes is seen as mental

deterioration becomes worse. The pattern of brain uptake, using either metabolic or perfusion agents, in

multi-infarct dementia usually shows multiple asymmetric defects.5

CISTERNOGRAPHY

Radionuclide cisternography demonstrates the flow of CSF.10

With nuclear medicine CSF dynamic studies,

information can be used in the diagnosis of hydrocephalus, in the evaluation of shunt patency, and in the

diagnosis of CSF leaks.1

111In-pentetate is the radiopharmaceutical used in the study of CSF dynamics, and it is administered via

lumbar puncture into the thecal sac. An example of a protocol that can be used- would be planar imaging

acquired at 1 to 4 hours, 24 hours, and up to 48 hours or even 72 hours. In selected patients, SPECT can be

conducted.10

At one hour in normal patients, the radiopharmaceutical reaches the basal cisterns. From 2 to 6 hours in

normal subject, 111

In-pentetate should be in the frontal poles and Sylvian fissures; the convexities should be

demonstrated by 12 hours.

The radiopharmaceutical should normally be at the sagittal sinus by 24 hours, and the radiopharmaceutical

should be undergoing clearance by this time. Activity is not normally demonstrated in the ventricles but

there could be a brief transient reflux.10

Refer to Figure 3 for an example of a cisternography study.



Figure 3 Normal cisternography study

In patients with normal-pressure hydrocephalus, the CSF flow pattern demonstrated via radionuclide

cisternography is different from the normal patient.

In this condition, there is reflux of the radiopharmaceutical into the lateral ventricles which persists on

delayed imaging. Also, there is usually a significant delay in the ascent over the cerebral convexities.5

In a patient with non-communicating hydrocephalus, there is continuous production of CSF and no way to

escape; thus, causing the ventricles to enlarge resulting in cerebral cortex compression and atrophy and

dementia.

In order to allow the CSF to flow out of the ventricles, ventriculoperitoneal shunts are implanted. These

shunts are made up of a proximal tubing, a reservoir, and a tubing.

The proximal tubing originates in the cerebral ventricles and connects to the reservoir which is connected to

the peritoneal cavity via the distal tubing.1

When complications occur, the shunt can become blocked.3

To determine the patency of the shunt, 111

In-

pentetate is injected into the reservoir.

Head and abdominal imaging is immediately acquired and 3 hours post-injection. If necessary, images can

be obtained 24 hours post-injection.1With a patent shunt, normal flow through the tubing should be

observed with considerable clearance of the reservoir by 30 minutes post-injection.10

CSF leaks appear as rhinorrhea (drainage from the nose) or otorrhea (drainage from the ears).10

CT and

MRI provide superior information in the detection of the leak, and locating the anatomic site. However, a



nuclear medicine CSF leak study can be ordered when MRI and CT are negative, inconclusive or if the CSF

leakage is intermittent.17

Prior to the nuclear medicine study, an otolaryngology surgeon places cotton pledgets into the nasal cavity

and/or ears of the patient. After intrathecal administration of 111

In-pentetate, planar and/or SPECT imaging

is acquired at 1 to 4 hours. Usually the pledgets are removed when a leak is detected, or at 4 to 24 hours.10

The pled gets are then weighed and counted for radioactivity using a well scintillation counter.10,17

Since CSF and 111

In-pentetate are absorbed into the bloodstream and will be present in normal nasal

secretions, a plasma sample is frequently collected to determine a pledget-to-plasma radioactivity ratio.

Additional views may be acquired up to 72 hours.10

QUIZ

QUESTION #1

All of the following are lobes of the cerebrum EXCEPT:

○ frontal

○ temporal

○ pons

○ occipital

QUESTION #2

Which of the following is a nondiffusible brain imaging radiopharmaceutical?

○ 99mTc-exametazime

○ 123I-Iofetamine

○ 99mTc-pentetate

○ 99mTc-biscisate

QUESTION #3

Which of the following is a diffusible brain imaging radiopharmaceutical?

○ 99mTc-pertechnetate

○ 99mTc-exametazime

○ 99mTc-pentetate

○ 99mTc-gluceptate



QUESTION #4

In comparison to 99mTc- exametazime, 99mTc-biscisate:

○ has faster blood clearance

○ has less renal excretion

○ demonstrates perfusion pattern at time of imaging

○ lower accumulation in the parietal lobe

QUESTION #5

Which statement is true concerning 18F-FDG?

○ The primary elimination route is via the gastrointestinal tract.

○ The brain localizes approximately 95% of the injected dose.

○ Accurate assessment of regional glucose metabolism is possible with this agent.

○ Resolution of 18

F-FDG PET is less than SPECT’s resolution.

QUESTION #6

111In-pentetate is used in all of the following studies EXCEPT:

○ Shunt patency

○ Cisternography

○ Assessment of rCBF

○ CSF leaks

QUESTION #7

Which of the following is true regarding radionuclide brain death studies?

○ SPECT studies are mandatory for an accurate diagnosis.

○ Radionuclide angiogram is the only study needed for the diagnosis of brain death.

○ 99mTc-pentetate is the only acceptable radiopharmaceutical for these studies.

○ Both the diffusible and nondiffusible brain imaging agents may be used for these studies.



QUESTION #8

Which of the following is true concerning imaging of brain tumors?

○ Degree of malignancy correlates well with blood volume.

○ PET imaging can be useful in grading tumors and directing biopsy sites.

○ Necrotic tissue readily takes up 18

F-FDG.

○ Aggressive tumors have lower metabolic activity so 18

F-FDG uptake is reduced.

REFERENCES

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Physiology 3rd

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computed tomography in epilepsy care. Semin Nucl Med. 2003;33:88-104.

13. Murray AD. The brain, salivary and lacrimal glands. In: Sharp PF, Gemmell HG, Murray, AD, ed.

Practical Nuclear Medicine. 3rd

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Tcm

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