brain perfusion imaging in nuclear medicine department

1. BRAIN
PERFUSION
OWES SAMAD
MTIT
AIIMS BBSR
2018 BATCH

2. • INTRODUCTION
• ANATOMY
• INDICATION
• CONTRAINDICATION
• PATIENT PREPARATION
• RADIOPHARMACEUTICALS & DOSE PREPARATION
• DOSIMETRY & METHOD OF INJECTION
• PROCEDURE
• IMAGE ACQUISITION

3. • A cerebral perfusion study is a nuclear medicine scan that looks at brain
function by demonstrating the amount of blood taken up by the brain
cells.
• The most common nuclear medicine imaging procedures of the brain can be
divided into three different approaches relative to this principle:
i. Planar brain imaging:- which uses radiopharmaceuticals that are perfusion agents.
Planar imaging is usually performed for brain death studies only.
ii. SPECT Brain perfusion imaging:- which uses lipophilic radiopharmaceuticals that
routinely cross blood-brain barrier in proportion to rCBF.
iii. PET Brain imaging:- which uses positron emitting radiopharmaceuticals such as
radiolabeled Fluorodeoxyglucose which reflect regional glucose metabolism.

4. Here we study SPECT brain perfusion imaging in details.
Brain perfusion single-photon emission computed tomography (SPECT)
imaging is a functional nuclear imaging technique performed to
evaluate regional cerebral perfusion. Because cerebral blood flow is
closely linked to neuronal activity, the activity distribution is presumed to
reflect neuronal activity levels in different areas of the brain. A lipophilic,
PH-neutral radiopharmaceutical (most commonly technetium-99m-
hexamethylpropyleneamine oxime [HMPAO] and 99mTc-ethylene
cysteine dimer [ECD] is injected into the patient, which crosses the
blood-brain barrier and continues to emit gamma rays. A 3-dimensional
representation of cerebral blood flow can be iterated using gamma
detectors, allowing for interpretation.

7.  Evaluation of suspected Dementia
 Evaluation of traumatic head injury
 Evaluation of cerebrovascular disease
 Evaluation of suspected inflammation
 Assessment of brain death
 Parkinson's disease

8.  Pregnancy
 Lack of cooperation or non-cooperative patient
 Recent contrast or pertechnetate study

9. Depending on the brain target of imaging, tracers can be divided into several group:-
 Perfusion through blood brain barrier-
1) Tc-99m HMPAO (Hexamethylpropyleneamineoxime)
2) Tc-99m ECD (Ethyl cysteinate dimer)
3) I-123 IMP (Isopropyl idoamphetamine)
 Tracers that doesn’t crosses the blood brain barrier-
1) Tc-99m Pertechnetate
2) Tc-99m DTPA (Diethyltriamine pentaacetic acid)
3) Tc-99m GH (Glucoheptonate)
4) Thallium 201

10.  Tc-99m pertechnetate & Tc-99m DTPA are the first radionuclide agents, they did
not cross the blood brain barrier. Brain uptake occurred only if there was
disruption, for example with tumor or stroke.
Image shows the delayed Tc-99m DTPA planer image.
(A large amount of activity is normally seen in the face and base
of skull.)
 SPECT brain perfusion imaging uses several groups of lipophilic
radiopharmaceuticals. These radiopharmaceuticals cross the intact blood-brain
barrier and are retained by the brain tissue in proportion to regional cerebral
blood flow (rCBF).These are :-
1) Tc-99m HMPAO (exametazime)
2) Tc-99m ECD (bicisate)

11. Favorable characteristics of these 2 radiopharmaceutical (HMPAO &
ECD):-
1) Neutral
2) Lipophilic agents include high first pass extraction across the blood brain barrier.
3) Distribution corresponding to rCBF.
4) Desirable 140 KeV gamma photons.
NOTE:- The Tc-99m perfusion agents are relatively fixed in the neurons, therefore delayed imaging
shows what the perfusion pattern looked like at the time of injection.

12.  Hexamethylpropyleneamine oxime.
 Tc-99m HMPAO (Tc-99m exametazime [Ceretec]) was first introduced in the mid-1980s.
 It was originally available as a kit requiring use within 30 minutes of radiolabeling; however,
stabilizers{Gentisic acid (2,5-dihydroxybenzoic acid; GA)}, have since been added, allowing a
4-hour shelf life after addition of the radiolabel.
 Care must be taken that doses from the radiopharmacy have been labeled with fresh
generator eluate (<2hrs) just before delivery.
 It has a good first-pass extraction of approximately 80%, with 3.5% to 7% of the injected dose
localizing in the brain within 1 minute of injection.
 Once across the blood–brain barrier, it enters the neuron and becomes a polar hydrophilic
molecule trapped inside the cell.
 Although up to 15% of the dose washes out in the first 2 minutes, little loss occurs over the
next 24 hours.
 SPECT images can be acquired from 20 minutes to 2 hours after injection. Excretion is largely
renal (40%) and gastrointestinal (15%).

13. Cont…
 99mTc-HMPAO is highly unstable in vitro and high radiochemical purity must be assured before injection.
 Stabilized forms of 99mTc-HMPAO allow easier labeling and improvement of image quality by reducing
background activity.
• They enter the brain cells because of their lipophilic nature and remain there because of conversion into
hydrophilic compounds.
• However, in patients with brain disease, the distribution of these compounds may differ because of the
biochemistry of lipophilic-to-hydrophilic conversion.
• Instability of the lipophilic form have been proposed for 99mTc-HMPAO.
• A perfusion-metabolic (de-esterification) coupling is needed in case of 99mTc-ECD to be trapped within
cell, whereas only perfusion matters in 99mTc-HMPAO.
PHARMACOKINETICS

14.  Ethylene cysteine dimer.
 Tc-99m ECD (Tc-99m bicisate, Neurolite) is a neutral lipophilic agent that passively diffuses
across the blood– brain barrier like Tc-99m HMPAO.
 Once prepared, the Tc-99m ECD dose is stable for 6 hours.
 It has a first-pass extraction of 60% to 70%, with peak brain activity reaching 5% to 6% of the
injected dose.
 The blood clearance is more rapid than Tc-99m HMPAO, resulting in better brain-to-background
ratios.
 At 1 hour, less than 5% of the dose remains in the blood, compared to more than 12% of a Tc-
99m HMPAO dose.
 Once inside the cell, Tc-99m ECD undergoes enzymatic deesterification, forming polar
metabolites unable to cross the cell membrane.
 However, slow (roughly 6% per hour) washout of some labeled metabolites occurs, with almost
25% of the brain activity cleared by 4 hours.

15. Cont….
 Although images may be superior to those with Tc-99m HMPAO 15 to 30 minutes after injection,
they may be suboptimal if imaging is delayed.
 A perfusion-metabolic (de-esterification) coupling is needed in case of 99mTc-ECD to be trapped within
cell, whereas only perfusion matters in 99mTc-HMPAO.
 Thus, 99mTc-ECD would have a predominant cellular-metabolic uptake, and 99mTc-HMPAO would reflect
blood flow arrival to cerebral regions.
 After background clearance brain images may be obtained from 10min to 6h after injection,
However optimum imaging time being 30 to 60min after injection.
 The primary route of excretion is via kidneys, 75% cleared through bladder and 11% via
Gastrointestinal.
 The main differences between 99mTc-HMPAO and 99mTc-ECD relate to their in vitro stability,
uptake mechanism, and dosimetry.

16.  Two components:-
i. Component A :- 1mg ECD , 60-75microgram stannous chloride hydrate, 0.3mg
sodium EDTA, 20mg mannitol.
ii. Component B -1ml of 0.02M phosphate buffer at pH 7-8.
 Allow the component A vial to attain ambient temperature.
 Add 1-2 ml of sterile Tc-99m sodium pertechnetate containing the required
activity of Tc-99m to the Component B-vial, Mix well. This is called Reaction Vial.
 Dissolve the contents of component A-vial in 1ml of 0.9% sodium chloride
solution, and withdraw equal amount of Air from the vial. Withdraw all the contents
of the vial and immediately add to the reaction vial, Mix well.
Preparation of ECD

17. Cont…
 Allow it to stand at room temperature for 30min.
 The preparation is now ready for use.
NOTE :- Approximately a 45-min delay from injection to imaging gives the best image
quality. Images obtained after a 20-min delay will be interpretable.

18.  Tc-99m ECD reflects both the perfusion and the metabolic state of brain cells.
 I- 123 Ioflupane - high binding affinity to DAT( Dopamine transport). Its availability is limited in
India.
 TRODATE -1 :-
For Parkinson's disease.
It binds to dopamine transporters.
Trodat-1 has been shown to bind with Basal Ganglia, specifically to caudate & Putamen.
A single bolus injection (20mCi) inject immediately before injection.
A total of 42 dynamic images of brain acquired over 4h.
SOME BRIEF ABOUT OTHER PHARMACEUTICALS

19. 1) Camera: Dual-head or triple-head SPECT
2) Head-holder attachment: Head extends beyond table for minimum camera radius
3) Collimators: High resolution, parallel hole
4) Computer setup: SPECT acquisition parameters
5) Matrix size: 64 × 64
6) Rotation: Step and shoot
7) Orbit: Circular
8) Angle step size: 3 degrees
9) Stops: 40 per head
10) Time per stop: 40 seconds (total time, 27 minutes)

21. 1. Before arrival patients should be instructed to avoid, if possible, caffeine, alcohol, or
other drugs known to affect cerebral blood flow.
2. Before injection:-
a) The most important aspect of patient preparation is to evaluate the patient for ability
to cooperate.
b) A consistent environment must be maintained at the time of injection and uptake:
1. Place the patient in a quiet, dimly lit room.
2. Instruct the patient to keep eyes and ears open.
3. Ensure that the patient is seated or reclining comfortably.
4. Place intravenous access at least 10 min before injection to permit accommodation.
5. Instruct the patient not to speak or read.
6. Have no interaction with the patient before, during, or for 5 min after injection.

22. Cont…
Information Pertinent to Performing the Procedure
Relevant patient data suggested for optimal interpretation of scans includes patient history (including
any past drug use or trauma), neurologic examination, psychiatric examination, mental status
examination (e.g., Folstein mini-mental examination or other neuropsychologic tests), recent
morphologic imaging studies (e.g., CT, MRI), and current medications and when last taken.
Precautions
1.Patients with neurologic deficits may require special care and monitoring.
2.If sedation is required, it should be given after injection of the radiopharmaceutical, when possible.
3.Demented patients must be closely monitored at all times.

23. 3. Inject the patient :-
 Inject the radiopharmaceutical in the dimly lit room.
 Unstabilized 99mTc-HMPAO: Inject tracer no sooner than 10 min before and no more than 30
min after reconstitution. For seizure disorders, it is important to inject the tracer as soon as
possible after reconstitution (within 1 min).
 Stabilized 99mTc-HMPAO: Inject tracer no sooner than 10 min before and no more than 4 h
after reconstitution.
 99mTc-ECD: Inject tracer no sooner than 10 min before and no more than 6 h after
reconstitution.
 Instruct patients to void within 2 h after injection to minimize radiation exposure.

24.  99mTc-HMPAO (unstabilized and stabilized):- A 90-min delay from injection to imaging gives
the best image quality. Images obtained after a 40-min delay will be interpretable. For best
image quality allow a delay of 30–90 min
 99mTc-ECD:- For best image quality allow a delay of 30–60 min since wash-out from no-
specific uptake improves the signal to noise ratio in this period.
 Imaging should be completed within 4 h after injection, if possible. An excessive delay
should be avoided.
 Try always to keep the same time delay from injection to the start of data acquisition
Time delay from injection to imaging

25. RADIOPHARMACEUTICALS ADMINISTERED DOSE
ADULT Tc-99m HMPAO 15-30 mCi (usually 20mCi)
Tc-99m ECD 15-30 mCi (usually 20mCi)
CHILDREN Tc-99m HMPAO 0.2-0.3 mCi
Tc-99m ECD 0.2-0.3 mCi
Note:- In case of children Webster rule should be followed.
age(yrs)+1 X(adult dose)
age(yrs)+7

26. AGENT ORGAN
RECEIVING
HIGHER DOSE
DOSE
(mGy/MBq)
EFFECTIVE
DOSE
(mSv/MBq)
HMPAO Kidney 0.034 0.0093
ECD Urinary Bladder 0.05 0.0077
QUALITY CONTROL :- Radiochemical purity should be determined on each vial prior to
injection using the methods outlined in the package inserts. It should be >90% for ECD and
>80% for HMPAO.

27.  Multiple-detector or other dedicated SPECT cameras generally produce results superior to
single-detector general-purpose units. However, with meticulous attention to procedure, high-
quality images can be produced on single-detector units with appropriately longer scan times
(5 × 106 total counts or more are desirable).
 The patient should void before the study for maximum comfort during the study.
 The patient should be positioned for maximum comfort. Minor obliquities of head orientation
can be corrected in most systems during processing.
 The patient's head should be lightly restrained to facilitate cooperation in minimizing motion
during acquisition. It is not possible to rigidly bind the head in place. Patient cooperation is
necessary. Sedation may be used after injection of the radiopharmaceutical if the patient is
uncooperative.
 Use the smallest radius of rotation possible with appropriate patient safeguards.
 Use of high-resolution or ultra-high-resolution collimation is recommended. All-purpose
collimation is not suitable. As a general rule of thumb, use the highest-resolution collimation
available.

28. CONT….
 Fanbeam or other focused collimators are generally preferable to parallel-hole, as they provide
improved resolution and higher counting rates. Parallel-hole collimation is acceptable if adequate
counts are obtained. Slant-hole collimation may be used.
 A 128 × 128 or greater acquisition matrix should be used.
 Use 3° or better angular sampling. The acquisition pixel size should be one third to one half the
expected reconstructed resolution. It may be necessary to use a hardware zoom to achieve an
appropriate pixel size. Different zoom factors may be used in the x and y dimensions of a
fanbeam collimator.
 Compared with step-and-shoot technique, continuous acquisition may provide a shorter total
scan duration and reduced mechanical wear to the system.
 Segmentation of data acquisition into multiple sequential acquisitions will permit exclusion of bad
data, for example, removing segments of projection data with patient motion.
 It is frequently useful to use detector pan and zoom capabilities to ensure that the entire brain is
included in the field of view while allowing the detector to clear the patient's shoulders.

29.  Vasodilatory challenge with acetazolamide or the equivalent is indicated to evaluate
cerebrovascular reserve in transient ischemic attacks, to evaluate completed stroke or
vascular anomalies (e.g., arterial–venous malformation), and to aid in distinguishing vascular
from neuronal causes of dementia.
 Various protocols have been used, including a split-dose 2-d repeated study and dual-isotope
techniques.
 Acetazolamide contraindications: Known sulfa allergy is a contraindication (skin rash,
bronchospasm, anaphylactoid reaction)
 Acetazolamide dosage: In adults, give 1,000 mg by slow intravenous push for a typical
patient. In children, give 14 mg/kg. Wait 15–20 min after administering acetazolamide before
injecting tracer.

30.  DIAMOX STRESSS TEST:-
 Acetazolamide(ACZ) is used which inhibits carbonic anhydrase , so concentration of CO2 is
increased.
 Brain vascular dilation occurs.
Clinical:-
 Silent Brain ischemia.
 Cerebrovascular reserve assessment.
Procedure:-
 Get baseline image.
 Inject DIAMOX 15-20 mg/kg I.V before tracer injection.
 Take stress images.

31.  Reconstruction
Methods:
1) Filtered back-projection.
2) Iterative reconstruction. Iterative reconstruction methods, including ordered-subset
expectation maximization (OSEM) are currently available, and may improve lesion detection
accuracy.
3) Ensure that the entire brain volume is reconstructed.
4) Reconstruct data at the highest pixel resolution, i.e. one-pixel slice thickness.

32.  The normal distribution of lipophilic brain perfusion agents is proportional to
regional blood flow, with significantly greater activity seen in the cortical gray
matter.
 Activity is also high in the regions corresponding to subcortical gray matter, including the basal
ganglia and the thalamus.
 The primary purpose of SPECT imaging is to evaluate relative rCBF rather than structural
detail.
 The cerebral perfusion images should be inspected for symmetry of radiopharmaceutical
distribution and for continuity of perfusion in the rim of cortical gray matter.
 In general, local perfusion is measured as increased, similar, or decreased relative to the
perfusion in the identical area in the contralateral cerebral hemisphere.
 Pathologic processes that alter local brain perfusion produce areas of increased or decreased
activity, depending on the changes in blood flow relative to the normal adjacent brain tissue.

33. NORMAL SPECT

34. Tc-99m ECD brain perfusion SPECT (in transaxial, coronal ,sagittal section)

35. Tc-99m HMPAO