The agent used for perfusion imaging is Tc-99m
macroaggregated albumin (Tc-99m MAA). Particle size is
generally between 10 to 90 microns (90% of particles) and no
particles should be larger than 150 microns. Tc-99m MAA is
injected slowly IV and lodges in percapillary arterioles,
obstructing approximately 0.1% of their total number. The
particles clear by enzymatic hydrolysis and are phagocytized by RE
cells (the agent has a biologic half-life in the lungs of between
6-8 hours). Normally, only 3 to 6% of the injected Tc-99m MAA will
bypass the pulmonary vasculature. The critical organ is the lungs
which receive a dose of about 1 rad (1 cGy) from a typical 5 mCi
dose. The kidneys and bladder receive moderate exposure largely
from the excretion of degraded albumin. For pediatric patients,
the dose is 0.03 mCi/kg .
A 5 mCi dose usually contains on average 500,000 . The
arterioles are only temporarily occluded because the material
degrades into smaller particles which are eventually phagocytized
by cells of the reticuloendothelial system . The biological
half-life of MAA in the lungs is about 6 to 8 hours . The
number of particles used for the exam should be reduced to about
100,000 in patients with pulmonary arterial hypertension, and in
those with known right to left shunts. To label a smaller number
of particles while maintaining the dose of Tc-99m, the vial should
be reconstituted with a larger amount of activity. A given number
of mCi then represents a smaller portion of the total vial, and
thus contains fewer particles. A minimum of 70,000 particles is
necessary to obtain a diagnostic quality scan in an adult. It is
estimated that neonates have about 10% of the eventual number of
adult pulmonary capillaries. In neonates, the number of particles
should be reduced to between 10,000 to 50,000 to maintain an
adequate margin of safety. The number of capillaries increases to
half of the adult value by age 3 years, and reaches an adult level
by age 8 to 12 years. A dose should be administered only if the
preparation is less than 6 hours old. This is because Tc-99m MAA
tends to aggregate and Tc-99m slowly dissociates from Tc-99m MAA
over time. Also, decay of the radiopharmaceutical over time
results in the need for a larger volume (and hence greater number
of particles) to obtain the same dose. For imaging, a large field
of view camera with a parallel hole, high-resolution collimator
should be used. Images should contain at least 750,000 counts.
Xenon-133 (Beta-minus decay):
Xe-133 is a fission product of U-235. It has a physical half-life
of 5.24 days and a low energy gamma emission (81keV) that will be
rapidly attenuated by overlying tissue; therefore, scanning is
performed posteriorly. The typical dose used for the exam is 15-25
mCi, most commonly inhaled, but can be administered in saline IV.
The critical organ is the trachea and airways which receive about
100 mrad/mCi/liter/min (total dose to the trachea is approximately
28 mrad from inhalation and 11 mrad following IV injection [R]). Less than 15% of the dose
is absorbed by the body. The Xe-133 ventilation scan is generally
performed prior to the Tc-99m MAA perfusion exam, as downscatter
from the Tc-99m would severely degrade image quality. Some centers
perform the Xenon exam after the perfusion study by administering
a very low dose (1-2 mCi) of Tc-99m MAA and a much higher dose of
Xenon-133 (20-30 mCi). A narrow window setting (10%) on the
Xenon-133 gamma energy is also applied to reduce the contribution
from scatter. Images can then be obtained in the projection which
best demonstrates the perfusion defects.
Computer subtraction techniques have been developed to correct
for Tc-99m scatter in the Xenon-133 energy window, but the method
is difficult to apply and not routinely used.
The gamma camera is placed behind the patient's back and a bolus
of 15-20 mCi of Xe133 is injected into the mouthpiece of the
spirometer system at a time when the patient begins maximal
inspiration . The xenon exam consists of 3 phases:
- Single breath: The patient takes a single deep inspiration and
holds it for as long as possible. This view reflects regional
ventilation and can detect approximately 66% of ventilation
defects associated with obstructive airway disease.
- Equilibrium: During this phase, the patient performs normal
tidal respirations for at least 3 minutes, and 5 minutes
if possible, while rebreathing a mixture of Xenon-133 and
oxygen. This view demonstrates the overall lung volume as tracer
equilibrates between all aerated portions of the lungs. It is
the least sensitive for detecting obstructive airway
abnormalities. However, adequate duration of rebreathing ensures
diagnostic quality washout phase.
- Washout: Inhalation of Xenon-133 is discontinued and the
patient breaths room air or oxygen while exhaling the xenon into
a charcoal trap. Xenon-133 should clear from the lungs normally
in 2-3 minutes. Retention of tracer activity beyond 3 minutes is
observed in areas of air trapping (obstructive airway disease).
The washout phase of the exam will detect about 90% of
abnormalities associated with obstructive airway disease (it is
the phase of the exam that is most likely to show ventilation
abnormalities ). It is therefore more sensitive than the
single breath view in this regard. Posterior oblique views may
also be obtained to improve spatial localization of lung zones
with slow washout . Xenon is overall more sensitive than
aerosolized Tc-DTPA for detecting obstructive lung disease.
Xenon 127 (Electron capture):
Xe-127 is cyclotron produced and has a longer physical half-life
(36.4 days) than Xe-133. Its gamma emissions: 172 keV (25%), *203
keV (68%), and 375 keV (18%) are of higher energy than 140 keV
emission of Tc99m. It can be used post-perfusion to evaluate
specific defects. The higher photon energies require the use of a
medium or high energy collimator. Additionally, the xenon trap
system must be more heavily shielded and stored for a considerably
longer period of time prior to adequate decay for disposal.
Tc-99m DTPA Aerosol:
Using an aerosol delivery system that generates submicronic
particles, 30 mCi of Tc-DTPA in 3ml of saline (3 to 5 minutes of
rebreathing on the system with the oxygen at 8 to 10 liters/min.)
delivers about 500 to 750 uCi of tracer to the lungs . This
dose yields 100K counts images in about 2 minutes on a standard
gamma camera with a low energy general purpose collimator . The
typical radiation exposure to the lungs is about 100 mrads. This
is less than the several hundred millirad exposure from a typical
Xe133 rebreathing ventilation exam. The dose to the lungs is also
less than that from a Kr-81 exam . Images should be acquired
for 100k counts or 5 minutes. Exposure to personnel is usually
less than that delivered during a Xenon study. The count rate of
the Tc-MAA activity (measured as counts per minute) in the
perfusion portion of the exam must be at least four times the
count rate of the acitvity in the ventilation portion of the study
. Verification of the count rates allows detection of an
inadequate number of injected Tc-MAA particles- which can occur
due to extravasation of the injected dose .
Nebulizers produce particles that are generally between 0.5 to 2
microns in diameter . Because of their small size, these
particles can be delivered to the alveoli like gases during
inhalation. Deposition of particles larger than 1 micron in the
tracheobronchial tree is influenced primarily by inertial
impaction and gravitational sedimentation. Even larger particles
will deposit more proximal in the airways. Benefits of this
procedure are that collection devices are not necessary as they
are for radioactive gases, and persistence of activity in the
lungs permits images in multiple projections to be obtained.
Disadvantages are the inability to demonstrate areas of air
trapping and excessive tracer is often seen in the proximal
bronchial tree in patients with obstructive airway disease due to
turbulent airflow. Tachypneic patients also tend to have prominent
central deposition of the tracer.
Radioaerosol imaging studies can be performed in patients on
ventilator assistance, but to avoid central tracer deposition from
turbulent air flow, the ventilator should be set to the lowest
peak flow rate possible and it is best to turn off PEEP during the
inhalation portion of the study. Nonetheless, the correlation
between regional ventilation and aerosol deposition is poor in
ventilated patients and better definition of ventilated segments
can be obtained by using a gas .
The ventilation portion of the exam may be performed before or
after the perfusion study. If it is done after the Tc-99m MAA
exam, the dose placed in the nebulizer should be increased to 45
mCi (or more) and the inhalation of the aerosol should continue
until the count rate obtained is 3 times the count rate of a
posterior Tc-99m MAA image in order to overwhelm the activity
present in the lungs (perfusion defects will "fill-in" with
activity in areas of pulmonary embolism). Most authorities,
however, believe that Tc-DTPA aerosol images should be obtained before
the Tc-99m MAA exam.
Over time, aerosolized Tc-DTPA crosses the alveolar-capillary
membrane and enters the bloodstream where it is then filtered by
the kidneys and excreted. The critical organ is the urinary
bladder. In normal patients, the pulmonary clearance of Tc-DTPA
has a half-time of over 60 minutes (1 to 1.5 hours). The
disappearance rate from the lungs has been found to be more rapid
in patients with pulmonary embolism (affected lung segments
primarily), lung injury (ARDS), pulmonary
fibrosis, and in smokers (as rapid as 20 minutes).
Aerosolized Tc-PYP has a significantly slower clearance rate than
Tc-DTPA in both smokers and non-smokers.
Tc04 is vaporized in a microfurnace to produce
ultrafine labeled carbon particles (hexagonal platelets of
metallic technetium each encapsulated within a thin layer of
graphite carbon ). The material is produced by heating 5mCi of
Tc-pertechnetate to very high temperatures (2500 degrees Celsius)
in a crucible in the presence of 100% argon gas. A soot or ash
material is produced which is thought to be a Tc-carbon particle
that is so small it acts like a gas . The median size of the
technegas particles is between 0.05 and 0.15 microns (others
report 30-60 nm [11,14]), and there is good peripheral deposition
even in patients with COPD. Since the material is produced in
argon, inhalation may cause transient hypoxemia; this can be
overcome by giving oxygen via nasal canula. No severe adverse
reactions have been reported to date. There is longer pulmonary
retention of Technegas with no effective clearance (the clearance
half-time is 6 hours- the physical half-life of Tc-99m). Since the
material produced is not filtered and contains up to 50% of the
initial radioactivity, a large number of appropriately sized
particles are inhaled with each breath. Thus, only a few
inspirations (typically 2 to 10) are needed to reach an adequate
dose. Usually about 1 mCi is deposited in the lung. Extrapulmonary
activity in the oropharynx, trachea, and stomach can be seen in
about 30% of patients. The exam may be technically inadequate in
up to 15% of patients - particularly in severely ill patients
that cannot be instructed for inhalation, or in patients with very
shallow or rapid breathing . However, for SPECT perfusion
imaging, Technegas has a more homogeneous tracer distribution
compared to DTPA, partciularly in patients with obstructive
airways disease .
If the Technegas portion of the exam is performed following the
perfusion study, a counting rate of at least two times the count
rate of the perfusion exam is considered adequate . Remember,
if the inhaled activity is insufficient, the perfusion
distribution will continue to dominate the final images .
If the reaction is produced in an atmosphere which contains 2 to
5% oxygen, a different agent is produced called `Pertechnegas,'
which is a vapor of pertechnetate. This agent also demonstrates
excellent distribution in the lungs, but it is absorbed relatively
rapidly (half time clearance from the lungs is 7 to 10 minutes
), and repeat administration of the agent may be necessary
during the exam.
Krypton-81m (Isomeric transition):
Produced from a Rubidium Krypton-81m generator. Krypton-81m
decays by isomeric transition, with a gamma emission of 191 keV
(65%), and a physical half-life of only 13 seconds . Because it
is not a nuclear byproduct material and it decays so rapidly to
relatively stable Krypton-81, Krypton-81m is not considered an
environmental hazard and storage/collecting devices are not
necessary. As the energy is higher than Tc-99m, and the physical
half-life is so short, ventilation images are usually recorded
immediately after each perfusion view without moving the patient.
This provides an exact comparison of ventilation and perfusion.
Regions of abnormal ventilation are scintigraphically portrayed as
areas of diminished or absent activity. In effect, the radioactive
gas decays before it reaches the small airspaces of poorly
ventilated regions. Because physical decay occurs before an
equilibrium distribution can be attained, washout information
regarding obstructive lung disease cannot be obtained and some
zones of mild obstructive disease may not be detected. The
radiation dose to the lungs is significantly lower than with other
agents (about 15 mrad per view). Because the parent isotope
Rubidium 81m has a physical half-life of about 4.5 hours, the use
of the generator is usually 1 working day which makes it
impractical for most clinical situations.
Modifications to the V/Q exam:
Decreased Particle Count:
A decreased number of particles (approximately 100,000) should be
used when performing perfusion imaging in some patients:
1- Severe pulmonary hypertension:
These patients have a limited pulmonary vascular reserve, and
acute right heart failure may occur. Death has been reported in
these patients immediately following injection of a standard
dose of particles.
2- Right to Left shunt:
Will see immediate renal activity. May produce symptoms due to
lodging of particles in the cerebral/coronary circulations.
3- Surgically absent lung (s/p pneumonectomy)
4- Patients with poor respiratory function:
Intubated ICU patient with cardiopulmonary instability.
5- Pediatric patients:
Etiologies of V/Q Mismatch:
* Pulmonary Embolism (thrombotic, septic, air, etc.):
Acute or Chronic. Note: Fat emboli typically produce a mottled
appearance to the scan due to the presence of many small fat
* Pleural effusion/Atelectasis: More typically, atelectasis
produces a ventilatory abnormality that demonstrates normal or
minimally reduced perfusion.
* Tumor/Hilar adenopathy: Bronchi are more resistant to
extrinsic compression than are the pulmonary arteries because of
their rigid cartilaginous rings.
* Vasculitis/Radiation Treatment: Can reduce regional lung
perfusion. Radiation treatment results in obliteration of the
microvasculature. Perfusion defects from radiation are usually
geometric and follow the treatment port. They are typically
non-segmental. Ventilation may also be reduced in the irradiated
area, but it is usually less affected than perfusion.
* Pulmonary artery atresia or hypoplasia. Segmental or branch
pulmonary artery stenosis.
* Fibrosing mediastinitis can lead to central vascular
* AVM: Short circuits delivery of the particulate tracer to the
regional pulmonary precapillary arterioles.
* CHF: Multiple non-segmental perfusion defects can be seen.
* Pulmonary artery sarcoma.
* Intravenous drug use: Can see bizarre perfusion patterns
resulting from embolization of materials such as talc. Multiple
small defects are most commonly seen, but larger defects may be
noted and can occur in the absence of ventilatory abnormalities.
Etiologies of a
heterogeneous perfusion pattern:
(Many small and medium sized defects scattered throughout both
* CHF: May be characterized by diffuse or scattered
non-segmental perfusion defects. Typically there is
redistribution with reversal of the normal perfusion gradien;
i.e.. upper lobes better perfused than lower lobes in an upright
patient. A fissure sign refers to an oblique linear area of
decreased perfusion due to pleural fluid tracking in the
* Lymphangitic carcinomatosis: Hematogenous microemboli which
grow from the capillaries into the lymphatics. Contour
Mapping in lymphangitic carcinomatosis appears as linear
defects outlining the margins of the bronchopulmonary segments.
* Non-thrombogenic emboli: Fat, Septic, Amniotic Fluid.
* Chronic Interstitial Lung Disease.
* Primary Pulmonary Hypertension : A characteristic
"mottled" perfusion pattern consisting of multiple non-segmental
perfusion defects with a normal ventilation exam has been
described in patients with primary pulmonary hypertension (PPH)
. The pattern is thought to be secondary to vasoconstrictive
occlusion of small pulmonary arteries . The degree of
heterogeneity to the perfusion pattern correlates with the
clinical severity of PPH .
Unilateral decreased perfusion (or predominantly decrease
unilateral perfusion) can be seen in 2% to 6% of V/Q scans [1,3].
* Pulmonary embolism: Thromboembolism as a cause of unilateral
decreased pulmonary perfusion was previously felt to be
uncommon. Unilateral decreased perfusion can be secondary to PE
in up to 23% of cases . Generally perfusion defects are noted
in the opposite lung as well. However, chronic PE has been shown
to be the etiology for unilateral hypoperfusion in up to 67% of
* Pulmonary agenesis: There will also be absent ventilation and
the CXR will show a small, opaque hemithorax.
* Hypoplastic lung (Pulmonary artery atresia): There is usually
ventilation to a small lung which demonstrates no evidence of
perfusion. On CXR the involved lung is usually small,
hyperlucent, and contains few normal pulmonary markings [Miller,
* Swyer-James Syndrome: Characterized by bronchial destruction.
Ventilation images with Xenon-133 reveal decreased wash-in and
delayed clearance of the tracer on the involved side. Images
acquired with Krypton-81m generally demonstrate absent
ventilation. Perfusion will typically be decreased and
inhomogeneous, but may be severely reduced and nearly
inapparent. In general, however, the disorder produces a more
severe impairment of ventilation than of perfusion in the
* Massive pleural effusion
* Tumor/Mediastinal mass: A central mass can compress or
occlude the pulmonary artery resulting in absent perfusion.
Endobronchial obstruction can produce hypoxic vasoconstriction.
* Pulmonary artery sarcoma
* Aortic dissection: Results in unilateral right lung absent
perfusion due to direct compression of the right pulmonary
artery by the intramural hemorrhage within the adjacent
* Fibrosing mediastinitis: Vessels (soft walls) will be
occluded by the progressive fibrosis prior to occlusion of the
bronchi (cartilagenous walls)
* Shunt procedures for congenital heart disease
* Lung transplantation with non-perfusion of the native
Artifacts on V/Q scintigraphy:
* "Hot Spots": Occur due to injection of blood clots which
inadvertently formed in the syringe.
* Effusions: If the patient is scanned supine, effusions may
collect posteriorly/superiorly and mimic a defect due to
* Liver uptake on ventilation images: Xenon is fat soluble (and
somewhat soluble in blood) and it may be deposited in the liver-
especially when there is fatty infiltration. Increased RUQ
activity should not be mistaken for RLL trapping.
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