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.
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
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: 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.
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 ), 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
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
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 emboli.
* 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
* Fibrosing mediastinitis can lead to central vascular obstruction.
* AVM: Short circuits delivery of the particulate tracer to the regional pulmonary
* 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
(Many small and medium sized defects scattered throughout both lungs.)
* 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 cases .
* 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, p.68].
* 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 affected lung.
* 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
* 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 (diseased) lung
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 attenuation.
* 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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