Download PET On-Cology physics

105th Annual Meeting of the American Roentgen Ray Society
Positron Emission Tomography:
A Practical Review of Clinical Applications
and a Self-examination
1
2
2
Neville Irani MD, Jorge Vidal MD, Natasha Acosta MD,
1
Mark Redick2 MD, Akash Sharma MD.
1
2
Allegheny General Hospital, Pittsburgh, PA
St. Luke’s Hospital of Kansas City/ UMKC, Kansas City, MO
St. Luke’s Hospital
of Kansas City
Radioactive Decay & Nuclear Imaging
Example
•
•
•
•
•
Isomeric transition
Alpha
Beta Beta + [positron]
Electron Capture
•
99mTc 99Tc+
•
18F 18O+++
Remember: In AX, A = atomic mass (# protons + neutrons)
Tc = Technetium [nuclear medicine workhorse]
U = Uranium
Th = Thorium
Pa = Protactinium
F = Fluorine [Most widely used PET Agent]
O = Oxygen
Kr = Krypton
Br = Bromine
Positron Basics
• A Positron is a positively charged
electron emitted during the decay
of a proton to a neutron in the
atom’s nucleus.
• During decay, the positron that
exits the nucleus encounters an
electron, usually within 2-16
millimeters. The subsequent
annihilation results in two
annihilation photons which travel
in 180° opposite directions.
PN

+ e-

Positron Radionuclides
Most positron emitters have high energy photons but short half-lives:
Positron Source
Half-Life (minutes)
Maximum Energy
20
960keV
N => 13C
9
1.19 MeV
O = > 15N
2
1.72 MeV
F = > 18O
110
640 keV
Ga = > 68Zn
68
1.89 MeV
1.3
3.35 MeV
11
C = > 11B
13
15
18
68
82
Rb = > 82Kr
Note: Mean photon energy for 18F is 511 keV.
Why 18Fluorine?
• Most positron emitters are created at a cyclotron facility. Up to
1-2 Curies of 18F are produced per cycle by bombarding 18O
with protons. Typical clinical patient dose is 10-20 mCi.
• An ideal PET agent should be available to the patient within 1
half life. 18Fluorine has a half-life of about 2 hours allowing
adequate time for transportation.
• For this reason, 18Fluorine tagged biologic compounds are the
most practical positron radiopharmaceuticals.
Radiopharmaceuticals
Radiopharmaceuticals are made by conjugating a radioactive
atom with a biologically active compound.
Bone scans, for example, are done with 99mTc conjugated with
MDP (99mTc - MDP).
• The most commonly used positron
radiopharmaceutical to date is 18F
conjugated with glucose to form
Fluoro-DeoxyGlucose [FDG]. 
How FDG Works
• Following injection, during the distribution phase (usually one
hour) cells take up and phosphorylate FDG. Non-phosphorylated
FDG is excreted by the kidneys.
• Phosphorylated FDG does not proceed to the next step in
glycolysis due to altered configuration (substitution of Fluorine
for a hydroxyl group).
• Malignant cells demonstrate a difference in accumulation due to
increased cell membrane transporters and underexpression of
glucose 6-phosphatase.
• This leads to a greater tumor to background uptake, thereby
differentiating malignant lesions from benign tissue.
18
Glucose
Glut Transporter
How FDG Works
C
E
L
L
Hexokinase
18
18
Glucose
Phosphotase
P
Glucose-6-
18
Glucose
Glut Transporter
Normal cells
M
E
M
B
R
A
N
E
Abnormal Cells
Hexokinase
18
18
Glucose-6-P
Glucose
Phosphotase
Common Indications
Medicare Approved:
• Solitary Pulmonary Nodule
• Melanoma
• Lymphoma
• Thyroid Cancer
• Colorectal Cancer
• Breast Cancer
• Lung cancer
• Alzheimer’s Dementia
• Head and Neck cancers
• Myocardial Viability
Not Yet Approved:
• Ovarian, GYN tumors
*Better than CT for Peritoneal carcinomatosis
• Testicular cancer
• Pancreatic cancer
Common Oncologic Applications
• Initial staging of biopsy proven cancer (prior to any
treatment)
• Restaging after irradiation, chemotherapy, or surgical
resection.
*Serves as an indicator of response to therapy -- some treatment protocols
base regimen changes upon SUV differences.
• Rarely, diagnosis of malignancy. e.g. indeterminate
solitary pulmonary nodule on CT scan
FDG-PET has Low Sensitivity for:
• Prostate Cancer [C-11 Acetate PET shows promise]
• Renal Cell Carcinoma
• Hepatocellular Carcinoma
• Mucinous carcinomas
• Neuroendocrine tumors [use MIBG instead]
• Bronchioalveolar carcinoma
• Teratoma or ovarian adenocarcinoma
• CNS neoplasms [due to high background uptake]*
• Villous adenomas
• Adrenal Adenomas
* PET is helpful in distinguishing scarring and necrosis from recurrent tumor following treatment.
Physiologic Uptake Seen in
– Brain
– Heart [non-fasting; during fasting fatty acids are preferentially used]
– Kidney [Unlike glucose, FDG is not reabsorbed in the proximal tubules]
– Liver
– Intestinal Mucosa [especially when loops are clustered together]
– Skeletal and smooth muscle (neck, larynx, diaphragm)
– Laryngeal muscle and muscles of mastication [esp. if pt is talking]
– Periareolar breast [esp. lactating breast]
– Thymus [in children]
– Bone Marrow [normally increased post-chemotherapy or following Colony
Stimulating Factor administration]
– Thyroid [in grave’s disease]
All have low intracellular glucose-6-phosphate  high glucose uptake and utilization.
Normal FDG Uptake
Larynx
Salivary Glands
Patchy Atrial uptake
Intestinal
Mucosa
Base of Tongue
Base of Brain
Left Ventricle
Ureter
Liver
Marrow Uptake
Bladder
Kidneys
Quantification of PET Data
• On CT, each pixel in the field of view represents a Hounsefield
unit (HU) of attenuation to x-ray transmission (water = 0 HU;
bone  1000 HU).
• On a PET image, each pixel represents the number of coincident
photons (> 480 keV) originating from FDG uptake at that
position.
• SUV is a ratio to compare relative uptake in a Volume of
Interest compared to expected background uptake.
Tissue _ Concentration(mCi / kg)
SUV 
Total _ Dose (mCi)
Patient _ Weight (kg)
Standardized Uptake Value (SUV)
• Initial studies using SUV were done in studying pulmonary
nodules led to an SUV of 2.5 as demarcation of benign from
malignant pulmonary lesions.
• Higher SUV in pulmonary lesion is an independent predictor
of poorer prognosis.
– Ahuja V, Coleman RE, Herndon J, Patz EF Jr. Cancer. 1998 Sep
1;83(5):918-24.
• It’s a good practice to report the maximum SUV in the ROI.
• Mean SUV is dependent upon the ROI and sensitivity is more
important in oncologic imaging.
Inter-examination SUV variation
(within the same patient) may be due to:
• Serum glucose level
– Hyperglycemic state will result in false negative scan
• Fasting vs. Non-fasting [affects cardiac uptake]
• Change in body fat [fat cells don’t take up FDG]
• Duration between injection and imaging
Non-malignant causes of FDG uptake
• Inflammatory changes
–
–
–
–
–
–
–
Inflammatory bowel disease [CRP is usually also elevated]
Reflux esophagitis & Gastritis
Active granulomatous disease
Pneumonitis
Radiation-induced inflammation
Conjunctivitis
Degenerative joint disease
• Post-Exercise increased muscle uptake
• Hyperinsulinemia (increased muscle uptake)
Fasting = Less Cardiac Uptake
Gastritis, Inflammatory Hilar Nodes
Normal Patchy atrial Uptake;
This patient was likely not fasting
*Usually it is difficult to differentiate physiologic vs inflammatory uptake on PET alone
Image Acquisition
• The diagnostic images shown so far are processed by applying
attenuation correction.
• Fewer photons from deeper body structures are detected due
to attenuation from surrounding tissue prior to registration on
the crystal surface.
• Transmission images are, therefore, acquired with an emission
source such as 137CS (662keV), 68Ge or a CT scanner’s x-ray
source.
• The amount of attenuation in the transmission images at a
given position is then used to correct the emission image and
produce the attenuation corrected image.
Image Construction
Emission
*Non-attenutation corrected
[NAC]
Transmission
Attenuation
corrected
[AC]
Clinical Value of emission images
• Occasionally lesions in liver can be masked by heterogeneity
from attenuation correction. Small lung lesions may be
missed due to smoothing effect of correction.
• Improper correction can result from metallic implants and
retained bowel contrast causing pseudo-hot spots to appear
on attenuation correction images. This occurs mostly when
using CT transmission attenuation data for attenuationcorrection.
Attenuation Correction
Attenuation
Corrected
[AC]
Emission
Image
Liver metastasis is more apparent on emission image
Acquisition - Transmission Imaging
Field Of View
Transmission Image Example
Photon source
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0
Imaging in one plane with triangular phantom gives relative attenuation
Transmission Image Example
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Source
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Imaging in perpendicular plane with same phantom
Composite Summation Image
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Complete ring or circular detector will do this in more than just
two directions resulting in better resolution and sharper image
Emission Coincidence Detection
• The positron emitted from the Fluorine nucleus only travels
a short distance before annihilating with an electron and
producing two equal energy (511 keV) photons which travel
in exact 180° opposite directions.
• Conicidence detection distinguishes photons from a true
events at a site somewhere along a line between two
detectors located directly opposite each other in the ring
from scatter photons. Less than 1% of photons included in
making the image will be due to scatter if you use this
method to ‘screen the photons’.
Photon Coincidence
Coincidence Detection in Field of View
Detector Signals
Represents true event
Represents Scatter
Coincident photon energies at each detector can be put into a
matrix similar to the transmission data to construct an
intensity-weighted image
*Minimum photon energy allowable for inclusion by detector is about 480 keV
Ideal Detection System
• Dedicated PET scanner
– (full ring of gamma detectors).
• Best resolution: 3-7 mm
– depends on total number of
detectors
• Scatter photons included in
image only 1% of time
Image courtesy of http://tezpur.keck.waisman.wisc.edu/ PET.html
Cheaper Alternative for PET Imaging
• Coincidence SPECT
system
– Incomplete detection ring
• Cheapest solution but
resolution is only 5-10
mm
• Wastes many photons;
longer scan time or higher
dose required than
dedicated PET
Another SPECT Modification
• Modified SPECT
– High Energy NaI collimator for
511 keV
• Photons are imaged without
coincidence counting
• High photon attenuation;
poor resolution (15-30 mm)
• Longer acquisition time than
dedicated PET
Patient Exposure: Effective Biological t1/2
Effective_ T1/ 2
Bio log ic  Physical

Bio log ic  Physical
• Typical PET examination is done with 10-20 mCi
of FDG.
• Increasing starting counts to compensate for poor
photon detection with modified SPECT systems
will increase patient exposure.
• In general, modified SPECT systems should be
avoided.
Fusion of 3D Imaging Modalities
Self-Examination
• The following ten cases review most of the
concepts we have covered.
• These cases also demonstrate the variety of
display methods possible to display PET
images: color vs. grayscale, sequential multiplanar images vs. multi-planar maximum
intensity projection [MIP].
Fusion of 3D Imaging Modalities
Case 1
• Patient with lymphoma
• Pre and post-treatment PET scan,
multi-planar images at same level.
• PET used to determine whether to change
current regimen - 5 months elapsed between
pre and post-treatment imaging.
Effective treatment regimen
Pre-Rx
Resolution of mediastinal &
retroperitoneal lymphadenopathy
Normal bowel Uptake
Post-Rx
Normal Penile Uptake
Fusion of 3D Imaging Modalities
Case 2
• Solitary pulmonary nodule on CT
-- evaluate for malignancy.
Most Likely Benign SPN
CT
PET MIP
No lung uptake; this lesion was a hamartoma. Keep in mind that
some malignant lesions can have false negative PET...
Fusion of 3D Imaging Modalities
Case 3
• Unresolved ‘pneumonia’ x 6 months
Broncho-Alveolar Cell Carcinoma
CT
PET MIP
PET has poor sensitivity for BAC and is often falsely negative! This one
just happened to have enough FDG avidity to be detected.
Don’t forget the serendipitous findings. This patient has hydronephrosis.
Case 4
Fusion of 3D Imaging Modalities
• Cough and hemoptysis
Selected MIP images from PET
FDG avid Nodule
Brown Fat Physiology
Brown Fat and LUL Mass
• LUL mass with SUV 2.1, concerning for malignancy.
Infectious process is also possible.
• Extensive uptake in the paraspinous and supraclavicular
regions noted bilaterally consistent with activation of
brown fat. Brown fat is activated to generate heat (such
as when the patient is shivering). Glucose is required to
fuel this process. Increased muscle activity is usually
also seen in cold or tense patients and part of the
increased paraspinal uptake may also be due to
paraspinal muscle activity.
Case 5
Fusion of 3D Imaging Modalities
• Patient had CT showing a lung mass.
Assess for malignancy
CT Chest
Fusion of 3D Imaging Modalities
Continued
PET Done 1 Month Later
Fusion of 3D Imaging Modalities
Malignancy in larynx (note asymmetry on CT), lung (biopsy proven
small-cell carcinoma), and mid-retro-peritoneum (not appreciable
on prior CT).
Case 6
Fusion of 3D Imaging Modalities
• Patient post right hemicolectomy for cancer
presents with retroperitoneal stranding on
CT- hemorrhage or metastatic tumor?
• Proposed chemotherapy is contraindicated in
a patient with active hemorrhage.
• PET and CT Images were fused to better
correlate functional and anatomic findings
(Software-based) PET-CT Fusion
High uptake – Recurrent tumor much more likely than Hemorrhage
Fusion of 3D Imaging Modalities
Case 7
• Patient with lung cancer to undergo radiation
treatment.
• Planning CT shows RLL atelectasis -- can’t
exclude tumor in this region.
• PET recommended to determine whether to
include this portion of lung as well within
radiation portal.
(Software-based) PET-CT Fusion
Continued
Avid uptake at hilar mass superior to atelectasis
(Software-based) PET-CT Fusion
Non-FDG avid RLL = no significant tumor. Do not irradiate this region
Case 8
• Initial staging for biopsy proven colon
cancer.
• Simultaneous acquisition PET, CT, and
fusion imaging provided.
Coronal PET MIP Images
Metastatic focus?
Continued
AC
NAC [emission]
Courtesy of Barry A Siegel, M.D. -- Mallinckrodt Institute of Radiology, St. Louis, MO.
PET
Fused PET-CT
CT
Barium
Courtesy of Barry A Siegel, M.D. -- Mallinckrodt Institute of Radiology, St. Louis, MO.
CT Attenuation Correction Artifact
• The apparent metastatic focus is an over-correction artifact
due to residual barium in the patient’s colon.
• This artifact is a product of an error in most algorithms
using CT transmission attenuation data to correct PET
emission images.
• The heavier density of barium is not accounted for by the
lower density value assignment for bone (usually the highest
preset value in Hounsfield range on CT) which results in the
over-correction..
Case 9
• 61 yo for colorectal restaging
• CT shows a large low attenuation lesion in
the liver. Evaluate for metastatic disease.
• Software fusion of CT/PET provided.
61 yo for CRC Restaging
Continued
Fusion of 3D Imaging Modalities
61 yo for restaging
• Fusion with CT image shows the photopenic area to
match the low attenuation lesion.
• PET shows low FDG uptake in this region; unlikely
to be a metastatic deposit -- pattern is compatible
with large hepatic cyst.
• If the border of this lesion on PET showed high
activity the differential would be abscess,
hematoma, or large centrally necrotic tumor.
Fusion of 3D Imaging Modalities
Case 10
• Patient with glioblastoma with abnormal
signal on MR close to site of previous tumor
• Is this post-surgical scar or tumor?
• Software MR/PET fusion provided
Fusion of 3D Imaging Modalities
PET of Whole Brain
Uptake next
to prior resection
Notice diminished uptake in right cortex due to resection / necrosis
Fusion of 3D Imaging Modalities
MR fusion with PET
Recurrent tumor
Fusion vs simultaneous acquisition
• Simultaneous acquisiton of PET
and CT images avoids
– Interval change in lesion if
enough time passes between
acquisitions
– Gross Software misregistration
• Transmission data can be acquired
with CT portion of scan = reduced
scan time
• Decreases artifacts due to
differences in patient positioning
Future of PET imaging …
Other (target-specific) radiopharmaceuticals
• Ammonia (13NH3) imaging for cardiac
lesions.
• Na18F for bone scans for non-FDG avid
metastatic disease.
• 11C acetate for prostate cancer.
Ammonia PET -- Dilated Cardiomyopathy
Normal NaF bone scan using PET…
• Gives higher resolution compared to Technetium bone scans.
Thank You
• We hope you enjoyed this basic tutorial on
PET imaging.
• Any comments are welcome at:
– nirani @ wpahs.org
– vidalja@ umkc.edu
References
• Mettler FA Jr., Guiberteau MJ. Essentials of Nuclear Medicine. 4th ed.
W.B. Saunders Company, 1998.
• Ruhlmann J, Oehr P, Biersack HJ (eds.). PET in Oncology Basics and
Clinical Applications. Springer-Verlag, 1999.
• Delbeke D, Martin WH, Patton JA, Sandler MP (eds.). Practical FDG
Imaging: A Teaching File. Springer-Verlag, 2002.