Nuclear Imaging Flashcards
Basic positron emission tomography (PET) physics
A positron emission tomography (PET) radiotracer emits a positron that that travels a small local distance within the tissue. After meeting an electron, both the positron and elctron annihilate and create two 511 keV photons traveling nearly 180 degrees apart.
The two high-energy photons travelling in opposite directions are simultaneously detected by a circular crystal, which can determine that the two photons arrived coincidentally.
Radiotracer: Fluorine-18 FDG
Fluorine-18 (F-18) is a positron emitter, half-life 110 minutes. F-18-fluorodeoxyglucose (F-18 FDG) is a glucse analog that competes with glucose for transport into cells by the GLUT 1 and 3 transporters. After becoming phosphorylated by hexokinase, FDG-phosphate cannot undergo glycolysis and is effectively trapped in cells.
Radiotracer uptake quantification
The standardized uptake value (SUV) roughly quantifies FDG uptake.
SUV is proportional to (ROI activity * body weight) / administered activity.
SUV of a region of interest can vary significantly depending on numerous factors including specific equipment, time elapsed since FDG admministered, amount of tracer extravasation, muscle uptake, glucose and insulin levels at time of injection, etc.
Malignancy can never be definitively diagnosed or excuded using SUV as the sole criterion.
A preferred approach to absolute SUV values is to use a ratio of background lvier, cerebellum, or basal ganglia to compare with a region of interest. For instance, using the basal ganglia uptake as a baseline, relative SUV of a region of interest <20% is “mild”; 20-60% is “moderate”; and >60% is “intense” uptake.
CT correlation (PET)
Most modern PET exams are performed together with a CT as a PET-CT. One important exception is in the pediatric population to reduce the risk of radiation exposure from CT.
The CT exam is often performed with a lower dose than a diagnostic-quality CT. The CT protocol varies by institution (e.g., whether intravenous contrast is administered).
The CT is used for anatomic localization and attenuation correction.
Very dense retained oral contrast (or dense metallic objects such as joint prostheses) may cause artifacts of FDG uptake due to miscalculation of attenuation correction.
Patient Preparation (PET)
The uptake of FDG in both normal and pathological tissues is dependent on the serum glucose and insulin levels.
Elevated insulin levels will cause increased muscle uptake and decreased sensitivity for detecting mildly PET-avid lesions.
Patients should be NPO for at least four hours to allow insulin to reach a basal level.
Blood glucose should be below 200 mg/dL, preferably below 150.
After injection of F-18 FDG, the patient should rest in a quiet room for 60 minutes. If the patient talks, the vocal cords may show FDG uptake. If the patient walks, the muscles may show FDG uptake.
Normal FDG distribution
Brain: The brain has intense FDG uptake. Brains love sugar. Despite instense uptake, with appropriate windowing, excellent detail of the cortex, basal ganglia, and cerebellum can be seen.
Kidneys, ureters, and bladder: FDG is concentrated in the urine, with very intense uptake in the renal collecting system, ureters, adn bladder.
Salivary glands, tonsils, thyroid: Mild to moderate symmetric uptake.
Liver: the liver is moderately FDG avid and typically shows inhomogenous uptake.
Bowel: Diffuse mild to moderate uptake is normal. Focal uptake within the bowel, however, should be regarded with suspicion. Note that metformin can increase colonic, and to a lesser extent, small bowel FDG uptake.
Heart: Uptake is totally variable, depending on insulin/glucose levels. The heart perfers fatty acids but will use glucose if available.
Muscles: FDG uptake is normally low. However, elevated insulin levels or recent exercise can cause increased muscle uptake. Brown fat: Brown fat is metabolically active adipose tissue typically found in the supraclavicular region and intercostal spaces that can be mild to moderately FDG avid, especially if the patient is cold.
Lung cancer
PET-CT plays a role both in the initial staging of patients with lung cancer, and in evaluating response to treatment. Typically, only non small-cell lung cancer is evaluated by PET as small-cell is considered to be metastatic at diagnosis.
For initial staging, PET-CT is most useful to evaluate local tumor extension and to search for distant metastases. Approximately 10% of patients with a negative metastaic workup by CT will have PET evidence of metastasis.
PET is very sensitive for detecting malignant lymph nodes; however, it is not specific. A negative PET would allow allow for surgery to proceed without further testing. Mediastinoscopy is the gold standard for lymph node staging. Given the lack of PET specificity, PET-positive mediastinal nodes must be followed by mediastinoscopy before potentially curative surgery is denied based solely on the PET.
Solitary pulmonary nodule (SPN)
Evaluation of a suspicious solitary pulmonary nodue (SPN) is an indication for PET-CT.
8 mm is typically the smallest size nodule that can be reliably evaluated by PET.
The majority of malignant SPNs are FDG avid. However, low-grade tumors such as bronchoalveolar cell carcinoma or carcinoid may not be metabolically active and may be falsely negative on PET.
Conversely, the majority of benign SPNs are not FDG avid. However, active granulomatous disease (including tuberculosis) may take up FDG and represent a false positive on PET.
It is never possible to definitively diagnose a nodule as benign or malignant based on SUV.
In general, if a nodule is not FDG avid, short-term follow-up is reasonable. If the nodule is FDG avid then biopsy or resection is preferred.
Colon cancer
PET-CT has a limited role in determining local extent of colon cancer due to poor spatial resolution and physiologic bowel uptake, but PET-CT does play a primary role in evaluating metastatic disease in colorectal malignancies. In particular, since isolated hepatic metastases can be resected or ablated, evaluation for extrahepatic metastases is a common indication for PET-CT.
After initial treatment, follow-up PET-CT is usually delayed approximately 2 months due to a flare phenomenon of increased FDG uptake in the peritreatment period.
Head and neck cancer
PET-CT is often used in the initial staging of head and neck squamous cell carcinoma, especially for evaluation of regional nodal metastases.
Specificity for evaluating recurrent disease after chemoradiation is limited due to altered anatomy and inflammation from treatment. Usually post-treatment scans should be delayed 4 months after treatment to minimize these effects.
Thyroid cancer
Undifferentiated or medullary thyroid cancers may not take up radioiodine but may be FDG avid. PET-CT is used in the clinical setting of a rising thyroglobulin level with negative whole-body radioiodine scans.
Lymphoma
PET-CT plays a role in the staging and restaging of patients with lymphoma.
Most histological types of lymphomas, including Hodgkin and non-Hodgkin lymphoma, are FDG avid. Some low-grade lymphomas, such as small lymphocytic and mantel cell tend to be less FDG avid, however.
Increased marrow uptake in lymphoma patients can be difficult to interpret. Diffuse marrow uptake may be due to granulocyte colony-stimulating factor (G-CSF) stimulation, rebound effect from chemotherapy, or malignant marrow infiltration. Focal increased uptake, however, is more likely to represent lymphoma.
Breast cancer
Although used in the staging and response to therapy of recurrent or stage IV breast cancer, PET-CT is not routinely used for patients with stage I-III breast cancer.
Esophageal cancer
The primary role of PET-CT in the initial evaluation of patients with esophageal cancer is to identify those with stage IV disease who are not surgical candidates.
After initial neoadjuvant treatment, a decrease in FDG avidity by at least 30% suggests a more favorable prognosis. In contrast, those patients who do not show a decrease in SUV values can potentially be spared ineffective chemotherapy regimens.
Hepatocellular carcinoma (HCC)
Only 50% of hepatocellular carcinoma (HCC) can be imaged with FDG PET due to high levels of phosphatase, which dephosphorylates FDG and allows it to diffuse out of cells.
Renal cell carcinoma (RCC) and bladder cancer
Only 50% of renal cell carcinomas are FDG avid, although PET may play a role in detecting metastatic disease.
Detection of ureteral or bladder lesions is extremely limited due to surrounding high urne FDG uptake.
Prostate cancer
FDG PET is not used for evaluation of prostate cancer. Recently, carbon-11 choline PET has been FDA approved for imaging prostate cancer, but is not yet in widespread use.
Perfusion imaging overview
Left ventricular perfusion imaging evaluates the blood flow to the myocardium.
If a perfusion abnormality is present, the following five questions help to characterize the perfusion abnormality: Is the perfusion abnormality reversible during rest, or is the defect fixed at both stress and rest. How large is it: Small, medium, or large? How severe is it: Mild (subendocardial), moderate, or severe (transmural)? Where is it: In which coronary artery territory? Are there any associated abnormalities, such as right ventricular uptake, ischemic dilation, or wall motion abnormalities?
Each perfusion test has two components: An element of stress, and a method of imaging. The stress component can be physical (treadmill), pharmacologic-adrenergic (dobutamine), or pharmacologic-vasodilatory (dipyridamole or adenosine).
All perfusion imaging commonly performed uses radionuclides with SPECT imaging. Some protocols include gated SPECT (GSPEC) as well. Other types of stress tests performed by cardiologists (EKG stress tests and echocardiographic stress tests) can be performed in lieu of imaging. These non-imaging tests can only detect secondary signs of perfusion abnormalities, such as ischemic EKG chages or wall motion abnormalities.
Clinical applications of myocardial perfusion imaging
There are several clinical indications for myocardial perfusion imaging.
Evaluation of acute chest pain. Myocardial perfusion imaging is often the gatekeeper to further cardiac workup in patients where there is clinical ambiguity for cardiac ischemia (e.g. chest pain wtih negative EKG and troponins). A negative myocardial perfusion exam allows safe discharge. A normal myocardial perfusion exam is associated with an annual rate of a cardiac event of 0.6% even among patients with a high pretest likelihood of coronary artery disease.
Evaluation of hemodynamic significance of coronary stenosis. Even with a coronary artery stenosis seen on angiography or CT, patients with a normal nuclear cardiac perfusion exam have a relatively low risk for cardiac events.
Risk stratification after MI. Findings that would classify a patient as high risk include: Significant peri-infarct ischemia. Defect in a different vascular territory (suggesting multi-vessel disease). Significant lung uptake, suggesting left ventricular dysfunction. Left ventricular aneurysm. Low ejection fraction (less than 40% seen) on GSPECT. Ejection fraction (EF) is calculated as EF= (EDC-ESC)/(EDC - BC) EDC = end diastolic counts; ESC = End systolic counts; BC = background counts.
Preoperative risk assessment for noncardiac surgery.
Evaluation of viability prior to revascularization therapy
Evaluation of myocardial revascularization status post CABG.
Viability imaging overview
Prior to a revascularization procedure (e.g., CABG or coronary angioplasty/stenting), it is important to know if the hypoperfused myocardium is viable, as the revascularization of scar tissue would not provide a cliical benefit. Hypoperfused myocardium that is viable is known as hibernating myocardium.
Viability imaging can be performed with rest-redistribution thallium-201 perfusion imaging or F-18 FDG PET. F-18 FDG PET is the gold standard for evaluation of myocardial viability, although unlike thallium FDG-PET does not evaluate perfusion.
Static SPECT images from a pure perfusion exam (such as Tc-99m sestamibi, rubidium-82 PET, or N-13 ammonia PET) cannot distinguish between hibernating myocardium or scar. Both of these entities appear as a fixed (present on both stress and rest images) myocardial perfusion defect. Evaluation of gated SPECT (GSPECT) functional data can suggest either hibernating myocardium or scar. Normal or nearly normal wall motion and wall thickening in the area of the perfusion defect suggests viability (hibernating myocardium), while a large defect with abnormal wall motion suggests scar.
If the region of the perfusion defect takes up FDG (a “mismatch” between FDG PET and perfusion imaging), that region of myocardium is viable and may benefit from an intervention (either CABG or percutaneous intervention).
In contrast, an FDG PET “match” of a photopenic region corresponding to the perfusion defect is consistent with non-viable scar, and the best treatment is medical therapy only.
Thallium-201
Thallium-201 is a cyclotron-produced radionuclide with a half-life of 73 hours. It decays by electron capture and emits characteristic X-rays of 69-81 keV. Relatively low energy characteristic X-rays attenuation artifact from chest wall soft tissues. It is necessary to administer fairly low doses due to its long half-life, with resultant lower count densities.
Physiologically, thallium acts like a potassium analog, crossing into the cell via active transport through the ATP-dependent sodium-potassium transmembrane pump.
Myocardial uptake is directly proportional ot myocardial perfusion.
A 50% stenosis will generally produce a perfusion defect upon maximal exercise.
Thallium undergoes redistribution with simultaneous cellular washout and re-ectraction of blood-pool radiotracer. Since ischemic myocardium progressively extracts thallium but washes out more slowly than normal myocardium, post-redistribution images will therefore show normalization of defects in ischemic but viable myocardium. In contrast, a scar will show a persistent defect.
Technetium-99m sestamibi (Cardiolite)
Unlike thallium, Tc-99m sestamibi does not undergo redistribution and remains fixed inthe myocardium.
Sestamibi enters myocardium via passive diffusion and binds to mitochondrial membrane proteins. Similar to thallium, myocardial uptake of sestamibi is proportional to myocardial perfusion.
Rubidium-82
Rubidium-82 is a positron-emitting PET perfusion agent that is generated from strontium-82. A very short half-life of 76 seconds allows high doses to be administered, although such a short half-life precludes the use of exercise stress. Pharmacologic stress is used instead.
Rubidium-82 acts as a potassium analog, similar to thallium.
Nitrogen-13 ammonia
Nitrogen-13 ammonia is a positron-emitting PET perfusion agent (like rubidium-82) that has a half-life of 10 minutes. Unlike rubidium-82, N-13 is cyclotron-produced and the cyclotron must be on-site due to its short half-life.
N-13 has excellent imaging characteristics. N-13 positrons have a low kinetic energy and don’t travel very far in the tissue before annihilating, which allows relatively high resolution. The short half-life makes use with exercise stress logistically challenging, and N-13 perfusion is almost always coupled with a pharmacologic stress.
F-18 FDG
F-18 FDG, the same radiotracer used for oncologic imaging, is a positron emitting PET viability agent with a half-life of 110 minutes. Unlike rubidium-82 and N-13 ammonia, FDG cannot be used for perfusion.
F-18 FDG PET images are correlated with a sestamibi perfusion study to evaluate viability. A defect on sestamibi rest perfusion with discordant FDG uptake represents viable hibernating myocardium that could potentially be revascularized. In contrast, a sestamibi perfusion defect correlating to lack of F-18 FDG uptake is a scar.
General exercise protocol
Prior to undergoing a myocardial perfusion study, the patient should be NPO for 6 hours to decrease splanchnic blood flow and therefore reduce liver and bowel uptake. Calcium channel blockers and B-blockers should be held to allow patient to reach target heart rate.
Exercise is performed with a multistage treadmill (Bruce of modified Bruce) protocol. The target heart rate, which is calculated as 85% of maximal heart rate, must be achieved for the study to be diagnostic. The maximal calculated heart rate is 220 bpm - age.
Dipyridamole stress - pharmacologic vasodilator
Dipyridamole is an adenosine deaminase inhibitor that allows endogenous adenosine to accumulate. Adenosine is a potent vasodilator, increasing coronary blood flow by 3-5 times.
A critical coronary artery stenosis cannot further dilate in response to adenosine. That coronary artery territory will appear as a relative perfusion defect on stress imaging.
Unlike a physical stress, a dipyridamole stress does not increase cardiac defect on stress imaging.
Unlike a physical stress, a dipyridamole stress does not increase cardiac work or O2 demand.
Caffeine and theophylline reverse the effects of dipyridamole and must be held for 24 hours.
The antidote is aminophylline (100-200 mg), which has a shorter half-life than dipyridamole, so the patient must be continuously monitored.
Adenosine stress - pharmacologic vasodilator
Adenosine has identical physiologic effects to dipyridamole but a more rapid effect.
Adenosine half-life is approximately 30 seconds and thus does not require a reversal agent.
Regadenoson - pharmacologic vasodilator
Regadenoson is an adenosine receptor agonist with a 2-3 minute half-life. It is easier to administer than adenosine with a convenient universal-dose intravenous injection.
Dobutamine stress - pharmacologic stress
Dobutamine is a B1 agonist that increases myocardial oxygen demand. Dobutamine is usually reserved for when adenosine is contraindicated (severe asthma, COPD, or recent caffeine).
Single-day Tc-99m sestamibi perfusion study
A single-day Tc-99m sestamibi perfusion study is the most common myocardial perfusion exam performed. Rest images are first obtained after 8-10 mCi Tc-99m sestamibi. Stress images are obtained after an additional 20-30 mCi Tc-99m sestamibi is administered during peak exercise, or after administration of pharmacologic stress.
Imaging is performed approximately 30 minutes after injection, to allow liver activity to clear. Because there is no redistribution, imaging can be delayed after tracer administration.
Gated SPECT images show wall motion at time of imaging, while perfusion images show perfusion at time of injection.
PET perfusion
PET rest-stress myocardial perfusion has greater sensitivity, specificity, and accuracy for diagnosis of coronary artery disease compared to SPECT imaging.
Attenuation-correction CT improves diagnostic accuracy by eliminating attenuation artifact.
Rubidium-82 and N-13 ammonia are perfusion agents and are imaged on a PET system using coincidence detection. The shorter half-life of these tracers allows higher activities to be administered with lower overall radiation exposure. For quantification of myocardial blood flow, N-13 ammonia is preferred as rubidium has a lower extraction fraction.
Exercise thallium
Because thallium undergoes redistribution, imaging is performed immediately post-exercise and approximately 3-4 hours later once redistribution has occured. Thallium is uncommonly used because of the long 73 hour half-life and resultant high patient dose.
Reconstruction axes and vascular territories
The heart is reconstructed into short axis (SA, the traditional “donut” view from apex of heart through the base), vertical long axis (VLA, a “U-shaped” view pointing to the left), and the horizontal long axis (HLA, a “U-shaped” view pointing down). The polar plot represents the entire three-dimensional left ventricle unfolded onto a two-dimensional map.
Myocardial segments
For evaluation of perfusion defect size, there are 17 standard left ventricular segments, evaluated on SA (“donut”) views. Each segment is usually supplied by the color-coded artery indicated above, although vascular supply is variable between patients.
Iodine-131
I-131 emits both beta particles and 364 keV gamma photons (only the gamma photons are used for imaging). The half-life is 8 days. I-131 is generator produced.
I-131 is only used for therapy. Indications include treatment of thyroid cancer status post thyroidectomy, and hyperparathyroidism from Graves disease or multinodular gland.
Iodine-123
I-123 decays by electron capture and produces 159 keV gamma photons. It has a half-life of 13 hours. I-123 is expensive as it is produced by cyclotron. It is administered orally.
I-123 is an excellent radioisotope for thyroid imaging, as it can image in high detail and obtain thyroid uptake values.
Tc-99m pertechnetate
Technetium-99m emits a 140 KeV gamma photon and has a half-life of 6 hours.
Unlike iodine, pertechnetate is not trapped by the thyroid. After initial uptake it is released into the blood pool. Thyroid uptake is not routinely quantified with Tc-99m (due to its rapid washout), but pertechnetate does provide excellent iamges of the thyroid gland.
Because pertechnetate does not specifically localize to the thyroid, high background counts are typical. Only 1-5% of administered activity is taken up by the thryoid.
In contrast to I-123, the salivary glands are clearly seen with pertechnetate.
Unlike I-123, Tc-99m is administered intravenously.
Tc-99m pertechnetate is preferred over I-123 when the patient has received recent intravenous iodinated contrast (iodine in contrast blocks thyroid uptake of additional iodine), when IV medication is necessary, or when a quick study is required.
Pregnancy and breast feeding
All thyrotropic agents cross the placenta and I-131 is contraindicated in pregnancy. Fetal iodine is taken up beginning at 12 weeks gestation.
A breast feeding mother who medically requires an I-131 ablative dose must stop breast feeding permanently for the current child.
For I-123, breast feeding can be resumed 2-3 days after administration.
For Tc-99m, breast feeding can be resumed 12-24 hours after administration.
Patient preparation
Patients undergoing I-123 or I-131 imaging/therapy must have non-suppressed TSH, which can be achieved by stopping exogenous thyroid hormone for 4 weeks, or by two intramuscular injections of recombinant TSH (rTSH).
Ectopic thyroid
Either I-123 or Tc-99m can be used to localize ectopic thyroid tissue.
Lingual thyroid is ectopic thyroid tissue at the base of the tongue.
Functional thyroid tissue must rarely be seen in an ovarian teratoma (struma ovarii).
Retrosternal thyroid tissue is most often due to a substernal goiter.
Thyroid nodule
Thyroid nodules are typically only imaged if the cytology is indeterminate.
Hyperfunctioning nodules are almost always benign adenomas.
Cold nodules have approximately 20% risk of malignancy, although the most common cold nodule (~70%-75%) is a benign colloid cyst.
A warm nodule usually represents a cold nodule with overlapping thyroid tissue. A warm nodule requires further investigation such as biopsy if oblique views are indeterminate.
A discordant thyroid nodule is “hot” on Tc-99m and “cold” on I-123 as it has maintained the ability to uptake technetium but is unable to trap iodine. Biopsy is usually recommended as a discordant nodule may be malignant.
Malignancy is relatively uncommon in a multinodular goiter. While a dominant cold nodule should undergo further investigation, smaller cold nodules are unlikely to be malignant.
Graves disease
Graves disease is an autoimmune disorder characterized by hyperthyroidism, thyromegaly, homogenously increased thyroid activity, and often a prominent pyramidal lobe.
Both 6-hour and 24-hour iodine uptake are elevated. Normal 6-hour uptake is 6-18% and normal 24 hour uptake is 10-30%.
Although usually an I-123 and a Tc-99m scan can be differentiated by the presence of salivary uptake with Tc-99m, in Graves disease this distinction is often not possible. In Graves disease, thyroid uptake can be so strong taht the salivary glands are often not seen, causing a similar appearance with either radiotracer.
Definitive treatment of Graves disease is I-131 radiotherapy or (less commonly) surgery. Antithyroid drugs (e.g., methimazole or propylthiouracil) are another option and may achieve a remission after 1-2 years of use.
Hashimoto thyroiditis
Hashimoto thyroiditis is the most common inflammatory disease of the thyroid.
Like Graves disease, Hashimoto thyroiditis also clinically presents with thyromegaly. In Hashimoto thyroiditis, however, thyroid hormone levels are variable depending on the disease stage. Most patients with Hashimoto thyroiditis are hypothyroid.
Appearance on thyroid scan is variable, ranging from diffusely increased activity that resembles Graves disease to patchy uptake similar to a multinodular goiter. The patchiness is thought to be due to cold areas from infiltration by lymphocytes and lymphoid follicles.
Subacute thyroiditis
The classical clinical presentation of subacute thyroditis is a painful swollen gland, although many patients present with silent hyperthyroidism.
Imaging shows decreased radiotracer uptake and a low 24-hour uptake.
Subacute thyroiditis is typically a self-limited condition. Treatment is directed towards symptom control with nonsteroidal anti-inflammatory drugs or steroid in severe cases.
Thyroid carcinoma, post-thyroidectomy
Approximately 1-2 months after thyroidectomy, I-131 is administered to treat and simultaneously image residual and potential metastatic disease.
Following thyroidectomy, thyroid replacement therapy is withheld to allow endogenous therapy is withheld to allow endogenous uptake of therapeutic I-131 by any residual or metastatic thyroid tissue. The goal TSH is 30-50 uIU/mL.
The dosing of I-131 is dependent on the oncologic risk: Low-risk patient (tumor <1.5 cm, no invasion of thyroid capsule): <30 mCi I-131 administered. High-risk patient: 100-200 mCi I-131 administered.
A new approach is a standard dose of 30 mCi for treatment of all T1, T2 and N2 cancers.
Thyroid carcinoma, post radioiodine therapy
After ablation with I-131, patients with thyroid carcinoma are monitored by following thyroglobulin levels. If thyroglobulin levels rise, an I-123 scan is performed to evalute for disease recurrence or metastasis. If the I-123 scan is positive, repeat I-131 radioiodine is adminstered for ablation. Note that the presence of anti-thyroglobulin antibodies precludes the ability to monitor the thyroglobulin levels.
Treatment of Graves Disease
I-131 is administered in a single oral dose to treat Graves disease. Contraindications to I-131 include pregnancy, lactation, and inability ot comply with radiation safety guidelines.
The dosing of I-131 for treatment of Graves varies by institution. Many endocrinologists advocate a calculated dose based on the estimated thyroid weight and 24-hour uptake, while another study has shown one of three fixed doses (up to 15 mCi) to be equally effective.
Adequate dosing of I-131 can treat greater than 90% of patients with Graves disease
