Advanced PET Imaging PDF

# Advanced PET Imaging ## Dusty M. York and Leesa A. Ross - Positron emission tomography (PET) is an advanced imaging modality used to image physiologic processes within the body. The emergence of PET as the functional modality of choice for imaging physiologic processes within the body, assessmen...

# Advanced PET Imaging ## Dusty M. York and Leesa A. Ross - Positron emission tomography (PET) is an advanced imaging modality used to image physiologic processes within the body. The emergence of PET as the functional modality of choice for imaging physiologic processes within the body, assessment of cancer recurrence has led to considerable growth in this field. ## Physics of Positron Emission and Annihilation - PET imaging is not intended to take the place of anatomic imaging, but to add to the biological evaluation of the processes taking place in the body. - PET consists of imaging positron-emitting radiopharmaceuticals. Positron emitters are neutron-deficient isotopes that achieve stability through the nuclear transformation of a proton into a neutron. These positron-rich nuclei then expel a positron, which is essentially a positively charged electron and a neutrino, from the nucleus of the atom. - The positrons travel a very short distance before pairing up with an electron. The average positron range in matter depends upon the positron's energy and material characteristics. - Upon reaching the end of its path, the positron will annihilate with an atomic electron. In the annihilation, electrons and positrons convert their masses into energy and produce a pair of 511 keV photons traveling in opposite directions, 180° apart, as seen in *Figure 21.1*. ## PET Radionuclides - Because radiopharmaceuticals used in PET imaging are proton-rich, its use requires a device that can add protons to the nucleus. Medical cyclotrons are the most common devices used to produce PET radiopharmaceuticals. - In a cyclotron, charged particles, such as protons, are accelerated in circular paths in "dees" (D-shaped hollow metallic electrodes) under a vacuum by means of an electromagnetic field. - Radiopharmaceuticals produced by this method include ¹¹C, ¹³N, ¹⁵O, and ¹⁸F. The majority of PET radiopharmaceuticals are cyclotron-produced; two exceptions are gallium-68 and rubidium-82, which are both generator-produced. - Gallium-68 is produced by the ⁶⁸Ge-⁶⁸Ga generator and is routinely used as a standard sealed source for calibration of PET systems, but its clinical use is very limited. Many PET radiopharmaceuticals are currently in the research phase of development and use. ## PET Radionuclides at a Glance ### [¹⁸F]Sodium Fluoride - Fluorine-18 is produced by irradiation of [¹⁸O] water with protons in a cyclotron and recovered as [¹⁸F]sodium fluoride by passing the irradiated water target mixture through a carbonate-type anion-exchange resin column. The water passes through the column, and then removed by elution with a potassium carbonate solution. [¹⁸F]sodium fluoride is most commonly used for the synthesis of [¹⁸F]fluorodeoxyglucose; it is also approved by the FDA for bone scintigraphy. ### [¹⁸F]Fluorodeoxyglucose (FDG) - [¹⁸F]FDG is the most-used PET radiopharmaceutical and can be given credit for the growth of PET over the last 20 years. - [¹⁸F]FDG is a glucose analog in which the hydroxyl group on the 2-carbon of a glucose molecule is replaced by a fluoride atom and is an excellent indicator of glucose uptake and cell viability. Like glucose, [¹⁸F]FDG is taken up into living cells by facilitated transport and then phosphorylated by hexokinase. Unlike glucose, [¹⁸F]FDG cannot undergo further metabolism and remains trapped in the cells. The most commonly used method for the production of [¹⁸F]FDG involves the method developed by Hamacher, et al. (1986). - This method uses a nucleophilic substitution reaction (see *Figure 21.2*). Nucleophilic substitution is a chemical reaction involving the addition of a highly negatively charged molecule into an electron drawing group attached to the parent molecule through an unstable chemical bond. Synthesis of [¹⁸F]FDG can be carried out in many different controlled synthesizers; the process consists of roughly the same stages, including: removal of ¹⁸F from the [¹⁸O] water dispensed from the cyclotron by ammonium anion exchange. The retained ¹⁸F is eluted with an acetonitrile solution of Kryptofix and potassium carbonate. Kryptofix is used to increase the reactivity of the ¹⁸F-labeled anion. The next step involves evaporation of residual ¹⁸O water from the ¹⁸F with acetonitrile. This is followed by adding mannose triflate to the ¹⁸F with acetonitrile, where the nucleophilic substitution takes place. The ¹⁸F-labeled ion approaches the mannose triflate, while the triflate group leaves the protected mannose molecule to form ¹⁸F-labeled mannose. After the nucleophilic replacement of the triflate group by ¹⁸F, the acetyl groups can easily be removed by hydrolysis to produce [¹⁸F]FDG. - The final step involves hydrolysis, which consists of removing the protective acetyl groups to form [¹⁸F]FDG and purification of the final product (see *Figure 21.2*). Most automatic synthesizers can produce [¹⁸F]FDG of over 95% routinely. [¹⁸F]FDG has a half-life of 110 min, allowing availability in most areas. [¹⁸F]FDG is primarily used for oncology applications. ### [¹⁸F]Flurodopa - 6-[¹⁸F]fluoro-3,4-dihydroxy-phenylalanine ([¹⁸F]Flurodopa) is cyclotron-produced. There are several methods of synthesizing 6-[¹⁸F]fluorodopa. [¹⁸F]Flurodopa is commonly produced by fluorodemetallation using electrophilic fluorinating agents. - [¹⁸F]Flurodopa is used for the assessment of the presynaptic dopaminergic function in the brain. ### [¹⁸F]Fluorothymidine (FLT) - [¹⁸F]Fluorothymidine (FLT) is prepared by nucleophilic reaction between [¹⁸F]fluoride and a precursor that is prepared by standard organic synthesis. Thymidine is incorporated into DNA and provides a measure of cell proliferation. [¹⁸F]FLT is used for in vivo diagnosis and characterization of tumors in humans. ### ¹⁵[O]Water - ¹⁵[O]oxygen is produced in the cyclotron by the ¹⁵N (p, n) ¹⁵O reaction, and the irradiated gas is transferred to a ¹⁵[O]water generator, which is then mixed with hydrogen and passed over a palladium/charcoal catalyst at 170°C. The H₂O vapor is then trapped in saline for injection in the patient. The short half-life of approximately 2 min limits the use and availability of ¹⁵[O]water. This tracer is most commonly used for myocardial and cerebral blood flow studies. ### ¹³[N]Ammonia - Nitrogen-13-labeled ammonia is cyclotron-produced by the ¹⁶O (p, α) ¹³N nuclear reaction. This reaction is performed using a solution of ethanol in water to yield ¹³N in the form of ammonia. ¹³N has a half-life of approximately 10 min and is primarily used as a myocardial perfusion imaging agent. ### ¹¹[C]Carbon - Carbon-11 is generally produced by the ¹⁰B(d, n) ¹¹C, ¹⁴N (p, n) ¹¹C, or ¹⁴N (p, α) ¹¹C nuclear reactions. A number of ¹¹C-labeled compounds have been synthesized as PET radiopharmaceuticals. The most common are discussed below. #### [¹¹C]Acetate - [¹¹C]Acetate, a tracer used in the study of myocardial metabolism, is currently being evaluated for use as a prospective agent in the evaluation of prostate cancer. #### [¹¹C]Choline - Choline is also a prospective agent in the evaluation of prostate cancer. #### [¹¹C]Glucose - [¹¹C]Glucose is also used to study metabolism. #### [¹¹C]Methionine - Carbon-11-labeled C-1-methionine has been used for detecting different types of malignancies. #### [¹¹C]Raclopride - [¹¹C]Raclopride is primarily used to detect various neurologic and psychiatric disorders. Carbon-11 has a half-life of 20 min. The short half-life of carbon will limit its use to sites with on-site cyclotrons. ### [⁶⁴Cu]Copper - Copper-64 is produced by the ⁶⁴Ni (p, n) ⁶⁴Cu reaction, which involves the irradiation of enriched ⁶⁴Ni. There are currently no FDA-approved ⁶⁴Cu radiopharmaceuticals. However, several potential agents are being researched. ⁶⁴Cu-Dotatate is a somatostatin analog offering improved sensitivity in the evaluation of neuroendocrine tumors. ⁶⁴Cu-ATSM is being evaluated as a tool to identify hypoxia in atherosclerotic plaques and tumors. ### [⁸²Rb]Rubidium Chloride - [⁸²Rb]Rubidium chloride is available from the ⁸²Sr-⁸²Rb generator, which is supplied monthly. ⁸²Rb is eluted with saline and must be checked for ⁸⁵Sr and ⁸⁹Sr breakthrough daily before the start of its use for patient studies. In recent years, these new alert limits and new expiration limits were established: * **Alert Limits**: - ⁸⁹Sr-82 level exceeds 0.002 µCi Sr-82/mCi Rb-82, or - ⁸⁹Sr-85 level exceeds 0.02 µCi Sr-85/mCi Rb-82, or - a total elution volume of 14 L has passed through the generator column * **Expiration limits**: - ⁸⁹Sr-82 level exceeds 0.01 µCi Sr-82/mCi Rb-82, or - ⁸⁹Sr-85 level exceeds 0.1 µCi Sr-85/mCi Rb-82, or - a total elution volume of 17 L has passed through the generator column, or - 42 days post-calibration date - ⁸²Rb has a very short half-life of 75 sec and is administered to the patient by using an infusion pump connected directly to the generator. ⁸²Rb is used for myocardial perfusion imaging. ### [⁶⁸Ga]Gallium - Gallium-68 is available from the ⁶⁸Ge/⁶⁸Ga generator. The parent radionuclide ⁶⁸Ge has a half-life of 271 days, while ⁶⁸Ga has a half-life of only 68 minutes. This generator system has primarily been used as a research tool. In recent years, a number of PET radiopharmaceuticals that have the potential to be used in clinical applications have been labeled with Ga. As of this publication, the only FDA-approved ⁶⁸Ga radiopharmaceutical is ⁶⁸Ga-Dotatate. ⁶⁸Ga-Dotatate is indicated for use in somatostatin receptor-positive neuroendocrine tumors. ## Quality Control for [¹⁸F]FDG - Since [¹⁸F]FDG is the most widely used and distributed PET radiopharmaceutical, it is important to discuss the quality control requirements specific to this agent. Due to the short half-life of [¹⁸F]FDG, not all of the required tests can be completed before release of the [¹⁸F]FDG product. Pre-release United States Pharmacopeia (USP) quality control testing for PET radiopharmaceuticals includes a visual inspection, identity testing, pH, radiochemical and chemical purity, and residual solvent analysis. Sterility testing and bacterial endotoxin test (BET) are required post-release for every production of [¹⁸F]FDG radiopharmaceutical prepared for human use. ### Visual Inspection - [¹⁸F]FDG should appear as a clear and colorless solution without particulate matter. ### Identity Testing - The radionuclidic identity can be confirmed by measuring the half-life of the product. This test is performed using a dose calibrator and involves decay analysis over a defined period of time. The acceptable half-life of [¹⁸F]FDG is 109.7 min, with an allowable range of 105-115 min. Radionuclidic purity should be determined with y spectroscopy. A multichannel analyzer (MCA) is used to determine the presence of any y photon energy other than that characteristic of ¹⁸F, which includes 511 keV, 1.02 MeV, or Compton scatter. The radionuclidic purity must be 99.5%. ### pH - The pH value of an injectable should be as close to the physiological pH as possible. The pH of [¹⁸F]FDG must be between 4.5 and 7.5. This test is performed using pH papers. ### Radiochemical Purity - The radiochemical purity of a radiopharmaceutical is the fraction of the total radioactivity in the desired chemical form in the radiopharmaceutical. The radiochemical purity of [¹⁸F]FDG can be determined by using silica gel Thin Layer Chromatography (TLC) plates developed in acetonitrile:water (95:5). The Rf values should be confirmed per the validation process: [¹⁸F]FDG (Rf= 0.4, [¹⁸F]fluoride (Rf= 0.6). Acceptable radiochemical purity is ≥90%. ### Chemical Purity - The chemical purity of a radiopharmaceutical is the fraction of the material in the desired chemical form. A variety of chemical purity tests may be required, if any of the following agents are used in the synthesis of [¹⁸F]FDG: Kryptofix, acetonitrile, ethanol, or ether. If the synthesis involves Kryptofix, the USP requires determination of the concentration before releasing the final product. The current USP-approved method uses silica gel TLC developed in a mixture of ethanol and water. The developed plate is dried and an iodine vapor chamber is used for visualization. A yellow spot indicates the presence of Kryptofix. The Kryptofix concentration must be less than 50 µg/mL. The maximum concentration of other solvents is: Acetonitrile must be 0.04 mg/mL, ethanol 5 mg/mL, and ether 5 mg/mL. ### Sterility - Sterility indicates the absence of any viable bacteria or microorganisms in a radiopharmaceutical preparation. Post-release sterility testing must be performed for each batch of [¹⁸F]FDG. The product must be inoculated on both soybean casein digest medium and fluid thioglycollate within 24 hr. The sterility test takes 14 days to complete, which does not allow for pre-release results. Since [¹⁸F]FDG is released and injected into patients before sterility results are available, the final product is passed through a 0.22 µm filter to ensure sterility. ### Bacterial Endotoxins (BET) Limulus Amoebocyte Lysate (LAL Test) - The BET is a test for pyrogens. The bacterial endotoxins level is tested using the LAL test. The sensitivity of the test is given in endotoxin units (EU). BET should be <175 EU/mL. Most testing kits require an incubation period of 20-60 min. Therefore, it is unlikely that the test will be completed before release of the product. ## Radiation Protection in PET - PET requires special consideration regarding radiation safety. A basic understanding of radiation safety techniques should be incorporated into staff training to keep clinical and occupational exposures as low as reasonably achievable (ALARA). Considerations should be incorporated in the design and setup of all PET facilities. PET/CT facilities can be even more challenging with the incorporation of shielding, due to the CT component. - Within a PET imaging department, the majority of exposure to personnel results from the injected patient; therefore, planning adequate shielding can be a challenge. When planning such a department, it is important to consider potential exposure of all personnel and plan for the appropriate amount of shielding to be incorporated-the scanner room, preparation room, and possibly a post-injection waiting area, such as a quiet room, may have to be considered for shielding. - To keep exposure to the technologist ALARA, the technologist should consider time, distance, and shielding. The time the technologist is exposed to the source, which includes the injected patient, should be limited. The technologist should explain the procedure and request a thorough patient history before injecting the patient. This will limit the time spent with the patient after injection. Technologists should maximize the distance between themselves and the patient and use lead shields or remote manipulators if possible. The technologist should use dosimetry badges to track the amount of radiation they receive. The source is inversely related to the square of the distance from the source. - Finally, the technologist should ensure proper shielding techniques when measuring doses and performing injections. Shielding devices require thicker shielding material. Doses should be prepared and measured behind a lead shield. Syringe shields should be used when injecting patients. Tungsten is preferable over lead for syringe shields used in PET. The 511 keV photons have a half-value layer of 4 mm in lead compared to 3 mm in tungsten. ## PET Instrumentation ### PET Detectors - PET imaging systems use scintillation crystals, but several additional considerations are necessary beyond those pertaining to general nuclear medicine. An ideal PET scintillation detector would have the following characteristics: high density to stop the high-energy photons; very efficient scintillation, which produces a large amount of light; and an exceptionally fast scintillator. Most scintillation crystals are lacking at least one of these ideal characteristics. *Table 21.2* lists several scintillation crystals that have been used as PET detectors, along with some properties of each. - The sodium iodide detector remains the detector of choice in single-photon emission tomography because of its excellent energy resolution and higher light output. The density of the NaI(Tl) detector is its limiting factor for PET application, though, it is not very effective at stopping the high-energy photons used in PET. - Several other detector materials have resulted in greater success. In the early PET scanners, bismuth germinate (Bi₄Ge₃O₁₂) or BGO were used. BGO detectors have a high density, which means they are more efficient at stopping the high-energy photons used in PET. However, the decay time and light yield of BGO are both limiting factors. BGO also has poor energy resolution, which requires energy windows to be wider than preferred. The latest detectors include lutetium orthosilicate (Lu₂SiO₄[Ce], or LSO), lutetium-yttrium orthosilicate (LuY₂O₅SiO₅[Ce] or LYSO), and gadolinium orthosilicate (Gd₂SiO₄[Ce] or GSO). These new detectors are all doped with cerium (Ce) to improve their scintillation efficiency; all have greater light output and shorter decay times when compared to BGO. - Current PET systems provide scintillators with a higher density, shorter decay time, and modern electronics that allow for faster computing power. The implementation of faster scintillators permitted ToF imaging. ToF imaging is not a new concept-it can be dated back to the 1980s on experimental systems. ToF systems were limited to research until the early 2000s and can estimate an annihilation event location accurately along the coincidence line of response (LOR), by measuring the difference in the arrival times of the annihilation photons at the opposing detectors. As a result, ToF-PET increases image resolution. The greatest benefit is found with larger patients, who suffer most from poor image quality. - ToF-PET requires additional considerations during reconstruction. The main benefit to ToF-PET is a significant improvement in the signal-to-noise ratio in the reconstructed 3D image. New scintillators are being evaluated for their effectiveness in ToF imaging. These detectors include barium fluoride (BaF₂) and lanthanum bromide (LaBr₃). Both of these detectors are faster scintillators and have shorter decay times. ### Scanner Design - The basic primary component of a PET system is two opposing detectors. Annihilation photons detected in PET are released simultaneously in 180° opposite directions. To be considered a valid event, the two annihilation photons must both be detected within a very short coincidence timing window of 5-12 nsec. The detectors used for coincidence detection identify an annihilation photon pair and determine a LOR path representing the path of the photon pair (see *Figure 21.3*). - The detectors used in PET are composed of small cube-shaped crystals about 4 mm in size and 20-30 mm in length. PET scanners typically have 18-40 rings of detectors for a total of approximately 10,000-35,000 small detectors. Electronically, the scintillation crystals are organized into detector blocks with multiple detectors coupled to a single photomultiplier tube. ### Types of Events in PET - True coincidences or true events occur when two annihilation photons from a single annihilation interaction are detected within the timing window. Several other possibilities exist, such as random and scatter coincidences (see *Figure 21.4*). - Random coincidences or events occur when two single events from two separate annihilations are detected within the timing window. When this happens, a false event is recorded. The randoms rate increases relative to the square of the dosage. Processing software attempts to estimate these false events and applies corrections during reconstruction. Another method to reduce the randoms rate is reducing the coincidence timing window. Using a fast scintillator, such as LSO, also decreases random coincidences. - Scatter events arise from the scatter of annihilation photons between their origin and the detectors. Scatter is affected by the distribution of radioactivity, size, and density of the object as well as its location relative to the detector. Randoms and scatter events are inevitable in imaging and corrections are essential for quantitative results to be obtained. ### Attenuation Correction - Attenuation correction is critical for both visual and quantitative accuracy of PET images. Attenuation will vary from patient to patient, since the make-up and size of the patient's body varies. The only way to accurately evaluate the attenuation coefficient is to pass a beam of radiation through the body and measure the attenuation. If the system is an independent PET system without the CT component, this is performed by rotating a radioactive rod source around the patient. This attenuation image is known as a transmission image. The radioactive sources are usually ⁶⁸Ge or ¹⁵⁷Cs, which are housed within the gantry and extended through the use of a robotic system only for the transmission portion of the exam. - A transmission image will have to be performed for each bed position along with an emission image. These images are usually interlaced by performing emission-transmission-transmission-emission (ETTE) to reduce total scan time. With the advent of CT into our PET scanner design, the CT scan replaces the need for the transmission scan. The transmission scan data are reconstructed into an attenuation correction map for each slice. - PET-only scanners can no longer be purchased; manufacturers provide only hybrid imaging with PET/CT. The advantage of using CT for attenuation correction is the technique is much faster and provides a high-resolution, fused anatomic image. There are some disadvantages, such as image misalignment, beam hardening artifacts, and metal or contrast artifacts, but the advantages of the hybrid system surpass the disadvantages. ### 2D and 3D Imaging - Some PET scanners have thin rings of lead or tungsten, known as septa, positioned between the rings of the detectors. The scanner has the capability to operate with the septa extended and in use, which is known as 2D mode. Retracting the septa places the scanner in 3D mode. - While operating in 2D mode, the septa serve to limit the FOV of events to those within the same detector ring and reduce the number of scatter and random coincidence events. When the septa are retracted in 3D mode, more annihilation events can be detected across the detector rings resulting in a drastic increase in sensitivity (see *Figure 21.5*). Unfortunately, the cost of increasing the detection of true events is that we also increase the detection of scatter and random events. - Correction techniques are crucial in processing 3D data. Modern scanners no longer have the capability to operate in 2D mode; with the introduction of faster detectors, timing windows can be reduced to help decrease the errors produced in 3D imaging. Along with the image quality being enhanced in 3D imaging, the gantry opening also increases due to the removal of the septa, allowing larger patients to benefit from PET imaging. With the initiation of these faster scintillators, along with improvements in correction techniques, 3D imaging has evolved into routine clinical use. ### Data Collection and Analysis #### Reconstruction Algorithms - During image reconstruction, data must first be reformatted into sinograms. A sinogram is simply a plot of counts registered in each LOR. PET data sets may be reconstructed with either analytic or iterative techniques. - The analytic method of performing filtered backprojection is probably the simplest way to perform reconstruction and definitely the fastest. However, filtered backprojection tends to create artifacts and results in increased image noise. - Another method is known as iterative reconstruction. Iterative reconstruction algorithms estimate image values and perform repeated calculations until the difference between the estimates and the measured values reach a specified value. At a point in the number of iterations, there will be no further improvement in image quality. Once this point is reached, further iterations can actually begin to degrade image quality, so it is important to determine the number of iterations that will create optimal image quality. The number of iterations is preset by the user. This ongoing repetition of estimations takes considerably more time, but can be accommodated by today's faster computers. - 3D image reconstruction requires additional steps beyond the requirements of 2D image reconstruction. Reconstruction options for 3D image data are determined by the age of the scanner and software limits. - The reconstruction of 3D data requires that the raw data-3D sinograms-be either rebinned into 2D information or reconstructed completely as a full 3D volume. Significantly more data are acquired in 3D mode due to the increase in sensitivity. Reconstructing 3D data in full 3D mode is computationally intense and currently only an option on newer scanners. Traditional methods require 3D data to be converted into 2D sinograms and then the process of iterative reconstruction be completed. - Methods available to complete this conversion of data from 3D to 2D include single-slice rebinning (SSRB) and Fourier rebinning (FORE). SSRB rebins 3D data into 2D projection sinograms. SSRB results in a blurring of image data, so this method is not commonly used today, since there are better approaches. FORE incorporates a more-accurate process for converting data from 3D to 2D projection data and is therefore the most common technique. - Rebinning results in reduced resolution, since the distance from the axial center of the FOV increases. Full 3D reconstruction does not require the conversion of data and is the optimal method to avoid resolution loss to rebinning; it is only available on modern scanners, but is the standard on new equipment. - There is a significant increase of data in the reconstruction process due to the increase in the number of LORs contained in each sinogram, requiring additional computer components devoted to this step. (The process of full 3D reconstruction is very complicated and beyond the scope of this chapter.) - Two iterative algorithms important to PET are maximum-likelihood expectation maximization (MLEM) and ordered subset expectation maximization (OSEM). It is important to note that both of these algorithms require a substantial amount of computations to complete and are both time-consuming when compared to filtered backprojection. - MLEM requires many iterations using the entire data set, which is very time-consuming. OSEM is a faster and more-efficient iterative algorithm. OSEM uses faster subsets of the data, which results in fewer iterations and reduces the amount of time required. - In addition to reconstruction algorithms, the data must also undergo filtering. The most-common filter used in PET whole-body imaging is the Gaussian filter, which is defined by a parameter in frequency space like most filters used in Nuclear Medicine. The filter is defined by its full width half-maximum (FWHM) in pixel space, which is more commonly known as the spatial domain. The width of the filter is measured in millimeters. Increasing the FWHM on the Gaussian filter will result in a smoother image. A high-resolution image can be produced by applying a FWHM value of 5 mm. #### Performance Evaluations - The National Electrical Manufacturers Association (NEMA) has developed guidelines on how some performance parameters, such as spatial resolution and sensitivity, should be evaluated and presented. These guidelines are used to make a better assessment of system performance. ##### Scatter Fraction - Scatter fraction is a measure that indicates a PET tomography's sensitivity to scatter coincidences. It is defined as the ratio of scatter coincidences to total counts: Scatter fraction (SF) = S(0) = 8 x S(4.5) + 10.75 × S(9) Tror(0) = 8 x Tror(4.5) + 10.75 × Tor(9) where S is the number of the scattered counts per unit activity and Tror is the total number of counts (true + scattered) per unit activity. - Several factors affect the scatter fraction, such as acquisition mode, energy mode, and the geometry of the scanner. The desire is to achieve a low scatter fraction. This value allows the user to verify that the scatter correction techniques used are accurate. ##### Noise Equivalent Count Rate - The noise equivalent count rate (NEC) is a measure of signal-to-noise ratio. The NEC is defined as: NEC = T² / (T + S + 2fR) where T, S, and R are the true, scatter, and random coincidence counting rates, f is the fraction of the sinogram width produced by the phantom, and the factor 2 comes from online randoms subtraction. #### Quantitative Image Analysis - Quantitative uptake value of a radiopharmaceutical can be measured in an attempt to analyze radiotracer distribution more thoroughly. The degree of radiotracer uptake is a determining factor used to evaluate malignant versus benign processes. Standardized uptake values (SUVs) give the user a better quantitative uptake ratio. Malignant processes will typically demonstrate higher SUVs when compared to normal tissue. SUVs require close attention to detail from the technologists to ensure accurate information regarding time of dose, activity administered, injection time, patient height and weight, and the time when images were actually obtained. The SUV is most often calculated using the weight-based calculation: SUV = ROI activity in millicuries per milliliter (injected activity in millicuries per milliliter per patient weight in grams) - Another factor in the accuracy of SUV values is cross-calibration between the tomograph obtained and the dose calibrators used to measure dose activity. Imaging parameter selection can also affect SUV values. Dual-point imaging may be performed, followed by SUV determination. - SUV values of malignant processes tend to increase or remain constant while SUV values of infectious processes tend to decrease on the delay images. There is still much controversy regarding the accuracy of SUVs, but it is still widely recognized. ### PET Scanner Calibration and Quality Control - Quality control on a PET camera is required and consists of a series of tests performed to ensure that the equipment is operating efficiently. A description of the various quality control procedures follows, summarized in *Table 21.3*. #### Energy Window Calibration - Energy window calibration is typically performed only after repairs during quarterly preventive maintenance. This application is performed to ensure that the energy window is correctly positioned around the 511 keV energy of PET radionuclides. The energy window calibration is performed using a source of ⁶⁸Ge that is placed into the bore of the gantry. Data is acquired and processed to adjust the detector module gain settings accordingly. #### Coincidence Timing Calibration - The coincidence timing window should be evaluated during quarterly preventive maintenance to ensure uniform timing windows for all detectors. Typical PET timing windows are set around 5-12 nsec. As timing windows are extended, significantly more random and scatter events are accepted. #### Normalization - The normalization calibration is an evaluation of the correction factors that are applied to every study. This calibration procedure is performed by using the radioactive rod sources housed in the gantry, or if the scanner does not have these sources, a ⁶⁸Ge canister source is used. This calibration requires a long acquisition to provide good statistical data and ultimately decrease the noise as much as possible. Therefore, the calibration is usually performed overnight and usually takes a minimum of 6 hr to complete. A normalization calibration for 3D mode may have to be acquired separately. This calibration can be compared to performing a high-count uniformity correction on gamma cameras. Normalization calibrations are performed quarterly and after repairs. #### Blank Scan - The blank scan is performed daily to make certain the scanner is operating properly. The blank scan is essentially a transmission scan without a patient in the gantry, hence the name blank scan. This scan is used to identify equipment failures before imaging patients. The blank scan is performed by acquiring a short, approximately 30 min, acquisition of the transmission rod sources housed in the gantry or a ⁶⁸Ge canister source. The sinogram is then evaluated for obvious malfunctions. ## Patient preparation. - Patient preparation for PET scans using [¹⁸F]FDG for oncology applications is a very important process. Taking correct patient preparation steps will enhance image quality. - Here is an example of a commonly used protocol. - **Before arrival in the department, patients should be instructed to fast, except for water, for at least 4-6 hr before the administration of [¹⁸F]FDG to decrease the physiologic glucose levels and reduce serum insulin levels to near-basal levels. Hydration with water is encouraged before imaging to reduce bladder radiation dose and improve image quality by reducing urinary artifacts.** - **A variety of additional factors may enhance image quality. Some examples include encouraging a low-carbohydrate/high-protein diet prior to the exam, which can decrease myocardial uptake. Avoiding strenuous exercise the day of the study may reduce muscle uptake, thus decreasing the possibility for image artifact. If intravenous contrast is administered, the patient should be screened for a history of iodinated contrast material allergy, use of metformin to treat diabetes mellitus, and renal disease.** - **Before injection of [¹⁸F]FDG, several steps should be followed * A thorough patient history allows time for the patient to ask questions and relax. * The patient should be placed in a quiet room-a dedicated uptake room, which provides a quiet, warm, low-lit environment. The room is usually equipped with a recliner or a stretcher to promote a resting position. The patient should remain in a latent state during injection and the subsequent uptake period. Quiet room characteristics promote resting and help prevent muscular uptake. * Patients can be provided with a warm blanket to help reduce the uptake of brown fat. Brown fat is usually represented as bilateral uptake in the areas of the supraclavicular region, as seen in * Figure 21.8*. Brown fat uptake has also been shown to be reduced by pharmacological intervention with diazepam. To reduce brown fat uptake, 5-10 mg of diazepam can be administered orally 1 hr before injection of [¹⁸F]FDG. * An intravenous catheter should be placed for the [¹⁸F]FDG administration. The size of the IV should be considered if IV contrast is to be administered. * The blood glucose level should be checked. The IV line can be used to gain a small amount of blood for glucose testing with a glucose meter. High glucose levels compete with [¹⁸F]FDG uptake. This can substantially degrade image quality and the accuracy of the results obtained. It is preferred that glucose levels be ≤ 150 mg/dL but scans are usually performed as long as levels are ≤ 200 mg/dL. Special consideration has to be given to diabetic patients. Recommended protocols include imaging Type I diabetes patients early in the morning, after an overnight fast. Type II diabetics may require the administration of insulin on the morning of the exam. If insulin is administered, the injection of [¹⁸F]FDG must be delayed for at least 1 hr and is ultimately dependent upon the type and route of administration of insulin. Patients who present with elevated blood glucose levels may demonstrate inhomogeneous activity resulting in poor image quality; thus, it is important to document the blood glucose level. * If a PET/CT scan is to be performed, an intraluminal gastrointestinal contrast agent may be administered to provide adequate visualization of the gastrointestinal tract. ## Image acquisition. - Patients typically wait 60-90 minutes after injection before beginning imaging. The majority of oncology PET exams are positioned and acquired from the skull base to the mid-thigh. This scan typically requires five to eight bed positions, depending on the dimensions of the scanner field of view and the patient's height. This particular body survey is recommended for most tumor types. - For imaging tumors with a high likelihood of scalp, skull, or brain involvement or lower extremity involvement, whole-body imaging is performed. Whole-body imaging includes the entire body, to include the skull and all extremities. Whole-body imaging should always be performed on patients who present with an indication of melanoma. - For optimal imaging of the body, the patients may be scanned on a standard PET scanner with their arms by their sides for comfort. When a patient undergoes