Physical Factors Affecting Radioactivity Quantification
The important physical factors are photon interactions in the patient, loss of spatial accuracy due to limited system resolution, partial volume effects (PVEs), and noise resulting from the random nature of radioactive decay and absorption. In PET, random coincidences play an additional role.
Attenuation and Scatter
Emitted photons undergo scattering and photoelectric absorption in the patient, which reduce the number of detected photons. Because projections are obtained at multiple views, the attenuation for a point inside an object depends on its average depth and the tissue composition between the point and the surface. Without compensation, attenuation results in interior regions having a lower estimated activity compared with superficial ones. For large objects, attenuation is the single largest factor degrading quantitative accuracy.
Compton scattering of a photon produces a change in both its direction and energy. Due to limited energy resolution, a significant number of scattered photons will be detected, and the change in direction means that scattered photons carry degraded information about the photons’ point of emission. The scatter point response function (SPRF) describes the distribution of detected scattered photons resulting from a point source. The SPRF depends on the patient and source position. It typically has a similar full-width at half maximum (FWHM) resolution but wider full-width at tenth maximum resolution than the point response function of unscattered photons. Scatter results in a loss of image contrast and degraded quantitative information. Images reconstructed with attenuation compensation but without scatter compensation result in a spurious increase in image intensity, especially in the interior of the image.
The magnitude of scatter effects depends on photon energy, source depth, energy window setting, and the energy resolution of the system. Scatter effects are larger for lower energy photons and for radionuclides with multiple-photon emission.
Imaging System Resolution
Nuclear medicine images have limited spatial resolution. This results in PVEs that worsen the quantitative accuracy more for smaller object sizes. In single-photon imaging, the resolution is determined largely by the collimator-detector response (CDR). For photons passing through the holes, the blurring is characterized by the geometric response function (GRF) with a width depending on both the hole dimensions and the distance from the collimator face.
Some photons penetrate through the collimator septa without interactions, whereas other scatter from the septa. Together these contribute long tails to the response function, especially for medium- and high-energy photons.
The final component of the CDR is the intrinsic response of the detector that results from imprecision in estimating the position of the interaction point of the gamma ray in the detector crystal due to crystal scatter and statistical variations.
In planar imaging, projecting activity in the patient to a single plane results in a mixture of resolutions for objects comprising the image. In SPECT, spatial variance of the CDR results in a spatially varying and asymmetric reconstructed point response function where the asymmetry depends on the collimator as well as the camera orbit. For a circular orbit, the resolution is the same on all radial lines. It is worst at the center, constant in the radial direction, and improves in the tangential direction with increasing distance from the center. For noncircular orbits there is even greater spatial variation in the resolution. Typical FWHM resolutions in SPECT range between 7 and 20 mm. The septal scatter and penetration components result in noise-like artifacts in the images and a contrast reduction.
In PET, the resolution is determined by crystal size, scatter in the crystals, positron range, and effects of annihilation photon acolinearity. Current whole-body scanners possess FWHM resolutions of between 5 and 7 mm at the center of the field-of-view (FOV); resolution degrades toward the edge of the FOV because of depth-of-interaction effects. For decays at the center of the detector ring, photons strike the detectors orthogonally. With increasing off-axis distances, the line of response of 2 such photons strikes the detectors at decreasing angles of incident, resulting in penetration into adjacent detector elements, and misregistration of the line of response. This parallax error decreases the image resolution with increasing distance from the scanner axis and becomes worse as the ring diameter decreases and as the cross sectional area of the detector is reduced.
Partial Volume Effects
PVEs are a combination of 2 factors. The first is image sampling, that is, each SPECT or PET voxel has a definite size, and the activity is assumed to be uniformly distributed inside the voxel. This is sometimes known as the partial voxel effect (thus a phantom in the shape of a true pyramid appears in the image like a stepped pyramid). The second factor is a consequence of the resolution properties of the detected photon events. For both PET and SPECT, these factors, described previously, blur the images, resulting in activity from multiple objects or organs contributing the intensity of a given image voxel. When imaging features in the body, PVEs can manifest as the spill-out of activity into surrounding objects from a hot object (typical of tumor imaging) and spill-over (or spill-in) of activity into a cold VOI (more typical in cardiac imaging). Partial volume corrections are especially important when quantifying the activity within objects of sizes less than twice the FWHM spatial resolution of the imaging system.
Because radioactive decay and photon interactions are independent random processes, the numbers of photons passing through an object and absorbed in a detector system are random variables governed by Poisson statistics. This produces statistical noise in the resulting images and imprecision in activity estimates.
Image reconstruction in SPECT and PET tends to correlate and amplify the high-frequency components of this noise, resulting in large voxel-to-voxel variations. Low-pass filtering can reduce the high-frequency noise, but at the expense of spatial resolution. Resolution recovery methods tend to correlate the midfrequency noise, resulting in a blobby noise texture.
Images can be degraded by involuntary (heart beating and respiration) or voluntary motions. If motions are periodic with a period short compared with the acquisition time, these manifest themselves as a loss of spatial resolution. Activity within a given structure will be attributed to a larger volume corresponding to the motion path of the object being imaged. For example, a tumor in the base of the lung that moves 8 mm due to diaphragmatic motion will result in an image in which the activity is smeared over this additional 8 mm, resulting in a significant underestimation of the relative specific activity. Nonperiodic motion produces more complicated artifacts in reconstructed SPECT or PET images depending on type of motion and the acquisition geometry.
Interacquisition motion is important to consider when images are taken at multiple time points to measure a timeactivity curve. For short-lived radionuclides, it may be possible to minimize motion by retaining the patient on the couch and using restraints. For long-lived tracers, careful repositioning is necessary. Inconsistent repositioning and reshaping of organ VOIs lead to inaccuracies and imprecision. For voxel-based dosimetry, accurate registration at the voxel level of activity or dose-rate images is needed.
The size, shape, and geometrical relationships between organs and tissues affect the attenuation and photon scattering in the body. Larger patients attenuate more, producing more noise for the same administered activity, and a larger fraction of detected scattered photons. Organs that are smaller or elongated will have greater PVEs. The size and shape of patients also determines the minimum radius of rotation and the orbit when using body contouring; these affect the resolution and spatial variation of the resolution and thus impact the PVEs. All these factors contribute to variations in accuracy that manifest as imprecision over a patient population.
Physiology and Function
Different imaging agents possess different pharmacokinetics and the macro- and microdistribution within tumors and organs, and these factors will have profound effects on the PVEs. Patient diet can also affect the uptake of a radiopharmaceutical. For example, the amount of iodine in the diet can significantly affect the percent radioiodine uptake in the thyroid when planning for therapy and food eaten before an fluorodeoxyglucose (FDG) PET scan can significantly reduce the standard uptake value (SUV). For PET scans, the time after injection can also have an effect on the magnitude of the SUV.
The collimator largely determines the sensitivity and resolution of a single-photon system. It also determines the magnitude and spatial variation of septal penetration and scatter effects that can introduce artifacts within images and biases into the quantitative estimates. Imaging smaller objects or objects in close proximity to a high-uptake organ requires a high-resolution collimator; isolated large organs with low uptake may benefit from using a higher sensitivity collimator to improve precision. To maximize spatial resolution, the minimum possible radius of rotation (or detector height) should be used. Noncircular orbits can exacerbate the nonuniform spatial resolution in SPECT but generally improve the overall image resolution and reduce PVEs. Generally, the number of projections over 360 degrees should be at least equal to the matrix size, although theoretically the value should be slightly more than 3 times the matrix size for a 360-degree acquisition to avoid angular aliasing. The matrix size should be chosen to avoid limiting image resolution, which means the voxel size should be one-half to one-third of the FWHM collimator resolution at a typical radius of rotation.
The use of wide energy windows increases both the number of scattered and unscattered photons that are counted. Energy window selection in both SPECT and PET has been shown to be less critical because the increased count statistics associated with the contribution from small angle scatter has been shown to improve the image quality.
The radiopharmaceutical is an important determinant of the reliability of quantitative estimates because it affects quantitative accuracy primarily through the biodistribution and kinetics. These have an important impact on PVEs as well as the number of counts in, and thus the precision of activity estimates for, objects of interest.
For single-photon imaging, the energy of the photons emitted can have an important impact on accuracy and precision. Intrinsic sensitivity of the scintillation camera is lower for high-energy photons than for medium-energy photons. In addition, high-energy collimators typically have poorer resolution and sensitivity characteristics than corresponding low-energy collimators. Isotopes with multiple photopeaks, including low-abundance high-energy photons, can also suffer from the effects of downscatter into the imaging energy windows. The choice of PET isotope can affect resolution through the differing positron range, and, for some isotopes (e.g., 124I, 86Y), the presence of prompt gamma-ray emission within the positron decay scheme can lead to an increase of coincidence events that do not provide spatial information about the site of radionuclide decay.
The reconstruction algorithm can have important effects on image noise properties. Generally, statistical image reconstruction algorithms will provide better results. The maximum likelihood-expectation maximization (ML-EM) algorithm and, to some extent, the closely related ordered subsets-expectation maximization (OS-EM) algorithm have the theoretical potential to produce unbiased estimates for objects larger than the image resolution when a sufficient number of iterations are used and all effects are modeled in the reconstruction. However, the resulting images will not be suitable for visual interpretation. Use of regularization, including postreconstruction filtering, will increase PVEs while improving precision. When regions of interest can be defined based on anatomical images, the overall reliability of activity estimates in large regions will likely be improved if unregularized images are used due to reduced PVEs.
Finally, image analysis, including registration of images in a time series and the method used to define the VOI, can result in bias and imprecision in activity estimates. Therefore, care should be taken to ensure the best possible registration between serial images, preferably using associated computed tomography (CT) scans from hybrid scanners if available.