Uniformity of gamma camera images

Introduction
In 1958, Hal Anger developed the first ?- camera and forever changed the area of nuclear medical imaging. Anger’s camera (also known as scintillation camera or gamma camera) used a 6 mm thick scintillation crystal (NaI) coupled to seven photomultiplier tubes (PMTs), each 3.5 cm diameter, arranged in a hexagonal shape. The crystal was used to convert the gamma rays into scintillation photos which would then be converted into electrical signals by the PMTs. The output of the PMTs in Anger’s camera was analogue and represented continuous values of gamma ray energy and the position of the event. The camera had a collimator mounted in front of the sodium iodine crystal, which was used to stop scattered gamma rays and essentially form the image. In the initial design of the gamma camera all the circuits were analogue and the camera is still known as an “analogue camera”. The images were displayed in cathode ray tubes (CRTs) or they were imprinted onto photographic films which were used as hard copies.

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        Later on, with the development of electronics and computer technology, the analogue output of the photomultiplier tubes would be fed into a digital computer which would process the signals to form the clinical image. In order to achieve that, analogue to digital converters (ADCs) were incorporated into Anger’s design which would digitize the signals before feeding it to the processing unit. Gradually all the major electrical components of the gamma camera were replaced by digital electronics and in modern cameras the signals are digitized by ADCs installed individually in every PMT. The complete digitization of the gamma camera allowed for significant improvements of the prototype gamma camera. With the increased processing power available, modern gamma cameras can nowadays image at high count rates, can store digital images and display them directly onto computer screens. Furthermore, they can implement a range of corrections which have drastically improved the quality of the modern clinical images.
Our objective in this essay is to describe the factors that affect the uniformity of gamma camera images, the technological advancements that have improved the camera’s imaging quality and capability as well as the methods that are currently used to assess and correct a ? – camera’s uniformity.
The basic components of a gamma camera and their function
The general principles behind the function of a gamma camera are rather simple to understand. So, before we proceed onto discussing the uniformity of a ?-camera, we ought to mention its basic components and their function since they can affect image uniformity.
The main components of a gamma camera are described below.
The gantry of the gamma camera provides mechanical support to the detector head. The scintillation crystal [usually NaI (TI)], is maybe the most important component of gamma camera. Its function is to convert the incident gamma rays, originating from the patient, into scintillation photons. Between the crystal and the photomultiplier tubes, a transparent light guide is put in place to maximize the optical transmission of light from the crystal to the PMTs.
Once the scintillation photons reach the photocathodes of the PMTs, they get converted into photoelectrons. The photoelectrons then, go through an amplification stage where their number is multiplied by a series of dynodes. Finally the electrons hit the PMT’s anode and we get the output voltage that represents our signal. The photomultiplier tubes are connected to the pulse arithmetic circuits where the position and the energy of each event are determined. In addition, at the PMT output, gamma cameras incorporate a pulse height analyzer that determines which events get accepted based on their energy. This mechanism is put in place in an effort to reject signals arising from scattered photons that have managed to penetrate the collimator. The pulse height analyzer is also known as the “energy window”. The energy window is usually set to accept events with energies ranging from -10% to +10% of the peak energy. For example, when imaging with 99mTc (? emitter, 140 KeV, T1/2 = 6 h) the energy window is set between 126 KeV and 154 KeV.
The final component of the detector head of the gamma camera is the collimator. It is a lead plate with a large number of holes which is placed in front of the scintillation crystal. The main function of this component is to control which of the gamma rays pass through to the crystal and which ones are stopped. Gamma rays that travel parallel to the collimator’s holes (perpendicular to the crystal) are allowed through while oblique rays are attenuated. The role of the collimator is essential because it provides the PMTs with the ability to identify the location of each event and it stops scattered x-rays which spoil the contrast of the images. In addition, the collimator provides physical protection to the extremely sensitive and fragile scintillation crystal that lies beneath it.
Camera Uniformity
The term uniformity refers to the variations of intensity present in an image acquired using a uniform radioactive source.
Factors that affect ? – camera uniformity
In the previous section of this essay we described briefly the function of the gamma camera. In reality however, things do not work perfectly. In fact there are numerous sources that can cause image imperfections and ruin the uniformity of our images. The most common sources and factors that affect image uniformity are:

variations in hole size and angulation
variations in septal thickness

non uniformities in the crystal’s stopping power
non uniformities in the number of scintillation photons emitted by the crystal
non uniformities in the transmission of light through the light guide and the optical grease

variations in light collection efficiency with the event’s position in the crystal due to geometry
variations in light collection efficiency with the depth of interaction in the crystal due to geometry
variations in the quantum efficiency of the photocathode across the face of the photomultiplier tubes
variations in PMT tuning – gain differences between PMTs

Count rate
Energy of incident gamma rays

To begin with, it is fairly obvious that a poorly constructed or damaged collimator will affect primarily the sensitivity of the gamma camera. The sensitivity variations arise from the fact that a defective collimator will attenuate gamma rays in a non uniform manner. That is to say, that the number of gamma rays which pass through the collimator’s holes will vary either due to differences in the septal thickness or due to differences in the angulation of the holes. So, the image will appear either “hot” or “cold” depending on the number of counts, thus ruining the uniformity of the image. The collimator, however, is not the only cause of imperfections.
In an ideal world, the scintillation crystal would exhibit properties such as homogeneous stopping power, interaction with gamma rays only through photoelectric absorption, transparency towards scintillation photons and high conversion efficiency (gamma to scintillation photons). However, in reality, the crystal presents with variations in its stopping power which ultimately lead to sensitivity imperfections and the appearance of “hot” and “cold” spots on our images. As we mentioned above, this variation in counts is a manifestation of non uniformity. Furthermore, the scintillation crystals exhibit incongruities in their light output. This is attributed to variations in the doping of the crystal with the chemical which serves as the activation centre for the luminescence phenomenon. (In the NaI crystal the doping is performed using thallium). In addition real crystals exhibit non uniform transmission of light, in cases where the optical grease used to couple Crystal-PMTs is dried out, or if the crystal has been exposed to moisture in which case opacities (yellowing) are developed. Finally, non uniformities in the images also originate from variations in the fraction of light that the photomultipliers collect. Light is lost between the gaps of the PMTs array but also near the edges of each individual PMT due to reflection. The majority of scintillation photons are collected near the center of the PMT, where the collection efficiency is best. This causes the counts to appear as if they were pulled towards the centre of the PMT and results to non- linearities. Even, the smallest non linearities will result in large non uniformities in the images.
Last but not least, we ought to mention non uniformities arising from variations in the function of the photomultiplier tubes. The photocathode of a PMT, in reality, does not convert photons into electrons uniformly. Its quantum efficiency is better near its center and deteriorates as we move toward the edges. In addition, different PMTs tend to exhibit slightly different gains which ultimately lead to non uniformities. For example, a PMT with a gain above/below the correct gain will result in fewer counts falling within the energy window, creating a cold area over the dysfunctional PMT. Drift in PMT gain is usually caused over time, due to ageing, exposure to magnetic fields (Earth, MRIs), temperature fluctuations or power supply instabilities.
So far we have discussed how the function of the gamma camera components can affect uniformity in practice. For completeness, we ought to mention that gamma camera uniformity (specifically the intrinsic uniformity) can also be affected by other factors such as: the activity of the radionuclide used to image, the number of acquired counts, the source-camera distance and the source volume. According to Elkamhawy, Rothenbach, Damaraju and Badruddin the intrinsic uniformity of the gamma camera increases with the increase of the source activity. However the increase in activity must not exceed the count rate capabilities of the camera otherwise non uniformities may be caused.
In addition, according to Elkamhawy et al., the intrinsic uniformity increases as the counts go up. This is something to be expected, considering the probabilistic nature of the phenomenon of radioactive decay. Poisson statistics teach us that as the counts become higher the relative standard deviation decreases. That is to say that the coefficient of variation is reduced as the number of counts goes up and the statistical noise decreases. Finally, there are reports of an inverse correlation between the source to camera distance and the intrinsic uniformity. As the distance increases the intrinsic uniformity is increased due to a more uniform attenuation of the gamma rays travelling towards the crystal. That is to say, when the source is close to the crystal the gamma rays have to travel longer to reach the edges of the crystal than the centre. (See figure 2). Therefore the gamma rays travelling towards B will suffer greater attenuation that gamma rays travelling to point A. This difference in attenuation will result in count differences thus increasing the intrinsic non uniformity. However, if we increase the source – to – crystal distance, the gamma rays will undergo more or less the same attenuation due to the inverse square law and the counts will be more uniform throughout the crystal.
Developments in gamma camera technology that have contributed in uniformity improvements.
In older, analogue gamma cameras, the only correction that could be performed was a sensitivity correction that dealt with sensitivity variations on the images. Following the technological developments, the high processing capabilities of modern microprocessors and the implementation of analog to digital converters into their design, modern gamma cameras have been equipped to deal with non uniformities through a series of corrections.
        Differences in photomultiplier gain used to be dealt with using the cosmetic approach which entailed the individual tuning of each PMT to match the other. Advances in microprocessors now allow for more advanced approaches. Maps containing the regional differences in pulse heights, as acquired from uniform flood sources, can be used to correct on an event to event basis (on the fly). As we mentioned earlier PMTs are affected by various external factors and they are caused to drift. Novel technologies have been introduced into gamma cameras which enables them to keep the gains stable in real time. For example, manufactures such as Toshiba, Elscint and IGE have implemented auto stabilization techniques where LEDs are used to tune the PMTs. The LEDs emit light which is detected by the tubes and the output voltage is then compared with a reference voltage and the gain is adjusted accordingly. With the increased processing power other corrections are currently being used too. Linearity and energy corrections are common ways to improve the degree of uniformity in modern cameras.
In the energy correction the most common practice is to expose the camera to a monochromatic gamma ray source (usually 99mTc) and acquire reading for the energy in various positions. Theoretically, the energy signal should remain constant independent of location on the crystal. However, as we have mentioned earlier there is always a small fraction of light which is lost. So, the readings are compared to the mean – expected energy and a map of correction factors is stored in the gamma camera’s memory which is used to rectify any errors in the energy signals.
The linearity correction has a similar function. We would expect every event’s position coordinates to appear as a linear combination of the PMTs output voltages. , Y. But again due to light losses that is never true in practice. Fortunately, this is easily corrected through the linearity correction maps similar to those that we acquire for the energy correction. First of all, we remove the collimator and we introduce a lead plate with parallel holes throughout its extent. Then the system is exposed to a uniform point source. The image is processed and the positional errors are determined and stored as a separate correction map.
The final correction to be applied on an image is the sensitivity correction, which has been used in the past as the only uniformity correction of analogue cameras. In modern cameras the technicians first stabilize the gains of the PMTs and then they proceed to apply the energy and linearity correction which have the greatest impact in the cameras uniformity. Then, and only then, they proceed with the sensitivity correction. The correction maps for the sensitivity are acquired by exposing the gamma camera (with the collimator mounted) to a uniform radioactive source. The counts are scaled up or down to eliminate any remaining cold or hot spots on the image. We should note that the individual correction maps should be acquired for each collimator since the sensitivity variations are primarily caused by collimator defects and other factors that we have already discussed.
The scientific community has not stopped at the abovementioned corrections. Manufacturers and researchers have shifted their focus to new technologies hoping to replace components that contribute to bad uniformity but also to improve other gamma camera properties (resolution, count rate capability e.t.ch). For example, position sensitive photomultiplier tubes have been introduced (Hamamatsu, Photonis et. al.), which are capable of detecting the location of the event more accurately and efficiently that conventional PMTs. In addition to that, silicon photodiode arrays are being used coupled to the scintillation crystals for improved light sensitivity and quantum efficiency. Finally, there is a shift of interest towards replacing scintillation crystals with semiconducting materials. The combination of cadmium telluride with zinc makes for a great x ray and gamma ray detector. The main advantage of semiconductors over scintillation crystals is that the first converts photons directly into electrical current. Contrary to the scintillation crystal that needs to use the photomultiplier tubes which are a significant source of non uniformities as we have mentioned.
Quality Control: Measurement of non – uniformity in gamma cameras
Maintaining good uniformity in clinical images is extremely important. Even the smallest degree of non uniformity can cause artifacts which can prevent doctors from diagnosing the patient or lead them to the wrong diagnosis. The assessment of a gamma camera’s uniformity is an integral part of its quality control and it is carried out in regular intervals (daily or weekly basis). These kind of investigations are carried out to ensure that there are no, non-uniform areas in the cameras field of view.
The uniformity of a gamma camera can be measured either intrinsically or extrinsically. In the intrinsic setup, the collimator is removed and the naked crystal is exposed to a low activity uniform flood source. This setup has the advantage that the measurements are not affected by collimator induced non uniformities. In the extrinsic setup the system uniformity is assesses and the collimator is mounted onto the crystal. The advantage in this case is that the conditions of measurement are closer clinical parameters since in clinical acquisition the collimator is always in place. As far as the flood sources are concerned, 99mTc and 57Co are the most common choices. The technetium has the advantage of being readily available in hospitals and can be used as a mixture of radioactive material and water to create a uniform flood source. Also technetium is the most common radionuclide used in daily medical practices. Moreover, the presence of water presents a more realistic scatter source resembling scattering conditions in patients. The main drawback of the technetium flood source is that it has a short half life and must be used soon after its creation. In addition, the construction method presents with the danger of spilling and contamination. An alternative to 99mTc is a 57Co source which has a convenient half life of 271 days. The peak energy of cobalt is close to that of technetium which is convenient in cases where the camera’s performance is energy dependent. On the other hand, cobalt flood sources are quite costly and are usable only for about a year. Furthermore, cobalt sources often contain amounts of other cobalt isotopes Co60 and Co58 which emit higher energy gammas and may affect our measurements.
A common testing protocol is the following. The radioactive source is placed at a distance approximately 4 times the field of view to ensure that the variation between the counts in the centre and the edge of the crystal is sufficiently small (as we have explained in figure 2) and can be ignored. The crystal is irradiated uniformly and a few million counts are acquired (approximately 1- 5 million counts). We need to acquire a statistically sufficient number of counts to ensure that the Poisson noise is minimal. We make sure that all the right corrections have been applied before we assess the images. A visual inspection of the images usually reveals gross deviations in performance. However, once the images have been acquired they are processed, using the camera’s software, to yield values for common parameters such as the mean uniformity and the corrected uniformity which are used to quantify the quality of the camera. The mean uniformity informs us for the overall uniformity of the camera throughout the FOV. The corrected uniformity is acquired by removing the Poisson noise from the mean uniformity. Those are not the only parameters that we can examine and other such as the integral uniformity and the differential uniformity are often assessed.
Conclusion
The uniformity of a gamma camera is maybe the most important parameter that expresses the quality of the cameras performance. Non uniform areas in the field of view can result in misdiagnosed patients and low quality of clinical services. Thus it is essential to perform regular checks to ensure optimal performance of the ? – camera. Assessing the uniformity of a camera is not easy. As a parameter, uniformity is dependent on many factors and there are many things that can go wrong. Gamma cameras require regular testing, responsible operation and expert knowledge of its governing principles to make sure that its performance stays within clinically acceptable levels.
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