According to the World Health Organization (WHO) worldwide, more than half of the total number of cancer cases is in developing countries. Some 75 percent of these patients have been found to be incurable at the time of diagnosis. These statistics are changing due to two distinct diagnostic techniques – In Vivo and In Vitro. These methods determine the presence of a disease and the extent to which it has invaded the body and can help to determine the best means of treatment.
a) In Vivo Techniques: In vivo diagnostic techniques are based on an approach called the “Tracer” principle. A radionuclide – in a carefully chosen chemical form and duration of being radioactive called a radiopharmaceutical – is administered to the patient to trace a specific physiological phenomenon by means of a special detector, often a gamma camera, placed outside the body. The radiopharmaceutical can be designed to seek out only desired tissues or organs, such as the lungs. By directing radiation only where it is needed, rather than randomly, modern techniques increase the health benefits available through nuclear applications.
Some 100-300 available radiopharmaceuticals mostly organic in nature and labelled with artificial radionuclides, such as indium-111 and gallium-67, are used to study organs and tissues without disturbing them. Nuclear diagnostic methods expose the patient to a small radiation dose. This is minimized further with more short-lived radioisotopes, such as technetium-99m, which decay to stable form within hours.
The radiopharmaceutical is administered to the patient, usually by intravenous injection, oral ingestion, or inhalation. With a special detecting device, a gamma camera, it is observed as it travels throughout the body where it is specifically concentrated in a given tissue or organ. A gamma camera detects photons escaping the body, creating a two-dimensional image with the help of a computer and a video display unit. These images depict the regional quality of a specific function in a given organ. This process is called planar imaging or static scintigraphy
These images, when received in a fast successive fashion, create a dynamic study of the radiopharmaceutical behaviour, revealing such detailed functional information as the emptying of the stomach, the breathing process in the lungs, or the pumping activity of the heart.
Such procedures, like an X-ray, may provide a picture of some particular body organ or part of it. The essential difference is that in nuclear medicine, the picture obtained provides a measure of the activity of a specific physiological or biochemical function in the body, while an X-ray image depicts anatomical details.
With the increased power of modern computers, clinical images can be acquired at multiple angles, creating a replica of the body’s cross-section, a technique called computerized tomography (CT). The two most advanced forms using radionuclides are single-photon emission computed tomography (SPECT) and position emission tomography (PET).
SPECT uses a rotating gamma camera to obtain images from multiple angles of the distribution of a conventional gamma emitting radiopharmaceutical within an organ. This technique is particularly valuable because of its unique ability to locate the exact position of a physiological abnormality in the body through a series of computer-generated bidimensional slices of the organ, from which three-dimensional pictures of the organ can be reconstructed.
PET, valuable in the detection and management of cancer, employs one or several rings of stationary detectors around the patient’s body to detect very strong diverging gamma rays (511 keV) produced by the interactions of positrons (emitted by a previously administered radionuclide) with the free electrons within the body. This information is then processed to create body slices similar to those obtained by SPECT. PET has the unique ability to depict regional biochemical processes within the body and can demonstrate the biochemical foundation of neurological disorders and mental diseases.
b) In Vitro Techniques: The second method of diagnosis, in vitro, allows clinical diagnosis without the patient being exposed to radiation. In fact, the patient need not even be present. A blood sample taken from the patient is sent to the laboratory and examined through nuclear techniques such as radioimmunoassay (RIA), or immunoradiometric assay. (IRMA).
These tests measure precisely previous and current exposure to infection by assessing antibodies. RIA is also used to measure substances such as hormones, vitamins, and drugs in the body fluids in the detection of nutritional and endocrinological disorders and to track bacterial and parasitical infections such as tuberculosis and malaria. Supported through IAEA co-ordinated research programmes, some 500 hospitals, universities, and laboratories in the developing world alone are engaged in RIA on some scale and the numbers are increasingly annually.
Another application of RIA and IRMA techniques includes the detection of tumour markers, which are specific substances secreted by many, but not all, tumours and can indicate the presence of malignancy. Nearly two dozen tumour markers are available. Despite the increased accuracy, as well as cost and convenience factors, tumour markers remain complementary to other diagnostic procedures in the detection of cancer during its early stages, but they are especially valuable in monitoring the progress of disease and the effects of treatment.
Diagnostic imaging is one of the most innovative areas of modern medicine. Diagnostic imaging can be divided into the following two broad categories:
- Modalities that very precisely define anatomical details and examples include Computed Tomography (CT), and Magnetic Resource Imaging (MRI), which identify structural changes down to the millimetre; and
- Modalities producing functional or molecular images and examples include Positron Emission Tomography (PET) and Single Emission Computed Tomography (SPECT), which investigate diseases down to the molecular level.
The hybrid imaging systems like SPECT/CT and PET/CT are the result of the merge of anatomical and functional modalities. These systems allow a combined investigation of both the anatomy and the function of human organs. The clinical benefits are numerous and include better identification and localization of lesions combined with better characterization of structural and metabolic changes within the identified lesions. Consequently, diseases are detected in their earliest phase with higher accuracy, signifying an early treatment with the highest chance of a complete and quick recovery. Hybrid imaging has been successfully applied in cardiology and cancer.
PET/CT is used to evaluate blood flow impairment in coronary artery blockage, which may lead to tissue necrosis. In oncology, hybrid imaging enables the early detection of cancer, demonstrating changes at the cellular level long before anatomical changes appear. In orthopaedic surgery, SPECT/CT and PET/CT are the best imaging modalities for the investigation of lower back pain and may be used in post-surgical and post-traumatic situations. Other areas of applications of hybrid imaging include the evaluation of benign diseases that affect the brain, thyroid, parathyroid and any other organs of the human body.The origins of PET, SPECT and CT date back into the early 1970s. Almost in parallel in the early 1970s, Ambrose and Hounsfield introduced a computerized x-ray tube based tomographic scanner providing images of tissue densities from acquired projections. In contrast to the evolution of SPECT/CT, the first PET/CT scanner was developed as a combination of a then state-of-the-art spiral CT and a partial-slip-ring “Poor Man’s PET” on a common rotational support within a single gantry with the PET components on the reverse side of the rotating support of the CT scanner. This design reduced the expensive detectors from 144 to 66 and brought the price tag down to below 1 Million USDS. Townsend published their combination SMART scanner providing sequential imaging using the table as shuttle using the advantage of having the patient in the same body position without changing.
Almost a decade later the first prototype, SPECT/CT system was developed. This prototype used the same high-purity germanium detector array for both x-ray and single-photon imaging. The same group developed a different design by combining a CT scanner with a commercial gamma camera but it was not until the millennium when a different design became the first commercially available SPECT/CT system. This was in part triggered by the fact that this manufacturer was the first who used a slip ring for its gamma camera gantry, allowing > 360° rotation. This design was based on low speed and low current CT (Hawkeye) that was explicitly developed for hybrid imaging with the Infinia gamma camera.
At this time, this was the logical approach as it provided sufficient topographic orientation and a transmission map for attenuation and scatter correction closely resembling the organ positions during the SPECT acquisition. The Hawkeye opened the market for SPECT/CT, but surprisingly or not in the end, the market voted for other designs with MD CT scanners. Siemens introduced the Symbia series in 2004 followed by Philips Precidence.
Nuclear medicine procedures have been performed for many years. These procedures use a scintillation camera. The scintillation camera is an imaging device used in the practice of nuclear medicine. It utilizes a thin but large area thallium activated sodium iodide crystal as the radiation detector. Originally, multiple planar projections were acquired to provide diagnostic information but more recently, the techniques of SPECT have been utilized. During this time, the scintillation camera has evolved to a high-quality imaging device, and much of this evolution is due to the integration of digital technology into
every aspect of the data acquisition, processing, and display processes.
Conventional planar images generally suffered from poor contrast due to the presence of overlying and underlying activity that interferes with imaging of the region of interest. This is caused by the superposition of depth information into single data points collected from perpendicular or angled lines of travel of photons from the distribution being studied into the holes of the parallel hole collimator fitted to the scintillation camera. The resulting planar image is low in contrast due to the effect of the superposition of depth information. This effect can be reduced by collecting images from multiple positions around the distribution and producing an image of a transverse slice through the distribution. The resulting tomographic image is of higher contrast than the planar image due to the elimination of contributions of activity above and below the region of interest. This is the goal of SPECT, i.e., to provide images of slices of radionuclide distributions with image contrast that is higher than that provided by conventional techniques.SPECT and PET systems are used to image distribution of radiopharmaceuticals in order to provide physicians with physiological information for diagnostic and therapeutic purposes. However, these images often lack sufficient anatomical detail, a fact that has triggered the development of a new technology termed hybrid imaging. Hybrid imaging is a term that is now being used to describe the combination of x-ray CT systems with nuclear medicine imaging devices, SPECT and PET systems, in order to provide the technology for acquiring images of anatomy and function in a registered format during a single imaging session with the patient positioned on a common imaging table.
Radionuclide imaging, including SPECT and PET, relies on the tracer principle, in which a small quantity of a radiopharmaceutical is administered in to the body of the patient to assess the physiology of the internal organs. The external radiation detectors detect the rays (gamma or positron) emanating from the patient, the quality of the image is degraded by cross talk of the adjacent tissues. The uptake of the tracer (tumor or infection) can be identified as a hotspot but to find out that exact anatomical location is a cumbersome process.
Combined SPECT/CT and PET/CT scanners revolutionized Nuclear Medicine. The software fusion of emission image and transmission image is labour intensive and complicated. The introduction of the combined PET/CT solves the problem through hardware rather than software. Hybrid scanners can acquire a patient study accurately and align anatomic and functional images from a single scanning session. Like PET/CT, SPECT/CT acquires both scans with the patient in the same position. Since the patient remains positioned on the same bed for both imaging modalities, temporal and spatial differences between two sets of images are minimized. Hybrid scanners (SPECT/CT and PET/CT) improve lesion localization and interpretation accuracy. Although SPECT/CT and PET/CT imaging offers many advantages, this dual modality imaging also poses some challenges. The use of the CT based attenuation correction has the drawback of producing artefacts on the resulting PET/SPECT imaging. At present 4D, respiratory gating technique is used to reduce respiratory motion artefact. In future, continuous bed motion PET/CT acquisition and improvement in detector efficiency and 64 or 256 slice CT scanner will play a lead role in molecular imaging.Here are some major advantages of hybrid cameras:
- Uniform distribution of the radiopharmaceuticals provides excellent functional information by PET/SPECT and CT provides superb spatial and contrast resolution;
- Dual or multislice with axial or spiral mode reduces the scan time and increases patient comfort;
- Image fusion is facilitated by the dual-modality imaging systems, this helps the oncologist to stage and to plan for treatment;
- Integrated patient couch allows both the x-ray and emission data to be acquired without removing the patient from the system;
- Consistent patient geometry facilitates co-registration of CT image with PET or SPECT image;
- Capability of the dual-modality imaging system to integrate CT and Emission data increases the diagnostic accuracy (91 percent to 98 percent);
- CT portion of the scan may demonstrate other diseases important in the clinical care of patients;
- CT image obtained with a dual-modality system can be used to generate a patient – specific attenuation map for correcting radionuclide image (SPECT or PET) for photon attenuation; and
- Dual –modality imaging system provides excellent anatomical detail which is not possible with PET/SPECT systems.
Here are some trade-offs and challenges associated with hybrid cameras:
a) Vertical Bed Deflection: To ensure accurate image registration, it is important that bed deflection be minimized as the table extends in to the FOV. Cantilever point of the table changes as it moves into the scanner. Conventional CT or PET/SPECT camera’s does not meet these requirements. To overcome this difficulty, Patient Handling System (PHS) is redesigned. The table is supported at one end on the pedestal that moves horizontally on floor-mounted rails; because of this cantilever, the point does not change. This design enables the CT and Emission data to register accurately;
b) Software Integration: Integration of CT and PET/SPECT control, processing and display software is a challenge because each modality has its own specific features, windowing and measurement tool of CT and region-of-interest (ROI) manipulation and standardized uptake value (SUV) calculations for PET. Integration was achieved by providing different task card for CT and PET/SPECT operation;
c) Image Display: Anatomical and functional images can be merged to display. Alpha blending method is used to display fusion images. In this method color, display values are averaged with those of CT. Over laying images causes a reduction in CT contrast is a trade-off;
d) Patient Port: PET scanner has a port of 60 cm and CT scanner has a port of 70 cm. Integrated PET/CT scanners have a patient port 70 cm that is larger than stand-alone PET systems this increases noise level in the emission images. Scatter and random correction algorithms reduces the noise level;
e) Attenuation Correction: Compton scattering and photoelectric effect interactions dominate attenuation of photons. X-ray source emits photons with energies in the range of 30 to 140 keV where photo electric absorption dominates, PET imaging occurs at 511 keV where Compton scattering dominates. Attenuation of photon energies depends on the tissue they traversed and there is no linear relationship between x-ray attenuation values and PET attenuation values. The challenge here is to use CT data for attenuation correction. Linear attenuation co-efficient obtained from the CT scan has to be converted those corresponding to the 5ll KEV. Conversion methods like scaling, segmentation; hybrid is used to solve this problem;
f) Respiratory Motion: PET scan require longer acquisition time when compare to CT scan. PET scan is acquired over multiple breathing cycles. Images from two scanning modalities show discrepancies in the anatomic localization of the organs. CT images are used for attenuation correction of the PET emission data because of the mismatch of the two data sets quantitative and qualitative errors occurs. To overcome this challenges different breathing techniques were employed during each modality scan – most centers use shallow breathing method. Now Gated 4D CT scan is used for motion correction;
g) Tube Current and Tube Voltage in Attenuation Correction: Tube current improves image quality at the expense of increasing the patient dose. To reduce patient dose is a challenge. Now it is proved for CT based attenuation correction low-current CT is sufficient. CT images may be acquired at different tube voltages depending on patient size and region under study, attenuation correction is overestimated if tube voltage is higher than 140 KVP and under estimated if it is less than 80 KVP. A bilinear calibration curve is used for conversion of CT numbers in to linear attenuation co-efficient at 511 Kev at different tube voltages. This solved the issue related to tube voltage; and
h) Other Challenges to Over Come: Metallic implants, obese patients, truncation, oral and IV contrast medium, hip prosthetic material, pacemaker and ICD leads creates problem when CT data is used for attenuation correction. Metallic implants produce streak artifacts, respiratory motion leads to image mismatch and contrast medium overestimates attenuation correction. Several mathematical computer algorithms were developed to solve these issues.
Until recently, most reviews about hybrid imaging have focused on the clinical advantages due to the better anatomical allocation of PET/SPECT images, but at least in PET/CT the biggest advantage was that of improving image reconstruction by speeding the transmission scan. Coincidence imaging in PET and Single Photon imaging in SPECT imaging, though completely different in some of their physical basics, need several corrections to improve imaging and to allow quantification, with attenuation and scatter correction being the most important. Whereas these corrections are now regarded as mandatory in PET, they may gain importance in quantitative SPECT, but at present are only implemented in myocardial perfusion imaging and brain imaging. Initially both, PET and SPECT, used radioactive sources for transmission imaging, but attenuation maps generated from CT scans can be acquired much faster. However, three issues may hamper this approach: Misalignment, energy dependent attenuation and CT artefacts. A recent survey showed PET is most frequently used in oncology (87 percent), followed by neurology (5 Percent), radiation therapy planning and cardiology (4 Percent), respectively. I.v oral contrast was used at 52 percent of the sites in up to 25 percent of patients but only 62 percent of the sites provided a fully integrated PET/CT report. As stand-alone PET systems have disappeared, the clinical question is not if CT is used but to what extent it is performed as a diagnostic CT.
- IAEA – Applications of Nuclear Techniques in Medicine;
- IAEA – Nuclear Technology Review 2010;
- Springer – Hybrid PET/CT and SPECT/CT Imaging;
- Knol – HYBRID CAMERAS – SPECT/PET/CT; and
- Hybrid PET/CT and SPECT/CT Imaging.
- This chapter was published on “Inuitech – Intuitech Technologies for Sustainability” on April 6, 2012; and
- This article was updated on 26 June 2020.