Current Medical Imaging - Volume 7, Issue 3, 2011

Over the past three decades, we have witnessed significant advances in medical imaging, which have improved the assessment of a multitude of disorders with higher accuracy and more precise spatial resolution. The introduction of Computed Tomography (CT) in 1973 opened a new era in structural imaging, which has continued up to now with further improvements in the practical applications of this powerful modality. CT has been of great value in a lot of disorders, particularly in a large number of surgical procedures, which are planned after acquisition of CT images demonstrating the anatomic lesions before operation. Soon after CT was introduced, Magnetic Resonance Imaging (MRI) became a main focus of interest because of its ability to investigate soft tissue abnormalities, particularly in the central nervous and musculoskeletal systems. For most neurological diseases, MRI has become the study of choice for detection and accurate characterization of the underlying disorder. Likewise, many musculoskeletal abnormalities lend themselves well to MR imaging because of its very high spatial and contrast resolutions in detecting lesions in this organ system. The practice of orthopedic surgery has also been substantially impacted upon by the capabilities that are provided by this very powerful modality. In spite of the enormous contributions made by these two very powerful structural imaging techniques, practitioners of medicine have realized that changes noted by CT and MRI are related to the appearance of the, often later, structural manifestations of disease, and may be rather insensitive to early pathological abnormalities or early changes in already known pathological lesions. By now, it has become clear that alterations in cellular metabolism at the molecular level are often early indicators of disease activity, sometimes even asymptomatic, and therefore detecting such changes may provide evidence for abnormalities not detectable by current anatomical imaging techniques. The changes on the molecular level may never translate to structural abnormalities or may be delayed for weeks or months after the disease process is initiated. Likewise, changes following treatment may not be apparent on these images for an extended period of time after therapeutic interventions are implemented. Since some treatments may not be effective and should be terminated and replaced with alternative therapies, such delays may adversely impact the optimal management of many serious diseases including cancer, cardiac diseases, and central nervous and orthopedic disorders. Positron Emission Tomography (PET), which utilizes positron emitting radionuclides labeled with biologically important analogues, has overcome many of the deficiencies that are enumerated above. This very powerful modality provides fairly high resolution images that are comparable to those of modern tomographic structural imaging techniques. In addition, this modality provides images with high contrast compared to the background. This allows detection of the disease in early stages, which leads to the introduction of rapid interventions soon after the disease has been discovered. Furthermore, PET is the only modality that allows accurate quantification of disease activity with high precision and reproducibility. The introduction of 18FfluoroDeoxyGlucose (FDG) by investigators at PENN started a new era in medical imaging, which has expanded into multiple domains over the past three decades. While the original intent for introducing this compound was to investigate neuropsychiatric disorders, it soon became apparent that FDG was an outstanding marker for assessing disease activity in cancer. Today FDG-PET is routinely employed for managing a large number of malignancies at diagnosis, staging, monitoring response to treatment, and detection of recurrence. However, FDG is a nonspecific tracer for detecting cancer and is also taken up by the inflammatory cells in various settings. This has led to the utility of this compound in assessing infection, inflammation, atherosclerosis, thrombosis and muscle disease. At the same time the obvious need of more specific tracers has resulted in a rapidly growing list of new, more specific PET compounds. In recent years, PET and CT instruments have been assembled as a unit and in fact a majority of studies performed around the globe employ this combination for an effective utilization of both modalities. This approach allows comparing images from both instruments side by side or fused together for precise localization of molecular abnormalities at different anatomical sites as visualized by CT scan. It has been clearly demonstrated that hybrid imaging with either SPECT or PET combined with CT hardware provides important information beyond that achievable with either technique alone. In addition, hybrid imaging reduces the number of equivocal results based on one imaging technique without the benefit of the other. For decades, physicians have employed sideby- side visual interpretation of images generated by different modalities obtained at different times. However, along with the introduction of combined hybrid imaging instruments, major efforts have been made in developing software that allows fusion images of various organs for research and clinical purposes particularly. This has been of great value in organs such as the brain where anatomic landmarks allow co-registration of structural and functional imaging successfully. However, the role of such approaches may disappear as hybrid imaging with dedicated instruments becomes widely available in the future......

There has been a longstanding interest in multi-modality imaging especially in nuclear medicine where the lack of structural information in Single Photon Emission Computed Tomography (SPECT) images and Positron Emission Tomography (PET) images makes it difficult to assess the precise location of tissue with metabolic uptake, whereas Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) can provide great anatomical details. The hardware approach to image fusion is to use hybrid scanners (SPECT/CT, PET/CT or PET/MRI). With this approach image fusion is simplified because the two scans are acquired sequentially (or simultaneously with PET/MR) which minimizes any motion. Hardware hybrid scanner designs are facing many challenges such as the conversion of CT numbers to attenuation coefficients, artefacts due to the presence of high Zeff material, and respiratory motion. Software approaches to multimodality imaging emerged in the late 1980's and were using semi-automated or automatic approaches by registering surface contours or surface points. The big step towards fully automated software based image fusion appeared when the registration method started to use a direct analysis of image data to achieve an optimal registration often using iterative approaches to maximize mutual information between images. Software based image fusion is complex and involves many decisions regarding fusion tools, reconstruction techniques and final image presentation of fused data.

Myocardial perfusion imaging (MPI), either using single photon emission computed tomography (SPECT) or positron emission tomography (PET), combined with noninvasive coronary angiography using multidetector computed tomography (MDCT) is now available for the diagnosis of coronary artery disease (CAD). The combination acquired in a hybrid scanner has shown to boost the advantages of either modality and compensate for their respective limitations. Generation of composite, fused, multimodality images containing detailed anatomic information from MDCT with their possible physiologic impact from MPI in a single setting makes the interpretation of the combined data sets easier and better than mental integration. This article describes the technical aspects of MPI and cardiac CT, and the role of cardiac hybrid imaging in providing unique information that may improve noninvasive diagnosis, risk assessment, and management of CAD.

Both structural and functional neuroimaging modalities have provided great insight into a variety of neurologic diseases. Techniques have now become available which allow coregistration of structural and functional imaging data, which have provided unique insights into neurologic function and pathophysiology. Hybrid SPECT/CT and PET/CT imaging platforms have further advanced understanding of brain structure/function. Recently, the first true hybrid PET/MRI devices have been introduced. This technologic breakthrough promises to contribute greatly to hybrid neuroimaging. Herein we review the impact of hybrid SPECT/CT and PET/CT, as well as PET/MRI coregistration techniques on a variety of neurologic diseases, including brain tumors, neurodegenerative diseases, epilepsy, cerebrovascular diseases, and pediatric conditions, with an emphasis on the future utility of hybrid PET/MRI imaging.

Combined structure-function approach utilizing the fusion of functional and anatomical modalities for more precise localization has been a major innovation of recent times in the arena of medical imaging. This approach is likely to make a major impact on the diagnosis and management of various benign and malignant disorders. The SPECT/CT and the PET/CT imaging systems are the two proof-of-principle examples that clearly depict the power of this approach. The advantages are particularly evident in patients with cancer where fused image obtained by the combination of functional data from PET/SPECT with high-resolution anatomical detail from a multi-slice CT scanner provides useful anatomical and functional information to detect, diagnose, characterize, or monitor tumors before and after therapeutic intervention and guide biopsies or surgical interventions. The approach is likely to be pivotal to optimize individualized treatment planning for several malignancies. Based upon available evidence at this point, the relatively established clinical applications of hybrid SPECT-CT in oncology include (a) lymphoscintigraphy, (b) bone imaging and (c) octreotide scintigraphy for investigating neuroendocrine tumors. The other emerging situations where it holds considerable potential include: patient specific dosimetry and estimation of organ residence time for planning of radionuclide therapy planning, as well as evaluation of malignancies where the role of FDG-PET imaging is limited (e.g. prostate cancer using capromab pendetide and brain tumors). Combined PET/CT imaging, on the other hand, has been integrated into the management of majority of the malignancies because it offers advantages in a large number of decision making steps in oncological practice including staging of the disease, therapy planning and monitoring treatment response and is considered as the ‘one stop shop’ investigation for the management of these patients. In this mini-review we discuss the impact of SPECT-CT and PET-CT imaging approaches which are becoming increasingly important for therapeutic decision making in the era of personalized medicine.

This mini-review describes how to perform PET/CT based radiotherapy dose planning and the advantages and possibilities obtained with the technique for radiation therapy. Our own experience since 2002 is briefly summarized from more than 2,500 patients with various malignant diseases undergoing radiotherapy planning with PET/CT prior to the treatment. The PET/CT, including the radiotherapy planning process as well as the radiotherapy process, is outlined in detail. The demanding collaboration between mould technicians, nuclear medicine physicians and technologists, radiologists and radiology technologists, radiation oncologists, physicists, and dosimetrists is emphasized. We strongly believe that PET/CT based radiotherapy planning will improve the therapeutic output in terms of target definition and non-target avoidance and will play an important role in future therapeutic interventions in many malignant diseases.

The appearance of hybrid PET/CT scanners has made quantitative whole body scanning of radioactive tracers feasible. This paper deals with the novel concepts for assessing global organ function and disease activity based on combined functional (PET) and structural (CT or MR) imaging techniques, their advantages over current quantitative techniques and their potential clinical applications in the management of various diseases. First the complicated kinetic modeling and methods for calculation of the standardized uptake value (SUV) that have been utilized in the practice of clinical PET are briefly described. Subsequently we discuss the quantitative concepts in PET-CT imaging that have been developed in recent years: (a) SUV analysis in the dual-time point and delayed PET imaging, (b) partial volume correction of SUV for small lesions (c) assessment of global metabolic activity in the whole organ or of diseased sites and (d) the novel image segmentation techniques with FDG-PET and newer tracers to precisely define the diseased or intended normal tissue which is of great value for image guided radiation therapy.

Small animal positron emission tomography (PET) and computer tomography (CT) is an emerging field in preclinical imaging. High quality, state-of-the-art instruments are required for full optimization of the translational value of the small animal studies with PET and CT. However, with this achieved the possibilities are numerous and the role of preclinical imaging crucial for a prompt movement from bench to bedside. Several new tracers are under preclinical and clinical evaluation and most are directed at central aspects of tumor biology. We hereby present some of the recent advances in this field of small animal molecular imaging with special emphasis on the targets for tissue characterization in tumor biology such as hypoxia, proliferation and cancer specific over-expression of receptors. The added value of applying CT imaging for anatomical localization and tumor volume measurements is also described. In addition, the noninvasive nature of molecular imaging and the targets of these promising new tracers are attractive for other research areas as well, although these fields are much less explored. We present an example of an interesting research field with the application of small animal PET/CT for studies of muscle and tendon in exercise models.

We present a method with fusion of images of three modalities 18F-FDG PET, CT, and 3-D ultrasound (US) applied to imaging of the anal canal and the rectum. To obtain comparable geometries in the three imaging modalities, a plexiglas rod, with the same dimensions as the US transducer, is placed in the anal canal prior to the PET-CT examination. The method is based on manual co-registration of PET-CT images and 3-D US images. The three-modality imaging of the rectum-anal canal may become useful as a supplement to conventional imaging in the external radiation therapy in the treatment of anal cancer, where the precise delineation of a tumor is crucial to avoid damage from radiation therapy to the healthy tissue surrounding it. The technique is still in a phase of development, and the demands for integration different company software systems are significant before commercial application. Three-modality imaging may also be used in certain other diagnostic or therapeutic fields.

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