الفهرس 
Anatomy of the head and neckOnly 14 pages are availabe for public view
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Abstract
In the last decade, Combined PET/CT has been introduced into the field of oncologic imaging representing a unique imaging modality that scans the whole body integrating functional information from a PET scan with anatomical information from a CT scan. Combined PET/CT is considered a major breakthrough in oncologic imaging where PET and CT complement each other’s strengths. Combined PET/CT adds a significant benefit compared to either of its components alone, as well as compared to side by side reading of separately acquired PET and CT. This can be explained by the integration of advantages of both modalities while overcoming the limitations of each.
18F labeled fluoro-deoxy-glucose (18F-FDG) is the most commonly used PET radiotracer for oncologic imaging. 18F-FDG PET provides valuable metabolic information based on the fact that malignant cells exhibit high uptake of FDG, as an analogue of glucose, due to increase of their metabolic rate. But FDG, by the same mechanism, will accumulate in other tissues with increased metabolic rate secondary to a wide range of benign etiologies (e.g. infectious and inflammatory processes). In addition, normal tissues may also accumulate FDG; this is a particular problem in the head and neck region where multiple normal structures physiologically and variably accumulating FDG are in close proximity to each other including:
Lymphatic structures (adenoids, lingual and palatine tonsils), Nasopharynx and Larynx, Salivary glands, Thyroid gland ( in case of toxic nodules, diffuse thyroiditis, Grave’s disease), Cervical muscles (sternocleidomastoid), extraocular muscles, muscles of the oral cavity and tongue and Activated brown fat.
Combined PET/CT is the integration of the most sensitive imaging modality (PET) with the highest resolution, cross-sectional imaging modality (CT) with a remarkable increased diagnostic accuracy. This is achieved through:
• Accurate anatomic correlation provided by CT allowing:
• Improved localization and determining extensions of malignant lesions
• Identification of false positive results by localizing physiologic FDG uptake to normal structures or benign pathologies
Hence, CT adds specificity to highly sensitive PET. CT may also be able to increase the sensitivity of PET examination, for example in determining small lesions beyond the spatial resolution of PET (micro metastases in the lung) or those at areas susceptible to respiratory motion.
• Attenuation correction for PET images provided by CT transmission scans resulting in: a better PET image quality with less noise and at a relatively short time.
• Valuable functional information provided by PET adding specificity to CT findings, e.g. in detecting malignancy in normal sized lymph nodes and in the differentiation of recurrent/residual malignancy from tissue necrosis.
Combined PET/CT has its own artifacts that are worth to mention to be aware of while interpreting images. The main PET/CT artifacts are:
• Misregistration of lesions resulting from motion during scans. The major incremented factor here is respiratory motion or more precisely difference in breathing patterns during the PET and CT scans. It results in misregistration of lesions at lung bases and liver dome.
• Attenuation artifacts resulting from difference in attenuation between X-ray and -ray photons being of different energy values. It is generated by dense structures (high density oral contrast agents, concentrated bolus of IV contrast in mediastinal vessels or urinary tract and metallic implants). They are only visualized on AC images, i.e. they can be identified by their absence on NAC images.
Adequate patient preparation and scanning regulations are essential to achieve a successful 18F-FDG PET/CT examination where the main goals are to achieve a good quality images and to reduce false positive results. Several instructions should be followed strictly regarding the dietary control, medications, contrast administration (oral and intravenous), positioning, controlling respiratory movement and of course proper scan timing whether relative to tracer injection or to previous therapeutic modalities. All of which serve to achieve acceptable blood glucose level, minimize physiologic FDG uptake and reduce artifacts.
Interpreting a PET/CT study is done by correlating PET and CT data and viewing fused PET/CT images. PET images (NAC and AC images) and CT images in different windows (soft tissue, bone and lung) are viewed in different reconstruction planes (axial, sagittal and coronal as well as maximum intensity projections). Integrated interpretation and correlation of all the available data should be done. The assessment of radiotracer uptake is done by visual assessment of the uptake pattern, its correlation to the background activity and measurement of standardized uptake value (SUV). SUV is the measured activity normalized for body weight / surface area and injected dose. The SUV of a tissue can be depicted as the minimum, maximum or mean in the region of interest. SUVs are variable from one institution to another or even from one examination to another in the same institution, depending on various technical factors. Therefore, published cutoff values should be used cautiously and it is advisable to standardize SUV parameters at each institution and record it for each patient. SUVs are considered a semi-quantitative assessment of the radiotracer uptake.
Dual time point imaging has been suggested as an approach to overcome the overlap between benign and malignant causes of increased FDG uptake. It depends on scanning at two time points; with a delayed scan after 30 minutes or more. The change in radiotracer uptake in-between the two scans is evaluated; FDG uptake increases over time in malignant lesions and usually decreases or remains stable in benign ones. This may serve to increase test specificity and reduce false positive results.
18F- FDG PET/CT has acquired a firm place in the evaluation of malignancies. The major applications of 18F-FDG PET/CT in oncologic imaging are:
• Initial staging of disease and detection of synchronous malignancies
• Monitoring response to therapy; it is gaining a widespread acceptance as a key tool used to demonstrate response to therapy:
• Early: Evaluation of early metabolic response in the form of quantitative changes in FDG uptake (SUV measurement) shortly after starting therapy. The plan of management can be adapted according to PET findings. A baseline pre treatment scan and standardized SUV parameters are essential for accurate response assessment. Tumor response is categorized into:
Progressive metabolic disease, Stable metabolic disease, Partial metabolic response, Complete metabolic response
• Late: Differentiation of post therapy changes from residual/recurrent lesions and to predict future outcome.
• Target volume delineation in radiotherapy planning:
18F-FDG PET/CT has a high sensitivity and specificity in detection of malignancy resulting in more accurate staging that may change the intent of radiotherapy, for instance from curative to palliative when distant metastasis is detected. Moreover, PET/CT reduces the inter-observer variability in target delineation and modifying the extensions of gross tumor volume, clinical tumor volume and planning target volume for both primary tumor and regional lymph nodes. PET/CT is particularly useful in radiation treatment planning in the head and neck region where a multitude of sensitive structures is confined to a small area of the body. One beneficial application is parotid gland sparing to preserve salivary function. Functional PET imaging introduced the definition of biological target volume which has different implications based upon the used radiotracer. Therefore, novel PET radiotracers that trace molecular processes other than metabolism, e.g. hypoxia are being investigated for this evolving role.
In the region of head and neck, 18F-FDG PET/CT is strongly applied in various malignancies: nasopharyngeal, oral and oropharyngeal, laryngeal and salivary glands malignancies. PET/CT is efficient in the primary staging and restaging of all these malignancies. The major benefit is its superior nodal staging; it upstages a large number of patients regarded as N0, particularly in oropharyngeal carcinoma in which occult nodal metastases is common. PET/CT is effective at detection of distant metastases and synchronous primary malignancies. PET/CT is very valuable for detecting residual/recurrent disease in the neck and differentiating it from post therapeutic tissue necrosis. At least, it can guide to a proper biopsy site.
The efficiency of PET/CT in evaluating primary tumor extensions is a matter of debate. PET alone is known for its poor resolution; it is assumed that CT images (with their higher resolution and accurate anatomical localization) can increase specificity of PET regarding this indication. It helps to identify areas of bone invasion, orbital invasion, skull base involvement, and vascular and/or neural invasion. However, PET/CT shouldn’t be used alone in initial staging particularly of nasopharyngeal carcinoma; MRI is yet regarded as the primary imaging modality for evaluating extensions of primary nasopharyngeal carcinoma and detection of retropharyngeal lymph node.
In salivary glands malignancies, false positive results should be considered because of FDG uptake by the more common benign tumors (Warthin’s tumors and oncocytomas). False negative results are also reported in case of low grade malignancies obscured by normal FDG uptake.
18F-FDG PET/CT can be added to the diagnostic work up of carcinoma of unknown primary. It can identify small or submucosal malignancies or those at areas non accessible to endoscopy. It allows more effective directed biopsies and permits more focused treatment with reduced morbidity.
In differentiated thyroid cancer, 18F-FDG PET/CT is useful in cases presenting with elevated Tg and normal 131I whole body scan. PET/CT can detect recurrent/metastatic lesions in these cases. Regarding incidentally discovered thyroid nodules, some features may help to characterize these nodules; associated diffuse FDG uptake on PET images, very low attenuation (cystic) nodules or no discernible nodules on CT images favor benignity. SUV max of malignant nodules should be significantly higher than benign ones but a significant overlap is noted. PET/CT was investigated for the possibility to reduce the number of unnecessary hemithyroidectomies for thyroid nodules with inconclusive cytology results, it showed a reliable negative predictive value of (100%), but yet may be considered not cost effective for this indication.
Whole body imaging by 18F-FDG PET/CT is increasingly regarded as a standard imaging modality for evaluation of lymphoma. This is because of the superiority of PET as a metabolic imaging technique in accurate detection of tumor involved lymph nodes regardless their size, appearance and enhancement and its high sensitivity for detecting splenic lymphoma. It is also suggested to be specific and sensitive in detecting bone marrow involvement. PET sensitivity for lymphoma varies depending on the histological subtype and its FDG avidity; high sensitivity is encountered in all histological subtypes of HD as well as diffuse large B-cell lymphoma and follicular lymphoma.
18F-FDG PET/CT has a significant impact on staging accuracy of lymphoma which interns influence the plan of management and prediction of outcome. PET/CT is very valuable at evaluating early metabolic response after few cycles of chemotherapy. Accordingly the international response criteria for monitoring treatment of lymphoma were recently revised after incorporating metabolic criteria from PET, to be categorized into: complete remission, partial remission, stable disease, relapsed disease and progressive disease. Visual analysis of uptake is sufficient for monitoring response of lymphoma.
Early prediction of the response to therapy introduced the concept of risk adapted therapy: PET/CT might identify patients who could be cured with less intensive/toxic regimens aiming to achieve a higher cure rate with a lower or equal risk of treatment related morbidity (however, it’s still uncertain whether radiotherapy can be safely omitted or not). Alternatively, identifying patients who need an early switch to an alternative more aggressive regimen may improve the likelihood and duration of remission. The predictive value of PET in these situations depends on the type and stage of disease before therapy.
At end of treatment, 18F-FDG PET/CT has also the ability to distinguish between viable lymphoma cells and necrosis or fibrosis in post treatment residual masses and is highly predictive of PFS and OS. Also, it is helpful in deciding whether to perform or not to perform biopsy in post treatment residual masses. PET/CT may have a role in the detection of preclinical relapse, allowing for patients to enter salvage therapy (stem cell transplantation) with minimal disease rather than overt relapse.
The future of Combined PET/CT seems bright with a stronger evolving role and wider valuable applications in oncology. A lot of future perspectives are awaited with great interest enabling better application of the device with maximum benefits and least pitfalls.
Modern PET/CT scanners incorporating new detectors elements with better efficiency and improved device spatial resolution will help to increase PET sensitivity and diagnostic accuracy. Also the incorporation of respiratory gating has been strongly advocated recently and introduced the definition of four-dimensional PET/CT. It has the potential to overcome respiratory motion artifacts and the subsequent lesions misregistration. Moreover, it permits more accurate image co-registration which is of extreme benefit in radiotherapy planning purposes.
Another advance in PET/CT seems to be the incorporation of novel radiotracers which trace molecular activities other than metabolism (e.g. hypoxia, proliferation or apoptosis). They are promising alternative for FDG which is considered a non tumor specific probe. Their application in radiotherapy planning is an exciting field; providing greater insight into different biologic pathways involved in radiation responses. They are investigated for their ability to overcome the problem of FDG avid radiotherapy induced inflammatory changes and to provide data about tumor response to radiation at early stages, thereby allowing better readjustment of radiation field. Novel radiotracers may also allow imaging of tumors that are non FDG avid (e.g. choline derivatives for prostatic carcinoma). Octreotide derivatives are tried for endocrine-active tumors and amino acid derivatives for brain tumors because, unlike FDG, they do not accumulate much in normal brain.
It is also essential to regularize criteria for response assessment using PET/CT particularly in lymphoma, such that patients can be enrolled in multicenter studies with defined objective guidelines and standardized scan parameters for comparative purposes. This topic is still evolving; retrospective studies evaluating the newly introduced therapy response criteria, recommendations and guidelines are awaited with great interest with the hope to develop new valuable probes.
Finally, Combined PET/CT using 18F-FDG is the best oncologic imaging modality at the time being with valuable applications in head and neck malignancies. It is very efficient with least possible pitfalls and false results compared to either of its components alone and to side by side reading of separately acquired PET and CT. It can be a standard modality for lymphoma providing a new vision to management and treatment plan. New applications for PET/CT are awaited with great interest.