Читать книгу Salivary Gland Pathology - Группа авторов - Страница 78

Positron emission tomography (PET) is a unique imaging modality that records a series of radioactive decay events. Positron emission is a form of radioactive decay in which a positron (positively charged electron) is emitted from the unstable atom to achieve a more stable state. The positron almost immediately collides with an electron (negatively charged) and undergoes an annihilation event in which both particles are destroyed and converted into pure energy. The annihilation event produces two gamma rays, each with 511 Kev (kilo electron volt) of energy, and traveling in 180‐degree opposition. By using sophisticated solid‐state detectors, and coincidence circuitry, the PET system can record the source of the event, thereby localizing the event in three‐dimensional space. Using a complex algorithm similar to SPECT and CT, a three‐dimensional block of data is produced and can be “sliced” in any plane, but most commonly in axial, coronal, and sagittal planes, as well as a maximum intensity projection (MIP) rendering.

Figure 2.25. Contrast‐enhanced axial CT exam through the parotid gland prior to biopsy demonstrates a relatively large heterogeneous mass with ill‐defined borders (a). (b) Ultrasound‐guided core needle biopsy. Note the biopsy needle passing into the hyperechoic mass within the parotid gland. (c) Fine needle aspiration biopsy: Note the darkly staining cells that appear atypical. A definitive diagnosis cannot be reached utilizing this cryptologic material. (d) Core needle biopsy. Note the darkly staining epithelial cells arranged in ductal groups. This biopsy was consistent with an atypical mixed tumor. (e) Surgical material from a parotidectomy. This lesion represents a carcinoma ex. mixed tumor. Note the similar cells seen in the core needle biopsy.

PET radionuclides are produced in a cyclotron and are relatively short lived. Typical radionuclides include ¹⁸F, ¹¹C, ¹⁵O, ⁸²Rb, and ¹³N. A variety of ligands have been labeled and studied for the evaluation of perfusion, metabolism, and cell surface receptors. The most commonly available is ¹⁸F‐deoxyglucose (FDG), which is used to study glucose metabolism of cells. Most common uses of FDG include oncology, cardiac viability, and brain metabolism. PET has a higher spatial resolution than SPECT. Both systems are prone to multiple artifacts, especially motion. Acquisition times for both are quite long, limiting the exam to patients who can lie still for prolonged periods of time. Both systems, but PET in particular, are very costly to install and maintain. Radiopharmaceuticals are now widely available to most institutions through a network of nuclear pharmacies.

The oncologic principle behind FDG PET is that neoplastic tissues can have a much higher metabolism than normal tissues and utilize glucose at a higher rate (Warburg 1925). Glucose metabolism in the brain was extensively studied using autoradiography by Sokoloff and colleagues at The National Institutes of Health (NIH) (Sokoloff 1961). The deoxyglucose metabolism is unique in that it mimics glucose and is taken up by cells using the same transporter proteins. Both glucose and deoxyglucose undergo phosphorylation by hexokinase to form glucose‐6‐phosphate. This is where the similarities end. Glucose‐6‐phosphate continues to be metabolized, eventually to form CO₂ and H₂O. Deoxyglucose‐6‐phosphate cannot be further metabolized and becomes trapped in the cell as it cannot diffuse out through the cell membrane. Therefore, the accumulation of FDG reflects the relative metabolism of tissues (Sokoloff 1986). The characteristic increased rate of glucose metabolism by malignant tumors was initially described by Warburg and is the basis of FDG PET imaging of neoplasms (Warburg 1925).

FDG PET takes advantage of the higher utilization of glucose by neoplastic tissues to produce a map of glucose metabolism. Although the FDG PET system is sensitive, it is not specific. Several processes can elevate glucose metabolism, including neoplastic tissue, inflammatory or infected tissue, and normal tissue in a high metabolic state. An example of the latter includes uptake of FDG in skeletal muscle that was actively contracting during the uptake phase of the study (Figure 2.26). Another peculiar hypermetabolic phenomenon is brown adipose tissue (BAT) FDG uptake (Figure 2.27). BAT is distributed in multiple sites in the body including interscapular, paravertebral, around large blood vessels, deep cervical, axillary, mediastinal, and intercostal fat, but is concentrated in the supraclavicular regions (Cohade et al. 2003b; Tatsumi et al. 2004). BAT functions as a thermogenic organ producing heat in mammals and most commonly demonstrates uptake in the winter (Tatsumi et al. 2004). BAT is innervated by the sympathetic nervous system, has higher concentration of mitochondria, and is stimulated by cold temperatures (Cohade et al. 2003a; Tatsumi et al. 2004). Administration of ketamine anesthesia in rats markedly increased FDG uptake presumably from sympathetic stimulation (Tatsumi et al. 2004). Although typically described on FDG PET/CT exams, it can be demonstrated with ¹⁸F‐Fluorodopamine PET/CT, ⁹⁹mTc‐Tetrofosmin, and ¹²³I‐MIBG SPECT as well as ²⁰¹TlCl, and ³H‐l‐methionine (Baba et al. 2007; Hadi et al. 2007). Propranalol and reserpine administration appears to decrease the degree of FDG uptake whereas diazepam does not appear to have as significant an effect (Tatsumi et al. 2004). Exposure to nicotine and ephedrine also resulted in increased BAT uptake; therefore, avoiding these substances prior to PET scanning can prevent or reduce BAT uptake (Baba et al. 2007). Preventing BAT uptake of FDG can be accomplished by having the patient stay in a warm ambient temperature for 48 hours before the study and by keeping the patient warm during the uptake phase of FDG PET (Cohade et al. 2003a; Delbeke et al. 2006). Although somewhat controversial, diazepam or lorazepam and propranalol can reduce BAT uptake by blocking sympathetic activity, as well as reducing skeletal muscle uptake from reduced anxiety and improved relaxation (Delbeke et al. 2006). Understanding the distribution of BAT and the physiology that activates BAT, as well as recognizing the uptake of FDG in BAT in clinical studies, is critical in preventing false positive diagnosis of supraclavicular, paravertebral, and cervical masses or lymphadenopathy.

Figure 2.26. CT (a), PET (b), and fused PET/CT (c) images in axial plane and an anterior maximum intensity projection (MIP) image (d) demonstrating skeletal muscle uptake in the sternocleidomastoid muscle and biceps muscle (arrows). Note also the intense uptake in the abdominal, psoas, and intercostal muscles on the MIP image. The very high focal uptake in the middle of the image is myocardial activity.

FDG uptake in all salivary glands in the normal state is usually mild and homogenous (Burrell and Van den Abbeele 2005; Wang et al. 2007) (Figures 2.28 and 2.29). After therapy, radiation or chemotherapy, the uptake can be very high (Burrell and Van den Abbeele 2005). Standardized uptake values (SUVs), a semiquantitative measurement of the degree of uptake of a radiotracer (FDG), may be calculated on PET scans. There are many factors that impact the measurement of SUVs, including the method of attenuation correction and reconstruction, size of lesion, size of region of interest, motion of lesion, recovery coefficient, plasma glucose concentration, body habitus and time from injection to imaging (Beaulier et al. 2003; Schoder et al. 2004; Wang et al. 2007).

A range of SUVs can be calculated in normal volunteers for each salivary gland. Wang et al. measured SUVs in normal tissues to determine the maximum SUV and mean SUV as well as assignment of an uptake grade ranging from none (mean SUV less than aortic blood pool) to mild (mean SUV greater than mean SUV of aortic blood pool but less than 2.5), moderate (mean SUV between 2.5 and 5.0), and intense (mean SUV greater than 5.0). SUV greater than 2.5 was considered significant (Wang et al. 2007). Parotid glands (n = 97) had a range of SUVmax of 0.78–20.45 and a SUVmean range of 1.75 ± 0.79. Fifty‐three percent of the SUV measurements fell into the “none” category, 33% into the “mild” category, and 14% into the “moderate” category. No SUV measurement fell into the “intense” category. Submandibular glands (n = 99) had a SUVmax range of 0.56–5.14 and a SUVmean of 2.22 ± 0.77. The uptake grades consisted of the following: 25% were in the “none” category, 44% in the “mild,” and 31% were in the “moderate.” The sublingual gland (n = 102) had a SUVmax range of 0.93–5.91 and a SUVmean of 4.06 ± 1.76. Four percent of these fell into the “none” category, 19% in the “mild,” 54% in the “moderate,” and 23% in the “intense” group (Wang et al. 2007). Similar work by Nakamoto et al. demonstrated SUVmean of 1.9 ± 0.68 for the parotid gland, 2.11 ± 0.57 for the submandibular gland and 2.93 ± 1.39 for the sublingual gland (Nakamoto et al. 2005). This demonstrates the wide range of normal uptake values (Table 2.3).

Figure 2.27. PET image (a), corresponding CT image (b) and a fused PET/CT image (c) in the axial plane demonstrating brown adipose tissue (BAT) uptake in the supraclavicular regions bilaterally, which could mimic lymphadenopathy (see arrows on a and b). Direct correlation enabled by the PET/CT prevents a false positive finding. Note the similar uptake on the MIP image (arrow) (d) including paraspinal BAT uptake.

Although, FDG does accumulate in the saliva, the concentration varies from 0.2–0.4 SUV but does not influence FDG imaging (Stahl et al. 2002). SUV of greater than 2.5 has become a threshold for abnormal or neoplastic uptake (originally described by Patz et al.) (Patz et al. 1993; Wang et al. 2007). However, careful analysis must be undertaken when evaluating lesions based on SUVs as there is a significant overlap of SUVs for malignant and benign tumors and inflammatory conditions. One cannot depend on SUV measurements alone, and must take into consideration clinical data as well as radiologic imaging findings.

Figure 2.28. CT (a) and PET (b) images in axial plane demonstrating normal parotid gland activity (arrow).

Figure 2.29. CT (a) and PET (b) images in axial plane demonstrating normal submandibular (long thin arrow) and sublingual gland (medium arrow) activity. Note the abnormal uptake higher than and anterior to the submandibular glands (short fat arrow). Metastatic lymphadenopathy was diagnosed at the time of surgery.

Table 2.3. Standard uptake value (SUV) of salivary glands.

Source: Data from Wang et al. (2007) and Nakamoto et al. (2005).

Gland	SUV max (range)a	SUV mean ± SDa	SUV mean ± SDb
Parotid gland	0.78–20.45	1.75 ± 0.79	1.90 ± 0.68
Submandibular gland	0.56–5.14	2.22 ± 0.77	2.11 ± 0.57
Sublingual gland	0.93–5.91	4.06 ± 1.76	2.93 ± 1.39

^a Wang (2007).

^b Nakamoto (2005).

SD = standard deviation.