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PET/CT Table of Contents   
Year : 2008  |  Volume : 18  |  Issue : 2  |  Page : 141-147
Pictorial essay: PET/CT in tuberculosis


1 Department of Nuclear Medicine and PET/CT Facility, Army Hospital (Research and Referral), Delhi Cantt, New Delhi - 110 010, India
2 Department of Radiodiagnosis and Imaging, Army Hospital (Research and Referral), Delhi Cantt, New Delhi - 110 010, India

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How to cite this article:
Harkirat S, Anand S S, Indrajit I K, Dash A K. Pictorial essay: PET/CT in tuberculosis. Indian J Radiol Imaging 2008;18:141-7

How to cite this URL:
Harkirat S, Anand S S, Indrajit I K, Dash A K. Pictorial essay: PET/CT in tuberculosis. Indian J Radiol Imaging [serial online] 2008 [cited 2019 Jul 22];18:141-7. Available from: http://www.ijri.org/text.asp?2008/18/2/141/40299
In routine practice, oncologic workup is responsible for the majority of referrals for whole-body FDG-PET/CT. The indications in oncology include staging, restaging, assessment of therapy response, and detection of recurrence. In spite of the great success achieved by FDG-PET imaging in the evaluation of malignant disorders, the modality is not specific for the diagnosis of cancer. [1] It has been noted that processes such as infection and inflammation, and particularly granulomatous diseases, also cause increased FDG uptake in the affected tissues. [2],[3],[4],[5],[6]

Tuberculosis (TB) is a chronic granulomatous inflammation caused by Mycobacterium tuberculosis . India accounts for nearly a third of the global burden of tuberculosis, with approximately 1.8 million new cases of tuberculosis reported every year. [7] Although it involves the thorax most frequently, any organ system in the body can be infected. The clinical and radiological features of tuberculosis are known to mimic those of many other diseases. The role of FDG PET and PET/CT in TB and other inflammatory diseases is evolving and is not as yet clearly defined.

At the same time, there is a considerable increase in PET/CT referrals for patients with fever of unknown origin (FUO), generalized lymph node (LN) enlargement, and mediastinal or abdominal lymphadenopathy, especially when other investigations are inconclusive. The aim of such referrals is generally to rule out an underlying malignant disease or to detect an inflammatory pathology. Infections remain the most frequent cause of FUO, followed by neoplasms and noninfectious inflammatory diseases. [8],[9] In India, TB is known to be the commonest infection to present as FUO. [10] 'The high sensitivity of FDG PET in detecting malignant lesions, infections, and other inflammatory processes alike, makes it an important tool that has the potential to play a role in the diagnostic protocol and management of patients with FUO.' [11],[12]

While performing FDG PET/CT for oncologic workup, we found TB to be a common cancer mimic, producing uptake patterns that are indistinguishable from that of cancer. Many studies have documented increased FDG uptake in active TB in diverse anatomical locations, mimicking malignant processes. [5],[6],[13],[14],[15],[16],[17] Though a high standardized uptake value (SUV), greater than 2.5, is attributed to malignant lesions, [18] we have encountered high values of peak SUV, upto 21.0 (range 2.2-21.0), in tuberculous lesions [Figure - 1],[Figure - 2],[Figure - 3],[Figure - 4],[Figure - 5],[Figure - 6],[Figure - 7].


   Case Material Top


All studies were performed on an integrated PET/CT scanner (Biograph 2, Siemens Medical Solutions, Erlangen, Germany). A whole-body PET/CT study, from the skull base to the mid-thigh level, was performed 1 h after intravenous injection of 370 MBq of FDG. Nonenhanced CT scan images were obtained, using 130 KV and 100 mAs. CT-based attenuation correction was done. Images were reconstructed using a standard iterative algorithm and reformatted into transaxial, coronal, and sagittal views. Fusion images of PET and CT were obtained. The PET/CT images were evaluated by one radiologist and one nuclear medicine physician in all cases. Focal accumulation of FDG above the background muscle uptake in an abnormal location was considered a positive finding. Areas of increased uptake were evaluated qualitatively and quantitatively using standard methods. [19] The peak SUV (SUV max ) of the abnormal areas was noted.

Patients with a diagnosis of tuberculosis were identified from the database. A large number of these were referred for workup of FUO or lymphadenopathy [Figure - 5],[Figure - 6],[Figure - 7],[Figure - 8],[Figure - 9]. Others included suspected cases of malignancy that turned out to have tuberculosis [Figure - 2],[Figure - 10],[Figure - 11],[Figure - 12] and follow-up cases of cancer found to have associated TB [Figure - 1]. A few patients had established TB and were referred for evaluation of the extent of disease or to monitor response to treatment [Figure - 3],[Figure - 13]. [Table - 1] lists all the cases described here.


   Role of Accompanying CT Scans Top


CT images of PET/CT were helpful in characterizing the lesions morphologically and in some instances, especially in lung and bone lesions, were indicative of a tuberculous etiology. We did not use intravenous contrast enhancement for our CT scans. However, the use of intravenous contrast may increase the specificity of diagnosis in some instances, by more accurately demonstrating the presence of necrosis in enlarged lymph nodes or the presence of typical focal lesions in the liver and spleen.


   Organs Top


Central nervous system

According to Kang et al ., 'the possibility of a tuberculous brain abscess should be considered when FDG accumulates at the periphery of a ring-enhancing lesion in a chronically ill or immunocompromised patient.' [20] FDG-PET shows intense tracer uptake at the periphery of the lesion in a ring-like or 'doughnut' pattern, with low uptake within the abscess cavity [Figure - 2].

Thorax

Intense FDG uptake is usually noted in active tuberculous lesions involving the lung parenchyma [6],[21] [Figure - 3]. This is attributed to the presence of a large number of activated macrophages which have a high glycolytic rate. The CT images in PET/CT may add useful morphological information in defining the nature of the lung lesions. PET may help in determining the activity in the lesions, define the extent of disease, and aid in assessing the response to therapy. High FDG uptake has been reported in tuberculomas [16] [Figure - 4].

A common dilemma faced during oncologic workup with FDG-PET/CT is the presence of FDG-avid mediastinal or hilar nodes in cases of extrathoracic malignancies (e.g., carcinoma colon, renal cell carcinoma, or carcinoma cervix). In these entities, isolated mediastinal nodal metastases are uncommon and tuberculosis may be the cause of FDG-avid mediastinal or hilar adenopathy [Figure - 1].

Lymphoreticular system

In mediastinal, supraclavicular, and intra-abdominal tuberculous lymphadenitis, a high focal uptake of FDG has been reported. [21],[22],[23] We found FDG-avid tuberculous nodes in diverse locations [Figure - 1],[Figure - 5],[Figure - 7],[Figure - 8]. Also, disseminated TB can variably involve the liver and spleen. In proven cases of disseminated TB, we found varied patterns of increased FDG uptake in the liver and spleen, some showing diffuse and others focal uptake [Figure - 7],[Figure - 8].

Skeletal system

Osteomyelitis: Tuberculous osteomyelitis is a common entity in Asian countries, with frequent involvement of the spinal column. This entity classically involves contiguous dorsal or lumbar vertebral bodies and the intervening discs, often associated with abscess formation and granulation tissue. FDG-PET has a high sensitivity for the detection of chronic osteomyelitis. [24] Tuberculous lesions are found to have increased FDG uptake in the active regions of granulomatous inflammation, with cold areas that represent necrosed tissue (pus) [25] [Figure - 9],[Figure - 13].

Abdomen

Although TB can involve any part of the gastrointestinal tract, from the esophagus to the anal canal, the most commonly involved regions are the distal ileum and cecum. The lesions may be ulcerative, proliferative, or ulceroproliferative. The latter type may present as a bowel mass, indistinguishable from bowel cancer on routine imaging modalities and may exhibit intense uptake on FDG-PET imaging [14] [Figure - 10],[Figure - 11]. Involvement of the adrenal gland may also present with FDG avidity [Figure - 12]. The role of FDG-PET in assessing the urinary system is limited because of the interference caused by the high concentration of the excreted FDG in urine, which masks FDG-avid lesions.

Dual time point imaging

Studies have documented the value of additional delayed images, obtained 90-120 min after FDG injection, in differentiating benign from malignant lesions. On delayed images, inflammatory lesions show increased FDG washout, whereas cancerous lesions usually exhibit further accumulation of tracer. [26],[27] However, in our experience, in 15 TB patients, we found equivocal results with dual time point imaging at 45 and 120 min post-FDG injection; a majority of the tuberculous lesions showed no reduction, a few showed mild reduction (up to 20%), and many showed an increase (varying from 10-40%), in peak SUV.

The future

FDG-PET has a high sensitivity for infection and inflammation but poor specificity. One approach that may increase the diagnostic accuracy of PET for tuberculosis includes the combined use of F-18 FDG and C-11 acetate, as the latter accumulates in tumors but not in inflammatory lesion. [28] Thus, C-11 acetate may help differentiate inflammation from neoplasms. In the future, labeling antituberculous drugs like isoniazid and rifampicin with positron emitting isotopes may culminate in the development of TB-specific PET radiopharmaceuticals.


   Conclusion Top


Due to the high prevalence of tuberculosis in India, false positive cases during oncologic workup with FDG-PET are commonly encountered in practice. Though FDG PET/CT is not specific for tuberculosis, it plays an important role in the evaluation of known or suspected TB cases. FDG PET/CT can determine the activity of lesions, guide biopsy from active sites, assess disease extent, detect occult distant foci, and evaluate response to therapy. Active tuberculous lesions often exhibit a high degree of FDG uptake, though this can vary, depending upon the grade of inflammatory activity. No characteristic pattern has been identified as yet that will definitely differentiate them from cancerous lesions.

With FDG-PET imaging per se , based on semiquantitative analysis using SUV and the dual time point imaging technique, it is currently not possible to differentiate malignant lesions from active tuberculosis consistently. However, with an integrated PET/CT technique, the CT scan images may help differentiate tuberculosis from malignant lesions, using morphologic criteria. The use of intravenous contrast increases this ability. In future, new, more specific radiotracers, like positron-emitter labeled antituberculous drug molecules may help to differentiate TB from cancer and nontuberculous inflammatory processes.

 
   References Top

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2.Yamada S, Kubota K, Kubota R, Ido T, Tamahashi N. High accumulation of fluorine-18-fluorodeoxyglucose in turpentine-induced inflammatory tissue. J Nucl Med 1995;36:1301-6.  Back to cited text no. 2    
3.Ichiya Y, Kuwabara Y, Sasaki M, Yoshida T, Akashi Y, Murayama S, et al . FDG-PET in infectious lesions: The detection and assessment of lesion activity. Ann Nucl Med 1996;10:185-91.  Back to cited text no. 3    
4.Yago Y, Yukihiro M, Kuroki H, Katsuragawa Y, Kubota K. Cold tuberculous abscess identified by FDG PET. Ann Nucl Med 2005;19:515-8.  Back to cited text no. 4    
5.Chen YK, Shen YY, Kao CH. Abnormal FDG PET imaging in tuberculosis appearing like lymphoma. Clin Nucl Med 2004;29:124.  Back to cited text no. 5    
6.Yang CM, Hsu CH, Lee CM, Wang FC. Intense uptake of [F-18]-fluoro-2 deoxy-D-glucose in active pulmonary tuberculosis. Ann Nucl Med 2003;17:407-10.  Back to cited text no. 6    
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8.Gelfand JA, Callahan MV. Fever of Unknown origin. In : Harrisons Principles of Internal Medicine. 16 th ed. Kasper DL, Fauci AS, Longo DL, et al , editors. McGraw Hill: New York; 2005. p. 116-21.  Back to cited text no. 8    
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11.Meller J, Altenvoerde G, Lehmann K, Sahlmann C, Meyer I, Behe M, et al . Fever of unknown origin - Prospective comparison of 18 FDG- imaging with a double head coincidence camera (DHCC) and Ga-67 citrate SPECT. Eur J Nucl Med 2001;28:OS387.  Back to cited text no. 11    
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13.Chang JM, Lee HJ, Goo JM, Lee HY, Lee JJ, Chung JK, et al . False positive and false negative FDG-PET scans in various thoracic diseases. Korean J Radiol 2006;7:57-69.  Back to cited text no. 13    
14.Wang HY, Lin WY. Jejunal tuberculosis: Incidental finding on an FDG-PET scan. Kaohsiung J Med Sci 2006;22:34-8.  Back to cited text no. 14    
15.Takalkar AM, Bruno GL, Reddy M, Lilien DL. Intense FDG activity in peritoneal tuberculosis mimics peritoneal carcinomatosis. Clin Nucl Med 2007;32:244.  Back to cited text no. 15    
16.Goo JM, Im JG, Do KH, Yeo JS, Seo JB, Kim HY, et al . Pulmonary tuberculoma evaluated by means of FDG PET: Findings in 10 cases. Radiology 2000;216:117-21.  Back to cited text no. 16    
17.Fernandez P, Guyot M, Lazaro E, Viallard JF, Allard M, Ducassou D. Systemic tuberculosis presenting as an epiglottic mass detected on F-18 FDG PET/CT. Clin Nucl Med 2007;32:719-24.  Back to cited text no. 17    
18.Lowe VJ, Delbeke D, Coleman RE. Applications of PET in oncologic imaging. In : Diagnostic Nuclear Medicine. Sandler MP, Colemen RE, Patton JA, Wackers FJ, Gotschalk A, editors. 4 th ed. Lippincot: Philadelphia; 2003. p. 987-1014.  Back to cited text no. 18    
19.Takalkar AM, El-Haddad G, Lilien DL. FDG-PET and PET/CT - Part I. Indian J Radiol Imaging 2007;17:169-80.  Back to cited text no. 19    
20.Kang K, Lim I, Roh JK. Positron emission tomographic findings in a tuberculous abscess. Ann Nucl Med 2007;21:303-6.  Back to cited text no. 20    
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22.Cook GJ, Fogelman I, Maisey MN. Normal physiological and benign pathological variants of 18-fluoro-2-deoxyglucose positron-emission-tomography scanning: Potential for error in interpretation. Semin Nucl Med 1996;26:308-14.  Back to cited text no. 22    
23.Obama K, Kanai M, Taki Y, Nakamoto Y, Takabayashi A. Tuberculous lymphadenitis as a cause of obstructive jaundice: Report of a case. Surg Today 2003;33:229-31.  Back to cited text no. 23    
24.Zhuang H, Duarte PS, Pourdehand M, Shnier D, Alavi A. Exclusion of chronic osteomyelitis with F-18 fluorodeoxyglucose positron emission tomographic imaging. Clin Nucl Med 2000;25:281-4.  Back to cited text no. 24    
25.James SL, Davies AM. Imaging of infectious spinal disorders in children and adults. Eur J Radiol 2006;58:27-40.  Back to cited text no. 25    
26.Zhuang H, Pourdehnad M, Lambright ES, Yamamoto AJ, Lanuti M, Li P, et al . Dual time point 18 F-FDG PET imaging for differentiating malignant from inflammatory processes. J Nucl Med 2001;42:1412-7.  Back to cited text no. 26    
27.Matthies A, Hickeson M, Cuchiara A, Alavi A. Dual time point 18 F-FDG PET for the evaluation of pulmonary nodules. J Nucl Med 2002;43:871-5.  Back to cited text no. 27    
28.Liu RS, Shei HR, Feng CF. Combined 18F-FDG and 11C-acetate PET imaging in diagnosis of pulmonary tuberculosis. J Nucl Med 2002;43:127.  Back to cited text no. 28    

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Correspondence Address:
S Harkirat
Department of Nuclear Medicine, Army Hospital (R and R), Delhi Cantt, New Delhi - 110 010
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0971-3026.40299

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    Figures

  [Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6], [Figure - 7], [Figure - 8], [Figure - 9], [Figure - 10], [Figure - 11], [Figure - 12], [Figure - 13]
 
 
    Tables

  [Table - 1]

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