Evaluation of Infection/Inflammation: What is the Role of PET/CT?

Transcription

1 Evaluation of Infection/Inflammation: What is the Role of PET/CT? Andrei Iagaru, MD School of of Medicine

2 Holy Grail: Ø The dish, plate or cup used by Jesus Christ at the Last Supper, said to possess miraculous powers Ø Later became the object of many chivalrous quests

3 Nuclear Medicine: What is the Holy Grail?

4 PET/CT in Infection/Inflammation ü 18 F FDG labeled WBC s vs. 18 F FDG ü Applications of 18 F FDG PET/CT in infection and/or inflammation: Ø Fever of unknown origin Ø Prosthesis evaluation Ø Chronic osteomyelitis Ø Diabetic foot Ø Vasculitidies

5 18 F FDG labeled WBC s vs. 18 F FDG 18 F FDG labeled WBC s 18 F FDG

6 18 F FDG labeled WBC s vs. 18 F FDG ü Specificity ü Risks associated with labeling ü Imaging at 3-5 hours enough for WBC localization??? ü How stable is the labeling ü Cost ü Non-specificity ü Can something (i.e., FDG) be good for everything??? ü Cost

7 ü 4 normal adult volunteers ü WBC s can be readily labeled with 18 F FDG ü Labeled WBC s show reasonable stability in vivo for several hours after injection ü Dosimetry data similar to 111 In labeled WBC s ü Good quality PET images can be obtained up to 6 hours after injection ü No GI uptake was appreciated on any of the scans

8 ü 21 patients (8 women, 13 men), years-old (mean: 56) ü Inclusion criteria: suspected infection and FUO ü Exclusion criteria: WBC<2000, favorable response to antibiotics, preganancy, age<18 years ü Results: median labeling efficiency 80% (24-96%; mean 75%) and mean labeling stability 90%

9 DIVERTICULITIS OSTEOMYELITIS Dumarey et al. JNM (4):

10 ENDOCARDITIS Dumarey et al. JNM (4):

11 ü 51 patients (26 women, 25 men), years-old (mean: 59) ü 8 subjects excluded: inadequate 18 F labeling (6), camera malfunction (1), non-cooperant (1) ü Labeling efficiency 72% for 18 F vs. 90% for 111 In (P < 0.001) ü WBC s viability of 98% for 18 F vs. 97% for 111 In

12 18 F FDG labeled WBC s Modality Sensitivity Specificity N PET (per patient) PET (per patient) PET (per lesion) PET (per lesion) PET (per patient) In WBC Dumarey et al. JNM (4): Rini et al. Radiology (3):

13 18 F FDG PET/CT in FUO Definition: a) Petersdorf and Beeson (1961) Ø recurrent fever of 38.3 or higher Ø lasting 2-3 weeks or longer Ø undiagnosed after 1 week of hospital evaluation (revised: after appropriate outpatient or inpatient evaluation) b) Durack and Street (1991) Ø classic FUO in non-immunocompromised patients Ø nosocomial FUO Ø neutropenic FUO Ø FUO associated with HIV infection

14 Sources of FUO ü Infections: 13-43% ü Autoimmune/colagen vascular disease/neoplasm: up to 54% ü Unknown: 10-40% 67 Ga citrate whole-body scan 18 F FDG PET/CT

15 ü 19 patients underwent 111 In WBC scan and 18 F FDG PET within 1 week ü Inclusion criteria: documented FUO ü Exclusion criteria: preganancy, age<18 years ü Results: Ø final diagnosis in 12/19 cases Ø 7 cases: infection/inflammation Ø 1 case: neoplasm Ø 4 cases: autoimmune disease

16 ü 35 patients underwent 18 F FDG PET ü Inclusion criteria: documented FUO ü Exclusion criteria: preganancy, age<18 years ü Results: Ø final diagnosis in 19/35 cases Ø 6 cases: infection Ø 4 cases: neoplasm Ø 6 cases: inflammation

17 LYMPHOMA SARCOID Bleeker-Rovers et al. EJNM :29-37.

18 ü 16 patients underwent 18 F FDG PET ü Inclusion criteria: documented FUO ü Exclusion criteria: preganancy, age<18 years ü Results: Ø final diagnosis in 11/16 cases

19 VASCULITIS TB & COLITIS Lorenzen et al. Nuc Med Comm :

20 ü 18 patients underwent 18 F FDG PET and 67 Ga scintigraphy ü Inclusion criteria: documented FUO ü Exclusion criteria: pregnancy, age<18 years ü Results: Ø 8 cases: infection Ø 2 cases: neoplasm Ø 5 cases: auto-immune disorders Ø 3 cases: unknown

21 TAKAYASU ADNEXITIS Meller et al. EJNM :

22 18 F FDG PET/CT in FUO Modality Sensitivity Specificity N PET In WBC PET PET PET Ga(SPECT) Kjaer et al. EJNM : Bleeker-Rovers et al. EJNM : Lorenzen et al. Nuc Med Comm : Meller et al. EJNM : Ga (planar)

23 18 F FDG PET/CT for Evaluation of Joint Prostheses Definitions: ü Total joint replacement is a surgical procedure in which a diseased or damaged joint, such as a hip or knee, is removed and replaced with artificial components ü Modern-day joint replacement surgery has been performed in the United States since the 1970s ü More than 700,000 individuals had hip or knee replacement surgery in 2002 ü Infected prostheses have mostly an indolent course, with progressive joint pain; however, some present acutely, with high fever, joint pain, swelling, and erythema

24 Normal Hip Arthritic Hip Replaced Hip

25 Normal Knee Arthritic Knee Replaced Knee

26 Infection in Joint Prostheses Risk factors: ü prior surgery at site of prosthesis ü rheumatoid arthritis ü corticosteroid therapy ü diabetes mellitus ü obesity ü malnutrition ü old age Pathogenesis: ü Occurs in osseous tissue adjacent to prosthesis: Ø bone cement interface Ø bone contiguous with prosthesis (cement-less devices) ü Results from: Ø local inoculation at surgery or post-op spread from wound sepsis Ø hematogenous spread

27 Infection in Joint Prostheses Management: ü Retain / replace prosthesis Ø simple debridement (retaining prosthesis) plus antibiotics - only successful in 20% of cases Ø removal of prosthesis, antibiotics for 6wks, reimplantation of prosthesis - 90%+ success Ø removal of prosthesis, immediate re-implantation, antibiotics - 70%+ success ü Resection arthroplasty ü Suppressive long-term antibiotics

28 ü 23 patients (14 women, 9 men), years-old ü Inclusion criteria: painful hip or knee prosthesis ü Results: Ø PET was false negative for loosening in 1 case ü Conclusion: Ø PET can be useful in differentiating between loose and infected prosthesis

29 SYNOVITIS LOOSENING AND SYNOVITIS INFECTION AND SYNOVITIS Manthey et al. Nuc Med Comm :

30 ü 50 patients (31 women, 19 men), years-old ü Inclusion criteria: painful hip prosthesis ü Results: Ø PET was 91% sensitive and 92% specific Ø 3 phase bone scan was 78% sensitive and 70% specific Ø no significant differences between cemented and uncemented ü Conclusion: Ø PET can better differentiate between aseptic loosening and infection

31 Mumme et al. Arch Orthop :322-9.

32 ü 21 patients (13 women, 8 men), years-old ü Inclusion criteria: suspicion for infected knee prosthesis ü Results: Ø WBC scan alone was 100% sensitive and 53% specific Ø PET alone was 100% sensitive and 73% specific Ø in combination with 3PBS, sensitivities increased to 93% for WBC scan and 80% for PET ü Conclusion: Ø PET seems to offer no additional benefit

33 INFECTION LOOSENING Van Acker et al. EJNM :

34 ü 59 patients (37 women, 22 men), years-old ü Inclusion criteria: painful prosthesis (40 hip, 19 knee) ü Results: Ø PET sensitivity was 100, 96, 52, 36% and specificity was 9, 35, 44, 97% based on different interpretation criteria Ø WBC/sulphur colloid scan was 100% sensitive and 91% specific ü Conclusion: Ø PET is less accurate and can t replace WBC/SC scanning

35 PET interpretation criteria: ü Positive criterion 1: Ø Any periprosthetic activity, regardless of location or intensity ü Positive criterion 2 (PET & SC scan): Ø Any periprosthetic activity on PET, without corresponding uptake on SC scan ü Positive criterion 3: Ø Only activity at the bone-prosthesis interface (femoral or tibial components), regardless of intensity ü Positive criterion 4: Ø Semi-quantitative analysis of FDG uptake at the bone-prosthesis interface Sensitivity Specificity 100% 9% 96% 35% 52% 44% 36% 97% Love et al. JNM :

36 18 F FDG PET/CT in Chronic Osteomyelitis ü Chronic osteomyelitis is a severe, persistent, and sometimes incapacitating infection of bone and bone marrow that results when the inflammatory process continues over time, leading to bone sclerosis and deformity ü It is often a recurring condition because it is difficult to treat definitively ü It may result from: Ø Ø Ø Ø Ø Ø Ø inadequately treated acute osteomyelitis; hematogenous osteomyelitis; trauma; iatrogenic causes such as joint replacements and the internal fixation of fractures; compound fractures; infection with organisms, such as Mycobacterium tuberculosis and Treponema species (syphilis); contiguous spread from soft tissues, as in diabetic ulcers or ulcers in peripheral vascular disease.

37 ü 33 patients (7 women, 26 men), years-old (mean: 50) ü Inclusion criteria: suspected chronic osteomyelitis (>6 weeks) ü Exclusion criteria: trauma/surgery within 6 months of PET, antibiotic therapy, preganancy, age<18 years ü PET/CT had overall sensitivity of 94% and specificity of 87% ü For lesions in the axial PET/CT was 88% sensitive and 100% specific, while for the appendicular skeleton it was 100% sensitive and 85% specific

38 OSTEOMYELITIS Hartmann et al. EJNM :

39 OSTEOMYELITIS FRACTURE Hartmann et al. EJNM :

40 18 F FDG PET/CT for Evaluation of the Diabetic Foot ü Osteomyelitis of the foot is a challenging diagnosis and affects up to 15% of diabetic patients, often as a result of direct contamination from a soft tissue lesion ü Early diagnosis of osteomyelitis in the diabetic foot is crucial because antibiotic therapy can be curative and prevent amputation ü Plain radiograph is the first-line imaging modality to evaluate the foot, BUT ü MRI is considered the modality of choice to evaluate for diabetic foot osetomyelitis and associated soft-tissue abnormalities

41 ü 14 patients (4 women, 10 men), years-old (mean: 54) ü Inclusion criteria: suspected infected diabetic foot ü Exclusion criteria: preganancy, age<18 years ü PET/CT correctly localized 8 foci in 4 patients to bone, indicating osteomyelitis ü PET/CT excluded osteomyelitis in 5 foci in 5 patients, indicating soft tissue uptake only

42 OSTEOMYELITIS Keidar et al. JNM :444-9.

43 SOFT TISSUE INFECTION Keidar et al. JNM :444-9.

44 ü 17 patients (6 women, 11 men) with Charcot s neuro-arthropathy, 59.4 ± 8.6 year-old ü Inclusion criteria: Charcot s neuro-arthropathy ü Exclusion criteria: preganancy, age<18 years ü PET/CT had a sensitivity of 100% and specificity of 93.8% ü MRI had a sensitivity of 76.9% and specificity of 75% ü Soft tissue infection was diagnosed in 7/17 patients (43.7%)

45 OSTEOMYELITIS Basu et al. Nuc Med Comm :

46 18 F FDG PET/CT in Vasculitides Definition: Presence of leukocytes in the vessel wall with reactive damage to mural structures Loss of integrity g bleeding Compromise of lumen g ischemia When to suspect? Systemic symptoms + Single or multi-organ dysfunction Pathophysiology of vessel damage in vasculitic syndromes: ü Pathogenic immune complex formation and/or deposition ü Production of antineutrophilic cytoplasmic antibodies ü Pathogenic T lymphocyte responses and granuloma formation

47 Classification of Vasculitides Large Vessel ü Takayasu arteritis ü Giant Cell Arteritis Medium Vessel ü PAN ü Kawasaki s ü Isolated CNS vasculitis Small Vessel ü Churg-Strauss ü Wegener s ü Microscopic Polyangiitis ü HSP ü Essential Cryoglobulinemia ü Hypersensitivity vasculitis ü Vasculitis 2 nd to CTD ü Vasculitis 2 nd to viral infection

48 Primary Vasculitis Syndromes ü Wegener's granulomatosis ü Churg-Strauss syndrome ü Polyarteritis nodosa ü Microscopic polyangiitis ü Giant cell arteritis ü Takayasu's arteritis ü Henoch-Schönlein purpura ü Idiopathic cutaneous vasculitis ü Essential mixed cryoglobulinemia ü Behçet's syndrome ü Isolated vasculitis of the central nervous system ü Cogan's syndrome ü Kawasaki disease Secondary Vasculitis Syndromes ü Drug-induced vasculitis ü Serum sickness ü Vasculitis associated with other primary diseases ü Infection ü Malignancy ü Rheumatic disease

49 Infectious Diseases ü Bacterial endocarditis ü Disseminated gonococcal infxn ü Pulmonary histoplasmosis ü Coccidioidomycosis ü Syphilis ü Lyme disease ü Rocky Mountain spotted fever ü Whipple's disease Drug toxicity ü Cocaine ü Amphetamines ü Ergot alkaloids ü Methysergide ü Arsenic Other disorders mimicking vasculitis Coagulopathies/thrombotic diseases ü Antiphospholipid antibody syndrome ü Thrombotic thrombocytopenic purpura Neoplasms ü Atrial myxoma ü Lymphoma ü Carcinomatosis Sarcoidosis Atheroembolic disease Goodpasture's syndrome Amyloidosis Migraine Cryofibrinogenemia

50 ü 35 patients (25 women, 10 men), 72.7±6.7 years-old ü Inclusion criteria: biopsy proven GCA ü Results: Ø vascular FDG uptake was noted in 29 patients (83%) Ø the patients who relapsed had similar decrese in uptake after therapy as the ones who where in remission ü Conclusion: Ø GCA relapse can not be predicted by PET

51 GIANT CELL ARTERITIS Blockmans et al. Arthritis :131-7.

52 ü 22 patients (16 women, 6 men), 73.3±7.5 years-old ü Inclusion criteria: clinical GCA; major vessel U/S examination ü Results: Ø all patients with signs of GCA on U/S had FDG uptake on PET Ø when U/S was only positive in the temporal arteries, PET was completely negative ü Conclusion: Ø PET is not suitable for diagnosis of temporal arteritis

53 ü 30 patients with large vessel vasculitis and 31 controls ü Results: Ø Sensitivity of 73.3% (95% CI %), specificity of 83.9% (95% CI %), PPV of 81.5% (95% CI %) NPV of 76.5% (95% CI %) Ø The diagnostic accuracy was higher in patients not receiving immunosuppressive drugs (93.3 vs 64.5%, p = 0.006) Ø FDG PET increased the clinical diagnostic accuracy from 54.1 to 70.5% (p = 0.04)

54 NORMAL vs. ABNORMAL Walter et al. EJNM :

55 TAKAYASU S Walter et al. EJNM :

56 ü 18 patients (17 women, 1 man), years-old ü Inclusion criteria: Takayasu s arteritis ü Results: Ø sensitivity was 92% and specificity was 100% Ø NPV of 85% and PPV of 100% in initial evaluation of patients with suspected vasculitis ü Conclusion: Ø FDG PET can be used to diagnose early disease, to detect active disease and to monitor the effectiveness of therapy

57 TAKAYASU S Webb et al. EJNM :

58 TAKAYASU S Webb et al. EJNM :

59 ü 15 patients (9 women, 6 men), years-old ü Inclusion criteria: early aortitis (FUO, elevated ESR/CRP, FDG uptake in the aorta); MRI available ü Results: Ø at baseline PET was abnormal in 56% of the cases, while MRI was abnormal in 53% Ø 80% showed normalization on PET after therapy ü Conclusion: Ø PET and MRI have comparable results, but PET showed more areas of disease involvement, with better evaluation of response to therapy

60 GIANT CELL ARTERITIS Meller et al. EJNM :730-6.

61 TAKAYASU S Meller et al. EJNM :730-6.

62 TB before/after treatment

63 a TB before/after treatment

64 TAKAYASU S

65 Stanford Charges Modality Technical Professional Radiotracer Total In111 WBC $2150 $283 $295 $ phase bone scan $1914 $334 $252 $7007 $2500 Tc99m SC scan $1294 $233 $252 $1779 Ga-67 scan $2150 $283 $279 $2712 PET/CT $6219 $524 $1774 $8517

66 FDG s exquisite sensitivity suggests that it may be useful in a FUO, an entity with diverse etiologies. In addition to tumor and infection, other conditions that may present as a FUO, including vasculitis, thromboembolic disease, sarcoidosis and chronic granulomatous disease, are associated with increased FDG uptake. FDG PET appears to be sensitive for detecting focal infection and may be useful for detecting infected prosthetic vascular grafts, mycotic aneurisms, lung abscesses and intra-abdominal infections. FDG PET also may be useful for diagnosing musculoskeletal infection, especially in the setting of previous trauma and metallic implants. The fact that increased FDG uptake occurs in many neoplasms is both a relative advantage and a relative disadvantage.

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68 THANK YOU!