Evaluation of Infection/Inflammation: What is the Role of PET/CT?med.stanford.edu/content/dam/sm/nuclearmedicine/documents/education/Lectures... · ADNEXITIS TAKAYASU Meller et al

MIPS Stanford University Molecular Imaging Program at Stanford

School of Medicine Department of Radiology

MIPS Molecular Imaging Program at Stanford

Stanford University School of Medicine

Department of Radiology

Andrei Iagaru, MD

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



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



Nuclear Medicine: What is the Holy Grail?



PET/CT in Infection/Inflammation

ü 18F FDG labeled WBC’s vs. 18F FDG

ü Applications of 18F FDG PET/CT in infection and/or inflammation: Ø  Fever of unknown origin

Ø  Prosthesis evaluation

Ø  Chronic osteomyelitis

Ø  Diabetic foot

Ø  Vasculitidies



18F FDG labeled WBC’s vs. 18F FDG

18F FDG labeled WBC’s 18F FDG



18F FDG labeled WBC’s vs. 18F 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



ü  4 normal adult volunteers

ü  WBC’s can be readily labeled with 18F FDG

ü  Labeled WBC’s show reasonable stability in vivo for several hours after injection

ü  Dosimetry data similar to 111In 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



ü  21 patients (8 women, 13 men), 24-84 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%

Dumarey et al. JNM. 2006 47(4):625-32.

DIVERTICULITIS

OSTEOMYELITIS

Dumarey et al. JNM. 2006 47(4):625-32.

ENDOCARDITIS




ü  8 subjects excluded: inadequate 18F labeling (6), camera malfunction (1), non-cooperant (1)

ü  Labeling efficiency 72% for 18F vs. 90% for 111In (P < 0.001)

ü  WBC’s viability of 98% for 18F vs. 97% for 111In



Modality Sensitivity Specificity N PET (per patient) 86 86 21

PET (per patient) 100 57 21

PET (per lesion) 91 85 21

PET (per lesion) 96 69 21

PET (per patient) 87 82 43 111In WBC 73 86 43

18F FDG labeled WBC’s

Dumarey et al. JNM. 2006 47(4):625-32.

Rini et al. Radiology. 2006 238(3):978-87.



18F 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



Sources of FUO ü  Infections: 13-43%

ü  Autoimmune/colagen vascular disease/neoplasm: up to 54%

ü  Unknown: 10-40%

67Ga citrate whole-body scan

18F FDG PET/CT



ü  19 patients underwent 111In WBC scan and 18F 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



ü  35 patients underwent 18F FDG PET



ü  Results:


Ø  6 cases: infection

Ø  4 cases: neoplasm

Ø  6 cases: inflammation

Bleeker-Rovers et al. EJNM. 2004 31:29-37.

LYMPHOMA SARCOID



ü  16 patients underwent 18F FDG PET



ü  Results:


Lorenzen et al. Nuc Med Comm. 2001 22:779-783.

VASCULITIS TB & COLITIS



ü  18 patients underwent 18F FDG PET and 67Ga scintigraphy


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

ADNEXITIS

TAKAYASU

Meller et al. EJNM. 2000 27:1617-25.



Modality Sensitivity Specificity N PET 50 46 19

111In WBC 71 92 19

PET 93 90 35

PET 92 75 16

PET 81 86 18 67Ga(SPECT) 67 78 18 67Ga (planar) 45 100 18

18F FDG PET/CT in FUO

Kjaer et al. EJNM. 2004 31:622-6.

Meller et al. EJNM. 2000 27:1617-25.

Bleeker-Rovers et al. EJNM. 2004 31:29-37.

Lorenzen et al. Nuc Med Comm. 2001 22:779-783.



18F 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

Normal Hip Arthritic Hip Replaced Hip

Normal Knee Arthritic Knee Replaced Knee



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



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, re-implantation of prosthesis - 90%+ success

Ø  removal of prosthesis, immediate re-implantation, antibiotics - 70%+ success

ü Resection arthroplasty ü  Suppressive long-term antibiotics



ü  23 patients (14 women, 9 men), 35-83 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

Manthey et al. Nuc Med Comm. 2002 23:645-53.

INFECTION AND SYNOVITIS

LOOSENING AND SYNOVITIS

SYNOVITIS




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

Mumme et al. Arch Orthop. 2005 125:322-9.




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

Van Acker et al. EJNM. 2001 28:1496-504.

INFECTION

LOOSENING




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



Sensitivity Specificity

100%

9%

96%

35%

52%

44%

36%

97%

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

Love et al. JNM. 2004 45:1864-71.



18F 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  inadequately treated acute osteomyelitis;

Ø  hematogenous osteomyelitis;

Ø  trauma;

Ø  iatrogenic causes such as joint replacements and the internal fixation of fractures;

Ø  compound fractures;

Ø  infection with organisms, such as Mycobacterium tuberculosis and Treponema species (syphilis);

Ø  contiguous spread from soft tissues, as in diabetic ulcers or ulcers in peripheral vascular disease.




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

Hartmann et al. EJNM. 2007 34:704-14.

OSTEOMYELITIS

Hartmann et al. EJNM. 2007 34:704-14.

OSTEOMYELITIS FRACTURE



18F 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




ü  Inclusion criteria: suspected infected diabetic foot


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

Keidar et al. JNM. 2005 46:444-9. OSTEOMYELITIS

Keidar et al. JNM. 2005 46:444-9.

SOFT TISSUE INFECTION



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  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%)

Basu et al. Nuc Med Comm. 2007 28:465-72.

OSTEOMYELITIS



18F 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



Small Vessel ü Churg-Strauss ü Wegener’s ü Microscopic Polyangiitis ü HSP ü  Essential Cryoglobulinemia ü Hypersensitivity vasculitis ü  Vasculitis 2nd to CTD ü  Vasculitis 2nd to viral infection

Classification of Vasculitides

Large Vessel ü  Takayasu arteritis ü Giant Cell Arteritis

Medium Vessel ü  PAN ü  Kawasaki’s ü  Isolated CNS vasculitis



Secondary Vasculitis Syndromes ü  Drug-induced vasculitis ü  Serum sickness ü  Vasculitis associated with other

primary diseases ü  Infection ü  Malignancy ü  Rheumatic disease

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



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

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



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

Blockmans et al. Arthritis. 2006 55:131-7.

GIANT CELL ARTERITIS



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



ü  30 patients with large vessel vasculitis and 31 controls

ü  Results:

Ø  Sensitivity of 73.3% (95% CI 54.1-87.7%), specificity of 83.9% (95% CI 66.3-94.5%), PPV of 81.5% (95% CI 61.9-93.7%) NPV of 76.5% (95% CI 58.8-89.3%)

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)

NORMAL vs. ABNORMAL Walter et al. EJNM. 2005 32:674-71.

TAKAYASU’S

Walter et al. EJNM. 2005 32:674-71.



ü  18 patients (17 women, 1 man), 23-64 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

TAKAYASU’S Webb et al. EJNM. 2004 31:627-34.

TAKAYASU’S

Webb et al. EJNM. 2004 31:627-34.




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

GIANT CELL ARTERITIS Meller et al. EJNM. 2003 30:730-6.

TAKAYASU’S

Meller et al. EJNM. 2003 30:730-6.

TB before/after treatment

TB before/after treatment

a

TAKAYASU’S



Modality Technical Professional Radiotracer Total

In111 WBC $2150 $283 $295 $2728

3 phase bone scan $1914 $334 $252 $2500

Tc99m SC scan $1294 $233 $252 $1779

Ga-67 scan $2150 $283 $279 $2712

PET/CT $6219 $524 $1774 $8517

Stanford Charges

$7007



“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.”

THANK YOU!

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Documents

Evaluation of Infection/Inflammation: What is the Role of PET/CT?med.stanford.edu/content/dam/sm/nuclearmedicine/documents/education/Lectures... · ADNEXITIS TAKAYASU Meller et al