John Buscombe Introduction Inflammation Simple imagingbone scintigraphy PET techniquies Infectionbone Infection SPECTCT Infection PETCT Summary Background Publishing on imaging infection since 1988 ID: 933766
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Slide1
Imaging infection and inflammation using nuclear medicine methods
John Buscombe
Slide2IntroductionInflammation
Simple imaging-bone scintigraphy
PET
techniquies
Infection-bone
Infection SPECT-CT
Infection PET-CT
Summary
Slide3Background
Publishing on imaging infection since 1988
Wide range of agents including PET and single photon
Member of EANM infection and inflammation committee for 7 years
Co-author of reviews and book chapters in infection
inc
EANM/SNMMI guidelines on FDG and infection
So do I use Single photon or PET?
Answer – both
Answer – depends on situation
Slide4SPECT-CT or PET-CT?
Slide5What can we do with each machine
Single photon
Tc-99m
MDP
Ga-67 citrate
In-111 labelled
WBCs
Tc-99m
HMPAO
WBCsTc-99m antibodies
PET-CT
F-18 FDG
F-18 WBCs
Ga-68 citrate
Slide6Radiopharmaceuticals
Targeting the host immune system
HIG
Labelled White Blood Cells
Monoclonal Antibodies against Granulocytes
IL-8 (acute)
IL-1, IL-2, Monoclonal Antibodies against TNF
α
(chronic)
18
Fluorodeoxyglucose (FDG)
(images the hypermetabolic state)
67Gallium Citrate, 68Gallium Citrate
Slide 6
Targeting
the infectious agent
67
Gallium Citrate
,
68
Gallium Citrate
Labelled anti-
microbials
Labelled vitamins
Labelled antimicrobial peptides
Slide7Bone scintigraphy in arthropathy
For local issues 2-phase imaging is useful though not good for axial skeleton
Can image whole body for same radiation dose – 2mSv
Normally extra images of hands and feet
Pattern may be useful
Personal view SIJ quant not very helpful
Slide8Radiotracer utilisation in RA
Indication
MDP Bone Scan
Sodium
Flouride
PET/CT
IgG (HIG) imaging
FDG PET/CT
Confirmation of suspected diagnosis
Yes
Yes
YesProbablyDepiction of joints involvedYesYesYesYesExtra-articular diseaseNoNoNoYesTherapy response assessmentMaybeNoYesYesSuitability for radiosynovectomyYesYesNoNo
Slide9PALM VIEW to depict small joints
Whole Body Bone Scan
Slide10Dual Phase Imaging
Slide11Early blood pool imaging to capture inflammatory process
Dual Phase Imaging-seronegative
Slide12SPECT-CT in hips/thighs
Normally studies performed in patients who have has THRs
Metal an issue in SPECT reconstruction can result in false positive “hot” spots by prostheses due to over zealous attenuation correction
Bladder activity may lead to count stealing and reduced uptake
Care is needed in reading images in this areas
Slide13Sappho causing focal femoral uptake note burnt out disease
Slide14Pain in the thigh following THR
Slide15Painful ankle despite screws for fracture
Slide16Glucose uptake into tumours
Slide17FDG and inflammation or infection
Increased uptake of FDG occurs when lymphocytes activated. Ishimori JNM 2002
Uptake not just related to perfusion but active uptake when FDG increased compared to FLT where no increased uptake van Gaarde JNM 2004
Uptake of FDG related to hypoxia and presence of cytokines Matsui JNM 2009
Slide18Uptake and cytokines-Matsui JNM
Macrophages
Neutrophils
Fibroblasts
Slide19Imaging inflammation
Most inflammatory diseases can be imaged using scintigraphic technique
Some techniques are blood flow dependent such as 2 phase bone and Tc-99m HIG
Some methods dependent on bone turnover such as Tc-99m bone scintigraphy and F-18 NaF
Other methods image inflammation more directly eg Labelled WBCs, and F-18 FDG
All can be quantified so useful in research
Slide20Sarcoid
Disseminated inflammatory disease
Characterised by granuloma
Various patterns
Salivary/lacrimal glands
Lymph nodes
CNSSkinJointPulmonary- the most dangerous
Slide21Imaging in sarcoid
Normally diagnosis clinical followed by biopsy
50% of patients have raised serum ACE
If lymph nodes involved may see symmetrical enlarged mediastinal/hilar nodes the lambda pattern
Since 1966 Ga-67 citrate used
Not very trendy
High radiation dose
Slide22Ga-67 in sarcoid
Panda sign, lacrimal and salivary glands
Lamba sign mediastinum and hilar nodes
Diffuse lung uptake
Lymphadanopathy (symmetrical)
Joints
Liver-diffuse
Slide23Use of F-18 FDG
Lymphocytes very FDG avid
Much improved resolution
Lower radiation dose (5mSv vs 18mSv)
Confirm sites of active disease esp in the abdomen
Quantify uptake which may be useful in treatment monitoring
Slide24FDG vs Ga-67
Nishiyama et el JNM 2006
18 sarcoid patients imaged with Ga-67 and FDG.
Pulmonary disease Ga-67 81%, FDG 100% - mean SUVmax 7
Extra-pulmonary disease Ga 48%, FDG 90% mean SUVmax 5
A= Ga-67
B= F-18 FDG
C= F-18 FDG post therapy
Slide25Using FDG to monitor therapy
Sobic-Saronovic, Clin Nucl Med 2013
30 patients imaged before and after steroids for active sarcoid
Observed reduction in sites and intensity of activity
Correlated well with clinical symptoms
SUVmax 8.5 to 4.9 (p<0.05)
Serum ACE did not predict response
Slide26Using FDG in RA
Beckers et al JNM 2004
21 patients with active RA
FDG imaging with views of knees and hands
FDG positive in 68% joints though 75% of joints swollen and 79% painful
Good correlation with increased blood flow on Doppler ultrasound
Slide27FDG uptake in RA
Beckers et al JNM 2004
Normal
Patient with RA
Slide28Monitoring response
Vijavant et al WJR 2012. 17 newly diagnosed RA and 11 newly diagnosed sero-neg arthropathy
Good correlation between symptoms and sites of increased uptake of FDG
Change in SUVmax correlated well with clinical response and change in CRP
Slide29FDG before and after TxVijavant et al WJR 2012
Slide30Atlantoaxial
synovitis
Extra-
articular
disease
18
F FDG PET/CT-staging a little like cancer
Slide31RA and PET in 2004-stll true 2016
However, much work remains to be done to gain more detailed information and to clarify the impact of
18
F-FDG PET on diagnosis and therapy of RA, in comparison with state-of-the-art MRI, ultrasound, and three-phase bone scanning. Eventually, we may be able to define indications for
18
F-FDG PET to improve and adjust RA management.-
Wilfred Brenner
Slide32FDG -psoriatic arthritis
Slide33F-18 FDG in RPF
Small volume of published work
Concentrates on the use of F-18 FDG in following inflammation in RPF
Jansen et al E J Int Med 2012
26 patients with iRPF 20 positive with FDG PET correlated with high initial CRP
F-18 FDG reduction correlated with reduction in inflammatory markers not CT thickness of RPF
Slide34F-18 FDG Imaging to monitoring treatment of unilateral RPF
Slide
34
Jan 09 Jan10 Oct 10 Oct 11
on steroids off steroids on steroids on steroids
Case of Prof A Signore
Slide35F-18 FDG in vasculitis
Walter et al EJNMMI 2005 used F-18 FDG imaging in 26 patients with giant cell artertitis
Good correlation with wall thickness on CT, ESR and CRP
Papathanasiou et al from UCL BJR imaged 16 patients with GCA before and after their forst dose of steroids
Mean SUVmax dropped from 3.38 to 2.32 with treatment
Slide36Giant cell arteritis
Slide37Aortitis
Slide38Single photon imaging of infection
Success depends on number of factors
Understanding the clinical background of the patient immunocompetent vs
immunodeficient
Understanding when a sensitive test is needed and when a specific agent is needed
Being pragmatic, look at availability, cost and time
Always do the best study you can for a specific clinical problem and situation in 2016 that means SPECT/CT or PET/CTEvery patient is different
Slide39Is there a role for bone scint
Advantage of Tc-99m MDP/HDP is that technology cheap
Can obtain idea of flow but beware foot shunting
Can determine if there is bone involvement
Sensitivities as high as 100%, specificity 40-60%
Asli et al JNMMT 2011
Slide403 phase bone scan
Disease
Dynamic
Static
Osteomyelitis
Pos
Pos
Cellulitis
Pos
Neg
Non infected
Bone
NegPos
Slide41False positives in 3 phase bone
Recent but treated infection
Fracture
Non-infected malunion
Inflammatory arthritis
Look for synovial uptake
Could be septic arthritis
Slide42Gallium-67 citrate
No cell labelling
90keV, 190keV, 300keV, 394keV gammas med energy collimator
Poor dosimetry limits activity that can be given
Indications now limited
Sarcoid
Spinal infectionsImmunocompremisedFDG PET-CT can do some of these
Slide43Other use of Ga-67 is discitis
85 year old man
Severe back pain
CRP 250
Gram positive rods in blood
Pacemaker
Slide44More specific agents
In-111 WBC
Limited access, needs cell labelling
174
keV
and 247
keV needs medium energy collimatorPoor dosimetry limits activity to 20MBqGold standard good specificityAll but spinal infections
Tc-99m HMPAO WBC
Needs cell labelling
Max 200MBq but lower radiation doseTheoretically less specific than In-111 WBC but no real evidence in skilled handsAll but spinal infections
Slide45In-111 WBC SPECT-CT in infected THR
Though planar image was positive the SPECT-CT images allow for good localisation of the labelled WBCs and show where the infection is sited so drainage and anti-biotics used
Slide4644 year old male
diabetic since aged 6
Had carpet changed
pain in heel
Use of In-111 WBC in diabetic foot
Slide47Antibodies
Tc-99m
granuolscint
Anti-CD66 on granulocytes
No cell labelling
Use similar to Tc-99m HMPAO WBC
Widely used in EuropeTc-99m leucoscanNo cell labelling
Mechanism not clear
No Fc on antibody so can do repeat scanning
Mainly in bone/joint infection
Slide48A
. PET/CT whole body MIP projection showing high
18
F-FDG uptake around the pre peritoneal part and
cutaneous
exit of the driveline(red arrow) and in the LVAD pocket (green arrow).
B
. CT scout view showing LVAD pocket and driveline.
C
. Anterior planar scintigraphy 24hours after injection of the
Tc
99m-anti-leucocyte antibodies showing uptake along the driveline
AGAB more specific than FDGImages from Prof A Boubaker
Slide49FDG Imaging in Infection
Clinical Indications based on EANM/SNMMI
Localized infection in chest & abdomen
Fever of unknown origin (FUO)
True FUO
Immune-deficiency & immune-compromised (AIDS)
Musculo-skeletal infections
Osteomyelitis
Spinal infection
Diabetic foot
Infected orthopedic prostheses
Vascular
Infected vascular graftVasculitisInflammatory vulnerable plaquesInflammation SarcoidosisForeign body reactionsInflammatory bowel diseaseFDG Imaging of InfectionPubMed Feb 2015: 645 papersPeer-reviewed 1994-2011>55 papers (>10 patients)>2,000 patientsCase reports not included
Slide50FDG Imaging of Infection
Pros & Cons
Advantages
F-18: good physical properties
FDG: good tracer kinetics
PET: high spatial & contrast resolution
good
image
quality
CT:
anatomic
information
Study duration:1.5 – 2hShort physical T1/2: lower radiationNo blood handlingLimitationsNonspecific uptake:PhysiologicMalignanciesForeign body reactionAvailability & Waiting listCost & [lack of] reimbursement
Slide51FDG Imaging in Infection
FUO in Immunocompromised Patient
F, 21, FUO, Polycystic kidneys
1 month after renal transplant
Infected renal cyst
Reactive LNs
Pelvic Abscess
Slide52Guidelines
Slide53FDG in infective discitis
Slide54FDG in multiple Staph infections
Slide55Warning FDG is not specific
Slide
55
41 year old swinging fever. FDG looks like an abscess but is Hodgkin’s Lymphoma in adrenals
Case supplied by Dr Gnanasegaran
Slide56Will NHS England pay
Slide57Single photon vs FDG PET
Single photon
A choice of agents for different types of patients and infections
Immunocompetent
SPECT-CT is now our standard
Need cell labelling
Time to do scanOffers specificity
FDG PET-CT
FDG can find infection and inflammation
Though more expensive in England maybe paid by NHS EnglandMay be quicker to get resultsImmunocompetent and
immunodeficient
Sensitivity better, specificity may be an issue