Loch Lomond

Infection & Inflammation Dr Sai Han Consultant in & PET/CT NHS Greater Glasgow & Clyde Topics

 Infection & Inflammation basics  Tracers  Clinical conditions  Example Images Inflammation/ Infection

 Local response to Injury (, trauma, immune..)  1st line of body defence

Vasodilatation vascular Permeability WBC migration

 Cardinal signs(Rubor, Dolar, Calor, Tumor, Functio Laesa) Inflamed (red, painful, hot, swollen, function loss)  Septic or Aseptic inflammation  Inflammation vs tumour  Acute or Chronic

 Treatment  treat the cause/ symptom/ complications Challenges

 Inflammtion vs Tumour  Septic vs aseptic inflammation  Reactive vs infection Some relevant infection/inflammation

 MSK Diabetic foot infection Discitis Prosthetic joint infection

 GI IBD, infection  Device site infection  FUO

 Vasculitis  Injury (infection, immune..)

Inflammatory Response

Vasodilatation Permeability Cell response WBC (warm, red) (swelling) Local Tissue

3 phase Bone scan WBC scans scan FDG PET Inflammation Acute Chronic onset cells Microphages (>) (Monocyte, lymphocyte) example  cellulitis  TB  pneumonia  Sarcoidosis outcome  resolution  persist  chronic   damage  fibrosis Diagnostics

Clinical  History (* technologist) Cardinal signs  Examination Labs  inflammatory markers ESR, CRP….  micro, immuno, path Culture, biopsy.. Imaging  Structural Swelling/ oedema, USS, MRI abscess, XR, CT destruction…  Functional Inflammation: ↑ General: WBC, Ga67, FDG Necrosis:  activity Specific: Bone  Hybrid (SPECT/CT, PET/CT) Conventional Nuclear Imaging (Planar & SPECT) Advantages Issues  Localisation & Characterisation High Sensitivity Low Specificity Widely available Often require further tests Radiation Hybrid SPECT/CT adding CT to Nuclear Medicine Improvements Issues  Localisation & Characterisation  Radiation  Attenuation Correction  Scan time (SPECT)  Specificity patient & staff  Sensitivity  Reporting time  Diagnostic confidence Multimodality training  Conclusive Reports  Inconclusive Reports  Further tests  Time to Treatment Tracers

• General Inflammatory (WBC, Ga67, FDG) • Specific Site (e.g. MDP..) Inflammatory Tracers (ARSAC)

Tracer s T 1/2 Energy DRL Dose (KeV) MBq mSv Investigations

Tc99m 6h 140 200 2.5 Infection/inflammation wbc In111 68h 173, 247 20 7.2 Infection/inflammation wbc Ga67 78h 93, 185, 150 15 Infection/Inflammation 300, 394 F18 110 511 400 7.6 Infection/Inflammation FDG min Tumour Labelled WBC

Precaution  Infection risk (staff + patient)  Careful not to damage WBC  Re inject ASAP (<1hr after labelling)

Procedure (EANM guidelines 2010) In-111 WBC

• Now largely replaced by Tc-99m HMPAO •  Image quality,  dose, but Better in specific conditions (GI, Renal) • Normal distribution: , Spleen, Bone Marrow. Transient • Very Low Urinary & GI excretion Tc99m HMPAO WBC

 Trapped in WBC  Physiological excretion (GI,Urinary) In-111 white cell Normal distribution : Transiently in lung but mainly in spleen, liver, bone marrow, vascular Tc-99m HMPAO wbc

Labelled cells •initially concentrate in Subsequent highest activity in spleen But also •Liver •Bone marrow •Blood pool Tc-99m vs In-111 Tc-HMPAO In-111 oxine  Better image quality  Better labelling efficiency  2.2mSv  7.2 mSv  Physiological GI & Renal  No physiological GI & Renal  Better availability  Dual tracer imaging (In111wbc/Tc colloid) EANM guidelines Tc99m WBC Bowel Infection/Inflammation

 WBC scan Case: SPECT/CT WBC perinephric abscess Case: PUO (Diverticular Abscess)

Pattern Recognition: Megacolon Crohn’s vs Ulcerative Colitis IBD Meta-analysis (1984-2004)

N SS SP  In 682 88 93  Tc 1427 88 92  Scope 58 91 72  Ba 167 67 77

(Alessio et al. NMC. 2005.26(7) 657-664) Other Colitis: C Dif Case: 30 y F post op ? underlying bowel inflammation

Wound Only + Ga67

 Excretion: Renal 10% in first 24hr  Colon excretion later  Soft tissue/liver/bone/bone marrow  Nasopharyngeal, lacrimal, Breast  Plasma protein bound ()  Increased flow, permeability  Wbc transport  Intake by bacteria e.g. Staph aureus (sideropores) CJ. Palestro et al. RadioGraphics 2000; 20:1649–1660 SARCOIDOSIS

 Chronic granulomatous inflammation  Nodes, skin, organs, high calcium

 Nuclear Medicine (Ga67, FDG) Activity ? Diagnosis of cardiac Sarcoidosis Ga-67 70 y lady with high Calcium (Sarcoidosis) FUO

 Infection, inflammation, tumour, drug

 Nuclear Medicine FDG (UK evidence based guidelines) Ga67 WBC Case: Fever of Unknown Origin: FDG PET-CT: Large Vessel Arteritis Steroid & Methotrexate→ good response Case: FUO In-111 wbc Tract in L thigh SPECT/CT= L femoral vein Doppler USS confirmed L femoral DVT Vascular device & Graft

 FDG

Ref: Martin Gotthardt et al. Imaging of Inflammation by PET, conventional , and other imaging techniques. JNMTech 70y F CXR CT smoker LUL mass

CT-PET

LUL Lobectomy: Granulomatous inflammation → anti TB 82y♂ Cerebellar symptoms, ? Occult

Small Neck node Biopsy: TB !

√ PET (+)ve lesion can be B9 curable disease FDG PET/CT in patients with HIV Cerebral Toxoplasmosis vs

JM. Davison et al. AJR 2011; 197:284–294 Semiquantitative Analysis of Brain Metabolism in Paraneoplastic Neurologic Syndrome AJ Clapp et al. Clin Nucl Med 2013 (Epub)

MRI

Limbic Encephalitis

FDG PET

Courtesy of P Peller, Mayo Clinic Specific sites e.g. Bone, Kidney, Gall Blasdder Skeletal infection/inflammation

 Osteomyelitis, Diabetic foot infection  Septic joint  Prosthetic joint infection

 Nuclear Medicine 3 phase bone WBC Diabetic Foot Infection Antibiotic: Soft tissue infection (7-10days) Bone (4 weeks)

• plain X-rays • MRI •When MRI not available or contraindicated, consider WBC scan, or (SPECT/CT) or (PET)

• 3phase bone SS 80-90 SP 30-45 (to exclude) • MR SS90 SP85 • WBC PPV 70-90 NPV 80 SS75-80 SP70-85 • WBC SPECT/CT SS 87.5 SP 71 PPV 83 NPV 78 Case. 55 y M DM; renal Transplant Ankle swelling 3 phase bone scan & In-111 WBC scan

Calcaneus Osteomyelitis Case: 35 year M

Bone scan Tibial Osteomyelitis Prosthetic Joint Pain

 Septic or Aseptic Loosening  Bone scan (? Reactive ? Infection)

C Love et al. Semin Nucl Med 2009. 39:66-78 In111 wbc / Tc99m Colloid Discordant WBC & Colloid uptake = ? infection

Test Accuracy (%) Bone 50 Bone/Gallium 66 WBC/bone 70 • WBC/ colloid 91

C Love et al. Semin Nucl Med 2009. 39:66-78 THYROIDITIS

 Clinical; hyperthyroid, Neck pain  Laboratory: increased inflammatory marker  Nuclear Medicine Thyroiditis (subacute; postpartum) Low Thyroid uptake Case. Subacute thyroiditis (low thyroid uptake) Pyelonephritis

 Effect: Scar  Nuclear Medicine DMSA Recurrent UTI Acalculous Cholecystitis

 Pain  Function loss

 Nuclear Medicine HIDA appearance, Gall bladder Ejection Fraction HIDA HIDA (time activity curve) Conclusions

• Nuclear Medicine helps diagnose/exclude Infection/inflammation CVS WBC & FDG (vascular graft, device, sarcoid) Sarcoid Ga67, FDG • MSK Diabetic foot (bone, wbc) Spine OM (Ga67, WBC) Prosthetic joint (bone, wbc/colloid) • PUO WBC, FDG • Also Functional effect: UTI(DMSA) GB(HIDA)

Hybrid imaging improves Thank You Acknowledgement

 Colleagues at NHS GGC & Glasgow University