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Claus Peter HeusselDiagnostic and Interventional Radiology

Chest-Clinic at University Hospital Heidelberg

Advances in the Understanding of Pulmonary Aspergillosis

CT Imaging in Aspergillus Lung Infections

A.Early detection

B.Characterisation

C.Monitoring

D.Intervention

Febrile day 8 Day 3 Day 3

Fungal Pneumonia Fungal Pneumonia

D5 Baseline

AML, FeverAML, Fever

D5 Baseline D31 D28

+3 weeks

AML, AML, NeutropeniaNeutropenia, Fever, Fever

Probability

time after HRCT until CXR positive [d]

HRCT: infiltrate

HRCT: normaln=76

n=112

Heussel et al., AJR 1997, JCO 1999

p < 10-7, nges = 188

100%

80%

60%10 20 30 40

Early DetectionEarly Detection

Kuiper et al., Eur Radiol 2003

Radiation ExposureRadiation Exposure

Nature p.a.

CXR

MSCTLow-dose

HRCT

PET

MRI

~1 mSv

0.1–0.2 mSv

2–6 mSv0.6–2 mSv

0.5–1 mSv

4 mSv

0 mSv

Courtesy of Yamamura et al., RöFo 2009

25 mAs♂1.2/♀1.5mSv

35 mAs…

50 mAs…

70 mAs♂3.2/♀4.2mSv

Immuncomp. pat. n=30, infiltrate n=23, 1mm SD dose simulation => speclow-dose 100%86%

Dose ReductionDose Reduction

HRCT MRT

Ground-Glass Opacification

Courtesy of Ley S

T1 T1 T1T1 + + GdGd 230877230877

A.Early detection

B.Characterisation

C.Monitoring

D.Intervention

• Major- Dense, well-circumscribed lesions - With or without a halo sign- Air-crescent sign

• Minor

De Pauw et al., Clin Infect Dis 2008

EORTC CriteriaEORTC CriteriaFungal PneumoniaFungal Pneumonia

1984 described1

1985 discussed in 9 patients2

1 Gefter et al. Radiology ’842 Kuhlman et al. Radiology ’85

Halo SignHalo Sign

200031

Halo signHalo signFungal Pneumonia Fungal Pneumonia

Candida sepsis (+ Candida sepsis (+ hepatolienalhepatolienal C.) C.)

319944

Fungal Pneumonia Fungal Pneumonia HepatosplenicHepatosplenic candidiasiscandidiasis

202555

HaloHalo

203187

HaloHalo

394377

HaloHalo

frequencyMacronodules 94%Halo 61% Consolidation 30%Infarct-shaped 27%Cavitation 20%Air-crescent 10%

Greene et al. CID ‘07

IPA, n=235IPA, n=235

Response52% vs 29%; p<0.001

3-month survival71 vs 53%; p<0.01

Value of Halo SignValue of Halo Sign

Pro•Many patients• Ante-mortem trial

Value of Halo SignValue of Halo SignIPA, n=235IPA, n=235

Contra• Halo = part of inclusion• 95% hardcopies• Thick section CT• 270° of halo not defined

Greene et al. CID ‘07

Infected portInfected port

95882

Septic EmbolismSeptic Embolism

M13

Galaxy-sign= Sarcoid Halo!Halo! 465250

Halo?Halo?

83390098341975

AdenoAdeno--caca.. Meta Meta leioleio--caca

HaloHalo

Consolidation

470067

Fungal Pneumonia Fungal Pneumonia

152287

Fungal Pneumonia Fungal Pneumonia CavitationCavitation

AirAir--crescent signcrescent sign

161295

Fungal Pneumonia Fungal Pneumonia

492289

Fungal Pneumonia Fungal Pneumonia AirAir--crescent signcrescent sign

8342237

Fungal Pneumonia Fungal Pneumonia AirAir--crescent signcrescent sign

IgG deficiency

8348263

Fungal Pneumonia Fungal Pneumonia Moving Fungus BallMoving Fungus Ball

+5 month+5 month

proneprone supinesupine

8340909AspergillomaAspergilloma

Feeding bronchusFeeding bronchus

CavitationCavitation

necrosisnecrosis

+6 weeks+6 weeks

+ 2 + 2 monthmonth 8347143

TrachealTracheal wall wall thickeningthickening

OligemiaOligemia

TracheobronchitisTracheobronchitis

8348508

oligemiaoligemia

+ 3 + 3 weeksweeks + 4 + 4 monthsmonths

TracheobronchitisTracheobronchitis

PlasmodiumPlasmodium falciparumfalciparum ass.ass.

Eckerle I et al., Malaria Journal 2009

PsudomembraneousPsudomembraneous

Courtesy of D. Denning

AspergillosisAspergillosis

1971198119851993199520021966

case 44 @ www.aspergillus.org.ukUpper Lobe Upper Lobe ShrinkageShrinkage

8318269

Allergic Allergic BronchopulomonaryBronchopulomonaryAspergillosisAspergillosis (ABPA)(ABPA)

TreeTree--inin--budbud

8318269+ 4 + 4 monthmonth

Allergic Allergic BronchopulomonaryBronchopulomonaryAspergillosisAspergillosis (ABPA)(ABPA)

8316750

+ 3.5 + 3.5 yearsyears

Allergic Allergic BronchopulomonaryBronchopulomonaryAspergillosisAspergillosis (ABPA)(ABPA)

A.Early detection

B.Characterisation

C.Monitoring

D.Intervention

ConsolidationConsolidationNoduleNodule

Fungal Pneumonia Fungal Pneumonia IllIll--defined nodules + halo signdefined nodules + halo sign

265250

week 1 week 2 week 3

Halo 68% 22% 19%Air-crescent 8% 28% 63%Consolidation 31% 50% 18%Volume = 1 x 4 x 4Hemoptysis 39%

Caillot et al., JCO ‘01

Day 19 of neutropenia

Fungal Pneumonia Fungal Pneumonia

335762

day 2 day 7 day 13 day 33 day 108

Normal ShrinkageIll-defined nodules

Hemat. recovery

Halo reduction

Radiological CourseRadiological Course

21.7.1029.7.1016.8.108352660

VoriconacoleVoriconacole……..ll--AmBAmB……..

Radiological CourseRadiological Course

A. Early detection

B. Characterisation

C. Monitoring

D. Intervention

Thrombocytopenia (44 x 10Thrombocytopenia (44 x 10--66))

16.8.108352660

CTCT--Guided BiopsyGuided Biopsy

16.8.108352660

CTCT--Guided BiopsyGuided Biopsy

Thrombocytopenia (44 x 10Thrombocytopenia (44 x 10--66))

16.8.108352660

Post-intervention

CTCT--Guided BiopsyGuided Biopsy

Thrombocytopenia (44 x 10Thrombocytopenia (44 x 10--66))

PcRPcR: : AspergillusAspergillus flavusflavus**

8352660Courtesy of P. Schnabel, Pathology, Heidelberg

*Courtesy of D. Buchheidt, Mannheim

CTCT--Guided BiopsyGuided Biopsy

n=61

Lass-Flörl et al., CID 2007

Fungi 49Aspergillus sp. 36Mucor sp. 5Rhizomucor sp. 3Absidia sp. 4Cunnighamella sp. 1

BC, Leukemia, TBC 9

46 hematological patients15 organ-Tx85% halo30% air-crescent

CTCT--Guided BiopsyGuided Biopsy

n=17Asper. sp.8Mucor sp.4Non-spec.4

2 laterBAC 1Nosari, Haematol. 03

n=16Asper. sp. 8Mold 2COP 4TBC 1PcP 1Shi, Int J Hematol. 09

• Hemoptysis in 10-40% of IPA• ~1 week after reconstitution• Acute pulmonary hemorrhage• Mortality ~10%• Contrast-enhanced CT• Bronchial- / pulmonary arteries• Resection ± embolisation

Bowler et al., Chest 1998Heussel et al., Eur Radiol 1997

Pagano et al., Br J Haematol 1995

Vessel Vessel ArrosionArrosion

AspergillusAspergillus PneumoniaPneumonia+ Vessel Erosion+ Vessel Erosion

PostPost--embolisationembolisation

Heussel et al., Eur Radiol ’97

PrePre--

AspergillusAspergillus PneumoniaPneumonia+ Pseudo+ Pseudo--AneurismAneurism

Guidelines: AGIHO Ann Hematol (2003) 82 Suppl. 2Halo: Greene et al. CID (2007) 44Halo: Horger et al. Br. J. Radiology (2005) 78Fungal Pneumonia: Heussel et al. Radiologe (2000) 40Pneum. in Neutrop.: Heussel et al. Eur Radiol (2004) 14MRI vs. CT: Eibel et al. Radiology (2006) 241heussel@uni-heidelberg.de

www.pneumotox.comwww.radiologyassistant.nlwww.ctisus.comwww.mevis.de/~jend/Lunge/inh.htmlwww.multislice-ct.comacademic.kellogg.cc.mi.us/herbrandsonc/bio201_McKinley/www.aspergillus.org.uk