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) [email protected]
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