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Claus Peter HeusselDiagnostic and Interventional Radiology
Chest-Clinic at University Hospital Heidelberg
Imaging Findings in Neutropenic vs. Non-Neutropenic Patients
A.Screening
B.Early detection
C.Characterisation
D.Monitoring
E.Intervention
CT-sinusn=80, pre-SCTn=17: therapy pre-SCT
15 conservative, 2 OPn=24: no treatmentn=39: normal
Paranasal SinusesScreening
Oberholzer K. et al., RöFo 1997
230661138748
Paranasal SinusesScreening
AspergillusAspergillus nigerniger
CT
bone erosionbone erosion brain invasionbrain invasion
T1T1--GdGd 368537
Paranasal Sinuses
MR-brainn=116, 1- 21J, pre-SCTn=5: surgery / intervention:
1x aspergilloma, 4x cavernoman=42: sinusitis
Zimmermann C. et al., RöFo 2008
Brain Screening
aspergillomacavernoma
Zimmermann C. et al., RöFo 2008
Brain Screening
A.Screening
B.Early detection
C.Characterisation
D.Monitoring
E.Intervention
Need for Early Detection?
delay ↑ ⇒ mortality ↑
Morrell et al., Antimicrob Agents Chemother. 2005
2
%
PEG-II, overall response at EOT, n=707FUO micro.Dx infiltrate other
9,5
9,5
97,7 94,5 76,7 87,8
16,7
1,6 5,5
0
10
20
30
40
50
60
70
80
90
100
Response after Infection
Death
ResponseAffected Organs• lungs (30%)
• para nasal sinuses• gastrointestinal tract• liver, spleen• central nervous system (Tx)• kidneys (BK)
fever + immunocompromisedno further symptoms
??normal chest x-ray
Exclusion of pneumonia?
Weber et al., RöFo 1999Butler et al., Am Surg 1999
BMT & FUO (n=40)• sensitivity: 1. Tag: 46%
follow-up: 81%• neg. prediction: 73%
Intensive Care (n=20)• sensitivity: 25%
→ supine position useful→ useless for pneumonia
Chest X-ray Supine
Heussel et al., AJR 1997, JCO 1999
Prospective Trial (n=230)
• fever (>38.3°C)• neutropenia (ANG < 0.5/µl) >48h• empiric antibiotic treatment
normal CXR HRCT same day
Early Detection
11261
42 39
0
30
60
90
120
76
749
HRCT: normal (40%)
HRCT: Infiltrate (60%)
allall MibiMibi / CXR/ CXR MibiMibi CXRCXR
Course after HRCT
Early Detection
AIDS, Fever
Day 8 Day 3 Day3
AML, Feverprobability
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 4
Early Detection
3
Time until defervescence (n=217)
70 2997
21
Heussel, AJR 1997, JCO 1999
Early Detection Early Detection
19608
febrile day 8 day 3 day 3
Early Detection
Fiebertag 8 Fiebertag 3 Fiebertag3
382063382063
Early Detection
Heussel et al., AJR 1997, JCO 1999
Early Detection• neutropenia & FUO: n=230• sensitivity: 87%• neg. prediction: 88%• time gain: ~ 5-7 days
Exclusion of Pneumonia?• normal CXR: no • normal HRCT: ~ 3-5 days
HRCT: single slicesHRCT: single slices
SpiralSpiral--CT: volume dataCT: volume data
Technique
Spiral-CT HRCT
noduleappearance
11
22
33
44
11........22
Technique
SpiralSpiral--CTCT HRCTHRCT 275875
Technique
false
pos
itive
false
pos
itive
SpiralSpiral--CTCT409659 HRCTHRCT 409659
Technique
false
neg
ative
false
neg
ative
4
HRCTHRCT SpiralSpiral--CTCT
Gap?
HRCTHRCT SpiralSpiral--CTCT
Gap?
HRCTHRCT SpiralSpiral--CTCT
Gap?
HRCTHRCT SpiralSpiral--CTCT
Gap? Multislice-CT (MSCT)
480438
Multislice-CT (MSCT)
C HRCT slice thickness 1 mmtable feed 10 mm
RecommendationA MSCT slice thickness 1 mm
pitch 2increment 1 mm
B HRCT slice thickness 1 mm+ table feed 10 mm
Spiral-CT slice thickness 4 mmpitch 2increment 4 mmro
ugh
valu
es
roug
h va
lues
Radiation Exposurenature p.a. ~1 mSvCXR 0.1 – 0.2 mSvMSCT 2 - 6 mSv
low-dose 0.6 - 2 mSvHRCT 0.5 - 1 mSvPET 4 mSvMRI 0 mSv
Kuiper et al., Eur Radiol 2003 courtesy of Yamamura et al., RöFo 2009
Dose Reduction
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%
5
MRI• “hip”• characterisation• T1w: signal ↑ = hemorrhage• T1w: target sign - peripheral rim
- central necrosis• T2w: reverse target sign• early: CT• late: CT ~ MRI• abscess: MRI > CT (pseudo capsule)
Herold et al. Radiology 1989; 173: 717-721Blum et al. RöFo 1994; 161:292-299Leutner et al. RöFo 1999; 170: 449-456 T1 T1 T1 + T1 + GdGd 230877230877
CT vs. MRIFUO, neutropenia, n=30neg CXR: CT & MRI
• sensitivity 95%• specificity 88%• pos. predictive value 95%• neg. predictive value 88%
Problems with - small lesions- cardiac motion
Eibel R. et al. Radiology. 2006
CXR
Fever > 48h
Follow-up
normal Infiltrate
Invasive Procedure
normalHRCT
Infiltrate
A. Early Detection
B. Characterisation
C. Intervention
D. Extra-pulmonary
hints for:– typical bacterial pneumonia
• positive bronchogram• consolidation• pleural effusion
Lobar PneumoniaLobar Pneumonia
379726379726 200851200851
BronchoBroncho-- Atypical PneumoniaAtypical Pneumonia
382063382063
After Kidney Transplantation (n=19)• TBC n=11 • CMV n=2• cryptococci• streptococci• aspergillus• HRCT - correct 60%
- non-specific 15%- normal 25%
GulatiGulati et al.(2000) Acta et al.(2000) Acta RadiolRadiol
6
hints for:– pulmonary tuberculosis
• cavitations• consolidation• well-defined nodules• bronchogenic distribution
HlawatschHlawatsch et al. (2000) Radiologeet al. (2000) Radiologe 396087 438365
TBC TBC hints for:– fungal pneumonia
• early: ill-defined nodules (“halo”)• angiotropic distribution• late - cavitations
- air-crescent sign• while hematological reconstitution
⇒ positive prognosis• vessel arosion / aneurysm
febrile day 8 day 3 day 3
Fungal Pneumonia Fungal Pneumonia
1984 described1
1985 discussed in 9 patients2
1 Gefter et al. Radiology ’842 Kuhlman et al. Radiology ’85
HaloHalo--signsign
• major- Dense, well-circumscribed lesions - with or without a halo sign- air-crescent sign
• minor
De Pauw et al., Clin Infect Dis 2008
EORTC CriteriaFungal Pneumonia
200031
halo signhalo signFungal Pneumonia Fungal Pneumonia
Candida sepsis (+ Candida sepsis (+ hepatolienalhepatolienal C.) C.)
319944
Fungal Pneumonia Fungal Pneumonia hepatosplenichepatosplenic candidiasiscandidiasis
7
465250
Halo
202555
HaloHalo
394377
HaloHalo
203187
HaloHalo
69533
Halo
599429
HaloHalo
frequencymakronodules 94%halo 61% consolidation 30%infarct-shaped 27%cavitation 20%air-crescend 10%
Greene et al. CID ‘07
Value of haloValue of halo--signsignIPA, n=235IPA, n=235
response52% vs. 29%; p<0.001
3 month survival71 vs. 53%; p<0.01
pro• many patients• ante-mortem trial
Greene et al. CID ‘07
Value of haloValue of halo--signsignIPA, n=235IPA, n=235
contra• halo = part of inclusion• 95% hardcopies• thick section CT• 270° of halo not defined
infected portinfected port
95882
Septic EmbolismSeptic Embolism
8
8336796 +59d.
explantationexplantation
infected portinfected portSeptic EmbolismSeptic Embolism Halo?
M13
galaxy-sign= Sarcoid Halo!Halo! 465250
CavitationCavitation
HaloHalo
83390098341975
adenoadeno--caca.. metameta leioleio--caca airair--crescent signcrescent sign
161295
Fungal Pneumonia Fungal Pneumonia Fungal Pneumonia Fungal Pneumonia airair--crescent signcrescent sign
Inversed Halo
IPAIPA
Inversed Halo
8335056
BCBC
0001649378
SarcoidSarcoid
8336995
PEPEconsolidationconsolidationnodulenodule
Fungal Pneumonia Fungal Pneumonia IllIll--defined nodules + halo signdefined nodules + halo sign
265250
9
consolidation
470067
Fungal Pneumonia Fungal Pneumonia
492289
Fungal Pneumonia Fungal Pneumonia airair--crescent signcrescent sign
152287
Fungal Pneumonia Fungal Pneumonia cavitationcavitation
A.Screening
B.Early detection
C.Characterisation
D.Monitoring
E.Intervention
Response EvaluationResponse Evaluation
8332285
+6 mo.metastases
Dijon:
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 Course
antifungal treatment131928
day 3 day 43 day 67 day 94 day 125
Radiological Course
shrinkageill-defined nodules
hemat. recovery
increasing volumen
antifungal treatment
shrinkage
10
recovery +air-crescent
shrinkage shrinkage increasing volumen
ill-defindednodule
day 75 day 57 day 50 day 43 day 27
Radiological Course Radiological Course
0d 10 20 30
Neutropenia Recovery
differential diagnosis
• bacterial pneumonia• mycobacteria• pneumocystis jiroveci• virus or GvHD• radiation toxicity• drug toxicity• congestion• ...
• metastases• bronchoalveolar carc.• lymphoma• COP (BOOP)• amyloidosis• M. Wegener• eosinophilic pneumonia• ...
febrile neutropeniafebrile neutropenia
Fungal Pneumonia Fungal Pneumonia
hints for:– pneumocystis jiroveci jiroveci pneumonia
• ground glass opacity (low °)• perihilar distribution
leaving out subpleural space• late stage: - intralobular septs
- air-space cystsStringer JR et al. (2002) Stringer JR et al. (2002) EmergEmerg InfectInfect DisDis
PcPPcP -- Pneumocystis jiroveci Pneumocystis jiroveci pneumoniapneumonia
Stringer JR et al. (2002) Stringer JR et al. (2002) EmergEmerg InfectInfect DisDisCransCrans CA et al. (1999) CA et al. (1999) CritCrit RevRev DiagnDiagn ImagingImaging
cytomegalo virus pneumonia (CMV) (n=32)
• ground glass opacification 66%• ill-defined nodules 59%• consolidation 59%• bronchovascular bundle 22%• pleural effusion 22%• tree-in-bud 13%
FranquetFranquet T et al. (2003) Am J T et al. (2003) Am J RoentgenolRoentgenol
hints for:– CMV pneumonia – graft versus host disease (GvHD)
• ground glass opacification ( high / low ° )• mosaic distribution (secondary lobe)• high-risk: - allo-Tx, AIDS
- T-cell depleted Tx- anti-CD20
CMV CMV chron. chron. GvHDGvHDakuteakute GvHDGvHD
11
hints for:– drug toxicity:
• ground glass opacification ( high / low ° )• mosaic distribution (secondary lobe)• Bleomycin, MTX, Ara-C etc.
BleomycinBleomycin hints for:
radiation toxicity:• paramediastinal distribution
- even after total body irradiation (TBI)
• ground glass opacification• intralobular sept• weeks to month later
Radiation ToxicityRadiation Toxicity
272067272067
hints for:
– congestion:• thickening of lymphatic sept• demarcation of secondary lobe • pleural effusion
CongestionCongestion
hints for:
– lymphangiosis carcinomatosa:
• conic thickening of lymphatic sept
• mikronodules
• breast / gastric cancer
LymphangiosisLymphangiosis CarcinomatosaCarcinomatosahints for:pulmonary hemorrhage:
• thrombocytes / platelets ↓• plasmatic coagulation ↓• hemoptysis• sedimentation phenomen• perifocal
12
hemorrhage hemorrhage A.Screening
B.Early detection
C.Characterisation
D.Monitoring
E.Intervention
CT Guided Biopsy
Hwang et al., AJR 2000
CTCT--FluoroscopyFluoroscopy CT guided Ampho B instillation• total: n = 15
– 3 repetition– CR / PR / SD: 0 / 12 / 3
• total: n = 13– 1-5 repetition– CR / PR / SD: 8 / 4 / 1
Giron et al., Radiology ‘93, Eur J Radiol ‘98
Veltri et al., Eur Radiol 2000preprepostpost
CT guided Ampho B instillation
Vessel Arrosion• 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 1997Pagano et al., Br J Haematol 1995
post post embolisationembolisation
Heussel et al., Eur Radiol ‘97
prepre
Aspergillus Pneumonia + Aspergillus Pneumonia + PseudoPseudo--AneurysmAneurysm
CT Guided Biopsy
Lass-Flörl et al., CID 2007
patients 61Aspergillus. sp. 36Mucor sp. 5Rhizomucor sp. 3Absidia sp. 4Cunnighamella sp. 1
BC, Leukemia, TB 9
46 hematological patients15 organ-Tx85% halo30% air-crescent
n=17Asper. sp.8Mucor sp.4non-spec.4
2 laterBAC 1Nosari, Haematol. 03
n=16Asper. sp. 8mould 2COP 4TBC 1PcP 1Shi, Int J Hematol. 09
13
A. Early Detection
B. Characterisation
C. Intervention
D. Extra-pulmonary
Sinusitis plus:- Acute localized pain - Nasal ulcer with black eschar- Extension from the paranasal
sinus across bony barriers, including into the orbit
De Pauw et al., Clin Infect Dis 2008
EORTC CriteriaFungal Sinusitis
230661138748
SinusitisSinusitis
levellevel bonebone--arrosionarrosion
SinusitisSinusitis
Bone Bone ArrosionArrosion
RhinoRhino--Cerebral InfectionCerebral InfectionAspergillus Aspergillus nigerniger
CT
bone bone arrosionarrosion brain invasionbrain invasion
T1T1--GdGd 368537
- Focal lesions on imaging- Meningeal enhancement on MRI or CT
De Pauw et al., Clin Infect Dis 2008
EORTC CriteriaFungal CNS Infection
?Cerebral LesionCerebral Lesion
CT
CTCT
T2T2
T1T1--GdGd 575080
MeningoencephalitisMeningoencephalitis
CT
T2w T1w + T1w + GdGd 313501
CTCT
Toxoplasmosis in HIVToxoplasmosis in HIV
FLAIRFLAIR T1w + T1w + GdGdT1wT1w 460382
14
After an episode of candidemiawithin the previous 2 weeks:- Small, target-like abscesses (bull’s-
eye lesions) in liver or spleen- Progressive retinal exudates on
ophthalmologic examination
De Pauw et al., Clin Infect Dis 2008
EORTC CriteriaDisseminated Candidiasis
T1wT1w
T2wT2w
T1w T1w GdGd
208383
NHL, PSCT, NHL, PSCT, hepatichepatic CandidiasisCandidiasis• adipositas, investigator, training
• i.v. contrast: allergy, renal impaiment, Metformin, thyroid autonomy
• oral contrast• breath-hold
• claustrophobia• pace maker, defibrillator, pump• foreign body containing iron• confusion, convulsion, agitation• limited monitoring• breath-hold
LimitsUS
CT
MRI
Summary
Chest:
Para Nasal:
Brain:
Abdomen:
thin section CT no supine chest x-rayCTno plain radiographMRICT in emergency (hemorrhage)liver → MR > CTvessels / peritoneum → CTVOD → duplex
LiteratureGuidelines: 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) 241