imaging findings in neutropenic vs. non- neutropenic patients

1

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


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


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?


Gap?


Gap?


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


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


335762

day 2 day 7 day 13 day 33 day 108

normal shrinkageill-defined nodules

hemat. recovery

halo reduction

Radiological Course

antifungal treatment131928


Radiological Course

shrinkageill-defined nodules

hemat. recovery

increasing volumen

antifungal treatment

shrinkage

10

recovery +air-crescent

shrinkage shrinkage increasing volumen

ill-defindednodule


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


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


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


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


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

imaging findings in neutropenic vs. non- neutropenic patients

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