Carlo AprileCarlo AprileSC Medicina NucleareSC Medicina Nucleare

Fond.Policlinico S.Matteo,IRCCSFond.Policlinico S.Matteo,IRCCSPaviaPavia

IMAGING IMAGING MEDICO-MEDICO-

NUCLEARENUCLEARE

Identification of CTEPH as the cause of PH is facilitated by several imaging techniques:

• Ventilation–Perfusion (V/Q) scintigraphy,

• multidetector CT Pulmonary Angiography (CTPA),

• High-Resolution CT (HRCT),• pulmonary Digital Subtraction

Angiography (DSA), • Magnetic Resonance Angiography

CTPA-large multicenter studyStein PD, et al. Multidetector computed tomography for acute pulmonary acute pulmonary embolismembolism. N Engl J Med. 2006;354:2317

sensitivity of 83% • specificity of 96%,• with even a lower sensitivity for segmental

(68%) and subsegmental (25%) branches

Pitton MB, et al. Chronic thromboembolic pulmonary Chronic thromboembolic pulmonary hypertensionhypertension: diagnostic impact of multislice-CT and selective pulmonary-DSA. Rofo. 2002;174:474.Multidetector CTPA

•sensitivity of 70.4% for segmental and• 63.6% for subsegmental branches

when compared with pulmonary DSA

Accuracy of Various Imaging Methods AgainstAccuracy of Various Imaging Methods AgainstPulmonary Angiography as the Reference Method to Pulmonary Angiography as the Reference Method to

Diagnose CTPHDiagnose CTPH

Lang et al. Imaging in Pulmonary Hypertension J A C C : C A R D I O V A S C U L A R I M A G I N G . 2 0 1 0; 3:1287

SCINTIGRAFIA POLMONARE DI PERFUSIONESCINTIGRAFIA POLMONARE DI PERFUSIONE

SCINTIGRAFIA POLMONARE VENTILATORIASCINTIGRAFIA POLMONARE VENTILATORIA

1. Sc VENTILATORIA CON AEROSOLAEROSOL : test diagnostico che visualizza la distribuzione broncopolmonare di un radioaerosol inalato

2. Sc. VENTILATORIA CON GAS RADIOATTIVIGAS RADIOATTIVI: test diagnostico che visualizza la distribuzione polmonare di un gas radioattivo inalato, durante le manovre respiratorie

3. Sc VENTILATORIA CON PSEUDOGASPSEUDOGAS (Technegas), range 60-160nm (media 97nm)

Limite dimensionale di valutazione del circolo periferico della metodica scintigrafica e TC.

F a.70 Ipertensione polmonare post-embolica, in attesa TEAP

SOSPETTA PE IN COPDSOSPETTA PE IN COPD

J Nucl Med 2007; 48:680–684

500 patients with PH referred to Hammersmith Hospital, London, between 2000 and 2005: 227 elegible pts

V/Q Images were interpreted according to the modified PIOPED criteria

1. A high-probability scan : suggestive of chronic thromboembolic pulmonary disease,

2. low-probability scan : suggestive of nonchronic thromboembolic pulmonary disease etiology.

1. For intermediate-probability scans: 2 separate datasets • In one as suggestive of chronic

thromboembolic pulmonary disease and, • in the other dataset, not suggestive of

chronic thromboembolic pulmonary disease

Multidetector CTPA- A report was considered as suggestive of chronic thromboembolic pulmonary disease if:

• visualization of the thrombus,• calcified thrombus, • recanalization, • sudden change in vessel caliber,• strictures,• poststenotic dilatation, • webs, or perfusion abnormality

Pulmonary DSA: indications (61/78 pts)

• (a) clinical suspicion of CTEPH,

• (b) at least one positive imaging modality for chronic thromboembolic pulmonary disease,and

• (c) whether the patient was being assessed for pulmonary thrombendarterectomy.

V/Q scan CTPAGroup Low

probabilityIntermediate

probabilityHigh

probabilityNegative Positive

A (n 78)

2FN

1 75 38FN

40

B (n 149)

134 78

FP148 1

Summary of V/Q Scans and CTPA Results

with CTEPH (group A, n 78 patients),

with non-CTEPH (group B, n 149 patients)

MP: Mosaic Perfusion

MP

43

10

V/Q Diagnosis

Intermediate probability

(n = 7)

IPAH (n = 4)

IPAH and emphysema (n = 1)

ASD and pulmonary fibrosis (n = 1)

Pulmonary fibrosis (n = 1)

High probability (n = 8)

IPAH (n = 3)

PVOD (n = 1)

APAH and ASD (n = 2)

Scleroderma and pulmonary fibrosis (n = 1)

Apical bullae: apical mismatch on V/Q (n = 1)

Summary of False-POSITIVE V/Q Scans

IPAH = idiopathic pulmonary arterial hypertension; ASD = atrial septal defect; PVOD = pulmonary venoocclusive disease; APAH = associated pulmonary arterial hypertension

Summary of False-NEGATIVE V/Q Scans

V/Q Diagnosis2 patients from group A with low probability scan

CTPA 1. calcified thrombus in one patient and

2. narrowed but patent pulmonary arterial branches

1 patient from group A with intermediate probability scan

CT severe emphysematous

changes without signs of CTEPH

DSA CTEPH

*Intermediate with high-probability scans as indicative of CTEPH.

  Only high-probability scans as indicative of CTEPH.

scan

Indicator V/Q (1)* V/Q (2) CTPA

Sensitivity (%) 97.4 96.2 51.3Specificity (%) 90 94.6 99.3Accuracy (%) 92.5 95.2 82.8NPV (%) 98.5 97.9 79.7

PPV (%) 83.5 90.3 97.6

Summary of Performance Indicators for V/Q Scintigraphy and CTPA

PISAPED PISAPED Q J Nucl Med 2001; 45: 281

Perfusione da sola, criteri interpretativi “nuovi”, risposta SI/NO:

1) scintigrafia normale;

2) scintigrafia anormale con aspetto non embolico;

3) scintigrafia anormale con aspetto embolico

PISAPED PISAPED Q J Nucl Med 2001; 45: 281

• 890 pazienti

• SENSIBILITA’: 92%

• SPECIFICITA’: 87%

Interpretazione Casistica CRITERI SENS SPECSostman (PIOPED)

PISAPED PISAPED 91 90

Miniati (PISAPED)

PIOPED PISAPED 80 83

Miniati (Am J Respir Crit Care Med 1996; 154: 1387 ; Am J Respir Crit Care Med 1999; 159: 864)

DE

CT

V/Q scantot

PE+PE+ e altro

Altre pat

NEG

A-operati

Q dif. 50 15 0 0 65

Q unif 0 0 0 0 0

A- non operati

Q dif. 9 3 2 0 14

Q unif 0 0 0 0 0

BQ dif. 0 2 1 0 3

Q unif 2 0 2 3 7

tot 61 20 5 3 89

Stoppa D. Tesi Laurea aa.2009-10

DECT DECT vs.vs. V/Q scan V/Q scan IRCCS S.Matteo -Pavia

VENTILATION–PERFUSION IN CTEPH • Tunariu et al.J Nucl Med 2007; 48:680

• normal V/Q scintigraphy practically rules out the presence of CTEPH,

• whereas normal CTPA does not exclude the presence of

CTEPH.

• high probability V/Q scintigraphy makes CTEPH the most likely diagnosis, although other conditions—including pulmonary venoocclusive disease—may result in similar findings.

• grouping intermediate- with low-probability V/Q scans as indicative of non-CTEPH etiology would maintain a high sensitivity and improve specificity, NPV,and PPV.

V/Q Scanning for Pulmonary Hypertension

Worsley DF et al. JNM 1994;35:793

National Pulmonary Hypertension Centres of the UK and Ireland

Consensus statement on the management of pulmonary

hypertension in clinical practice in the UK and Ireland

Heart 2008;94;1-41

Diagnostic approach to chronic thromboembolic pulmonary hypertension (CTEPH).

National Pulmonary Hypertension Centres of the UK and Ireland Heart 2008;94;1-41

ESC/ERS GUIDELINES

FOR THE DIAGNOSIS AND

TREATMENTOF PULMONARY HYPERTENSION

Eur Respir J 2009; 34: 1219–1263

Contemporary Diagnostic Imaging Algorithm

Lang et al. Imaging in Pulmonary Hypertension J A C C : C A R D I O V A S C U L A R I M A G I N G . 2 0 1 0; 3:1287

Caso 1 - DLS

V

Q

DLS ♂ 68 a.

Angio: ostruzione completa rami polmonari lobari medio e inf. Dx

EAP dx & CABG

V / Q BASALE

ANT POST RAO

LPO LAO RPO

DLS +16 d

ANT POST LAO

RPO RAO LPO

ANT POST RAO

LPO LAO RPO

DLS +4m

DLS +9m

ANT POST RAO

LPO LAO RPO

ANT POST LAO

RPO RAO LPO

DLS +38m

DLS +26m

DLS +48m

RPO

ANT POST LAO

Caso 2 -FA

ANT POST RAO

LPO LAO RPO

FA ♀ 44 a , PE in gravidanza a 26 a.,dai 43 a. dispnea da sforzo, NYHA III, CT trombosi bilat aa. Polmonari, PAPs 105mmHg, ECO-Doppler DVT aa.inf.

EAP sn sup,lingula, inf dx sup, inf - lobect inf dx

V/Q BASALE

ANT POST RAO

LPO LAO RPO

FA +9 d

FA +3 m

ANT POST RAO

LPO LAO RPO

FA +3 m

FA +13 m

FA +26 m

ANT POST RAO

LPO LAO RPO

P.F.#1166 basale V/P

P.F.#1166 TEAP bilat: Dx S,M,I ; Sn S, Li, I

8 d - 3mo

P.F.#1166 TEAP bilat: DxDx S,M,I ; Sn S, Li, I

BL#1903 basale VP: PAPs 80mmHg. Angio-CT embolia ramo principale a polm

dx e coinvolgimento ramo lobare inf, difetto di un ramo segmentario LIS

BL#1903 TEAP DX (S,M,I) 8 d - 200 d

BL#1903 TEAP DX (S,M,I)

CM #1895 46 a. VP basale

CM #1895 46 a. DX (S,M,I) Sn (S,Li,I)

“Steal” after PEA 1

The incidence of new defects was increased tenfold in segments that had

(1) normal preoperative angiographic findings,

(2) normal preoperative radionuclide perfusion, and

(3) not been entered at the time of surgery.

Olman MA et al. Chest. 1990 ;98:1430-4.

“Steal” after PEA 2

1- hypertensive changes induced by the high flows and pressures to which the “open” vascular bed is exposed for months to years, may reduce flow to these zones postoperatively as pulmonary flow is diverted to the relatively normal microcirculation distal to endarterectomized segmental arteries.

2- the neoendothelium in the operated-on segments may create an abnormally low resistance segment in endarterectomized lung zones by its effect on vascular smooth muscle, thus shunting flow toward zones that were endarterectomized.

Olman MA et al. Chest. 1990 ;98:1430-4.

Role of V/Q scan in CTEPH

DIAGNOSIS High accuracy established

EARLY CHANGES AFTER PEA

sensitivePrompt visualization of Q changes

LATE CHANGES AFTER PEA

Clinical impact?

FOLLOW-UPDetection of recurrent PE

established

Longitudinal analysis of perfusion lung scan of patients with unoperated

CTEPH Skoro-Sajer N et al Thromb Haemost 2004; 92: 201

Perfusion scan at (A) baseline and (B) 3 yrs after

•A decrease in the crosssectional area of the pulmonary vessels leads to a loss of the functional capillary bed and vascular remodeling similar to nonthromboembolic PAH.•Within the observation period cardiac index decreased, reflecting RV decline. •Thus, the data suggest that the diagnostic V/Q scan pattern of CTEPH is lost over time, and may be misleading as the disease progresses.

Pulmonary Perfusion Patterns

and Pulmonary ArterialPressure

Scott JA. Radiology 2002; 224:513–518

Scott JA 2002

• Higher total peripheral resistances were seen with chronic PE than with acute for a given degree of vascular obstruction

• This difference was attributed to small-vessel disease in the patients with chronic PE, which was inapparent at subjective evaluation of the Q scan.

• Changes in the peripheral small vessels may thus be an important parameter in determining the PA pressure.

• Patients with primary pulmonary hypertension and CTEPH medial hypertrophy and intimal proliferation in the small distal arteries of the lung .

• This small-vessel component may alter the appearance of the lung periphery on Q scans. Although the scans of most patients with primary pulmonary hypertension lack segmental perfusion defects, the images obtained in some of these patients show a nonspecific “patchiness” that may be related to small-vessel disease

Fractal dimension calculation in (top row) a patient with pulmonaryhypertension (predicted pressure, 75 mm Hg; measured PA systolic [sys] pressure, 80 mm Hg) and (bottom row) a normotensive patient

(predicted pressure, 16 mm Hg, actual18 mm Hg).

Scatterplot of ANN-predicted PA systolic pressures versus those measured at angiography in patients with and in those without

pulmonary embolism (r 0.846, P < .001).

Lung Perfusion Scans Lung Perfusion Scans and Hemodynamics in and Hemodynamics in

Acute and Chronic Acute and Chronic Pulmonary EmbolismPulmonary Embolism

Réza Azarian, Myriam Wartski, Marie-Anne Collignon, Florence Parent, Philippe Hervé,Hervé Sors and

Gerald Simonneau

J Nucl Med 1997; 38:980-983

Relation between PVOs and TPR in Relation between PVOs and TPR in APEAPE A strong hyperbolic correlation was found

between PVOs and TPR (y = 1578/(530 - 5.88x)).

J Nucl Med 1997; 38:980

Relation between PVOs and TPR in APE () and CTEPH ().

For a given degree of obstruction, patients with CTEPH had higher TPR values than patients with APE.

J Nucl Med 1997; 38:980

Pulmonary Vascular Obstruction Pulmonary Vascular Obstruction and Hemodynamics in Acute and and Hemodynamics in Acute and

Chronic PEChronic PE

Values are expressed as means mean±s.d. (range).APE = acute pulmonary embolism; CTEPH = chronic thromboembolic pulmonary hypertension; PVOs = pulmonary vascular obstruction scoreassessed by perfusion lung scanning; PAP = mean pulmonary artery pressure; TPR = total pulmonary resistance.

J Nucl Med 1997; 38:980

In CTEPH patients, the higher PAP and TPR values as compared to APE patients with comparable degrees of PVOs are consistent with previous reports that

PH in CTEPH is due not only to the obstruction of proximal pulmonary arteries but also to remodeling of small distal arteries in nonoccluded areas.

J Nucl Med 1997; 38:980

PET & LUNG

(A) Regional perfusion (Q˙ r) before embolism. (B) Q˙ r after embolism: dramatic redistribution of Q˙ r with many regions of the lungs essentially unperfused. (C)Tracer activity remaining in the lungs at the end of the WO after inhalational delivery of tracer. Note that higher activity corresponds to embolized areas, representing the slower washout rate of these regions.

Grazie dell’attenzione

The 4th WHO Symposium on Pulmonary Hypertension Dana Point, California, 2008

•group 1 as pulmonary arterial hypertension (PAH),

• group 2 as pulmonary hypertension due to left heart disease,

•group 3 as pulmonary hypertension due to lung diseases and/or hypoxia,

• group 4 as chronic thromboembolic pulmonary hypertension ,

•group 5 as pulmonary hypertension of othercauses.