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Contrast-enhanced ultrasound after devascularisation of neuroendocrine liver metastases: functional and morphological evaluation

  • Ultrasound
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Abstract

Objective

To evaluate morphological and perfusion changes in liver metastases of neuroendocrine tumours by contrast-enhanced ultrasound (CEUS) after transarterial embolisation with bead block (TAE) or trans-arterial chemoembolisation with doxorubicin-eluting beads (DEB-TACE).

Methods

In this retrospective study, seven patients underwent TAE, and ten underwent DEB-TACE using beads of the same size. At 1 day before embolisation, 2 days, 1 month and 3 months after the procedure, a destruction-replenishment study using CEUS was performed with a microbubble-enhancing contrast material on a reference tumour. Relative blood flow (rBF) and relative blood volume (rBV) were obtained from the ratio of values obtained in the tumour and in adjacent liver parenchyma. Morphological parameters such as the tumour’s major diameter and the viable tumour’s major diameter were also measured. A parameter combining functional and morphological data, the tumour vitality index (TVI), was studied. The Wilcoxon rank-sum test and Fisher’s test were used to compare treatment groups.

Results

At 3 months rBF, rBV and TVI were significantly lower (P = 0.005, P = 0.04 and P = 0.03) for the group with doxorubicin. No difference in morphological parameters was found throughout the follow-up.

Conclusions

One parameter, TVI, could evaluate the morphological and functional response to treatments.

Key Points

• Contrast-enhanced ultrasound provides morphological and functional information about neuroendocrine hepatic metastases

• CEUS can evaluate changes after transarterial chemoembolisation, transarterial-embolisation and transarterial radioembolisation

• Functional (but not morphological) imaging reveals differences between TAE and DEB-TACE therapy

• To combine morphological and functional parameters, a tumour vitality index is proposed

• TVI can be used to monitor treatments acting on tumour vascularisation

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Abbreviations

AST:

aspartate aminotransferase

ALT:

alanine aminotransferase

BF:

blood flow

BV:

blood volume

CEUS:

contrast-enhanced ultrasound

CHI:

contrast harmonic imaging

CR:

complete response

CRP:

C-reactive protein

DEB:

drug-eluting beads

LDH:

lactate dehydrogenase

MI:

mechanical index

NET:

neuroendocrine tumour

rBF:

relative blood flow

rBV:

relative blood volume

PD:

progressive disease

PR:

partial response

RECIST:

response evaluation criteria in solid tumours

ROI:

region of interest

SD:

stable disease

TACE:

trans-arterial chemoembolisation

TAE:

trans-arterial embolisation

TVI:

tumour vitality index

TMD:

tumour’s major diameter

VTMD:

viable tumour’s major diameter

WDEC:

well-differentiated endocrine carcinoma

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Author information

Authors and Affiliations

  1. Hospices Civils de Lyon, Hôpital Edouard Herriot, Service d’Imagerie Digestive, 69437, Lyon cedex 03, France

    Aymeric Guibal, Thibaud Lefort & Franck Pilleul

  2. Hospices Civils de Lyon, Hôpital Edouard Herriot, Fédération de Biochimie, 69437, Lyon cedex 03, France

    Laurence Chardon

  3. Hospices Civils de Lyon, Hôpital Edouard Herriot, Fédération des Spécialités Digestives, 69437, Lyon cedex 03, France

    Noura Benslama

  4. Laboratoire d’imagerie fonctionnelle, UMR-S 678, Université Paris 6, Paris, France

    Sébastien Mulé

  5. Hospices Civils de Lyon, Hôpital Edouard Herriot, Fédération des Spécialités Digestives, 69437, Lyon cedex 03, France

    Catherine Lombard-Bohas, Jean Alain Chayvialle & Thomas Walter

  6. Laboratoire d’imagerie paramétrique, UMR 7623, Université Paris 6, Paris, France

    Aymeric Guibal, Lori Bridal & Olivier Lucidarme

  7. Hopital Pitié Salpétrière, Service de radiologie polyvalente diagnostique et interventionnelle, 47-83 Boulevard de l’Hôpital, 75013, Paris, France

    Olivier Lucidarme

  8. Service de radiodiagnostic et radiologie interventionnelle, CHUV, 1011, Lausanne, Suisse, Switzerland

    Alban Denys

  9. Pavillon H, Hôpital Edouard Herriot, 69437, Lyon Cedex 03, France

    Aymeric Guibal

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  1. Aymeric Guibal
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Corresponding author

Correspondence to Aymeric Guibal.

Appendix: the monoexponential refilling model (CEUS with destruction-replenishment sequence—general case)

Appendix: the monoexponential refilling model (CEUS with destruction-replenishment sequence—general case)

During constant infusion of microbubbles, the regional concentration of refilling microbubbles after destruction can be described by the following equations according to the indicator-dilution theory with single open-compartment analysis:

$$ \frac{{dC(t)}}{{dt}} = \frac{F}{{Vf}}{C_{{0}}} - \frac{F}{{{V_f}}}C(t) $$
(A1)

where C0 is the regional concentration of microbubbles within the microcirculation outside the ultrasound field (quantity of microbubbles/100 g of tissue), F the regional blood flow (ml/min/100 g of tissue) and Vf the fractional blood volume (ml/100 g of tissue) (43). Considering that at time t = 0, C(t) = 0, the solution of Eq. (A1) is:

$$ C(t) = {C_0}\left( {1 - {e^{{ - \beta t}}}} \right) $$
(A2)

with β = F/Vf.

In the infusion conditions the concentration of microbubbles in the blood, Ci, is constant within the vascular space. Therefore, as C0 = Vf∙Ci, the plateau of the curve given by Eq. (A2), C0, is proportional to the fractional blood volume Vf.

The slope of the curve given by Eq. (A2) is given by:

$$ \frac{{dC(t)}}{{dt}} = {C_0}\beta {e^{{ - \beta t}}} $$
(A3)

; thus, the initial slope (t = 0) is C0β and is proportional to the blood flow F (26).

According to the central volume principle, mean vascular transit time = blood volume/blood flow (44); thus the value 1/β can be considered as an estimation of the regional mean transit time of microbubbles.

At the concentrations used in clinical CEUS practice, the signal intensity I is proportional to the concentration in microbubbles in the image (26); thus Eq. (A2) becomes:

$$ I(t) = A\left( {1 - {e^{{ - \beta t}}}} \right) $$
(A4)

with I(t) = k∙C(t) and A = k∙C0.

Considering tumoral and parenchymal ROIs in the same ultrasound field, the ratio of the initial signal intensity slopes (A∙β) equals the ratio of regional blood flow values, the ratio of the signal plateaus (A) equals the ratio of the regional fractional blood volumes, and the ratio of the 1/β values is an estimation of the ratio of the regional mean transit time values.

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Guibal, A., Lefort, T., Chardon, L. et al. Contrast-enhanced ultrasound after devascularisation of neuroendocrine liver metastases: functional and morphological evaluation. Eur Radiol 23, 805–815 (2013). https://doi.org/10.1007/s00330-012-2646-4

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  • DOI: https://doi.org/10.1007/s00330-012-2646-4

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