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Detectability and structural stability of a liquid fiducial marker in fresh ex vivo pancreas tumour resection specimens on CT and 3T MRI

Detektierbarkeit und strukturelle Stabilität eines flüssigen Bezugsmarkers in frisch resezierten Ex-vivo-Pankreastumorpräparaten in CT und 3T-MRT

Abstract

Purpose

To test the detectability of a liquid fiducial marker injected into ex vivo pancreas tumour tissue on magnetic resonance imaging (MRI) and computed tomography (CT). Furthermore, its injection performance using different needle sizes and its structural stability after fixation in formaldehyde were investigated.

Methods

Liquid fiducial markers with a volume of 20–100 µl were injected into freshly resected pancreas specimens of three patients with suspected adenocarcinoma. X‑ray guided injection was performed using different needle sizes (18 G, 22 G, 25 G). The specimens were scanned on MRI and CT with clinical protocols. The markers were segmented on CT by signal thresholding. Marker detectability in MRI was assessed in the registered segmentations. Marker volume on CT was compared to the injected volume as a measure of backflow.

Results

Markers with a volume ≥20 µl were detected as hyperintensity on X‑ray and CT. On T1- and T2-weighted 3T MRI, marker sizes ranging from 20–100 µl were visible as hypointensity. Since most markers were non-spherical, MRI detectability was poor and their differentiation from hypointensities caused by air cavities or surgical clips was only feasible with a reference CT. Marker backflow was only observed when using an 18-G needle. A volume decrease of 6.6 ± 13.0% was observed after 24 h in formaldehyde and, with the exception of one instance, no wash-out occurred.

Conclusions

The liquid fiducial marker injected in ex vivo pancreatic resection specimen was visible as hyperintensity on kV X‑ray and CT and as hypointensity on MRI. The marker’s size was stable in formaldehyde. A marker volume of ≥50 µL is recommended in clinically used MRI sequences. In vivo injection is expected to improve the markers sphericity due to persisting metabolism and thereby enhance detectability on MRI.

Zusammenfassung

Zielsetzung

Ziel war die Untersuchung der Detektierbarkeit eines flüssigen Bezugsmarkers mittels Magnetresonanztomographie (MRT) und Computertomographie (CT) nach Injektion in Ex-vivo-Pankreastumorgewebe. Weiterhin wurden die Injektionseigenschaften bei unterschiedlichen Nadelgrößen untersucht sowie seine strukturelle Stabilität nach Fixierung in Formaldehyd.

Methoden

Flüssigmarker mit einem Volumen von 20–100 µl wurden in frisch resezierte Pankreaspräparate von drei Patienten mit Verdacht auf Adenokarzinom injiziert. Die röntgenunterstützte Injektion wurde mit verschiedenen Nadelgrößen (18 G, 22 G, 25 G) durchgeführt. Die Bildgebung der Präparate im MRT und CT wurde mit klinischen Protokollen durchgeführt. In der CT-Bildgebung wurden die Marker durch Signal-Schwellenwertbildung segmentiert. Anschließend wurde auf den MRT-Bildern die Detektierbarkeit der Marker innerhalb der registrierten Segmentierungen bewertet. Das basierend auf den CT-Daten bestimmte Markervolumen wurde mit dem injizierten Volumen verglichen und als Maß für den Rückfluss gewertet.

Ergebnisse

Marker mit einem Volumen von ≥20 µl wurden in der Röntgen- und CT-Bildgebung als Hyperintensität nachgewiesen. In T1- und T2-gewichteter 3T-MRT-Bildgebung waren Marker im Bereich von 20–100 µl als Hypointensität sichtbar. Da diese keine Kugelform annahmen, war die Detektierbarkeit eingeschränkt und ihre Differenzierung von Hypointensitäten, die durch Luftkavitäten oder chirurgische Klammern verursacht wurden, nur durch ein Referenz-CT möglich. Ein Markerrückfluss wurde nur bei einer Verwendung einer 18-G-Nadel beobachtet. Nach 24-h-Fixierung in Formaldehyd wurde eine Volumenabnahme von nur 6,6 ± 13,0% beobachtet und mit Ausnahme eines Falls trat kein Auswaschen auf.

Schlussfolgerung

Der Flüssigmarker injiziert in ein Ex-vivo-Pankreaspräparat ist als Hyperintensität auf kV-Röntgen- und CT-Bildern und als Hypointensität in der MRT-Bildgebung sichtbar. Es wird ein Markervolumen von ≥50 µl in klinisch verwendeten MRT-Sequenzen empfohlen. Die Größe des Markers bleibt in Formaldehyd stabil. Aufgrund des anhaltenden Metabolismus wird eine verbesserte Sphärizität des Markers bei In-vivo-Injektion erwartet und damit eine verbesserte Detektierbarkeit in der MRT.

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Acknowledgements

The authors would like to thank T. Jepsen (Nanovi A/S) for providing BioXmark® fiducial markers for this study and Dr. D. Stange for his assistance in organizing and acquiring the pancreatic specimens directly after surgical resection. Furthermore, we would like to thank M. Steckler and her team for supporting us in the acquisition of the CT images.

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Correspondence to Sergej Schneider MSc.

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Conflict of interest

S. Schneider, D.E. Aust, S. Brückner, T. Welsch, J. Hampe, E.G.C. Troost and A.L. Hoffmann declare that they have no competing interests regarding the research presented in this article.

Caption Electronic Supplementary Material

66_2019_1474_MOESM1_ESM.pdf

Figure S1: Exemplary slices of all 17 marker injection sites in three patients showing the markers circled in yellow in (from top to bottom) T1 weighted gradient recalled echo (T1w GRE), T2 weighted turbo spin echo (T1w TSE) and computed tomography (CT) for patient 1-3. Marker injections were ordered form smallest too largest with marker volumes between 20-100μL. Figure S2: Transverse CT image showing 60μL marker injection close to specimen surface leading to partial protrusion. The part of the marker extending the specimen was found washed out after fixation in formaldehyde.

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Schneider, S., Aust, D.E., Brückner, S. et al. Detectability and structural stability of a liquid fiducial marker in fresh ex vivo pancreas tumour resection specimens on CT and 3T MRI. Strahlenther Onkol 195, 756–763 (2019). https://doi.org/10.1007/s00066-019-01474-1

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Keywords

  • Fiducial marker
  • Pancreatic adenocarcinoma
  • MRI detectability
  • Ex vivo

Schlüsselwörter

  • Bezugsmarker
  • Pankreas-Adenokarzinom
  • MRT Detektierbarkeit
  • Ex vivo