Skip to main content

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

Strahlentherapie und Onkologie volume 195, pages 756–763 (2019)Cite this article

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.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  1. Van der Horst A, Lens E, Wognum S et al (2014) Limited role for biliary stent as surrogate fiducial marker in pancreatic cancer: stent and Intratumoral fiducials compared. Int J Radiat Oncol Biol Phys 89(3):641–648

    Article  PubMed  Google Scholar 

  2. Packard M, Gayou O, Gurram K et al (2015) Use of implanted gold fiducial markers with MV-CBCT image-guided IMRT for pancreatic tumours. J Med Imaging Radiat Oncol 59:499–506

    Article  PubMed  Google Scholar 

  3. Chortogiannos C, Moseley D, Chen J et al (2017) Evaluation of bony anatomy versus endobiliary stents as surrogates for volumetric image guidance in pancreatic cancer. J Med Imaging Radiat Sci 48:352–359

    Article  PubMed  Google Scholar 

  4. Dobiasch S, Goerig NL, Fietkau R, Combs SE (2018) Essential role of radtiation therapy for the treatment of pancreatic cancer. Strahlenther Onkol 194:185–195

    Article  PubMed  Google Scholar 

  5. Van der Horst A, Wognum S, Fajardo RD et al (2013) Interfractional position variation of pancreatic tumors quantified using Intratumoral fiducial markers and daily cone beam computed tomography. Int J Radiat Oncol Biol Phys 87(1):202–208

    Article  PubMed  Google Scholar 

  6. Varadarajulu S, Trevino JM, Shen S et al (2010) The use of endoscopic ultrasound-guided gold markers in image-guided radiation therapy of pancreatic cancers: a case series. Endoscopy 42:423–425

    Article  CAS  PubMed  Google Scholar 

  7. Versteijne E, Lens E, van der Horst A et al (2017) Quality assurance of the PREOPANC trial (2012-003181-40) for preoperative radiochemotherapy in pancreatic cancer. Strahlenther Onkol 193:630–638

    Article  PubMed  PubMed Central  Google Scholar 

  8. Mazzola R, Fersino S, Aiello D et al (2018) Linac-based stereotactic body radiation therapy for unresectable locally advanced pancreatic cancer: risk-adapted dose prescription and image-guided delivery. Strahlenther Onkol 194:835–842

    Article  PubMed  Google Scholar 

  9. Panje C, Andratschke N, Brunner TB, Niyazi M, Guckenberger M (2016) Stereotactic body radiotherapy for renal cell cancer and pancreatic cancer. Strahlenther Onkol 192:875–885

    Article  PubMed  Google Scholar 

  10. Scherman Rydhög J, Jølck RI, Andresen TL et al (2015) Quantification and comparison of visibility and image artifacts of a new liquid fiducial marker in a lung phantom for image-guided radiation therapy. Med Phys 42:2818

    Article  PubMed  Google Scholar 

  11. Gurney-Champion OJ, Lens E, van der Horst A et al (2015) Visibility and artifacts of gold fiducial markers used for image guided radiation therapy of pancreatic cancer on MRI. Med Phys 42:2638–2647

    Article  PubMed  Google Scholar 

  12. Schneider S, Jølck RI, Troost EGC et al (2018) Quantification of MRI visibility and artifacts at 3T of liquid fiducial marker in a pancreas tissue-mimicking phantom. Med Phys 45(1):37–47

    Article  CAS  PubMed  Google Scholar 

  13. Giebeler A, Fontenot J, Balter P et al (2009) Dose perturbations from implanted helical gold markers in proton therapy of prostate cancer. J Appl Clin Med Phys 10:2875

    Article  PubMed  PubMed Central  Google Scholar 

  14. Newhauser W, Fontenot J, Koch N et al (2007) Monte Carlo simulations of the dosimetric impact of radiopaque fiducial markers for proton radiotherapy of the prostate. Phys Med Biol 52:2937–2952

    Article  PubMed  Google Scholar 

  15. Habermehl D, Henkner K, Ecker S et al (2013) Evaluation of different fiducial markers for image-guided radiotherapy and particle therapy. J Radiat Res 54:i61–i68

    Article  PubMed  PubMed Central  Google Scholar 

  16. Scherman Rydhög J, Perrin R, Jølck R et al (2017) Liquid fiducial marker applicability in proton therapy of locally advanced lung cancer. Radiother Oncol 122:393–399

    Article  PubMed  Google Scholar 

  17. Jølck RI, Binderup T, Hansen AE et al (2014) Injectable colloidal gold in a sucrose acetate isobutyrate gelating matrix with potential use in radiation therapy. Adv Healthc Mater 3:1680–1687

    Article  CAS  PubMed  Google Scholar 

  18. Troost EGC, Menkel S, Enghardt W et al (2017) BioXmark® remains chemically stable following normofractionated and single-fraction high-dose proton beam irradiation. Proceedings to the 56 Annual Meeting of the Particle Therapy Cooperative Group (PTCOG). Int J Part Ther 4(1):75

    Google Scholar 

  19. Dobiasch S, Kampfer S, Burkhardt R et al (2017) BioXmark for high-precision radiotherapy in an orthotopic pancreatic tumor mouse model. Strahlenther Onkol 193:1039–1047

    Article  CAS  PubMed  Google Scholar 

  20. Scherman Rydhög J, Mortensen S, Larsen K et al (2016) Liquid fiducial marker performance during radiotherapy of locally advanced non-small cell lung cancer. Radiother Oncol 121:64–69

    Article  Google Scholar 

  21. De Blanck SR, Scherman-Rydhög J, Larsen KL, al etl (2018) Long term safety and stability and visibility of a novel liquid fiducial marker for use in image guided radiotherapy of non-small cell lung cancer. Clin Transl Radiat Oncol 13:24–28

    Article  PubMed  PubMed Central  Google Scholar 

  22. De Blanck SR, Scherman-Rydhög J, Siemsen M, al etl (2018) Feasibility of a novel liquid fiducial marker for use in image guided radiotherapy of oesophageal cancer. Br J Radiol 91(1092):20180236

    Article  PubMed  Google Scholar 

  23. De Roover R, Crijns W, Poels K et al (2018) Characterization of a novel liquid fiducial marker for multi-modal image guidance in stereotactic body radiotherapy of prostate cancer. Med Phys 45:2205–2217

    Article  PubMed  Google Scholar 

  24. Mortensen SR, Scherman JB, Larsen KR et al (2014) Use of a novel liquid fiducial marker injected with endoscopic ultrasound equipment for use in image guided radiation therapy of thoracic tumors (porcine model). Int J Radiat Oncol Biol Phys 90(1):S651

    Article  Google Scholar 

  25. Pieper S, Halle M, Kikinis R (2004) 3D slicer. Proceedings of the 1st IEEE International Symposium on Biomedical Imaging: From Nano to Macro. vol 1, pp 632–635

    Google Scholar 

  26. Tanaka O, Nishigaki Y, Hayashi H et al (2017) The advantage of iron-containing fiducial markers placed with a thin needle for radiotherapy of liver cancer in therms of visualization on MRI: an initial experien of Gold Anchor. Radiol Case Rep 12(2):416–421

    Article  PubMed  PubMed Central  Google Scholar 

  27. Marsico M, Gabbani T, Lunardi S, Galli A, Biagini MR, Annese V (2017) Percutaneous ultrasound-guided fiducial marker placement for liver cancer robotic stereotactic radio-surgery treatment: A comparative analysis of three types of markers and needles. Arab J Gastroenterol 18(2):83–86

    Article  PubMed  Google Scholar 

  28. Larsen MH, Fristrup CW, Detlefsen S, Mortensen MB (2018) Prospective evaluation of EUS-guided fine needle biopsy in pancreatic mass lesions. Endosc Int Open 6(2):E242–E248

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  1. Institute of Radiooncology—OncoRay, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany

    Sergej Schneider MSc, Esther G. C. Troost MD, PhD & Aswin L. Hoffmann PhD

  2. OncoRay—National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Fetscherstraße 74, PF 41, 01307, Dresden, Germany

    Sergej Schneider MSc, Esther G. C. Troost MD, PhD & Aswin L. Hoffmann PhD

  3. Institute of Pathology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

    Daniela E. Aust MD, PhD

  4. Medical Department 1, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

    Stefan Brückner MD, PhD & Jochen Hampe MD, PhD

  5. Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

    Thilo Welsch MD, PhD

  6. Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

    Esther G. C. Troost MD, PhD & Aswin L. Hoffmann PhD

  7. German Cancer Consortium (DKTK), partner site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany

    Esther G. C. Troost MD, PhD

  8. National Center for Tumor Diseases (NCT), partner site Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden; and Helmholtz Association/Helmholtz-Zentrum Dresden – Rossendorf (HZDR), Dresden, Germany

    Esther G. C. Troost MD, PhD

Authors
  1. Sergej Schneider MSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniela E. Aust MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stefan Brückner MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thilo Welsch MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jochen Hampe MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Esther G. C. Troost MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Aswin L. Hoffmann PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sergej Schneider MSc.

Ethics declarations

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.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00066-019-01474-1

Keywords

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

Schlüsselwörter

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