Max Masthoff1, Anne Helfen1, Jing Claussen2, Angelos Karlas3,4, Niklas A Markwardt3,4, Vasilis Ntziachristos3,4, Michel Eisenblätter1,5, Moritz Wildgruber1,6. 1. Department of Clinical Radiology, University Hospital Muenster, Muenster, Germany. 2. iThera Medical GmbH, Munich, Germany. 3. Institute for Biological and Medical Imaging, Helmholtz Zentrum München, Munich, Germany. 4. Biological Imaging and Center for Translational Research, Technische Universität München, Munich, Germany. 5. Division of Imaging Sciences and Biomedical Engineering, King's College London, London, United Kingdom. 6. DFG (Deutsche Forschungsgemeinschaft) Cluster of Excellence Cells in Motion EXC 1003, University of Muenster, Muenster, Germany.
Abstract
Importance: Differential diagnosis of congenital vascular anomalies is challenging, and misdiagnosis is frequent. Vascular malformations are considered one of the most difficult vascular diseases to treat. A new imaging approach that visualizes anatomical features and quantitatively assesses molecular biomarkers noninvasively would aid diagnosis and monitoring of treatment response of vascular malformations. Objective: To evaluate multispectral optoacoustic tomography (MSOT) for noninvasive assessment of molecular biomarkers for diagnosis and therapeutic monitoring of vascular malformations. Design, Setting, and Participants: This pilot study examined 6 patients with arteriovenous malformation (AVM) and 6 patients with venous malformation (VM) diagnosed according to the classification system of the International Society for the Study of Vascular Anomalies. All patients underwent clinical hybrid MSOT/ultrasonographic (US) imaging before and after treatment at an interdisciplinary vascular malformations clinic by trained MSOT and US examiners. Examiners were blinded to the patient history and stage of disease. Data were collected from April 11 to 25, 2017, and analyzed from May 1 to October 31, 2017. Interventions: Clinical hybrid MSOT/US imaging was performed before or within 1 week after endovascular embolization (for AVM) or percutaneous sclerotherapy (for VM). Main Outcomes and Measures: Region-of-interest analysis of the lesion and contralateral healthy tissue revealed quantitative values for oxygenated (HbO2) and deoxygenated (HbR) hemoglobin by spectral unmixing of optoacoustic data acquired at multiple wavelengths. The HbO2:HbR ratio was calculated for healthy tissue and for AVM and VM before and after treatment. Results: Twelve patients (9 female and 3 male; mean [SD] age, 23 [18] years; age range, 6-59 years) with vascular malformations (6 with AVMs and 6 with VMs) were included. Significantly higher HbO2:HbR ratios for AVMs (mean [SEM], 1.82 [0.08] vs 0.89 [0.03]; P < .001) and for VMs (mean [SEM], 1.12 [0.04] vs 0.89 [0.03]; P = .001) were found on MSOT tissue compared with healthy tissue. Significantly higher HbO2:HbR ratios for AVMs compared with VMs (mean [SEM], 1.82 [0.08] vs 1.12 [0.04]; P < .001) were also found. Therefore, MSOT provided intrinsic biomarker patterns to distinguish both vascular malformations. After therapy, the HbO2:HbR ratio dropped in correlation to treatment success validated by magnetic resonance imaging or angiography. Conclusions and Relevance: This study suggests that different types of vascular malformations are clearly distinguished by MSOT-based, noninvasive assessment of hemoglobin levels in vascular malformations. The therapy effects found in this study could be instantly visualized, and this may offer a new tool for noninvasive diagnosis and monitoring of vascular malformations.
Importance: Differential diagnosis of congenital vascular anomalies is challenging, and misdiagnosis is frequent. Vascular malformations are considered one of the most difficult vascular diseases to treat. A new imaging approach that visualizes anatomical features and quantitatively assesses molecular biomarkers noninvasively would aid diagnosis and monitoring of treatment response of vascular malformations. Objective: To evaluate multispectral optoacoustic tomography (MSOT) for noninvasive assessment of molecular biomarkers for diagnosis and therapeutic monitoring of vascular malformations. Design, Setting, and Participants: This pilot study examined 6 patients with arteriovenous malformation (AVM) and 6 patients with venous malformation (VM) diagnosed according to the classification system of the International Society for the Study of Vascular Anomalies. All patients underwent clinical hybrid MSOT/ultrasonographic (US) imaging before and after treatment at an interdisciplinary vascular malformations clinic by trained MSOT and US examiners. Examiners were blinded to the patient history and stage of disease. Data were collected from April 11 to 25, 2017, and analyzed from May 1 to October 31, 2017. Interventions: Clinical hybrid MSOT/US imaging was performed before or within 1 week after endovascular embolization (for AVM) or percutaneous sclerotherapy (for VM). Main Outcomes and Measures: Region-of-interest analysis of the lesion and contralateral healthy tissue revealed quantitative values for oxygenated (HbO2) and deoxygenated (HbR) hemoglobin by spectral unmixing of optoacoustic data acquired at multiple wavelengths. The HbO2:HbR ratio was calculated for healthy tissue and for AVM and VM before and after treatment. Results: Twelve patients (9 female and 3 male; mean [SD] age, 23 [18] years; age range, 6-59 years) with vascular malformations (6 with AVMs and 6 with VMs) were included. Significantly higher HbO2:HbR ratios for AVMs (mean [SEM], 1.82 [0.08] vs 0.89 [0.03]; P < .001) and for VMs (mean [SEM], 1.12 [0.04] vs 0.89 [0.03]; P = .001) were found on MSOT tissue compared with healthy tissue. Significantly higher HbO2:HbR ratios for AVMs compared with VMs (mean [SEM], 1.82 [0.08] vs 1.12 [0.04]; P < .001) were also found. Therefore, MSOT provided intrinsic biomarker patterns to distinguish both vascular malformations. After therapy, the HbO2:HbR ratio dropped in correlation to treatment success validated by magnetic resonance imaging or angiography. Conclusions and Relevance: This study suggests that different types of vascular malformations are clearly distinguished by MSOT-based, noninvasive assessment of hemoglobin levels in vascular malformations. The therapy effects found in this study could be instantly visualized, and this may offer a new tool for noninvasive diagnosis and monitoring of vascular malformations.
Authors: Ferdinand Knieling; Clemens Neufert; Arndt Hartmann; Jing Claussen; Alexander Urich; Cornelia Egger; Marcel Vetter; Sarah Fischer; Lukas Pfeifer; Alexander Hagel; Christian Kielisch; Rüdiger S Görtz; Dane Wildner; Matthias Engel; Jens Röther; Wolfgang Uter; Jürgen Siebler; Raja Atreya; Wolfgang Rascher; Deike Strobel; Markus F Neurath; Maximilian J Waldner Journal: N Engl J Med Date: 2017-03-30 Impact factor: 91.245
Authors: Anne Becker; Max Masthoff; Jing Claussen; Steven James Ford; Wolfgang Roll; Matthias Burg; Peter J Barth; Walter Heindel; Michael Schäfers; Michel Eisenblätter; Moritz Wildgruber Journal: Eur Radiol Date: 2017-08-07 Impact factor: 5.315
Authors: Lacey R McNally; Megan Mezera; Desiree E Morgan; Peter J Frederick; Eddy S Yang; Isam-Eldin Eltoum; William E Grizzle Journal: Clin Cancer Res Date: 2016-05-20 Impact factor: 12.531
Authors: Gael Diot; Stephan Metz; Aurelia Noske; Evangelos Liapis; Barbara Schroeder; Saak V Ovsepian; Reinhard Meier; Ernst Rummeny; Vasilis Ntziachristos Journal: Clin Cancer Res Date: 2017-09-12 Impact factor: 12.531
Authors: Adrian Taruttis; Arwin C Timmermans; Philip C Wouters; Marcin Kacprowicz; Gooitzen M van Dam; Vasilis Ntziachristos Journal: Radiology Date: 2016-07-04 Impact factor: 11.105
Authors: Adrian Taruttis; Moritz Wildgruber; Katja Kosanke; Nicolas Beziere; Kai Licha; Rainer Haag; Michaela Aichler; Axel Walch; Ernst Rummeny; Vasilis Ntziachristos Journal: Photoacoustics Date: 2012-12-10
Authors: Wolfgang Roll; Niklas A Markwardt; Max Masthoff; Anne Helfen; Jing Claussen; Michel Eisenblätter; Alexa Hasenbach; Sven Hermann; Angelos Karlas; Moritz Wildgruber; Vasilis Ntziachristos; Michael Schäfers Journal: J Nucl Med Date: 2019-03-08 Impact factor: 10.057
Authors: Vanessa F Schmidt; Max Masthoff; Richard Brill; Peter B Sporns; Michael Köhler; Victor Schulze-Zachau; Martin Takes; Denis Ehrl; Daniel Puhr-Westerheide; Wolfgang G Kunz; Mwivano Dunstan Shemwetta; Eric M Mbuguje; Azza A Naif; Abizer Sarkar; Jens Ricke; Max Seidensticker; Walter A Wohlgemuth; Moritz Wildgruber Journal: Cardiovasc Intervent Radiol Date: 2022-06-02 Impact factor: 2.797
Authors: Angelos Karlas; Max Masthoff; Michael Kallmayer; Anne Helfen; Michail Bariotakis; Nikolina Alexia Fasoula; Michael Schäfers; Max Seidensticker; Hans-Henning Eckstein; Vasilis Ntziachristos; Moritz Wildgruber Journal: Ann Transl Med Date: 2021-01
Authors: Richard Brill; Moritz Wildgruber; Vanessa F Schmidt; Max Masthoff; Constantin Goldann; Sinan Deniz; Osman Öcal; Beate Häberle; Michael Köhler; Max Seidensticker; Jens Ricke; Walter A Wohlgemuth Journal: Cardiovasc Intervent Radiol Date: 2021-07-20 Impact factor: 2.740