First-in-Human Study: HIVEN® Performance and Safety Results

Tampere, Finland, 26 February 2026—Marginum Ltd, a Finnish medical technology company specialising in fluorescence-based tissue monitoring systems, announces results from the first-in-human clinical study evaluating intraoperative 5-aminolevulinic acid (5-ALA) fluorescence-guided aspirate tissue monitoring (ATM) in high-grade glioma (HGG) surgery.

The peer-reviewed first-in-human study published in Neuro-Oncology Advances assessed the clinical performance and safety of the HIVEN® ATM device, which provides near real-time auditory feedback from fluorescence detected in suction aspirates during tumour resection. It comprised 28 procedures conducted across three tertiary hospitals in which ATM provided real-time auditory feedback to surgeons during resection.

Findings indicate that the ATM technique provided significantly more information on intraoperative fluorescence than conventional visual inspection alone. Particularly, more fluorescence was observed under white-light conditions that limit fluorescence visibility. In addition, the safety and performance of the HIVEN® ATM device was evaluated by seven (n=7) experts with a total of 90 years of experience. The patients showed no adverse events or effects related to the use during the study.

Known Limitations of Fluorescence-Guided Surgery

Fluorescence-guided surgery (FGS) with 5-ALA is widely used to help neurosurgeons identify tumour tissue, yet visual fluorescence detection can be hindered by bleeding, tissue obstructions, deep surgical cavities, and the need to repeatedly switch between white- and blue-light modes. The ATM approach is designed to complement visual methods by continuously monitoring fluorescence from resected tissue as it travels through a suction tube, without requiring changes to operating-room illumination or additional invasive steps.

Key Findings: More Frequent and Longer Fluorescence Detection

Across the analysed surgical timelines, the ATM technique provided more information on tissue fluorescence and more frequent detection compared with conventional visual fluorescence guidance. In the timeline comparison, ATM was active for +513% longer with detection enabled and +383% longer with fluorescence detected.

Visual fluorescence was detected under white light by microscope in 0 of 16 areas, whereas ATM detected fluorescence in 11 (69%) areas in the comparison. Detection of fluorescence under white light is valuable in surgery, as most surgeons prefer white-light visualisation for anatomy and critical structures. In a detailed timeline analysis, fluorescence was visually detected for 63 minutes under blue light and 0 minutes under white light, whereas ATM detected fluorescent signal amplitudes for 185 minutes total, with equal time split between blue- and white-light illumination.

Seven experienced neurosurgeons with 90 years of experience, and >2400 HGG surgeries performed, reviewed the observational data to assess the ATM technique’s performance and safety. The experts reported an average overall agreement rate of 96.7%, concluding that the technique appeared safe and added value to contemporary navigation techniques.
 
In the study, ATM showed 100% sensitivity and 80% specificity for fluorescence detection compared with expert visual assessment.  All 12 visually detected fluorescent areas were histopathologically verified to contain HGG, supporting a strong association between fluorescence-positive signals and tumour tissues. Meanwhile, the study reported no false-positive findings in the biopsies. The study, however, highlights that the device targets PpIX fluorescence generated after 5-ALA administration rather than detecting tumour cells.

Augmenting the Workflow and Clinical Potential

From a clinical perspective, the study suggests that the ATM technique can help mitigate practical barriers to FGS. By enabling passive monitoring of fluorescence from aspirates, the ATM technique can support consistent intraoperative decision-making and expand the utility of 5-ALA fluorescence in challenging surgical conditions.

“The first-in-human results reinforce our belief that aspirate tissue monitoring can make a real difference in intraoperative fluorescence-guided surgery. We are encouraged by the strong expert agreement on the safety and performance in fluorescence detection, and we look forward to continuing clinical evaluation in broader settings,” says docent Antti-Pekka Elomaa MD PhD, a consultant neurosurgeon at Helsinki University Hospital, who is one of the inventors and in charge of the clinical design of HIVEN® ATM.

This research was sponsored by Marginum Ltd. Several authors of the publication are affiliated with Marginum. The full article is available in Neuro-Oncology Advances via the hyperlink below, published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology. 

Additional information:

This underlying research article is an Open Access publication distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted reuse, distribution and reproduction in any medium, provided the original work is properly cited. License details: https://creativecommons.org/licenses/by/4.0/

Samu Lehtonen
CEO, Marginum
samu.lehtonen@marginum.com
+358 40 579 7890

Marginum is a Finnish medical technology company founded in 2020 and a leading innovator in fluorescence-guided oncological surgery, developing optical tissue monitoring systems. The CE-marked HIVEN® by Marginum enables safe and efficient monitoring of tumour tissues during cancer surgery by seamlessly integrating into existing surgical workflows. Marginum’s vision is to enable surgeons worldwide to perform safer, more precise operations, ultimately improving patient survival and quality of life. www.marginum.com

Published in:

• Elomaa, A.P., Lehtonen, S.J.R., Vik-Mo, E., Charbel, F.T., von und zu Fraunberg, M., Visuri, M., Luoma, J., Kelahaara, M., Haapala, I., Huotarinen, A., Rantala, S., Konki, J., Leskinen, J., Semenov, D., Haapasalo, J., Puustinen, S. Intraoperative 5-ALA fluorescence-guided aspirate tissue monitoring in high-grade glioma surgery: the first-in-human study on clinical performance and safety. Neuro-Oncology Advances, 2026. DOI: 10.1093/noajnl/vdag029