The finding matters because ioPTH monitoring is used during thyroid and parathyroid operations to assess whether parathyroid function is likely to remain adequate after tissue removal. Surgeons may use declining hormone levels, absolute thresholds or kinetic criteria to guide decisions about parathyroid autotransplantation, calcium supplementation, postoperative monitoring and discharge planning. PTH has a circulating half-life typically estimated at three to five minutes, making rapid intraoperative measurements particularly useful in these settings. If a dye used in the same operative workflow falsely raises a PTH result, a surgeon could overestimate remaining parathyroid function or be misled about the likelihood of postoperative hypocalcemia.

Researchers divided the prospective experimental and observational study into paired in vitro spiking experiments involving six patient samples and an in vivo thyroidectomy cohort involving six patients. They also conducted limited exploratory testing on additional analytical platforms. The principal in vivo measurements were made with a Roche Cobas e601 electrochemiluminescence immunoassay platform for second-generation intact PTH, or i-PTH, and third-generation whole PTH (1–84). Before beginning the main experiments, the team validated sample handling: differences between standard and internal centrifugation protocols ranged from -2.79% to +4.69% across 10 samples, while storage and temperature tests remained within a predefined acceptance limit of plus or minus 25%.

For the in vitro experiment, blood from each of six patients was divided into paired aliquots. One aliquot served as a baseline control, and the other was spiked with 0.5 mL of ICG solution at 2.5 mg/mL to evaluate assay behavior under saturation conditions. The median third-generation PTH (1–84) concentration rose from 40.19 pg/mL to 235.10 pg/mL, corresponding to a median 5.98-fold increase among individual samples. The median second-generation i-PTH concentration increased from 36.26 pg/mL to 120.45 pg/mL, a median 3.34-fold increase. Both changes were statistically significant at p = 0.031 under the Wilcoxon signed-rank analysis.

The third-generation assay was affected more strongly. In every ICG-spiked specimen, the ratio of PTH (1–84) to i-PTH, which is normally not greater than 1.0, inverted to above 1.0. This reversal indicates that ICG exposure did not simply add the same proportional bias to both assays. Rather, the assay intended to detect biologically active, intact PTH registered a disproportionately larger response under the tested conditions. The controlled addition of ICG also showed that the interference could occur without neck dissection, tissue manipulation or a systemic physiological response to surgery.

For the in vivo component, investigators enrolled six patients undergoing elective total or near-total thyroidectomy. All six had normal liver-function test results and no history or diagnosis of liver cirrhosis. A baseline arterial blood sample was collected immediately before ICG was administered through a peripheral venous catheter in the contralateral arm. Additional arterial samples were taken 3, 6, 9, 15, 20, 25 and 30 minutes after injection. Surgical dissection and manipulation of the neck were paused throughout the sampling period to reduce biological fluctuations unrelated to ICG exposure, while separate vascular access sites were intended to minimize direct contamination of the sampling line or local venous retention of concentrated dye.

The in vivo results reproduced the direction seen in the laboratory experiments. At three minutes, third-generation PTH (1–84) reached 234.8% of baseline, a median increase of 50.25 pg/mL, while second-generation i-PTH reached 146.1% of baseline, a median increase of 13.53 pg/mL. Both peak changes were significant at p = 0.031. Positive interference remained substantial at six and nine minutes. By 15 minutes, i-PTH was close to baseline at 98.3%, although PTH (1–84) remained slightly elevated at 122.9%. Between 20 and 30 minutes, both assays approached baseline: at 30 minutes, i-PTH was at 96.6% of baseline and PTH (1–84) was at 103.1%, with neither difference statistically significant.

Exploratory comparisons suggested that the problem may not be confined to one assay system, but the evidence was limited. In paired serum samples from one surgery patient, i-PTH rose from 28.06 to 370.5 pg/mL on the Roche electrochemiluminescence system and from 29.6 to 382.0 pg/mL on Abbott’s Alinity i chemiluminescent microparticle immunoassay. That single-patient agreement cannot establish platform independence. A separate experiment using three whole-blood specimens produced inconsistent responses among systems: measurements increased on Roche, failed to report on Abbott because of an activated read error that persisted after dilution, and decreased on Siemens Atellica IM. These findings show that the direction and magnitude of interference may vary with the analytical method and specimen conditions rather than supporting one uniform response across platforms.

The mechanism remains unresolved. ICG is an amphiphilic dye that binds extensively to plasma proteins, particularly albumin and lipoproteins, forming large circulating complexes. Because ICG fluorescence near 800 to 830 nm does not overlap directly with the 620 nm ruthenium emission used by the Roche electrochemiluminescence system, simple optical cross-talk was considered less likely. The researchers proposed that ICG-protein complexes might instead interfere nonspecifically with antibody binding or signal generation, but they did not directly test this mechanism. The paired in vitro experiments support a direct analytical contribution from ICG exposure, although they do not establish the molecular pathway responsible. The study evaluated PTH only, so its findings cannot be extended to interference with other blood analytes.

Several limitations constrain interpretation. The operative cohort contained only six patients and had no contemporaneous control group receiving thyroidectomy without ICG. The cross-platform work involved one patient and a small number of additional specimens, and the observed return toward baseline over 20 to 30 minutes was not independently validated. The proposal that the effect reflects a washout period linked to hepatic clearance is also preliminary; the study measured the timing of assay interference but did not directly test that proposed explanation. Nevertheless, the agreement between controlled sample-spiking experiments and serial intraoperative measurements, together with the use of contralateral sampling sites and the pause in surgical manipulation, strengthens the evidence that ICG can transiently distort ioPTH assays.

The authors’ practical conclusion is limited but clear: when feasible, baseline ioPTH should be collected before ICG is administered, and subsequent results should be interpreted with the timing of the injection in mind. The data show that measurements can be falsely elevated soon after exposure, with the largest distortion occurring early and values tending back toward baseline later in the 30-minute observation period. They do not yet establish a universal waiting period, biological washout interval or post-ICG sampling schedule. For the six-patient operative cohort, the 20-to-30-minute return toward baseline is an observed preliminary pattern that requires validation in a larger cohort with an appropriate control group before it can guide routine timing decisions.

Subject of Research: Analytical interference between indocyanine green and intraoperative parathyroid hormone immunoassays

Article Title: Indocyanine green alters intraoperative parathyroid hormone measurements: a timing-dependent effect

Article References: Sung, C.-H., Huang, S.-M., Ye, R.-J., & Shih, P.-J. (2026). Indocyanine green alters intraoperative parathyroid hormone measurements: a timing-dependent effect. Frontiers in Endocrinology, 17, 1981095. https://doi.org/10.3389/fendo.2026.1981095

Image Credits: AI Generated

DOI: 10.3389/fendo.2026.1981095

Keywords: indocyanine green, parathyroid hormone, thyroidectomy, immunoassay interference, analytical bias, intraoperative monitoring, near-infrared fluorescence, postoperative hypocalcemia, Indocyanine, green, alters, intraoperative

The device, described in Nature Biomedical Engineering, is called a soft neural interface bioelectronic system, or SNIBS. It combines a flexible electronic sensor array with a responsive hydrogel interface layer built from thermally responsive hydrogel microspheres. The key insight behind the design is that a neural interface placed on the brain during surgery faces two conflicting demands. It must adhere seamlessly to the wet, curved, pulsating cortex to record high-fidelity signals, yet it must also detach benignly at the end of the operation without tearing or damaging the very tissue it was protecting. The team solved this by exploiting the swelling and deswelling behavior of the hydrogel microspheres, which is triggered by temperature.

At normal physiological and room temperatures, the hydrogel interface swells and conforms intimately to the cortical surface, establishing stable contact for both mechanical sensing and electrical recording. When gentle heat is applied, the microspheres deswell and the interface releases its grip, allowing the entire system to be peeled away cleanly. The researchers demonstrated this adhesion regulation on wet brain tissue, showing that the transition between strong attachment and benign detachment can be controlled on demand. This thermally triggered switch addresses one of the most persistent problems in cortical bioelectronics: devices that stick well to tissue are notoriously difficult and risky to remove, while devices that remove easily often fail to maintain the intimate contact needed for reliable signal acquisition.

Once laminated onto the cortex, the SNIBS functions as a multimodal monitoring platform. It measures contact pressure between surgical instruments and the brain surface, records somatosensory evoked potentials, captures electrocorticography signals across multiple channels, and tracks local temperature. Together, these streams give surgeons a direct, real-time assessment of neural status during the operation. The pressure sensor array quantifies the mechanical forces being applied, while the electrophysiological channels reveal whether those forces are beginning to compromise neural pathways. A graphical user interface presents the combined data stream to the surgical team, and the analysis software has been released publicly through a GitHub repository.

One of the most consequential findings of the study is the demonstration of a direct correlation between applied contact pressure and damage to cortical neural pathways, as reflected in somatosensory evoked potentials. Somatosensory evoked potentials are a standard intraoperative monitoring tool: electrical responses recorded from the brain in response to peripheral stimulation, with clinicians typically watching for a fifty percent drop in amplitude or a ten percent increase in latency as warning thresholds. By applying stepwise increasing pressure to brain tissue while recording continuously, the researchers mapped how these warning signals evolve as mechanical stress accumulates. Their data show that amplitude declines become statistically significant at higher pressure levels, providing a quantitative bridge between the physical force applied by an instrument and the functional state of the neural tissue beneath it.

To establish where reversible stress ends and irreversible injury begins, the team turned to histological and imaging validation. Evans blue staining, a classic method for revealing breakdown of the blood-brain barrier, and magnetic resonance imaging both confirmed that contact pressures exceeding roughly 80 kilopascals cause irreversible craniocerebral injury. That number is significant because it converts an abstract surgical risk into a concrete, measurable threshold. A surgeon watching a live pressure readout now has a defensible numerical boundary to work within, rather than relying solely on tactile judgment that varies between operators and cannot distinguish, for example, the force transmitted through a cottonoid patty from that transmitted through a rigid retractor blade.

The system was validated in rabbit brain tumor excision models, a demanding test because tumor resection is exactly the scenario in which instruments repeatedly contact and compress healthy cortical tissue adjacent to the lesion. In the surgical experiments, the SNIBS allowed the team to compare procedures performed with pressure control against procedures without it. Multichannel electrocorticography recordings captured before and after resection showed the difference between brains whose contact forces had been managed and those where they had not. The results support the central claim that quantifying and limiting intraoperative forces can meaningfully reduce surgical damage to the brain, and that a soft, conformal monitoring layer can deliver this information without itself becoming a hazard.

The materials science underlying the device is as important as the electronics. The hydrogel microspheres were characterized in detail across their thermal transition, with rheological measurements showing how viscosity, storage modulus, and loss modulus shift between room temperature and elevated temperature. The researchers compared multiple formulations of their thermally responsive microsphere system, and supplementary videos document the dehydration and rehydration behavior that underpins the swelling and deswelling cycle. Biocompatibility testing accompanied the mechanical characterization, an essential step for any material intended to sit directly against cortical tissue. The overall architecture is also remarkably thin; the team notes that the full system is comparable in thickness to a commercial cottonoid patty and a conventional electrocorticography electrode, meaning it should not meaningfully alter the surgical workspace or add bulk beneath retractors.

The broader context makes the work timely. Soft and stretchable bioelectronics have advanced rapidly over the past several years, with adhesive hydrogel interfaces, dissolvable silk films, endovascular probes, and shape-morphing cortex-adhesive sensors all pushing toward devices that integrate with neural tissue rather than fighting against it. What distinguishes the SNIBS is its explicit focus on the intraoperative window and on mechanical safety. Most neural interfaces are designed for chronic recording or stimulation; comparatively few are built to protect the brain during the hours in which it is most vulnerable to iatrogenic, meaning treatment-induced, injury. By pairing force quantification with functional monitoring in a single detachable platform, the system addresses a gap that existing electrocorticography electrodes and monitoring techniques leave open.

The researchers argue that the technology holds strong potential for establishing safety evaluation standards for neurosurgery, and the logic is straightforward. Anesthesia monitoring, cardiac surgery, and many other high-stakes fields became safer once continuous quantitative metrics replaced subjective judgment. Brain surgery has had electrophysiological monitoring for decades, but the mechanical side of the equation has remained unmeasured. A validated injury threshold, a device that can detect approach to that threshold in real time, and a warning system built on established somatosensory evoked potential criteria together form the ingredients of such a standard. Translation from rabbit models to human operating rooms will require further studies, regulatory review, and integration with surgical workflow, and the current work is an early-stage demonstration rather than an approved clinical tool. Still, the prospect is striking: a future in which every retraction of the brain is measured, every pressure spike is flagged, and the surgeon knows, in numbers, when the brain is being pushed toward harm. For a procedure where millimeters and grams of force can separate recovery from disability, that kind of visibility could prove transformative.

Subject of Research: A soft hydrogel-based bioelectronic neural interface for real-time quantification of intraoperative craniocerebral injury during neurosurgery

Article Title: A soft bioelectronic system with a responsive hydrogel neural interface for direct force quantification and real-time intraoperative craniocerebral injury monitoring

Article References: Pang, B., Yang, G., Cheng, Q., Zhou, S., Wang, Z., Xuan, W., Qiu, Y., Gong, H., Bu, T., Xie, B., Fu, P., Yin, Z., Lim, C. T., Wu, C., Jiang, X., & Wu, H. (2026). A soft bioelectronic system with a responsive hydrogel neural interface for direct force quantification and real-time intraoperative craniocerebral injury monitoring. Nature Biomedical Engineering. https://doi.org/10.1038/s41551-026-01814-4

Image Credits: AI Generated

DOI: 10.1038/s41551-026-01814-4

Keywords: neurosurgery, brain injury, hydrogel, neural interface, bioelectronics, somatosensory evoked potentials, electrocorticography, pressure sensors, intraoperative monitoring, craniotomy, biocompatibility, translational research