The challenge is rooted in basic physics and physiology. When radiologists assess technical success after thermal ablation of liver or kidney tumors, they rely on contrast-enhanced CT performed shortly after the procedure. A successful treatment produces a discrete zone of non-enhancing, dead tissue that completely surrounds the original tumor, providing a measurable ablation margin. In the lung, however, the parenchyma is filled with air, which attenuates X-rays so weakly that any subtle enhancement from intravenous contrast is essentially drowned out. The normal lung simply does not enhance enough for the eye, or the scanner, to distinguish treated from untreated tissue with confidence.

Radiologists have therefore leaned on a surrogate: the ground-glass opacity, a hazy region of hemorrhage and edema that appears on CT as the ice ball forms and the surrounding lung becomes injured. During the procedure, serial CT imaging tracks this evolving ground glass as a rough proxy for the ablation zone. But studies have shown that these opacities are unreliable indicators of the true extent of tissue destruction. They evolve over time, they do not map neatly onto the final zone of coagulative necrosis, and they cannot tell a clinician whether the lethal freeze front actually extended far enough beyond the tumor’s edge to catch every viable cancer cell. In lung metastasis-directed therapy, where a residual margin of living tumor means local recurrence, that uncertainty is not a trivial inconvenience.

The Mayo Clinic team, led by radiologist Rebecca Hibbert together with Thomas Atwell, Nathan Huber, Christopher Favazza, Andrea Ferrero and Ahmad Parvinian, turned to an approach borrowed from a different corner of thoracic imaging: the evaluation of pulmonary embolism. Dual-energy and multi-energy CT scanners acquire data at two or more X-ray energy levels simultaneously, which allows the reconstruction of so-called iodine density images. Because iodinated contrast material attenuates X-rays differently depending on the energy of the beam, the scanner can mathematically separate the signal contributed by iodine from that contributed by all other tissues. The result is a map that shows, pixel by pixel, where contrast agent, and therefore blood flow, has actually reached within the lung.

This capability has already proven its worth in vascular disease. In patients with pulmonary embolism, iodine density maps reveal relative deficits of iodine content in lung parenchyma downstream of a clot, highlighting perfusion defects that conventional CT images can miss. Japanese researchers had previously applied the same principle to lung radiofrequency ablation, demonstrating that dual-energy CT could depict diminished perfusion in the lung periphery of treated nodules. Crucially, however, that earlier work used iodine imaging to characterize collateral changes around the tumor rather than to answer the question that matters most to the patient and the treating physician: did the ablation zone completely cover the tumor with an adequate margin?

In a letter published in CVIR Oncology, the Mayo group describes its initial experience doing exactly that. After obtaining an institutional review board exemption, the team treated three patients with clinically indicated cryoablation of lung metastases in a dedicated hybrid procedural imaging suite equipped with a Philips Spectral 7500 multi-energy CT system. Using conventional technique, the radiologists placed two to three cryoprobes directly into each index tumor and delivered a triple-freeze cycle, monitoring the procedure with serial CT imaging and watching the hemorrhagic ground-glass opacity evolve as a surrogate for the growing ablation zone.

The pivotal step came immediately after ablation. With the cryoprobes removed and the patients still under general anesthesia, the team performed a contrast-enhanced CT of the chest, injecting 80 milliliters of iohexol 300 in two patients and 100 milliliters of iohexol 350 in the third, with image acquisition timed 25 to 40 seconds after the contrast injection. From the spectral imaging data, the researchers generated iodine density maps and compared them with images obtained before and during the ablation, viewing the datasets on a dedicated advanced visualization workstation. In all three patients, a distinct ablation margin emerged on the iodine density images, defined by an absence of iodine in the treated lung parenchyma that corresponded closely to the ground-glass changes seen immediately after treatment.

The three cases illustrate the range of the technique. The first was a 61-year-old woman with metastatic sarcomatoid carcinoma, in whom a 1.0-centimeter metastasis in the right lung was surrounded by a 2.4 by 4.8-centimeter zone of ground-glass hemorrhage and edema on conventional CT, while the iodine density map showed a 2.0 by 4.8-centimeter iodine defect corresponding to the ablation zone. The second, a 57-year-old woman with metastatic leiomyosarcoma, underwent treatment of a 1.4-centimeter right lung metastasis with two IceRod cryoprobes made by Boston Scientific; coronally reformatted iodine images after 100 milliliters of iohexol 350 revealed a well-demarcated iodine defect incorporating the tumor. The third patient, an 80-year-old woman with recurrent FDG-avid squamous cell carcinoma in the left upper lung four years after radiation therapy, had a 1.3-centimeter malignant nodule that was likewise fully enclosed by an iodine defect on post-ablation imaging.

What makes these observations potentially transformative is the analogy to established practice in abdominal ablation. In the liver and kidney, the post-procedure contrast-enhanced ablation defect is the gold standard for defining technical success, allowing immediate recognition of an inadequate margin and, in some cases, prompt repeat treatment within the same session. If iodine density imaging can provide the equivalent information in the lung, radiologists would gain, for the first time, a quantitative imaging biomarker of pulmonary ablation completeness, one grounded in the actual perfusion status of the treated tissue rather than in the shifting appearance of post-procedural hemorrhage. The authors describe the iodine defect as analogous to the ablation defects seen after liver or renal ablation, a framing that, if validated, would bring lung ablation into line with its better-characterized cousins.

The researchers are careful to frame this as an early experience rather than a validated standard. Three patients constitute a proof of concept, not a clinical guideline, and the team emphasizes that further work is warranted to refine the details of contrast administration, including optimal contrast volume, concentration and timing, and to correlate the iodine density defect with the historical surrogate ground-glass findings generated during ablation. One of the co-authors, Nathan Huber, is an employee of Philips Healthcare, whose Spectral 7500 system was used in the study, though the remaining authors report no conflicts of interest and the work received no external funding. Still, the optimism is palpable. If larger studies confirm that the iodine defect reliably delineates the ablation margin in the lung, the technique could reshape how pulmonary cryoablation is monitored, turning a procedure long guided by imperfect surrogates into one that can be verified in real time, and giving patients with lung metastases a clearer answer to the question that matters most: did we get it all?

Subject of Research: Iodine density imaging for assessing technical success of pulmonary cryoablation of lung metastases

Article Title: Potential role of iodine density imaging in determining technical success of pulmonary cryoablation

Article References: Hibbert, R., Atwell, T. D., Huber, N. R., Favazza, C. P., Ferrero, A., & Parvinian, A. (2025). Potential role of iodine density imaging in determining technical success of pulmonary cryoablation. CVIR Oncology, 1(1), Article 7. https://doi.org/10.1007/s44343-025-00008-0

Image Credits: AI Generated

DOI: 10.1007/s44343-025-00008-0

Keywords: iodine density imaging, dual-energy CT, pulmonary cryoablation, lung metastases, interventional radiology, ablation margin, ground-glass opacity, multi-energy CT, contrast-enhanced CT, imaging biomarker, cancer imaging, Mayo Clinic