These cases were identified through the first author’s routine clinical practice at a tertiary level oncologic hospital. Institutional ethics committee approval was received for a waiver of patient consent. SRS was delivered either using a Varian TrueBeam linear accelerator with dynamic conformal arc therapy (DCAT) or with the Gamma Knife radiosurgery machine. The SRS schedules used in each case are specified in the respective figure legends.

IM generally enlarge in one of two ways. Most commonly, IM enlarge in a relatively concentric manner, with progressive enlargement of a nodular lesion. Less commonly, metastases may extend along an anatomical surface, such as along the cortex or pial surface of the brain, or along the ependymal surface of the ventricular system. The frequency with which metastases enlarge in these two ways depends, in part, on the histology. For example, intracranial metastases from melanoma have a particular predilection to developing at the interface between the pia mater and the cortex [12], and curvilinear extension along the pial surface is a common occurrence. As such, the pattern of IM progression or recurrence is affected by the local anatomy. In contrast, the distribution of the radiation dose administered with SRS in general does not respect these anatomical boundaries, but rather is largely concentric around the treated lesion. This is illustrated by the isodose distributions as depicted in Figs. 3 and 6.

Several such anatomical boundaries exist in the brain. Firstly, this includes the major dural reflections: the falx cerebri (Figs. 1 and 2) and the tentorium cerebelli (Fig. 3). In our experience, the development of new enhancement on the other side of a dural reflection after SRS is strongly suggestive of RN rather than PD. A sulcus and CSF may provide a similar barrier (Figs. 4 and 5). In our experience of both above scenarios, the new enhancement occurring with RN preferentially involves the subcortical white matter, sparing the intervening cortex, and thus the new lesion can be anatomically distinct from, or non-contiguous with, the originally treated lesion. It is important, however, to ensure that there is no contiguous involvement of the intervening meninges, which would otherwise raise concern for PD.

Axial post-contrast T1WI in a patient with an esophageal carcinoma metastasis (a, dotted circle) to the left cingulate gyrus, treated with 20 Gy single-fraction SRS. The lesion enlarged after SRS, with extension to the adjacent corpus callosum. On the 12-month post-SRS MRI (b), a small focus of enhancement developed in the right cingulate gyrus (arrow), discontinuous with the dominant lesion, which allowed a more confident diagnosis of RN. Note the “open ring” enhancement to the left of the falx cerebri; in contrast, if this was contiguous metastatic disease, abnormal enhancement of the falx cerebri would be expected. RN was supported by subsequent follow-up imaging, which demonstrated a change in the shape of the overall abnormality, with some regression of the dominant left-sided component, but further mild enlargement on the right. The appearances stabilized thereafter, and remain stable at most recent follow-up more than 12 months later. The patient also had a right frontal metastasis (b, arrowhead) treated with SRS, but this developed appearances suggestive of PD, prompting resection (which confirmed PD)

Axial post-contrast T1WI demonstrating a left cingulate gyrus metastasis (a, dotted circle) from a breast carcinoma primary, treated with 20 Gy single-fraction SRS. At 18-month follow-up (b), the metastasis had decreased in size, but a new peripherally-enhancing lesion had developed in the splenium of the corpus callosum (arrow); there was also new, subtle enhancement (arrowhead) in the right cingulate gyrus at this time. The abnormalities continued to evolve – another 19 months later (c), the splenial component had resolved, while the right cingulate gyrus component had mildly enlarged. The appearances stabilized thereafter, consistent with RN

Axial post-contrast T1WI demonstrating a right occipital melanoma metastasis (a, dotted circle), which was treated with 20 Gy single-fraction SRS. The metastasis responded to SRS (arrow), but subtle linear enhancement developed in the adjacent right cerebellar hemisphere (b, arrowhead) four years later. Despite the linear appearance raising the possibility of leptomeningeal disease, this enhancement convincingly involved the cerebellar parenchyma rather than the folia. Geographic correlation of the area of enhancement with the high radiation dose region is illustrated by the 20 Gy, 15 Gy and 10 Gy isodose lines (in decreasing grayscale brightness) from the SRS plan (c). Ongoing stability of the cerebellar enhancement confirmed RN

Axial (a) and sagittal (b) post-contrast T1WI shows a lung adenocarcinoma metastasis (arrowheads) to the left pre-central gyrus, which was treated with 20 Gy single fraction SRS. The sagittal plane best demonstrates that this arises anterior to the central sulcus, displacing it posteriorly. Ten months later (c & d), the lesion had resolved, but a peripherally-enhancing lesion (arrows) had developed in the adjacent post-central gyrus. This subsequently resolved without any specific treatment, confirming RN

This patient had previously undergone resection of a left temporal melanoma metastasis and cavity SRS at an external institution (radiation dose-fractionation unclear), followed by intensity-modulated RT (20 Gy in 5 fractions) for localized leptomeningeal recurrence about two years later. Coronal post-contrast T1WI performed 15 months after the last episode of irradiation demonstrates separate (non-contiguous) areas of enhancement (arrowheads) around the left Sylvian fissure. The distribution, morphology and non-contiguous nature of this enhancement, conforming to the RT field, suggests RN, which was confirmed by subsequent regression

Similar considerations exist for IM located close to the ventricular system (Figs. 6 and 7), though the MRI appearances differ to a degree, related to the anatomical differences compared to the more peripheral lesions discussed above. In contrast to more peripheral lesions, there is often no intervening grey matter between the treated IM and the white matter on the other side of the ventricle. As a result, in our experience, such RN lesions tend to develop in continuity, wrapping around the ventricle. Of note, and in contrast to metastatic disease, there is often no enhancement along the ventricle surface, producing an “open ring” appearance. This open ring appearance can also occur with treated metastases located away from the ventricular surface (see Fig. 1), related to the lower differential radiosensitivity of the cortex and the effect this in turn has on the MRI appearances (the ring potentially being open on the side of the cortex). Notably, in all our illustrated cases, the area of enhancement correlates geographically with the high radiation dose regions, as highlighted in Figs. 3 and 6.

Coronal post-contrast T1WI in a patient with a left caudate nucleus metastasis (a, dotted circle) from a small cell lung cancer primary, treated with SRS (24 Gy in 3 fractions). The first post-treatment MRI at five months (b) shows that the lesion has substantially enlarged to involve the adjacent corpus callosum (arrowhead), wrapping around the adjacent lateral ventricle. Note the lack of enhancement along the ventricular surface, producing an “open ring” appearance. The eccentric morphology of the enlargement (with respect to the initial lesion), predominantly occurring superomedially across the ventricle, is more in keeping with RN than PD, which was confirmed by subsequent regression. There was also geographic correlation with the radiation high dose region, as illustrated by the 24 Gy, 15 Gy and 10 Gy isodose lines (in decreasing grayscale brightness) from the SRS plan (c)

Coronal post-contrast T1WI demonstrates a metastasis (a, dotted circle) to the left caudate nucleus from breast cancer, treated with 27 Gy in 3 fractions of SRS at an external institution. Fifteen months after SRS (b), new extensive enhancement developed in the corpus callosum (arrowheads). Again note the absence of enhancement along the ventricular surface. At 2 years post-SRS (c), the callosal component has receded, but new enhancement (arrow) has development lateral to the treated lesion. This also subsequently receded without specific treatment, consistent with RN

The progression and evolution of IM tends to occur in a relatively simple manner. Prior to treatment, or if not responding to treatment, the entirety of an IM will enlarge, without regression of any particular components. While subsequent recurrence (and hence enlargement) may occur within only a portion of the initial lesion, often at its margin, any post-treatment regression will have already occurred. Thus, it would be very uncommon for different components of the same IM to enlarge and regress simultaneously. In contrast, RN is a more variable and dynamic process, affected by a variety of factors inherent to that particular part of the brain (or voxel), such as the dose received and the sensitivity to radiation effects. These factors vary from voxel to voxel, often leaving to a complex evolution of RN lesions. Radiologically, this can manifest as a change in the shape of the lesion, with different portions of the given lesions simultaneously enlarging and regressing (Figs. 7, and 8). Given that such evolution would not be expected for recurrent IM, such an appearance can be more confidently attributed to RN.

Axial (a) and coronal (b) post-contrast T1WI in a patient who was treated with a right orbital exenteration and adjuvant intensity-modulated RT (60 Gy in 30 fractions) for metastatic cutaneous squamous cell carcinoma to the medial canthus. Three years later, new enhancement developed in the right temporal lobe. While FET-PET (not shown) suggested true tumor progression, the suspicion of RN remained based on MRI, prompting a short-interval follow-up MRI (c & d). While the lesion is similar in size overall, multiplanar assessment reveals a change in the shape. The temporo-occipital sulcus (arrowheads) and adjacent cortex, which are spared, divide the overall lesion into two contiguous components: medial and lateral. While the medial component has enlarged, the lateral component has receded. The lesion continued to regress thereafter, confirming RN