Acute susceptibility changes of deep gray matter nuclei to gadobutrol: a prospective longitudinal study using quantitative susceptibility mapping

Introduction

Gadolinium-based contrast agents (GBCAs) are extensively utilized in magnetic resonance imaging (MRI) enhancement examinations. They not only enhance the contrast between lesions and normal tissues but also reveal hemodynamic characteristics of lesions, thereby enabling quantitative detection of lesions that are difficult to identify on unenhanced scans or other imaging modalities (1-3). Historically considered safe and stable with rapid renal excretion, GBCAs were later linked to nephrogenic systemic fibrosis by Grobner in 2006 (4), raising significant safety concerns. Subsequent studies detected gadolinium deposition within the brain tissues of patients with normal renal function (5,6) raising serious safety concerns. Kanda et al. (7) first reported that repeated GBCA administration could lead to signal alterations in brain parenchyma, manifesting as increased signal intensity (SI) in the dentate nucleus and pallidum on unenhanced T1-weighted imaging (T1WI). Although the precise mechanism of gadolinium deposition remains unclear, research suggests that it can cross the blood-brain barrier (BBB) (8-11).

SI elevation is primarily associated with linear GBCAs, and shows a weaker association with macrocyclic agents (6,7,12,13), likely due to the unstable structure and lower thermodynamic stability of linear GBCAs facilitating the release of free gadolinium ions (Gd³⁺), which are key contributors to toxicity and intracranial deposition. Most early studies used T1 relaxation time shortening as a marker for gadolinium deposition. While gadolinium’s paramagnetic properties enable in vivo MRI detection, conventional T1WI relies solely on SI changes, lacks precise quantification and is unable to reliably distinguish gadolinium deposition from other factors (e.g., calcification or iron deposition). In contrast, a retrospective analysis by Choi et al. (14) demonstrated that quantitative susceptibility mapping (QSM) offers advantages in evaluating brain gadolinium deposition after repeated macrocyclic GBCA injections. As a phase-based post-processing technique, QSM enables precise localization and quantification of gadolinium deposition in the brain through direct measurement of tissue magnetic susceptibility. This technique significantly enhances the detection sensitivity for trace amounts of gadolinium, and its utility in detecting and quantifying deposits from various types of GBCAs has been demonstrated (15,16).

Recent findings, however, indicate that cerebral hemorrhage, radiotherapy, chemotherapy, and brain tumor type may influence post-GBCA brain nucleus SI measurements (9). Nevertheless, existing research on the relationship between brain gadolinium deposition and QSM primarily consists of cross-sectional retrospective studies. A notable lack of longitudinal data tracking changes over time exists within the same patients, which is crucial for accurately assessing the cumulative dose effects of GBCAs (7,11,14).

To address this gap, this study employs a prospective longitudinal design and integrates a flexible multiparametric magnetic resonance imaging (MTP) approach (including QSM, T1, and T2*). It aims to investigate the patterns of susceptibility changes within deep gray matter nuclei before and after a single gadobutrol injection through longitudinal analysis, and to further validate the sensitivity of QSM in detecting subtle susceptibility changes in these nuclei following serial gadobutrol administrations in brain tumor patients. This prospective, multiparametric approach would provide critical longitudinal imaging evidence for establishing potential links between gadolinium deposition burden and neurological dysfunction (e.g., cognitive impairment, motor decline), thereby making a significant contribution to the assessment of gadobutrol’s long-term safety. We present this article in accordance with the STROBE reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-aw-2261/rc).

Methods

Participants

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the institutional review board of the Nanjing Drum Tower Hospital (No. 2024-JS-32), with a waiver of informed consent justified by: prospective analysis of clinically indicated scans using de-identified data. Patients were enrolled in Nanjing Drum Tower Hospital from June 2023 to January 2026. Gadobutrol injection was the only contrast medium used for imaging in these patients during the study period. Initially, 80 patients were enrolled, undergoing a total of 144 enhanced head MRI examinations. “MRI examination” refers to a complete contrast-enhanced MRI procedure, which includes one set of pre-contrast and one set of post-contrast MTP sequence acquisitions. In other words, one MRI examination corresponds to one paired dataset (pre + post).

Inclusion criteria were: QSM scanned before and after enhancement; known history of at least one GBCA administration. Exclusion criteria were: incomplete pre- or post-enhancement QSM images (n=3); ventricular enlargement affecting QSM registration [n=1, Evans’ index >0.3 on axial T2-weighted imaging (T2WI)]; severe motion artifacts (n=3, defined as a visual rating score ≥4 on a 5-point scale, obscuring anatomical details). Finally, 72 patients were enrolled and underwent 136 MRI examinations. A flow chart of patient inclusion is provided (Figure 1). Among the 72 patients, 37 underwent a single MRI examination (providing one pre-post paired dataset for acute effect analysis), while 35 patients underwent between 2 and 5 repeated examinations over the study period, offering longitudinal data for exploratory analysis of cumulative. Patient age, sex, and number of prior gadobutrol injections were obtained from the hospital healthcare system. All patients received gadobutrol (0.1 mmol/kg) for each enhanced MRI. Confounding factors affecting brain magnetic susceptibility were considered, including the absence of obvious brain mass, tumor type (metastatic tumor, glioma, or other), history of radiotherapy and chemotherapy, and presence of enhancing brain lesions or hemorrhage.

Figure 1 Flow chart of patient enrollment. MTP, flexible multiparametric magnetic resonance imaging; QSM, quantitative susceptibility mapping.

MRI parameters and their QSM processing

All participants were scanned using a 3.0T MRI system with a 32-channel head-dedicated coil (uMR790, United Imaging Healthcare, Shanghai, China). MTP is a 3D multi-parametric sequence proposed by Ye et al. (15) using dual-repetition time (TR), dual flip angle (FA), a multi-echo gradient echo-based method, which can generate T1WI, T2*-weighted imaging, proton-density weighted imaging (PDWI), susceptibility-weighted images (SWIs), and corresponding T1 maps, T2* maps, proton-density (PD) maps, QSM maps in a single scan. The MTP parameters were as follows: TR1/TR2 =8.45/35.75 ms, 7 echoes with echo time (TE) =4.15 ms and ΔTE =4.55 ms, dual FA α1/α2=4°/16°, field of view (FOV) =190 mm × 224 mm, scan matrix =185×272, slice number =64, thickness =2 mm, transverse axis, acquisition time =4 min 48 s. The reconstruction of mutli-parametric images was automatically performed using in-house C++ programs intergrated into the MRI reconstruction platform (United Imaging Healthcare).

To assess the magnetic susceptibility, MTP was performed pre- and post-gadobutrol injection. Gadobutrol (Gadovist, Bayer Pharma, Shanghai, China) injection was used for contrast enhancement at a dose of 0.1 mmol/kg body weight and a flow rate of 2.5 mL/s. The MTP sequence was scanned from 5 min and 8 s after the enhanced injection.

MRI post-processing

To minimize interference from local lesions, all deep gray matter nucleus regions of interest (ROIs) on the MRI scans were visually inspected. If an ROI was affected by an enhancing lesion, hemorrhage, or significant edema, it was excluded from the analysis for that subject at the corresponding time point. As shown in Figure 2, T1W, QSM, T1 mapping and T2* mapping images acquired from pre- and post-contrast MTP images were registered to the Montreal Neurological Institute (MNI) space using the Advanced Normalization Tools (https://www.nitrc.org/projects/ants). For each subject, after skull stripping, the enhanced MTP-T1W image (T1Wpost) was first registered to the pre-enhanced MTP-T1W image (T1Wpre), whereas the QSMpost image was co-registered to the T1Wpre space. Then, T1Wpre was normalized to the standard MNI space, followed by applying the transformation matrix to QSMpre and QSMpost. The average magnetic susceptibility values of 14 deep gray matter nuclei, including bilateral accumbens, amygdala, caudate, hippocampus, globus pallidus (pallidum), putamen and thalamus, were extracted from QSM images.

Figure 2 MRI data processing pipeline. MNI, Montreal Neurological Institute; MRI, magnetic resonance imaging; T1W, T1-weighted; QSM, quantitative susceptibility mapping.

Statistical analysis

Patient characteristics are summarized using descriptive statistics. Continuous variables (e.g., age, number of gadobutrol injections, QSM values) are expressed as mean ± standard deviation; categorical variables as frequencies or percentages. Paired t-tests compared deep gray matter nucleus susceptibility before and after enhancement. A Bonferroni correction for 14 comparisons was applied, setting the significance threshold at P<0.0036. Cohen’s d measured effect size: d >0.8 (large), 0.5< d ≤0.8 (medium), 0.2< d ≤0.5 (small), confidence intervals (CIs) were calculated for all estimates. For nuclei with significant post-enhancement QSM changes, Spearman correlation analyzed the relationship between ΔQSM and ΔT1/ΔT2* to explore reasons for QSM changes. The association between deep gray nucleus QSM values and the number of gadobutrol injections was initially examined using simple linear regression, followed by a linear mixed-effects model. The dependent variable (QSM values) was modeled as a function of the number of prior gadobutrol injections, age, gender, enhancement patterns, and radio-chemotherapy history (fixed effects). Given that only a subset of subjects underwent multiple contrast-enhanced MRI examinations and that higher numbers of prior injections were relatively uncommon, cumulative exposure analyses were considered exploratory and association-based, rather than confirmatory assessments of cumulative or dose-dependent effects. A random intercept for each subject accounted for inter-individual variability. Analyses used R statistical software (version 4.3.1); P<0.05 was considered statistically significant.

Results

Baseline patient characteristics

Our study encompassed 136 MRI examinations conducted on 72 patients (mean age 59±10 years; 39 males and 33 females); 136 MRI examinations were performed, yielding 136 paired datasets (136 pre-contrast QSM + 136 post-contrast QSM) for acute effect analysis. The baseline characteristics of all participants are presented in Table 1. Enhanced lesions were observed in imaging results for 53 patients (53 of 72, 74%). Final diagnoses included metastatic tumors (24%, n=17), glioblastoma (1%, n=1), no tumor (22%, n=13), and other diseases accounted for 57% (n=40), including abnormal space-occupying lesions that did not undergo pathological examination (metastases: n=21; abnormal enhancing lesions: n=18; alcoholic encephalopathy: n=1). Lesion localization predominantly occurred in the left brain region (22%, n=16), bilateral brain regions (35%, n=25), right brain region (15%, n=8) and no lesion involvement (32%, n=11). Ten patients underwent radiotherapy, of whom four received whole-brain radiotherapy and six received localized lung radiotherapy. Forty-five patients received pulmonary chemotherapy. Among the 72 patients, 37 completed one injection of gadobutrol scan (including one paired pre- and post-enhancement MTP scan), 16 completed two injections of gadobutrol scan, 12 completed three injections of gadobutrol scan, four completed four injections of gadobutrol scan, and three completed five gadobutrol scans.

Differences in QSM values of deep gray matter nuclei before and after enhancement

Changes in magnetization values are illustrated in Figure 3, all observed acute effect sizes were small (|d| <0.5), indicating subtle changes relative to baseline variability, the detailed QSM values before and after enhancement for all nuclei are presented in Table S1. Among the 14 nuclei, QSM values increased in the left amygdala (P<0.001, pre: −15.61 ppb, post: −14.42 ppb, Cohen’s d =0.20) and right hippocampus (P<0.001, pre: 2.44 ppb, post: 4.41 ppb, Cohen’s d =0.48). Conversely, QSM values decreased in the left hippocampus (P<0.001, pre: 1.64 ppb, post: 0.87 ppb, Cohen’s d =−0.19), bilateral putamen (left: P<0.001, pre: 48.55 ppb, post: 47.13 ppb, Cohen’s d =−0.12; right: P=0.04, pre: 22.45 ppb, post: 21.56 ppb, Cohen’s d =−0.09), and bilateral pallidum (P<0.001, left: pre: 35.04 ppb, post: 30.71 ppb, Cohen’s d =−0.21; right: pre: 98.99 ppb, post: 93.05 ppb, Cohen’s d =−0.20). Representative MRI scans are in Figure 4. The remaining 7 nuclei showed no significant pre-post enhancement differences (P>0.05).

Figure 3 Box plot of QSM values of deep gray matter nuclei before and after enhancement. Cohen’s d was listed to show the effect size of the comparison. *, P<0.05; **, P<0.01; ***, P<0.001. L, left; R, right; QSM, quantitative susceptibility mapping.

Figure 4 QSM of the brain in a 60-year-old male with malignant metastatic tumor. Significantly decreased magnetic susceptibility in the bilateral pallidum pre-gadolinium injection (A) versus post-injection (B) in the transverse plane. Significantly increased magnetic susceptibility in the left amygdala pre-gadolinium injection (C) versus post-injection (D) in the coronal plane. L, left; R, right; QSM, quantitative susceptibility mapping.

Lateralized QSM differences in deep gray nuclei: correlations with T1/T2* differences and lesion laterality mechanisms

Based on the QSM differences (ΔQSM) in the 7 gray matter nuclei identified previously, we analyzed their correlations with concomitant T1 differences (ΔT1) and T2* differences (ΔT2*) (Figure S1). A significant negative correlation was observed between ΔQSM and ΔT2* in both the left (R=−0.35, P<0.001) and right (R=−0.27, P=0.003) pallidum. In the right putamen, these measures also showed a significant negative correlation (R=−0.25, P=0.005). However, in the right hippocampus, ΔQSM and ΔT2* exhibited a significant positive correlation (R=0.21, P=0.021). No significant correlations were found between ΔQSM and ΔT2* in the other five nuclei (all P>0.05). Additionally, ΔQSM showed no significant correlations with ΔT1 in the 7 gray matter nuclei (all P>0.05) (Table S2).

To investigate the lateralization mechanisms of ΔQSM across these 7 gray matter nuclei (Figure S2), we stratified subjects by lesion laterality (left/right hemisphere) to assess the effect of lesion lateralization on hippocampal ΔQSM values. A significant difference was found in the right hippocampus based on lesion presence (P<0.001), but had no significant effect on the left hippocampus (P=0.51).

Relationship between QSM values and clinical variables in deep gray matter nuclei in multivariate mixed-effect model

Linear regression showed that there was no significant association between the number of gadobutrol injections and the examined deep gray matter nuclei (all P>0.05) (Table S3). Multivariate mixed-effects models analyzed associations between QSM values in the 7 significant nuclei and clinical variables. Table 2 summarizes results for the left amygdala. Specifically, the number of gadobutrol injections (β =0.88; 95% CI: 0.06, 1.73; P=0.04) was associated with QSM values (Figure 5). No other predictors showed significant associations. In other nuclei, QSM values in the left putamen was positively correlated with age (β =0.49; 95% CI: 0.23, 0.74; P<0.001); in the right putamen, QSM values were positively correlated with both age (β =0.25; 95% CI: 0.04, 0.46; P=0.03) and history of pulmonary chemotherapy (β =6.02; 95% CI: 1.37, 10.67; P=0.02). QSM values in the left pallidum was negatively correlated with disease diagnosis (β =−6.99; 95% CI: −13.10, −0.87; P=0.03) and QSM values in the right pallidum were negatively correlated with history of pulmonary chemotherapy (β =−23.54; 95% CI: −41.35, −5.71; P=0.01). No significant associations were found between QSM values in the other 6 nuclei and the number of gadobutrol injections.

Figure 5 Scatter plot showing the relationship between QSM values in the left amygdala and the number of gadodiamole injections. QSM, quantitative susceptibility mapping.

Discussion

Using prospectively acquired MTP-derived QSM images, this study longitudinally monitored cerebral susceptibility changes after gadobutrol exposure in the same subjects, effectively controlling for inter-individual variability and scanning parameter differences, thus reducing confounding biases common in retrospective studies. We observed that even a single gadobutrol injection significantly increased magnetic susceptibility in the left amygdala and right hippocampus, while decreasing it in the left hippocampus, bilateral putamen, and bilateral pallidum. After accounting for iron deposition effects, correlation analysis revealed a significant negative association between ΔQSM and ΔT2* in both the bilateral pallidum and the right putamen, whereas a significant positive correlation was observed in the right hippocampus. A multivariate mixed-effects model indicated a dose-dependent association between the number of gadobutrol injections and susceptibility changes in the left amygdala. Our findings demonstrated that gadobutrol deposition may exhibit spatial heterogeneity within the deep gray matter nuclei.

MTP is an advanced MRI technique based on a 3D gradient-echo sequence that simultaneously acquires multiple weighted images and generates corresponding quantitative parameter maps in a single scan (15). This reduces scanning time while achieving whole-brain multi-parametric quantitative imaging, improving efficiency and informational richness. QSM utilizes multi-echo phase data to accurately quantify tissue magnetic susceptibility. Its advanced post-processing algorithms enhance quantitative accuracy and tissue contrast compared to conventional SWI. The multi-echo acquisition improves SNR and robustness of susceptibility calculation, mitigating phase wrapping and estimation errors inherent in single-echo imaging, thereby enhancing reproducibility and accuracy for gadolinium deposition quantification. This technique reliably detects subtle dynamic susceptibility changes, providing a crucial means for precisely quantifying low-level gadolinium deposition and its evolution. This study not only confirms intracranial gadolinium deposition but also offers a more precise and reliable quantitative imaging tool, establishing a technical foundation for further research on GBCA pharmacokinetics and long-term safety.

Previous studies demonstrated dose-dependent gadolinium-induced susceptibility alterations after serial GBCA injections, but the time course of gadobutrol on deep gray matter nucleus susceptibility remained unclear (14,17,18). This study found that even a single dose of gadobutrol could lead to a significant increase in magnetic susceptibility in the left amygdala. This phenomenon persisted in patients who received multiple doses after adjusting for confounding factors such as history of radiotherapy/chemotherapy and tumor type. The observed acute susceptibility changes, while statistically significant in certain regions after correction for multiple comparisons, are associated with small effect sizes. This underscores the subtle nature of these alterations occurring immediately after contrast administration. The underlying mechanism may be related to BBB properties and cerebral hemispheric lateralization: as a limbic system structure, the amygdala exhibits higher vascular endothelial permeability, which may facilitate the deposition of gadolinium chelates (19,20). Furthermore, the left middle cerebral artery territory typically has higher cerebral blood flow, potentially increasing local exposure to GBCAs in this region (21,22). In the hippocampal region, however, an opposite lateralization effect was observed after a single injection: magnetic susceptibility increased on the right side but decreased on the left. This discrepancy may be related to the influence of intravascular contrast effects, local cerebral blood flow perfusion, hemodynamics, and lesion location on gadobutrol. Specifically, the right hippocampus—responsible for high-metabolic functions such as spatial memory—is more susceptible to gadolinium permeation in brain tumor patients due to greater BBB disruption (23,24), which aligns with the significant elevation of its ΔQSM values influenced by lesion laterality. In contrast, the left hippocampus, which is primarily involved in semantic memory and likely has a lower resting metabolic rate, retains less gadolinium (25-27); therefore, its ΔQSM values showed no significant association with lesion laterality.

Prior research has predominantly utilized increased SI on T1WI or a shortened T1 relaxation time as markers for gadolinium deposition. However, these metrics not only lack precise quantification capability but are also susceptible to interference from factors such as iron deposition, calcification, and tissue edema (7,12,14). For instance, Kanda et al. (7) observed a significant increase in T1 SI in the dentate nucleus and pallidum following repeated administration of GBCAs, yet this method struggled to effectively differentiate whether the signal changes resulted from gadolinium deposition or endogenous iron accumulation. QSM demonstrates high sensitivity for detecting paramagnetic substances (e.g., iron, gadolinium), directly reflecting tissue magnetic susceptibility distributions. However, distinguishing between substances with similar paramagnetic strengths (e.g., iron and gadolinium) may be limited (28). Deposition of either elevates local magnetic susceptibility. Evaluating GBCA’s paramagnetic effect requires distinguishing its contribution from intrinsic brain iron deposition. Hinoda et al. (17) used QSM to assess gadolinium deposition in the dentate nucleus but did not account for concurrent iron deposition. In contrast, this study confirms that QSM can directly quantify susceptibility changes induced by gadolinium deposition. The results show a significant correlation between ΔQSM and ΔT2* in the bilateral pallidum and right putamen, while no clear association was found between ΔQSM and ΔT1. This highlights the advantage of QSM in detecting subtle, region-specific gadolinium deposition, particularly for macrocyclic GBCAs such as gadobutrol, which exhibit low in vivo deposition levels. Such changes are often difficult to detect using conventional T1WI/T2WI sequences (14,18). This study found that a single administration of gadobutrol resulted in decreased magnetic susceptibility in the bilateral putamen and pallidum. This reduction may be associated with the inherently iron-rich environment of these nuclei, which could lead to a diminished sensitivity of QSM in detecting trace amounts of gadobutrol deposition (29). Langkammer et al. (30) demonstrated through postmortem brain tissue analysis that the pallidum is the region with the highest iron content among the deep brain nuclei, followed by the putamen. Under baseline conditions, the presence of ferritin already renders these regions markedly heterogeneous in terms of magnetic field distribution (29-31). Consequently, gadolinium may, through competitive displacement or other interaction mechanisms, manifest as an apparent reduction in susceptibility or an alteration in its distribution within this high-iron background.

Multiple studies have investigated the effects of repeated gadobutrol injections on deep gray matter nuclei; however, the findings exhibit considerable heterogeneity (18,32). While macrocyclic GBCAs demonstrate high thermodynamic stability in vitro, animal experiments by Schlatt et al (33). indicate that they still undergo a certain degree of dissociation in vivo: the vast majority of gadolinium deposited in bone exists in a dechelated state (either free or bound to endogenous components), with only a small fraction remaining as intact chelates. This confirms the biological relevance of this process. Furthermore, research by Funke et al. (34) further indicates that macrocyclic GBCAs retained long-term in the brains of healthy rats primarily exist in a low-molecular-weight form, rather than as free Gd³⁺. Currently, the specific biodistribution mechanisms of Gd³⁺ in the body are not yet fully understood. Therefore, in the absence of direct pathological evidence, it remains uncertain whether observed increases in magnetic susceptibility originate from free Gd³⁺ or from the gadolinium chelates themselves (35). Choi et al. (14) reported that high cumulative doses of GBCAs can lead to increased magnetic susceptibility in the pallidum. In contrast, in the present study, after adjusting for potential confounders such as history of radiotherapy/chemotherapy and tumor type, patients who received multiple gadobutrol injections did not show a significant increase in magnetic susceptibility within deep gray matter nuclei. This discrepancy may be related to the relatively lower average number of injections in our study, suggesting that the doses used remain within a safe range. Although a slight increase in magnetic susceptibility was observed in the left amygdala, the changes noted may stem from the deposition of free Gd³⁺ or alternatively from the accumulation of gadolinium chelates or their metabolites.

Other studies have identified age as a primary risk factor for neurodegenerative changes. With aging, leukocyte telomeres progressively shorten, an indicator of “biological” age (36,37). Studies show mean telomere length in the putamen significantly decreases with age (38). Several reports note a positive correlation between putamen magnetic susceptibility and age. Liu et al. (39) used QSM to comprehensively analyze the relationship between deep gray matter nucleus susceptibility and age, revealing a robust association between putamen susceptibility and advancing age, consistent with our finding of a significant positive correlation between bilateral putamen susceptibility and age.

This study has several limitations. First, the sample size was limited, with insufficient patients receiving multiple gadobutrol injections, potentially leading to effect overestimation. Second, pathological validation was lacking due to ethical and practical challenges in obtaining postmortem brain tissue. Finally, inherent confounding factors in the patients (e.g., microhemorrhages, tumor effects, and treatments) and the study’s single-center design limit the generalizability of the findings.

Conclusions

In summary, we revealed for the first time that deep gray matter nuclei exhibit spatial heterogeneity in susceptibility response to gadobutrol enhancement: a single administration can induce acute susceptibility changes in specific nuclei, and an association was observed between the number of prior injections and susceptibility alterations in the left amygdala. These findings confirm the technical potential of QSM in monitoring the acute cerebral effects of gadolinium-based agents and suggest that clinical practice requires careful consideration to balance definitive diagnostic benefits against potential risks.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-aw-2261/rc

Data Sharing Statement: Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-aw-2261/dss

Funding: This work was supported by the National Natural Science Foundation of China (No. 81971596), Clinical Research Special Fund from the Affiliated Drum Tower Hospital, Medical School of Nanjing University (No. 2022-LCYJ-MS-25), and Medical Imaging Department Research Project of the Affiliated Drum Tower Hospital, Medical School of Nanjing University (No. JKP-MS-01-2025-02).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-aw-2261/coif). R.T. and Z.L. are employees of United Imaging Healthcare. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the institutional review board of the Nanjing Drum Tower Hospital (No. 2024-JS-32), with a waiver of informed consent justified by: prospective analysis of clinically indicated scans using de-identified data.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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