The diagnostic accuracy of WB-MRI was comparable to the one of mIBG images for all the lesions and organs considered in patients with metastatic PPGL in the study. WB-MRI was considered more valuable than 123I-mIBG scintigraphy because it detects lesions around organs with physiologic mIBG accumulation and allows clinical follow-up without exposing the patients to radiation. Additionally, the kappa coefficient revealed a substantial concordance among reviewers, indicating high reproducibility of the obtained results.
WB-MRI is currently an established screening tool for malignancies [10], and international guidelines recommend it for screening patients with malignant tumors [5]. WB-MRI exhibits high diagnostic performances in identifying several tumor types, with 86% sensitivity for tumors, 80% sensitivity and 75% specificity for lymph node metastases, and 96% sensitivity and 82% specificity for metastatic disease determination [11]. WB-MRI demonstrated better screening performances for PPGL predisposition to biochemical tests. However, a comprehensive comparison with other imaging modalities was unaddressed. This study revealed that WB-MRI demonstrated a detection rate similar to that of mIBG imaging, which is currently used as a standard tool in Japan to assess tumor progression in patients with metastatic PPGL.
Our study used both WB-MRI and mIBG imaging techniques to assess the detectability of tumor lesions and explore the diagnostic performances specific to each of the five organs included in the analysis. We classified images as “positive” if they detected one or more lesions (Table 2). The detection in each of the organs was inconsistent, with no significant difference in detection performances for lesions with organ metastasis.
WB-MRI’s detectability in the liver demonstrated no significant differences compared to 123I-mIBG or 131I-mIBG scintigraphy. However, WB-MRI holds greater potential for detecting liver metastases than 123I-mIBG and 131I-mIBG scintigraphy due to the physiological accumulation of mIBG in the liver. Congruently, both 123I-mIBG and 131I-mIBG images demonstrated lower sensitivity in detecting liver tumor lesions. These results are consistent with previous studies reporting the superiority of diffusion-weighted whole-body imaging with background body signal (DWIBS) over mIBG scintigraphy for detecting metastatic lesions [12]. The number of cases with liver metastasis was small which could potentially bias the results, but our study revealed that WB-MRI can be used as a tool to detect liver metastases.
In lung metastases assessment, WB-MRI exhibited low detectability compared to 123I mIBG and 131I-mIBG images. Petralia et al. [13] revealed the detection of false-negative when analyzing lung metastases of < 4 mm and Nicholas et al. [14] reported a low detection rate with MRI imaging for pulmonary nodules of < 4 mm. Hence, further technical improvements are required before considering WB-MRI a viable alternative to CT in routine clinical lung assessments. The limited spatial resolution may have hindered WB-MRI detection of diffuse micro-metastases. Resolution concerns could also arise concerning 123I-mIBG and 131I-mIBG scintigraphy, but this was not an issue in our study given the good mIBG accumulation in the included patients.
The high physiological signal intensity had the potential drawback of hindering WB-MRI assessment in case of LN metastases, but it also has some advantages, as it can detect lesions around organs with physiologically high mIBG accumulation. Both WB-MRI and 123I-mIBG scintigraphy require the combination of physiological and pathological findings for proper detection. This study demonstrated that two reviewers revealed almost identical detection capabilities in identifying lesions with minimal or negligible knowledge of physiological features. The detectability and concordance of others did not significantly differ with physiological findings, including pleural dissemination, retroperitoneal and pelvic dissemination, pleural invasion, local recurrence of retroperitoneal paraganglioma, posterior mediastinum, and peritoneal dissemination in 2, 1, 1, 1, 1, and 2 cases, respectively.
Previous reports have revealed the superior diagnostic performance of post-therapy 131I-mIBG images in PPGL and neuroblastoma compared to 123I-mIBG images [3, 15]. However, the diagnostic performance of both modalities, including whole-body and individual organ assessments, revealed comparable results in this study. The kappa coefficients of the reviewers for WB-MRI, 123I-mIBG, and post-therapy 131I-mIBG images exhibited similar concordance levels. This similarity in diagnostic performance may be associated with the specific criteria selected, where a lesion was considered “positive” if it was detectable across multiple lesions (Table 2).
This study included patients with mIBG-avid metastases in the therapy, but notably, several factors, including genetic information and tumor heterogeneity, influenced the varying detection rate of 123I-mIBG scintigraphy. Previous studies reported the diagnostic performance of 123I-mIBG in primary or metastatic PPGL, indicating sensitivity of 28–100% and specificity of 70–100% [2, 16]. Therefore, a combination of imaging evaluations, including mIBG scintigraphy, somatostatin receptor imaging, and 18F-FDG-PET, is necessary to prepare for nuclear medicine treatment in a clinical setting. This indicates that results may differ when mIBG-negative patients are included. Future studies focusing on the mIBG-negative patient group are required to further consolidate data on detection rates. Conducting follow-up observations in mIBG-negative patients using radiation-free imaging techniques may be possible if a high detection rate similar to the one of WB-MRI could be achieved.
This study is not without limitations. First, the number of patients included was limited, but this reflects the rarity of PPGL as a disease. Hence, minor differences observed among the imaging modalities under evaluation may not have reached statistical significance. Second, not all the metastatic lesions that demonstrated positive findings in WB-MRI and mIBG images underwent pathological diagnosis. This may introduce the possibility of false-positive findings. Third, the assessment did not account for the precise number of metastases because this study focused on the presence and extent of metastases, and any abnormal mIBG accumulation was considered “positive.”