Positron emission tomography-magnetic resonance imaging applications in pediatric musculoskeletal tumors

Introduction

There are numerous pediatric bone tumors, diagnosis requires a multimodality approach with radiography, computed tomography (CT), magnetic resonance imaging (MRI) and in recent times nuclear medicine has an important role in the diagnosis, surgical planning and follow-up monitoring of this pathology (1). Advances in genetic sequencing techniques have allowed for a more precise characterization of malignant musculoskeletal pathologies for therapeutic management and predicting the prognosis of these tumors.

The evaluation of pediatric bone tumors necessarily includes an MRI for local-regional staging of the tumor and whole-body (WB) bone scintigraphy and/or positron emission tomography (PET) to identify systemic disease.

The PET/MRI technique is a unique imaging diagnostic model because it combines, in a single scan, the information on biochemical and molecular processes provided by PET with the anatomical characterization of soft tissues, multiparametric, and functional information provided by MRI.

The development of PET/MRI hybrid systems began in the late 1990s. It is a technology that, after complex development and overcoming multiple technical limitations, managed to adapt PET detectors to the magnetic field action of 3T MRI (2).

Conventional PET detectors had to be physically separated from the MRI magnetic field using long cables. Recently, they have been replaced by semiconductor detectors, including avalanche photodiode detectors or silicon photomultipliers that are not sensitive to magnetic fields. Another challenge was to create suitable attenuation correction maps. In PET, positrons emitted by the radioisotopes injected into the patient interact with electrons in the body, producing gamma-ray photons. These photons travel in opposite directions and are detected by the PET scanner. However, as the photons traverse the body, they are absorbed or scattered by tissues, attenuating the signal, and potentially causing artifacts and errors in the final image. To correct this attenuation in PET/MRI hybrid systems, MRI is used to create attenuation maps. This process is more complex than in PET/CT because MR images do not directly provide information on tissue density in terms of gamma-ray attenuation. Instead, various techniques are used to infer tissue attenuation based on MR image characteristics. The technique most used is segmentation-based correction. This technique involves segmenting patient images into different tissue classes (e.g., background air, fat, muscle, lung tissue), based on their image based grey scales and assigning standard attenuation values to each region. Dedicated fast MRI sequences, mostly using the Dixon-technique providing fat and water images, are used to obtain images of tissue distribution and subsequent segmentation. Although less precise than CT or MR-based corrections, it is useful in situations where a detailed attenuation map is not available (Figure 1). Currently, the use of specialized MRI sequence techniques (i.e., ultra-short or zero-echo time sequences) has been implemented to generate even more precise attenuation correction maps, particularly in PET/MRI attenuation of the skull and brain. The MRI coils, both rigid and flexible, used in PET/MRI pose a challenge in creating attenuation correction maps because the former contains elements that alter these maps.

Figure 1 Soft-tissue AC based on MR imaging. Allows segmentation into 5 tissues: water, air, soft tissues, lung, and bone. (A,B) Dixon MR sequence providing separate water/fat ‘in-phase’ T1 (A) and ‘opposed phase’ T1 (B) images that serve as basis for soft-tissue segmentation. (C,D) Segmented tissue groups (air, fat, muscle, lungs) that can be assigned to 511 keV attenuation maps. AC, attenuation correction; MR, magnetic resonance.

PET/MRI allows for the identification of the body’s and sectorial distribution of different metabolic tracers [¹⁸F-fluorodeoxyglucose (¹⁸F-FDG), ¹⁸F-fluorocholine, ¹⁸F-fluoride, ¹⁸F-fluorodopa, ⁶⁸Ga-DOTA...]. Simultaneously, it correlates the distribution of these radiopharmaceuticals with the structural and functional characterization provided by MRI sequences, with 80% less exposure to ionizing radiation than conventional PET/CT scans, making it particularly suitable for pediatric patients who will require successive follow-ups due to their condition.

In PET/MRI, there are two acquisition modalities: sequential and simultaneous (3). Fully integrated simultaneous PET/MR imaging scanning is now possible in a simultaneous way with motion-free PET images and advance PET attenuation correction (Figure 2). The simultaneous acquisition of PET and MRI is especially useful in pediatric patients where cooperation may be limited, reducing acquisition time, and decreasing motion artifact, while obtaining advanced PET attenuation correction with magnetic resonance (MR) attenuation correction (AC) sequences.

Figure 2 The simultaneous acquisition of PET and T2 HASTE sequence ensures that the visualized lesions have perfect morpho-functional correlation. The T1 FS post-contrast sequence is acquired at the end of PET acquisition, so the lesion is observed in another section. (A) PET, (B) T2 HASTE, (C) T1 FS post-contrast. PET, positron emission tomography; HASTE, Half Fourier Acquisition Single Shot Turbo Spin Echo; FS, fat suppression.

The aim of this study was to present the practical application of the PET/MRI technique and our clinical experience at our center in the diagnosis and follow-up of primary bone tumors and soft-tissue sarcomas in children. We present this article in accordance with the STROBE reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-24-621/rc).

Methods

Study design, participants and variables

We performed an observational retrospective study that included pediatric patients diagnosed with primary bone or soft-tissue sarcomas in the Pediatric Hematology and Oncology Unit at the HM Montepríncipe University Hospital, Boadilla del Monte, Madrid (Spain) from September 2017 to January 2023.

Patients underwent whole body ¹⁸F-FDG PET/MRI as a staging study and for follow-up evaluation for treatment response. At our institution, imaging data were acquired on a hybrid 3T Biograph mMR^® MR-PET system (Siemens Healthcare, Erlangen, Germany) which allows for simultaneous acquisition. PET/MRI combining state-of-the-art 3T MRI with proven molecular imaging, fully integrated in one system.

It has a gantry of approximately 60 cm and an axial PET coverage of about 25 cm, providing sufficient space for pediatric patients and allowing WB PET studies using five to seven beds in most patients.

The PET/MRI application protocol in our center was applied following the main indications in pediatric musculoskeletal tumors.

The source of information was the electronic clinical history. The variables registered were age (in years), sex (male/female), and type of tumor (primary bone tumor/soft-tissue sarcoma). For those classified as primary bone tumor the followed variables were described: involvement of long bones of the extremities and affected bone, follow-up study (yes/no), metastases at the initial diagnosis (yes/no), metastases at follow up study (yes/no) and anatomical location of the metastases.

PET-MR imaging application protocol

Common indications for ¹⁸F-FDG PET/MR imaging in pediatric oncology include musculoskeletal tumors, providing prognostic information, and potentially for restaging and detection of relapse.

Primary malignant bone tumors

Malignant bone tumors account for 6% of all childhood neoplasms; typically, aggressive with a high tendency to metastasize, their treatment requires a multidisciplinary approach, combining surgery, chemotherapy (QT), and radiotherapy (RT) (1). Osteosarcoma (OS) is the most common primary malignant bone tumor in children, a rare malignancy accounting for only 2% of all cancers with a peak age between 10 and 14 years (4). It is an aggressive lesion with bone formation and typically presents with pulmonary metastases at diagnosis in 10–20% of cases (Figures 3-5).

Figure 3 A 10-year-old male presenting with right knee pain for 2 months. Osteosarcoma in the right distal femur confirmed with biopsy. (A) PA and (B) lateral radiograph demonstrate a highly aggressive lesion with involvement of the distal right femoral metaphysis-diaphysis (arrow), osteosclerosis with aggressive periosteal reaction posteriorly (C,D) axial CT image shows the destructive lesion and the soft tissue mass. (E) Sagittal MRI T2 hyperintense mass (F) Sagittal MRI T1 hypointense and heterogeneous mass. (G,H) Axial MRI images reveals typical signs of osteosarcoma. PA, posterior anterior; MRI, magnetic resonance imaging.

Figure 4 A 9-year-old boy with left distal femur osteosarcoma. (A) COR STIR, (B) COR T1 and (C) COR STIR + PET fusion. A heterogeneous and hypermetabolic lesion affecting both bone and adjacent soft tissue is observed (red arrow, left distal femur osteosarcoma). There is no evidence of nodal or distant metastases. PET-MRI follow-up study after surgery and chemotherapy. (D) COR STIR: the proximal two thirds of the left tibia show bone marrow signal alteration, with anfractuous and hypointense images that corresponded to bone infarcts and (E) COR STIR + PET fusion: left inguinal and external iliac hypermetabolic adenopathy (blue arrow, hypermetabolic adenopathy) that were thought to be metastatic. However, they resolved in successive imaging studies. COR, coronal; STIR, short tau inversion recovery; PET, positron emission tomography; MRI, magnetic resonance imaging.

Figure 5 A ten-year-old boy with right tibia Ewing sarcoma concerning for metastatic disease. PET-MRI extension study. (A) WB COR STIR + C, (B) WB PET MIP, (C) fused PET/WB COR STIR, (D) AXIAL T1 FS VIBE + C, (E) AXIAL T2 HASTE and (F) fused PET AXIAL T2 HASTE. Demonstrating a large, infiltrative, lobulated, and heterogeneous mass that associates soft tissue component, T2w hyperintense and FDG uptake mass arising from right tibia. In the right popliteal fossa, a nodular image with increased 18F-FDG uptake is observed (yellow circle). It is suspicious for adenopathy, denoting nodal involvement. PET, positron emission tomography; MRI, magnetic resonance imaging; WB, whole-body; COR, coronal; STIR, short tau inversion recovery; MIP, maximum intensity projection; FS, fat suppression; VIBE, volume interpolated breath-hold examination; HASTE, Half Fourier Acquisition Single Shot Turbo Spin Echo; ¹⁸F-FDG, ¹⁸F-fluorodeoxyglucose.

Ewing sarcoma, the second most common bone malignancy in the pediatric population, typically occurring around 10–15 years of age. It is centrally located, diaphyseal, lytic, with an onion-skin appearance, and highly aggressive. Most frequently locate in the femur, tibia, fibula, and pelvis. It mimics osteomyelitis and has a poor prognosis as metastasizes at diagnosis in 30% of cases, commonly involving the lungs, bones, adrenal glands, and brain. Aggressive periosteal reaction, Codman’s triangle, spiculated appearance, and often associated soft tissue mass are observed (5,6).

Malignant bone tumors often affect the metaphysis of long bones, especially around the knee and shoulder (1), and the distal femur, proximal tibia, and proximal humerus in the case of OS (5). However, they can also affect the pelvis, ribs, and vertebral bodies, especially in Ewing sarcoma. The presence of persistent localized pain and swelling warrants the performance of radiography (Figures 6-8).

Figure 6 A 14-year-old boy with back pain. MRI study shows an hyperintense lesion in the vertebral body of T2. Extensive hyperintense signal is seen in soft tissue around dorsal vertebral bodies and posterior soft tissue (arrow). (A-C) SAG T1, (D-F) SAG STIR. MRI, magnetic resonance imaging; SAG, sagittal; STIR, short tau inversion recovery.

Figure 7 Vertebral body lesion and soft tissue mass show enhancement after gadolinium administration. Hyperintensity is also seen in diffusion image. Axial MRI images reveals typical signs of Ewing sarcoma. (A) Axial T2; (B,C) axial T1 with fat suppression and gadolinium administration; (D) axial CT. A lytic lesion is seen in the right lateral pedicle of T2 with a paravertebral soft tissue mass Ewing sarcoma (yellow arrow). MRI, magnetic resonance imaging; CT, computed tomography.

Figure 8 Whole-body PET-MR study. (A) Sagittal MRI T1, (B) PET, (C) PET/MRI fusion, (D) PET/MRI axial fusion: the uptake is only present in the vertebral body of T2, (E) SUVmax of the lesion 6.17. (F) We perform a biopsy with the result of osteoblastoma. (G,H) The tumor was treated with percutaneous cryoablation. SUVmax, maximal standardized uptake value; PET/MR, positron emission tomography/magnetic resonance; MRI, magnetic resonance imaging; PET, positron emission tomography.

MRI is the preferred modality for the diagnosis and local staging. The utility of PET with ¹⁸F-FDG is not fully defined, although it presents greater diagnostic accuracy in detecting nodal and distant metastases and is more sensitive for bone metastases in Ewing sarcoma and OS, probably related to the predominant medullary infiltration in Ewing’s case and the osteoblastic metastases in OS. Combined PET/MRI images with ¹⁸F-FDG are likely to increase the overall accuracy of staging and response assessment. A significant disadvantage of PET/MR images is the limitation in detecting small pulmonary nodules (7).

PET allows differentiating perilesional edema and tumor infiltration and detects the presence of tumor thrombi because perilesional edema has a low or absent FDG uptake, while tumor thrombi have a high FDG uptake due to the presence of metabolically active tumor cells. Tumor thrombi are often associated with visible masses and may show invasion into adjacent structures.

The soft-tissue component of conventional OS is often hyperintense on T2 and has high uptake for ¹⁸F-FDG on PET, while the bone-forming component is usually hypointense on T2 and has low uptake for ¹⁸F-FDG. Descriptions of the extent of intra- and extra-osseous soft tissue, neurovascular bundle involvement, presence of intraarticular extension, and tumor thrombus are important as they may have implications for surgical treatment planning.

The main advantage of PET-MRI in Ewing sarcoma is that it is very useful as a guide for biopsy of hypermetabolic regions since it is a tumor with heterogeneous appearance on MRI. ¹⁸F-FDG PET/MRI can help evaluate tumor chemotherapy response based on a reduction of ¹⁸F-FDG uptake of more than 30%.

Soft-tissue sarcomas

Pediatric soft-tissue sarcomas constitute about 7% of all solid pediatric tumors. Rhabdomyosarcoma is the most common subtype (3), most frequently located in the head, neck, and genitourinary tract.

MRI is the preferred modality for diagnosis and local staging. Soft-tissue sarcomas have high uptake of ¹⁸F-FDG, and it is useful in detecting lymph node and bone metastases. Combined PET/MRI imaging with ¹⁸F-FDG, including diffusion weighted imaging (DWI), is likely to increase overall staging accuracy and response assessment (Figure 9), as it results in higher detection compared to MRI or PET alone (2).

Figure 9 A 15-year-old girl with synovial sarcoma in the right ankle. (A,B) WB PET-MRI follow-up study after surgery shows uptake in the surgical bed is seen related with tumor remains (arrow). Right inguinal adenopathy is also seen. (C-E) WB PET-MRI follow-up study 4 years later is normal without evidence of metastasis and adenopathy. WB, whole-body; PET/MRI, positron emission tomography/magnetic resonance imaging.

Langerhans cell histiocytosis (LCH)

LCH is a granulomatous disease in which dendritic cells proliferate abnormally, infiltrating various organs or tissues with significant variability in clinical presentation and biological behavior, thus mimicking different diseases. It can affect bones, skin, teeth, gingival tissue, ears, endocrine organs, lungs, liver, spleen, lymph nodes, and bone marrow. Bone involvement can be either unifocal or multifocal. The average age at diagnosis is 5–10 years. The most common site of involvement is flat bones (65–70%). Early lesions may appear highly aggressive (8).

Diagnostic imaging is of utmost importance. Lesions are visible on plain radiographs, CT scans, and MRI, thus initial evaluation with conventional radiography and bone scintigraphy (both with low specificity) has routinely been used as imaging modalities in the extension study of LCH, which is a crucial factor in defining treatment and prognosis. PET/MR imaging with ¹⁸F-FDG, including DWI, allows identification of active lesions and monitoring of therapeutic response in pediatric patients with LCH. Additionally, it has higher sensitivity for detecting marrow lesions compared to PET/CT and entails lower radiation exposure (Figure 10).

Figure 10 A 3-year-old boy diagnosed with multifocal LCH. WB PET-MRI extension study of four well defined, predominantly hyperintense on T2WI and ¹⁸F-FDG avid bone lesions are observed in the right front-orbital region, left frontal bone, proximal end of the left femoral shaft and middle third of the right tibial shaft. These lesions do not associate aggressive periosteal reaction or soft tissue component. (A) AXIAL T2, (B) AXIAL T2 + PET fusion, (C) AXIAL T2, (D) AXIAL T2 + PET fusion, (E) COR STIR and (F) COR T1 + PET fusion. LCH, Langerhans cell histiocytosis; WB, whole-body; PET-MRI, positron emission tomography-magnetic resonance imaging; T2WI, T2-weighted imaging; ¹⁸F-FDG, ¹⁸F-fluorodeoxyglucose; COR, coronal; STIR, short tau inversion recovery.

Patient preparation

The nuclear medicine physician explains in detail the study to the patient and parents/caregivers, who have been provided with information delivered verbally. Patients should be fasting for 4–6 h before ¹⁸F-FDG injection to decrease serum glucose level and to maintain a low insulin level. The serum glucose level is measured before the radiotracer administration. The glucose level should be below 200 mg/dL (11.1 mmol/L); the optimal level is below 140 mg/dL (7.8 mmol/L). The height and weight of the patient is measured on the day of the examination. The patient lying on a bed in a quiet, warm room for ¹⁸F-FDG injection and during the uptake phase. It is important that patients avoid talking, playing, exercising, or chewing before and after ¹⁸F-FDG is administered. Some small children required general anesthesia, they were previously evaluated by the anesthesiologist, and it was administered immediately before image acquisition.

Radiotracer

¹⁸F-FDG is the most common radiotracer used for PET imaging, with a half-life of approximately 110 min. FDG is an analog of glucose, which is taken up by cells via cell membrane glucose transporters and subsequently incorporated into the first step of the physiologic glycolytic pathway. The dose of ¹⁸F-FDG to be administered to patients can vary based on several factors, including patient weight, clinical indication, and institutional protocols. The administered activity should be the lowest possible dose that will produce diagnostic image quality. The administered activity follows the 2016 Update of the North American Consensus Guidelines for Pediatric Administered Radiopharmaceutical Activities and the 2016 EANM pediatric Dosage Card. The administered activity of ¹⁸F-FDG is 3.7–5.2 MBq/kg (0.10–0.14 mCi/kg) for a body PET/CT scan [with a minimum of 26 MBq (0.7 mCi)]. The administered dose is optimized according to the institutional policy and for PET/MRI systems. Our institutional guidelines protocol uses intravenous injection of 3 MBq/kg of ¹⁸F-FDG, which is lower than the standard dose, because the acquisition of MR sequences increases the PET image acquisition time, allowing for a significant reduction in the dose adjusted to the individual needs of the patient.

PET/MRI protocol

Considering the time to place the patient in the PET/MRI scanner and apply the surface coils, the PET scan starts 60 min after injection (9). The patient is lying decubitus supine on the table with arms close to the body. Specific mMR Tim radiofrequency coils (head and neck coil, spine coil and up to four body array coils) are placed under, on and around the patient’s body, respectively, covering the entire acquisition field. Imaging acquisition is performed caudally to cranially, typically starting from the feet up to the cranial vertex to avoid bladder image artifact (3) (Figures 11,12). The study usually starts with a basic module consisting of a WB PET acquisition accompanied by simultaneous WB MR imaging. In our protocol, PET acquisition time is usually 4 minutes per bed position and acquisition of MR sequence T2 Half Fourier Acquisition Single Shot Turbo Spin Echo (HASTE), and DWI axial MRI sequences with values b50, 500 y 1,000. Subsequently, intravenous gadolinium is administered and a volumetric gradient echo sequence with T1-weighted fat suppression (FS) is obtained (T1 VIBE). The different sequences are summarized in Table 1.

Figure 11 Simultaneous PET-MRI protocol. The examination usually starts with a basic module consisting of a whole-body PET acquisition accompanied by simultaneous whole-body MR imaging, mostly using coronal fat-saturated T2-weighted, in a bed-per-bed manner. PET acquisition time is 4 minutes per bed position. In addition, a dedicated MR sequence must be acquired for each bed position for MRAC. PET, positron emission tomography; MRAC, MR-based attenuation correction; HASTE, Half Fourier Acquisition Single Shot Turbo Spin Echo; PET-MRI, positron emission tomography-magnetic resonance imaging; MR, magnetic resonance; DIFU, diffusion.

Figure 12 Positioning of the pediatric patient. It is advisable to use a vacuum cushion between the patient’s body and the antennas in the case of non-anesthetized children, to prevent motion artifacts.

Interpretation of images

The interpretation of PET/MR studies is complex, as numerous MRI sequences and the PET study are available, thus a joint report is generated between a pediatric radiologist and a nuclear medicine physician, both specialists in pediatric pathology. Compared to adults, children exhibit different physiological and anatomical characteristics such as the presence of thymic tissue or physiological uptake of brown fat, as well as visualization of growth cartilage that must be considered to avoid incorrect interpretation (3,10,11) (Figure 13).

Figure 13 PET-MRI ¹⁸F-FDG Whole body of a child: we can see the visualization of the growth cartilages (yellow circle). (A) Coronal T2 HASTE, (B) PET, (C) fusion PET-MRI. PET-MRI, positron emission tomography-magnetic resonance imaging; ¹⁸F-FDG, ¹⁸F-fluorodeoxyglucose; HASTE, Half Fourier Acquisition Single Shot Turbo Spin Echo.

At our institution, radiological studies are reported by consensus among multidisciplinary teams consisting of a radiologist and a nuclear medicine physician. Complex cases are discussed in a multidisciplinary pediatric oncology committee that meets every Wednesday. In radiological reports of ¹⁸F-FDG PET/MRI, it is important to include the tumor size, presence or absence of metastatic disease, location of metastases, and changes in the size of index lesions for treatment monitoring (8).

Statistical analysis

Variables were described using percentages or medians and interquartile range (IQR). Since the inspection of the quantitative variables indicated a deviation from the normal distribution, the Kruskal-Wallis test for association was applied. To explore association between qualitative variables the Chi-squared test was performed. If the expected value in a cell was less than 5, Fisher’s exact test was performed.

Statistical significance was set at a two-tailed P value <0.05. The analysis was performed using the IBM SPSS Version 28.0 package.

Ethical considerations

The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). All the cases presented were part of routine clinical practice. Verbal informed consent was obtained from all patients or their legal guardians prior to the performance of the diagnostic tests.

Results

A total of 71 ¹⁸F-FDG PET/MR studies were performed on 39 patients. Most of them (55%) were initial extension studies and (45%) were follow-up studies. Most of the patients studied were male (74.4%) with a median age of 15 years. The distribution of sex and age depending on the diagnosis and the initial finding of metastases can be seen in Table 2.

Of the 39 cases, 51% were primary bone tumors (OS 28.2% and Ewing sarcoma 23.1%) while 18% were LCH and 21% soft tissue tumors and 10% other tumors (Table 2, Figure 14). There were no statistically significant differences in age or sex depending on the type of tumor diagnosed. Multifocal bone lesions were present in 7.6% of the cases. Among those with primary bone tumors, in 46.8% long bones of the extremities were involved, with the femur being the most affected one (25% of bone lesions and 20.5% of the total). Of the 71 studies, 5 (12.8%) showed metastases at the initial diagnosis, three presented lymph node involvement, one with local infiltration, and one with pulmonary metastasis. During follow-up, two cases with distant metastases were diagnosed. The different locations are summarized in Table 3.

Figure 14 Results of the 39 cases: 51% were primary bone tumors (osteosarcoma 28.2% and Ewing sarcoma 23.1%), 18% were Langerhans Cell Histiocytosis and 21% soft tissue tumors.

Discussion

The combined use of PET and MRI has represented a significant advancement in the evaluation of pediatric malignant neoplasms, with specific applications in musculoskeletal tumors showing clear benefits over PET/CT (12,13).

PET-MRI is superior to PET/CT in soft tissue assessment, combining tumor metabolism evaluation through PET and morphological, parametric, and functional assessment by MRI. The superior soft tissue contrast of MR is in general relevant for all types of soft tissue tumors regarding detection, delineation, characterization, and staging.

The reduction in ionizing radiation dose and the decrease in total examination time are notable advantages in pediatric patients. However, both MRI and PET have limited sensitivity for the detection of subcentimetric pulmonary nodules (14). Its sensitivity for detecting lung nodules is low due to the limited lung resolution of PET-MRI, thus requiring additional chest CT in the extension study to identify pulmonary metastases (7,12,13).

PET/MRI utility includes the characterization of the primary tumor, local-regional and distant staging, therapy planning, and post-treatment follow-up. It allows for WB evaluation in a single session, providing efficient staging and avoiding the need for the patient to undergo anesthesia twice. Additionally, estimation of tumor volume provides prognostic information.

Pediatric patients who underwent the described protocol at our center during the period of the study present an expected distribution of primary malignant bone tumors and soft tissue tumors. The characteristics of the described lesions are also in line with those described in the reviewed literature for their group of age.

The ¹⁸F-FDG PET/MRI has shown to increase diagnostic accuracy in primary bone and soft tissue tumors, as it allows for the comprehensive evaluation of their morpho-metabolic characteristics, locoregional, and distant involvement in a single study. This is particularly beneficial in the pediatric population as it avoids the need for multiple anesthesia procedures. It is also useful in surgical planning and post-treatment follow-up. The reduction in ionizing radiation dose and overall scanning time are notable advantages.

In heterogeneous tumors, PET is also useful for guiding biopsies towards areas of highest metabolic activity. Its main drawback is the low sensitivity for detecting pulmonary nodules; hence, chest CT remains essential in thoracic staging. Lymph node evaluation remains a limitation for WB MRI due to the lack of standardized apparent diffusion coefficient (ADC) values for distinguishing benign from malignant nodes, a limitation that PET-MR resolves.

Acknowledgments

We thank Lina Garcia Cañamaque, Chief of the PET/MRI Metabolic Service Center for their assistance with the acquisition of PET/MRI scans at the University Hospital HM Puerta del Sur at Móstoles (Madrid), and we thank Blanca Lopez Ibor, Chief of the Pediatric Hematology and Oncology Service at the HM Montepríncipe Hospital, who cares for children and adolescents.

Funding: None.

Footnote

Provenance and Peer Review: With the arrangement by the Guest Editors and the editorial office, this article has been reviewed by external peers.

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at: https://qims.amegroups.com/article/view/10.21037/qims-24-621/rc

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-621/coif). The special issue “Advances in Diagnostic Musculoskeletal Imaging and Image-guided Therapy” was commissioned by the editorial office without any funding or sponsorship. J.M.V. served as the unpaid Guest Editor of the issue. The authors have no other 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 (as revised in 2013). All the cases presented were part of routine clinical practice. Verbal informed consent was obtained from all patients or their legal guardians prior to the performance of the diagnostic tests.

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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