No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Whole-Body MRI in Children: Concepts and Controversies-AJR Expert Panel Narrative Review
Abstract
The use of whole-body MRI (WBMRI) in children, from infancy to adolescence, has expanded rapidly over the past decade, with increasing uptake and a broadening range of clinical indications. Current indications include screening for presymptomatic lesions in cancer predisposition syndromes; tumor staging in known malignancies; investigating fevers of unknown origin; as well as diagnosing and monitoring rheumatologic diseases, vascular anomalies and neuromuscular disorders. This AJR Expert Panel Narrative Review aims to offer a comprehensive discussion of WBMRI in pediatric patients, exploring protocols and other technical considerations, clinical indications, implementation challenges and troubleshooting, as well as controversies in widespread adoption, while considering emerging trends and directions. Commonalities and variations in WBMRI protocols across indications and institutions are presented, highlighting the need for greater standardization. Barriers to WBMRI access, particularly in resource-limited settings, are considered, along with potential solutions. The available evidence regarding potential patient benefit from WBMRI across various applications is summarized.
Central conducting lymphatic anomaly (CCLA) is a complex lymphatic anomaly characterized by abnormalities of the central lymphatics and may present with nonimmune fetal hydrops, chylothorax, chylous ascites, or lymphedema. CCLA has historically been difficult to diagnose and treat; however, recent advances in imaging, such as dynamic contrast magnetic resonance lymphangiography, and in genomics, such as deep sequencing and utilization of cell-free DNA, have improved diagnosis and refined both genotype and phenotype. Furthermore, in vitro and in vivo models have confirmed genetic causes of CCLA, defined the underlying pathogenesis, and facilitated personalized medicine to improve outcomes. Basic, translational, and clinical science are essential for a bedside-to-bench and back approach for CCLA.
Objective
Inflammatory myopathies (IIM) include dermatomyositis (DM), sporadic inclusion body myositis (sIBM), immune-mediated necrotizing myopathy (IMNM), and overlap myositis (OLM)/antisynthetase syndrome (ASyS). There is also a rare variant termed polymyositis with mitochondrial pathology (PM-Mito), which is considered a sIBM precursor. There is no information regarding muscle MRI for this rare entity. The aim of this study was to compare MRI findings in IIM, including PM-Mito.
Methods
This retrospective analysis included 41 patients (7 PM-Mito, 11 sIBM, 11 PM/ASyS/OLM, 12 IMNM) and 20 healthy controls. Pattern of muscle involvement was assessed by semiquantitative evaluation, while Dixon method was used to quantify muscular fat fraction.
Results
The sIBM typical pattern affecting the lower extremities was not found in the majority of PM-Mito-patients. Intramuscular edema in sIBM and PM-Mito was limited to the lower extremities, whereas IMNM and PM/ASyS/OLM showed additional edema in the trunk. Quantitative assessment showed increased fat content in sIBM, with an intramuscular proximo-distal gradient. Similar changes were also found in a few PM-Mito- and PM/ASyS/OLM patients. In sIBM and PM-Mito, mean fat fraction of several muscles correlated with clinical involvement.
Interpretation
As MRI findings in patients with PM-Mito relevantly differed from sIBM, the attribution of PM-Mito as sIBM precursor should be critically discussed. Some patients in PM/ASyS/OLM and PM-Mito group showed MR-morphologic features predominantly observed in sIBM, indicative of a spectrum from PM/ASyS/OLM toward sIBM. In some IIM subtypes, MRI may serve as a biomarker of disease severity.
Background
Whole-body magnetic resonance imaging (WB-MRI) has emerged as a valuable tool for cancer detection. This study evaluated the prevalence rates of cancer in asymptomatic individuals undergoing WB-MRI according to the Oncologically Relevant Findings Reporting and Data System (ONCO-RADS) classifications in order to assess the reliability of the classification method.
Methods
We retrospectively enrolled 2064 asymptomatic individuals who participated in a WB-MRI cancer screening program between 2017 and 2022. WB-MRI was acquired on a 3-T system with a standard protocol, including regional multisequence and gadolinium-based contrast agent-enhanced oncologic MRI. Results of further examinations, including additional imaging and histopathology examinations, performed at our institute were used to validate the WB-MRI findings. Two radiologists blinded to the clinical outcome classified the WB-MRI findings according to the ONCO–RADS categories as follows: 1 (normal), 2 (benign finding highly likely), 3 (benign finding likely), 4 (malignant finding likely), and 5 (malignant finding highly likely). Firth logistic regression analysis was performed to determine the associations between participant characteristics and findings of ONCO-RADS category ≥ 4.
Results
Of the 2064 participants with median age of 55 years, 1120 (54.3%) were men, 43 (2.1%) had findings of ONCO-RADS category ≥ 4, and 24 (1.2%) had confirmed cancer. The cancer prevalence rates were 0.1%, 5.4%, 42.9%, and 75% for ONCO-RADS categories 2, 3, 4, and 5, respectively. In the multivariable model, older age (OR: 1.035, p = 0.029) and history of hypertension (OR: 2.051, p = 0.026), hepatitis B carrier (OR: 2.584, p = 0.013), or prior surgery (OR: 3.787, p < 0.001) were independently associated with the findings for ONCO-RADS category ≥ 4.
Conclusions
The ONCO-RADS categories for cancer risk stratification were validated and found to be positively correlated with cancer risk. The application of ONCO-RADS facilitates risk-based management after WB-MRI for cancer screening.
Improving access to magnetic resonance imaging (MRI) in childhood can be facilitated by making it faster and cheaper and reducing need for sedation or general anesthesia (GA) to mitigate motion. Some children achieve diagnostic quality MRI without GA through the use of non- practices fostering their cooperation and/or alleviating anxiety. Employed before and during MRI, these variably educate, distract, and/or desensitize patients to this environment.
To assess current utilization of non-sedate practices in pediatric MRI, including variations in practice and outcomes.
A survey-based study was conducted with 1372 surveys emailed to the Society for Pediatric Radiology members in February 2021, inviting one response per institution.
Responses from 50 unique institutions in nine countries revealed 49/50 (98%) sites used ≥ 1 non-sedate practice, 48/50 (96%) sites in infants < 6 months, and 11/50 (22%) for children aged 6 months to 3 years. Non-sedate practices per site averaged 4.5 (range 0–10), feed and swaddle used at 47/49 (96%) sites, and child life specialists at 35/49 (71%). Average success rates were moderate (> 50–75%) across all sites and high (> 75–100%) for 20% of sites, varying with specific techniques. Commonest barriers to use were scheduling conflicts and limited knowledge.
Non-sedate practice utilization in pediatric MRI was near-universal but widely variable across sites, ages, and locales, with room for broader adoption. Although on average non-sedate practice success rates were similar, the range in use and outcomes suggest a need for standardized implementation guidelines, including patient selection and outcome metrics, to optimize utilization and inform educational initiatives.
Autoimmune neuromuscular diseases are a group of heterogenous pathologies secondary to the activation of the immune system that damage the structures of the peripheric nerve, the neuromuscular junction, or the skeleton muscle. The diagnosis of autoimmune neuromuscular disorders comprises a combination of data from clinical, laboratory, electromyography, imaging exam, and biopsy. Particularly, the whole-body MRI examination in the last two decades has been of great use in the assessment of neuromuscular disorders. MRI provides information about the structures involved and the status of activity of the disease. It can also be used as a biomarker, detect the pattern of specific muscle involvement, and is a useful tool for targeting the optimal muscle site for biopsy. In this work, we summarized the most used technical protocol of whole-body MRI and the role of this imaging technique in autoimmune neuromuscular disorders.
People with Li–Fraumeni syndrome (LFS) harbor a germline pathogenic variant in the TP53 tumor suppressor gene, face a near 100% lifetime risk of cancer, and routinely undergo intensive surveillance protocols. Liquid biopsy has become an attractive tool for a range of clinical applications, including early cancer detection. Here, we provide a proof-of-principle for a multimodal liquid biopsy assay that integrates a targeted gene panel, shallow whole-genome, and cell-free methylated DNA immunoprecipitation sequencing for the early detection of cancer in a longitudinal cohort of 89 LFS patients. Multimodal analysis increased our detection rate in patients with an active cancer diagnosis over uni-modal analysis and was able to detect cancer-associated signal(s) in carriers prior to diagnosis with conventional screening (positive predictive value = 67.6%, negative predictive value = 96.5%). Although adoption of liquid biopsy into current surveillance will require further clinical validation, this study provides a framework for individuals with LFS.
Significance
By utilizing an integrated cell-free DNA approach, liquid biopsy shows earlier detection of cancer in patients with LFS compared with current clinical surveillance methods such as imaging. Liquid biopsy provides improved accessibility and sensitivity, complementing current clinical surveillance methods to provide better care for these patients.
See related commentary by Latham et al., p. 23.
This article is featured in Selected Articles from This Issue, p. 5
Background
Whole-body magnetic resonance imaging (WB-MRI) is an increasingly used guideline-based imaging modality for oncological and non-oncological pathologies during childhood and adolescence. While diffusion-weighted imaging (DWI), a part of WB-MRI, enhances image interpretation and improves sensitivity, it also requires the longest acquisition time during a typical WB-MRI scan protocol. Interleaved short tau inversion recovery (STIR) DWI with simultaneous multi-slice (SMS) acquisition is an effective way to speed up examinations.
Objective
In this study of children and adolescents, we compared the acquisition time, image quality, signal-to-noise ratio (SNR) and apparent diffusion coefficient (ADC) values of an interleaved STIR SMS-DWI sequence with a standard non-accelerated DWI sequence for WB-MRI.
Materials and methods
Twenty children and adolescents (mean age: 13.9 years) who received two WB-MRI scans at a maximum interval of 18 months, consisting of either standard DWI or SMS-DWI MRI, respectively, were included. For quantitative evaluation, the signal-to-noise ratio (SNR) was determined for b800 images and ADC maps of seven anatomical regions. Image quality evaluation was independently performed by two experienced paediatric radiologists using a 5-point Likert scale. The measurement time per slice stack, pause between measurements including shim and total measurement time of DWI for standard DWI and SMS-DWI were extracted directly from the scan data.
Results
When including the shim duration, the acquisition time for SMS-DWI was 43% faster than for standard DWI. Qualitatively, the scores of SMS-DWI were higher in six locations in the b800 images and four locations in the ADC maps. There was substantial agreement between both readers, with a Cohen’s kappa of 0.75. Quantitatively, the SNR in the b800 images and the ADC maps did not differ significantly from one another.
Conclusion
Whole body-MRI with SMS-DWI provided equivalent image quality and reduced the acquisition time almost by half compared to the standard WB-DWI protocol.
Magnetic resonance imaging (MRI) has emerged as the preferred imaging modality for evaluating a wide range of pediatric medical conditions. Nevertheless, the long acquisition times associated with this technique can limit its widespread use in young children, resulting in motion-degraded or non-diagnostic studies. As a result, sedation or general anesthesia is often necessary to obtain diagnostic images, which has implications for the safety profile of MRI, the cost of the exam and the radiology department’s clinical workflow. Over the last decade, several techniques have been developed to increase the speed of MRI, including parallel imaging, single-shot acquisition, controlled aliasing techniques, compressed sensing and artificial-intelligence-based reconstructions. These are advantageous because shorter examinations decrease the need for sedation and the severity of motion artifacts, increase scanner throughput, and improve system efficiency. In this review we discuss a framework for image acceleration in children that includes the synergistic use of state-of-the-art MRI hardware and optimized pulse sequences. The discussion is framed within the context of pediatric radiology and incorporates the authors’ experience in deploying these techniques in routine clinical practice.
Background
Millions of children experienced surgery procedures requiring general anesthesia (GA). Any potential neurodevelopmental risks of pediatric anesthesia can be a serious public health issue. Various animal studies have provided evidence that commonly used GA induced a variety of morphofunctional alterations in the developing brain of juvenile animals.
Methods
We conducted a systematic review to provide a brief overview of preclinical studies and summarize the existing clinical studies. Comprehensive literature searches of PubMed, EMBASE, CINAHL, OVID Medline, Web of Science, and the Cochrane Library were conducted using the relevant search terms “general anesthesia,” “neurocognitive outcome,” and “children.” We included studies investigating children who were exposed to single or multiple GA before 18, with long-term neurodevelopment outcomes evaluated after the exposure(s).
Results
Seventy-two clinical studies originating from 18 different countries published from 2000 to 2022 are included in this review, most of which are retrospective studies ( n = 58). Two-thirds of studies ( n = 48) provide evidence of negative neurocognitive effects after GA exposure in children. Neurodevelopmental outcomes are categorized into six domains: academics/achievement, cognition, development/behavior, diagnosis, brain studies, and others. Most studies focusing on children <7 years detected adverse neurocognitive effects following GA exposure, but not all studies consistently supported the prevailing view that younger children were at greater risk than senior ones. More times and longer duration of exposures to GA, and major surgeries may indicate a higher risk of negative outcomes.
Conclusion
Based on current studies, it is necessary to endeavor to limit the duration and numbers of anesthesia and the dose of anesthetic agents. For future studies, we require cohort studies with rich sources of data and appropriate outcome measures, and carefully designed and adequately powered clinical trials testing plausible interventions in relevant patient populations.
Background
Chronic nonbacterial osteomyelitis (CNO), also known as chronic recurrent multifocal osteomyelitis, is a noninfectious autoinflammatory disorder that occurs primarily in children and adolescents and is characterized by episodic musculoskeletal pain with a protracted course.
Main body
Traditionally, the diagnosis of CNO is made by exclusion and commonly requires bone biopsy to rule out infection and malignancy. However, bone biopsy may be avoided when imaging and clinical characteristic features are present, such as multifocal bone lesions at typical sites, no constitutional symptoms and no signs of infection in laboratory test results. Whole-body magnetic resonance imaging (WB-MRI) can assess signs of acute and chronic inflammation and enables the detection of CNO typical patterns of lesion location and distribution, thereby helping to exclude differential diagnosis. The goal of the present study paper is to review the main clinical and imaging aspects of the disease with emphasis on the role of WB-MRI in the diagnosis, assessment of disease burden and follow-up monitoring.
Conclusion
Radiologists need to be familiar with the imaging features to suggest the diagnosis as the early therapy may help to avoid irreversible secondary damage of skeletal system.
Whole-body MRI is increasingly used in the evaluation of a range of oncological and non-oncological diseases in infants, children and adolescents. Technical innovation in MRI scanners, coils and sequences have enabled whole-body MRI to be performed more rapidly, offering large field-of-view imaging suitable for multifocal and multisystem disease processes in a clinically useful timeframe. Together with a lack of ionizing radiation, this makes whole-body MRI especially attractive in the pediatric population. Indications include lesion detection in cancer predisposition syndrome surveillance and in the workup of children with known malignancies, and diagnosis and monitoring of a host of infectious and non-infectious inflammatory conditions. Choosing which patients are most likely to benefit from this technology is crucial, but so is adjusting protocols to the patient and disease to optimize lesion detection. The focus of this review is on protocols and the elements impacting image acquisition in pediatric whole-body MRI. We consider the practical aspects, from scanner and coil selection to patient positioning, single-center generic and indication-specific protocols with technical parameters, motion reduction strategies and post-processing. When optimized, collectively these lead to better standardization of whole-body MRI, and when married to systematic analysis and interpretation, they can improve diagnostic accuracy.
Background
The Toronto protocol for cancer surveillance in children with Li-Fraumeni syndrome has been adopted worldwide.
Objective
To assess the diagnostic accuracy of the imaging used in this protocol.
Materials and methods
We conducted a blinded retrospective review of imaging modalities in 31 pediatric patients. We compared imaging findings with the reference standards, which consisted of (1) histopathological diagnosis, (2) corresponding dedicated imaging or subsequent surveillance imaging or (3) clinical outcomes. We individually analyzed each modality’s diagnostic performance for cancer detection and assessed it on a per-study basis for chest and abdominal regional whole-body MRI (n=115 each), brain MRI (n=101) and abdominal/pelvic US (n=292), and on a per-lesion basis for skeleton/soft tissues on whole-body MRI (n=140).
Results
Of 763 studies/lesions, approximately 80% had reference standards that identified 4 (0.7%) true-positive, 523 (85.3%) true-negative, 5 (0.8%) false-positive, 3 (0.5%) false-negative and 78 (12.7%) indeterminate results. There were 3 true-positives on whole-body MRI and 1 true-positive on brain MRI as well as 3 false-negatives on whole-body MRI. Sensitivities and specificities of tumor diagnosis using a worst-case scenario analysis were, respectively, 40.0% (95% confidence interval [CI]: 7.3%, 83.0%) and 38.2% (95% CI: 29.2%, 48.0%) for skeleton/soft tissues on whole-body MRI; sensitivity non-available and 97.8% (95% CI: 91.4%, 99.6%) for chest regional whole-body MRI; 100.0% (95% CI: 5.5%, 100.0%) and 96.8% (95% CI: 90.2%, 99.2%) for abdominal regional whole-body MRI; sensitivity non-available and 98.3% (95% CI: 95.3, 99.4) for abdominal/pelvic US; and 50.0% (95% CI: 2.7%, 97.3%) and 93.8% (95% CI: 85.6%, 97.7%) for brain MRI.
Conclusion
Considerations for optimizing imaging protocol, defining criteria for abnormalities, developing a structured reporting system, and practicing consensus double-reading may enhance the diagnostic accuracy for tumor surveillance.
Objective
To assess the effectiveness of whole-body MRI (WB-MRI) in early diagnosis of chronic recurrent multifocal osteomyelitis (CRMO) and the prediction of clinical response through quantitative MRI features.
Methods
20 children (mean age, 10.3 years; range, 5–14 years) with CRMO underwent WB-MRI and were assessed with a clinical score (Jansson) at baseline (median time after first encounter, 8 months) and follow-up (median time after baseline, 11.5 months). Baseline WB-MRI scans were classified as early (within 6 months after first encounter) and late. Clinical responders and non-responders were compared regarding number and localization of bone lesions, lesion volume and T2 signal intensity (SI) ratio (lesion to muscle).
Results
Diagnosis of CRMO was made promptly in the early WB-MRI group (n = 10; median, 3 months) compared to the late WB-MRI group (n = 10; 18 months; p = 0.006). Bone lesions were mainly located in the lower extremities (n = 119/223; 53%). No significant difference was detected regarding the number of bone lesions and lesion volume in the subgroups of clinical responders (n = 10) and non-responders (n = 10). Responders showed a higher volume reduction of bone lesions at follow-up compared to non-responders (p = 0.03). Baseline and follow-up SI ratios were lower in responders (5.6 and 5.8 vs 6.1 and 7.2; p = 0.047 and p = 0.005).
Conclusion
The use of WB-MRI within 6 months of disease suspicion may serve as a benchmark to support early diagnosis of CRMO. T2 SI ratios and the reduction of lesions’ volume correlate with clinical outcome.
Advances in knowledge
WB-MRI at an early stage of suspected CRMO plays a key role for early diagnosis. This is the first study showing that quantitative MRI features are suitable for response assessment and can be used as prognostic markers for the prediction of clinical response.
Whole-body magnetic resonance imaging (WB-MRI) is a noninvasive imaging method that can be used to diagnose and stage tumors, as well as to assess therapeutic responses in oncology. The objective of this meta-analysis was to evaluate the accuracy of WB-MRI for the diagnosis of metastases in pediatric patients. The following electronic databases were searched: Medline, Embase, Cochrane Central Register of Controlled Trials, Scientific Electronic Library Online, Latin-American and Caribbean Health Sciences Literature, Cumulative Index to Nursing and Allied Health Literature, Web of Science, and ClinicalTrials.gov. All of the selected studies included children and adolescents with histopathological confirmation of a primary tumor. Collectively, the studies included 118 patients ranging in age from 7 months to 19 years. The pooled sensitivity and specificity of WB-MRI were, respectively, 0.964 (95% CI: 0.944-0.978; I2 = 0%) and 0.902 (95% CI: 0.882-0.919; I2 = 98.4%), with an area under the curve (AUC) of 0.991. We found that WB-MRI had good accuracy for the diagnosis of metastases in pediatric patients and could therefore provide an alternative to complete the staging of tumors in such patients, being a safer option because it does not involve the use of ionizing radiation.
Whole-body magnetic resonance imaging (WB-MRI) is currently recommended for cancer screening in adult and paediatric subjects with cancer predisposition syndromes, representing a substantial aid for prolonging health and survival of these subjects with a high oncological risk. Additionally, the number of studies exploring the use of WB-MRI for cancer screening in asymptomatic subjects from the general population is growing. The primary aim of this review was to analyse the acquisition protocols found in the literature, in order to identify common sequences across published studies and to discuss the need of additional ones for specific populations. The secondary aim of this review was to provide a synthesis of current recommendations regarding the use of WB-MRI for cancer screening.
Whole-body magnetic resonance imaging (WB-MRI) has gained importance in the field of musculoskeletal oncology over the last decades, consisting in a one-stop imaging method that allows a wide coverage assessment of both bone and soft tissue involvement. WB-MRI is valuable for diagnosis, staging, and follow-up in many oncologic diseases and is especially advantageous for the pediatric population since it avoids redundant examinations and exposure to ionizing radiation in patients who often undergo long-term surveillance. Its clinical application has been studied in many pediatric neoplasms, such as cancer predisposition syndromes, Langerhans cell histiocytosis, lymphoma, sarcomas, and neuroblastoma. The addition of diffusion-weighted sequences allows functional evaluation of neoplastic lesions, which is helpful in the assessment of viable tumor and response to treatment after neoadjuvant or adjuvant therapy. WB-MRI is an excellent alternative to fluorodeoxyglucose-positron emission tomography/computed tomography in oncologic children, with comparable accuracy and the convenience of being radiation-free, fast to perform, and available at a similar cost. The development of new techniques and protocols makes WB-MRI increasingly faster, safer, and more accessible, and it is important for referring physicians and radiologists to recognize the role of this imaging method in pediatric oncology.
Level of Evidence
4
Technical Efficacy Stage
2
Approximately 20% of patients diagnosed with a phaeochromocytoma or paraganglioma carry a germline mutation in one of the succinate dehydrogenase (SDHx) genes (SDHA, SDHB, SDHC and SDHD), which encode the four subunits of the SDH enzyme. When a pathogenic SDHx mutation is identified in an affected patient, genetic counselling is proposed for first-degree relatives. Optimal initial evaluation and follow-up of people who are asymptomatic but might carry SDHx mutations have not yet been agreed. Thus, we established an international consensus algorithm of clinical, biochemical and imaging screening at diagnosis and during surveillance for both adults and children. An international panel of 29 experts from 12 countries was assembled, and the Delphi method was used to reach a consensus on 41 statements. This Consensus Statement covers a range of topics, including age of first genetic testing, appropriate biochemical and imaging tests for initial tumour screening and follow-up, screening for rare SDHx-related tumours and management of elderly people who have an SDHx mutation. This Consensus Statement focuses on the management of asymptomatic SDHx mutation carriers and provides clinicians with much-needed guidance. The standardization of practice will enable prospective studies in the near future.
Artificial intelligence (AI) uses computers to mimic cognitive functions of the human brain, allowing inferences to be made from generally large datasets. Traditional machine learning (e.g., decision tree analysis, support vector machines) and deep learning (e.g., convolutional neural networks) are two commonly employed AI approaches both outside and within the field of medicine. Such techniques can be used to evaluate medical images for the purposes of automated detection and segmentation, classification tasks (including diagnosis, lesion or tissue characterization, and prediction), and image reconstruction. In this review article we highlight recent literature describing current and emerging AI methods applied to abdominal imaging (e.g., CT, MRI and US) and suggest potential future applications of AI in the pediatric population.
Pediatric patients with cancer predisposition syndromes are at increased risk of developing malignancies compared with their age-matched peers, necessitating regular surveillance. Screening protocols differ among syndromes and are composed of a number of elements, imaging being one. Surveillance can be initiated in infants, children and adolescents with a tumor known or suspected of being related to a cancer predisposition syndrome or where genetic testing identifies a germline pathogenic gene variant in an asymptomatic child. Pre-symptomatic detection of malignant neoplasms offers potential to improve treatment options and survival outcomes, but the benefits and risks of screening need to be weighed, particularly with variable penetrance in many cancer predisposition syndromes. In this review we discuss the benefits and risks of surveillance imaging and the importance of integrating imaging and non-imaging screening elements. We explore the principles of surveillance imaging with particular reference to whole-body MRI, considering the strategies to minimize false-negative and manage false-positive whole-body MRI results, the value of standardized nomenclature when reporting risk stratification to better guide patient management, and the need for timely communication of results to allay anxiety. Cancer predisposition syndrome screening is a multimodality, multidisciplinary and longitudinal process, so developing formalized frameworks for surveillance imaging programs should enhance diagnostic performance while improving the patient experience.
The rhabdoid tumor (RT) predisposition syndromes 1 and 2 (RTPS1 and 2) are rare genetic conditions rendering young children vulnerable to an increased risk of RT, malignant neoplasms affecting the kidney, miscellaneous soft-part tissues, the liver and the central nervous system (Atypical Teratoid Rhabdoid Tumors, ATRT). Both, RTPS1&2 are due to pathogenic variants (PV) in genes encoding constituents of the BAF chromatin remodeling complex, i.e. SMARCB1 (RTPS1) and SMARCA4 (RTPS2). In contrast to other genetic disorders related to PVs in SMARCB1 and SMARCA4 such as Coffin-Siris Syndrome, RTPS1&2 are characterized by a predominance of truncating PVs, terminating transcription thus explaining a specific cancer risk. The penetrance of RTPS1 early in life is high and associated with a poor survival. However, few unaffected carriers may be encountered. Beyond RT, the tumor spectrum may be larger than initially suspected, and cancer surveillance offered to unaffected carriers (siblings or parents) and long-term survivors of RT is still a matter of discussion. RTPS2 exposes female carriers to an ill-defined risk of small cell carcinoma of the ovaries, hypercalcemic type (SCCOHT), which may appear in prepubertal females. RT surveillance protocols for these rare families have not been established. To address unresolved issues in the care of individuals with RTPS and to propose appropriate surveillance guidelines in childhood, the SIOPe Host Genome working group invited pediatric oncologists and geneticists to contribute to an expert meeting. The current manuscript summarizes conclusions of the panel discussion, including consented statements as well as non-evidence-based proposals for validation in the future.
Background
Postmortem magnetic resonance imaging (MRI) in perinatal and childhood deaths is increasingly used as a noninvasive adjunct or alternative to autopsy. Imaging protocols vary between centres and consensus guidelines do not exist.
Objective
Our aim was to develop practical, standardised recommendations for perinatal postmortem MRI.
Materials and methods
Recommendations were based on the results of two surveys regarding local postmortem MRI practices sent electronically to all 14 members of the European Society of Paediatric Radiology (ESPR) Postmortem Imaging Task Force and 17 members of the International Society of Forensic Radiology and Imaging Task Force (25 different centres).
Results
Overall, 11/14 (78.6%) respondents from different institutions perform postmortem MRI. All of these centres perform postmortem MRI for perinatal and neonatal deaths, but only 6/11 (54.5%) perform imaging in older children.
Conclusion
We propose a clinical standard for postmortem MRI sequences plus optional sequences for neuroimaging and cardiac anatomy depending on available scanning time and referral indications.
Importance
Previous studies have demonstrated that adolescents and young adults (AYAs) with cancer are a distinct cancer population; however, research on long-term epidemiological trends and characteristics of cancers in AYAs is lacking.
Objective
To characterize the epidemiology of cancer in AYAs aged 15 to 39 years with respect to (1) patient demographic characteristics, (2) frequencies of cancer types, and (3) cancer incidence trends over time.
Design, Setting, and Participants
This retrospective, serial cross-sectional, population-based study used registry data from the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 1973, to December 31, 2015 (SEER 9 and SEER 18). The study population was from geographically distinct US regions, chosen to represent the racial and ethnic heterogeneity of the country. Initial analyses were performed from January 1 to August 31, 2019.
Main Outcomes and Measures
Incidence rates and descriptive epidemiological statistics for patients aged 15 to 39 years with invasive cancer.
Results
A total of 497 452 AYAs diagnosed from 1973 to 2015 were included in this study, with 293 848 (59.1%) female and 397 295 (79.9%) White participants. As AYAs aged, an increase in the relative incidence of carcinomas and decrease in the relative incidence of leukemias, lymphomas, germ cell and trophoblastic neoplasms, and neoplasms of the central nervous system occurred. Among the female AYAs, 72 564 (24.7%) were diagnosed with breast carcinoma; 48 865 (16.6%), thyroid carcinoma; and 33 828 (11.5%), cervix and uterus carcinoma. Among the male AYAs, 37 597 (18.5%) were diagnosed with testicular cancer; 20 850 (10.2%), melanoma; and 19 532 (9.6%), non-Hodgkin lymphoma. The rate of cancer in AYAs increased by 29.6% from 1973 to 2015, with a mean annual percentage change (APC) per 100 000 persons of 0.537 (95% CI, 0.426-0.648; P < .001). Kidney carcinoma increased at the greatest rate for both male (APC, 3.572; 95% CI, 3.049-4.097; P < .001) and female (APC, 3.632; 95% CI, 3.105-4.162; P < .001) AYAs.
Conclusions and Relevance
In this cross-sectional, US population-based study, cancer in AYAs was shown to have a unique epidemiological pattern and is a growing health concern, with many cancer subtypes having increased in incidence from 1973 to 2015. Continued research on AYA cancers is important to understanding and addressing the distinct health concerns of this population.
Background
The purpose of this study was to determine whether whole-body MRI (WBMRI) with diffusion-weighted sequences, which is free of ionizing radiation, can perform as well as traditional methods when used alone for staging or follow-up of pediatric cancer patients.
Methods
After obtaining approval from our institutional research ethics committee and appropriate informed consent, we performed 34 examinations in 32 pediatric patients. The examinations were anonymized and analyzed by two radiologists with at least 10 years’ experience.
Results
The sensitivity and specificity findings, respectively, were as follows: 100% and 100% for primary tumor; 100% and 86% for bone metastasis; 33% and 100% for lung metastasis; 85% and 100% for lymph node metastasis; and 100% and 62% for global investigation of primary or secondary neoplasias. We observed excellent interobserver agreement for WBMRI and excellent agreement with standard staging examination results.
Conclusions
Our results suggest that pediatric patients can be safely imaged with WBMRI, although not as the only tool but in association with low-dose chest CT (for subcentimeter pulmonary nodules). However, additional exams with ionizing radiation may be necessary for patients who tested positive to correctly quantify and locate the lesions.
Background:
To analyse the influence of whole body (wb)-MRI on patient management compared to routine diagnostic tests in patients with fever of unknown origin (FUO).
Methods:
Twenty-four patients with FUO, defined as illness of more than three weeks with fever greater than 38.3 °C, underwent wb-MRI at a 1.5 T MR-system. The MR-protocol consisted of the following sequences: axial T1 VIBE, coronal T2-TIRM and a coronal echoplanar diffusion weighted sequence (overall acquisition time 29:39 min:s). Furthermore, laboratory findings, chest-x-ray, abdominal ultrasound, CT-scans and/or PET-CT scans were evaluated and compared to the wb-MRI findings in regard to treatment changes.
Results:
Wb-MRI yielded a correct diagnosis in 70% of the patients. In 46% the inflammatory focus was exclusively detected by wb-MRI. Focus detection by wb-MRI led to a subsequent change of the clinical management in 92% of the patients. In 6 patients both a wb-MRI and a PET-CT were performed yielding the correct diagnosis in the same 4 of 6 patients for both imaging modalities.
Conclusions:
Wb-MRI appears to be of value in the evaluation of FUO patients, allowing for optimized treatment by increasing diagnostic certainty. Due to its lack of nephrotoxicity and ionizing radiation it may be preferred over standard imaging techniques and PET-CT in the future. However, given the low number of patients in our trial, further prospective studies have to be performed to confirm our results.
Purpose of review:
To describe in detail the clinical synopsis and pathophysiology of chronic non-bacterial osteomyelitis and SAPHO syndrome.
Recent findings:
Chronic non-bacterial osteomyelitis (CNO) has been identified as a disease entity for almost 50 years. This inflammatory bone disorder is characterized by osteolytic as well as hyperostotic/osteosclerotic lesions. It is chronic in nature, but it can present with episodic flairs and phases of remission, which have led to the denomination "chronic recurrent osteomyelitis", with its severe multifocal form "chronic recurrent multifocal osteomyelitis" (CRMO). For almost three decades, an infectious aetiology had been considered, since especially Propionibacterium acnes had been isolated from bone lesions of individual patients. However, this concept has been challenged since long-term antibiotic therapy did not alter the course of disease and modern microbiological techniques (including PCR) failed to confirm bone infection as an underlying cause. Over recent years, a profound dysregulation of cytokine expression profiles has been demonstrated in innate immune cells of CNO patients. A hallmark of monocytes from CNO patients is the failure to produce immune regulatory cytokines interleukin-10 (IL-10) and IL-19, which have been linked with genetic and epigenetic alterations. Subsequently, a significant upregulation of pro-inflammatory, NLRP3 inflammasome-dependent cytokines (IL-1β and TNF-α), has been demonstrated. The current knowledge on CNO, the underlying molecular pathophysiology, and modern imaging strategies are summarized; differential diagnoses, treatment options, outcome measures, as well as quality of life studies are discussed.
Whole-body magnetic resonance imaging (MRI) is increasingly being used for a number of indications. Our aim was to review and describe indications and scan protocols for diagnostic value of whole-body MRI for multifocal disease in children and adolescents, we conducted a systematic search in Medline, Embase and Cochrane for all published papers until November 2018. Relevant subject headings and free text words were used for the following concepts: 1) whole-body, 2) magnetic resonance imaging and 3) child and/or adolescent. Included were papers in English with a relevant study design that reported on the use and/or findings from whole-body MRI examinations in children and adolescents. This review includes 54 of 1,609 papers identified from literature searches. Chronic nonbacterial osteomyelitis, lymphoma and metastasis were the most frequent indications for performing a whole-body MRI. The typical protocol included a coronal STIR (short tau inversion recovery) sequence with or without a coronal T1-weighted sequence. Numerous studies lacked sufficient data for calculating images resolution and only a few studies reported the acquired voxel volume, making it impossible for others to reproduce the protocol/images. Only a minority of the included papers assessed reliability tests and none of the studies documented whether the use of whole-body MRI affected mortality and/or morbidity. Our systematic review confirms significant variability of technique and the lack of proven validity of MRI findings. The information could potentially be used to boost attempts towards standardization of technique, reporting and guidelines development.
To date, diffusion weighted imaging (DWI) is included in routine magnetic resonance imaging (MRI) protocols for several cancers. The real additive role of DWI lies in the “functional” information obtained by probing the free diffusivity of water molecules into intra and inter-cellular spaces that in tumors mainly depend on cellularity. Although DWI has not gained much space in some oncologic scenarios, this non-invasive tool is routinely used in clinical practice and still remains a hot research topic: it has been tested in almost all cancers to differentiate malignant from benign lesions, to distinguish different malignant histotypes or tumor grades, to predict and/or assess treatment responses, and to identify residual or recurrent tumors in follow-up examinations. In this review, we provide an up-to-date overview on the application of DWI in oncology.
The purpose of this recommendation of the Oncology Task Force of the European Society of Paediatric Radiology (ESPR) is to indicate reasonable applications of whole-body MRI in children with cancer and to address useful protocols to optimize workflow and diagnostic performance. Whole-body MRI as a radiation-free modality has been increasingly performed over the last two decades, and newer applications, as in screening of children with germ-line mutation cancer-related gene defects, are now widely accepted. We aim to provide a comprehensive outline of the diagnostic value for use in daily practice. Based on the results of our task force session in 2018 and the revision in 2019 during the ESPR meeting, we summarized our group’s experiences in whole-body MRI. The lack of large evidence by clinical studies is challenging when focusing on a balanced view regarding the impact of whole-body MRI in pediatric oncology. Therefore, the final version of this recommendation was supported by the members of Oncology Task Force.
Background:
The number of studies describing the use of whole-body magnetic resonance imaging (WB-MRI) for screening of malignant tumours in asymptomatic subjects is increasing. Our aim is to review the methodologies used and the results of the published studies on per patient and per lesion analysis, and to provide recommendations on the use of WB-MRI for cancer screening.
Main body:
We identified 12 studies, encompassing 6214 WB-MRI examinations, which provided the rates of abnormal findings and findings suspicious for cancer in asymptomatic subjects, from the general population. Eleven of 12 studies provided imaging protocols that included T1- and T2-weighted sequences, while only five included diffusion weighted imaging (DWI) of the whole body. Different categorical systems were used for the classification and the management of abnormal findings. Of 17,961 abnormal findings reported, 91% were benign, while 9% were oncologically relevant, requiring further investigations, and 0.5% of lesions were suspicious for cancer. A per-subject analysis showed that just 5% of subjects had no abnormal findings, while 95% had abnormal findings. Findings requiring further investigation were reported in 30% of all subjects, though in only 1.8% cancer was suspected. The overall rate of histologically confirmed cancer was 1.1%.
Conclusion:
WB-MRI studies of cancer screening in the asymptomatic general population are too heterogeneous to draw impactful conclusions regarding efficacy. A 5-point lesion scale based on the oncological relevance of findings appears the most appropriate for risk-based management stratification. WB-MRI examinations should be reported by experienced oncological radiologists versed on WB-MRI reading abnormalities and on onward referral pathways.
Background:
Feed and swaddle is a technique in which an infant is fed and allowed to fall asleep to facilitate diagnostic imaging. This study reviews our experience and diagnostic success in premature and term infants up to 6 months old undergoing brain magnetic resonance imaging (MRI) using a feed and swaddle technique and with comparable patients imaged under anesthesia.
Methods:
We reviewed the charts of all infants ≤ 6 months who underwent brain MRI at our institution between January 1, 2013 and March 3, 2016. We recorded and analyzed demographic information, scan indication, scan length, prematurity status, anesthetic technique if used, complications, and diagnostic success or failure.
Results:
164 term infants underwent brain MRI using a feed and swaddle technique. The success rate in term infants < 90 days was 91.1% (113/124) versus 95.0% (38/40) in infants ≥ 90 days and ≤ 181 days old. 53 premature infants underwent feed and swaddle for brain MRI with a diagnostic success rate of 92.5% (49/53). No complications were noted in any feed and swaddle patients. Those who received anesthesia had a diagnostic success rate of 100% (70/70) but experienced complications including hypoxemia, 14.3% (10/70); hypothermia, 18.9% (10/53); bradycardia, 10.1% (7/69); and hypotension, 4.2% (3/70).
Conclusion:
Given the high rate of success and absence of complications with feed and swaddle in children ≤ 6 months for brain MRI and the presence of anesthesia-related complications, most infants should undergo a trial of feed and swaddle prior to undergoing brain MRI with anesthesia.
Background
The yield of whole‐body MRI for preventive health screening is currently not completely clear.
Purpose
To systematically review the prevalence of whole‐body MRI findings in asymptomatic subjects.
Study Type
Systematic review and meta‐analysis.
Subjects
MEDLINE and Embase were searched for original studies reporting whole‐body MRI findings in asymptomatic adults without known disease, syndrome, or genetic mutation. Twelve studies, comprising 5373 asymptomatic subjects, were included.
Field Strength/Sequence
1.5T or 3.0T, whole‐body MRI.
Assessment
The whole‐body MRI literature findings were extracted and reviewed by two radiologists in consensus for designation as either critical or indeterminate incidental finding.
Statistical Tests
Data were pooled using a random effects model on the assumption that most subjects had ≤1 critical or indeterminate incidental finding. Heterogeneity was assessed by the I² statistic.
Results
Pooled prevalences of critical and indeterminate incidental findings together and separately were 32.1% (95% confidence interval [CI]: 18.3%, 50.1%), 13.4% (95% CI: 9.0%, 19.5%), and 13.9% (95% CI: 5.4%, 31.3%), respectively. There was substantial between‐study heterogeneity (I² = 95.6–99.1). Pooled prevalence of critical and indeterminate incidental findings together was significantly higher in studies that included (cardio)vascular and/or colon MRI compared with studies that did not (49.7% [95% CI, 26.7%, 72.9%] vs. 23.0% [95% CI, 5.5%, 60.3%], P < 0.001). Pooled proportion of reported verified critical and indeterminate incidental findings was 12.6% (95% CI: 3.2%, 38.8%). Six studies reported false‐positive findings, yielding a pooled proportion of 16.0% (95% CI: 1.9%, 65.8%). None of the included studies reported long‐term (>5‐year) verification of negative findings. Only one study reported false‐negative findings, with a proportion of 2.0%.
Data Conclusion
Prevalence of critical and indeterminate incidental whole‐body MRI findings in asymptomatic subjects is overall substantial and with variability dependent to some degree on the protocol. Verification data are lacking. The proportion of false‐positive findings appears to be substantial.
Level of Evidence: 4
Technical Efficacy: Stage 3
J. Magn. Reson. Imaging 2019.
Whole-body MRI (WBMRI) is an integral part of screening infants, children and adolescents for pre-symptomatic neoplasms in certain cancer predisposition syndromes (CPS). This includes Li-Fraumeni and Constitutional Mismatch Repair Deficiency syndromes, among others. The list of syndromes where WBMRI adds value, as part of a comprehensive surveillance protocol, continues to evolve in response to new evidence, growing experience and more widespread adoption of WBMRI. In July 2023, the American Association of Cancer Research (AACR) reconvened an international, multidisciplinary panel to revise and update recommendations stemming from the 2016 AACR Special Workshop on Childhood Cancer Predisposition. That initial meeting resulted in a series of publications in Clinical Cancer Research in 2017, including “Pediatric Cancer Predisposition Imaging: Focus on Whole Body MRI”. This 2024 review of WBMRI in CPS updates the 2017 WBMRI publication, the revised recommendations derived from the 2023 AACR Childhood Cancer Predisposition Workshop based on available data, societal guidelines and expert opinion. Different aspects of acquiring and interpreting WBMRI including diagnostic accuracy are discussed. Application of WBMRI in resource poor environments, as well as integration of whole-body imaging techniques with emerging technologies such as cell-free DNA, or liquid biopsies, and artificial intelligence/machine learning are also considered.
Artificial intelligence (AI) is transforming medical imaging of adult patients. However, its utilization in pediatric oncology imaging remains constrained, in part due to the inherent data scarcity associated with childhood cancers. Pediatric cancers are rare, and imaging technologies are evolving rapidly, leading to insufficient data of a particular type to effectively train these algorithms. The small market size of pediatrics compared to adults could also contribute to this challenge, as market size is a driver of commercialization. This article provides an overview of the current state of AI applications for pediatric cancer imaging, including applications for medical image acquisition, processing, reconstruction, segmentation, diagnosis, staging, and treatment response monitoring. While current developments are promising, impediments due to diverse anatomies of growing children and nonstandardized imaging protocols have led to limited clinical translation thus far. Opportunities include leveraging reconstruction algorithms to achieve accelerated low-dose imaging and automating the generation of metric-based staging and treatment monitoring scores. Transfer-learning of adult-based AI models to pediatric cancers, multi-institutional data sharing, and ethical data privacy practices for pediatric patients with rare cancers will be keys to unlocking AI's full potential for clinical translation and improved outcomes for these young patients.
Background Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare and aggressive cancer predisposition syndrome. Because a scarcity of data on this condition contributes to management challenges and poor outcomes, we aimed to describe the clinical spectrum, cancer biology, and impact of genetics on patient survival in CMMRD.
Background
Whole‐body metaiodobenzylguanidine ( ¹³¹ I‐MIBG) scintigraphy is the gold standard method to detect neuroblastoma; however, it depends on radioactive material and is expensive. In contrast, whole‐body magnetic resonance imaging (WB‐MRI) is affordable in developing countries and has been shown to be effective in the evaluation of solid tumors. This study aimed to compare the sensitivity and specificity of WB‐MRI with MIBG in the detection of primary tumors and neuroblastoma metastases.
Procedure
This retrospective study enrolled patients with neuroblastoma between 2013 and 2020. All patients underwent WB‐MRI and MIBG at intervals of up to 15 days. The results were marked in a table that discriminated anatomical regions for each patient. Two experts evaluated, independently and in anonymity, the WB‐MRI images, and two others evaluated MIBG. The results were compared in terms of sensitivity and specificity, for each patient, considering MIBG as the gold standard. This study was approved by the UNIFESP Ethics Committee.
Results
Thirty patients with neuroblastoma were enrolled in this study. The age ranged from 1 to 15 years, with a mean of 5.7 years. The interval between exams (WB‐MRI and MIBG) ranged from 1 to 13 days, with an average of 6.67 days. Compared to MIBG, WB‐MRI presented a sensitivity and specificity greater than or equal to 90% for the detection of primary neuroblastoma in bones and lymph nodes. When we consider the patient without individualizing the anatomical regions, WB‐MRI presented sensitivity of 90% and specificity of 73.33%.
Conclusion
In conclusion, WB‐MRI is a sensitive and specific method to detect neuroblastoma in bone and lymph nodes and highly sensible to primary tumor diagnosis, suggesting that this test is a viable alternative in places where MIBG is difficult to access. Studies with a larger number of cases are necessary for definitive conclusions.
Objective
To compare tumor therapy response assessments with whole-body diffusion-weighted imaging (WB-DWI) and 18F-fluorodeoxyglucose ([18F]FDG) PET/MRI in pediatric patients with Hodgkin lymphoma and non-Hodgkin lymphoma.Materials and methodsIn a retrospective, non-randomized single-center study, we reviewed serial simultaneous WB-DWI and [18F]FDG PET/MRI scans of 45 children and young adults (27 males; mean age, 13 years ± 5 [standard deviation]; age range, 1–21 years) with Hodgkin lymphoma (n = 20) and non-Hodgkin lymphoma (n = 25) between February 2018 and October 2022. We measured minimum tumor apparent diffusion coefficient (ADCmin) and maximum standardized uptake value (SUVmax) of up to six target lesions and assessed therapy response according to Lugano criteria and modified criteria for WB-DWI. We evaluated the agreement between WB-DWI- and [18F]FDG PET/MRI–based response classifications with Gwet’s agreement coefficient (AC).ResultsAfter induction chemotherapy, 95% (19 of 20) of patients with Hodgkin lymphoma and 72% (18 of 25) of patients with non-Hodgkin lymphoma showed concordant response in tumor metabolism and proton diffusion. We found a high agreement between treatment response assessments on WB-DWI and [18F]FDG PET/MRI (Gwet’s AC = 0.94; 95% confidence interval [CI]: 0.82, 1.00) in patients with Hodgkin lymphoma, and a lower agreement for patients with non-Hodgkin lymphoma (Gwet’s AC = 0.66; 95% CI: 0.43, 0.90). After completion of therapy, there was an excellent agreement between WB-DWI and [18F]FDG PET/MRI response assessments (Gwet’s AC = 0.97; 95% CI: 0.91, 1).Conclusion
Therapy response of Hodgkin lymphoma can be evaluated with either [18F]FDG PET or WB-DWI, whereas patients with non-Hodgkin lymphoma may benefit from a combined approach.Clinical relevance statementHodgkin lymphoma and non-Hodgkin lymphoma exhibit different patterns of tumor response to induction chemotherapy on diffusion-weighted MRI and PET/MRI.Key Points
• Diffusion-weighted imaging has been proposed as an alternative imaging to assess tumor response without ionizing radiation.
• After induction therapy, whole-body diffusion-weighted imaging and PET/MRI revealed a higher agreement in patients with Hodgkin lymphoma than in those with non-Hodgkin lymphoma.
• At the end of therapy, whole-body diffusion-weighted imaging and PET/MRI revealed an excellent agreement for overall tumor therapy responses for all lymphoma types.
Purposes:
To review the uses of AI for magnetic resonance (MR) imaging assessment of primary pediatric cancer and identify common literature topics and knowledge gaps. To assess the adherence of the existing literature to the Checklist for Artificial Intelligence in Medical Imaging (CLAIM) guidelines.
Materials and methods:
A scoping literature search using MEDLINE, EMBASE and Cochrane databases was performed, including studies of > 10 subjects with a mean age of < 21 years. Relevant data were summarized into three categories based on AI application: detection, characterization, treatment and monitoring. Readers independently scored each study using CLAIM guidelines, and inter-rater reproducibility was assessed using intraclass correlation coefficients.
Results:
Twenty-one studies were included. The most common AI application for pediatric cancer MR imaging was pediatric tumor diagnosis and detection (13/21 [62%] studies). The most commonly studied tumor was posterior fossa tumors (14 [67%] studies). Knowledge gaps included a lack of research in AI-driven tumor staging (0/21 [0%] studies), imaging genomics (1/21 [5%] studies), and tumor segmentation (2/21 [10%] studies). Adherence to CLAIM guidelines was moderate in primary studies, with an average (range) of 55% (34%-73%) CLAIM items reported. Adherence has improved over time based on publication year.
Conclusion:
The literature surrounding AI applications of MR imaging in pediatric cancers is limited. The existing literature shows moderate adherence to CLAIM guidelines, suggesting that better adherence is required for future studies.
Aim:
To evaluate the diagnostic accuracy of whole-body (WB) magnetic resonance imaging (MRI) utilising three-dimensional (3D) short tau inversion recovery (STIR) and T1-weighted in/opposed-phase MRI in the detection of neuroblastoma bone marrow metastasis compared to 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)/computed tomography (CT).
Materials and methods:
A prospective study of 20 consecutive histopathologically proven neuroblastoma patients enrolled in this study from January 2021 to August 2022. WB MRI and FDG-PET/CT were performed for all cases. Bone marrow biopsy served as the standard of reference. Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy were calculated. In addition, lesion-by-lesion analysis was performed and the number of bone marrow metastatic lesions in different body segments using both imaging methods was recorded and compared.
Results:
WB MRI correctly identified true positives and true negatives in all cases with a sensitivity and specificity of 100%. In contrast, FDG-PET/CT showed two false-negative cases that resulted in a sensitivity, specificity, PPV, NPV, and accuracy of 86.7%, 100%, 100%, 71.4%, and 92%, respectively. In the lesion-by-lesion analysis, WB MRI detected more (24.3%) bone marrow metastatic lesions than FDG-PET/CT.
Conclusion:
Whole-body MRI can reliably identify neuroblastoma bone marrow infiltration, and could be an alternative to PET/CT in that regard.
Purpose
To evaluate the whole-body MRI (WBMRI) findings in children with juvenile dermatomyositis (JDM) and correlate them with clinical and laboratory results.
Method
We conducted the present prospective study from October 2019 to September 2021. Thirty children (8.2 ± 3.88 years) with a diagnosis of JDM based on EULAR/ACR classification criteria underwent WBMRI using short tau inversion recovery, diffusion-weighted, and T1 modified DIXON (precontrast and postcontrast) sequences. WBMRI scans were analysed independently by two radiologists for abnormal signal intensity and enhancement in the different muscle groups. Radiological findings were correlated with clinical examination, muscle enzymes, and inflammatory markers.
Results
WBMRI revealed abnormal signal intensity and diffusion restriction, predominantly in the thigh (n=21, 70% children), calf (n=18, 60% children), and hip (n=16, 53.3% children) muscles. A significant positive correlation was observed between the serum total creatinine kinase and lactic dehydrogenase levels, with altered signal intensity and diffusion restriction in the paraspinal and thigh muscles. Diffusion restriction in the hip and calf muscles also showed significant positive correlations with these enzymes. Significant positive correlations were detected between lower limb muscle strength and altered signal intensity and diffusion restriction in the thigh (p=0.023) and calf (p=0.002) muscles. Postcontrast images did not yield any additional useful information.
Conclusions
WBMRI provided useful information in evaluation of the extent and distribution of findings in children with JDM. There were significant positive correlations between MRI findings and muscle enzymes and clinical examination results. The addition of contrast to the WBMRI protocol did not provide any additional advantage.
Introduction/aim:
The most common limb girdle muscular dystrophy (LGMD) worldwide is LGMD type R1 (LGMDR1). The aim of this study was to correlate the magnetic resonance imaging (MRI) findings with functional scores and to describe the whole-body MRI (WBMRI) pattern in a LGMDR1 Brazilian cohort.
Methods:
LGMDR1 patients under follow-up in three centers were referred for the study. Clinical data were collected and a functional evaluation was performed, consisting of Gardner-Medwin and Walton (GMW) and Brooke scales. All patients underwent a WBMRI study (1.5T) with axial T1 and STIR images. Fifty-one muscles were semiquantitatively assessed regarding fatty infiltration and muscle edema.
Results:
The study group consisted of 18 patients. The highest fatty infiltration scores involved the serratus anterior, biceps femoris long head, adductor magnus and lumbar erector spinae. There was a latero-medial and caudo-cranial descending gradient of involvement of the paravertebral muscles, with erector spinae being significantly more affected than the transversospinalis muscles (p<0.05). A striped appearance that has been dubbed the "pseudocollagen sign" was present in 72% of the patients. There was a positive correlation between the MRI score and GMW (Rho:0.83) and Brooke (Rho:0.53) scores.
Discussion:
WBMRI in LGMDR1 allows a global patient evaluation including involvement of the paraspinal muscles, usually an underestimated feature in the clinical and imaging study of myopathies. Knowledge of the WBMRI pattern of LGMDR1 involvement can be useful in the diagnostic approach and in future studies to identify the best target muscles to serve as outcome measures in clinical trials.
Lymphatic anomalies comprise a spectrum of disorders ranging from common localized microcystic and macrocystic lymphatic malformations (LMs) to rare complex lymphatic anomalies, including generalized lymphatic anomaly, Kaposiform lymphangiomatosis, central conducting lymphatic anomaly, and Gorham-Stout disease. Imaging diagnosis of cystic LMs is generally straightforward, but complex lymphatic anomalies, particularly those with multi-organ involvement or diffuse disease, may be more challenging to diagnose. Complex lymphatic anomalies are rare but associated with high morbidity. Imaging plays an important role in their diagnosis, and radiologists may be the first clinicians to suggest the diagnosis. Furthermore, radiologists are regularly involved in management given the frequent need for image-guided interventions. For these reasons, it is crucial for radiologists to be familiar with the spectrum of entities comprising complex lymphatic anomalies and their typical imaging findings. In this article, we review the imaging findings of lymphatic anomalies, including LMs and complex lymphatic anomalies. We discuss characteristic imaging findings, multimodality imaging techniques used for evaluation, pearls and pitfalls in diagnosis, and potential complications. We also review recently discovered genetic changes underlying lymphatic anomaly development and the advent of new molecularly targeted therapies.
Integrated PET/MRI has shown significant clinical value for staging and restaging of children with cancer by providing functional and anatomic tumor evaluation with a 1-stop imaging test and with up to 80% reduced radiation exposure compared with 18F-FDG PET/CT. This article reviews clinical applications of 18F-FDG PET/MRI that are relevant for pediatric oncology, with particular attention to the value of PET/MRI for patient management. Early adopters from 4 different institutions share their insights about specific advantages of PET/MRI technology for the assessment of young children with cancer. We discuss how whole-body PET/MRI can be of value in the evaluation of certain anatomic regions, such as soft tissues and bone marrow, as well as specific PET/MRI interpretation hallmarks in pediatric patients. We highlight how whole-body PET/MRI can improve the clinical management of children with lymphoma, sarcoma, and neurofibromatosis, by reducing the number of radiologic examinations needed (and consequently the radiation exposure), without losing diagnostic accuracy. We examine how PET/MRI can help in differentiating malignant tumors versus infectious or inflammatory diseases. Future research directions toward the use of PET/MRI for treatment evaluation of patients undergoing immunotherapy and assessment of different theranostic agents are also briefly explored. Lessons learned from applications in children might also be extended to evaluations of adult patients.
Vascular anomalies represent a spectrum of commonly encountered pediatric soft tissue masses, ranging from a localized cutaneous “birthmark” to systemic and/or life-threatening entities. Many of these lesions have specific implications for the growing musculoskeletal system, potentially affecting lifelong function. Establishing the correct diagnosis can be challenging, but an awareness of typical radiologic and clinical features of the most common entities will expedite the workup and enable appropriate family counseling and therapeutic implementation. This review will focus on the most commonly encountered vascular anomalies, including neoplasms and malformations, affecting the pediatric musculoskeletal system.
Acknowledging the increasing number of studies describing the use of whole-body MRI for cancer screening, and the increasing number of examinations being performed in patients with known cancers, an international multidisciplinary expert panel of radiologists and a geneticist with subject-specific expertise formulated technical acquisition standards, interpretation criteria, and limitations of whole-body MRI for cancer screening in individuals at higher risk, including those with cancer predisposition syndromes. The Oncologically Relevant Findings Reporting and Data System (ONCO-RADS) proposes a standard protocol for individuals at higher risk, including those with cancer predisposition syndromes. ONCO-RADS emphasizes structured reporting and five assessment categories for the classification of whole-body MRI findings. The ONCO-RADS guidelines are designed to promote standardization and limit variations in the acquisition, interpretation, and reporting of whole-body MRI scans for cancer screening. Published under a CC BY 4.0 license Online supplemental material is available for this article.
Childhood malignancies are rarely related to known environmental exposures, and it has become increasingly evident that inherited genetic factors play a substantial causal role. Large-scale sequencing studies have shown that approximately 10% of children with cancer have an underlying cancer predisposition syndrome. The number of recognised cancer predisposition syndromes and cancer predisposition genes are constantly growing. Imaging and laboratory technologies are improving, and knowledge of the range of tumours and risk of malignancy associated with cancer predisposition syndromes is increasing over time. Consequently, surveillance measures need to be constantly adjusted to address these new findings. Management recommendations for individuals with pathogenic germline variants in cancer predisposition genes need to be established through international collaborative studies, addressing issues such as genetic counselling, cancer prevention, cancer surveillance, cancer therapy, psychological support, and social-ethical issues. This Review represents the work by a group of experts from the European Society for Paediatric Oncology (SIOPE) and aims to summarise the current knowledge and define future research needs in this evolving field.
Germline biallelic mutations in one of the mismatch repair genes, mutS homolog 2, mutS homolog 6, mutL homolog 1, or postmeiotic segregation increased 2, result in one of the most aggressive cancer syndromes in humans termed as constitutional mismatch repair deficiency (CMMRD). Individuals with CMMRD are affected with multiple tumors arising from multiple organs during childhood, and these individuals rarely reach adulthood without specific interventions. The most common tumors observed are central nervous system, hematological, and gastrointestinal malignancies. The incidence of CMMRD is expected to be high in low‐resource settings due to a high rate of consanguinity in these regions, and it is thought to be underrecognized and consequently underdiagnosed. This position paper is therefore important to provide a summary of the current situation, and to highlight the necessity of increasing awareness, diagnostic criteria, and surveillance to improve survival for patients and family members.
Objectives
To evaluate musculoskeletal (MSK) radiologist whole-body magnetic resonance imaging (WBMRI) practice patterns in an effort to better understand current MSK clinical utilization and the need for standardized coding.MethodsA 12-question survey was created in Survey Monkey®. The survey was e-mailed to Society of Skeletal Radiology (SSR) members on September 19, 2018. The survey included questions on SSR member demographics and on their experience with WBMRI.ResultsOne hundred sixty-four of 1454 (11%) SSR members responded to the survey. A minority (32%; n = 52/164) of respondents reported that their institutions routinely perform WBMRI. The most common indication was multiple myeloma (78%, n = 51/65). The most commonly utilized sequences were coronal short tau inversion recovery (STIR) (79%, n = 52/66) and coronal T1 without fat saturation (73%, n = 48/66). A large proportion of respondents (48%, n = 31/64) did not know the code used for billing WBMRI at their institutions. Of the remaining respondents, 23% (n = 15/64) reported use of the bone marrow MRI code, 16% (n = 10/64) the chest/abdomen/pelvis combination code, and 9% (n = 6/64) the unlisted MRI procedure code.Conclusion
There is variation in who is responsible for the protocol and interpretation of WBMRI, as well as how the exam is performed and how the exam is coded, which raise barriers to broad implementation. Recent WBMRI guidelines for multiple myeloma and prostate cancer can mitigate many of these barriers, but they do not address the coding and reimbursement challenges. Collaborative multi-society development of a new CPT® code for WBMRI may be a worthwhile endeavor.
We estimate that there will be 13·7 million new cases of childhood cancer globally between 2020 and 2050. At current levels of health system performance (including access and referral), 6·1 million (44·9%) of these children will be undiagnosed. Between 2020 and 2050, 11·1 million children will die from cancer if no additional investments are made to improve access to health-care services or childhood cancer treatment. Of this total, 9·3 million children (84·1%) will be in low-income and lower-middle-income countries. This burden could be vastly reduced with new funding to scale up cost-effective interventions. Simultaneous comprehensive scale-up of interventions could avert 6·2 million deaths in children with cancer in this period, more than half (56·1%) of the total number of deaths otherwise projected. Taking excess mortality risk into consideration, this reduction in the number of deaths is projected to produce a gain of 318 million life-years. In addition, the global lifetime productivity gains of US594 billion, producing a net benefit of 3 for every $1 invested. In sum, the burden of childhood cancer, which has been grossly underestimated in the past, can be effectively diminished to realise massive health and economic benefits and to avert millions of needless deaths.
Imaging and image-guided procedures play an imperative role in the screening, diagnosis, and surveillance of cancer. Although emerging imaging techniques now enable more precise molecular characterization of tumors, multigenetic tumor profiling for targeted therapeutic selection remains limited to direct tissue acquisition. Even in the context of targeted therapy, tumors adapt to acquire resistance. This necessitates serial monitoring, traditionally through tissue acquisition, to identify the molecular mechanism of resistance and to guide second-line therapy. An alternative to tissue acquisition is the collection of circulating tumor markers such as cell-free nucleic acids and circulating tumor cells in the peripheral blood. This noninvasive diagnostic approach is referred to as the liquid biopsy. The liquid biopsy is currently used clinically for therapeutic guidance when tissue acquisition is impossible or when the specimen is inadequate. It is also being studied in the context of screening, diagnosis, and surveillance. As cancer treatment continues to move toward a focus on precision medicine, this developing technology may alter and/or augment the role of imaging in the management of cancer. This review aims to outline the use of liquid biopsy in cancer and its potential impact on diagnostic imaging and image-guided procedures.