Automatic assessment of body composition in children with lymphoma: results of a [18F]FDG-PET/MR study.

OBJECTIVES: To use Dixon-MR images extracted from [18F]FDG-PET/MR scans to perform an automatic, volumetric segmentation and quantification of body composition in pediatric patients with lymphoma. MATERIALS AND METHODS: Pediatric patients with lymphoma examined by [18F]FDG-PET/MR at diagnosis and restaging were included. At each time point, axial fat and water Dixon T1w images of the thighs were automatically segmented and muscle volume, subcutaneous, intramuscular, and intermuscular fat volume were quantified. The metabolic activity of the largest nodal lesion and of muscles and subcutaneous fat was recorded. The paired samples t-test and Spearman's correlation coefficient were applied to evaluate potential differences between the two time points and the relationship between metabolic and body composition metrics, respectively. By logistic regression analysis, the prognostic role of the investigated variables was assessed. The applied significance level was p < 0.05 for all analyses. RESULTS: Thirty-seven patients (mean age ± SD 14 ± 3-years-old; 20 females) matched the inclusion criteria. After chemotherapy (interval between the two PET/MR scans, 56-80 days; median 65 days), muscle volume significantly decreased (629 ± 259 cm3 vs 567 ± 243 cm3, p < 0.001) while subcutaneous, intramuscular and intermuscular fat increased (476 ± 255 cm3 vs 607 ± 254 cm3, p < 0.001; 63 ± 20 cm3 vs 76 ± 26 cm3, p < 0.001; 58 ± 19 cm3 vs 71 ± 23 cm3, p < 0.001); the metabolic activity of the main nodal lesion, muscles, and subcutaneous fat significantly decreased (p < 0.05, each). None of the examined variables acted as predictors of the response to treatment (p = 0.283). A strong correlation between BMI and subcutaneous fat volume at diagnosis (r = 0.675, p < 0.001) and restaging (r = 0.600, p < 0.001) emerged. CONCLUSIONS: The proposed method demonstrated that pediatric patients with lymphoma undergo muscle loss and an increase of subcutaneous fat during treatment. CLINICAL RELEVANCE STATEMENT: The proposed automatic and volumetric MR-based assessment of body composition in children with lymphoma can be used to monitor the effect of chemotherapy and may guide tailored exercise programs during chemotherapy. KEY POINTS: T1w Dixon images can be used for the automatic segmentation and quantification of body composition. Muscle and subcutaneous fat volume do not act as predictors of the response to treatment in children with lymphoma. Chemotherapy induces changes in body composition in children with lymphoma.

Performance evaluation of the 3D-ring cadmium-zinc-telluride (CZT) StarGuide system according to the NEMA NU 1-2018 standard.

BACKGROUND: The application of semi-conductor detectors such as cadmium-zinc-telluride (CZT) in nuclear medicine improves extrinsic energy resolution and count sensitivity due to the direct conversion of gamma photons into electric signals. A 3D-ring pixelated CZT system named StarGuide was recently developed and implemented by GE HealthCare for SPECT acquisition. The system consists of 12 detector columns with seven modules of 16 × 16 CZT pixelated crystals, each with an integrated parallel-hole tungsten collimator. The axial coverage is 27.5 cm. The detector thickness is 7.25 mm, which allows acquisitions in the energy range [40-279] keV. Since there is currently no performance characterization specific to 3D-ring CZT SPECT systems, the National Electrical Manufacturers Association (NEMA) NU 1-2018 clinical standard can be tailored to these cameras. The aim of this study was to evaluate the performance of the SPECT/CT StarGuide system according to the NEMA NU 1-2018 clinical standard specifically adapted to characterize the new 3D-ring CZT. RESULTS: Due to the integrated collimator, the system geometry and the pixelated nature of the detector, some NEMA tests have been adapted to the features of the system. The extrinsic measured energy resolution was about 5-6% for the tested isotopes (99mTc, 123I and 57Co); the maximum count rate was 760 kcps and the observed count rate at 20% loss was 917 kcps. The system spatial resolution in air extrapolated at 10 cm with 99mTc was 7.2 mm, while the SPECT spatial resolutions with scatter were 4.2, 3.7 and 3.6 mm in a central, radial and tangential direction respectively. Single head sensitivity value for 99mTc was 97 cps/MBq; with 12 detector columns, the system volumetric sensitivity reached 520 kcps MBq-1 cc-1. CONCLUSIONS: The performance tests of the StarGuide can be performed according to the NEMA NU 1-2018 standard with some adaptations. The system has shown promising results, particularly in terms of energy resolution, spatial resolution and volumetric sensitivity, potentially leading to higher quality clinical images.

Cutting-Edge Strategies for Renal Tumour-like Lesions in Granulomatosis with Polyangiitis: A Systematic Review.

BACKGROUND: Granulomatosis with polyangiitis (GPA) is characterised by granulomatous inflammation and small-to-medium vessel necrotising vasculitis, mainly affecting respiratory tract and kidneys. Renal involvement presenting as tumour-like lesions poses diagnostic and treatment challenges. METHODS: Following the observation of a GPA patient presenting with multiple renal tumour-like lesions, we conducted a systematic literature review on MEDLINE/PubMed, EMBASE, and Cochrane databases. Data gathered from the literature were analysed to summarise the diagnostic approach, management, and outcome of renal GPA-related tumour-like lesions. RESULTS: a 49-year-old female presented with persistent constitutional symptoms and multiple bilateral renal lesions. Renal biopsy showed chronic interstitial inflammation with necrotising granulomas. Laboratory tests disclosed positive anti-proteinase 3 (PR3) anti-neutrophil cytoplasmic antibody (ANCA) leading to a final diagnosis of GPA. She was effectively treated with high-dose glucocorticoids and rituximab. Literature search yielded 41 articles, concerning 42 GPA patients with renal masses, presenting bilaterally in 23.8% of the cases. Positive PR3-ANCA was observed in 86.5% of the cases. Half of 42 patients showed kidney abnormalities. Treatment with glucocorticoids (83.3%) and immunosuppressive agents (80.9%) resulted in an overall good remission rate and favourable prognosis. CONCLUSIONS: GPA should be considered in the differential diagnoses of kidney tumour-like lesions. The diagnosis is challenging, and histological examination greatly contributes to the diagnostic work-up.

Data-driven analysis of regional brain metabolism in behavioral frontotemporal dementia and late-onset primary psychiatric diseases with frontal lobe syndrome: A PET/MRI study.

Late-onset primary psychiatric disease (PPD) and behavioral frontotemporal dementia (bvFTD) present with a similar frontal lobe syndrome. We compare brain glucose metabolism in bvFTD and late-onset PPD and investigate the metabolic correlates of cognitive and behavioral disturbances through FDG-PET/MRI. We studied 37 bvFTD and 20 late-onset PPD with a mean clinical follow-up of three years. At baseline evaluation, metabolism of the dorsolateral, ventrolateral, orbitofrontal regions and caudate could classify the patients with a diagnostic accuracy of 91% (95% CI: 0.81-0.98%). 45% of PPD showed low-grade hypometabolism in the anterior cingulate and/or parietal regions. Frontal lobe metabolism was normal in 32% of genetic bvFTD and bvFTD with motor neuron signs. Hypometabolism of the frontal and caudate regions could help in distinguishing bvFTD from PPD, except in cases with motor neuron signs and/or genetic bvFTD for which brain metabolism may be less informative.

EANM practice guidelines for an appropriate use of PET and SPECT for patients with epilepsy.

Epilepsy is one of the most frequent neurological conditions with an estimated prevalence of more than 50 million people worldwide and an annual incidence of two million. Although pharmacotherapy with anti-seizure medication (ASM) is the treatment of choice, ~30% of patients with epilepsy do not respond to ASM and become drug resistant. Focal epilepsy is the most frequent form of epilepsy. In patients with drug-resistant focal epilepsy, epilepsy surgery is a treatment option depending on the localisation of the seizure focus for seizure relief or seizure freedom with consecutive improvement in quality of life. Beside examinations such as scalp video/electroencephalography (EEG) telemetry, structural, and functional magnetic resonance imaging (MRI), which are primary standard tools for the diagnostic work-up and therapy management of epilepsy patients, molecular neuroimaging using different radiopharmaceuticals with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) influences and impacts on therapy decisions. To date, there are no literature-based praxis recommendations for the use of Nuclear Medicine (NM) imaging procedures in epilepsy. The aims of these guidelines are to assist in understanding the role and challenges of radiotracer imaging for epilepsy; to provide practical information for performing different molecular imaging procedures for epilepsy; and to provide an algorithm for selecting the most appropriate imaging procedures in specific clinical situations based on current literature. These guidelines are written and authorized by the European Association of Nuclear Medicine (EANM) to promote optimal epilepsy imaging, especially in the presurgical setting in children, adolescents, and adults with focal epilepsy. They will assist NM healthcare professionals and also specialists such as Neurologists, Neurophysiologists, Neurosurgeons, Psychiatrists, Psychologists, and others involved in epilepsy management in the detection and interpretation of epileptic seizure onset zone (SOZ) for further treatment decision. The information provided should be applied according to local laws and regulations as well as the availability of various radiopharmaceuticals and imaging modalities.

Theranostics in Neurooncology: Heading Toward New Horizons.

Therapeutic approaches to brain tumors remain a challenge, with considerable limitations regarding delivery of drugs. There has been renewed and increasing interest in translating the popular theranostic approach well known from prostate and neuroendocrine cancer to neurooncology. Although far from perfect, some of these approaches show encouraging preliminary results, such as for meningioma and leptomeningeal spread of certain pediatric brain tumors. In brain metastases and gliomas, clinical results have failed to impress. Perspectives on these theranostic approaches regarding meningiomas, brain metastases, gliomas, and common pediatric brain tumors will be discussed. For each tumor entity, the general context, an overview of the literature, and future perspectives will be provided. Ongoing studies will be discussed in the supplemental materials. As most theranostic agents are unlikely to cross the blood-brain barrier, the delivery of these agents will be dependent on the successful development and clinical implementation of techniques enhancing permeability and retention. Moreover, the international community should strive toward sufficiently large and randomized studies to generate high-level evidence on theranostic approaches with radioligand therapies for central nervous system tumors.

The evidence-based role of catecholaminergic PET tracers in Neuroblastoma. A systematic review and a head-to-head comparison with mIBG scintigraphy.

BACKGROUND: Molecular imaging is pivotal in staging and response assessment of children with neuroblastoma (NB). [123I]-metaiodobenzylguanidine (mIBG) is the standard imaging method; however, it is characterised by low spatial resolution, time-consuming acquisition procedures and difficult interpretation. Many PET catecholaminergic radiotracers have been proposed as a replacement for [123I]-mIBG, however they have not yet made it into clinical practice. We aimed to review the available literature comparing head-to-head [123I]-mIBG with the most common PET catecholaminergic radiopharmaceuticals. METHODS: We searched the PubMed database for studies performing a head-to-head comparison between [123I]-mIBG and PET radiopharmaceuticals including meta-hydroxyephedrine ([11C]C-HED), 18F-18F-3,4-dihydroxyphenylalanine ([18F]DOPA) [124I]mIBG and Meta-[18F]fluorobenzylguanidine ([18F]mFBG). Review articles, preclinical studies, small case series (< 5 subjects), case reports, and articles not in English were excluded. From each study, the following characteristics were extracted: bibliographic information, technical parameters, and the sensitivity of the procedure according to a patient-based analysis (PBA) and a lesion-based analysis (LBA). RESULTS: Ten studies were selected: two regarding [11C]C-HED, four [18F]DOPA, one [124I]mIBG, and three [18F]mFBG. These studies included 181 patients (range 5-46). For the PBA, the superiority of the PET method was reported in two out of ten studies (both using [18F]DOPA). For LBA, PET detected significantly more lesions than scintigraphy in seven out of ten studies. CONCLUSIONS: PET/CT using catecholaminergic tracers shows superior diagnostic performance than mIBG scintigraphy. However, it is still unknown if such superiority can influence clinical decision-making. Nonetheless, the PET examination appears promising for clinical practice as it offers faster image acquisition, less need for sedation, and a single-day examination.

Prevalence of Incidental Findings Suspicious for Transthyretin Cardiac Amyloidosis among Patients Undergoing Bone Scintigraphy: A Systematic Review and a Meta-Analysis.

BACKGROUND: The myocardial uptake of bone-seeking tracers suspicious for transthyretin cardiac amyloidosis (ATTR-CA) can be incidentally detected in patients undergoing bone scintigraphy for noncardiac reasons. We conducted a systematic review and meta-analysis to assess the prevalence of these scintigraphic findings. METHODS: A comprehensive literature search was performed using two bibliographic databases (PubMed/MEDLINE and Cochrane Library), searching for articles related to the review question. Eligible articles were selected, and relevant data were extracted by two authors. The pooled prevalence of incidental findings suspicious for ATTR-CA among patients undergoing bone scintigraphy was calculated on a per-patient-based analysis using a random-effects model. The pooled measure was provided with 95% confidence interval (95% CI) values. RESULTS: Among 219 records, 11 articles were selected for the systematic review and 10 for the meta-analysis. The pooled prevalence of incidental findings suspicious for ATTR-CA was 1.1% (95% CI: 0.7-1.4%) with heterogeneity due to the characteristics of the included studies, patients, and index tests. These findings are more prevalent in older men. CONCLUSIONS: The prevalence of incidental findings of ATTR-CA among patients undergoing bone scintigraphy is low but not negligible. Nuclear medicine physicians should suggest, in the scintigraphic report, further clinical investigations when these findings are detected. Prospective studies are warranted.

Pediatric Imaging Using PET/MR Imaging.

PET/MR imaging is a one-stop shop technique for pediatric diseases allowing not only an accurate clinical assessment of tumors at staging and restaging but also the diagnosis of neurologic, inflammatory, and infectious diseases in complex cases. Moreover, applying PET kinetic analyses and sequences such as diffusion-weighted imaging as well as quantitative analysis investigating the relationship between disease metabolic activity and cellularity can be applied. Complex radiomics analysis can also be performed.

Chest pain in cardiac amyloidosis: occurrence, causes and prognostic significance.

BACKGROUND: Chest pain is experienced by patients with cardiac amyloidosis (CA), but a systematic investigation of its frequency, underlying etiologies and clinical significance is lacking. METHODS: Clinical, echocardiographic, laboratory characteristics, available coronary arteries imaging and endomyocardial biopsy (EMB) findings of 174 patients with CA (n = 104 with transthyretin, ATTR; n = 70 with light chains, AL) were analyzed. RESULTS: Chest pain was reported in 66 (38%) CA patients. Compared to those without, patients with chest pain had more frequently a history of coronary artery disease (CAD) (27% vs 15%, p = 0.048) and heart failure (HF) symptoms (62% vs 43%, p = 0.015), higher high sensitivity troponin I (hs-cTnI, 101 vs 65 ng/L, p = 0.032) and higher brain natriuretic peptide (597 vs 407 ng/L, p = 0.024). Among CA patients with chest pain undergoing coronary arteries imaging (n = 37), obstructive CAD was detected in 14 (38%), 13 of whom with ATTR-CA. Of these 37 patients, EMB was available in 10 and vascular/perivascular amyloid deposition was detected in 4/5 (80%) of AL-CA patients and 1/5 ATTR-CA. Among patients with suspected acute coronary syndrome (n = 22), obstructive CAD was detected in 9/17 (53%) ATTR-CA and 0/5 AL-CA; hs-cTnI levels were similar between those with and without obstructive CAD. During a follow-up of 17 (8-34) months, chest pain was a significant predictor of HF hospitalization (HR1.86, 95% CI 1.02-3.39, p = 0.042), even after adjustment for CA subtype and CAD. CONCLUSION: Chest pain is a common symptom in patients with CA, reflects a more advanced cardiac impairment and predicts future HF hospitalization. The etiology of chest pain seems to differ, with obstructive CAD more frequent in ATTR-CA whilst amyloid vascular/perivascular involvement more common in AL-CA.

Radiomics of spinal muscles: toward a radiological biomarker for allograft rejection in lung transplant.

PURPOSE: To assess the role of muscle composition and radiomics in predicting allograft rejection in lung transplant. MATERIAL AND METHODS: The last available HRCT before surgery of lung transplant candidates referring to our tertiary center from January 2010 to February 2020 was retrospectively examined. Only scans with B30 kernel reconstructions and 1 mm slice thickness were included. One radiologist segmented the spinal muscles of each patient at the level of the 11th dorsal vertebra by an open-source software. The same software was used to extract Hu values and 72 radiomic features of first and second order. Factor analysis was applied to select highly correlating features and then their prognostic value for allograft rejection was investigated by logistic regression analysis (level of significance p < 0.05). In case of significant results, the diagnostic value of the model was computed by ROC curves. RESULTS: Overall 200 patients had a HRCT prior to the transplant but only 97 matched the inclusion criteria (29 women; mean age 50.4 ± 13 years old). Twenty-one patients showed allograft rejection. The following features were selected by the factor analysis: cluster prominence, Imc2, gray level non-uniformity normalized, median, kurtosis, gray level non-uniformity, and inverse variance. The radiomic-based model including also Hu demonstrated that only the feature Imc2 acts as a predictor of allograft rejection (p = 0.021). The model showed 76.6% accuracy and the Imc2 value of 0.19 demonstrated 81% sensitivity and 64.5% specificity in predicting lung transplant rejection. CONCLUSION: The radiomic feature Imc2 demonstrated to be a predictor of allograft rejection in lung transplant.

COVID-19 musculoskeletal involvement in children.

Since the early phases of the COVID-19 pandemic, it has become clear that children are affected by mild respiratory symptoms rather than the critical pneumonia typical in adults. Nevertheless, it took longer to understand that pediatric patients with SARS-COV2 may develop a severe multisystem inflammatory response (a.k.a. multisystem inflammatory syndrome in children (MIS-C)), which can include musculoskeletal symptoms, and/or arthritis and myositis independently from MIS-C. Diagnostic imaging significantly contributed to the assessment of pulmonary disease due to COVID-19 but it has been rarely applied to evaluate musculoskeletal involvement in children with or without previous rheumatic diseases. Despite the paucity of radiological literature, muscle edema at magnetic resonance and synovitis at ultrasound have been described. Further use of diagnostic imaging for children with articular and muscular symptoms due to COVID-19 is strongly encouraged.

The dynamic functional connectivity fingerprint of high-grade gliomas.

Resting state fMRI has been used in many studies to investigate the impact of brain tumours on functional connectivity (FC). However, these studies have so far assumed that FC is stationary, disregarding the fact that the brain fluctuates over dynamic states. Here we utilised resting state fMRI data from 33 patients with high-grade gliomas and 33 healthy controls to examine the dynamic interplay between resting-state networks and to gain insights into the impact of brain tumours on functional dynamics. By employing Hidden Markov Models, we demonstrated that functional dynamics persist even in the presence of a high-grade glioma, and that patients exhibited a global decrease of connections strength, as well as of network segregation. Furthermore, through a multivariate analysis, we demonstrated that patients' cognitive scores are highly predictive of pathological dynamics, thus supporting our hypothesis that functional dynamics could serve as valuable biomarkers for better understanding the traits of high-grade gliomas.