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.

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.

Impressive response to dabrafenib and trametinib plus silybin in a heavily pretreated IDH wild-type glioblastoma patient with BRAFV600E -mutant and SOX2 amplification.

Isocitrate dehydrogenase wild-type glioblastoma is the most frequent primary brain tumor in adult patients and its prognosis is still dismal with a median survival of about 1 year. BRAF V600E mutation, an important target for personalized therapy, has been identified in about 3% of these patients, but few data are available from prospective studies on the role of anti-BRAF drugs in adult glioblastoma patients. Moreover, SOX2 gene amplification and overexpression can represent an important mechanism of resistance to BRAF inhibitors by STAT3 gene activation. We present the case of a heavily pretreated 42-year-old man with BRAF V600E mutant and SOX2 amplification glioblastoma having a radiologic and metabolic [analyzed by a brain 18F-fluoro-ethyl-tyrosine([18F]FET) PET/MRI] complete response to the combination therapy with dabrafenib plus trametinib and silybin, a potent STAT3 inhibitor. The patient is currently undergoing treatment after a total of 24 months of continuation therapy with a good safety profile. In conclusion, we showed a promising activity of the personalized treatment of BRAF and MEK inhibitors in patient with BRAF V600E mutant glioblastoma; silybin can play an important role in decreasing drug resistance during BRAF inhibitor therapy, especially in patients with SOX2 amplification.

Ankle and Foot: Focus on Inflammatory Disease.

The ankle and foot have numerous bones and complex joints that can be affected by several types of inflammatory arthritis with different patterns and various radiologic signs, depending on the phase of the disease. Involvement of these joints is most frequently seen in peripheral spondyloarthritis and rheumatoid arthritis in adults and juvenile idiopathic arthritis in children. Although radiographs are a mainstay in the diagnostic process, ultrasonography and especially magnetic resonance imaging allow early diagnosis and are crucial diagnostic tools. Some diseases have typical features based on target populations (e.g., adults versus children, men versus women), but others may have overlapping imaging characteristics. We highlight key diagnostic features and describe appropriate investigations to guide clinicians toward the correct diagnosis and provide support during disease monitoring.

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.

Variability of regional glucose metabolism and the topology of functional networks in the human brain.

The brain consumes the most energy per relative mass amongst the organs in the human body. Theoretical and empirical studies have shown that behavioral processes are relatively inexpensive metabolically, and that most energy goes to maintaining the status quo, i.e., the balance of cell membranes' resting potentials and subthreshold spontaneous activity. Spontaneous activity fluctuates across brain regions in a correlated fashion that defines multi-scale hierarchical networks called resting-state networks (RSNs). Different regions of the brain display different metabolic consumption, but the relationship between regional brain metabolism and RSNs is still under investigation. Here, we examine the variability of glucose metabolism across brain regions, measured with the relative standard uptake value (SUVR) using 18F-FDG PET, and the topology of RSNs, measured through graph analysis applied to fMRI resting-state functional connectivity (FC). We found a moderate linear relationship between the strength (STR) of pairwise regional FC and metabolism. Moreover, the linear correlation between SUVR and STR grew stronger as we considered more connected regions (hubs). Regions connecting different RSNs, or connector hubs, showed higher SUVR than regions connecting nodes within the same RSN, or provincial hubs. Our results show that functional connections as probed by fMRI are related to glucose metabolism, especially in a system of provincial and connector hubs.

Radionuclide Delivery Strategies in Tumor Treatment: A Systematic Review.

The aim of this review was to assess recent progress in targeted radionuclide tumor therapy, focusing on the best delivery strategies. A literature search was conducted in PubMed, Web of Science, and Scopus using the terms "radionuclides", "liposomes", "avidin-biotin interaction", "theranostic", and "molecular docking". The 10 year filter was applied, except for the avidin-biotin interaction. Data were retrieved from both preclinical and clinical settings. Three targeting strategies were considered: pretargeting, liposomes, and ligands. Pretargeting can be achieved by exploiting the avidin-biotin interaction. This strategy seems very promising, although it has been investigated mainly in resectable tumors. Radiolabeled liposomes have attracted new interest as probes to identify the most suitable patients for treatment with liposomal formulations of common chemotherapeutics. The use of ligands for the delivery of radiotherapeutics to a specific target is still the most appealing strategy for treating tumors. The most appropriate ligand can be identified by virtually simulating its interaction with the receptor. All strategies showed great potential for use in targeted radionuclide therapy, but they also have numerous drawbacks. The most promising option is probably the one based on the use of new ligands.

Head-to-Head Comparison between Peptide-Based Radiopharmaceutical for PET and SPECT in the Evaluation of Neuroendocrine Tumors: A Systematic Review.

We compared head-to-head the most used radiolabeled peptides for single photon computed emission tomography (SPECT) and positron emission tomography (PET) imaging of neuroendocrine tumors (NETs). A comprehensive literature search was performed in PubMed, Web of Science, and Scopus databases. The following words, coupled two by two, were used: 68Ga-DOTATOC; 68Ga-DOTATATE; 68Ga-DOTANOC; 99mTc-EDDA/HYNIC-TOC; 64Cu-DOTATATE; and 111In-DTPA-octreotide. Moreover, a second-step search strategy was adopted by using the following combined terms: "Somatostatin receptor imaging,"; "Somatostatin receptor imaging" and "Functional,"; "Somatostatin receptor imaging" and "SPECT,"; and "Somatostatin receptor imaging" and "PET". Eligible criteria were: (1) original articles focusing on the clinical application of the radiopharmaceutical agents in NETs; (2) original articles in the English language; (3) comparative studies (head-to-head comparative or matched-paired studies). Editorials, letters to the editor, reviews, pictorial essays, clinical cases, or opinions were excluded. A total of 1077 articles were found in the three electronic databases. The full texts of 104 articles were assessed for eligibility. Nineteen articles were finally included. Most articles focused on the comparison between 111In-DTPA-Octreotide and 68Ga-DOTATOC/TATE. Few papers compared 64Cu-DOTATATE and 68Ga-DOTATOC/TATE, or SPECT tracers. The rates of true positivity were 63.7%, 58.5%, 78.4% and 82.4%, respectively, for 111In-DTPA-Octreotide, 99mTc-EDDA/HYNIC-TOC, 68Ga-DOTATATE/TOC and 64Cu-DOTATATE. In conclusion, as highly expected, PET tracers are more suitable for the in vivo identification of NETs. Indeed, in comparative studies, they demonstrated a higher true positive rate than SPECT agents.

A comparison of advanced semi-quantitative amyloid PET analysis methods.

PURPOSE: To date, there is no consensus on how to semi-quantitatively assess brain amyloid PET. Some approaches use late acquisition alone (e.g., ELBA, based on radiomic features), others integrate the early scan (e.g., TDr, which targets the area of maximum perfusion) and structural imaging (e.g., WMR, that compares kinetic behaviour of white and grey matter, or SI based on the kinetic characteristics of the grey matter alone). In this study SUVr, ELBA, TDr, WMR, and SI were compared. The latter - the most complete one - provided the reference measure for amyloid burden allowing to assess the efficacy and feasibility in clinical setting of the other approaches. METHODS: We used data from 85 patients (aged 44-87) who underwent dual time-point PET/MRI acquisitions. The correlations with SI were computed and the methods compared with the visual assessment. Assuming SUVr, ELBA, TDr, and WMR to be independent measures, we linearly combined them to obtain more robust indices. Finally, we investigated possible associations between each quantifier and age in amyloid-negative patients. RESULTS: Each quantifier exhibited excellent agreement with visual assessment and strong correlation with SI (average AUC = 0.99, ρ = 0.91). Exceptions to this were observed for subcortical regions with ELBA and WMR (ρELBA = 0.44, ρWMR = 0.70). The linear combinations showed better performances than the individual methods. Significant associations were observed between TDr, WMR, SI, and age in amyloid-negative patients (p < 0.05). CONCLUSION: Among the other methods, TDr came closest to the reference with less implementation complexity. Moreover, this study suggests that combining independent approaches gives better results than the individual procedure, so efforts should focus on multi-classifier systems for amyloid PET. Finally, the ability of techniques integrating blood perfusion to depict age-related variations in amyloid load in amyloid-negative subjects demonstrates the goodness of the estimate.

EANM procedure guidelines for brain PET imaging using [18F]FDG, version 3.

The present procedural guidelines summarize the current views of the EANM Neuro-Imaging Committee (NIC). The purpose of these guidelines is to assist nuclear medicine practitioners in making recommendations, performing, interpreting, and reporting results of [18F]FDG-PET imaging of the brain. The aim is to help achieve a high-quality standard of [18F]FDG brain imaging and to further increase the diagnostic impact of this technique in neurological, neurosurgical, and psychiatric practice. The present document replaces a former version of the guidelines that have been published in 2009. These new guidelines include an update in the light of advances in PET technology such as the introduction of digital PET and hybrid PET/MR systems, advances in individual PET semiquantitative analysis, and current broadening clinical indications (e.g., for encephalitis and brain lymphoma). Further insight has also become available about hyperglycemia effects in patients who undergo brain [18F]FDG-PET. Accordingly, the patient preparation procedure has been updated. Finally, most typical brain patterns of metabolic changes are summarized for neurodegenerative diseases. The present guidelines are specifically intended to present information related to the European practice. The information provided should be taken in the context of local conditions and regulations.

Fully integrated [18F]FDG PET/MR in large vessel vasculitis.

BACKGROUND: The aim of this study is to evaluate the usefulness of [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET)/magnetic resonance (MR) in large vessels vasculitis (LVV) patients. METHODS: We performed an observational retrospective study based on our records. Images were acquired on a PET/MR scanner using [18F]FDG-PET whole body imaging. For each PET scan, a qualitative analysis and a semi-quantitative measure using the maximum of the standardized uptake value (SUVmax) were performed. SUVmax measurements normalized to the liver uptake were categorized using a grading scale. Vessel's wall thickness (WT) was measured at five fixed points (inferior margin of T5, T9, T12, L3, thickest area [max WT]). RESULTS: Twenty-three LVV patients were included, 56.5% giant cells arteritis, 34.8% Takayasu's arteritis and 8.7% isolated aortitis, all Caucasian, mostly females (82%). We considered 32 PET scans for the LVV group (from a minimum of one to a maximum of three scans per patient) mainly during follow-up (29/32 scans), and 23 PET scans from a control group of non-metastatic malignancies patients. We found higher SUVmax compared to controls, in all sites, irrespective of clinical disease activity. Mean WT resulted higher in patients than in controls but was not correlated to SUVmax. Mean WT positively correlated with age in both cohorts, inversely correlated to disease duration, while no correlation with SUVmax was observed. The concordance between clinically active disease and PET hypermetabolism was poor (Cohen' κ=0.33). CONCLUSIONS: PET/MR is a safe imaging technique capable of detecting inflammation in aortic wall. Low radiological exposure of PET/MR should be considered especially in young women receiving follow-up studies.

PET/MRI in prostate cancer: a systematic review and meta-analysis.

AIM: In recent years, the clinical availability of scanners for integrated positron emission tomography (PET) and magnetic resonance imaging (MRI) has enabled the practical potential of multimodal, combined metabolic-receptor, anatomical, and functional imaging to be explored. The present systematic review and meta-analysis summarize the diagnostic information provided by PET/MRI in patients with prostate cancer (PCa). MATERIALS AND METHODS: A literature search was conducted in three different databases. The terms used were "choline" or "prostate-specific membrane antigen - PSMA" AND "prostate cancer" or "prostate" AND "PET/MRI" or "PET MRI" or "PET-MRI" or "positron emission tomography/magnetic resonance imaging." All relevant records identified were combined, and the full texts were retrieved. Reports were excluded if (1) they did not consider hybrid PET/MRI; or (2) the sample size was < 10 patients; or (3) the raw data were not enough to enable the completion of a 2 × 2 contingency table. RESULTS: Fifty articles were eligible for systematic review, and 23 for meta-analysis. The pooled data concerned 2104 patients. Initial disease staging was the main indication for PET/MRI in 24 studies. Radiolabeled PSMA was the tracer most frequently used. In primary tumors, the pooled sensitivity for the patient-based analysis was 94.9%. At restaging, the pooled detection rate was 80.9% and was higher for radiolabeled PSMA than for choline (81.8% and 77.3%, respectively). CONCLUSIONS: PET/MRI proved highly sensitive in detecting primary PCa, with a high detection rate for recurrent disease, particularly when radiolabeled PSMA was used.

(+)-[18F]Flubatine as a novel α4ß2 nicotinic acetylcholine receptor PET ligand-results of the first-in-human brain imaging application in patients with ß-amyloid PET-confirmed Alzheimer's disease and healthy controls.

PURPOSES: We present the first in-human brain PET imaging data of the new α4ß2 nicotinic acetylcholine receptor (nAChR)-targeting radioligand (+)-[18F]Flubatine. Aims were to develop a kinetic modeling-based approach to quantify (+)-[18F]Flubatine and compare the data of healthy controls (HCs) and patients with Alzheimer's disease (AD); to investigate the partial volume effect (PVE) on regional (+)-[18F]Flubatine binding; and whether (+)-[18F]Flubatine binding and cognitive test data respective ß-amyloid radiotracer accumulation were correlated. METHODS: We examined 11 HCs and 9 mild AD patients. All subjects underwent neuropsychological testing and [11C]PiB PET/MRI examination. (+)-[18F]Flubatine PET data were evaluated using full kinetic modeling and regional as well as voxel-based analyses. RESULTS: With 270-min p.i., the unchanged parent compound amounted to 97 ± 2%. Adequate fits of the time-activity curves were obtained with the 1 tissue compartment model (1TCM). (+)-[18F]Flubatine distribution volume (binding) was significantly reduced in bilateral mesial temporal cortex in AD patients compared with HCs (right 10.6 ± 1.1 vs 11.6 ± 1.4, p = 0.049; left 11.0 ± 1.1 vs 12.2 ± 1.8, p = 0.046; one-sided t tests each). PVE correction increased not only (+)-[18F]Flubatine binding of approximately 15% but also standard deviation of 0.4-70%. Cognitive test data and (+)-[18F]Flubatine binding were significantly correlated in the left anterior cingulate, right posterior cingulate, and right parietal cortex (r > 0.5, p < 0.05 each). In AD patients, (+)-[18F]Flubatine binding and [11C]PiB standardized uptake value ratios were negatively correlated in several regions; whereas in HCs, a positive correlation between cortical (+)-[18F]Flubatine binding and [11C]PiB accumulation in the white matter was found. No adverse event related to (+)-[18F]Flubatine occurred. CONCLUSION: (+)-[18F]Flubatine is a safe and stable PET ligand. Full kinetic modeling can be realized by 1TCM without metabolite correction. (+)-[18F]Flubatine binding affinity was high enough to detect group differences. Of interest, correlation between white matter ß-amyloid PET uptake and (+)-[18F]Flubatine binding indicated an association between white matter integrity and availability of α4ß2 nAChRs. Overall, (+)-[18F]Flubatine showed favorable characteristics and has therefore the potential to serve as α4ß2 nAChR-targeting PET ligand in further clinical trials.

The role of the deep convolutional neural network as an aid to interpreting brain [18F]DOPA PET/CT in the diagnosis of Parkinson's disease.

OBJECTIVES: To test the performance of a 3D convolutional neural network (CNN) in analysing brain [18F]DOPA PET/CT in order to identify patients with nigro-striatal neurodegeneration. We evaluated the robustness of the 3D CNN by testing it against a manual regional analysis of the striata by using a striatal-to-occipital ratio (SOR). METHODS: We analyzed patients who had undergone [18F]DOPA PET/CT from 2016 to 2018. Two examiners interpreted PET/CT images as positive or negative. Only patients with at least 2 years of follow-up and an ascertained neurological diagnosis were included. A 3D CNN was developed to evaluate [18F]DOPA PET/CT and refine the diagnosis of movement disorder. This system required training and testing, which were carried out on 2/3 and 1/3 of patients, respectively. A regional analysis was also conducted by drawing region of interest on T1-weighted 3D MRI scans, on which the [18F]DOPA PET images were first co-registered. RESULTS: Ninety-eight patients were enrolled: 43 presented nigro-striatal degeneration and 55 negative cases used as controls. After training on 69 patients, the diagnostic performance of the 3D CNN was then calculated in 29 patients. Sensitivity, specificity, negative predictive value, positive predictive value and accuracy were 100%, 89%, 100%, 85% and 93%, respectively. When we compared the 3D CNN results with the SOR analysis, we found that the two patients falsely classified as positive by the 3D CNN procedure showed SOR values ≤ 5th percentile of the negative cases' distribution. CONCLUSIONS: 3D CNNs are able to interpret [18F]DOPA PET/CT properly, revealing patients affected by Parkinson's disease. KEY POINTS: • [18F]DOPA PET/CT is a sensitive diagnostic tool to identify patients with nigro-striatal neurodegeneration. • A semiquantitative evaluation of the images allows a more confident interpretation of the PET findings. • 3D convolutional neural network allows an accurate interpretation of 18F-DOPA PET/CT images, revealing patients affected by Parkinson's disease.

Challenges in theragnostics.

Precision medicine (or personalized medicine) is an intriguing, and still involving part of modern medicine. Theragnostics is a combination of therapies and diagnostics targeting pathophysiological processes at molecular level using radiopharmaceuticals. It is a valuable resource in efforts to implement precision medicine in clinical practice, but the theragnostic era poses an abundance of challenges. The aim of the present paper study was to analyze some of these challenges in the field of theragnostics, irrespective of their clinical applications. Three experts in this field discussed the balance between the demand, the costs of theragnostics, the need of appropriate infrastructures, and the opportunities for new developments in this area.

Volumetric histograms-based analysis of apparent diffusion coefficients and standard uptake values for the assessment of pediatric sarcoma at staging: preliminary results of a PET/MRI study.

PURPOSE: To assess the relationship between apparent diffusion coefficients (ADC) and standard uptake values (SUV) of pediatric sarcomas at staging by using volumetric histograms analyses. METHODS: Children with histologically proven sarcoma, referring to our tertiary center for a whole-body 18F-FDG PET/MRI for staging and including diffusion weighted imaging in the MRI protocol were investigated. Firstly, turbo inversion recovery magnitude (TIRM) and PET images were resliced and resampled according to the ADC maps. Regions of interests were drawn along tumor margins on TIRM images and then copied on PET and ADC datasets. Pixel-based SUVs and ADCs were collected from the entire volume of each lesion. Mean, median, skewness, and kurtosis of SUVs and ADCs values were computed, and the Pearson correlation coefficient was then applied (for the entire population and for histological subgroups with more than five patients). RESULTS: Thirteen patients met the inclusion criteria (six females; mean age 8.31 ± 6.03 years). Histology revealed nine rhabdomyosarcomas, three Ewing sarcomas, and one chondroblastic osteosarcoma. A significant negative correlation between ADCs' and SUVs' mean (rmean = - 0.501, P < 0.001), median (rmedian = - 0.519, P < 0,001), and skewness (rskewness = - 0.550, P < 0.001) emerged for the entire population and for rhabdomyosarcomas (rmean = - 0.541, P = 0.001, rmedian = - 0.597, P < 0.001, rskewness = - 0.568, P < 0.001), whereas a significant positive correlation was found for kurtosis (rkurtosis = 0.346, P < 0.001, and rkurtosis = 0.348, P < 0.001 for the entire population and for rhabdomyosarcomas, respectively). CONCLUSION: Our preliminary results demonstrate that, using volumetric histograms, simultaneously collected SUVs and ADCs are dependent biomarkers in pediatric FDG-avid sarcomas. Further studies, on a larger population, are necessary to confirm this evidence and assess its clinical implications.

The role of radiological and hybrid imaging for muscle metastases: a systematic review.

AIM OF THE STUDY: Skeletal muscle metastases (SMM) are a rare entity, mainly detected at autopsy. Nevertheless, radiological and nuclear medicine imaging can contribute to the diagnosis with a significant impact on the treatment and prognosis of neoplastic patients. This study aimed to systematically review the features of SMM at imaging considering the primary tumors and the sites of occurrence. MATERIALS AND METHODS: We conducted a systematic search of three electronic database (i.e., PubMed, Science Direct, and Web of Science) up to May 2019, without any language or time interval restriction. Two reviewers performed the search and selection process, data extraction, and synthesis. We resolved disagreements by consensus and/or involving a third reviewer. The included studies have been classified according to the Oxford Centre for Evidence Based Medicine (CEBM) grading system. RESULTS: Out of 8598 and 1077 articles respectively for radiological and hybrid imaging, 29 papers were included. According to CEBM, twelve were level 4. Computed tomography (CT) is mainly applied and, despite the existence of CT and magnetic resonance-based classifications, these are rarely used. Positron emission tomography/CT allowed the detection of small and subtle lesion also in the extremities. Muscles of the trunk were mostly affected and mainly respiratory tumors are associated with this type of metastatic spread. CONCLUSION: Radiological and hybrid imaging allow a precise characterization of SMM. However, a more systematic approach, including also the application of available classification systems, may increase the diagnostic accuracy for this rare type of metastases. KEY POINTS: • Skeletal muscle metastases have heterogeneous characteristics at imaging but mostly abscess-like features and high metabolic activity are described. • Skeletal muscle metastases mainly affect the muscles of the trunk. • Pulmonary, urological, and gastrointestinal cancers are the most frequent cause of skeletal muscle metastases.

18F-FDG PET/MRI for Rectal Cancer TNM Restaging After Preoperative Chemoradiotherapy: Initial Experience.

OBJECTIVE: F-FDG-PET/MRI is a novel hybrid techinque that has been recently introduced in oncological imaging, showing promising results. The aim of this study is to assess the value of whole-body F-FDG-PET/MRI for predicting the pathological stage of locally advanced rectal cancer after preoperative chemoradiotherapy. DESIGN: This was a prospective observational study. SETTINGS: The study was conducted at a tertiary care hospital. PATIENTS: Thirty-six patients with locally advanced rectal cancer (25 male, median age 68.5 years) were prospectively assessed with PET/MRI and thoracoabdominal CT before and after preoperative chemoradiotherapy. Twenty-seven patients underwent low anterior or abdominoperineal resection. Nine patients with a complete clinical response underwent organ-preserving treatment (8 local excision and 1 watch-and-wait approach) with >1-year follow-up. MAIN OUTCOME MEASURES: One radiologist evaluated pelvic MRI and CT. A second radiologist and a nuclear medicine physician jointly assessed PET/MRI. The imaging was compared with histology or follow-up (ypT0 vs T ≥1 and ypN0 vs ypN+ categories). Metastases were confirmed with biopsy or a follow-up CT scan at least at 1 year after preoperative chemoradiotherapy. The sensitivity, specificity, and accuracy values of the imaging techniques were calculated using standard formulas. RESULTS: The accuracy for ypT staging was 89% and 92%, and the accuracy for ypN was 86% and 92% for MRI and PET/MRI. Compared with CT, PET/MRI correctly diagnosed 4 of 5 metastases, but it did not detect a lung metastatic nodule. In 11% of the patients, the PET/MRI changed the treatment strategy. LIMITATIONS: This study is limited by its small sample size. CONCLUSIONS: Although the whole-body PET/MRI was more accurate than the pelvic MRI alone for the prediction of tumor and node response to preoperative chemoradiotherapy, the technique performed worse than CT in detecting small lung metastasis. See Video Abstract at http://links.lww.com/DCR/B108. TOMOGRAFÍA POR EMISIÓN DE POSITRONES DE 18F- FLUORODEOXIGLUCOSA (FDG) / RESONANCIA MAGNÉTICA (TEP/RM) PARA ESTADIFICACIÓN TUMORAL TNM DE CÁNCER DEL RECTO DESPUÉS DE LA QUIMIORRADIOTERAPIA PREOPERATORIA - EXPERIENCIA INICIAL: Evaluar el valor de la tomografía por emisión de positrones de 18F-fluorodeoxiglucosa / resonancia magnética (TEP/RM) para predecir el estadio patológico del cáncer de recto localmente avanzado después de la quimiorradioterapia preoperatoria.Este fue un estudio prospectivo observacional.El estudio se realizó en un hospital de atención terciaria.Treinta y seis pacientes con cáncer rectal localmente avanzado (25 hombres, edad media de 68.5 años) fueron evaluados prospectivamente con TEP/RM y tomografía computarizada (TC) toraco-abdominal antes y después de la quimiorradioterapia preoperatoria. Veintisiete pacientes se sometieron a resección anterior baja o abdominoperineal. Nueve pacientes con una respuesta clínica completa se sometieron a un tratamiento de preservación de órganos (8 escisión local y 1 un enfoque de observar y esperar) con un seguimiento de> 1 año.Un radiólogo evaluó la RM pélvica y la TC. Un segundo radiólogo y un médico de medicina nuclear evaluaron conjuntamente TEP / RM. La imagen se comparó con la histología o el seguimiento (ypT0 vs T ≥1 y ypN0 vs ypN + categorías). Las metástasis se confirmaron con biopsia o una TC de seguimiento al menos 1 año después de la quimiorradioterapia preoperatoria. Los valores de sensibilidad, especificidad y precisión de las técnicas de imagen se calcularon utilizando fórmulas estándar.La precisión para la estadificación ypT fue del 89% y 92%, y la precisión para ypN fue del 86% y 92% para RM y TEP/RM respectivamente. En comparación con la TC, la TEP / RM diagnosticó correctamente 4 de 5 metástasis, pero no detectó un nódulo metastásico pulmonar. En el 11% de los pacientes, la TEP / RM cambió la estrategia de tratamiento.Este estudio está limitado por su pequeño tamaño de muestra.Si bien la TEP / RM de todo el cuerpo fue más precisa que la RM pélvica sola para la predicción de la respuesta tumoral y ganglionar a la quimiorradioterapia preoperatoria, la técnica funcionó peor que la TC para detectar metástasis pulmonares pequeños. Consulte Video Resumen en http://links.lww.com/DCR/B108.

MRI T2-weighted sequences-based texture analysis (TA) as a predictor of response to neoadjuvant chemo-radiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC).

PURPOSE: To determine whether MRI T2-weighted sequences-based texture analysis (TA) can predict histopathological tumor regression grade (TRG) in patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemo-radiotherapy (nCRT). METHODS: Data on patients undergoing curative-intent surgery for LARC were collected. Patients with a complete pathological response, or TRG1 according to Mandard's system were classified as responders, while patients with TRG ≥ 2 were classified as non-responders. Tumor TA was performed on each patient's paraxial T2w MRI in both pre- and post-nCRT scans, in order to extract histograms, gray-level co-occurrence matrix (GLCM) and run-length matrix (RLM) texture parameters. For features that showed a significant difference between the two groups, a receiver operating characteristic (ROC) curve was drawn. RESULTS: Overall, 62 patients with LARC, treated with nCRT and resective surgery at our institution between 2013 and 2019 were identified. Only post-nCRT GLCM maximum probability showed a significant difference between the two groups (2909 ± 4479 in responders vs. 6515 ± 8990 in non- responders; p = 0.039); at the ROC curve, Youden index showed a sensitivity of 14% and a specificity of 100% for this parameter. CONCLUSIONS: MRI T2-weighted sequences-based TA was not effective in predicting pathological complete response to nCRT in patients with LARC. Further studies are needed to thoroughly investigate the potential of MRI TA in this setting.

Molecular Imaging of Pulmonary Inflammation and Infection.

Infectious and inflammatory pulmonary diseases are a leading cause of morbidity and mortality worldwide. Although infrequently used in this setting, molecular imaging may significantly contribute to their diagnosis using techniques like single photon emission tomography (SPET), positron emission tomography (PET) with computed tomography (CT) or magnetic resonance imaging (MRI) with the support of specific or unspecific radiopharmaceutical agents. 18F-Fluorodeoxyglucose (18F-FDG), mostly applied in oncological imaging, can also detect cells actively involved in infectious and inflammatory conditions, even if with a low specificity. SPET with nonspecific (e.g., 67Gallium-citrate (67Ga citrate)) and specific tracers (e.g., white blood cells radiolabeled with 111Indium-oxine (111In) or 99mTechnetium (99mTc)) showed interesting results for many inflammatory lung diseases. However, 67Ga citrate is unfavorable by a radioprotection point of view while radiolabeled white blood cells scan implies complex laboratory settings and labeling procedures. Radiolabeled antibiotics (e.g., ciprofloxacin) have been recently tested, although they seem to be quite unspecific and cause antibiotic resistance. New radiolabeled agents like antimicrobic peptides, binding to bacterial cell membranes, seem very promising. Thus, the aim of this narrative review is to provide a comprehensive overview about techniques, including PET/MRI, and tracers that can guide the clinicians in the appropriate diagnostic pathway of infectious and inflammatory pulmonary diseases.