Recommendations in Second Opinion Reports of Neurologic Head and Neck Imaging:Frequency, Referring Clinicians? Compliance, and Diagnostic Yield

BACKGROUND AND PURPOSE: Second opinion reports of neurologic head and neck imaging are requested with increased regularity, and they may contain a recommendation to the clinician. Our aim was to investigate the frequency and determinants of the presence of a recommendation and the adherence by the referring physician to the recommendation in a second opinion neurology head and neck imaging report and the diagnostic yield of these recommendations. MATERIALS AND METHODS: This retrospective study included 994 consecutive second opinion reports of neurology head and neck imaging examinations performed at a tertiary care center. RESULTS: Of the 994 second opinion reports, 12.2% (121/994) contained a recommendation. An oncologic imaging indication was significantly (P = .030) associated with a lower chance of a recommendation in the second opinion report (OR = .67; 95% CI, 0.46?0.96). Clinicians followed 65.7% (88/134) of the recommendations. None of the investigated variables (patient age, sex, hospitalization status, indication for the second opinion report, experience of the radiologist who signed the second opinion report, strength of the recommendation, and whether the recommendation was made due to apparent quality issues of the original examination) were significantly associated with the compliance of the referring physician to this recommendation. The 134 individual recommendations eventually led to the establishment of 52 (38.2%) benign diagnoses and 28 (20.6%) malignant diagnoses, while no definitive diagnosis could be established in 56 (41.2%) cases. CONCLUSIONS: Recommendations are relatively common in second opinion reports of neurology head and neck imaging examinations, though less for oncologic indications. They are mostly followed by requesting physicians, thus affecting patient management. In most cases, they also lead to the establishment of a diagnosis, hence adding value to patient care

Time to Reconsider Routine Percutaneous Biopsy in Spondylodiscitis?

Percutaneous image-guided biopsy currently has a central role in the diagnostic work-up of patients with suspected spondylodiscitis. However, on the basis of recent evidence, the value of routine image-guided biopsy in this disease can be challenged. In this article, we discuss this recent evidence and also share a new diagnostic algorithm for spondylodiscitis that was recently introduced at our institution. Thus, we may move from a rather dogmatic approach in which routine image-guided biopsy is performed in any case to a more individualized use of this procedure. Percutaneous image-guided biopsy, while valuable, is an invasive procedure, and evidence has shown rather disappointing positive microbiologic culture yields of around 33%. Recent evidence also has shown that percutaneous image-guided biopsy rarely adds any new information when blood cultures have positive findings and that an effective empiric treatment can be started in most of cases even when the microbiologic culprit remains unknown. Finally, there is currently no evidence that percutaneous image-guided biopsy improves patient outcome

Therapy-Induced Changes in CXCR4 Expression in Tumor Xenografts Can Be Monitored Noninvasively with N-[C-11]Methyl-AMD3465 PET

Purpose Chemokine CXCL12 and its receptor CXCR4 are constitutively overexpressed in human cancers. The CXCL12-CXCR4 signaling axis plays an important role in tumor progression and metastasis, but also in treatment-induced recruitment of CXCR4-expressing cytotoxic immune cells. Here, we aimed to demonstrate the feasibility of N-[C-11]methyl-AMD3465 positron emission tomography (PET) to monitor changes in CXCR4 density in tumors after single-fraction local radiotherapy or in combination with immunization. Procedure TC-1 cells expressing human papillomavirus antigens E6 and E7 were inoculated into the C57BL/6 mice subcutaneously. Two weeks after tumor cell inoculation, mice were irradiated with a single-fraction 14-Gy dose of X-ray. One group of irradiated mice was immunized with an alpha-viral vector vaccine, SFVeE6,7, and another group received daily injections of the CXCR4 antagonist AMD3100 (3 mg/kg -intraperitoneal (i.p.)). Seven days after irradiation, all animals underwent N-[C-11]methyl-AMD3465 PET. Results PET imaging showed N-[C-11]methyl-AMD3465 uptake in the tumor of single-fraction irradiated mice was nearly 2.5-fold higher than in sham-irradiated tumors (1.07 +/- 0.31 %ID/g vs. 0.42 +/- 0.05 % ID/g, p <0.01). The tumor uptake was further increased by 4-fold (1.73 +/- 0.17 % ID/g vs 0.42 +/- 0.05 % ID/g, p <0.01) in mice treated with single-fraction radiotherapy in combination with SFVeE6,7 immunization. Administration of AMD3100 caused a 4.5-fold reduction in the tracer uptake in the tumor of irradiated animals (0.24 +/- 0.1 % ID/g, p <0.001), suggesting that tracer uptake is indeed due to CXCR4-mediated chemotaxis. Conclusion This study demonstrates the feasibility of N-[C-11]methyl-AMD3465 PET imaging to monitor treatment-induced changes in the density of CXCR4 receptors in tumors and justifies further evaluation of CXCR4 as a potential imaging biomarker for evaluation of anti-tumor therapies

Ovariectomy-induced depressive-like behavior and brain glucose metabolism changes in female rats are not affected by chronic mild stress

The increased incidence of depression in women going through peri-menopause suggests that fluctuations in estrogen levels may increase the risk of developing depression. Nonetheless, this psychiatric disorder is likely to be multifactorial and consequently an additional trigger may be needed to induce depression in this population. Stress could be such a trigger. We therefore investigated the effect of ovarian estrogen depletion and chronic mild stress (CMS) on depressive-like behavior and brain metabolism in female rats. Approximately 2 and 9 weeks after estrogen depletion by ovariectomy, behavioral changes were assessed in the open-field test and the forced swim test, and brain metabolism was measured with [18F]FDG PET imaging. A subset of animals was subjected to a 6-weeks CMS protocol starting 17 days after ovariectomy. Short-term estrogen depletion had a significant effect on brain metabolism in subcortical areas, but not on behavior. Differences in depressive-like behavior were only found after prolonged estrogen depletion, leading to an increased immobility time in the forced swim test. Prolonged estrogen depletion also resulted in an increase in glucose metabolism in frontal cortical areas and hippocampus, whereas a decrease glucose metabolism was found in temporal cortical areas, hypothalamus and brainstem. Neither short-term nor prolonged estrogen depletion caused anxiety-like behavior. Changes in body weight, behavior and brain glucose metabolism were not significantly affected by CMS. In conclusion, ovarian estrogen depletion resulted in changes in brain metabolism and depressive-like behavior, but these changes were not enhanced by CMS

[18F]FDG PET in conditions associated with hyperkinetic movement disorders and ataxia:a systematic review

PURPOSE: To give a comprehensive literature overview of alterations in regional cerebral glucose metabolism, measured using [18F]FDG PET, in conditions associated with hyperkinetic movement disorders and ataxia. In addition, correlations between glucose metabolism and clinical variables as well as the effect of treatment on glucose metabolism are discussed.METHODS: A systematic literature search was performed according to PRISMA guidelines. Studies concerning tremors, tics, dystonia, ataxia, chorea, myoclonus, functional movement disorders, or mixed movement disorders due to autoimmune or metabolic aetiologies were eligible for inclusion. A PubMed search was performed up to November 2021.RESULTS: Of 1240 studies retrieved in the original search, 104 articles were included. Most articles concerned patients with chorea (n = 27), followed by ataxia (n = 25), dystonia (n = 20), tremor (n = 8), metabolic disease (n = 7), myoclonus (n = 6), tics (n = 6), and autoimmune disorders (n = 5). No papers on functional movement disorders were included. Altered glucose metabolism was detected in various brain regions in all movement disorders, with dystonia-related hypermetabolism of the lentiform nuclei and both hyper- and hypometabolism of the cerebellum; pronounced cerebellar hypometabolism in ataxia; and striatal hypometabolism in chorea (dominated by Huntington disease). Correlations between clinical characteristics and glucose metabolism were often described. [18F]FDG PET-showed normalization of metabolic alterations after treatment in tremors, ataxia, and chorea.CONCLUSION: In all conditions with hyperkinetic movement disorders, hypo- or hypermetabolism was found in multiple, partly overlapping brain regions, and clinical characteristics often correlated with glucose metabolism. For some movement disorders, [18F]FDG PET metabolic changes reflected the effect of treatment.</p

SMART (SiMulAtion and ReconsTruction) PET:an efficient PET simulation-reconstruction tool

Background: Positron-emission tomography (PET) simulators are frequently used for development and performance evaluation of segmentation methods or quantitative uptake metrics. To date, most PET simulation tools are based on Monte Carlo simulations, which are computationally demanding. Other analytical simulation tools lack the implementation of time of flight (TOF) or resolution modelling (RM). In this study, a fast and easy-to-use PET simulation-reconstruction package, SiMulAtion and ReconsTruction (SMART)-PET, is developed and validated, which includes both TOF and RM. SMART-PET, its documentation and instructions to calibrate the tool to a specific PET/CT system are available on Zenodo.SMART-PET allows the fast generation of 3D PET images. As input, it requires one image representing the activity distribution and one representing the corresponding CT image/attenuation map. It allows the user to adjust different parameters, such as reconstruction settings (TOF/RM), noise level or scan duration. Furthermore, a random spatial shift can be included, representing patient repositioning. To evaluate the tool, simulated images were compared with real scan data of the NEMA NU 2 image quality phantom. The scan was acquired as a 60-min list-mode scan and reconstructed with and without TOF and/or RM. For every reconstruction setting, ten statistically equivalent images, representing 30, 60, 120 and 300 s scan duration, were generated. Simulated and real-scan data were compared regarding coefficient of variation in the phantom background and activity recovery coefficients (RCs) of the spheres. Furthermore, standard deviation images of each of the ten statistically equivalent images were compared.Results: SMART-PET produces images comparable to actual phantom data. The image characteristics of simulated and real PET images varied in similar ways as function of reconstruction protocols and noise levels. The change in image noise with variation of simulated TOF settings followed the theoretically expected behaviour. RC as function of sphere size agreed within 0.3-11% between simulated and actual phantom data.Conclusions: SMART-PET allows for rapid and easy simulation of PET data. The user can change various acquisition and reconstruction settings (including RM and TOF) and noise levels. The images obtained show similar image characteristics as those seen in actual phantom data.</p

Prognostic value of 11C-methionine volume-based PET parameters in IDH wild type glioblastoma

PURPOSE: (11)C-Methionine ((11)C-MET) PET prognostication of isocitrate dehydrogenase (IDH) wild type glioblastomas is inadequate as conventional parameters such as standardized uptake value (SUV) do not adequately reflect tumor heterogeneity. We retrospectively evaluated whether volume-based parameters such as metabolic tumor volume (MTV) and total lesion methionine metabolism (TLMM) outperformed SUV for survival correlation in patients with IDH wild type glioblastomas. METHODS: Thirteen IDH wild type glioblastoma patients underwent preoperative (11)C-MET PET. Both SUV-based parameters and volume-based parameters were calculated for each lesion. Kaplan-Meier curves with log-rank testing and Cox regression analysis were used for correlation between PET parameters and overall survival. RESULTS: Median overall survival for the entire cohort was 393 days. MTV (HR 1.136, p = 0.007) and TLMM (HR 1.022, p = 0.030) were inversely correlated with overall survival. SUV-based (11)C-MET PET parameters did not show a correlation with survival. In a paired analysis with other clinical parameters including age and radiotherapy dose, MTV and TLMM were found to be independent factors. CONCLUSIONS: MTV and TLMM, and not SUV, significantly correlate with overall survival in patients with IDH wild type glioblastomas. The incorporation of volume-based (11)C-MET PET parameters may lead to a better outcome prediction for this heterogeneous patient population

Repeatability of 18 F-FDG PET radiomic features:A phantom study to explore sensitivity to image reconstruction settings, noise, and delineation method

BACKGROUND: 18 F-fluoro-2-deoxy-D-Glucose positron emission tomography (18 F-FDG PET) radiomics has the potential to guide the clinical decision making in cancer patients, but validation is required before radiomics can be implemented in the clinical setting. The aim of this study was to explore how feature space reduction and repeatability of 18 F-FDG PET radiomic features are affected by various sources of variation such as underlying data (e.g., object size and uptake), image reconstruction methods and settings, noise, discretization method, and delineation method.METHODS: The NEMA image quality phantom was scanned with various sphere-to-background ratios (SBR), simulating different activity uptakes, including spheres with low uptake, that is, SBR smaller than 1. Furthermore, images of a phantom containing 3D printed inserts reflecting realistic heterogeneity uptake patterns were acquired. Data were reconstructed using various matrix sizes, reconstruction algorithms, and scan durations (noise). For every specific reconstruction and noise level, ten statistically equal replicates were generated. The phantom inserts were delineated using CT and PET-based segmentation methods. A total of 246 radiomic features was extracted from each image dataset. Images were discretized with a fixed number of 64 bins (FBN) and a fixed bin width (FBW) of 0.25 for the high and a FBW of 0.05 for the low uptake data. In terms of feature reduction, we determined the impact of these factors on the composition of feature clusters, which were defined on the basis of Spearman's correlation matrices. To assess feature repeatability, the intraclass correlation coefficient was calculated over the ten replicates.RESULTS: In general, larger spheres with high uptake resulted in better repeatability compared to smaller low uptake spheres. In terms of repeatability, features extracted from heterogeneous phantom inserts were comparable to features extracted from bigger high uptake spheres. For example, for an EARL-compliant reconstruction, larger and smaller high uptake spheres yielded good repeatability for 32% and 30% of the features, while the heterogeneous inserts resulted in 34% repeatable features. For the low uptake spheres, this was the case for 22% and 20% of the features for bigger and smaller spheres, respectively. Images reconstructed with point-spread-function (PSF) resulted in the highest repeatability when compared with OSEM or time-of-flight, for example, 53%, 30%, and 32% of repeatable features, respectively (for unsmoothed data, discretized with FBN, 300 s scan duration). Reducing image noise (increasing scan duration and smoothing) and using CT-based segmentation for the low uptake spheres yielded improved repeatability. FBW discretization resulted in higher repeatability than FBN discretization, for example, 89% and 35% of the features, respectively (for the EARL-compliant reconstruction and larger high uptake spheres).CONCLUSION: Feature space reduction and repeatability of 18 F-FDG PET radiomic features depended on all studied factors. The high sensitivity of PET radiomic features to image quality suggests that a high level of image acquisition and preprocessing standardization is required to be used as clinical imaging biomarker.</p

A retrospective analysis of the diagnostic performance of 11C-choline PET/CT for detection of hyperfunctioning parathyroid glands after prior negative or discordant imaging in primary hyperparathyroidism

BACKGROUND: Identifying the correct location of a parathyroid adenoma in patients with primary hyperparathyroidism (pHPT) is crucial as it can guide surgical treatment. This study aimed to determine the diagnostic performance of 11C-choline PET/CT in patients with pHPT as a next in-line scan after primary negative or discordant first-line imaging. METHODS: This was a retrospective single-center cohort study. All patients with pHPT that were scanned utilizing 11C-choline PET/CT, after prior negative or discordant imaging, between 2015 and 2019 and who subsequently underwent parathyroid surgery were included. The results of the 11C-choline PET/CT were evaluated lesion-based, with surgical exploration and histopathological examination as the gold standard. RESULTS: In total, 36 patients were included of which three patients were known to have Multiple Endocrine Neoplasia (MEN) syndrome. In these 36 patients, 40 lesions were identified on 11C-choline PET/CT and 37 parathyroid lesions were surgically removed. In 34/36 (94%) patients a focused parathyroidectomy was performed, in one patient a cervical exploration due to an ectopically identified adenoma, and in one patient a bilateral exploration was performed because of a double adenoma. Overall, per-lesion sensitivity of 11C-choline PET/CT was 97%, the positive predictive value was 95% and the accuracy was 94% for all parathyroid lesions. CONCLUSIONS: In patients with pHPT and prior negative or discordant first-line imaging results, pathological parathyroid glands can be localized by 11C-choline PET/CT with high sensitivity and accuracy

A light-responsive liposomal agent for MRI contrast enhancement and monitoring of cargo delivery

Medical magnetic resonance imaging (MRI) produces high-resolution anatomical images of the human body, but has limited capacity to provide useful molecular information. The light-responsive, liposomal MRI contrast agent described herein could be used to provide an intrinsic theranostic aspect to MRI and enable tracking the distribution and cargo release of drug delivery systems upon light-triggered activation