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Objective: Proof‐of‐concept trial to determine the effects of tumor necrosis factor inhibitor (TNFi) therapy on osteoblastic activity at sites of inflammatory and structural lesions in patients with radiographic axial spondyloarthritis (SpA), using fluorine 18–labeled NaF (18F‐NaF) positron emission tomography/magnetic resonance imaging (PET/MRI). Methods: Sixteen patients with clinically active radiographic axial SpA were prospectively enrolled to receive TNFi treatment and undergo 18F‐NaF PET/MRI of the sacroiliac (SI) joints and spine at baseline and at a follow‐up visit 3–6 months after treatment initiation. Three readers (1 for PET/MRI and 2 for conventional MRI) evaluated all images, blinded to time point. Bone marrow edema, structural lesions (i.e., fat lesions, sclerosis, erosions, and ankylosis), and 18F‐NaF uptake at SI joint quadrants and vertebral corners (VCs) were recorded. Results: Overall, 11 male and 5 female patients (mean age ± SD 38.6 ± 12.0 years) were followed up for a mean duration of 4.6 months (range 3–6). 18F‐NaF PET/MRI was conducted on SI joints for 16 patients and the spine for 10; 128 SI joint quadrants and 920 VCs were analyzed at each time point. At baseline, 18F‐NaF uptake was demonstrated in 96.0% of SI joint quadrants with bone marrow edema, 94.2% with sclerosis, and 88.3% with fat lesions. At follow‐up, 65.3% of SI joint quadrants with bone marrow edema (P < 0.001), 33.8% with sclerosis (P = 0.23), and 24.5% with fat lesions (P = 0.01) had less 18F‐NaF uptake, compared with baseline. For VCs, 18F‐NaF uptake at baseline was found in 81.5% of edges with sclerosis, 41.9% with fat lesions, and 33.7% with bone marrow edema. At follow‐up, 73.5% of VCs with bone marrow edema (P = 0.01), 53.3% with fat lesions (P = 0.03), and 55.6% with sclerosis (P = 0.16) showed less 18F‐NaF uptake, compared with baseline. Conclusion: Anti‐TNF antibody treatment led to a significant decrease in osteoblastic activity within 3–6 months, especially, but not solely, at sites of inflammation. Larger data sets are needed for confirmation of the antiosteoblastic effects of TNFi for the prevention of radiographic progression in axial SpA. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to compare and evaluate three different bilinear conversion curves for attenuation correction (AC) of a 16‐channel radiofrequency (RF) coil in positron emission tomography/magnetic resonance (PET/MR) breast cancer imaging. Methods: The quantitative impact of three different bilinear conversions of computed tomography (CT) data for the AC of a 16‐channel RF breast coil was systematically evaluated in phantom measurements and on n = 20 PET/MR patients with breast cancer. PET data were reconstructed four times: (1) no coil AC (C‐NAC) serving as a reference, (2) established bilinear conversion by Carney et al., (3) bilinear conversion by Paulus et al., and (4) bilinear conversion by Oehmigen et al. Relative differences in PET data were calculated. Results: Independent of the choice of bilinear conversion, significant gains in PET signal, compared to C‐NAC, were measurable in all phantom and patient measurements. Mean relative differences of ca. 10% in SUVmean (i.e., standardized uptake value; maximal relative differences up to 30%) due to the integration of the coil AC were calculated, compared to C‐NAC in phantom and patient measurements. Relative difference images depict that the quantitative impact of coil AC is highest in regions close to the RF coil when compared to no AC data. Bilinear conversion by Carney et al. shows a slightly overcorrection (2.9%), whereas the conversion by Paulus et al. provides a slight undercorrection of the PET images (−1.6%) in comparison to the no‐coil measurement. The bilinear conversion proposed by Oehmigen et al. provides the most appropriate AC for the breast coil in this phantom experiment (−0.2%). A total of 23 congruent lesions could be detected in all patients. All lesions could be detected in all reconstructions. Conclusions: For the best possible PET image quality and accurate PET quantification in breast PET/MRI, the AC of MR hardware components is important. The bilinear conversion proposed by Oehmigen et al. provides the most appropriate AC for the breast coil in this study. [ABSTRACT FROM AUTHOR]

Objective: To analyze why numerous acute stroke treatments were successful in the laboratory but failed in large clinical trials.Methods: We searched all phase 3 trials of medical treatments for acute ischemic stroke and corresponding early clinical and experimental studies. We compared the overall efficacy and assessed the impact of publication bias and study design on the efficacy. Furthermore, we estimated power and true report probability of experimental studies.Results: We identified 50 phase 3 trials with 46,008 subjects, 75 early clinical trials with 12,391 subjects, and 209 experimental studies with >7,141 subjects. Three (6%) phase 3, 24 (32%) early clinical, and 143 (69.08%) experimental studies were positive. The mean treatment effect was 0.76 (95% confidence interval [CI] = 0.70-0.83) in experimental studies, 0.87 (95% CI = 0.71-1.06) in early clinical trials, and 1.00 (95% CI = 0.95-1.06) in phase 3 trials. Funnel plot asymmetry and trim-and-fill revealed a clear publication bias in experimental studies and early clinical trials. Study design and adherence to quality criteria had a considerable impact on estimated effect sizes. The mean power of experimental studies was 17%. Assuming a bias of 30% and pre-study odds of 0.5 to 0.7, this leads to a true report probability of <50%.Interpretation: Pivotal study design differences between experimental studies and clinical trials, including different primary end points and time to treatment, publication bias, neglected quality criteria and low power, contribute to the stepwise efficacy decline of stroke treatments from experimental studies to phase 3 clinical trials. Even under conservative estimates, less than half of published positive experimental stroke studies are truly positive. ANN NEUROL 2020;87:40-51. [ABSTRACT FROM AUTHOR]

Purpose: Aim of this study was to evaluate the use of computer‐aided design (CAD) models for attenuation correction (AC) of hardware components in positron emission tomography/magnetic resonance (PET/MR) imaging. Methods: The technical feasibility and quantitative impact of CAD‐AC compared to computer tomography (CT)‐based AC (reference) was investigated on a modular phantom consisting of 19 different material samples (plastics and metals arranged around a cylindrical emission phantom) typically used in phantoms, patient tables, and radiofrequency (RF) coils in PET/MR. The clinical applicability of the CAD‐AC method was then evaluated on a 16‐channel RF breast coil in a PET/MR patient study. The RF breast coil in this study was specifically designed PET compatible. Using this RF breast coil, the impact on clinical PET/MR breast imaging was systematically evaluated in breast phantom measurements and, furthermore, in n = 10 PET/MR patients with breast cancer. PET data were reconstructed three times: (1) no AC (NAC), (2) established CT‐AC, and (3) CAD‐AC. For both phantom measurements, a scan without attenuating hardware components (material probes or RF breast coil) was acquired serving as reference. Relative differences in PET data were calculated for all experiments. Results: In all phantom and patient measurements, significant gains in PET signal compared to NAC data were measurable with CT and CAD‐AC. In initial phantom experiments, mean relative differences of –0.2% for CT‐AC and 0.2% for CAD‐AC were calculated compared to reference measurements without the material probes. The application to a RF breast coil depicts that CAD‐AC results in significant gains compared to NAC data (10%) and a slight underestimation in PET signal of –1.3% in comparison to the no‐coil reference measurement. In the patient study, a total of 15 congruent lesions in all 10 patients with a mean relative difference of 14% (CT and CAD‐AC) in standardized uptake value compared to NAC data could be detected. Conclusions: To ensure best possible PET image quality and accurate PET quantification in PET/MR imaging, the AC of hardware components such as phantoms and RF coils is important. In initial phantom experiments and in clinical application to an RF breast coil, it was found that CAD‐based AC results in significant gains in PET signal compared to NAC data and provides comparably good results to the established method of CT‐based AC. [ABSTRACT FROM AUTHOR]

Introduction: To correlate tumour grading and prognostic immunohistochemical markers of lung cancer with simultaneously acquired standardised uptake values (SUV) and apparent diffusion coefficient (ADC) derived from hybrid PET/MRI. Methods: In this retrospective study, 55 consecutive patients (mean age 62.5 ± 9.2 years) with therapy‐naïve, histologically proven lung cancer were included. All patients underwent whole‐body PET/MRI using 18F‐flourdeoxyglucose (18F‐FDG) as a radiotracer. Diffusion‐weighted imaging of the chest (DWI, b‐values: 0, 500, 1000 s/mm2) was performed simultaneously with PET acquisition. Histopathological tumour grading was available in 43/55 patients. In 15/55 patients, immunohistochemical markers, that is, phospho‐AKT Ser473 (pAKTS473), phosphorylated extracellular signal‐regulated kinase (pERK), phosphatase and tensin homolog (PTEN), and human epidermal growth factor receptor 2 (erbB2) were available. Results: The average SUVmax, SUVmean, ADCmin and ADCmean in lung cancer primaries were 12.6 ± 5.9, 7.7 ± 4.6, 569.9 ± 96.1 s/mm2 and 825.8 ± 93.2 s/mm2, respectively. We found a significant inverse correlation between the ADCmin and SUVmax (r = −0.58, P < 0.001) as well as between the ADCmin and SUVmean (r = −0.44, P < 0.001). Tumour grading showed a significant positive correlation with SUVmax and SUVmean (R = 0.34 and R = 0.31, both P < 0.05) and a significant inverse correlation with ADCmin and ADCmean (r = −0.30 and r = −0.40, both P < 0.05). In addition, erbB2 showed a significant inverse correlation with SUVmax and SUVmean (r = −0.50 and r = −0.49, both P < 0.05). The other immunohistochemical markers did not show any significant correlation. Conclusion: 18F‐FDG‐PET/MRI showed weak to moderate correlations between SUV, ADC, tumour grading and erbB2‐expression of lung cancer. Hence, 18F‐FDG‐PET/MRI may, to some extent, offer complementary information to the histopathology of lung cancer, for the evaluation of tumour aggressiveness and treatment response. [ABSTRACT FROM AUTHOR]