Faculty Bibliography

Thyroid hormone (TH) is an important regulator of mammalian metabolism and facilitates cold induced thermogenesis (CIT) in brown adipose tissue (BAT). Profound hypothyroidism or hyperthyroidism lead to alterations in BAT function and CIT. In euthyroid humans the inter-individual variation of thyroid hormones is relatively large. Therefore, we investigated whether levels of free thyroxine (T4) or free triiodothyronine (T3) are positively associated with CIT in euthyroid individuals. We performed an observational study in 79 healthy, euthyroid volunteers (mean age 25.6 years, mean BMI 23.0 kg · m^-2). Resting energy expenditure (REE) was measured by indirect calorimetry during warm conditions (EE_warm) and after a mild cold stimulus of two hours (EE_cold). CIT was calculated as the difference between EE_cold and EE_warm. BAT activity was assessed by ¹⁸F-FDG-PET after a mild cold stimulus in a subset of 26 participants. EE_cold and CIT were significantly related to levels of free T4 (R² = 0.11, p=0.0025 and R² = 0.13, p=0.0011, respectively) but not to free T3 and TSH. Cold induced BAT activity was also associated with levels of free T4 (R² = 0.21, p=0.018). CIT was approximately fourfold higher in participants in the highest tertile of free T4 as compared to the lowest tertile. Additionally, free T4 was weakly, albeit significantly associated with outdoor temperature seven days prior to the respective study visit (R² = 0.06, p=0.037). These finding suggests that variations in thyroid hormone levels within the euthyroid range are related to the capability to adapt to cool temperatures and affect energy balance.

INTRODUCTION/BACKGROUND:The role of positron-emission tomography/computed-tomography (PET/CT) in the management of sarcomas and as a prognostic tool has been studied. However, it remains unclear which metric is the most useful. We aimed to investigate if volume-based PET metrics (Tumor volume (TV) and total lesions glycolysis (TLG)) are superior to maximal standardized uptake value (SUVmax) and other metrics in predicting survival of patients with soft tissue and bone sarcomas. MATERIALS AND METHODS/METHODS:In this retrospective cohort study, we screened over 52'000 PET/CT scans to identify patients diagnosed with either soft tissue, bone or Ewing sarcoma and had a staging scan at our institution before initial therapy. We used a Wilcoxon signed-rank to assess which PET/CT metric was associated with survival in different patient subgroups. Receiver-Operating-Characteristic curve analysis was used to calculate cutoff values. RESULTS:= 0.03). DISCUSSION/CONCLUSIONS:Our analysis shows that the outcome of soft tissue, bone and Ewing sarcomas is associated with different PET/CT metrics. We could not confirm the previously suggested superiority of volume-based metrics in soft tissue sarcomas, for which we found SUVmax to remain the best prognostic factor. However, bone sarcomas should probably be evaluated with tumor volume rather than FDG PET activity.

OBJECTIVE:While single sugar tests are controversially discussed, combination tests with meals are gaining more attention. The aim of this study was to analyze the impact of adding a test meal to lactulose hydrogen breath tests (LHBT) on hydrogen values and abdominal symptoms in patients with functional gastrointestinal disorders (FGIDs). METHODS:Data of 81 FGID patients between 2014-2018 were analyzed. Patients underwent LHBT with 30 g lactulose + 300 mL water and a nutrient challenge test (NCT) including 400 mL liquid test meal + 30 g lactulose. To statistically assess the effect of a test meal on abdominal symptoms and H2, mixed-effect models were used. RESULTS:Adding a test meal to LHBT showed a significant increase in nausea [odds ratio (OR) 1.4; 95% confidence interval (CI), 1.1-1.7], decrease in abdominal pain (OR 0.7; 95% CI, 0.6-0.9), borborygmi (OR 0.5; 95% CI, 0.4-0.6), diarrhea (OR 0.4; 95% CI, 0.3-0.6), and H2 production (estimate -5.3, SE 0.7, P < 0.001). The effect on bloating was only significant in functional dyspepsia, irritable bowel syndrome-functional dyspepsia mixed type and functional abdominal pain/bloating (OR 0.1; 95% CI, 0.0-0.2; OR 1.7; 95% CI, 1.2-2.3 resp OR 4.4; 95% CI, 1.8-10.6). CONCLUSIONS:Significant effects on abdominal symptoms and H2 production by adding a test meal to LHBT in FGID patients are shown. Increased occurrence of nausea may be caused by gastric/duodenal hypersensitivity; decreased H2, diarrhea and borborygmi by slower and more physiologic gastric emptying resulting in later arrival of the test substance in the bowel. We recommend NCTs instead of LHBT to more physiologically represent FGID patients' meal-induced burden.

BACKGROUND:F-fluorodeoxyglucose (FDG) PET or PET/CT has shown the capacity to better identify the primary tumour site and detect additional sites of metastasis. However, its clinical impact is not well established. We performed a systematic review and meta-analysis of prior studies to assess the impact of FDG-PET or PET/CT on the management of patients with CUP. MATERIALS AND METHODS:Pubmed and EMBASE databases were searched up to 4th February 2021. Studies that reported the proportion of patients with CUP who experienced a management change after FDG-PET or PET/ computed tomography (CT) were included and the proportions were pooled using the random-effects model. Study quality was assessed using QUADAS-2. Subgroup analysis was conducted to explore heterogeneity. RESULTS: = 82%). The specific reason for management change was more commonly detection of the primary site (22% [95% CI 18-28%]) than detection of additional metastatic sites (14% [95% CI 10-19%]). The pooled proportions of patients with management changes were similar among numerous subgroups (range, 32.8%-38.2%). CONCLUSION:FDG-PET or PET/CT had a meaningful impact on the management of patients with CUP. Approximately, a third of patients had their management changed because of FDG-PET or PET/CT results, and this finding was consistent across numerous subgroups.

Bone regeneration is a complex process and the clinical translation of tissue engineered constructs (TECs) remains a challenge. The combination of biomaterials and mesenchymal stem cells (MSCs) may enhance the healing process through paracrine effects. Here, we investigated the influence of cell format in combination with a collagen scaffold on key factors in bone healing process, such as mineralization, cell infiltration, vascularization, and ECM production. MSCs as single cells (2D-SCs), assembled into microtissues (3D-MTs) or their corresponding secretomes were combined with a collagen scaffold and incubated on the chicken embryo chorioallantoic membrane (CAM) for 7 days. A comprehensive quantitative analysis was performed on a cellular level by histology and by microcomputed tomography (microCT). In all experimental groups, accumulation of collagen and glycosaminoglycan within the scaffold was observed over time. A pronounced cell infiltration and vascularization from the interface to the surface region of the CAM was detected. The 3D-MT secretome showed a significant mineralization of the biomaterial using microCT compared to all other conditions. Furthermore, it revealed a homogeneous distribution pattern of mineralization deposits in contrast to the cell-based scaffolds, where mineralization was only at the surface. Therefore, the secretome of MSCs assembled into 3D-MTs may represent an interesting therapeutic strategy for a next-generation bone healing concept.

RATIONALE AND OBJECTIVES:Prostate gland volume (PGV) should be routinely included in MRI reports of the prostate. The recently updated Prostate Imaging Reporting and Data System (PI-RADS) version 2.1 includes a change in the recommended measurement method for PGV compared to version 2.0. The purpose of this study was to evaluate the agreement of MRI-based PGV calculations with the volumetric manual slice-by-slice prostate segmentation as a reference standard using the linear measurements per PI-RADS versions 2.0 and 2.1. Furthermore, to assess inter-reader agreement for the different measurement approaches, determine the influence of an enlarged transition zone on measurement accuracy and to assess the value of the bullet formula for PGV calculation. MATERIALS AND METHODS:Ninety-five consecutive treatment-naive patients undergoing prostate MRI were retrospectively analyzed. Prostates were manually contoured and segmented on axial T2-weighted images. Four different radiologists independently measured the prostate in three dimensions according to PI-RADS v2.0 and v2.1, respectively. MRI-based PGV was calculated using the ellipsoid and bullet formulas. Calculated volumes were compared to the reference manual segmentations using Wilcoxon signed-rank test. Inter-reader agreement was calculated using intraclass correlation coefficient (ICC). RESULTS:Inter-reader agreement was excellent for the ellipsoid and bullet formulas using PI-RADS v2.0 (ICC 0.985 and 0.987) and v2.1 (ICC 0.990 and 0.994), respectively. The median difference from the reference standard using the ellipsoid formula derived PGV was 0.4 mL (interquartile range, -3.9 to 5.1 mL) for PI-RADS v2.0 (p = 0.393) and 2.6 mL (interquartile range, -1.6 to 7.3 mL) for v2.1 (p < 0.001) with a median difference of 2.2 mL. The bullet formula overestimated PGV by a median of 13.3 mL using PI-RADS v2.0 (p < 0.001) and 16.0 mL using v2.1 (p < 0.001). In the presence of an enlarged transition zone the PGV tended to be higher than the reference standard for PI-RADS v2.0 (median difference of 4.7 mL; p = 0.018) and for v2.1 (median difference of 5.7 mL, p < 0.001) using the ellipsoid formula. CONCLUSION:Inter-reader agreement was excellent for the calculated PGV for both methods. PI-RADS v2.0 measurements with the ellipsoid formula yielded the most accurate volume estimates. The differences between PI-RADS v2.0 and v2.1 were statistically significant although small in absolute numbers but may be of relevance in specific clinical scenarios like prostate-specific antigen density calculation. These findings validate the use of the ellipsoid formula and highlight that the bullet formula should not be used for prostate volume estimation due to systematic overestimation.

Vaccination-associated adenopathy is a frequent imaging finding after administration of COVID-19 vaccines that may lead to a diagnostic conundrum in patients with manifest or suspected cancer, in whom it may be indistinguishable from malignant nodal involvement. To help the medical community address this concern in the absence of studies and evidence-based guidelines, this special report offers recommendations developed by a multidisciplinary panel of experts from three of the leading tertiary care cancer centers in the United States. According to these recommendations, some routine imaging examinations, such as those for screening, should be scheduled before or at least 6 weeks after the final vaccination dose to allow for any reactive adenopathy to resolve. However, there should be no delay of other clinically indicated imaging (eg, for acute symptoms, short-interval treatment monitoring, urgent treatment planning or complications) due to prior vaccination. The vaccine should be administered on the side contralateral to the primary or suspected cancer, and both doses should be administered in the same arm. Vaccination information-date(s) administered, injection site(s), laterality, and type of vaccine-should be included in every preimaging patient questionnaire, and this information should be made readily available to interpreting radiologists. Clear and effective communication between patients, radiologists, referring physician teams, and the general public should be considered of the highest priority when managing adenopathy in the setting of COVID-19 vaccination.

OBJECTIVES/OBJECTIVE:To assess interreader agreement of manual prostate cancer lesion segmentation on multiparametric MR images (mpMRI). The secondary aim was to compare tumor volume estimates between MRI segmentation and transperineal template saturation core needle biopsy (TTSB). METHODS:We retrospectively reviewed patients who had undergone mpMRI of the prostate at our institution and who had received TTSB within 190 days of the examination. Seventy-eight cancer lesions with Gleason score of at least 3 + 4 = 7 were manually segmented in T2-weighted images by 3 radiologists and 1 medical student. Twenty lesions were also segmented in apparent diffusion coefficient (ADC) and dynamic contrast enhanced (DCE) series. First, 20 volumetric similarity scores were computed to quantify interreader agreement. Second, manually segmented cancer lesion volumes were compared with TTSB-derived estimates by Bland-Altman analysis and Wilcoxon testing. RESULTS:Interreader agreement across all readers was only moderate with mean T2 Dice score of 0.57 (95%CI 0.39-0.70), volumetric similarity coefficient of 0.74 (0.48-0.89), and Hausdorff distance of 5.23 mm (3.17-9.32 mm). Discrepancy of volume estimate between MRI and TTSB was increasing with tumor size. Discrepancy was significantly different between tumors with a Gleason score 3 + 4 vs. higher grade tumors (0.66 ml vs. 0.78 ml; p = 0.007). There were no significant differences between T2, ADC, and DCE segmentations. CONCLUSIONS:We found at best moderate interreader agreement of manual prostate cancer segmentation in mpMRI. Additionally, our study suggests a systematic discrepancy between the tumor volume estimate by MRI segmentation and TTSB core length, especially for large and high-grade tumors. KEY POINTS/CONCLUSIONS:• Manual prostate cancer segmentation in mpMRI shows moderate interreader agreement. • There are no significant differences between T2, ADC, and DCE segmentation agreements. • There is a systematic difference between volume estimates derived from biopsy and MRI.

OBJECTIVES:Non-Cartesian Spiral readout can be implemented in 3D Time-of-flight (TOF) MR angiography (MRA) with short acquisition times. In this intra-individual comparison study we evaluated the clinical feasibility of Spiral TOF MRA in comparison with compressed sensing accelerated TOF MRA at 1.5T for intracranial vessel imaging as it has yet to be determined. MATERIALS AND METHODS:Forty-four consecutive patients with suspected intracranial vascular disease were imaged with two Spiral 3D TOFs (Spiral, 0.82x0.82x1.2 mm3, 01:32 min; Spiral 0.8, 0.8x0.8x0.8 mm3, 02:12 min) and a Compressed SENSE accelerated 3D TOF (CS 3.5, 0.82x0.82x1.2 mm3, 03:06 min) at 1.5T. Two neuroradiologists assessed qualitative (visualization of central and peripheral vessels) and quantitative image quality (Contrast Ratio, CR) and performed lesion and variation assessment for all three TOFs in each patient. After the rating process, the readers were questioned and representative cases were reinspected in a non-blinded fashion. For statistical analysis, the Friedman and Nemenyi post-hoc test, Kendall W tests, repeated measure ANOVA and weighted Cohen's Kappa tests were used. RESULTS:The Spiral and Spiral 0.8 outperformed the CS 3.5 in terms of peripheral image quality (p<0.001) and performed equally well in terms of central image quality (p>0.05). The readers noted slight differences in the appearance of maximum intensity projection images. A good to high degree of interstudy agreement between the three TOFs was observed for lesion and variation assessment (W = 0.638, p<0.001 -W = 1, p<0.001). CR values did not differ significantly between the three TOFs (p = 0.534). Interreader agreement ranged from good (K = 0.638) to excellent (K = 1). CONCLUSIONS:Compared to the CS 3.5, both the Spiral and Spiral 0.8 exhibited comparable or better image quality and comparable diagnostic performance at much shorter acquisition times.

PURPOSE/OBJECTIVE:To evaluate a deep learning based image analysis software for the detection and localization of distal radius fractures. METHOD/METHODS:A deep learning system (DLS) was trained on 524 wrist radiographs (166 showing fractures). Performance was tested on internal (100 radiographs, 42 showing fractures) and external test sets (200 radiographs, 100 showing fractures). Single and combined views of the radiographs were shown to DLS and three readers. Readers were asked to indicate fracture location with regions of interest (ROI). The DLS yielded scores (range 0-1) and a heatmap. Detection performance was expressed as AUC, sensitivity and specificity at the optimal threshold and compared to radiologists' performance. Heatmaps were compared to radiologists' ROIs. RESULTS:The DLS showed excellent performance on the internal test set (AUC 0.93 (95% confidence interval (CI) 0.82-0.98) - 0.96 (0.87-1.00), sensitivity 0.81 (0.58-0.95) - 0.90 (0.70-0.99), specificity 0.86 (0.68-0.96) - 1.0 (0.88-1.0)). DLS performance decreased on the external test set (AUC 0.80 (0.71-0.88) - 0.89 (0.81-0.94), sensitivity 0.64 (0.49-0.77) - 0.92 (0.81-0.98), specificity 0.60 (0.45-0.74) - 0.90 (0.78-0.97)). Radiologists' performance was comparable on internal data (sensitivity 0.71 (0.48-0.89) - 0.95 (0.76-1.0), specificity 0.52 (0.32-0.71) - 0.97 (0.82-1.0)) and better on external data (sensitivity 0.88 (0.76-0.96) - 0.98 (0.89-1.0), specificities 0.66 (0.51-0.79) - 1.0 (0.93-1.0), p < 0.05). In over 90%, the areas of peak activation aligned with radiologists' annotations. CONCLUSIONS:The DLS was able to detect and localize wrist fractures with a performance comparable to radiologists, using only a small dataset for training.