The significance of central blood pressure for cardiovascular target organ damage in children and adolescents after kidney transplantation.

BACKGROUND: Cardiovascular (CV) complications are important causes of morbidity and mortality in children after kidney transplantation (KTx). In adults, central blood pressure (cBP) is an accepted predictor of CV sequelae. We aimed to assess the prognostic value of cBP over peripheral blood pressure (pBP) for existing CV damage. METHODS: We measured cBP and pBP in 48 pediatric KTx recipients (mean age: 13.5 ± 4.2 years). Assessment of left ventricular mass index (LVMI) and aortic pulse wave velocity (PWV) allowed detection of CV target organ damage. LVMI and PWV were used as endpoints in multivariable linear regression models, in which cBP and pBP were compared for their predictive value. RESULTS: Using cBP z-scores, we identified a larger number of patients with uncontrolled or untreated hypertension compared to pBP (36% vs. 7%). Central systolic blood pressure (cSBP) was a significant independent predictor of LVMI, while peripheral systolic blood pressure (pSBP) was not. Comparing central (cDBP) and peripheral (pDBP) diastolic blood pressure for their predictive value on PWV revealed a greater estimate for cDBP (0.035 vs. 0.026 for pDBP) along with a slightly better model fit for cDBP. CONCLUSIONS: Our data in a small group of patients provide first evidence that cBP measurements in pediatric KTx recipients might be helpful in identifying patients at risk for the development of CV sequelae. Investigating a larger patient number, ideally repeatedly, is needed to create further evidence supporting our findings. In light of available devices measuring cBP noninvasively, the implementation of such clinical studies post-KTx care should be feasible. A higher resolution version of the Graphical abstract is available as Supplementary information.

Arterial stiffness and blood pressure increase in pediatric kidney transplant recipients.

BACKGROUND: Pulse wave velocity (PWV) is a measure of arterial stiffness. We investigated PWV and blood pressure (BP) to determine to what extent BP changes contribute to arterial stiffness, and secondly, to identify influencing factors on BP in children after kidney transplantation. METHODS: Seventy children ≥ 2.5 years post-transplantation with at least two PWV measurements were included. Changes of systolic (Δ SBP) and diastolic BP (Δ DBP) were classified into "stable/decreasing," "1-10 mmHg increase," and " > 10 mmHg increase." Linear mixed modeling for PWV z-score (PWVz) adjusted either for Δ SBP or Δ DBP was performed. An extended dataset with monthly entries of BP, immunosuppression, and creatinine was obtained in 35 participants over a median of 74 months to perform linear mixed modeling for SBP and DBP. RESULTS: PWVz increased with a rate of 0.11/year (95% CI 0.054 to 0.16). Compared to participants with stable BP, those with 1-10-mmHg SBP and DBP increase showed a higher PWVz of 0.59 (95% CI 0.046 to 1.13) and 0.86 (95% CI 0.43 to 1.30), respectively. A > 10-mmHg BP increase was associated with an even higher PWVz (SBP ß = 0.78, 95% CI 0.22 to 1.34; DBP ß = 1.37, 95% CI 0.80 to 1.94). Female sex and participants with lower eGFR showed higher PWVz. In the extended analysis, DBP was positively associated with cyclosporin A and everolimus trough levels. CONCLUSIONS: A higher increase of PWV is seen in patients with greater BP increase, with higher cyclosporin A and everolimus trough levels associated with higher BP. This emphasizes the role of BP as a modifiable risk factor for the improvement of cardiovascular outcome after transplantation. A higher resolution version of the Graphical abstract is available as Supplementary information.

Telomere length is associated with intima-media thickness in pediatric liver transplant patients: A prospective cohort study.

Leukocyte telomere length (LTL) is a marker for biological age. Pediatric liver transplant recipients show a high rate of subclinical atherosclerosis, indicated by elevated intima-media thickness (IMT). We hypothesized that atherosclerosis is associated with biological age in these patients and investigated the course of LTL over time. We measured LTL from peripheral blood leukocytes by quantitative polymerase chain reaction and IMT from 97 pediatric patients after liver transplantation in a prospective cohort study. Of the patients, 71% (n = 69) had two or more assessments (total, 228 observations; median follow-up, 1.1 years). Lower LTL was associated with higher IMT (ß = -0.701, p = 0.01) and higher aspartate aminotransferase (ß = -0.001, p = 0.02), adjusted for age, sex, and age at transplantation. Of the patients, 45% showed decreasing LTL over time, whereas 55% exhibited stable LTL. Patients with stable LTL showed a decrease in IMT (median, -0.02 mm/year) and a decrease of tacrolimus trough levels (median, -0.08 µg/L/year). LTL is associated with IMT independent of age in pediatric liver transplant patients, suggesting that early aging contributes to the high burden of subclinical cardiovascular damage and may furthermore negatively affect the graft.

Efficacy and tolerability of regorafenib in pretreated patients with progressive CNS grade 3 or 4 gliomas.

BACKGROUND: The phase 2 REGOMA trial suggested an encouraging overall survival benefit in glioblastoma patients at first relapse treated with the multikinase inhibitor regorafenib. Here, we evaluated the efficacy and side effects of regorafenib in a real-life setting. METHODS: From 2018 to 2021, 30 patients with progressive WHO CNS grade 3 or 4 gliomas treated with regorafenib (160 mg/day; first 3 weeks of each 4-week cycle) with individual dose adjustment depending on toxicity were retrospectively identified. Side effects were evaluated according to the Common Terminology Criteria for Adverse Events (version 5.0). MRI was obtained at baseline and after every second cycle. Tumor progression was assessed according to RANO criteria. After regorafenib initiation, the median PFS and OS were calculated. RESULTS: The median number of treatment lines before regorafenib was 2 (range 1-4). Most patients (73%) had two or more pretreatment lines. At first relapse, 27% of patients received regorafenib. A total of 94 regorafenib cycles were administered (median 2 cycles; range 1-9 cycles). Grade 3 and 4 side effects were observed in 47% and 7% of patients, respectively, and were not significantly increased in patients with two or more pretreatments (P > 0.05). The most frequent grade 3 or 4 side effects were laboratory abnormalities (62%). PFS was 2.6 months (range 0.8-8.2 months), and the OS was 6.2 months (range 0.9-24 months). CONCLUSIONS: In patients with progressive WHO grade 3 or 4 gliomas, predominantly with two pretreatment lines or more, regorafenib seems to be effective despite considerable grade 3 or 4 side effects.

Impact of Sex and Obesity on Echocardiographic Parameters in Children and Adolescents.

Subclinical alterations in left ventricular structure and function are detectable in adolescents with hypertension or obesity. However, data on early echocardiographic abnormalities in seemingly healthy children are lacking. Sex differences in cardiac structure and function have been previously reported, but sex-specific reference values are not available. Specifically, the potential interaction of sex and overweight has not been addressed at all. Anthropometric data, blood pressure and exercise tests were obtained in 356 healthy children. Echocardiographic parameters comprised peak early (E) and late (A) mitral inflow Doppler velocities, E/A ratio, tissue Doppler peak velocities of early (e') and late diastolic (a') excursion of mitral/septal annulus and isovolumetric relaxation time (IVRT). Left ventricular mass index (LVMI) and LVMI z-score were calculated. Interaction terms between BMI and sex and stratification by sex were used for analysis. We provide values for echocardiographic parameters for children of two age groups separated by BMI. Overweight/obese children had a significant higher LVMI, lower E/A ratio, higher E/e' ratios and a longer IVRT. For a given BMI in the upper ranges we demonstrated a higher LVMI in girls than in boys, the IVRT extended significantly more in girls than in boys with increasing BMI. There are sex differences in structural and functional echocardiographic parameters in children and adolescents. Our data not only confirms the importance of overweight and obesity, but demonstrates important interactions between sex and overweight. The greater susceptibility of overweight girls toward echocardiographic changes associated with potential long-term functional impairment needs further exploration and follow-up.Trial registration number DRKS00012371; Date 18.08.2017.

Prospective assessment of subclinical cardiovascular damage and associated factors in liver transplant recipients.

Cardiovascular (CV) disease plays a major role after liver transplantation (LT). This prospective study assessed subclinical CV damage after LT by measuring pulse wave velocity (PWV), intima-media thickness (IMT) and left-ventricular mass index (LVMI) and characterized associated risk factors. We included 112 patients with a median of 1.8 years after LT (q1-q3 0.9-9.2). Fifty-three percent (n = 59) of patients had ≥2 annual assessments (median follow-up 1.6 years, q1-q3 1.1-2.0), with a total of 195 assessments. We found increased PWV (indicating arteriosclerosis) in 16% (n = 17), elevated IMT in 5% (n = 5; indicating atherosclerosis) and increased LVMI in 25% (n = 24; indicating left-ventricular hypertrophy). A linear mixed model analysis using all 195 assessments revealed that higher age and systolic blood pressure (BP) were associated with higher PWV (ß = 0.069, P < 0.001 and ß = 0.022, P = 0.005) and higher IMT (ß = 0.005, P < 0.001 and ß = 0.001, P = 0.029), while higher body mass index was associated with higher IMT (ß = 0.004, P = 0.023). Higher systolic BP (ß = 0.200, P = 0.034), male sex (ß = 8.847, P = 0.031) and lower glomerular filtration rate (ß = -0.288, P < 0.001) were associated with higher LVMI. Our data highlight not only the rate of subclinical CV damage in LT patients, but also the impact of classical CV risk factors (such as BP and body mass index) which outweighed LT-related factors. These modifiable risk factors are suitable targets for interventions to reduce CV morbidity in LT patients.

Prediction of survival in patients with IDH-wildtype astrocytic gliomas using dynamic O-(2-[18F]-fluoroethyl)-L-tyrosine PET.

PURPOSE: Integrated histomolecular diagnostics of gliomas according to the World Health Organization (WHO) classification of 2016 has refined diagnostic accuracy and prediction of prognosis. This study aimed at exploring the prognostic value of dynamic O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET in newly diagnosed, histomolecularly classified astrocytic gliomas of WHO grades III or IV. METHODS: Before initiation of treatment, dynamic FET PET imaging was performed in patients with newly diagnosed glioblastoma (GBM) and anaplastic astrocytoma (AA). Static FET PET parameters such as maximum and mean tumour/brain ratios (TBRmax/mean), the metabolic tumour volume (MTV) as well as the dynamic FET PET parameters time-to-peak (TTP) and slope, were obtained. The predictive ability of FET PET parameters was evaluated concerning the progression-free and overall survival (PFS, OS). Using ROC analyses, threshold values for FET PET parameters were obtained. Subsequently, univariate Kaplan-Meier and multivariate Cox regression survival analyses were performed to assess the predictive power of these parameters for survival. RESULTS: Sixty patients (45 GBM and 15 AA patients) of two university centres were retrospectively identified. Patients with isocitrate dehydrogenase (IDH)-mutant or O6-methylguanine-DNA-methyltransferase (MGMT) promoter-methylated tumours had a significantly longer PFS and OS (both P < 0.001). Furthermore, ROC analysis of IDH-wildtype glioma patients (n = 45) revealed that a TTP > 25 min (AUC, 0.90; sensitivity, 90%; specificity, 87%; P < 0.001) was highly prognostic for longer PFS (13 vs. 7 months; P = 0.005) and OS (29 vs. 12 months; P < 0.001). In contrast, at a lower level of significance, TBRmax, TBRmean, and MTV were only prognostic for longer OS (P = 0.004, P = 0.038, and P = 0.048, respectively). Besides complete resection and a methylated MGMT promoter, TTP remained significant in multivariate survival analysis (all P ≤ 0.02), indicating an independent predictor for OS. CONCLUSIONS: Our data suggest that dynamic FET PET allows the identification of patients with longer OS among patients with newly diagnosed IDH-wildtype GBM and AA.

High Burden of Subclinical Cardiovascular Target Organ Damage After Pediatric Liver Transplantation.

Cardiovascular (CV) events account for 8%-13% of deaths after liver transplantation (LT) in adulthood. Although CV risk factors (RFs) are present, little is known about the prevalence of subclinical CV target organ damage (TOD) in children after LT. The aim of this prospective observational study was to assess the prevalence of subclinical CV TOD in children after LT and to identify RFs contributing to CV damage as potential targets for clinical intervention. In this study, 104 children after LT (54% female, 46% male; aged 11.5 ± 3.8 years) underwent cross-sectional assessment of subclinical TOD by carotid-femoral pulse wave velocity (PWV), carotid intima-media thickness (IMT), and left ventricular mass index (LVMI). Results were correlated with the presence of CV RFs (obesity, hypertension, dyslipidemia, renal impairment, anemia, and microinflammation). Of the patients, 22% were exposed to 2 CV RFs, and 36% displayed 3 or more CV RFs. Pathological results for PWV, IMT, and LVMI were found in 21.9%, 57.0%, and 11.1% of patients, respectively. In the multivariate analysis, diastolic blood pressure (P = 0.01) and estimated glomerular filtration rate (eGFR; P = 0.03) were independently associated with PWV, eGFR (P = 0.005), and age at LT (P = 0.048) with IMT and body mass index with LVMI (P = 0.004). In conclusion, patients after pediatric LT carry a substantial burden of subclinical CV TOD. Identification of modifiable CV RFs opens opportunities for targeted intervention in order to reduce CV morbidity and mortality in the future.

FET PET reveals considerable spatial differences in tumour burden compared to conventional MRI in newly diagnosed glioblastoma.

PURPOSE: Areas of contrast enhancement (CE) on MRI are usually the target for resection or radiotherapy target volume definition in glioblastomas. However, the solid tumour mass may extend beyond areas of CE. Amino acid PET can detect parts of the tumour that show no CE. We systematically investigated tumour volumes delineated by amino acid PET and MRI in patients with newly diagnosed, untreated glioblastoma. METHODS: Preoperatively, 50 patients with neuropathologically confirmed glioblastoma underwent O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET, and fluid-attenuated inversion recovery (FLAIR) and contrast-enhanced MRI. Areas of CE were manually segmented. FET PET tumour volumes were segmented using a tumour-to-brain ratio of ≥1.6. The percentage overlap volumes, and Dice and Jaccard spatial similarity coefficients (DSC, JSC) were calculated. FLAIR images were evaluated visually. RESULTS: In 43 patients (86%), the FET tumour volume was significantly larger than the CE volume (21.5 ± 14.3 mL vs. 9.4 ± 11.3 mL; P < 0.001). Forty patients (80%) showed both increased uptake of FET and CE. In these 40 patients, the spatial similarity between FET uptake and CE was low (mean DSC 0.39 ± 0.21, mean JSC 0.26 ± 0.16). Ten patients (20%) showed no CE, and one of these patients showed no FET uptake. In five patients (10%), increased FET uptake was present outside areas of FLAIR hyperintensity. CONCLUSION: Our results show that the metabolically active tumour volume delineated by FET PET is significantly larger than tumour volume delineated by CE. Furthermore, the results strongly suggest that the information derived from both imaging modalities should be integrated into the management of patients with newly diagnosed glioblastoma.

Static and dynamic 18F-FET PET for the characterization of gliomas defined by IDH and 1p/19q status.

PURPOSE: The molecular features isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion have gained major importance for both glioma typing and prognosis and have, therefore, been integrated in the World Health Organization (WHO) classification in 2016. The aim of this study was to characterize static and dynamic O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) PET parameters in gliomas with or without IDH mutation or 1p/19q co-deletion. METHODS: Ninety patients with newly diagnosed and untreated gliomas with a static and dynamic 18F-FET PET scan prior to evaluation of tumor tissue according to the 2016 WHO classification were identified retrospectively. Mean and maximum tumor-to-brain ratios (TBRmean/max), as well as dynamic parameters (time-to-peak and slope) of 18F-FET uptake were calculated. RESULTS: Sixteen (18%) oligodendrogliomas (IDH mutated, 1p/19q co-deleted), 27 (30%) astrocytomas (IDH mutated only), and 47 (52%) glioblastomas (IDH wild type only) were identified. TBRmean, TBRmax, TTP and slope discriminated between IDH mutated astrocytomas and IDH wild type glioblastomas (P < 0.01). TBRmean showed the best diagnostic performance (cut-off 1.95; sensitivity, 89%; specificity, 67%; accuracy, 81%). None of the parameters discriminated between oligodendrogliomas (IDH mutated, 1p/19q co-deleted) and glioblastomas or astrocytomas. Furthermore, TBRmean, TBRmax, TTP, and slope discriminated between gliomas with and without IDH mutation (p < 0.01). The best diagnostic performance was obtained for the combination of TTP with TBRmax or slope (accuracy, 73%). CONCLUSION: Data suggest that static and dynamic 18F-FET PET parameters may allow determining non-invasively the IDH mutation status. However, IDH mutated and 1p/19q co-deleted oligodendrogliomas cannot be differentiated from glioblastomas and astrocytomas by 18F-FET PET.

Early treatment response evaluation using FET PET compared to MRI in glioblastoma patients at first progression treated with bevacizumab plus lomustine.

BACKGROUND: The goal of this prospective study was to compare the value of both conventional MRI and O-(2-18F-fluoroethyl)-L-tyrosine (FET) PET for response evaluation in glioblastoma patients treated with bevacizumab plus lomustine (BEV/LOM) at first progression. METHODS: After chemoradiation with concomitant and adjuvant temozolomide, 21 IDH wild-type glioblastoma patients at first progression (age range, 33-75 years; MGMT promoter unmethylated, 81%) were treated with BEV/LOM. Contrast-enhanced MRI and FET-PET scans were performed at baseline and after 8-10 weeks. We obtained FET metabolic tumor volumes (MTV) and tumor/brain ratios. Threshold values of FET-PET parameters for treatment response were established by ROC analyses using the post-progression overall survival (OS) ≤/>9 months as the reference. MRI response assessment was based on RANO criteria. The predictive ability of FET-PET thresholds and MRI changes on early response assessment was evaluated subsequently concerning OS using uni- and multivariate survival estimates. RESULTS: Early treatment response as assessed by RANO criteria was not predictive for an OS>9 months (P = 0.203), whereas relative reductions of all FET-PET parameters significantly predicted an OS>9 months (P < 0.05). The absolute MTV at follow-up enabled the most significant OS prediction (sensitivity, 85%; specificity, 88%; P = 0.001). Patients with an absolute MTV below 5 ml at follow-up survived significantly longer (12 vs. 6 months, P < 0.001), whereas early responders defined by RANO criteria lived only insignificantly longer (9 vs. 6 months; P = 0.072). The absolute MTV at follow-up remained significant in the multivariate survival analysis (P = 0.006). CONCLUSIONS: FET-PET appears to be useful for identifying responders to BEV/LOM early after treatment initiation.

The role of amino-acid PET in the light of the new WHO classification 2016 for brain tumors.

Since its introduction in 2016, the revision of the World Health Organization (WHO) classification of central nervous system tumors has already changed the diagnostic and therapeutic approach in glial tumors. Blurring the lines between entities formerly labelled as "high-grade" or "low-grade", molecular markers define distinct biological subtypes with different clinical course. This new classification raises the demand for non-invasive imaging methods focusing on depicting metabolic processes. We performed a review of current literature on the use of amino-acid PET (AA-PET) for obtaining diagnostic or prognostic information on glioma in the setting of the current WHO 2016 classification. So far, only a few studies have focused on combining molecular genetic information and metabolic imaging using AA-PET. The current review summarizes the information available on "molecular grading" as well as prognostic information obtained from AA-PET and delivers an insight into a possible interrelation between metabolic imaging and glioma genetics. Within the framework of molecular characterization of gliomas, metabolic imaging using AA-PET is a promising tool for non-invasive characterization of molecular features and to provide additional prognostic information. Further studies incorporating molecular and metabolic features are necessary to improve the explanatory power of AA-PET in glial tumors.

Factors associated with cardiovascular target organ damage in children after renal transplantation.

BACKGROUND: Cardiovascular disease is the second-most common cause of death in pediatric renal transplant recipients. The aim of this study was to evaluate subclinical cardiovascular target organ damage defined as the presence of arterio- and atherosclerotic lesions and cardiac remodeling and to analyze contributing risk factors in a large cohort of children after renal transplantation (RT). METHODS: A total of 109 children aged 13.1 ± 3.3 years who had undergone RT at one of three German transplant centers were enrolled in this study. Patients had been transplanted a mean of 5.5 (±4.0) years prior to being enrolled in the study. Anthropometric data, laboratory values and office- and 24-h ambulatory blood pressure monitoring (ABPM) were evaluated. Cardiovascular target organ damage was determined through non-invasive measurements of aortic pulse wave velocity (PWV), carotid intima-media thickness (IMT) and left ventricular mass (LVM). RESULTS: Elevated PWV or IMT values were detected in 22 and 58% of patients, respectively. Left ventricular hypertrophy was found in as many as 43% of patients. The prevalence of uncontrolled or untreated hypertension was 41%, of which 16% of cases were only detected by ABPM measurements. In the multivariable analysis, higher diastolic blood pressure, everolimus intake and lower estimated glomerular filtration rate were independently associated with high PWV. Higher systolic blood pressure and body mass index were associated with elevated LVM. CONCLUSIONS: Our results showed an alarming burden of cardiovascular subclinical organ damage in children after RT. Hypertension, obesity, immunosuppressive regimen and renal function emerged as independent risk factors of organ damage. Whereas the latter is not modifiable, the results of our study strongly indicate that the management of children after RT should focus on the control of blood pressure and weight.

Prediction of response to lomustine-based chemotherapy in glioma patients at recurrence using MRI and FET PET.

BACKGROUND: We evaluated O-(2-[18F]fluoroethyl)-l-tyrosine (FET) PET and MRI for early response assessment in recurrent glioma patients treated with lomustine-based chemotherapy. METHODS: Thirty-six adult patients with WHO CNS grade 3 or 4 gliomas (glioblastoma, 69%) at recurrence (median number of recurrences, 1; range, 1-3) were retrospectively identified. Besides MRI, serial FET PET scans were performed at baseline and early after chemotherapy initiation (not later than two cycles). Tumor-to-brain ratios (TBR), metabolic tumor volumes (MTV), the occurrence of new distant hotspots with a mean TBR >1.6 at follow-up, and the dynamic parameter time-to-peak were derived from all FET PET scans. PET parameter thresholds were defined using ROC analyses to predict PFS of ≥6 months and OS of ≥12 months. MRI response assessment was based on RANO criteria. The predictive values of FET PET parameters and RANO criteria were subsequently evaluated using univariate and multivariate survival estimates. RESULTS: After treatment initiation, the median follow-up time was 11 months (range, 3-71 months). Relative changes of TBR, MTV, and RANO criteria predicted a significantly longer PFS (all P ≤ .002) and OS (all P ≤ .045). At follow-up, the occurrence of new distant hotspots (n ≥ 1) predicted a worse outcome, with significantly shorter PFS (P = .005) and OS (P < .001). Time-to-peak changes did not predict a significantly longer survival. Multivariate survival analyses revealed that new distant hotspots at follow-up FET PET were most potent in predicting non-response (P < .001; HR, 8.578). CONCLUSIONS: Data suggest that FET PET provides complementary information to RANO criteria for response evaluation of lomustine-based chemotherapy early after treatment initiation.

Participating in a School-Integrated Daily Exercise Program Improves Motor Performance Significantly in School-Children.

Children's sedentary time has increased, while daily physical activity and motor performance have decreased. We evaluated an integrated school-based exercise program by assessing changes in motor skills after one year and comparing these changes to children who did not participate. We included 303 children from five schools in this longitudinal study and assigned them either to the exercise group (EG; n = 183 with daily exercise program) or the waiting group (WG; n = 120). Motor skills were assessed at baseline and after one year. Mixed modeling was used to analyze inter-group differences of change in motor skills and to determine the effect of sex, age group, and weight status. EG improved more strongly than WG for sprint, side jumps (both p = 0.017), stand and reach (p = 0.012), and ergometry (p ≤ 0.001) when compared to WG. Girls improved more strongly in the sit-ups than boys, second graders more than fifth graders in the backwards balance and the ergometry, and non-overweight children more in the standing long jump than overweight children. The exercise program is effective in increasing motor skills and physical fitness. Girls were not disadvantaged, and overweight children profited as much as their non-overweight peers in all categories but one.

Use of advanced neuroimaging and artificial intelligence in meningiomas.

Anatomical cross-sectional imaging methods such as contrast-enhanced MRI and CT are the standard for the delineation, treatment planning, and follow-up of patients with meningioma. Besides, advanced neuroimaging is increasingly used to non-invasively provide detailed insights into the molecular and metabolic features of meningiomas. These techniques are usually based on MRI, e.g., perfusion-weighted imaging, diffusion-weighted imaging, MR spectroscopy, and positron emission tomography. Furthermore, artificial intelligence methods such as radiomics offer the potential to extract quantitative imaging features from routinely acquired anatomical MRI and CT scans and advanced imaging techniques. This allows the linking of imaging phenotypes to meningioma characteristics, e.g., the molecular-genetic profile. Here, we review several diagnostic applications and future directions of these advanced neuroimaging techniques, including radiomics in preclinical models and patients with meningioma.

Cost Effectiveness of 18F-FET PET for Early Treatment Response Assessment in Glioma Patients After Adjuvant Temozolomide Chemotherapy.

In light of increasing health-care costs, higher medical expenses should be justified socioeconomically. Therefore, we calculated the effectiveness and cost effectiveness of PET using the radiolabeled amino acid O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) compared with conventional MRI for early identification of responders to adjuvant temozolomide chemotherapy. A recently published study in isocitrate dehydrogenase wild-type glioma patients suggested that 18F-FET PET parameter changes predicted a significantly longer survival already after 2 cycles whereas MRI changes were not significant. Methods: To determine the effectiveness and cost effectiveness of serial 18F-FET PET imaging, we analyzed published clinical data and calculated the associated costs from the perspective of the German Statutory Health Insurance system. Based on a decision-tree model, the effectiveness of 18F-FET PET and MRI was calculated-that is, the probability to correctly identify a responder as defined by an overall survival of at least 15 mo. To determine the cost effectiveness, the incremental cost effectiveness ratio (ICER) was calculated-that is, the cost for each additionally identified responder by 18F-FET PET who would have remained undetected by MRI. The robustness of the results was tested by deterministic and probabilistic Monte Carlo sensitivity analyses. Results: Compared with MRI, 18F-FET PET increased the rate of correctly identified responders to chemotherapy by 26%; thus, 4 patients needed to be examined by 18F-FET PET to identify 1 additional responder. Considering the respective costs for serial 18F-FET PET and MRI, the ICER resulted in €4,396.83 for each additional correctly identified responder by 18F-FET PET. Sensitivity analyses confirmed the robustness of the results. Conclusion: In contrast to conventional MRI, the model suggests that 18F-FET PET is cost-effective in terms of ICER values. Considering the high cost of temozolomide, the integration of 18F-FET PET has the potential to avoid premature chemotherapy discontinuation at reasonable cost.

Cardiovascular Burden Is High in Pediatric Lung Transplant Recipients.

BACKGROUND: Cardiovascular morbidity is common in adults after lung transplantation (LTx) but has not been described for pediatric LTx recipients. Early subclinical cardiovascular damage is reflected by increases in pulse wave velocity (PWV; indicating arteriosclerosis), intima-media thickness (IMT; indicating atherosclerosis), and left ventricular mass index (LVMI; indicating left ventricular hypertrophy). METHODS: We annually assessed 47 pediatric LTx recipients in a prospective longitudinal study (144 observations, mean 3.1 visits/patient, range of 1-4 visits, mean follow-up 2.2 y). RESULTS: At inclusion, increased PWV and IMT were detected in 13% and 30%, respectively, and elevated LVMI was detected in 33%. Higher PWV was associated with male sex, longer time since LTx, higher diastolic blood pressure, and lower glomerular filtration rate. Male sex and lower hemoglobin levels were associated with higher IMT, and the presence of diabetes was associated with higher LVMI. CONCLUSIONS: Pediatric LTx recipients suffer from a high and sustained burden of subclinical cardiovascular damage. In light of improving long-term outcomes, cardiovascular morbidity needs to be addressed. Our analysis identified classical and nonclassical risk factors to be associated with the measures for cardiovascular damage, which could serve as targets for intervention.

Two Decades of Brain Tumour Imaging with O-(2-[18F]fluoroethyl)-L-tyrosine PET: The Forschungszentrum Jülich Experience.

O-(2-[18F]fluoroethyl)-L-tyrosine (FET) is a widely used amino acid tracer for positron emission tomography (PET) imaging of brain tumours. This retrospective study and survey aimed to analyse our extensive database regarding the development of FET PET investigations, indications, and the referring physicians' rating concerning the role of FET PET in the clinical decision-making process. Between 2006 and 2019, we performed 6534 FET PET scans on 3928 different patients against a backdrop of growing demand for FET PET. In 2019, indications for the use of FET PET were as follows: suspected recurrent glioma (46%), unclear brain lesions (20%), treatment monitoring (19%), and suspected recurrent brain metastasis (13%). The referring physicians were neurosurgeons (60%), neurologists (19%), radiation oncologists (11%), general oncologists (3%), and other physicians (7%). Most patients travelled 50 to 75 km, but 9% travelled more than 200 km. The role of FET PET in decision-making in clinical practice was evaluated by a questionnaire consisting of 30 questions, which was filled out by 23 referring physicians with long experience in FET PET. Fifty to seventy per cent rated FET PET as being important for different aspects of the assessment of newly diagnosed gliomas, including differential diagnosis, delineation of tumour extent for biopsy guidance, and treatment planning such as surgery or radiotherapy, 95% for the diagnosis of recurrent glioma, and 68% for the diagnosis of recurrent brain metastases. Approximately 50% of the referring physicians rated FET PET as necessary for treatment monitoring in patients with glioma or brain metastases. All referring physicians stated that the availability of FET PET is essential and that it should be approved for routine use. Although the present analysis is limited by the fact that only physicians who frequently referred patients for FET PET participated in the survey, the results confirm the high relevance of FET PET in the clinical diagnosis of brain tumours and support the need for its approval for routine use.

Case Report: Detection of Symptomatic Treatment-Related Changes in a Patient With Anaplastic Oligodendroglioma Using FET PET.

Following local and systemic treatment of gliomas, the differentiation between glioma relapse and treatment-related changes such as pseudoprogression or radiation necrosis using conventional MRI is limited. To overcome this limitation, various amino acid PET tracers such as O-[2-(18F)-fluoroethyl]-L-tyrosine (FET) are increasingly used and provide valuable additional clinical information. We here report neuroimaging findings in a clincally symptomatic 53-year-old woman with a recurrent anaplastic oligodendroglioma with MRI findings highly suspicious for tumor progression. In contrast, FET PET imaging suggested treatment-related changes considerably earlier than the regression of contrast enhancement on MRI. In patients with oligodendroglioma, the phenomenon of symptomatic treatment-related changes is not well described, making these imaging findings unique and important for clinical decision-making.