Johann-Martin Hempel

In vivo molecular profiling of human glioma using diffusion kurtosis imaging

The purpose of this study is to assess the diagnostic performance of diffusion kurtosis imaging (DKI) for in vivo molecular profiling of human glioma. Normalized mean kurtosis (MKn) and mean diffusivity (MDn) metrics from DKI were assessed in 50 patients with histopathologically confirmed glioma. The results were compared in regard to the WHO-based histological findings and molecular characteristics leading to integrated diagnosis (Haarlem Consensus): isocitrate-dehydrogenase (IDH1/2) mutation status, alpha-thalassemia/mental retardation syndrome X-linked (ATRX) expression, chromosome 1p/19q loss of heterozygosity (LOH), and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status. MKn was significantly lower in tumors with IDH1/2 mutation (0.43 ± 0.09) and ATRX loss of expression (0.41 ± 0.11) than in those with IDH1/2 wild type (0.57 ± 0.09, p < 0.001) and ATRX maintained expression (0.51 ± 0.10, p = 0.004), respectively. Regarding the integrated molecular diagnosis, MKn was significantly higher in primary glioblastoma (0.57 ± 0.10) than in astrocytoma (0.39 ± 0.11, p < 0.001) and oligodendroglioma (0.47 ± 0.05, p = 0.003). MK may be used to provide insight into the human glioma molecular profile regarding IDH1/2 mutation status and ATRX expression. Considering the diagnostic and prognostic significance of these molecular markers, MK appears to be a promising in vivo biomarker for glioma. The diagnostic performance of MK seems to fit more with the integrated molecular approach than the conventional histological findings of the current WHO 2007 classification.

Erfassung und Monitoring der radiologischen Strahlenexposition

Strategies for reducing radiation exposure are an important part of optimizing medical imaging and therefore a relevant quality factor in radiology. Regarding the medical radiation exposure, computed tomography has a special relevance. The use of the integrating the healthcare enterprise (IHE) radiation exposure monitoring (REM) profile is the upcoming standard for organizing and collecting exposure data in radiology. Currently most installed base devices do not support this profile generating the required digital imaging and communication in medicine (DICOM) dose structured reporting (SR). For this reason different solutions had been developed to register dose exposure measurements without having the dose SR object.Registration and analysis of dose-related parameters is required for constantly optimizing examination protocols, especially computed tomography (CT) examinations based on the latest research results in order to minimize the individual radiation dose exposure from medical imaging according to the principle as low as reasonably achievable (ALARA).

Impact of combined FDG-PET/CT and MRI on the detection of local recurrence and nodal metastases in thyroid cancer

BackgroundSuspected recurrence of thyroid carcinoma is a diagnostic challenge when findings of both a radio iodine whole body scan and ultrasound are negative. PET/CT and MRI have shown to be feasible for detection of recurrent disease. However, the added value of a consensus reading by the radiologist and the nuclear medicine physician, which has been deemed to be helpful in clinical routines, has not been investigated. This study aimed to investigate the impact of combined FDG-PET/ldCT and MRI on detection of locally recurrent TC and nodal metastases in high-risk patients with special focus on the value of the multidisciplinary consensus reading.Materials and methodsForty-six patients with suspected locally recurrent thyroid cancer or nodal metastases after thyroidectomy and radio-iodine therapy were retrospectively selected for analysis. Inclusion criteria comprised elevated thyroglobulin blood levels, a negative ultrasound, negative iodine whole body scan, as well as combined FDG-PET/ldCT and MRI examinations.Neck compartments in FDG-PET/ldCT and MRI examinations were independently analyzed by two blinded observers for local recurrence and nodal metastases of thyroid cancer. Consecutively, the scans were read in consensus. To explore a possible synergistic effect, FDG-PET/ldCT and MRI results were combined. Histopathology or long-term follow-up served as a gold standard.For method comparison, sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy were calculated.ResultsFDG-PET/ldCT was substantially more sensitive and more specific than MRI in detection of both local recurrence and nodal metastases. Inter-observer agreement was substantial both for local recurrence (κ = 0.71) and nodal metastasis (κ = 0.63) detection in FDG-PET/ldCT. For MRI, inter-observer agreement was substantial for local recurrence (κ = 0.69) and moderate for nodal metastasis (κ = 0.55) detection. In contrast, FDG-PET/ldCT and MRI showed only slight agreement (κ = 0.21). However, both imaging modalities identified different true positive results. Thus, the combination created a synergistic effect. The multidisciplinary consensus reading further increased sensitivity, specificity, and diagnostic accuracy.ConclusionsFDG-PET/ldCT and MRI are complementary imaging modalities and should be combined to improve detection of local recurrence and nodal metastases of thyroid cancer in high-risk patients. The multidisciplinary consensus reading is a key element in the diagnostic approach.

In vivo assessment of tumor heterogeneity in WHO 2016 glioma grades using diffusion kurtosis imaging: Diagnostic performance and improvement of feasibility in routine clinical practice

PURPOSE To assess the diagnostic performance of normalized and non-normalized diffusion kurtosis imaging (DKI) metrics extracted from different tumor volume data for grading glioma according to the integrated approach of the revised 2016 WHO classification. MATERIALS AND METHODS Sixty patients with histopathologically confirmed glioma, who provided written informed consent, were retrospectively assessed between 01/2013 and 08/2016 from a prospective trial approved by the local institutional review board. Mean kurtosis (MK) and mean diffusivity (MD) metrics from DKI were assessed by two blinded physicians from four different volumes of interest (VOI): whole solid tumor including (VOItu-ed) and excluding perifocal edema (VOItu), infiltrative zone (VOIed), and single slice of solid tumor core (VOIslice). Intra-class correlation coefficient (ICC) was calculated to assess inter-rater agreement. One-way ANOVA was used to compare MK between 2016 CNS WHO tumor grades. Friedmans test compared MK and MD of each VOI. Spearmans correlation coefficient was used to correlate MK with 2016 CNS WHO tumor grades. ROC analysis was performed on MK for significant results. RESULTS The MK assessment showed excellent inter-rater agreement for each VOI (ICC, 0.906-0.955). MK was significantly lower in IDHmutant astrocytoma (0.40±0.07), than in 1p/19q-confirmed oligodendroglioma (0.54±0.10, P=0.001) or IDHwild-type glioblastoma (0.68±0.13, P<0.001). MK and 2016 WHO tumor grades were strongly and positively correlated (VOItu-ed, r=0.684; VOItu, r=0.734; VOIed, r=0.625; VOIslice, r=0.698; P<0.001). CONCLUSIONS Non-normalized MK values obtained from VOItu and VOIslice showed the best reproducibility and highest diagnostic performance for stratifying glioma according to the integrated approach of the recent 2016 WHO classification.

Histogram analysis of diffusion kurtosis imaging estimates for in vivo assessment of 2016 WHO glioma grades: A cross-sectional observational study

PURPOSE To assess the diagnostic performance of histogram analysis of diffusion kurtosis imaging (DKI) maps for in vivo assessment of the 2016 World Health Organization Classification of Tumors of the Central Nervous System (2016 CNS WHO) integrated glioma grades. MATERIALS AND METHODS Seventy-seven patients with histopathologically-confirmed glioma who provided written informed consent were retrospectively assessed between 01/2014 and 03/2017 from a prospective trial approved by the local institutional review board. Ten histogram parameters of mean kurtosis (MK) and mean diffusivity (MD) metrics from DKI were independently assessed by two blinded physicians from a volume of interest around the entire solid tumor. One-way ANOVA was used to compare MK and MD histogram parameter values between 2016 CNS WHO-based tumor grades. Receiver operating characteristic analysis was performed on MK and MD histogram parameters for significant results. RESULTS The 25th, 50th, 75th, and 90th percentiles of MK and average MK showed significant differences between IDH1/2wild-type gliomas, IDH1/2mutated gliomas, and oligodendrogliomas with chromosome 1p/19q loss of heterozygosity and IDH1/2mutation (p<0.001). The 50th, 75th, and 90th percentiles showed a slightly higher diagnostic performance (area under the curve (AUC) range; 0.868-0.991) than average MK (AUC range; 0.855-0.988) in classifying glioma according to the integrated approach of 2016 CNS WHO. CONCLUSIONS Histogram analysis of DKI can stratify gliomas according to the integrated approach of 2016 CNS WHO. The 50th (median), 75th, and the 90th percentiles showed the highest diagnostic performance. However, the average MK is also robust and feasible in routine clinical practice.

Characterization of a novel murine model for spontaneous hemorrhagic stroke using in vivo PET and MR multiparametric imaging

ABSTRACT The clinical use of Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) has proven to be a strong diagnostic tool in the field of neurology. The reliability of these methods to confirm clinical diagnoses has guided preclinical research to utilize these techniques for the characterization of animal disease models. Previously, we demonstrated that an endothelial cell‐specific ablation of the murine Serum Response Factor (Srf iECKO) results in blood brain barrier (BBB) breakdown and hemorrhagic stroke. Taking advantage of this mouse model we here perform a comprehensive longitudinal, multiparametric and in vivo imaging approach to reveal pathophysiological processes occurring before and during the appearance of cerebral microbleeds using combined PET and MRI. We complement our imaging results with data regarding animal behavior and immunohistochemistry. Our results demonstrate diffusion abnormalities in the cortical brain tissue prior to the onset of cerebral microbleeds. Diffusion reductions were accompanied by significant increments of [18F]FAZA uptake before the onset of the lesions in T2WI. The Open Field behavioral tests revealed reduced activity of Srf iECKO animals, whereas histology confirmed the presence of hemorrhages in cortical regions of the mouse brain and iron deposition at lesion sites with increased hypoxia inducible factor 1&agr;, CD31 and glial fibrillary acidic protein expression. For the first time, we performed a thorough evaluation of the prodromal period before the occurrence of spontaneous cerebral microbleeds. Using in vivo PET and MRI, we show the pathological tissue changes that occur previous to gross blood brain barrier (BBB) disruption and breakage. In addition, our results show that apparent diffusion coefficient (ADC) reduction may be an early biomarker of BBB disruption proposing an alternate clinical interpretation. Furthermore, our findings remark the usefulness of this novel Srf iECKO mouse model to study underlying mechanisms of hemorrhagic stroke. HIGHLIGHTSPET‐MRI characterization of an endogenous spontaneous stroke modelBBB breakage courses with reductions in water diffusionEvolution of microangiopathies not associated to amyloid plaque deposition.

Structured Reporting in Clinical Routine

BACKGROUND  The radiology report is the key component in the communication between radiologists and referring clinicians. Traditionally, reports are written as free text. Several studies have shown that structured reporting using dedicated report templates has a number of advantages compared to conventional reports. Therefore, many radiological societies have recommended the implementation of structured reporting in clinical routine. METHOD  In the meantime, collections of freely available templates have been presented and software solutions for structured reporting have been made commercially available. These allow for quality improvements in the written radiology report as they ensure that all relevant clinical information is included. Most vendors mainly supply proprietary report templates or allow users to create templates for their own institution. The German Radiological Society (DRG) has the goal of developing consensus-based, quality-assured report templates and providing them under a free license. RESULTS  The DRG has developed its first consensus-based report templates and provides them at www.befundung.drg.de. Further report templates will be developed in close cooperation with the respective committees of the DRG and referring clinicians. CONCLUSION  Structured reporting allows for a significant improvement in the quality of written radiology reports. The use of report templates requires personal and technical changes to the reporting process itself. Radiology should face these challenges in its leading role in the application of modern IT-based solutions. Vendors are now encouraged to provide practical solutions. KEY POINTS   · Structured reports have numerous advantages over conventional narrative reports.. · The German Radiological Society is developing consensus-based and quality assured report templates.. · Report templates are provided at www.befundung.drg.de under a free license.. · Vendors are now encouraged to provide solutions for the implementation of structured reporting.. CITATION FORMAT · Pinto dos Santos D, Hempel J, Mildenberger P et al. Structured Reporting in Clinical Routine. Fortschr Röntgenstr 2019; 191: 33 - 39.

Value of computed tomography texture analysis for prediction of perioperative complications during laparoscopic partial nephrectomy in patients with renal cell carcinoma

Purpose Tumorous texture is a marker for tumor tissue inhomogeneity. Based on this assumption, this study aims to evaluate the value of computed tomography texture analysis for imaging-based prediction of perioperative complications during laparoscopic partial tumor nephrectomy. Methods A total of 106 patients with histologically confirmed renal cell carcinoma and pre-operative CT were included and volumetric texture analysis of the tumors was performed by two readers. Texture analysis parameter ratios and differences were calculated using the kidney parenchyma as reference (“reference-corrected”). Regression analysis was performed, regarding the value of the texture analysis parameters, for assessment of the tumor nuclear grade and the prediction of peri- and postoperative complications and approximated blood loss. Moreover, the inter-rater agreement in terms of the intra-class correlation coefficient (ICC) was calculated. Results Regarding the reference-corrected values, the predictive value of texture analysis parameters for severe perioperative complications was highest for the standard deviation of the mean attenuation (Area under curve/AUC, .615; sensitivity, 93.8%, specificity, 30.0%), followed by the uniformity (AUC, .599; sensitivity, 62.5%, specificity, 60.0%), and the uniformity of distribution of positive pixels (AUC, .597; sensitivity, 62.5%; specificity, 61.1%). Regarding the blood loss, the uniformity of positive pixel values (UPP; AUC, 0.638), uniformity (AUC, 0.635), and entropy (AUC, 0.633) yielded the best predictive values, whilst the tumor grade was a weaker predictor (AUC, 0.574). The applied texture analysis parameters did not correlate with the time of surgery or the warm ischemic time. All measured parameters were better predictors for complications than the tumor diameter alone. The inter-rater agreement was almost perfect (ICC, .982). Conclusion CT and CT texture analysis parameters are valuable for prediction of perioperative outcome before laparoscopic partial nephrectomy in patients with renal cell carcinoma.

Glioma grading by dynamic susceptibility contrast perfusion and 11 C-methionine positron emission tomography using different regions of interest

PurposeThe use of dynamic susceptibility contrast (DSC) perfusion and 11C-methionine positron emission tomography (MET-PET) for glioma grading is currently not standardized. The purpose of this study was to identify regions of interest (ROIs) that enable the best performance and clinical applicability in both methods, as well as to evaluate the complementarity of DSC perfusion and MET-PET in spatial hotspot definition.MethodsIn 41 patient PET/MRI datasets, different ROIs were drawn: in T2-hyperintense tumour, in T2-hyperintense tumour and adjacent oedema and in tumour areas with contrast enhancement, altered perfusion or pathological radiotracer uptake. The performance of DSC perfusion and MET-PET using the different ROIs to distinguish high- and low-grade gliomas was assessed. The spatial overlap of hotspots identified by DSC perfusion and MET-PET was assessed visually.ResultsROIs in T2 fluid attenuated inversion recovery (FLAIR) sequence-hyperintense tumour revealed the most significant differences between high- and low-grade gliomas and reached the highest diagnostic performance in both DSC perfusion (p = 0.046; area under the curve = 0.74) and MET-PET (p = 0.007; area under the curve = 0.80). The combination of methods yielded an area under the curve of 0.80. Hotspots were completely overlapped in one half of the patients, partially overlapped in one third of the patients and present in only one method in approximately 20% of the patients.ConclusionsFor multi-parametric examinations with DSC perfusion and MET-PET, we recommend an ROI definition based on T2-hyperintense tumour. DSC perfusion and MET-PET contain complementary information concerning the spatial hotspot definition.

Contrast enhancement predicting survival in integrated molecular subtypes of diffuse glioma: an observational cohort study

IntroductionTo assess the predictive value of magnetic resonance imaging (MRI) gadolinium enhancement as a prognostic factor in the 2016 World Health Organization Classification of Tumors of the Central Nervous System integrated glioma groups.MethodsFour-hundred fifty patients with histopathologically confirmed glioma were retrospectively assessed between 07/1997 and 06/2014 using gadolinium enhancement, survival, and relevant prognostic molecular data [isocitrate dehydrogenase (IDH); alpha-thalassemia/mental retardation syndrome X-linked (ATRX); chromosome 1p/19q loss of heterozygosity; and O6-methylguanine DNA methyltransferase (MGMT)]. The Kaplan–Meier method was used to assess univariate survival data. A multivariate Cox proportional hazards model was performed on significant results from the univariate analysis.ResultsThere were significant differences in survival between patient age (p < 0.0001), WHO glioma grades (p < 0.0001), and integrated molecular profiles (p < 0.0001). Patients with IDH1/2 mutation, loss of ATRX expression, and methylated MGMT promoter showed significantly better survival than those with the IDHwild-type (p < 0.0001), retained ATRX expression (p < 0.0001), and unmethylated MGMT promoter (p = 0.019). Survival was significantly better in patients without gadolinium enhancement (p = 0.009) who were in the IDHwild-type glioma and glioma with retained ATRX expression groups (p = 0.018 and 0.030, respectively).ConclusionsIn univariate analysis, the presence of gadolinium enhancement on preoperative MRI scans is an unfavorable factor for survival. Regarding the molecular subgroups, gadolinium enhancement is an unfavorable prognostic factor in gliomas with IDHwild-type and those with ATRX retention. However, in multivariate analysis only patient age, IDH1/2 mutation status, MGMT promoter methylation status, and WHO grade IV are relevant for predicting survival.