Multicenter Standardization of Phase-Resolved Functional Lung MRI in Patients With Suspected Chronic Thromboembolic Pulmonary Hypertension

BACKGROUND Detection of pulmonary perfusion defects is the recommended approach for diagnosing chronic thromboembolic pulmonary hypertension (CTEPH). This is currently achieved in a clinical setting using scintigraphy. Phase-resolved functional lung (PREFUL) magnetic resonance imaging (MRI) is an alternative technique for evaluating regional ventilation and perfusion without the use of ionizing radiation or contrast media. PURPOSE To assess the feasibility and image quality of PREFUL-MRI in a multicenter setting in suspected CTEPH. STUDY TYPE This is a prospective cohort sub-study. POPULATION Forty-five patients (64 ± 16 years old) with suspected CTEPH from nine study centers. FIELD STRENGTH/SEQUENCE 1.5 T and 3 T/2D spoiled gradient echo/bSSFP/T2 HASTE/3D MR angiography (TWIST). ASSESSMENT Lung signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were compared between study centers with different MRI machines. The contrast between normally and poorly perfused lung areas was examined on PREFUL images. The perfusion defect percentage calculated using PREFUL-MRI (QDP$_{PREFUL}$ ) was compared to QDP from the established dynamic contrast-enhanced MRI technique (QDP$_{DCE}$ ). Furthermore, QDP$_{PREFUL}$ was compared between a patient subgroup with confirmed CTEPH or chronic thromboembolic disease (CTED) to other clinical subgroups. STATISTICAL TESTS t-Test, one-way analysis of variance (ANOVA), Pearson's correlation. Significance level was 5%. RESULTS Significant differences in lung SNR and CNR were present between study centers. However, PREFUL perfusion images showed a significant contrast between normally and poorly perfused lung areas (mean delta of normalized perfusion -4.2% SD 3.3) with no differences between study sites (ANOVA: P = 0.065). QDP$_{PREFUL}$ was significantly correlated with QDP$_{DCE}$ (r = 0.66), and was significantly higher in 18 patients with confirmed CTEPH or CTED (57.9 ± 12.2%) compared to subgroups with other causes of PH or with excluded PH (in total 27 patients with mean ± SD QDP$_{PREFUL}$  = 33.9 ± 17.2%). DATA CONCLUSION PREFUL-MRI could be considered as a non-invasive method for imaging regional lung perfusion in multicenter studies. LEVEL OF EVIDENCE 3 TECHNICAL EFFICACY: Stage 1

DNA methylation-based classification of sinonasal tumors

The diagnosis of sinonasal tumors is challenging due to a heterogeneous spectrum of various differential diagnoses as well as poorly defined, disputed entities such as sinonasal undifferentiated carcinomas (SNUCs). In this study, we apply a machine learning algorithm based on DNA methylation patterns to classify sinonasal tumors with clinical-grade reliability. We further show that sinonasal tumors with SNUC morphology are not as undifferentiated as their current terminology suggests but rather reassigned to four distinct molecular classes defined by epigenetic, mutational and proteomic profiles. This includes two classes with neuroendocrine differentiation, characterized by IDH2 or SMARCA4/ARID1A mutations with an overall favorable clinical course, one class composed of highly aggressive SMARCB1-deficient carcinomas and another class with tumors that represent potentially previously misclassified adenoid cystic carcinomas. Our findings can aid in improving the diagnostic classification of sinonasal tumors and could help to change the current perception of SNUCs

DNA methylation-based classification of sinonasal tumors

The diagnosis of sinonasal tumors is challenging due to a heterogeneous spectrum of various differential diagnoses as well as poorly defined, disputed entities such as sinonasal undifferentiated carcinomas (SNUCs). In this study, we apply a machine learning algorithm based on DNA methylation patterns to classify sinonasal tumors with clinical-grade reliability. We further show that sinonasal tumors with SNUC morphology are not as undifferentiated as their current terminology suggests but rather reassigned to four distinct molecular classes defined by epigenetic, mutational and proteomic profiles. This includes two classes with neuroendocrine differentiation, characterized by IDH2 or SMARCA4/ARID1A mutations with an overall favorable clinical course, one class composed of highly aggressive SMARCB1-deficient carcinomas and another class with tumors that represent potentially previously misclassified adenoid cystic carcinomas. Our findings can aid in improving the diagnostic classification of sinonasal tumors and could help to change the current perception of SNUCs

Value of Left Ventricular Feature Tracking Strain Analysis for Detection of Early Cardiac Involvement in Fabry Disease (FD)

Purpose: Detection of cardiac involvement in Fabry disease (FD) is of high importance for treatment management. Native T1 mapping especially showed great potential for detection of early cardiac manifestations. Echocardiographic studies showed strain abnormalities in FD patients, but data on MRI feature tracking strain analysis (FT-SA) is limited. Therefore, the aim of our study was to evaluate the potential of FT-SA compared to native T1 and the FD specific biomarker Globotriaosylsphingosine (LysoGb3). Methods: 28 consecutive FD patients (18 female; 47.8 years ± 17.4 standard deviation (SD)) and 28 control subjects (18 female; 46.6 years ± 18.2 SD) underwent cardiac MRI at 1.5 Tesla. Global native T1 times and left ventricular FT-SA were evaluated. Results were correlated to serum Lyso-Gb3-levels. Results: Native T1 times, global longitudinal (GLS) and global radial strain (GRS) were significantly reduced in FD patients (p < 0.0064, p = 0.0009 and p = 0.0184, respectively). Moreover, native T1 times and GLS were significantly lower in Lyso-Gb3 positive FD patients (p < 0.005 and p = 0.03). GLS, native T1 times showed significant moderate correlations to LysoGb3 (p = 0.002 and p < 0.001). Furthermore, GLS and native T1 times reduce when LysoGb3 was elevated and increasingly with presence of left ventricular hypertrophy (LVH) or late gadolinium enhancement (LGE). Conclusions: Native T1 times and strain values differ significantly between FD patients and control subjects and showed promising correlations to the FD specific biomarker LysoGb3. We therefore conclude that strain abnormalities occur early beside native T1 reductions in cardiac FD involvement. Large scale trials are needed to verify our findings

Osseous Union after Jaw Reconstruction with Fibula-Free Flap: Conventional vs. CAD/CAM Patient-Specific Implants

This is a monocentric, retrospective study of patients who underwent successful immediate or delayed maxilla or mandible reconstructions with FFF from January 2005 to December 2021. Panoramic radiograph, computed tomography scans, and cone-beam CTs were analyzed concerning the osseous union of the intersegmental junctions between maxillary or mandibular native jaw and fibular bone. The primary parameter was to estimate the status of osseous union according to osteosynthesis type. A total number of 133 patients (PSI: n = 64, non-PSI: n = 69) were included in the present study. The mean age was 56.7 ± 14.0 (Range: 14.7–82.7); the primary diagnosis was in 105 patients a malignant (78.9%) and in 20 patients a benign (15.0%) tumor. Mandible reconstruction was performed on 103 patients (77.4%), and on 30 patients (22.6%), maxilla reconstruction was performed. The radiographic images provided a rate of incomplete osseous union (IOU) of about 90% in both groups in the first 6 months. Imaging between 6 and 12 months reveals an IOU rate in the non-PSI group of 46.3% vs. 52.5% in the PSI group, between 12 and 24 months, an IOU rate of 19.6% vs. 26.1%, between 24 and 36 months 8.9% vs. 21.7%, and after 36 months the IOU rate decreases to 4.2% vs. 18.2%. Multivariate logistic regression shows that only osteosynthesis type (OR = 3.518 [95%-CI = 1.223–10.124], p = 0.02) and adjuvant radiotherapy (OR = 4.804 [95%-CI = 1.602–14.409], p = 0.005) are independent risk factors for incomplete osseous union. Cox regression revealed that the variables plate-system (Hazard ratio, HR = 5.014; 95 %-CI: 1.826–3.769; p = 0.002) and adjuvant radiotherapy (HR = 5.710; 95 %-CI: 2.066–15.787; p < 0.001) are predictors for incomplete osseous union. In our study, the rate of incomplete bony fusion was significantly higher in the PSI group. Jaw-to-fibula apposition zones were significantly more affected than intersegmental zones. In multivariate analysis, a combination of osteosynthesis with PSI and adjuvant radiotherapy could be identified as a risk constellation for incomplete ossification