Accuracy of electroanatomical mapping-guided cardiac radiotherapy for ventricular tachycardia: pitfalls and solutions.

AIMS: To analyse and optimize the interobserver agreement for gross target volume (GTV) delineation on cardiac computed tomography (CCT) based on electroanatomical mapping (EAM) data acquired to guide radiotherapy for ventricular tachycardia (VT). METHODS AND RESULTS: Electroanatomical mapping data were exported and merged with the segmented CCT using manual registration by two observers. A GTV was created by both observers for predefined left ventricular (LV) areas based on preselected endocardial EAM points indicating a two-dimensional (2D) surface area of interest. The influence of (interobserver) registration accuracy and availability of EAM data on the final GTV and 2D surface location within each LV area was evaluated. The median distance between the CCT and EAM after registration was 2.7 mm, 95th percentile 6.2 mm for observer #1 and 3.0 mm, 95th percentile 7.6 mm for observer #2 (P = 0.9). Created GTVs were significantly different (8 vs. 19 mL) with lowest GTV overlap (35%) for lateral wall target areas. Similarly, the highest shift between 2D surfaces was observed for the septal LV (6.4 mm). The optimal surface registration accuracy (2.6 mm) and interobserver agreement (Δ interobserver EAM surface registration 1.3 mm) was achieved if at least three cardiac chambers were mapped, including high-quality endocardial LV EAM. CONCLUSION: Detailed EAM of at least three chambers allows for accurate co-registration of EAM data with CCT and high interobserver agreement to guide radiotherapy of VT. However, the substrate location should be taken in consideration when creating a treatment volume margin.

Multisize Electrode Field-of-View: Validation by High Resolution Gadolinium-Enhanced Cardiac Magnetic Resonance.

BACKGROUND: Voltage mapping to detect ventricular scar is important for guiding catheter ablation, but the field-of-view of unipolar, bipolar, conventional, and microelectrodes as it relates to the extent of viable myocardium (VM) is not well defined. OBJECTIVES: The purpose of this study was to evaluate electroanatomic voltage-mapping (EAVM) with different-size electrodes for identifying VM, validated against high-resolution ex-vivo cardiac magnetic resonance (HR-LGE-CMR). METHODS: A total of 9 swine with early-reperfusion myocardial infarction were mapped with the QDOT microcatheter. HR-LGE-CMR (0.3-mm slices) were merged with EAVM. At each EAVM point, the underlying VM in multisize transmural cylinders and spheres was quantified from ex vivo CMR and related to unipolar and bipolar voltages recorded from conventional and microelectrodes. RESULTS: In each swine, 220 mapping points (Q1, Q3: 216, 260 mapping points) were collected. Infarcts were heterogeneous and nontransmural. Unipolar and bipolar voltage increased with VM volumes from >175 mm3 up to >525 mm3 (equivalent to a 5-mm radius cylinder with height >6.69 mm). VM volumes in subendocardial cylinders with 1- or 3-mm depth correlated poorly with all voltages. Unipolar voltages recorded with conventional and microelectrodes were similar (difference 0.17 ± 2.66 mV) and correlated best to VM within a sphere of radius 10 and 8 mm, respectively. Distance-weighting did not improve the correlation. CONCLUSIONS: Voltage increases with transmural volume of VM but correlates poorly with small amounts of VM, which limits EAVM in defining heterogeneous scar. Microelectrodes cannot distinguish thin from thick areas of subendocardial VM. The field-of-view for unipolar recordings for microelectrodes and conventional electrodes appears to be 8 to 10 mm, respectively, and unexpectedly similar.

Identification of Incidental Skin Cancers Among Adults Referred to Dermatologists for Suspicious Skin Lesions.

Importance: The incidence of skin cancer is increasing and evaluation of the utility of total body skin examination (TBSE) in detecting incidental skin cancers is warranted. Objectives: To evaluate the proportion and rate of incidental skin cancer detection in urgent skin cancer clinics and investigate the rate of incidental skin cancer detection in 2 groups based on the degree of clinical suspicion of the index lesion for malignancy. Design, Setting, and Participants: A multicenter retrospective cohort study with a case note review of consecutive secondary care consultations was conducted using data from 2 urgent suspected skin cancer screening clinics in UK National Health Service trusts. The study was performed from January 1, 2015, to March 31, 2016, and data analysis was performed from October 14, 2018, to February 1, 2019. Patients included those presenting with a skin lesion suspicious of malignancy who were referred to the urgent suspected skin cancer clinic (N = 5944) over 15 months. Patients who accepted and received a TBSE were subsequently included in the analysis. Main Outcomes and Measures: The proportion and rate of incidental skin cancer detection through TBSE and whether a clinically suspicious (malignant) index lesion was associated with a higher chance of having a malignant incidental lesion. Results: Of the 5944 patients referred to the clinic, 4726 individuals (79.5%) were evaluated. In the cohort included in the analyses, the median age was 57 years (interquartile range, 39-73 years); 2567 patients (54.3%) were women. A total of 1117 skin cancers were identified; of these, 242 lesions (21.7%) were detected incidentally through TBSE, including 197 of 570 (34.6%) basal cell carcinomas, 16 of 250 (6.4%) squamous cell carcinomas, and 25 of 215 (11.6%) melanomas. The detection rate of incidental malignant lesions was 5.1 lesions per 100 patients examined (5.1%; 95% CI, 4.5%-5.8%). There was a higher detection rate of histologically confirmed incidental malignant lesions in individuals with clinically suspicious index lesions requiring biopsy (10.9%; 95% CI, 9.5%-12.5%) compared with those presenting with clinically benign index lesions (2.0%; 95% CI, 1.6%-2.5%) (P < .001). Conclusions and Relevance: The findings of this study support the use of TBSE for urgent skin cancer referrals, highlighting the potential harms of solitary lesion assessment in a subgroup. Individuals presenting with a clinically suspicious index lesion requiring biopsy are most likely to benefit from TBSE and should be counseled regarding the benefit.

The Molecular Basis of Radial Intercalation during Tissue Spreading in Early Development.

Radial intercalation is a fundamental process responsible for the thinning of multilayered tissues during large-scale morphogenesis; however, its molecular mechanism has remained elusive. Using amphibian epiboly, the thinning and spreading of the animal hemisphere during gastrulation, here we provide evidence that radial intercalation is driven by chemotaxis of cells toward the external layer of the tissue. This role of chemotaxis in tissue spreading and thinning is unlike its typical role associated with large-distance directional movement of cells. We identify the chemoattractant as the complement component C3a, a factor normally linked with the immune system. The mechanism is explored by computational modeling and tested in vivo, ex vivo, and in vitro. This mechanism is robust against fluctuations of chemoattractant levels and expression patterns and explains expansion during epiboly. This study provides insight into the fundamental process of radial intercalation and could be applied to a wide range of morphogenetic events.