Accuracy of an MR-only workflow for prostate radiotherapy using semi-automatically burned-in fiducial markers.

BACKGROUND: The benefit of MR-only workflow compared to current CT-based workflow for prostate radiotherapy is reduction of systematic errors in the radiotherapy chain by 2-3 mm. Nowadays, MRI is used for target delineation while CT is needed for position verification. In MR-only workflows, MRI based synthetic CT (sCT) replaces CT. Intraprostatic fiducial markers (FMs) are used as a surrogate for the position of the prostate improving targeting. However, FMs are not visible on sCT. Therefore, a semi-automatic method for burning-in FMs on sCT was developed. Accuracy of MR-only workflow using semi-automatically burned-in FMs was assessed and compared to CT/MR workflow. METHODS: Thirty-one prostate cancer patients receiving radiotherapy, underwent an additional MR sequence (mDIXON) to create an sCT for MR-only workflow simulation. Three sources of accuracy in the CT/MR- and MR-only workflow were investigated. To compare image registrations for target delineation, the inter-observer error (IOE) of FM-based CT-to-MR image registrations and soft-tissue-based MR-to-MR image registrations were determined on twenty patients. Secondly, the inter-observer variation of the resulting FM positions was determined on twenty patients. Thirdly, on 26 patients CBCTs were retrospectively registered on sCT with burned-in FMs and compared to CT-CBCT registrations. RESULTS: Image registration for target delineation shows a three times smaller IOE for MR-only workflow compared to CT/MR workflow. All observers agreed in correctly identifying all FMs for 18 out of 20 patients (90%). The IOE in CC direction of the center of mass (COM) position of the markers was within the CT slice thickness (2.5 mm), the IOE in AP and RL direction were below 1.0 mm and 1.5 mm, respectively. Registrations for IGRT position verification in MR-only workflow compared to CT/MR workflow were equivalent in RL-, CC- and AP-direction, except for a significant difference for random error in rotation. CONCLUSIONS: MR-only workflow using sCT with burned-in FMs is an improvement compared to the current CT/MR workflow, with a three times smaller inter observer error in CT-MR registration and comparable CBCT registration results between CT and sCT reference scans. Trial registry Medical Research Involving Human Subjects Act (WMO) does apply to this study and was approved by the Medical Ethics review Committee of the Academic Medical Center. Registration number: NL65414.018.18. Date of registration: 21-08-2018.

Placental fetal vascular thrombosis lesions and maternal thrombophilia.

AIMS: Following intrauterine fetal death (IUFD), the placental fetal vessels undergo regressive changes. These changes are virtually indistinguishable from lesions that are the result of fetal vascular thrombosis (FVT). This study investigated the relation between these lesions and maternal thrombophilia. METHODS: Placenta slides of 65 IUFDs with known maternal thrombophilia test results (compound MTHFR C677T and A1298C heterozygosity, n = 10; MTHFR 677TT homozygosity, n = 3; protein S deficiency, n = 0; factor V Leiden mutation, n = 2; prothrombin gene mutation G20210A, n = 1; lupus anticoagulant, n = 2; antiphospholipid syndrome, n = 1; MTHFR C677T heterozygosity, n = 5; MTHFR A1298C heterozygosity, n = 4; and MTHFR 1298CC homozygosity, n = 2) and of 30 livebirths with positive maternal thrombophilia test results (n = 5, 2, 0, 9, 2, 0, 2, 7, 2 and 1, respectively, for those thrombophilias) were microscopically examined for septation, fetal vessel thrombosis, intimal fibrin cushions, avascular villi, haemorrhagic endovasculitis and fibromuscular sclerosis. RESULTS: Thirty of the 65 IUFDs had a positive maternal thrombophilia test; 22 of these 30 had FVT lesions. Thirty two of the 35 IUFDs with a negative maternal thrombophilia test had FVT lesions. Septation, defined as multiple lumens or 'recanalisation' in a placental vessel, was the lesion seen most often in IUFD (n = 41) whether by itself (n = 13) or in combination with other FVT lesions. Five of the 30 livebirths had FVT lesions but septation was not seen in any of the placentas from the 30 livebirths. FVT lesions did not have a significant relation with maternal thrombophilia. CONCLUSIONS: The finding of fetal vascular thrombosis lesions in stillbirths does not imply thrombophilia as the cause of the fetal death. Factors other than thrombophilia may play a role in the cause of FVT lesions.