Placental vessel segmentation and registration in fetoscopy: Literature review and MICCAI FetReg2021 challenge findings.

Fetoscopy laser photocoagulation is a widely adopted procedure for treating Twin-to-Twin Transfusion Syndrome (TTTS). The procedure involves photocoagulation pathological anastomoses to restore a physiological blood exchange among twins. The procedure is particularly challenging, from the surgeon's side, due to the limited field of view, poor manoeuvrability of the fetoscope, poor visibility due to amniotic fluid turbidity, and variability in illumination. These challenges may lead to increased surgery time and incomplete ablation of pathological anastomoses, resulting in persistent TTTS. Computer-assisted intervention (CAI) can provide TTTS surgeons with decision support and context awareness by identifying key structures in the scene and expanding the fetoscopic field of view through video mosaicking. Research in this domain has been hampered by the lack of high-quality data to design, develop and test CAI algorithms. Through the Fetoscopic Placental Vessel Segmentation and Registration (FetReg2021) challenge, which was organized as part of the MICCAI2021 Endoscopic Vision (EndoVis) challenge, we released the first large-scale multi-center TTTS dataset for the development of generalized and robust semantic segmentation and video mosaicking algorithms with a focus on creating drift-free mosaics from long duration fetoscopy videos. For this challenge, we released a dataset of 2060 images, pixel-annotated for vessels, tool, fetus and background classes, from 18 in-vivo TTTS fetoscopy procedures and 18 short video clips of an average length of 411 frames for developing placental scene segmentation and frame registration for mosaicking techniques. Seven teams participated in this challenge and their model performance was assessed on an unseen test dataset of 658 pixel-annotated images from 6 fetoscopic procedures and 6 short clips. For the segmentation task, overall baseline performed was the top performing (aggregated mIoU of 0.6763) and was the best on the vessel class (mIoU of 0.5817) while team RREB was the best on the tool (mIoU of 0.6335) and fetus (mIoU of 0.5178) classes. For the registration task, overall the baseline performed better than team SANO with an overall mean 5-frame SSIM of 0.9348. Qualitatively, it was observed that team SANO performed better in planar scenarios, while baseline was better in non-planner scenarios. The detailed analysis showed that no single team outperformed on all 6 test fetoscopic videos. The challenge provided an opportunity to create generalized solutions for fetoscopic scene understanding and mosaicking. In this paper, we present the findings of the FetReg2021 challenge, alongside reporting a detailed literature review for CAI in TTTS fetoscopy. Through this challenge, its analysis and the release of multi-center fetoscopic data, we provide a benchmark for future research in this field.

Monochorionic twins discordant for trisomy 13: A case report, systematic literature search and synthesis of available evidence.

This article presents the tenth reported case of monochorionic twins discordant for trisomy 13. Discordant aneuploidies in monochorionic twins are rare. Aetiologies include mitotic error in early cell division and "rescue" chromosome loss in an initially trisomic zygote. Clinicians should offer early amniocentesis of both sacs and consider selective termination.

Fetal surgery for open spina bifida.

KEY CONTENT: Spina bifida is a congenital neurological condition with lifelong physical and mental effects.Open fetal repair of the spinal lesion has been shown to improve hindbrain herniation, ventriculoperitoneal shunting, independent mobility and bladder outcomes for the child and, despite an increased risk of prematurity, does not seem to increase the risk of neurodevelopmental impairment.Open fetal surgery is associated with maternal morbidity.Surgery at our institution is offered and performed according to internationally agreed criteria and protocols.Further evidence regarding long-term outcomes, fetoscopic repair and alternative techniques is awaited. LEARNING OBJECTIVES: To understand the clinical effects, potential prevention and prenatal diagnosis of spina bifida.To understand the rationale and evidence supporting the benefits and risks of fetal repair of open spina bifida.To understand the criteria defining those who are likely to benefit from fetal surgery. ETHICAL ISSUES: The concept of the fetus as a patient, and issues surrounding fetal death or the need for resuscitation during fetal surgery.The associated maternal morbidity in a procedure performed solely for the benefit of the fetus/child.The financial implications of new surgical treatments.

A double dilemma: treatment of stage IV fetal twin-twin transfusion syndrome in the setting of maternal recurrent venous thromoembolism: a case report.

BACKGROUND: Fetal conditions can pose significant challenges in the management of pregnancies complicated by pre-existing maternal medical conditions. CASE PRESENTATION: We report a case of a 34-year-old woman with Stage IV Twin Twin Transfusion syndrome in the presence of maternal recurrent complex venous thromboembolic disease. Following a previous pregnancy loss, complicated by a third episode of thromboembolic disease, an inferior vena cava filter was placed. One month later, a pregnancy was confirmed and subsequently identified as a monochorionic twin pregnancy. Twin-Twin Transfusion syndrome was identified at 18 weeks' gestation and progressed rapidly to Quintero Stage IV. In consultation with a multi-disciplinary international team, fetoscopic laser photocoagulation was performed. The pregnancy progressed to delivery of female infants at 33 weeks gestation, who have achieved all developmental milestones at 2 years of age. CONCLUSIONS: We describe the multi-disciplinary effort to optimise the maternal condition to allow fetoscopic laser photocoagulation and continued management of the maternal and fetal conditions to a successful pregnancy outcome.

Retrieval and registration of long-range overlapping frames for scalable mosaicking of in vivo fetoscopy.

PURPOSE: The standard clinical treatment of Twin-to-Twin transfusion syndrome consists in the photo-coagulation of undesired anastomoses located on the placenta which are responsible to a blood transfer between the two twins. While being the standard of care procedure, fetoscopy suffers from a limited field-of-view of the placenta resulting in missed anastomoses. To facilitate the task of the clinician, building a global map of the placenta providing a larger overview of the vascular network is highly desired. METHODS: To overcome the challenging visual conditions inherent to in vivo sequences (low contrast, obstructions or presence of artifacts, among others), we propose the following contributions: (1) robust pairwise registration is achieved by aligning the orientation of the image gradients, and (2) difficulties regarding long-range consistency (e.g. due to the presence of outliers) is tackled via a bag-of-word strategy, which identifies overlapping frames of the sequence to be registered regardless of their respective location in time. RESULTS: In addition to visual difficulties, in vivo sequences are characterised by the intrinsic absence of gold standard. We present mosaics motivating qualitatively our methodological choices and demonstrating their promising aspect. We also demonstrate semi-quantitatively, via visual inspection of registration results, the efficacy of our registration approach in comparison with two standard baselines. CONCLUSION: This paper proposes the first approach for the construction of mosaics of placenta in in vivo fetoscopy sequences. Robustness to visual challenges during registration and long-range temporal consistency are proposed, offering first positive results on in vivo data for which standard mosaicking techniques are not applicable.

Ultrasound diagnosis of bilateral cataracts in a fetus with possible cerebro-ocular congential muscular dystrophy during the routine second trimester anomaly scan.

The finding of bilateral congenital cataracts in the fetus is rare. We report bilateral congenital cataracts detected during the routine second trimester anomaly scan, which subsequently were found to be associated with other congenital anomalies and the parents opted for a termination of pregnancy. At post-mortem, Muscle-Eye Brain disease or Walker-Warburg Syndrome was considered likely, which are autosomal recessive congenital muscular dystrophy disorders associated with cerebral, cerebellar, muscle and eye anomalies. On ultrasound, bilateral cataracts appear as echogenic, solid areas within the fetal orbits. The examination of the fetal face and orbits plays an important role in confirming fetal well-being antenatally. We propose that it should become a routine part of the structural survey of fetal anatomy during the obstetric anomaly scan. This is especially important in pregnancies previously affected by fetal cataracts or pregnancies at risk of rare genetic syndromes.

Perinatal- and procedure-related outcomes following radiofrequency ablation in monochorionic pregnancy.

OBJECTIVE: We sought to assess the efficacy, complication rates, and outcomes for complex monochorionic pregnancies undergoing selective fetal reduction using radiofrequency ablation (RFA). STUDY DESIGN: In this prospective observational study, 100 consecutive cases of selective fetal reduction using RFA were analyzed. All cases were managed at the Centre for Fetal Care at Queen Charlotte's and Chelsea Hospital in London. Indications for offering RFA, details of the procedure, and pregnancy outcomes were collected and analyzed. RESULTS: The main indications for RFA were discordant fetal anomaly and twin-twin transfusion syndrome. Overall live birth rate was 78% and the median gestation at delivery was 35.15 weeks. Delivery <32 weeks' gestation occurred in 17.9% of cases. Postprocedure abnormal antenatal magnetic resonance imaging occurred in 3% of cases. There was no statistical difference in outcomes with regard to gestation when the procedure was performed or the indication for the RFA. CONCLUSION: RFA appears to be a reasonable option for selective fetal reduction in complex monochorionic pregnancies with an overall survival rate of 78%.

Ventricular strain changes in monochorionic twins with and without twin-to-twin transfusion syndrome.

OBJECTIVE: The objective of the study was to investigate whether vector velocity imaging (VVI), a non-Doppler speckle tracking ultrasound technology, is feasible in twin pregnancies and can aid management of twin-twin transfusion syndrome (TTTS). STUDY DESIGN: Twenty-seven women pregnant with monochorionic diamniotic twins affected by TTTS and 28 monochorionic pregnancies that did not develop TTTS were included in a prospective case-control study at a fetal medicine center. Fetal echocardiograms were recorded with dummy electrocardiography to retain original frame rates when exported for offline speckle tracking analysis using Syngo-VVI software (Siemens Corp, Munich, Germany). Right and left ventricular (LV) free wall Lagrangian strain was measured from the original coordinates. Within-twin pair ventricular strain differences including relationship to Quintero staging and response to laser therapy for TTTS were analyzed by Wilcoxon signed-rank test. RESULTS: The VVI strain measurements could be analyzed in 182 of 200 TTTS and 96 of 112 non-TTTS control ventricles. Within-pair strain was concordant in non-TTTS controls. Recipient LV strain was reduced at all Quintero stages compared with donors (P < .01). Recipient right ventricular strain was reduced only in stages 3 and 4 (P < .01). Strain improved at a median of 2 weeks following successful laser therapy. Intertwin differences in strain were independent of weight discordance. CONCLUSION: Recipient LV strain is reduced in stages 1 and 2 TTTS. Within-pair strain discordance may distinguish early TTTS from growth discordance and guide timing of and management following treatment.

Impaired recovery of intracellular calcium and force after activation in isolated myometrial and subcutaneous resistance arteries from women with preeclampsia.

OBJECTIVES: Preeclampsia is a major cause of maternal and perinatal morbidity and mortality, but its cause is poorly understood. This study investigated whether there is an abnormality of intracellular calcium ([Ca2=]i) and tension during recovery from activation in isolated resistance arteries in preeclampsia and investigated the underlying mechanisms. METHODS: Subcutaneous and myometrial resistance arteries from preeclamptic, normotensive pregnant and nonpregnant women were mounted on an isometric myograph and loaded with fura-2 to allow simultaneous measurement of force and [Ca2+]i. Arteries were activated by a high-potassium solution or noradrenaline, and the rate of decline in force and [Ca2+]i examined following washout. RESULTS: Basal tone and [Ca2+]i and rise in force and [Ca2+]i induced by high-potassium solution did not differ between groups but the rate of decline after washout was significantly slowed in both subcutaneous and myometrial arteries from preeclamptic women as compared with normotensive pregnant or nonpregnant women. The rate of decline in force after noradrenaline was also slowed in arteries from preeclamptic women. In subcutaneous resistance arteries from nonpregnant women, removal of the endothelium did not affect the rate of decline in force after high-potassium solution. However, inhibition of the plasma membrane Ca ATPase with carboxyeosin mimicked the findings seen in preeclampsia. In contrast, inhibition of the sarcoplasmic endoreticulum Ca ATPase with cyclopiazonic acid had no effect on the rate of decline in force or [Ca2+]i. CONCLUSION: The rate of relaxation and decline in [Ca2+]i in resistance arteries are impaired in preeclampsia. This may be mediated by decreased activity of plasma membrane Ca2+ ATPase and could be a mechanism contributing to elevated peripheral resistance and raised blood pressure in preeclampsia.

The effect of polyhydramnios on cervical length in twins: a controlled intervention study in complicated monochorionic pregnancies.

OBJECTIVE: To test the hypothesis that cervical shortening in polyhydramnios reflects the degree of excess amniotic fluid, and increases with normalisation of amniotic fluid volume. STUDY DESIGN: Prospective cohort study of 40 women with monochorionic twins undergoing interventional procedures between 16-26 weeks. Cervical length was assessed via transvaginal sonography pre-procedure, 1 and 24 hours post-procedure, and results compared between amnioreduction and control procedures. Amniotic fluid index (AFI) was measured pre- and post-procedure. RESULTS: Pre-procedural cervical length correlated with AFI (linear fit = 5.07 -0.04x, R(2) = 0.17, P = 0.03) in patients with polyhydramnios (n = 28). Drainage of 2000 ml fluid (range 700-3500 ml), reduced AFI from 42 cm to 21 cm (P<0.001). Their pre-procedural cervical length did not change at one (mean Delta:-0.1cm, 95%CI, -0.4 to 0.2) or 24 hours (0.2 cm, -0.1 to 0.6) after amnioreduction. There was no change in cervical length at control procedures. CONCLUSION: Cervical shortening in twins with polyhydramnios does not appear to be an acute process; cervical length can be measured before or after therapeutic procedures.

Interstitial laser therapy for fetal reduction in monochorionic multiple pregnancy: loss rate and association with aplasia cutis congenita.

OBJECTIVE: To evaluate experience with interstitial laser therapy for intrafetal vascular ablation in monochorionic (MC) multiple pregnancy. METHODS: MC pregnancies that underwent fetal reduction between 1998 and 2007 by interstitial laser therapy were reviewed. Indications were twin reversed arterial perfusion sequence (TRAP) (n = 10), twin-to-twin transfusion (6), discordant abnormality (7) or growth (1) and high-order multiples (6). RESULTS: Thirty pregnancies treated at 15 weeks (median, range: 11 weeks-20 weeks, 5 days) had no technical failures but four manifested procedure-related amniorrhexis. Four of 38 remaining fetuses suffered intrauterine death (IUFD) within 24 h, giving an early procedure-related fetal loss rate of 10% per pregnancy and 11% per fetus. A further five IUFDs occurred within 2 weeks, giving a maximum procedure-related loss rate of 27% per pregnancy and 24% per fetus. Median gestation at delivery was 37 weeks (18 weeks, 1 day-41 weeks, 3 days) for pregnancies continuing > 2 weeks. Perinatal survival was 26 of 38 (68%) in nonreduced fetuses. Two of 26 neonates (8%) were diagnosed with aplasia cutis congenita (ACC). CONCLUSION: Interstitial laser therapy in complicated MC pregnancies carries significant risks of unintended fetal loss and may be associated with ACC.

Fetal ECG: a novel predictor of atrioventricular block in anti-Ro positive pregnancies.

OBJECTIVE: Approximately 2.8% of pregnancies are Ro/La antibody positive. 3-15% of fetuses develop complete heart block (CHB). First-degree atrioventricular heart block (1 degrees AVB) is reported in a third of Ro/La fetuses but as most have a normal postnatal ECG this may reflect inadequacies of Doppler measurement techniques. METHODS: Comparison was made between mechanical (mPR) and electrical (ePR) intervals obtained prospectively using Doppler and non-invasive fetal ECG (fECG) in 52 consecutive Ro/La pregnancies in 46 women carrying 54 fetuses in an observational study at a fetal medicine unit. 121 mPR and 37 ePR intervals were recorded in 49 Ro/La fetuses. Five were referred with CHB and excluded. ePR was measured successfully in 35/37 (94%) and mPR was measured in all cases. 1 degrees AVB was defined as PR >95% CI. Logistic regression predicted abnormal final fetal rhythm from first mPR or ePR. RESULTS: The ePR model gave 66.7% sensitivity (6 of 8 final abnormal fetal rhythm cases were predicted correctly in fetuses >20 weeks) and 96.2% specificity. mPR gave 44.4% sensitivity (4 of 9 cases) and 88.5% specificity. Z scores for ePR (zPR) were calculated from 199 normal fetuses. The area under the receiver operator characteristic (ROC) curve was 0.88 (95% CI, 0.754 to 1.007). A cut-off of 1.65 gave a sensitivity of 87.5% and specificity of 95% for those with prolonged and normal ePR intervals, respectively. CONCLUSION: zPR is better than mPR at differentiating between normal and prolonged PR intervals, suggesting that fECG is the diagnostic tool of choice to investigate the natural history and therapy of conduction abnormalities in Ro/La pregnancies.

Effects of vasoactive agents on intracellular calcium and force in myometrial and subcutaneous resistance arteries isolated from preeclamptic, pregnant, and nonpregnant woman.

OBJECTIVE: Preeclampsia is a common and serious complication of pregnancy, characterized by maternal hypertension and proteinuria, placental insufficiency, and fetal growth restriction. The purpose of this study was to investigate whether intracellular Ca 2+ ([Ca 2+ ] i ) and contractile responses of vascular smooth muscle to vasoactive agents are altered in preeclampsia compared with normal pregnancy and the nonpregnant state. STUDY DESIGN: Subcutaneous and myometrial resistance arteries from women who had preeclampsia, normal pregnancy, and nonpregnant women were obtained at the time of cesarean section or hysterectomy. Arteries were mounted on an isometric myograph and loaded with the Ca 2+ indicator, fura-2AM, to permit simultaneous measurement of force and [Ca 2+ ] i . Reponses to endothelium-dependent relaxants (acetylcholine and substance P) and vasoconstrictors (depolarizing potassium solution, phenylephrine, and angiotensin II) were examined. RESULTS: The fall in [Ca 2+ ] i and relaxation in response to acetylcholine was significantly inhibited in both myometrial and subcutaneous arteries from preeclamptic women compared with arteries from nonpregnant or normal pregnant women. However, responses to substance P did not differ between the 3 groups. There were no significant differences in [Ca 2+ ] i or force responses to high potassium, phenylephrine, or angiotensin II in myometrial and subcutaneous resistance vessels in women with preeclampsia compared with normal pregnant women. However, force, but not [Ca 2+ ] i responses to angiotensin II, in subcutaneous vessels from normal pregnant and preeclamptic women were reduced compared with subcutaneous arteries from nonpregnant women, indicating that pregnancy is associated with a reduction in Ca 2+ sensitization in this tissue. A similar effect was not seen in myometrial arteries. CONCLUSION: Endothelial function is altered in preeclampsia, with loss of effect of acetylcholine, but not substance P. Vasoconstrictor reactivity is not increased in preeclampsia compared with uncomplicated normal pregnancy, and this is unlikely to be an explanation for the increased peripheral vascular resistance seen in preeclampsia.

Doppler for artery-artery anastomosis and stage-independent survival in twin-twin transfusion.

OBJECTIVE: Treatment selection in twin-twin transfusion syndrome is increasingly determined by disease severity. We investigated whether detection of arterio-arterial anastomoses predicts perinatal survival. METHODS: An artery-artery anastomosis was sought by Doppler and disease stage was determined in 105 cases of twin-twin transfusion syndrome at presentation, first treatment, and worst stage. Outcome measures were perinatal, double, and any (1 or more babies) survival rates. RESULTS: After exclusion of 10 noninformative pregnancies, perinatal, double, and any survival rates were 61%, 44%, and 77%, respectively. When an anastomosis was detected at each of the 3 time points, perinatal and double survival rates were higher than when one was not (at first treatment, perinatal survival 83% versus 53%, respectively, P =.003; double survival 78% versus 33%, P <.001). Perinatal and double survival (P < or =.01) were poorer with more advanced stage, but any survival rates were not influenced by stage or anastomosis detection. Multiple logistic regression demonstrated that anastomosis detection at treatment increased the chance of perinatal (odds ratio [OR] 5.1, 95% confidence interval [CI] 1.6, 15.9) and double survival (OR 19.3, 95% CI 2.7, 138), independently of stage. For stages I-III at treatment, anastomosis detection predicted better perinatal (100% versus 63%, 100% versus 59%, and 83% versus 44%, respectively) and double survival rates (100% versus 52%, 100% versus 46%, and 78% versus 26%). Stage III, with anastomoses detected, had better perinatal (83% versus 63%) and double survival (78% versus 52%) than did stage I without detection. CONCLUSION: Antenatal detection of artery-to-artery anastomosis predicts higher perinatal and double survival in twin-twin transfusion syndrome, independently of disease stage. LEVEL OF EVIDENCE: II-3

Reversal of twin-twin transfusion syndrome: frequency, vascular anatomy, associated anomalies and outcome.

OBJECTIVE: To determine the frequency of reversal of transfusional gradient and phenotype in a large cohort of prospectively studied cases of twin-twin transfusion syndrome (TTTS) and seek evidence of clinical or placental anastomotic associations. METHODS: Consecutive cases of TTTS seen over an eight-year period with serial documentation of ultrasonic growth, liquor volume and fetal and placental Doppler studies were reviewed. Postnatal injection studies were inspected. RESULTS: Reversal of TTTS occurred in 5 of 96 affected pregnancies (5%). Two of the five cases had underlying aneuploidy or genetic syndrome, higher than the 2% frequency found in cases without reversal of TTTS (p < 0.05). Placental anastomotic configurations provided no consistent explanation for reversal of phenotype. CONCLUSION: This study documents the frequency of reversal of the direction of TTTS, and suggests that it is a heterogeneous condition. Reversal of donor-recipient phenotype may be explained by haemodynamic changes secondary to underlying aneuploidy/genetic syndromes, to the presence of multiple anastomoses in either direction or following laser ablation. This series together with previous case reports argues for a high level of suspicion for underlying aneuploidy, genetic syndrome or structural defects where there is reversal of the donor-recipient phenotype.

Second-trimester sonographic findings in trisomy 22: report of 3 cases and review of the literature.

OBJECTIVE: To describe cases of trisomy 22 detected prenatally on second-trimester sonography and to review the literature on similar cases, with special emphasis on the prenatal findings and pregnancy outcome. METHODS: We performed follow-up second-trimester sonography and fetal karyotyping on 3 pregnant women who were referred because of abnormal findings on initial second-trimester scans. We also conducted a literature search for other reports of sonographic findings in trisomy 22. RESULTS: Fetal abnormalities shown on sonography included nuchal thickening, mild generalized skin edema, an atrioventricular septal defect, an interventricular septal defect, edema of the scalp, face, and neck, severe left pleural effusion with a marked mediastinal shift, ascites, agenesis of the diaphragm, ambiguous genitalia, a single umbilical artery, bradycardia, a multicystic left kidney, and an absent right kidney. All 3 fetuses had karyotypes indicating trisomy 22. One pregnancy was terminated at the parents' request, and 2 ended in fetal death at 23 and 26 weeks. Our literature search revealed only 1 previous report of second-trimester sonographic diagnosis of trisomy 22. We found 3 other reports describing prenatal diagnosis in the third trimester, but only limited information on the sonographic findings was available. CONCLUSIONS: Second-trimester sonography provides valuable clues for the prenatal diagnosis of several chromosomal disorders, including trisomy 22. Prenatal karyotyping is warranted if fetal growth restriction is detected in the second trimester, especially if associated with congenital defects.