Chirped flicker optoretinography for in vivo characterization of human photoreceptors' frequency response to light.

Flicker electroretinography (ERG) has served as a valuable noninvasive objective tool for investigating retinal physiological function through the measurement of electrical signals originating from retinal neurons in response to temporally modulated light stimulation. Deficits in the response at certain frequencies can be used as effective biomarkers of cone-pathway dysfunction. In this Letter, we present the progress we made on its optical counterpart-photopic flicker optoretinography (f-ORG). Specifically, we focus on the measurement of the response of light-adapted retinal photoreceptors to a flicker stimulus with chirped frequency modulation. In contrast to measurements performed at discrete frequencies, this technique enables a significantly accelerated characterization of photoreceptor outer segment optical path length modulation amplitudes in the nanometer range as a function of stimulus frequency, enabling the acquisition of the characteristic frequency response in less than 2 sec.

Review of the Evaluation of Pulmonary Hypoplasia as an Important Determinant of Clinical Outcomes in Infants with Congenital Diaphragmatic Hernia.

Pulmonary hypoplasia is one of main causes of neonatal mortality and morbidity in patients with congenital diaphragmatic hernia. With most cases diagnosed prenatally, the emphasis is put on prediction of the severity of this defect. Several attempts are made to reduce the mortality and provide optimal prenatal and postnatal care. Appropriate estimation of risk of pulmonary hypoplasia also provides an important inclusion criterion for prenatal intervention. The main tool used for the detection and prediction of pulmonary hypoplasia is ultrasound, with an increasing number of available formulas to estimate the risk of occurrence of this phenomenon and complication associated with it. For most of the formulas used in this measurement method, the main limitations are either gestational-age dependency or limited research. Other imaging methods used to assess the risk of pulmonary hypoplasia involve magnetic resonance imaging and vascular assessment of affected lungs. The limitation in these remains the limited accessibility. Currently, the most widely used indexes are observed-to-expected lungs-to-head ratio and presence of liver herniation. These are the 2 most commonly used measurement methods, as they are the basis for patient qualification for fetoscopic endoluminal tracheal occlusion. This article aims to review the evaluation of pulmonary hypoplasia or hypoplastic lung disease as an important determinant of clinical outcomes in infants with congenital diaphragmatic hernia. In this review, we emphasize the importance of early prenatal diagnosis of congenital diaphragmatic hernia and present a summary of different methods of prenatal risk assessment of lung hypoplasia in congenital diaphragmatic hernia.

Identification of MicroRNA Profiles in Fetal Spina Bifida: The Role in Pathomechanism and Diagnostic Significance.

Distinct miRNA expression patterns may reflect anomalies related to fetal congenital malformations such as spinal bifida (SB). The aim of this preliminary study was to determine the maternal miRNA expression profile of women carrying fetuses with SB. Therefore, six women carrying fetuses with SB and twenty women with euploid healthy fetuses were enrolled in this study. Using NanoString technology, we evaluated the expression level of 798 miRNAs in both plasma and amniotic fluid samples. A downregulation of miR-1253, miR-1290, miR-194-5p, miR-302d-3p, miR-3144-3p, miR-4536-5p, miR-548aa + miR-548t-3p, miR-548ar-5p, miR-548n, miR-590-5p, miR-612, miR-627-5p, miR-644a, and miR-122-5p, and an upregulation of miR-320e, let-7b-5p, miR-23a-3p, miR-873-3p, and miR-30d-5p were identified in maternal amniotic fluid samples in SB when compared to the control group. The target genes of these miRNAs play a predominant role in regulating the synthesis of several biological compounds related to signaling pathways such as those regulating the pluripotency of stem cells. Moreover, the maternal plasma expression of miR-320e was increased in pregnancies with SB, and this marker could serve as a valuable non-invasive screening tool. Our results highlight the SB-specific miRNA signature and the differentially expressed miRNAs that may be involved in SB pathogenesis. Our findings emphasize the role of miRNA as a predictive factor that could potentially be useful in prenatal genetic screening for SB.

Poster Session: Optoretinography-based frequency characterization of the retinal response to a chirped flickering light.

In this contribution, we present experimental results of in vivo characterization of the photoreceptor's response to a chirped flickering white light stimulating the retina. We acquire the ORG signal with Spatio-Temporal Optical Coherence Tomography (STOC-T) setup, which combines both temporal and coherence gating to overcome limitations present in Full Field Fourier Domain Optical Coherence Tomography. From the acquired volumes, we extract the changes in optical path length (OPL) between the inner and outer photoreceptor junction (ISOS) and the cone outer segment tips (COST). We perform the measurements for frequencies ranging from 5 Hz to 50 Hz. The chirped flickering facilitates significantly shorter data acquisition time. We present results of in vivo measurement from three volunteers. Our results show that we can measure OPL changes between ISOS and COST occurring in response to a chirped flickering stimulation in a reproducible manner and resolve the amplitude of the response in the function of flicker frequency.

Multimode fiber as a tool to reduce cross talk in Fourier-domain full-field optical coherence tomography.

Fourier-domain full-field optical coherence tomography (FD-FF-OCT) is an emerging tool for high-speed eye imaging. However, cross-talk formation in images limits the imaging depth. To this end, we have recently shown that reducing spatial coherence with a fast deformable membrane can suppress the noise but over a limited axial range and with substantial data processing. Here, we demonstrate that a multimode fiber with carefully chosen parameters enables cross-talk-free imaging over a long axial range and without significant artifacts. We also show that it can be used to image the human retina and choroid in vivo with exceptional contrast.

A new approach to study human perivascular adipose tissue of the internal mammary artery by fiber-optic Raman spectroscopy supported by spectral modelling.

Perivascular adipose tissue (PVAT) regulates vascular function and represents a novel therapeutic target in vascular diseases. In this work, a new approach based on fiber-optic Raman spectroscopy and spectral modelling was used to characterize the chemical content of the PVAT of the internal mammary artery (IMA) of patients with advanced coronary atherosclerosis (n = 10) undergoing coronary bypass surgery. Our results showed a high degree of lipid unsaturation and low carotenoid content in the PVAT of the IMA of patients with more advanced coronary artery disease. Moreover, the spectral modelling of the IMA's PVAT composition indicated that glyceryl trioleate was a major PVAT lipid and for patients with relatively low levels of ß-carotene, it was accompanied by arachidonic acid and glyceryl trilinolenate. In summary, our proof-of-concept study suggests that carotenoid content and lipid unsaturation degree may reflect the PVAT functional status and a Raman-based assessment of the PVAT of the IMA could prove useful as a novel diagnostic tool to rapidly define the PVAT phenotype in a grafted artery in patients undergoing coronary bypass.

Computational aberration correction in spatiotemporal optical coherence (STOC) imaging.

Spatiotemporal optical coherence (STOC) imaging is a new technique for suppressing coherent cross talk noise in Fourier-domain full-field optical coherence tomography (FD-FF-OCT). In STOC imaging, the time-varying inhomogeneous phase masks modulate the incident light to alter the interferometric signal. Resulting interference images are then processed as in standard FD-FF-OCT and averaged incoherently or coherently to produce cross-talk-free volumetric optical coherence tomography (OCT) images of the sample. Here, we show that coherent averaging is suitable when phase modulation is performed for both interferometer arms simultaneously. We explain the advantages of coherent over incoherent averaging. Specifically, we show that modulated signal, after coherent averaging, preserves lateral phase stability, enabling computational phase correction to compensate for geometrical aberrations. Ultimately, we employ it to correct for aberrations present in the image of the photoreceptor layer of the human retina that reveals otherwise invisible photoreceptor mosaics.

Insomnia, postpartum depression and estradiol in women after delivery.

After childbirth, women may develop symptoms of depression with the associated sleep disturbances. This study assessed the relationship between insomnia and both depression symptoms and blood estradiol levels in women during the early postpartum period. 84 patients were assessed 24-48 h after labor. The main assessment methods were the following psychometric scales: Beck Depression Inventory (BDI), Edinburgh Postnatal Depression Scale (EPDS) and Athens Insomnia Scale (AIS). Serum estradiol levels were measured using ELISA assay. Women who developed postpartum insomnia significantly more often reported insomnia during pregnancy (P = 0.001), were more likely to have suffered from depression in the past (P = 0.007) and had significantly higher BDI (P = 0.002) and EPDS (P = 0.048) scores. Our study demonstrated no significant association between Restless Legs Syndrome (RLS) during pregnancy and postpartum insomnia. The groups of women with and without postpartum RLS showed no significant differences in the incidence of postpartum insomnia. No significant differences in estradiol levels were observed in women with and without postpartum insomnia. The study showed the following factors to play a major role in development of postpartum insomnia: an increase in Beck Depression Inventory score, a history of depression and a history of insomnia during pregnancy.

Influence of first trimester biochemistry methodology on detection rate in screening for trisomy 21.

OBJECTIVES: The purpose of the study was to compare detection rates (DR) of FMF-certified and non-certified biochemical tests (BC) in trisomy 21 screening at 11-13 + 6 weeks. MATERIAL AND METHODS: In 2267 singleton pregnancies FMF-certified doctors measured crown to rump length (CRL) and nuchal translucency (NT). Serum samples were tested for free ß-hCG and the PAPP-A using 2 analysers (Delfia - Perkin Elmer and Immulite 2000 - DPC), the results were expressed in MoM values and used for computer calculation of the risk for trisomy 21. The cut-off value for the high trisomy 21 risk was 1:300. RESULTS: Comparison of free ß-hCG MoMs by DPC and Delfia demonstrated statistically significant differences in normal, and trisomy 21 fetuses respectively. Similarly, statistically significant differences were noted for PAPP-A MoMs. The above differences in MoMs resulted in altered sensitivity in screening for aneuploidy. The application of the FMF-certified method ensures a markedly higher DR = 74%, compared to non-certified tests (64%), both at 5% FPR. The ROC analysis was performed in order to assess the efficacy of both tests. Results of trisomy 21 BC + NT risk scales using the Delfia and DPC methods are highly significant (p < 0.0001), which means that their discrimination ability is > 90%. The difference between results obtained using the Delfia and DPC methods is AUC = 0.0150 and is statistically significant (Z = 2.4728, p = 0.0134). CONCLUSIONS: The use of FMF-certified first trimester biochemistry analysers improves DR for trisomy 21. The use of non-certified analysers causes reduction of DR and an increase of invasive procedure rate.

Anxiety and depression in women undergoing infertility treatment.

Infertility is a significant problem for millions of couples. Recently more attention is being paid to the relationship between infertility treatment with the use of Assisted Reproductive Techniques and the presence of mental disturbances, of which anxiety and depression are the most common. We present a review of recent studies evaluating the influence of anxiety and depression on fertility treatment outcomes and the effect of Assisted Reproductive Techniques treatment on the presence of anxiety and depression among women. The studies show conflicting results concerning the effect of anxiety on Assisted Reproductive Techniques treatment outcomes, but most reveal that Assisted Reproductive Techniques treatment leads to an increased level of anxiety, especially in cases of treatment failure and longer durations of treatment. Most studies do not show a relationship between depression and Assisted Reproductive Techniques treatment outcomes, but it seems that severe depression can lead to lower rates of pregnancy during infertility treatment with Assisted Reproductive Techniques. Moreover, women who become pregnant after Assisted Reproductive Techniques treatment seem to have an increased risk of depression in later life.

Screening for trisomy 21 based on maternal age, nuchal translucency measurement, first trimester biochemistry and quantitative and qualitative assessment of the flow in the DV - the assessment of efficacy.

OBJECTIVES: The aim of the study was to compare effects of addition of two methods of ductus venosus (DV) flow assessment: qualitative - the assessment of shape of the A-wave (positive or negative), and quantitative - based on the pulsatility index for veins (DVPI) to the basic screening for trisomy 21 at 11 to 13 + 6 weeks of pregnancy. MATERIAL AND METHODS: The ultrasound examination was performed in 8230 fetuses in singleton pregnancies at 11- -13 + 6 wks, as a part of a routine screening for chromosomal defects. In DV A-wave was assessed and DVPI was calculated. After the scan blood sample was taken for first trimester biochemistry (BC). Risk for chromosomal defects was calculated and high-risk patients were offered an invasive test for karyotyping. RESULTS: Basic screening with following combination of markers: MA, NT and BC provided lowest detection rate (DR) 87.50% for FPR = 6.94%. After adding qualitative DV A-wave assessment DR increased to 88.75% for FPR = 5.65%. The best DR = 93.75% for FPR = 5.55% was achieved when quantitative DVPI was added. The application of the Receiver Operating Curves curve confirmed validity of the addition of DV flow assessment to the screening model. The highest diagnostic power of the test was achieved when DVPI was added, with the ROC AUC of 0.974. CONCLUSIONS: The assessment of DV flow performed at 11-13 + 6 weeks increases DR for trisomy 21 and reduces FPR. The screening model based on the quantitative DV flow analysis (DVPI) gives better results compared to the qualitative flow assessment.

Placental examination with dye injections in post-delivery chorionicity assessment in dichorionic triplet pregnancy.

The incidence of spontaneous triplet pregnancy is approximately 1 in 7000 deliveries. Due to the fact that every presentation of a triplet and higher order pregnancy is associated with high rate of morbidity and preterm delivery, chorionicity and amnionicity remain significant predictive factors which determine specific management throughout the pregnancy. Ultrasound chorionicity assessment in triplet pregnancies is more complex than in twins, and in many cases it remains unknown. We present a case report of a 24-year-old primipara in a spontaneous dichorionic triplet pregnancy, qualified for a cesarean section at 33 weeks of gestation, with subsequent placental examination with dye injections and post-delivery chorionicity assessment.

Nasal bone in screening for T21 at 11-13 + 6 weeks of gestation - a multicenter study.

OBJECTIVES: Trisomy 21 is one of the most common chromosomal defects diagnosed prenatally. Screening for Down syndrome is based on maternal age, measurement of crown-rump length, nuchal translucency and fetal heart rate, together with free ß-hCG and PAPP-A at 11 to 13 + 6 weeks. Introduction of additional ultrasound marker of trisomy 21 (evaluation of the nasal bone) may result in increased DR and decreased invasive diagnostic testing rates (FPR). MATERIAL AND METHODS: Ultrasound scan with NB evaluation was performed in 5814 fetuses during routine screening for chromosomal defects at 11 to 13 + 6 weeks of gestation. DR and FPR coefficients were calculated for 4 levels of risk as cut-off points for screening model 1, based on MA, NT, and first trimester biochemistry, as well as for screening model 2, based on MA, NT, first trimester biochemistry and NB. RESULTS: There were 5708 normal cases, 71 cases of trisomy 21 and 35 cases of other chromosomal defects. NB was absent in 46 (64.8%) cases and present in 25 (35.3%) cases of trisomy 21, comparing to present NB in 5463 (95.7%) and absent in 245 (4.3%) of normal cases. CONCLUSIONS: First-semester screening with additional NB assessment significantly increases the detection rate for trisomy 21 and decreases the rate of false-positive results. Adding NB evaluation at the risk level of 1:50 causes only a small increase in detection rate. Invasive procedures should be performed in that group regardless NB assessment.

The evolution of fetal presentation during pregnancy: a retrospective, descriptive cross-sectional study.

We investigated changes in the frequencies of four primary types of singleton fetal lie/presentation for each gestational week from 18 to 39 weeks in a retrospective, cross-sectional study which analyzed ultrasound examination records of fetal positions, in the outpatient prenatal diagnosis clinics in two cities in Poland. We calculated the prevalence and 95% confidence intervals for each type of lie/presentation. We then identified the gestational age after which no statistically significant changes in terms of prevalence were observed, by comparing the results at each week with the prevalence of cephalic presentation at 39(+0) weeks, used as reference. A total of 18 019 ultrasound examinations were used. From 22 to 36 weeks of gestation, the prevalence of cephalic presentation increased from 47% (45-50%) to 94% (91-96%), before and after which times plateaus were noted. Spontaneous change from breech to cephalic is unlikely to occur after 36 weeks of gestation.

Phosphorylated IGFBP-1 in predicting successful vaginal delivery in post-term pregnancy.

PURPOSE: To estimate whether phosphorylated IGFBP-1 (phIGFBP-1) in cervical secretion in term and post-term pregnancies can predict spontaneous onset of labor or vaginal delivery. METHODS: A prospective cohort study of 167 women in singleton term and post-term pregnancies, was conducted at 1st Department of Obstetrics and Gynecology, Medical University of Warsaw, between 2013 and 2014. phIGFBP-1 test (Actim Partus Medix Biochemica), ultrasound cervix assessment and Bishop score were analyzed in the study group. Spontaneous onset of labor was the primary and vaginal delivery was the secondary outcome. RESULTS: In 32.5 % of patients, spontaneous uterine contractions appeared. 67.5 % of women delivered vaginally, 32.5 % had cesarean section. phIGFBP-1 test predicted spontaneous onset of labor (sensitivity 0.69, specificity of 0.42) and successful vaginal delivery (0.67, 0.48). In the prediction of spontaneous delivery onset ultrasound cervical assessment and phIBFBP-1 had comparable sensitivity and in the prediction of successful vaginal birth all three tests had comparable sensitivity. The time from preinduction to spontaneous onset of delivery was significantly shorter in women with positive phIGFBP-1 test (13.65 ± 6.7 vs 20.75 ± 2.6 h; p = 0.006). CONCLUSION: A test for phIGFBP1 presence might be an additional tool for predicting both spontaneous onset of labor and successful vaginal delivery in post-term pregnancies.

Evaluation of sonographic assessment of the progress of labor.

OBJECTIVE: To evaluate the practical application of intrapartum sonographic assessment of the progress of labor. MATERIAL AND METHODS: Eighty three full-term pregnant women who delivered at the Obstetrics and Gynecology Department were enrolled into this study. Transperineal ultrasonographic examinations were conducted with a convex transducer at the onset of active labor, yielding mid-sagittal and coronal images. Three parameters were measured: 1) the angle between the long axis of the symphysis pubis and the line joining its lowest margin to the contour of the fetal head (angle of progression); 2) the distance between the presenting point and the line perpendicular to the symphysis pubis and passing through its lowest margin; 3) the fetal head-perineum distance. The relationship between measurement results and the period from examination to delivery was also analyzed. RESULTS: There were 73 vaginal deliveries and 10 women underwent a cesarean section due to failure to progress. The two groups (vaginal vs. cesarean delivery) differed significantly in terms of the angle of progression (131 vs. 110 degrees, respectively p<0.01) and the distance between the presenting point and the infrapubic line (34 vs. 20 mm, respectively p<0.01). The inter-group difference in fetal head-peritoneum distances (53 and 61 mm, respectively) was noticeable but non-significant (p>0.05). The study also demonstrated a relationship between all three of the measured values and the time to second labor phase completion. CONCLUSIONS: Ultrasonography may be useful in assessing the progress of labor as well as in predicting or early diagnosis of abnormal fetal head descent.

Siamese twins--prenatal diagnosis in the first trimester of pregnancy. Case study and review.

Conjoined twins are a unique type of monozygotic twins. All monozygotic twins should be thoroughly evaluated for incomplete separation and, if incomplete separation is diagnosed, the extent of internal organ connection and the presence of additional developmental anomalies of the foetuses should be assessed. Common heart of foetuses is particularly difficult to diagnose and crucial for prognosis. We present an example of female thoracoomohalopagus twins with a common triventricular heart, connate livers, and joined hepatic vessels, diagnosed in week 12 of pregnancy Due to the high complexity of foetal connection, separation was not possible and following interdisciplinary consultation, the pregnancy was aborted upon the patient's request in week 16.

[Postpartum levator ani muscle injuries. Diagnosis and treatment]. / Poporodowe uszkodzenia dzwigacza odbytu. Diagnostyka i terapia.

Levator ani muscle (LAM) injuries are much more frequent than trauma to sphincter ani muscles, but so far they have been omitted in obstetric handbooks. Levator ani avulsion is observed only after vaginal delivery. Forceps delivery second stage of labor ≥ 110 min., fetal head circumference ≥ 35 cm, episiotomy and coincidence of anal sphincter trauma are risk factors for levator ani avulsion. The most vital issue in that type of trauma is pelvic organ prolapse and 2-4-fold higher risk of recurrence after prolapse surgery. The current level of evidence does not allow to conclusively determine the of role of levator avulsion in urinary incontinence. Levator injuries are occult, what constitutes the main diagnostic problem. Until recently magnetic resonance imaging has been the only diagnostic method until the development of 3-dimensional ultrasound. Nowadays, 3-D ultrasound is an essential technique in static and functional diagnosis of the levator ani. There are no effective methods of levator trauma prevention. Except the risk factors reduction, there are some pilot data about positive role of antepartal perineal muscle training. Physiotherapy plays the main role in reducing the effects of levator trauma. Mesh techniques are the most effective operative methods in coincident pelvic organ prolapse with levator avulsion, but there is still a 2-fold higher risk of recurrence.

Does prior knowledge of maternal age affect judgment of operators measuring nuchal translucency?

OBJECTIVES: To test the hypothesis that, in real life standard clinical practice, knowledge of maternal age (MA) by operators measuring nuchal translucency (NT) for screening of aneuploidy may influence their judgment, resulting in a tendency to over-measurement in older women. MATERIAL AND METHODS: We retrospectively analyzed the correlation between MA and NT MoMs in data from a group of operators from several clinical practices, with different levels of experience. RESULTS: We assessed 66,918 measurements by 41 operators. There was no association between NT and MA in all the measurements analyzed together In 3 experienced operators (N > 1900), there was a significant association between the variables, although all were negative and its effect size was very small (0.004, 0.006 and 0.01). However one of the less experienced operators (N = 47) had a statistically significant (p = 0.0002) and strong (R2 = 0.2634) association. We tested the hypothesis that this bias could occur in less experienced operators but time/experience would correct it. We did the same analyses for each set of 50 tests, sorted by date, for each operator up to the 7th set. No significant progression was identified in association with increase in experience. CONCLUSIONS: Our data does not support the hypothesis that operators might be biased towards over-measuring NT in older women.

[Fetal hepatic artery flow assessment in prenatal diagnostics--a review of the literature]. / Ocena przeplywów w tetnicy watrobowej plodu w diagnostyce prenatalnej. Przeglad literatury.

Standards of screening tests for the most frequent fetal chromosomal defects in modern non-invasive prenatal diagnostics provide sensitivity of about 93-96%, with the false positive rate of 2.5%. During the first trimester scan, routinely performed between 11 and 13+6 week of pregnancy the calculation of the risk for chromosomal aberrations is based on maternal age (MA), nuchal translucency (NT), levels of free beta human chorionic gonadotropin (free beta-hCG), pregnancy associated plasma protein A (PAPP-A) in maternal blood, as well as the parameters from extended ultrasound examination like evaluation of the nasal bone (NB), blood flow in ductus venosus (DV), visualization of the tricuspid valve with potential regurgitation (TR) or measurement of the frontomaxillary facial angle (FMFA). The 100% detection rate remains unachievable at present, despite constantly improving guidelines for specialists, quality of imaging, and advancement in ultrasound technology Therefore, several studies have been undertaken to establish the group of 'additional markers' of chromosomal defects which, when combined with basic markers of routine screening tests, might increase the detection rate and approach it to 100%. Results of recent studies imply that evaluation of blood flow in fetal hepatic artery performed during the first trimester scan may become a new additional marker for chromosomal defects.