Impact of COVID-19 Related Maternal Stress on Fetal Brain Development: A Multimodal MRI Study

Background: Disruptions in perinatal care and support due to the COVID-19 pandemic was an unprecedented but significant stressor among pregnant women. Various neurostructural differences have been re-ported among fetuses and infants born during the pandemic compared to pre-pandemic counterparts. The relationship between maternal stress due to pandemic related disruptions and fetal brain is yet unexamined. Methods: Pregnant participants with healthy pregnancies were prospectively recruited in 2020–2022 in the greater Los Angeles Area. Participants completed multiple self-report assessments for experiences of pandemic related disruptions, perceived stress, and coping behaviors and underwent fetal MRI. Maternal perceived stress exposures were correlated with quantitative multimodal MRI measures of fetal brain development using multivariate models. Results: Increased maternal perception of pandemic related stress positively correlated with normalized fetal brainstem volume (suggesting accelerated brainstem maturation). In contrast, increased maternal perception of pandemic related stress correlated with reduced global fetal brain temporal functional variance (suggesting reduced functional connectivity). Conclusions: We report alterations in fetal brainstem structure and global functional fetal brain activity associated with increased maternal stress due to pandemic related disruptions, suggesting altered fetal programming. Long term follow-up studies are required to better understand the sequalae of these early multi-modal brain disruptions among infants born during the COVID-19 pandemic

Low-frequency fluctuation amplitude analysis of resting-state fMRI for sickle cell disease patients

International audienceSickle cell disease may result in neurological damage and strokes, leading to morbidity and mortality. The inability of conventional magnetic resonance imaging to predict impending stroke underlies the need for other neuroimaging markers risk. In this study, we analyzed neuronal processes at resting state and more particularly how this disease affects the default mode network. The amplitude of low frequency fluctuations was used to reflect areas of spontaneous BOLD signal across brain regions. We compared the activations of sickle cell disease patients to a control group with variance analysis and t-test. Significant differences in different parts among the two groups were observed, especially in the default mode network areas and cortical regions near large cerebral arteries. These findings suggest that sickle cell disease can cause some activation modifications near vessels, and these changes could be used a biomarker of the malady

BOLD delay times using group delay in sickle cell disease

International audienceSickle cell disease (SCD) is an inherited blood disorder that effects red blood cells, which can lead to vasoocclu-sion, ischemia and infarct. This disease often results in neurological damage and strokes, leading to morbidity and mortality. Functional Magnetic Resonance Imaging (fMRI) is a non-invasive technique for measuring and mapping the brain activity. Blood Oxygenation Level-Dependent (BOLD) signals contain also information about the neurovascular coupling, vascular reactivity, oxygenation and blood propagation. Temporal relationship between BOLD fluctuations in different parts of the brain provides also a mean to investigate the blood delay information. We used the induced desaturation as a label to profile transit times through different brain areas, reflecting oxygen utilization of tissue. In this study, we aimed to compare blood flow propagation delay time between these patients and healthy subjects in areas vascularized by anterior, middle and posterior cerebral arteries. At first, BOLD changes in these areas were almost simultaneous and shorter in the SCD patients, because of their increased brain blood flow. Secondly, the analysis of a patient with a stenosis on the anterior cerebral artery indicated that signal of the area vascularized by this artery lagged the MCA signal. These findings suggested that sickle cell disease causes blood propagation modifications, and these changes could be used as a biomarker of vascular damage

Impact of COVID-19 Related Maternal Stress on Fetal Brain Development: A Multimodal MRI Study

Background: Disruptions in perinatal care and support due to the COVID-19 pandemic was an unprecedented but significant stressor among pregnant women. Various neurostructural differences have been re-ported among fetuses and infants born during the pandemic compared to pre-pandemic counterparts. The relationship between maternal stress due to pandemic related disruptions and fetal brain is yet unexamined. Methods: Pregnant participants with healthy pregnancies were prospectively recruited in 2020–2022 in the greater Los Angeles Area. Participants completed multiple self-report assessments for experiences of pandemic related disruptions, perceived stress, and coping behaviors and underwent fetal MRI. Maternal perceived stress exposures were correlated with quantitative multimodal MRI measures of fetal brain development using multivariate models. Results: Increased maternal perception of pandemic related stress positively correlated with normalized fetal brainstem volume (suggesting accelerated brainstem maturation). In contrast, increased maternal perception of pandemic related stress correlated with reduced global fetal brain temporal functional variance (suggesting reduced functional connectivity). Conclusions: We report alterations in fetal brainstem structure and global functional fetal brain activity associated with increased maternal stress due to pandemic related disruptions, suggesting altered fetal programming. Long term follow-up studies are required to better understand the sequalae of these early multi-modal brain disruptions among infants born during the COVID-19 pandemic

Parametric Mapping of Oxygen Activity in Human Placenta across Gestation using in utero BOLD imaging

International audienceSynopsis We present here, for the rst time, parametric maps of oxygen activity in normal human placenta using in utero functional MR imaging. Our method highlights anatomical and gestational age dependent patterns in placental activity. These maps can be used to gain insight into normative placental function and identifying insuucient or abnormal placental functioning at various points in gestation. Introduction Our current understanding of placental development and function is based on animal imaging and ex-vivo studies of placenta obtained after delivery or interrupted pregnancies. Previous human imaging studies were restricted to understanding hyperoxygentation or adverse developmental conditions such as fetal growth restriction (FGR), placental previa, placenta accrete, etc.. These studies strongly indicate that improved in-vivo delineation of vasculogenesis and angiogenesis of the placenta has the potential to provide better insight into the pathogenesis of placental dysfunction. By leveraging non-invasive, high-resolution imaging capabilities of in utero fetal MRI, we present a spatiotemporal analysis of normative fetoplacental oxygenation patterns at various time points in gestation. We hypothesize that (a) spatial variance of BOLD placental signal would age-dependent , and (b) that serial parametric maps of BOLD signal would reveal important anatomic insights about the feto-placental and maternal circulation. Methods We conducted a prospective two-site study of placental development in which 20 maternal subjects with normal pregnancies were recruited between 26-37 gestational weeks (GW). Images were acquired using 3T Philips Ingenia or Siemens Skyra machines. Over a 5-10 minute total acquisition time, BOLD images (1.5 mm x 1.5 mm x 4 mm) were acquired using an EPI sequence in blocks of 60 images with TR/TE = 3000/35 ms, ip angle = 90°. In addition, a high resolution T2 weighted images (1 mm x 1 mm x 3 mm) were acquired using a 3D FFE sequence (TR/TE = 3.1/1.6 ms, ip angle = 75°). BOLD images were processed using the "Functional MRI of the Brain" Software Library (FSL). The BOLD signal was motion corrected, co registered to the T2 images and ltered to remove physiological noise such as cardiac, breathing and metabolic uctuations. An F test was used to test the relationship between spatial signal variations and gestational age. To compare oxygenation levels within the placenta, we computed the normalized BOLD values after averaging the amplitude of the BOLD signal over the duration of the study for each time point. Results We found that the spatial variance of the BOLD signal was age dependent (F= 2.25, p<0.001). We then generated parametric maps of oxygen activity in a subset of fetuses at various gestational ages. Figure 1 shows the mean BOLD signal values across the placenta between 26 and 36 GW. The parametric mapping delineates two distinct regions of high oxygenation activity, corresponding to the fetal side (adjacent to the site of umbilical cord attachment) and the maternal side (along the uterine wall). The regions of high activity also occurred in speciic clusters. The size and number if these high-activity regions increased from 26 to 28 GW. We then observed a drop in the number and size of these regions at 29 GW with a further decrease at 36 GW. Discussion Our results clearly indicate that oxygenation is spatially heterogenous across the placenta with oxygen activity concentrated at speciic anatomical locations. The spatial variance in oxygen activity is also age-dependent. The reduction in size and number of high activity clusters at 29 GW and beyond correlates with the involution of the placenta in the third trimester leading to birth. Lower BOLD signal values in the middle of the placenta could correspond to the lack of deoxyhemoglobin as these regions only transport oxygen to the umbilical cord. The oxygenation maps provide a baseline for how oxygen activity occurs and changes over gestation giving us a better understanding of fetoplacental haemodynamics and placental transfer. They may also be used to identify abnormal oxygenation patterns in a placenta thereby acting as a marker for early detection of FGR or insuucient placental function. Conclusion There are age-dependent, spatial variances of BOLD signal in the placenta which may correlate with angiogenesis. Using parametric mapping of placental BOLD signal, we have demonstrated that placental oxygenation activity is concentrated at speciic anatomical locations associated with feto-maternal oxygen exchange. The non-invasive and repeatable methods presented here may facilitate better predictions of placental dysfunction in high-risk pregnancies and inform perinatal care

Diffuse T1-MRI White Matter Volume Decrease in Patients with Sickle Cell Disease

International audienceSickle cell disease (SCD) is a genetic blood disorder associated with anemia, chronic vascular damage, overt stroke, silent cerebral infarctions, and early mortality. Patients with SCD have increased cerebral blood flow to compensate for their anemia but nevertheless exhibit regional cerebralhypo-perfusion and neurocognitive decline. Previous volumetric studies in SCD have shown delayed growth, gray matter (GM) loss, white matter (WM) loss, and decreased cortical thickness compared with control subjects. Diffusion-tensor imaging have demonstrated compromised WM integrity in major fiber pathways diffusely throughout the brain. Further regional investigations of structural outcome could potentially help expand our understanding of the neurobiology of SC

Novel euglycemic and hypolipidemic agents: Pyridine containing unsaturated thiazolidinediones

403-406Pyridyl containing 2,4-thiazolidinediones having cyclic amine as linker have been synthesized. Both unsaturated thiazolidinedione <span style="font-size:15.5pt; mso-bidi-font-size:8.5pt;font-family:" times="" new="" roman";mso-fareast-font-family:="" "times="" roman";mso-ansi-language:en-us;mso-fareast-language:en-us;="" mso-bidi-language:ar-sa"="">6<span style="font-size:15.5pt;mso-bidi-font-size: 8.5pt;font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"=""> and saturated thiazolidinedione 5 and their various salts have been evaluated in db/db mice for euglycemic and hypolipidemic effects. The maleate salt of TZD 6a is found to be a very potent euglycemic and hypolipidemic compound.</span