ABSTRACT
OBJECTIVES: T2*-weighted magnetic resonance imaging (MRI) sequences have been identified as non-invasive tools with which to study placental oxygenation in vivo. This study aimed to use these to investigate both static and dynamic responses to hyperoxia of the normal placenta across gestation. METHODS: We conducted a single-center prospective study including 52 uncomplicated pregnancies. Two T2*-weighted sequences (T2* relaxometry) were performed, one before and one after maternal hyperoxia. The distribution of placental T2* values was modeled by fitting a gamma probability density function (T2* ~ Γ α ß ), describing the structure of the histogram using the mean T2* value, the shape parameter (α) and the rate (ß). A dynamic acquisition (blood-oxygen-level-dependent (BOLD) MRI) was also performed before and during maternal oxygen supply, until placental oxygen saturation had been achieved. The signal change over time was modeled using a sigmoid function, to determine the intensity of enhancement (ΔBOLD (% with respect to baseline)), a temporal variation coefficient (λ (min-1), controlling the slope of the curve) and the maximum steepness (Vmax (% of placental enhancement/min)). RESULTS: The histogram analysis of the T2* values in normoxia showed a whole-placenta variation, with a decreasing linear trend in the mean T2* value (Pearson's correlation coefficient (R) = -0.83 (95% CI, -0.9 to -0.71), P < 0.001), along with an increasingly peaked and narrower distribution of T2* values with advancing gestation. After maternal hyperoxia, the mean T2* ratios (mean T2*hyperoxia/mean T2*baseline) were positively correlated with gestational age, while the other histogram parameters remained stable, suggesting a translation of the histogram towards higher values with a similar appearance after maternal hyperoxia. ΔBOLD showed a non-linear increase across gestation. Conversely, λ showed an inverted trend across gestation, with a weaker correlation (R = -0.33 (95% CI, -0.58 to -0.02), P = 0.04, R2 = 0.1). As a combination of ΔBOLD and λ, the changes in Vmax throughout gestation were influenced mainly by the changes in ΔBOLD and showed a positive non-linear correlation with gestational age. CONCLUSIONS: Our results suggest that the decrease in the T2* placental signal as gestation progresses does not reflect placental dysfunction. The BOLD dynamic signal change is representative of a free-diffusion model of oxygenation and highlights the increasing differences in oxygen saturation between mother and fetus as gestation progresses (ΔBOLD) and in the placental permeability to oxygen (λ). © 2024 International Society of Ultrasound in Obstetrics and Gynecology.
Subject(s)
Hyperoxia , Magnetic Resonance Imaging , Placenta , Humans , Female , Pregnancy , Placenta/diagnostic imaging , Placenta/metabolism , Hyperoxia/diagnostic imaging , Magnetic Resonance Imaging/methods , Prospective Studies , Adult , Gestational Age , Oxygen/metabolismABSTRACT
INTRODUCTION: Twin-twin transfusion syndrome (TTTS) and selective fetal growth restriction (sFGR) are common complications in monochorionic diamniotic (MCDA) pregnancies. The Diffusion-rElaxation Combined Imaging for Detailed Placental Evaluation (DECIDE) model, a placental-specific model, separates the T2 values of the fetal and maternal blood from the background tissue and estimates the fetal blood oxygen saturation. This study investigates diffusion and relaxation differences in uncomplicated MCDA pregnancies and MCDA pregnancies complicated by TTTS and sFGR in mid-pregnancy. METHODS: This prospective monocentric cohort study included uncomplicated MCDA pregnancies and pregnancies complicated by TTTS and sFGR. We performed MRI with conventional diffusion-weighted imaging (DWI) and combined relaxometry - DWI-intravoxel incoherent motion. DECIDE analysis was used to quantify different parameters within the placenta related to the fetal, placental, and maternal compartments. RESULTS: We included 99 pregnancies, of which 46 were uncomplicated, 12 were complicated by sFGR and 41 by TTTS. Conventional DWI did not find differences between or within cohorts. On DECIDE imaging, fetoplacental oxygen saturation was significantly lower in the smaller member of sFGR (p = 0.07) and in both members of TTTS (p = 0.01 and p = 0.004) compared to the uncomplicated pairs. Additionally, average T2 relaxation time was significantly lower in the smaller twin of the sFGR (p = 0.004) compared to the uncomplicated twins (p = 0.03). CONCLUSION: Multicompartment functional MRI showed significant differences in several MRI parameters between the placenta of uncomplicated MCDA pregnancies and those complicated by sFGR and TTTS in mid-pregnancy.
ABSTRACT
OBJECTIVES: Prenatal surgery is offered for selected fetuses with open spina bifida (OSB) to improve long-term outcome. We studied the effect of fetal OSB surgery on brain development using advanced magnetic resonance imaging (MRI) techniques to quantify the volume, surface area and shape of cerebral structures and to analyze surface curvature by means of parameters that correspond to gyrification. METHODS: We compared MRI data from 29 fetuses with OSB before fetal surgery (mean gestational age (GA), 23 + 3 weeks) and at 1 and 6 weeks after surgery, with that of 36 GA-matched control fetuses (GA range, 21 + 2 to 36 + 2 weeks). Automated super-resolution reconstruction provided three-dimensional isotropic volumetric brain images. Unmyelinated white matter, cerebellum and ventricles were segmented automatically and refined manually, after which volume, surface area and shape parameter (volume/surface area) were quantified. Mathematical markers (shape index (SI) and curvedness) were used to measure gyrification. Parameters were assessed according to lesion type (myelomeningocele vs myeloschisis (MS)), postoperative persistence of hindbrain herniation (HH) and the presence of supratentorial anomalies, namely partial agenesis of the corpus callosum (pACC) and heterotopia (HT). RESULTS: Growth in ventricular volume per week and change in shape parameter per week were higher at 6 weeks after surgery in fetuses with OSB compared with controls (median, 2500.94 (interquartile range (IQR), 1689.70-3580.80) mm3 /week vs 708.21 (IQR, 474.50-925.00) mm3 /week; P < 0.001 and 0.075 (IQR, 0.047-0.112) mm/week vs 0.022 (IQR, 0.009-0.042) mm/week; P = 0.046, respectively). Ventricular volume growth increased 6 weeks after surgery in cases with pACC (P < 0.001) and those with persistent HH (P = 0.002). During that time period, the change in unmyelinated white-matter shape parameter per week was decreased in OSB fetuses compared with controls (0.056 (IQR, 0.044-0.092) mm/week vs 0.159 (IQR, 0.100-0.247) mm/week; P = 0.002), particularly in cases with persistent HH (P = 0.011), MS (P = 0.015), HT (P = 0.022), HT with corpus callosum anomaly (P = 0.017) and persistent HH with corpus callosum anomaly (P = 0.007). At 6 weeks postoperatively, despite OSB fetuses having a lower rate of change in curvedness compared with controls (0.061 (IQR, 0.040-0.093) mm-1 /week vs 0.094 (IQR, 0.070-0.146) mm-1 /week; P < 0.001), reversing the trend seen at 1 week after surgery (0.144 (IQR, 0.099-0.236) mm-1 /week vs 0.072 (IQR, 0.059-0.081) mm-1 /week; P < 0.001), gyrification, as determined using SI, appeared to be increased in OSB fetuses overall compared with controls. This observation was more prominent in fetuses with pACC and those with severe ventriculomegaly (P-value range, < 0.001 to 0.006). CONCLUSIONS: Following fetal OSB repair, volume, shape and curvedness of ventricles and unmyelinated white matter differed significantly compared with those of normal fetuses. Morphological brain changes after fetal surgery were not limited to effects on the circulation of cerebrospinal fluid. These observations may have implications for postnatal neurocognitive outcome. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Subject(s)
Meningomyelocele , Spina Bifida Cystica , Female , Pregnancy , Humans , Spina Bifida Cystica/diagnostic imaging , Spina Bifida Cystica/surgery , Meningomyelocele/surgery , Brain/diagnostic imaging , Fetus , Gestational Age , Magnetic Resonance Imaging/methods , Retrospective Studies , Ultrasonography, PrenatalABSTRACT
OBJECTIVE: We hypothesised that a multi-compartment magnetic resonance imaging (MRI) technique that is sensitive to fetal blood oxygenation would identify changes in placental blood volume and fetal blood oxygenation in pregnancies complicated by early-onset fetal growth restriction (FGR). DESIGN: Case-control study. SETTING: London, UK. POPULATION: Women with uncomplicated pregnancies (estimated fetal weight [EFW] >10th centile for gestational age [GA] and normal maternal and fetal Doppler ultrasound, n = 12) or early-onset FGR (EFW <3rd centile with or without abnormal Doppler ultrasound <32 weeks GA, n = 12) were studied. METHODS: All women underwent MRI examination. Using a multi-compartment MRI technique, we quantified fetal and maternal blood volume and feto-placental blood oxygenation. MAIN OUTCOME MEASURES: Disease severity was stratified according to Doppler pulsatility index and the relationship to the MRI parameters was investigated, including the influence of GA at scan. RESULTS: The FGR group (mean GA 27+5 weeks, range 24+2 to 33+6 weeks) had a significantly lower EFW compared with the control group (mean GA 29+1 weeks; -705 g, 95% CI -353 to -1057 g). MRI-derived feto-placental oxygen saturation was higher in controls compared with FGR (75 ± 9.6% versus 56 ± 16.2%, P = 0.02, 95% CI 7.8-30.3%). Feto-placental oxygen saturation estimation correlated strongly with GA at scan in controls (r = -0.83). CONCLUSION: Using a novel multimodal MRI protocol we demonstrated reduced feto-placental blood oxygen saturation in pregnancies complicated by early-onset FGR. The degree of abnormality correlated with disease severity defined by ultrasound Doppler findings. Gestational age-dependent changes in oxygen saturation were also present in normal pregnancies. TWEETABLE ABSTRACT: MRI reveals differences in feto-placental oxygen saturation between normal and FGR pregnancy that is associated with disease severity.
Subject(s)
Fetal Growth Retardation/diagnostic imaging , Magnetic Resonance Imaging , Oxygen/blood , Placenta/diagnostic imaging , Placental Circulation/physiology , Adult , Case-Control Studies , Cohort Studies , Female , Fetal Growth Retardation/blood , Fetal Growth Retardation/physiopathology , Gestational Age , Humans , Placenta/blood supply , Pregnancy , Prenatal DiagnosisABSTRACT
INTRODUCTION: There are considerable variations in villous morphology within a normal placenta. However, whether there is a reproducible spatial pattern of variation in villous vascular density is not known. Micro-CT provides three-dimensional volume imaging with spatial resolution down to the micrometre scale. In this study, we applied Micro-CT and histological analysis to investigate the degree of heterogeneity of vascularisation within the placenta. METHOD: Ten term placentas were collected at elective caesarean section, perfused with contrast agent and imaged whole with Micro-CT. Eight full depth tissue blocks were then taken from each placenta and imaged. Sections were taken for histological analysis. Data was analysed to investigate vascular fill, and vascular density in relation to location from cord insertion to placental edge at each scale. RESULTS: Whole placental imaging revealed no spatially consistent difference in villous vessel density within the main placental tissue, although there was a great degree of heterogeneity. Both block imaging and histological analysis found a large degree of heterogeneity of vascular density within placentas, but no strong correlation between villous vascular density and block location (rsâ¯=â¯0.066, pâ¯=â¯0.7 block imaging, rsâ¯=â¯0.06, pâ¯=â¯0.6 histological analysis). DISCUSSION: This work presents a novel method for imaging the human placenta vascular tree using multiscale Micro-CT imaging. It demonstrates that there is a large degree of variation in vascular density throughout normal term human placentas. The three-dimensional data created by this technique could be used, with more advanced computer analysis, to further investigate the structure of the vascular tree.
Subject(s)
Placenta/blood supply , X-Ray Microtomography , Adult , Anatomic Variation , Female , Humans , Placenta/diagnostic imaging , PregnancyABSTRACT
BACKGROUND: Surgery or multiple procedural interventions in extremely preterm neonates influence neurodevelopmental outcome and may be associated with long-term changes in somatosensory function or pain response. METHODS: This observational study recruited extremely preterm (EP, <26 weeks' gestation; n=102, 60% female) and term-born controls (TC; n=48) aged 18-20 yr from the UK EPICure cohort. Thirty EP but no TC participants had neonatal surgery. Evaluation included: quantitative sensory testing (thenar eminence, chest wall); clinical pain history; questionnaires (intelligence quotient; pain catastrophising; anxiety); and structural brain imaging. RESULTS: Reduced thermal threshold sensitivity in EP vs TC participants persisted at age 18-20 yr. Sex-dependent effects varied with stimulus intensity and were enhanced by neonatal surgery, with reduced threshold sensitivity in EP surgery males but increased sensitivity to prolonged noxious cold in EP surgery females (P<0.01). Sex-dependent differences in thermal sensitivity correlated with smaller amygdala volume (P<0.05) but not current intelligence quotient. While generalised decreased sensitivity encompassed mechanical and thermal modalities in EP surgery males, a mixed pattern of sensory loss and sensory gain persisted adjacent to neonatal scars in males and females. More EP participants reported moderate-severe recurrent pain (22/101 vs 4/48; χ2=0.04) and increased pain intensity correlated with higher anxiety and pain catastrophising. CONCLUSIONS: After preterm birth and neonatal surgery, different patterns of generalised and local scar-related alterations in somatosensory function persist into early adulthood. Sex-dependent changes in generalised sensitivity may reflect central modulation by affective circuits. Early life experience and sex/gender should be considered when evaluating somatosensory function, pain experience, or future chronic pain risk.
Subject(s)
Infant, Extremely Premature/physiology , Pain/physiopathology , Premature Birth/physiopathology , Sensory Thresholds/physiology , Somatosensory Cortex/physiopathology , Surgical Procedures, Operative , Adolescent , Cognition/physiology , Cohort Studies , Female , Humans , Infant, Newborn , Longitudinal Studies , Male , Neurodevelopmental Disorders/etiology , Neurodevelopmental Disorders/physiopathology , Neuropsychological Tests , Pain/etiology , Sex Factors , Surgical Procedures, Operative/adverse effects , Young AdultABSTRACT
A dynamic-contrast-enhanced magnetic resonance imaging (DCE-MRI) dataset consists of many imaging frames, often acquired both before and after contrast injection. Due to the length of time spent acquiring images, patient motion is likely and image re-alignment or registration is required before further analysis such as pharmacokinetic model fitting. Non-rigid image registration procedures may be used to correct motion artefacts; however, a careful choice of registration strategy is required to reduce misregistration artefacts associated with enhancing features. This work investigates the effect of registration on the results of model-fitting algorithms for 52 DCE-MR mammography cases for 14 patients. Results are divided into two sections: a comparison of registration strategies in which a DCE-MRI-specific algorithm is preferred in 50% of cases, followed by an investigation of parameter changes with known applied deformations, inspecting the effect of magnitude and timing of motion artefacts. Increased motion magnitude correlates with increased model-fit residual and is seen to have a strong influence on the visibility of strongly enhancing features. Motion artefacts in images close to the contrast agent arrival have a disproportionate effect on discrepancies in parameter estimation. The choice of algorithm, magnitude of motion and timing of the motion are each shown to influence estimated pharmacokinetic parameters even when motion magnitude is small.
Subject(s)
Artifacts , Contrast Media/pharmacokinetics , Magnetic Resonance Imaging/methods , Movement , Algorithms , Breast/metabolism , Female , Humans , Image Processing, Computer-AssistedABSTRACT
This article presents a method to reconstruct liver MRI data acquired continuously during free breathing, without any external sensor or navigator measurements. When the deformations associated with k-space data are known, generalized matrix inversion reconstruction has been shown to be effective in reducing the ghosting and blurring artifacts of motion. This article describes a novel method to obtain these nonrigid deformations. A breathing model is built from a fast dynamic series: low spatial resolution images are registered and their deformations parameterized by overall superior-inferior displacement. The correct deformation for each subset of the subsequent imaging data is then found by comparing a few lines of k-space with the equivalent lines from a deformed reference image while varying the deformation over the model parameter. This procedure is known as image deformation recovery using overlapping partial samples (iDROPS). Simulations using 10 rapid dynamic studies from volunteers showed the average error in iDROPS-derived deformations within the liver to be 1.43 mm. A further four volunteers were imaged at higher spatial resolution. The complete reconstruction process using data from throughout several breathing cycles was shown to reduce blurring and ghosting in the liver. Retrospective respiratory gating was also demonstrated using the iDROPS parameterization.
Subject(s)
Abdomen/anatomy & histology , Algorithms , Artifacts , Image Enhancement/methods , Image Interpretation, Computer-Assisted/methods , Liver/anatomy & histology , Magnetic Resonance Imaging/methods , Pattern Recognition, Automated/methods , Respiratory Mechanics , Subtraction Technique , Humans , Movement , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
We present an exploration of the interplay between the extent of organ motion and contrast-enhancement on image registration success. A model of a DCE MRI of the liver incorporating an isotropic elastic non-rigid deformation is used to simulate both breathing and breath-hold data, a volume-preserving modification for tumour regions is included. Contrast enhancement is simulated by applying a pharmacokinetic model. For each simulated dataset, a direct fluid registration of each image to the first in the dataset is compared to a contrast-enhancement guided method known as Progressive Principal Component Registration (PPCR). Analysis of the correction to the deformation fields, tumour volume change and dispersion of joint image histograms are used to show the importance of motion type on PPCR success and of enhancement level on direct fluid registration success. For breathing motion, PPCR registers groups of images to separate locations, but maintains enhancing tumour volume. This is not the case for direct registration with volume changes of up to 7%. For inconsistent breath-hold depth, PPCR out-performs direct registration, particularly for large enhancement levels. Analysis of the joint histograms suggests that the generation of target images using PPCR reduces dispersion due to contrast enhancement. Since this distinction is not made using direct registration, it is unable to register images when large enhancement intensity changes are present.
Subject(s)
Algorithms , Artifacts , Image Interpretation, Computer-Assisted/methods , Liver Neoplasms/pathology , Magnetic Resonance Imaging/methods , Pattern Recognition, Automated/methods , Subtraction Technique , Contrast Media , Humans , Image Enhancement/methods , Motion , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
Registration of dynamic contrast-enhanced magnetic resonance images (DCE-MRI) of soft tissue is difficult. Conventional registration cost functions that depend on information content are compromised by the changing intensity profile, leading to misregistration. We present a new data-driven model of uptake patterns formed from a principal components analysis (PCA) of time-series data, avoiding the need for a physiological model. We term this process progressive principal component registration (PPCR). Registration is performed repeatedly to an artificial time series of target images generated using the principal components of the current best-registered time-series data. The aim is to produce a dataset that has had random motion artefacts removed but long-term contrast enhancement implicitly preserved. The procedure is tested on 22 DCE-MRI datasets of the liver. Preliminary assessment of the images is by expert observer comparison with registration to the first image in the sequence. The PPCR is preferred in all cases where a preference exists. The method requires neither segmentation nor a pharmacokinetic uptake model and can allow successful registration in the presence of contrast enhancement.
Subject(s)
Algorithms , Contrast Media , Image Enhancement/methods , Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Subtraction Technique , Principal Component Analysis , Reproducibility of Results , Sensitivity and SpecificitySubject(s)
Adenosine Triphosphate/metabolism , Aminoisobutyric Acids/metabolism , Adenosine Triphosphatases/antagonists & inhibitors , Adenosine Triphosphate/pharmacology , Aerobiosis , Anaerobiosis , Anti-Bacterial Agents/pharmacology , Biological Transport, Active/drug effects , Carbon Radioisotopes , Carcinoma/metabolism , Cell Line , Culture Media , Evaluation Studies as Topic , Glycolysis , Humans , Kinetics , Mouth Neoplasms/metabolism , Oligomycins/pharmacology , Oxidative Phosphorylation/drug effects , Potassium/pharmacology , Sodium , Uncoupling Agents/pharmacologyABSTRACT
Plasma membranes from KB cells were isolated by the method of latex bead ingestion and were compared with those obtained by the ZnCl(2) method. Optimal conditions for bead uptake and the isolation procedure employing discontinuous sucrose gradient centrifugation are described. All steps of preparative procedure were monitored by electron microscopy and specific enzyme activities. The plasma membrane fraction obtained by both methods is characterized by the presence of the Na(+) + K(+)-activated ATPase and 5'-nucleotidase, and contains NADPH-cytochrome c reductase and cytochrome b(5). The latter two enzymes are also present in lower concentrations in the microsomal fraction. Unlike microsomes which are devoid of the Na(+) + K(+)-activated ATPase and which contain only traces of 5'-nucleotidase activity, the plasma membrane fraction contains only trace amounts of the rotenone-insensitive NADH-cytochrome c reductase but no cytochrome P-450, both of which are mainly microsomal components. Morphologically the plasma membrane fraction isolated by the latex bead method is composed of vesicles of 0.1-0.3 microm in diameter. On the basis of the biochemical and morphological criteria presented, it is concluded that the plasma membrane fraction isolated by the above methods are of high degree of purity.