Quyen N. Do

ObjectiveRecent guidelines have identified magnetic resonance (MR) placenta accreta spectrum (PAS) markers. The purpose of this study is to evaluate these markers ability to predict need for cesarean hysterectomy due to PAS.Study DesignThis was a single-center retrospective study of pregnancies referred with suspected PAS between September 2019-February 2023. MR reports were prospectively interpreted by two investigators, and MR parameters were extracted from the clinical reports, blinded to clinical outcomes. Medical records were reviewed to determine surgical outcomes, and patients were grouped according to the outcome of hysterectomy. Patient demographics were compared between those who required hysterectomy and those that did not using T-tests and Fisher’s Exact test. Univariate logistic regression models and area under the receiver operating characteristics curve (AUC) for MRI …

Prospective first-trimester transvaginal 3-dimensional power Doppler and hysterectomy association in placenta accreta spectrum Prospective first-trimester transvaginal 3-dimensional power Doppler and hysterectomy association in placenta accreta spectrum Am J Obstet Gynecol. 2024 Mar 2:S0002-9378(24)00423-X. doi: 10.1016/j.ajog.2024.02.310. Online ahead of print. Authors Christina L Herrera 1 , Quyen N Do 2 , Yin Xi 2 , Catherine Y Spong 3 , Diane M Twickler 4 Affiliations 1 Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9032; Parkland Health, Dallas, TX. Electronic address: christina.herrera@utsouthwestern.edu. 2 Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX. 3 Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, …

ObjectiveThe placenta accreta index (PAI) is a standardized method for the ultrasound (US) prediction of placenta accreta spectrum (PAS). Since 2019, we have prospectively applied the PAI in pregnancies in the second and third trimester identified to be at risk for PAS due to prior history of cesarean and placenta previa or low-lying placenta or other sonographic signs of PAS. We sought to determine clinically meaningful cutoffs to guide the decision to obtain adjunct magnetic resonance imaging (MRI).Study DesignWe analyzed pregnant individuals who underwent assessment with the PAI from 2019-2023. The last PAI prior to delivery was analyzed for prediction of hysterectomy. Two cut off values were determined for a 96% sensitivity and specificity for the outcome of cesarean hysterectomy. Associated sensitivity, specificity, positive predictive and negative predictive values were determined.ResultsOf 126 with a …

BACKGROUNDMagnetic resonance imaging has been used increasingly as an adjunct for ultrasound imaging for placenta accreta spectrum assessment and preoperative surgical planning, but its value has not been established yet. The ultrasound-based placenta accreta index is a well-validated standardized approach for placenta accreta spectrum evaluation. Placenta accreta spectrum–magnetic resonance imaging markers have been outlined in a joint guideline from the Society of Abdominal Radiology and the European Society of Urogenital Radiology.OBJECTIVEThis study aimed to compare placenta accreta spectrum–magnetic resonance imaging parameters with the ultrasound-based placenta accreta index in pregnancies at high risk for placenta accreta spectrum and to assess the additional diagnostic value of magnetic resonance imaging for placenta accreta spectrum that requires a cesarean …

BACKGROUNDMagnetic resonance imaging has been used increasingly as an adjunct for ultrasound imaging for placenta accreta spectrum assessment and preoperative surgical planning, but its value has not been established yet. The ultrasound-based placenta accreta index is a well-validated standardized approach for placenta accreta spectrum evaluation. Placenta accreta spectrum–magnetic resonance imaging markers have been outlined in a joint guideline from the Society of Abdominal Radiology and the European Society of Urogenital Radiology.OBJECTIVEThis study aimed to compare placenta accreta spectrum–magnetic resonance imaging parameters with the ultrasound-based placenta accreta index in pregnancies at high risk for placenta accreta spectrum and to assess the additional diagnostic value of magnetic resonance imaging for placenta accreta spectrum that requires a cesarean …

Translocation Renal Cell Carcinoma (tRCC) most commonly involves an ASPSCR1-TFE3 fusion, but molecular mechanisms remain elusive and animal models are lacking. Here, we show that human ASPSCR1-TFE3 driven by Pax8-Cre (a credentialed ccRCC driver) disrupted nephrogenesis and glomerular development causing neonatal death, whilst the ccRCC failed driver, Sglt2-Cre, induced aggressive tRCC (as well as ASPS) with complete penetrance and short latency. However, in both contexts, ASPSCR1-TFE3 led to characteristic morphological cellular changes, loss of epithelial markers, and an EMT program. Electron microscopy of tRCC tumors showed lysosome expansion and functional studies revealed simultaneous activation of autophagy and mTORC1 pathways. Comparative genomic analyses encompassing an institutional human tRCC cohort (including a hitherto unreported SFPQ-TFEB fusion …

ObjectiveIn placental disease, spiral artery remodeling is thought to be more aberrant at the periphery but remains normal in the central area near the cord. Considering this pathology, we aimed to investigate the impact of chronic hypertension (cHTN) during pregnancy on placental diffusion in vivo. Water diffusion is relatively stable against aging changes represented by connective tissue or calcifications, making diffusion mapping a tool to evaluate placenta pathology.Study Design:In this prospective study, pregnant individuals with and without chronic hypertension were imaged at 16-20 (visit 1) and 24-28 (visit 2) weeks gestation on a Phillips 3T Ingenia MRI. Sagittal diffusion weighted-imaging (DWI) was obtained during free breathing with 7 b-values-0, 50, 100, 150, 400, 700, 1000 sec/mm2. Apparent diffusion coefficient (ADC) map was generated using mono-exponential fit.

Introduction. Translocation Renal Cell Carcinoma (tRCC) is a distinct and aggressive molecular subtype of kidney cancer unusually prevalent in children and adolescents. tRCC has a poor prognosis with no specific therapies and is incurable in the metastatic setting. tRCC is characterized by chromosomal translocations involving three out of the four Microphthalmia (MiT) family transcription factors, TFE3, TFE3, and MITF. The most commonly involved gene is TFE3, which most often fuses with ASPSCR1. However, the molecular mechanisms by which ASPSCR1-TFE3 (and more broadly MiT/TFE fusion proteins) dictates tRCC tumorigenesis remain unclear and advances are hampered by the paucity of animal models. Herein, we sought to model tRCC and performed integrative genomic analyses to dissect molecular mechanisms underpinning tRCC tumorigenesis with the goal of translating this knowledge into …

Magnetic resonance imaging (MRI) has gained popularity in the field of prenatal imaging due to the ability to provide high quality images of soft tissue. In this paper, we presented a novel method for extracting different textural and morphological features of the placenta from MRI volumes using topographical mapping. We proposed polar and planar topographical mapping methods to produce common placental features from a unique point of observation. The features extracted from the images included the entire placenta surface, as well as the thickness, intensity, and entropy maps displayed in a convenient two-dimensional format. The topography-based images may be useful for clinical placental assessments as well as computer-assisted diagnosis, and prediction of potential pregnancy complications.

Phyllodes tumors (PTs) are rare tumors that comprise 0.3%–1% of all primary breast tumors. The name is of Greek origin meaning “leaf,” referring to the leaf-like morphology of the tumor. Per recommendations by the World Health Organization (WHO), 1 PTs are classified into benign, borderline, and malignant based on a constellation of histological parameters. PTs are treated by surgical excision. Pathological tumor grade determines the choice of surgical method and the extent of surgical excision. While there is no consensus on the definition of an appropriate surgical margin, margin status is a strong predictor of local recurrence. Risk of recurrence and metastasis also increases with increasing tumor grade. Even though the number of deaths represented a small percentage of the total population, all of the PT deaths (7) reported by Tan et al2 were preceded by a malignant primary diagnosis. Benign tumors do not …

ObjectivesTo evaluate longitudinal placental perfusion using pseudo-continuous arterial spin–labeled (pCASL) MRI in normal pregnancies and in pregnancies affected by chronic hypertension (cHTN), who are at the greatest risk for placental-mediated disease conditions.MethodsEighteen normal and 23 pregnant subjects with cHTN requiring antihypertensive therapy were scanned at 3 T using free-breathing pCASL-MRI at 16–20 and 24–28 weeks of gestational age.ResultsMean placental perfusion was 103.1 ± 48.0 and 71.4 ± 18.3 mL/100 g/min at 16–20 and 24–28 weeks respectively in normal pregnancies and 79.4 ± 27.4 and 74.9 ± 26.6 mL/100 g/min in cHTN pregnancies. There was a significant decrease in perfusion between the first and second scans in normal pregnancies (p = 0.004), which was not observed in cHTN pregnancies (p = 0.36). The mean perfusion was not statistically different between …

Magnetic resonance imaging (MRI) has potential benefits in understanding fetal and placental complications in pregnancy. An accurate segmentation of the uterine cavity and placenta can help facilitate fast and automated analyses of placenta accreta spectrum and other pregnancy complications. In this study, we trained a deep neural network for fully automatic segmentation of the uterine cavity and placenta from MR images of pregnant women with and without placental abnormalities. The two datasets were axial MRI data of 241 pregnant women, among whom, 101 patients also had sagittal MRI data. Our trained model was able to perform fully automatic 3D segmentation of MR image volumes and achieved an average Dice similarity coefficient (DSC) of 92% for uterine cavity and of 82% for placenta on the sagittal dataset and an average DSC of 87% for uterine cavity and of 82% for placenta on the axial dataset …

MethodsIn a prospective IRB-approved trial, NSCLC patients underwent pre-operative FDG-PET imaging. Patients were infused intra-operatively with 13 C-labeled glucose and resected tissue samples were analyzed by mass spectrometry. Glycolytic 13 C enrichment was compared to SUV m, tumor diameter and proliferation index (MIB1).ResultsFrom 2012 to 2022, 225 patients were enrolled and 66 were infused with 13 C glucose (Table 1). Patients had an overall survival of 37 months (30-44 95% CI). Figure 1 demonstrates an inverse relationship between SUV m and glucose enrichment, but a positive correlation between SUV m with MIB1, tumor diameter and Lactate/3-Phosphoglycerate (3-PG) enrichment. Survival analysis was performed for SUV m and Lactate/3PG (Figure 2).ConclusionsIn early-stage NSCLC, SUV m does not correlate with 13 C glycolytic intermediate enrichment indicating that SUV m does …

ObjectivePerfusion may be a sensitive biomarker for in vivo assessment of normal and abnormal placental function. We sought to evaluate longitudinal placental perfusion using pseudo-continuous arterial spin labeled (pCASL) MRI in normal pregnancies and in pregnancies affected by chronic hypertension (cHTN), who are at the greatest risk for placental-mediated conditions of preeclampsia and fetal growth restriction.Study DesignEight normal and 17 pregnant women with cHTN on antihypertensive therapy were scanned on a Phillips 3T Ingenia MRI using pCASL at 16-20 and 24-28 weeks of gestational age. pCASL-MRI including perfusion quantification was acquired in less than 6 minutes. Mean placental blood flow (PBF) comparisons between gestational ages were performed using paired Wilcoxon tests, and comparisons between normal and cHTN groups were performed using unpaired Wilcoxon tests …

The placenta plays a critical role in fetal development. It serves as a multi-functional organ that protects and nurtures the fetus during pregnancy. However, despite its importance, the intricacies of placental structure and function in normal and diseased states have remained largely unexplored. Thus, in 2014, the National Institute of Child Health and Human Development launched the Human Placenta Project (HPP). As of May 2023, the HPP has awarded over $101 million in research funds, resulting in 41 funded studies and 459 publications. We conducted a comprehensive review of these studies and publications to identify areas of funded research, advances in those areas, limitations of current research, and continued areas of need. This paper will specifically review the funded studies by the HPP, followed by an in-depth discussion on advances and gaps within placental-focused imaging. We highlight the …

Objectiveeovascularization along the bladder-serosal interface is often observed in cases of placenta accreta spectrum (PAS) requiring hysterectomy. We sought to determine the relationship between 3-dimensional power Doppler (3D PD) quantification of vascular indices along the bladder-serosal interface–a potential surrogate marker of vascularization–and the outcome of hysterectomy in women with concern for PAS in the first trimester.Study DesignWomen with a prior cesarean and low implantation in the first trimester underwent 3D PD as part of standardized ultrasound assessment for PAS. The ultrasound imaging device used was a GE Voluson E10. An investigator blinded to clinical information employed a standardized reading protocol to select the 3D PD study with the best visualization of the bladder-serosal interface and minimal aliasing. 3D volumes were constructed from the entire placental mass …

In women with placenta accreta spectrum (PAS), patient management may involve cesarean hysterectomy at delivery. Magnetic resonance imaging (MRI) has been used for further evaluation of PAS and surgical planning. This work tackles two prediction problems: predicting presence of PAS and predicting hysterectomy using MR images of pregnant patients. First, we extracted approximately 2,500 radiomic features from MR images with two regions of interest: the placenta and the uterus. In addition to analyzing two regions of interest, we dilated the placenta and uterus masks by 5, 10, 15, and 20 mm to gain insights from the myometrium, where the uterus and placenta overlap in the case of PAS. This study cohort includes 241 pregnant women. Of these women, 89 underwent hysterectomy while 152 did not; 141 with suspected PAS, and 100 without suspected PAS. We obtained an accuracy of 0.88 for predicting …

Targeting metabolic vulnerabilities has been proposed as a therapeutic strategy in renal cell carcinoma (RCC). Here, we analyzed the metabolism of patient-derived xenografts (tumorgrafts) from diverse subtypes of RCC. Tumorgrafts from VHL-mutant clear cell RCC (ccRCC) retained metabolic features of human ccRCC and engaged in oxidative and reductive glutamine metabolism. Genetic silencing of isocitrate dehydrogenase-1 or isocitrate dehydrogenase-2 impaired reductive labeling of tricarboxylic acid (TCA) cycle intermediates in vivo and suppressed growth of tumors generated from tumorgraft-derived cells. Glutaminase inhibition reduced the contribution of glutamine to the TCA cycle and resulted in modest suppression of tumorgraft growth. Infusions with [amide-15N]glutamine revealed persistent amidotransferase activity during glutaminase inhibition, and blocking these activities with the …

Magnetic resonance imaging (MRI) is useful for the detection of abnormalities affecting maternal and fetal health. In this study, we used a fully convolutional neural network for simultaneous segmentation of the uterine cavity and placenta on MR images. We trained the network with MR images of 181 patients, with 157 for training and 24 for validation. The segmentation performance of the algorithm was evaluated using MR images of 60 additional patients that were not involved in training. The average Dice similarity coefficients achieved for the uterine cavity and placenta were 92% and 80%, respectively. The algorithm could estimate the volume of the uterine cavity and placenta with average errors of less than 1.1% compared to manual estimations. Automated segmentation, when incorporated into clinical use, has the potential to quantify, standardize, and improve placental assessment, resulting in improved …

Purpose HIF2α is a key driver of kidney cancer. Using a belzutifan analogue (PT2399), we previously showed in tumorgrafts (TG) that ∼50% of clear cell renal cell carcinomas (ccRCC) are HIF2α dependent. However, prolonged treatment induced resistance mutations, which we also identified in humans. Here, we evaluated a tumor-directed, systemically delivered, siRNA drug (siHIF2) active against wild-type and resistant-mutant HIF2α. Experimental Design Using our credentialed TG platform, we performed pharmacokinetic and pharmacodynamic analyses evaluating uptake, HIF2α silencing, target gene inactivation, and antitumor activity. Orthogonal RNA-sequencing studies of siHIF2 and PT2399 were pursued to define the HIF2 transcriptome. Analyses were extended to a TG line generated from a study biopsy of a siHIF2 phase I clinical trial (NCT04169711) participant and …