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Placental function is vitally important, but placental assessment is limited by current imaging methods in vivo. The goal of this study is to determine if ferumoxytol-enhanced MR studies might be used to depict placental structure during pregnancy.Ten pregnant women were referred for MRI evaluation of abnormal placentation. The study group was composed five of these patients whose placentas were normal at pathology. MR studies consisted of pre-contrast SSFSE (single-shot fast spin-echo), SSFP (steady-state free procession), diffusion, and ferumoxytol-enhanced acquisitions. The post-contrast sequences were compared to pre-contrast SSFSE, SSFP, and diffusion acquisitions for features of correspondence. MR images were also compared to histopathology for anatomic landmarks including the three-ring pattern of the functional vascular exchange unit (the placentone) created by this central cavity surrounded by a ring of clustered villi, and an outer ring of dispersed villi corresponding to the maternal venous outflow channel. The measured sizes of these features on MR were compared to reported sizes.Post-ferumoxytol images showed enhancement of the maternal blood within the placenta, notably the intervillous space and the myometrial vessels. The unenhanced fetal vessels were most visible on the MinIP (minimum intensity projection) images; the enhanced maternal vessels were most visible on the MIP (maximum intensity projection) images. Composite MIP/MinIP images show the relation of maternal and fetal circulations. The signal intensities replicate the relative contributions from enhanced maternal blood and unenhanced chorionic villi.Ferumoxytol-enhanced MR imaging can depict the internal anatomy of the placenta in vivo of clarity and detail. This could represent a new diagnostic approach to placental disorders.

Waldenström macroglobulinemia (WM) is a rare, indolent lymphoma, that predominately affects the elderly. We report the outcomes of young WM patients, evaluated over five decades, compared to their older counterparts, matched for the time of diagnosis. Between January 1, 1960 and October 31, 2013, 140 (11.8%) WM patients were ≤50 years of age at diagnosis in our database, and their estimated 10-year overall survival (OS) was 74%, with death attributable to WM in a higher proportion of patients compared to their older (≥65 years) counterparts (91% vs. 58%, p = .0001). Young patients were grouped into three cohorts based on the timing of the initiation of therapy: Group 1 (1960-1977, n = 12), Group 2 (1978-1995, n = 48), and Group 3 (1996-2013, n = 74). Among young patients, there was no disease-specific survival (DSS) difference across the three periods, [median DSS at 13 years (95% CI 5-23), 16 years (95% CI 14-22), and 15 years (95% CI 10-NR; p = .41), respectively]. However, DSS for the older cohort incrementally improved (Group 1, median 5.2 years, Group 2: 9.6 years, Group 3: 12 years; p = .05) over these periods. The estimated average years-of-life lost for the young cohort was 11.2 years from diagnosis, based on the expected survival for a normal age- and sex-matched population. Despite a protracted disease course, nearly all young patients succumb to their disease. In contrast to the improved survival of the elderly patient population, the evolving treatment strategies in WM have not impacted the outcome of young patients; however, the impact of Bruton tyrosine kinase inhibitors on this unique patient population remains to be determined.

Chronic liver disease (CLD) is a large and ever-growing problem in both the US and world health care systems. While histologic analysis through liver biopsy is the gold standard for hepatic parenchymal evaluation, this is not feasible in such a large population of patients or as a way of monitoring change over time. This review discusses MRI-based techniques for assessing hepatic fibrosis, hepatic steatosis, and hepatic iron content, with discussions of both current techniques and future advancements.

Considerable healthcare resource utilization and financial burden have been associated with the treatment of WM; however, the impact of health insurance status on outcomes has not been previously reported. We conducted a National Cancer Database analysis of newly diagnosed cases of active WM between 2004 and 2017 to evaluate the impact of insurance status on outcomes. For patients65 years old (

To determine the variability of blood flow measurements using 4D flow MRI in the portal and mesenteric circulations and to characterize the effects of meal ingestion, time of day, and between-day (diurnal) variations on portal and mesenteric hemodynamics.In this IRB-approved and HIPAA-compliant study, 7 healthy and 7 portal hypertension patients imaged. MRI exams were conducted at 3 T using a 32-channel body coil with large volumetric coverage and 1.25-mm isotropic true spatial resolution. Blood flow was quantified (L/min) in the hepatic and splanchnic vasculature. The first MR scan was performed after at least 8 h of fasting. Subsequently, subjects ingested 574 mL EnSure Plus® orally. A second acquisition was started 20 min after the meal ingestion. A third scan was performed before lunch and a fourth acquisition took place 20 min after lunch. A fifth scan was performed around 4 pm. Finally, subjects returned one week later for a repeat morning visit, with identical conditions as the first visit.In healthy controls significant increase in blood flow was seen in the PV, SMV, SMA, HA, and SCAo in response to breakfast but only the SCAo, SMA, SMV, and PV had a significant response to lunch. In general, patients with cirrhosis showed reduced response to meals compared to that in healthy controls. Additionally, PV flow in patients had the highest value in the afternoon.Effects of meal ingestion, time of day, and between-day variations were characterized using Radial 4D flow MRI in patients with cirrhosis and healthy controls.

Germinal center B-cell-like diffuse large B cell lymphoma (GCB-DLBCL) at diagnosis is associated with superior long-term outcomes compared to non-GCB-DLBCL in patients treated with conventional chemo-immunotherapy. Whether cell of origin (COO) by Hans algorithm retains its prognostic significance in patients with (R/R) relapsed/refractory DLBCL undergoing autologous hematopoietic cell transplant (auto-HCT) is not well established. Three hundred and fifty-seven patients underwent auto-HCT between 2005 and 2018. The COO status was determined in 284 patients and these were included in the analysis. One hundred ninety-four patients had GCB-DLBCL while 90 had non-GCB-DLBCL. Median follow up was 1.7 (0-13) years. The GCB-DLBCL was associated with inferior 5-year overall survival at 44% (95%CI, 36-52) versus 64% (95%CI, 54-77) (P = .004) and a higher relapse incidence at 67% (95%CI, 58-74) versus 49% (95%CI, 35-60) (P = .01) in the non-GCB-DLBCL. The difference between GCB and non-GCB-DLBCL remained statistically significant in multivariate analysis. Additionally, response at the time of transplant was an independent prognostic factor. GCB-DLBCL was enriched in double-hit and triple hit phenotype based on available fluorescence in situ hybridization data. These results suggest an enrichment of high-risk genetic rearrangements in R/R GCB-DLBCL resulting in limited efficacy of auto-HCT.

Supplementary Figure 6 Boxplots showing the expression of indicated metabolites in C1 (red), C2 (blue) and C3d (green). Differences between groups were calculated with the Mann-Whitney U test. ns, non-significant.

Supplemental Fig. 2. Gene expression of non-tumor cells by cluster.

Purpose:IgM monoclonal gammopathy of undetermined significance (MGUS) and Waldenström macroglobulinemia (WM) represent a disease spectrum with highly varied therapeutic management, ranging from observation to chemoimmunotherapy. The current classification relies solely on clinical features and does not explain the heterogeneity that exists within each of these conditions. Further investigation is warranted to shed light on the biology that may account for the clinical differences.Experimental Design:We used bone marrow (BM) clonal CD19+ and/or CD138+ sorted cells, matched BM supernatant, and peripheral blood serum from 32 patients (7 MGUS, 25 WM) to perform the first multi-omics approach including whole-exome sequencing, RNA sequencing, proteomics, metabolomics, and mass cytometry.Results:We identified three clusters with distinct pathway activation, immune content, metabolomic, and clinical features. Cluster 1 included only patients with WM and was characterized by transcriptional silencing of genes involved in cell cycle and immune response, enrichment of mitochondrial metabolism, infiltration of senescent T effector memory cells, and aggressive clinical behavior. Genetic/structural alterations of TNFAIP3 were distinct events of this cluster. Cluster 2 comprised both MGUS and WM patients with upregulation of inflammatory response, senescence and glycolysis signatures, increased activated T follicular helper and T regulatory cells, and indolent clinical behavior. Cluster 3 also included both MGUS and WM patients and exhibited intermediate features, including proliferative and inflammatory signaling, as well as glycolysis and mitochondrial metabolism.Conclusions:We have identified three distinct molecular clusters, suggesting a potential biologic classification that may have therapeutic implications.

Supplementary Figure 4. Schematic representation of the mechanism associated with the three clusters.

Supplementary Figure 8 Boxplots showing the expression of CD69 (A), BTLA (B), and CD25+CTLA-4+ (C) in CD4+ T cells.

Supplementary Material

Supplementary Figure 5 A. Heat map of Spearman's correlation coefficients among paired proteins in the bone marrow (BM) supernatant and peripheral blood (PB) serum of 16 patients with WM (n=11) and IgM MGUS (n=5). Positive correlations are shown in red, whereas negative correlations are indicated in blue. B. Heat maps showing expression of (i) 12 proteins significantly different between C1 vs C2 plus C3, and (i) 74 proteins significantly different between C2 vs C1 plus C3 in the PB serum. The left bar shows correlation coefficients between BM and PB proteins. Gray squares indicate non significance.

Supplementary Figure 3 Boxplot showing that 6q deletion resulted in decreased expression of TNFAIP3.

Supplementary Figure 9 SPADE maps of CD4+ CTLA-4+ T cells from concatenated files (C1, n=7; C2, n=4). The dots in red and blue indicate high and low expression, respectively. The dot size is representative of cell events, with the big size containing more cell events.

Supplementary Figure 7 A. Heat map of Spearman's correlation coefficients among paired metabolites in the bone marrow (BM) supernatant and peripheral blood (PB) serum of 12 patients with WM. Positive correlations are shown in red, whereas negative correlations are indicated in blue. B. Heat map showing different expression of 44 metabolites in the BM supernatant among the three molecular clusters. The left bar shows correlation coefficients between BM and PB metabolites. Gray squares indicate non significance.

International audience; Accumulation of excess iron in the body, or systemic iron overload, results from a variety of causes. The concentration of iron in the liver is linearly related to the total body iron stores and, for this reason, quantification of liver iron concentration (LIC) is widely regarded as the best surrogate to assess total body iron. Historically assessed using biopsy, there is a clear need for noninvasive quantitative imaging biomarkers of LIC. MRI is highly sensitive to the presence of tissue iron and has been increasingly adopted as a noninvasive alternative to biopsy for detection, severity grading, and treatment monitoring in patients with known or suspected iron overload. Multiple MRI strategies have been developed in the past 2 decades, based on both gradient-echo and spin-echo imaging, including signal intensity ratio and relaxometry strategies. However, there is a general lack of consensus regarding the appropriate use of these methods. The overall goal of this article is to summarize the current state of the art in the clinical use of MRI to quantify liver iron content and to assess the overall level of evidence of these various methods. Based on this summary, expert consensus panel recommendations on best practices for MRI-based quantification of liver iron are provided.

There is an unmet need for fully automated image prescription of the liver to enable efficient, reproducible MRI.To develop and evaluate artificial intelligence (AI)-based liver image prescription.Prospective.A total of 570 female/469 male patients (age: 56 ± 17 years) with 72%/8%/20% assigned randomly for training/validation/testing; two female/four male healthy volunteers (age: 31 ± 6 years).1.5 T, 3.0 T; spin echo, gradient echo, bSSFP.A total of 1039 three-plane localizer acquisitions (26,929 slices) from consecutive clinical liver MRI examinations were retrieved retrospectively and annotated by six radiologists. The localizer images and manual annotations were used to train an object-detection convolutional neural network (YOLOv3) to detect multiple object classes (liver, torso, and arms) across localizer image orientations and to output corresponding 2D bounding boxes. Whole-liver image prescription in standard orientations was obtained based on these bounding boxes. 2D detection performance was evaluated on test datasets by calculating intersection over union (IoU) between manual and automated labeling. 3D prescription accuracy was calculated by measuring the boundary mismatch in each dimension and percentage of manual volume covered by AI prescription. The automated prescription was implemented on a 3 T MR system and evaluated prospectively on healthy volunteers.Paired t-tests (threshold = 0.05) were conducted to evaluate significance of performance difference between trained networks.In 208 testing datasets, the proposed method with full network had excellent agreement with manual annotations, with median IoU 0.91 (interquartile range 0.09) across all seven classes. The automated 3D prescription was accurate, with shifts2.3 cm in superior/inferior dimension for 3D axial prescription for 99.5% of test datasets, comparable to radiologists' interreader reproducibility. The full network had significantly superior performance than the tiny network for 3D axial prescription in patients. Automated prescription performed well across single-shot fast spin-echo, gradient-echo, and balanced steady-state free-precession sequences in the prospective study.AI-based automated liver image prescription demonstrated promising performance across the patients, pathologies, and field strengths studied.4.Stage 1.

Purpose:IgM monoclonal gammopathy of undetermined significance (MGUS) and Waldenström macroglobulinemia (WM) represent a disease spectrum with highly varied therapeutic management, ranging from observation to chemoimmunotherapy. The current classification relies solely on clinical features and does not explain the heterogeneity that exists within each of these conditions. Further investigation is warranted to shed light on the biology that may account for the clinical differences.Experimental Design:We used bone marrow (BM) clonal CD19+ and/or CD138+ sorted cells, matched BM supernatant, and peripheral blood serum from 32 patients (7 MGUS, 25 WM) to perform the first multi-omics approach including whole-exome sequencing, RNA sequencing, proteomics, metabolomics, and mass cytometry.Results:We identified three clusters with distinct pathway activation, immune content, metabolomic, and clinical features. Cluster 1 included only patients with WM and was characterized by transcriptional silencing of genes involved in cell cycle and immune response, enrichment of mitochondrial metabolism, infiltration of senescent T effector memory cells, and aggressive clinical behavior. Genetic/structural alterations of TNFAIP3 were distinct events of this cluster. Cluster 2 comprised both MGUS and WM patients with upregulation of inflammatory response, senescence and glycolysis signatures, increased activated T follicular helper and T regulatory cells, and indolent clinical behavior. Cluster 3 also included both MGUS and WM patients and exhibited intermediate features, including proliferative and inflammatory signaling, as well as glycolysis and mitochondrial metabolism.Conclusions:We have identified three distinct molecular clusters, suggesting a potential biologic classification that may have therapeutic implications.

Background MRI is a standard of care tool to measure liver iron concentration (LIC). Compared with regulatory-approved R2 MRI, R2* MRI has superior speed and is available in most MRI scanners; however, the cross-vendor reproducibility of R2*-based LIC estimation remains unknown. Purpose To evaluate the reproducibility of LIC via single-breath-hold R2* MRI at both 1.5 T and 3.0 T with use of a multicenter, multivendor study. Materials and Methods Four academic medical centers using MRI scanners from three different vendors (three 1.5-T scanners, one 2.89-T scanner, and two 3.0-T scanners) participated in this prospective cross-sectional study. Participants with known or suspected liver iron overload were recruited to undergo multiecho gradient-echo MRI for R2* mapping at 1.5 T and 3.0 T (2.89 T or 3.0 T) on the same day. R2* maps were reconstructed from the multiecho images and analyzed at a single center. Reference LIC measurements were obtained with a commercial R2 MRI method performed using standardized 1.5-T spin-echo imaging. R2*-versus-LIC calibrations were generated across centers and field strengths using linear regression and compared using

To validate QSM-based biomagnetic liver susceptometry (BLS) to measure liver iron overload at 1.5 T and 3.0 T using superconducting quantum interference devices (SQUID)-based BLS as reference.Subjects with known or suspected iron overload were recruited for QSM-BLS at 1.5 T and 3.0 T using eight different protocols. SQUID-BLS was also obtained in each subject to provide susceptibility reference. A recent QSM method based on data-adaptive regularization was used to obtain susceptibility andSusceptibility maps showed high subjective quality for each acquisition protocol across different iron levels. High linear correlation was observed between QSM-BLS and SQUID-BLS at 1.5 T (rThis work evaluated the feasibility and performance of liver QSM-BLS across iron levels and acquisition protocols at 1.5 T and 3.0 T. High correlation and reproducibility were observed between QSM-BLS and SQUID-BLS across protocols and field strengths. In summary, QSM-BLS may enable reliable and reproducible quantification of liver iron concentration.

Ferumoxytol, an intravenous iron supplement, is commonly used to treat anemia in pregnancy. Ferumoxytol-enhanced magnetic resonance angiography (Fe-MRA) is a viable off-label alternative to gadolinium-enhanced MRA for assessment of pulmonary embolism (PE) in pregnancy.To describe our clinical experience with Fe-MRA in pregnant women with suspected PE.Retrospective, observational, cohort.A total of 98 Fe-MRA exams (consecutive sample) performed in 94 pregnant women.A 1.5 T and 3.0 T, 3D T1-weighted MRA.After IRB approval including a waiver of informed consent, electronic health records were reviewed retrospectively for all Fe-MRA exams performed at our institution in pregnant between January, 2017 and March, 2022. The Fe-MRA protocol included 3D-MRA for assessment of pulmonary arteries, and T1-weighted imaging for ancillary findings. Fe-MRA exam duration was measured from image time stamps. Fe-MRA exams were reviewed by three cardiovascular imagers using a 4-point Likert scale for image quality and confidence for PE diagnosis (score 4 = best, 1 = worst), and tabulation of ancillary findings.Continuous data are presented as mean ± standard deviation. The overall image quality and confidence score is given as the mean of three readers.The 98 Fe-MRA exams were performed in 94 pregnant women (age 30 ± 6, range 19-48 years, gestational week 23 ± 10, range 3-38 weeks), with four undergoing two Fe-MRA exams during their pregnancy. Median Fe-MRA exam durration was 8 minutes (interquantile range 6 minutes). Overall image quality score was 3.3 ± 0.9. Confidence score for diagnosing PE was 3.5 ± 0.8. One subject was positive for PE (1/94, 1%); 42 of the 94 (45%) subjects Fe-MRA had ancillary findings including hydronephrosis or pneumonia.Ferumoxytol enhanced MRA is a radiation- and gadolinium-free alternative for diagnosis of PE during pregancy.4 TECHNICAL EFFICACY: Stage 5.