Association of intraplacental oxygenation patterns on dual-contrast MRI with placental abnormality and fetal brain oxygenation.

OBJECTIVES: Most human in-vivo placental imaging techniques are unable to distinguish and characterize various placental compartments, such as the intervillous space (IVS), placental vessels (PV) and placental tissue (PT), limiting their specificity. We describe a method that employs T2* and diffusion-weighted magnetic resonance imaging (MRI) data to differentiate automatically placental compartments, quantify their oxygenation properties and identify placental lesions (PL) in vivo. We also investigate the association between placental oxygenation patterns and fetal brain oxygenation. METHODS: This was a prospective study conducted between 2018 and 2021 in which dual-contrast clinical MRI data (T2* and diffusion-weighted MRI) were acquired from patients between 20 and 38 weeks' gestation. We trained a fuzzy clustering method to analyze T2* and diffusion-weighted MRI data and assign placental voxels to one of four clusters, based on their distinct imaging domain features. The new method divided automatically the placenta into IVS, PV, PT and PL compartments and characterized their oxygenation changes throughout pregnancy. RESULTS: A total of 27 patients were recruited, of whom five developed pregnancy complications. Total placental oxygenation level and T2* did not demonstrate a statistically significant temporal correlation with gestational age (GA) (R2 = 0.060, P = 0.27). In contrast, the oxygenation level reflected by T2* values in the placental IVS (R2 = 0.51, P = 0.0002) and PV (R2 = 0.76, P = 1.1 × 10-7 ) decreased significantly with advancing GA. Oxygenation levels in the PT did not show any temporal change during pregnancy (R2 = 0.00044, P = 0.93). A strong spatial-dependent correlation between PV oxygenation level and GA was observed. The strongest negative correlation between PV oxygenation and GA (R2 = 0.73, P = 4.5 × 10-7 ) was found at the fetal-vessel-dominated region close to the chorionic plate. The location and extent of the placental abnormality were automatically delineated and quantified in the five women with clinically confirmed placental pathology. Compared to the averaged total placental oxygenation, placental IVS oxygenation level best reflected fetal brain oxygenation level during fetal development. CONCLUSION: Based on clinically feasible dual-MRI, our method enables accurate spatiotemporal quantification of placental compartment and fetal brain oxygenation across different GAs. This information should improve our knowledge of human placenta development and its relationship with normal and abnormal pregnancy. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The Resolution Rate of Pulmonary Embolism on CT Pulmonary Angiography: a Prospective Study.

PURPOSE: To prospectively assess the rate of clot resolution from CT pulmonary angiography (CTPA) in patients with acute pulmonary embolism (PE). MATERIALS AND METHODS: This prospective cohort study included 290 patients (136 men, 154 women; mean age, 51.9 years) with acute PE. All patients had a CTPA at the presentation and had at least one follow-up within 6 months (mean 72.7 days). Sixty-four percent of patients had follow-up scans for research purposes within a pre-determined period (between 28 and 184 days; mean, 78.27 days) and 36 % had (between 2 and 184 days; mean, 62.78 days) for a clinical indication. The volume of each clot was measured using a semi-automated quantification program. The resolution rate was evaluated by interval-censored analysis. RESULTS: The overall estimated probability of complete resolution was 42 % at 7 days, 56 % at 10 days, and 71 % at 45 days. Achieving complete resolution was significantly faster in patients with peripheral clots (HR: 1.78; CI: 1.05-3.03, p = 0.032) but slower in patients with consolidation and history of venous thromboembolism (VTE), (HR: 0.37; CI: 0.18-0.79, p = 0.01 and HR: 0.57; CI: 0.35-0.91, p = 0.019, respectively). Although the patients with cancer showed a faster resolution rate (HR: 1.67; CI: 1.05-2.68, p = 0.032), the mortality rate was significantly higher than non-cancer patients. CONCLUSION: The resolution rate of clot burden in acute PE was associated with patients' clinical presentation variables and CTPA imaging biomarkers. This information may be incorporated into designing a prediction rule and determining the appropriate duration of anticoagulation therapy in patients with acute PE.

Evaluation of attenuation correction in cardiac PET using PET/MR.

BACKGROUND: Simultaneous acquisition Positron emission tomography/magnetic resonance (PET/MR) is a new technology that has potential as a tool both in research and clinical diagnosis. However, cardiac PET acquisition has not yet been validated using MR imaging for attenuation correction (AC). The goal of this study is to evaluate the feasibility of PET imaging using a standard 2-point Dixon volume interpolated breathhold examination (VIBE) MR sequence for AC. METHODS AND RESULTS: Evaluation was performed in both phantom and patient data. A chest phantom containing heart, lungs, and a lesion insert was scanned by both PET/MR and PET/CT. In addition, 30 patients underwent whole-body 18F-fluorodeoxyglucose PET/CT followed by simultaneous cardiac PET/MR. Phantom study showed 3% reduction of activity values in the myocardium due to the non-inclusion of the phased array coil in the AC. In patient scans, average standardized uptake values (SUVs) obtained by PET/CT and PET/MR showed no significant difference (n = 30, 4.6 ± 3.5 vs 4.7 ± 2.8, P = 0.47). There was excellent per patient correlation between the values acquired by PET/CT and PET/MR (R 2 = 0.97). CONCLUSIONS: Myocardial SUVs PET imaging using MR for AC shows excellent correlation with myocardial SUVs obtained by standard PET/CT imaging. The 2-point Dixon VIBE MR technique can be used for AC in simultaneous PET/MR data acquisition.

Risk factors for hemorrhagic cystitis in pediatric allogeneic hematopoietic stem cell transplant recipients.

BACKGROUND: Hemorrhagic cystitis (HC) results in significant morbidity among hematopoietic stem cell transplant (HSCT) recipients. Several potential causes for HC have been postulated, including viral infection, but definitive evidence is lacking, particularly in pediatric HSCT patients. METHODS: Ninety pediatric HSCT recipients were prospectively tested on a weekly basis for adenovirus (ADV) and BK virus (BKV) by quantitative real-time polymerase chain reaction in blood and urine samples. Results were correlated with the occurrence of grade II-IV HC. The odds ratio (OR) of HC (95% confidence interval) for BKV ≥1 × 10(9) copies/mL of urine was 7.39 (1.52, 35.99), with a P-value of 0.013. Those with acute graft-versus-host disease (aGVHD) also had higher odds of developing HC, with an OR of 5.34. Given a 20% prevalence rate of HC, positive and negative predictive values of 29% and 95% were seen with a cutoff of 10(9) copies/mL. RESULTS: BK viremia did not reach significance as a risk factor for development of HC (P = 0.06). Only 8 patients showed ADV viruria and 7 showed ADV viremia; all had low viral loads and 4 had no evidence of HC. CONCLUSION: HC in pediatric HSCT is correlated most strongly to elevated urinary viral load of BKV and to aGVHD, but less strongly to BK viremia.

The coronary CT angiography vision protocol: a prospective observational imaging cohort study in patients undergoing non-cardiac surgery.

INTRODUCTION: At present, physicians have a limited ability to predict major cardiovascular complications after non-cardiac surgery and little is known about the anatomy of coronary arteries associated with perioperative myocardial infarction. We have initiated the Coronary CT Angiography (CTA) VISION Study to (1) establish the predictive value of coronary CTA for perioperative myocardial infarction and death and (2) describe the coronary anatomy of patients that have a perioperative myocardial infarction. METHODS AND ANALYSIS: The Coronary CTA VISION Study is prospective observational study. Preoperative coronary CTA will be performed in 1000-1500 patients with a history of vascular disease or at least three cardiovascular risk factors who are undergoing major elective non-cardiac surgery. Serial troponin will be measured 6-12 h after surgery and daily for the first 3 days after surgery. Major vascular outcomes at 30 days and 1 year after surgery will be independently adjudicated. ETHICS AND DISSEMINATION: Coronary CTA results in a measurable radiation exposure that is similar to a nuclear perfusion scan (10-12 mSV). Treating physicians will be blinded to the CTA results until 30 days after surgery in order to provide the most unbiased assessment of its prognostic capabilities. The only exception will be the presence of a left main stenosis >50%. This approach is supported by best available current evidence that, excluding left main disease, prophylatic revascularisation prior to non-cardiac surgery does not improve outcomes. An external safety and monitoring committee is overseeing the study and will review outcome data at regular intervals. Publications describing the results of the study will be submitted to major peer-reviewed journals and presented at international medical conferences.

A novel approach for quantification of KIR expression in healthy donors and pediatric recipients of hematopoietic SCTs.

The killer cell Ig-like receptor (KIR) expression repertoire may offer valuable information for hematopoietic SCT (HSCT). We designed a quantitative KIR RNAtype assay and used it to determine KIR gene expression in healthy donors and patients before HSCT. The specificity of the assay was ensured by specific primers and by electrophoretic distinction of PCR products of unique length. In 87 healthy donors, the KIR repertoire was broadly distributed (32 categories of profiles). There was an overall trend toward inverse correlation of KIR expression level and donor age. Age affected mainly the activating KIR families. Leukemia patients showed lower KIR expression before transplantation than healthy donors. Stem cell mobilization caused a transient increase of KIR expression. We conclude that KIR expression differs quantitatively with age and primary disease and is transiently altered by stem cell recruitment and selection.

Safety of gadoversetamide in patients with acute and chronic myocardial infarction.

PURPOSE: To assess the safety data from two large, multicenter, phase 2 trials on the use of gadoversetamide (OptiMARK, Tyco Healthcare/Mallinckrodt, St. Louis, MO) as a contrast agent in delayed hyperenhancement magnetic resonance imaging (DE-MRI) in patients with acute and chronic myocardial infarction (MI). MATERIALS AND METHODS: The study population from both trials comprised 577 patients who were randomly assigned to one of four dose groups (0.05, 0.1, 0.2, or 0.3 mmol/kg) before undergoing DE-MRI. Safety evaluations included physical and electrocardiographic (ECG) examinations. Vital signs, laboratory values, adverse events (AE), and serious adverse events (SAE) were monitored before and after contrast administration. RESULTS: Of the 577 patients who received gadoversetamide, 124 (21.5%) reported a total of 164 AEs; most were mild (139 AEs; 84.8%) or moderate (25 AEs; 15.2%). ECG-related changes were the most frequent AE. Site investigators judged only eight AEs as likely related to gadoversetamide and only two of the eight as clinically relevant. Further evaluation suggested neither AE was related to gadoversetamide. Two SAEs were reported, but none was judged related to gadoversetamide by the site investigators. CONCLUSION: Gadoversetamide is safe for use in patients with acute or chronic MI up to a dose of 0.3 mmol/kg.

Cardiac magnetic resonance imaging abnormalities in systemic lupus erythematosus: a preliminary report.

The purpose of this prospective, pilot study was to determine whether differences in myocardial T2 relaxivity can be identified among active systemic lupus erythematosus (SLE) patients with clinically suspected SLE myocarditis, other active SLE patients, inactive SLE patients and age and gender matched controls. Eleven consecutive female patients (six with active SLE and five with inactive SLE), and five age, gender and race matched healthy controls underwent imaging with echocardiography and cardiac magnetic resonance imaging (MRI). Echocardiographic measurements included left ventricular end diastolic (LVEDV) and end systolic volumes (LVESV), and mass (LVM) (all indexed to body mass); ejection fraction and cardiac output. The cardiac MRI measurement was the T2 relaxation time (an index of soft tissue signal, with higher levels suggestive of increased tissue water content). Patients with active SLE had significantly higher LVEDV and LVM than inactive SLE patients and healthy controls, and significantly larger LVESV than healthy controls. Myocardial T2 relaxation times were significantly higher in patients with active SLE compared to those with inactive SLE and to healthy controls, and remained higher even after excluding the two active SLE patients who had clinical myocarditis. The four active SLE patients who underwent repeat cardiac imaging studies after clinical improvement showed normalization of these myocardial abnormalities. The conclusion was that active SLE patients demonstrate abnormalities in myocardial structure manifested by high myocardial T2 relaxation times that normalized after clinical improvement in disease activity. These findings suggest that T2 relaxation values are a sensitive indicator of myocardial disease in patients with SLE and that myocardial T2 relaxation abnormality frequently occur in patients with active SLE, even in the absence of myocardial involvement by clinical criteria.

Encephalopathy in pediatric patients after allogeneic hematopoietic stem cell transplantation is associated with a poor prognosis.

SUMMARY: Encephalopathy is a poorly characterized complication of hematopoietic stem cell transplantation (HSCT). No comprehensive report of encephalopathy exists for children, and the literature contains only a few for adults. We analyzed a large cohort of 405 pediatric patients who underwent allogeneic HSCT during a 10-year period and identified 26 patients (6.4%) who experienced encephalopathy. Identifiable causes of encephalopathy included infection (n=5), single or multiorgan failure (n=4), medication-related complications (n=3), nonconvulsive seizures (n=4), acute disseminated encephalomyelitis (n=2), thrombotic thrombocytopenic purpura (n=2), and stroke (n=1). We were unable to identify the etiology of encephalopathy in five (19%) patients. The prognosis for pediatric patients with encephalopathy was poor: only four (15%) experienced complete neurologic recovery, and 10 (38%) patients experienced partial recovery with residual neurologic deficits. Nine (35%) patients with complete or partial recovery survive long term. A total of 17 patients died; one died of progressive encephalopathy, and 16 died of either relapse of primary disease or toxicity. MRI, CSF analysis including molecular testing for infectious pathogens, and brain biopsy were helpful in obtaining a diagnosis in most of our patients. However, a standardized approach to accurate and timely diagnosis and treatment is needed to improve outcome in these patients.

Effective donor lymphohematopoietic reconstitution after haploidentical CD34+-selected hematopoietic stem cell transplantation in children with refractory severe aplastic anemia.

Peritransplant toxicity and a delay in effective immune reconstitution have limited the utility of alternate donor transplantation for children with refractory severe aplastic anemia. We have assessed the effectiveness of infusing large numbers of highly purified haploidentical CD34+ cells after immunoablative conditioning in three patients who had failed intensive immunosuppression, lacked unrelated donors, and had active or recent serious infections. One patient rejected the first infusion, but engrafted after a second infusion from the same donor. This patient died 4 months after hematopoietic stem cell transplantation with no evidence of lymphoid reconstitution. Two patients experienced mixed chimerism requiring treatment with antibodies and/or donor lymphocyte infusion. Both currently survive more than 1 year after transplantation with normal blood counts, 100% donor engraftment, effective lymphoid reconstitution, and no chronic graft-versus-host disease. We observed functional thymopoiesis as measured by lymphocyte immunophenotyping, T cell receptor excision circles and T cell receptor Vbeta spectratyping complexity analysis. Further study is required to validate the initial promise of these preliminary observations.

Hemorrhagic cystitis after allogeneic bone marrow transplantation in children: clinical characteristics and outcome.

Hemorrhagic cystitis (HC) is a well-documented adverse event experienced by patients undergoing hematopoietic stem cell transplantation. When severe, HC causes significant morbidity, leads to renal complications, prolongs hospitalization, increases health-care costs, and occasionally contributes to death. We retrospectively studied the medical records of 245 children undergoing an initial allogeneic bone marrow transplantation for malignant disease at St. Jude Children's Research Hospital between 1992 and 1999 to describe the clinical course of HC in all patients and to identify the risk factors for HC in this cohort. Conditioning regimens included cyclophosphamide, cytarabine, and total body irradiation. Grafts from unrelated or mismatched related donors were depleted of T lymphocytes, whereas matched sibling grafts were unmanipulated. All patients received cyclosporine as prophylaxis for graft-versus-host disease. Recipients of grafts from matched siblings also received pentoxifylline or short-course methotrexate. Severe HC developed in 27 patients (11.0%). The median duration of HC was 73 days (range, 5-619 days); 12 patients had ongoing HC at the time of death. In univariate analyses, patients were at increased risk of severe HC if they were male (P =.021) or had received T cell-depleted grafts (P =.017), grafts from unrelated donors (P =.021), a lower total nucleated cell dose (P =.032), or antithymocyte globulin (P =.0446). Multiple regression analysis revealed male sex (beta =.97; P =.027) and unrelated donor graft recipients (beta =.83; P =.039) to be significant factors.

Benign metastasizing leiomyoma: clinical, imaging, and pathologic correlation.

OBJECTIVE: We describe the clinical presentation and the radiographic and CT findings of benign metastasizing leiomyoma. CONCLUSION: Benign metastasizing leiomyoma is an asymptomatic disease characterized by well-defined, numerous, pulmonary lesions without a preponderant distribution.

Allogeneic bone marrow transplantation for infants with acute leukemia or myelodysplastic syndrome.

The objective of this study is to investigate the outcome of children 24 months of age or younger (infants) at the time of allogeneic bone marrow transplantation (BMT) for acute leukemia or myelodysplasia. We analyzed the survival rate, prognostic factors, incidences of late sequelae, and immune reconstitution in 22 infants who underwent allogeneic BMT. The 5-year event-free survival estimate was 45.5% (95% confidence interval (CI), 24.4% to 63.3%). Six patients died of transplant-related complications and six died of disease relapse. Remission status at the time of BMT was the most important prognostic factor (P = 0.005): no patient who received a transplant while their disease was not in remission survived, whereas the 5-year survival estimate for infants who underwent BMT during remission was 56% (95% CI, 31% to 75%). Long-term outcomes in the 10 infant survivors were compared with those of 10 older controls matched for diagnosis, disease status at the time of BMT, calendar year at the time of BMT, and source of stem cells. Immune function 1 year after transplantation and the incidences and spectra of late sequelae were similar for both groups during a median of 3.5 years (range, 1.5 to 7.2 years) of follow-up.

Successful unrelated donor bone marrow transplantation for paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disease of hematopoiesis due to a mutation in the PIG-A gene. Affected patients may demonstrate hemolysis or venous thrombosis, and may develop MDS or aplastic anemia. Successful results may be obtained after conditioning and transplantation from syngeneic or genotypically matched sibling donors. Experience with transplantation from matched unrelated donors (MUD) is limited to eight patients, with only one survivor. We report three patients who underwent successful MUD BMT for PNH. All three patients had severe aplastic anemia (SAA) and PNH at the time of BMT. Unrelated donors were six-antigen HLA-matched (n = 2) or HLA-A mismatched (n = 1). Conditioning consisted of cytarabine, cyclophosphamide, TBI, and ATG. Grafts were T cell-depleted by anti-CD6/CD8 antibodies + complement. Further GVHD prophylaxis consisted of cyclosporine. Patients received 0.7-1.1 x 10(8) nucleated cells/kg and 1.1-2.1 x 10(6) CD34(+) cells/kg. Neutrophil engraftment occurred at 16-21 days. One patient developed grade 1 acute GVHD. Although all three patients experienced significant transplant-related complications, they ultimately resolved and all patients are alive and well 30-62 months after BMT. T cell-depleted MUD BMT is an effective treatment option for PNH-related MDS and SAA.

Effect of HLA class I or class II incompatibility in pediatric marrow transplantation from unrelated and related donors.

The degree of histoincompatibility that can be tolerated, and the relative importance of matching at individual HLA class I and class II locus in bone marrow transplantation (BMT) has not been established. We hypothesized that matching for HLA-DR may not be more important than matching for HLA-A or HLA-B in selection of a donor for successful BMT. We retrospectively analyzed the outcomes of 248 consecutive pediatric patients who received allogeneic BMT from related donors (RD, n = 119) or unrelated donors (URD, n = 129). HLA-A and HLA-B were serologically matched, and HLA-DRB1 were identical by DNA typing in 69% of donor-recipient pairs. Most patients (89%) had hematologic malignancies; the rest had aplastic anemia or a congenital disorder. One HLA-A antigen mismatch was associated with a decrease in survival (p = 0.003) and a delay in granulocyte engraftment (p = 0.02) in recipients of RD marrow; as well as a decrease in survival (p = 0.02) and the development of severe acute graft-versus-host disease (GVHD) (p = 0.03) in recipients of URD marrow. One HLA-B antigen mismatch was associated with a decrease in the survival (p = 0.05) and the development of severe GVHD (p = 0.0007) in recipients of RD marrow. One HLA-DRB1 allele mismatch was associated only with a decrease in the survival (p = 0.0003) of recipients of RD marrow. Results of this study suggest that disparity in HLA-A and HLA-B antigens may not be better tolerated than disparity in HLA-DR allele in allogeneic BMT. Further studies are warranted to confirm our results.

Metastatic involvement of the heart and pericardium: CT and MR imaging.

Metastases to the heart and pericardium are much more common than primary cardiac tumors and are generally associated with a poor prognosis. Tumors that are most likely to involve the heart and pericardium include cancers of the lung and breast, melanoma, and lymphoma. Tumor may involve the heart and pericardium by one of four pathways: retrograde lymphatic extension, hematogenous spread, direct contiguous extension, or transvenous extension. Metastatic involvement of the heart and pericardium may go unrecognized until autopsy. Impairment of cardiac function occurs in approximately 30% of patients and is usually attributable to pericardial effusion. The clinical presentation includes shortness of breath, which may be out of proportion to radiographic findings in patients with pericardial effusion or may be the result of associated pleural effusion. Patients may also present with cough, anterior thoracic pain, pleuritic chest pain, or peripheral edema. The differential diagnosis of pericardial effusion in a patient with known malignancy includes malignant pericardial effusion, radiation-induced pericarditis, drug-induced pericarditis, and idiopathic pericarditis. Any disease process that causes thickening or nodularity of the pericardium or myocardium or masses within the cardiac chambers can mimic metastatic disease.