Pseudotime dynamics of T cells in pancreatic ductal adenocarcinoma inform distinct functional states within the regulatory and cytotoxic T cells.

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest types of cancer and has a 5-year survival of less than 8% owing to its complex biology. As PDAC is refractory to immunotherapy, we need to understand the functional dynamics of T cells in the PDAC microenvironment to develop alternative therapeutic strategies. In this study, we performed RNA velocity-based pseudotime analysis on a scRNA-seq dataset from surgically resected human PDAC specimens to gain insight into temporal gene expression patterns that best characterize the cell fates.

Brain BOLD and NIRS response to hyperoxic challenge in sickle cell disease and chronic anemias.

Purpose: Congenital anemias, including sickle cell anemia and thalassemia, are associated with cerebral tissue hypoxia and heightened stroke risks. Recent works in sickle cell disease mouse models have suggested that hyperoxia respiratory challenges can identify regions of the brain having chronic tissue hypoxia. Therefore, this work investigated differences in hyperoxic response and regional cerebral oxygenation between anemic and healthy subjects.

Reduced global cerebral oxygen metabolic rate in sickle cell disease and chronic anemias.

Anemia is the most common blood disorder in the world. In patients with chronic anemia, such as sickle cell disease or major thalassemia, cerebral blood flow increases to compensate for decreased oxygen content. However, the effects of chronic anemia on oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO ) are less well understood.

Calibration of T oximetry MRI for subjects with sickle cell disease.

Purpose: Cerebral T oximetry is a non-invasive imaging method to measure blood T and cerebral venous oxygenation. Measured T values are converted to oximetry estimates using carefully validated and potentially disease-specific calibrations. In sickle cell disease, red blood cells have abnormal cell shape and membrane properties that alter T oximetry calibration relationships in clinically meaningful ways.

Tricuspid regurgitant jet velocity and myocardial tissue Doppler parameters predict mortality in a cohort of patients with sickle cell disease spanning from pediatric to adult age groups - revisiting this controversial concept after 16 years of additional evidence.

Sickle cell disease (SCD) is a monogenic hemoglobinopathy associated with significant morbidity and mortality. Cardiopulmonary, vascular and sudden death are the reasons for the majority of young adult mortality in SCD. To better understand the clinical importance of multi-level vascular dysfunction, in 2009 we assessed cardiac function including tricuspid regurgitant jet velocity (TRV), tissue velocity in systole(S') and diastole (E'), inflammatory, rheologic and hemolytic biomarkers as predictors of mortality in patients with SCD.

Quantitative perfusion mapping with induced transient hypoxia using BOLD MRI.

Purpose: Gadolinium-based dynamic susceptibility contrast (DSC) is commonly used to characterize blood flow in patients with stroke and brain tumors. Unfortunately, gadolinium contrast administration has been associated with adverse reactions and long-term accumulation in tissues. In this work, we propose an alternative deoxygenation-based DSC (dDSC) method that uses a transient hypoxia gas paradigm to deliver a bolus of paramagnetic deoxygenated hemoglobin to the cerebral vasculature for perfusion imaging.

Transient Hypoxia Model Revealed Cerebrovascular Impairment in Anemia Using BOLD MRI and Near-Infrared Spectroscopy.

Background: Obstructive sleep apnea and nocturnal oxygen desaturations, which are prevalent in sickle cell disease (SCD) and chronic anemia disorders, have been linked to risks of stroke and silent cerebral infarcts (SCI). Cerebrovascular response to intermittent desaturations has not been well studied and may identify patients at greatest risk.

Purpose: To investigate the cerebral dynamic response to induced desaturation in SCD patients with and without SCI, chronic anemia, and healthy subjects.

Rosette Trajectories Enable Ungated, Motion-Robust, Simultaneous Cardiac and Liver T * Iron Assessment.

Background: Quantitative T * MRI is the standard of care for the assessment of iron overload. However, patient motion corrupts T * estimates.

Purpose: To develop and evaluate a motion-robust, simultaneous cardiac and liver T * imaging approach using non-Cartesian, rosette sampling and a model-based reconstruction as compared to clinical-standard Cartesian MRI.

Veterinary utility of dried blood spots for detailed analysis of chlorinated pesticides and polychlorinated biphenyls by gas chromatography tandem mass spectrometry.

Persistent organic pollutants (POPs) are organic compounds of anthropogenic origin that resist atmospheric and microbial degradation and thus persist in the environment and in food chains for exceptionally long periods of time. Veterinarians and wildlife researchers need simple methodologies for monitoring and measuring such compounds including two large and diverse categories, organochlorine pesticides (OCs) and polychlorinated biphenyls (PCBs), compounds that have been largely banned from production and use except for specific exceptions. We present development of methodologies for detection and quantitation of 22 OCs and 10 PCB congeners by tandem quadrupole gas chromatography-mass spectrometric analysis of Dried Blood Spots (DBS).

Anemia predicts lower white matter volume and cognitive performance in sickle and non-sickle cell anemia syndrome.

Severe chronic anemia is an independent predictor of overt stroke, white matter damage, and cognitive dysfunction in the elderly. Severe anemia also predisposes to white matter strokes in young children, independent of the anemia subtype. We previously demonstrated symmetrically decreased white matter (WM) volumes in patients with sickle cell disease (SCD).

White matter has impaired resting oxygen delivery in sickle cell patients.

Although modern medical management has lowered overt stroke occurrence in patients with sickle cell disease (SCD), progressive white matter (WM) damage remains common. It is known that cerebral blood flow (CBF) increases to compensate for anemia, but sufficiency of cerebral oxygen delivery, especially in the WM, has not been systematically investigated. Cerebral perfusion was measured by arterial spin labeling in 32 SCD patients (age range: 10-42 years old, 14 males, 7 with HbSC, 25 HbSS) and 25 age and race-matched healthy controls (age range: 15-45 years old, 10 males, 12 with HbAS, 13 HbAA); 8/24 SCD patients were receiving regular blood transfusions and 14/24 non-transfused SCD patients were taking hydroxyurea.

Pseudo continuous arterial spin labeling quantification in anemic subjects with hyperemic cerebral blood flow.

Purpose: To investigate possible sources of quantification errors in global cerebral blood flow (CBF) measurements by comparing pseudo continuous arterial spin labeling (PCASL) and phase contrast (PC) MRI in anemic, hyperemic subjects.

Methods: All studies were performed on a Philips 3T Achieva MRI scanner. PC and PCASL CBF examinations were performed in 10 healthy, young adult subjects and 18 young adults with chronic anemia syndromes including sickle cell disease and thalassemia.

Diminished cerebral oxygen extraction and metabolic rate in sickle cell disease using T2 relaxation under spin tagging MRI.

Purpose: T MRI oximetry can noninvasively determine oxygen saturation (Y) but requires empirical MR calibration models to convert the measured blood transverse relaxation (T ) into Y. The accuracy of existing T models in the presence of blood disorders such as sickle cell disease (SCD) remains unknown.

Methods: A Carr Purcell Meiboom Gill T preparation sequence was used to make 83 whole blood measurements from 11 subjects with SCD to derive an ex vivo sickle hemoglobin (HbS) T model.

Contrasting resting-state fMRI abnormalities from sickle and non-sickle anemia.

Sickle cell disease (SCD) is a chronic blood disorder that is often associated with acute and chronic cerebrovascular complications, including strokes and impaired cognition. Using functional resting state magnetic resonance images, we performed whole-brain analysis of the amplitude of low frequency fluctuations (ALFF), to detect areas of spontaneous blood oxygenation level dependent signal across brain regions. We compared the ALFF of 20 SCD patients to that observed in 19 healthy, age and ethnicity-matched, control subjects.

Hemoglobin and mean platelet volume predicts diffuse T1-MRI white matter volume decrease in sickle cell disease patients.

Sickle cell disease (SCD) is a life-threatening genetic condition. Patients suffer from chronic systemic and cerebral vascular disease that leads to early and cumulative neurological damage. Few studies have quantified the effects of this disease on brain morphometry and even fewer efforts have been devoted to older patients despite the progressive nature of the disease.

Empirical model of human blood transverse relaxation at 3 T improves MRI T oximetry.

Purpose: We sought a human blood T -oximetery calibration curve over the wide range of hematocrits commonly found in anemic patients applicable with T relaxation under spin tagging (TRUST).

Methods: Blood was drawn from five healthy control subjects. Ninety-three in vitro blood transverse relaxation (T ) measurements were performed at 37°C over a broad range of hematocrits (10-55%) and oxygen saturations (14-100%) at 3 Tesla (T).

Determinants of resting cerebral blood flow in sickle cell disease.

Stroke is common in children with sickle cell disease and results from an imbalance in oxygen supply and demand. Cerebral blood flow (CBF) is increased in patients with sickle cell disease to compensate for their anemia, but adequacy of their oxygen delivery has not been systematically demonstrated. This study examined the physiological determinants of CBF in 37 patients with sickle cell disease, 38 ethnicity matched control subjects and 16 patients with anemia of non-sickle origin.

FUNCTIONAL CONNECTIVITY ANALYSIS FOR THALASSEMIA DISEASE BASED ON A GRAPHICAL LASSO MODEL.

Thalassemia is a congenital disorder of hemoglobin synthesis which can lead to thromboembolic events and stroke in the brain. In this work we propose to use a functional connectivity model to discriminate between control and diseased subjects. Our connectivity measure is based on functional magnetic resonance imaging, and hence common variations of the blood oxygenation level in spatially distant areas.

BOLD delay times using group delay in sickle cell disease.

Sickle cell disease (SCD) is an inherited blood disorder that effects red blood cells, which can lead to vasoocclusion, 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.

Predictors of cerebral blood flow in patients with and without anemia.

Sickle cell disease (SCD) is the most common cause of stroke in childhood and results primarily from a mismatch of cerebral oxygen supply and demand rather than arterial obstruction. However, resting cerebral blood flow (CBF) has not been examined in the general African American population, in whom obesity, hypertension, cerebrovascular disease, and diminished cerebrovascular reserve capacity are common. To better understand the underlying physiological substrate upon which SCD is superimposed, we measured CBF in 32 young (age 28 ± 10 yr), asymptomatic African American subjects with and without sickle cell trait (n= 14).

Tract specific analysis in patients with sickle cell disease.

Sickle cell disease (SCD) is a hereditary blood disorder in which the oxygen-carrying hemoglobin molecule in red blood cells is abnormal. It affects numerous people in the world and leads to a shorter life span, pain, anemia, serious infections and neurocognitive decline. Tract-Specific Analysis (TSA) is a statistical method to evaluate white matter alterations due to neurocognitive diseases, using diffusion tensor magnetic resonance images.

Low-frequency fluctuation amplitude analysis of resting-state fMRI in sickle cell disease.

Sickle cell disease may result in neurological damage and strokes, leading to morbidity and mortality. Currently, there are no dependable biomarkers to predict impending strokes. In this study, we analyzed neuronal processes at resting state and more particularly how this disease affects the default mode network.

Autonomic responses to cold face stimulation in sickle cell disease: a time-varying model analysis.

Sickle cell disease (SCD) is characterized by sudden onset of painful vaso-occlusive crises (VOC), which occur on top of the underlying chronic blood disorder. The mechanisms that trigger VOC remain elusive, but recent work suggests that autonomic dysfunction may be an important predisposing factor. Heart-rate variability has been employed in previous studies, but the derived indices have provided only limited univariate information about autonomic cardiovascular control in SCD.