[show abstract][hide abstract] ABSTRACT: Pulmonary hypertension is a condition of varied etiology, commonly associated with poor clinical outcome. Patients are categorized on the basis of pathophysiological, clinical, radiologic, and therapeutic similarities. Pulmonary arterial hypertension (PAH) is often diagnosed late in its disease course, with outcome dependent on etiology, disease severity, and response to treatment. Recent advances in quantitative magnetic resonance imaging (MRI) allow for better initial characterization and measurement of the morphologic and flow-related changes that accompany the response of the heart-lung axis to prolonged elevation of pulmonary arterial pressure and resistance and provide a reproducible, comprehensive, and noninvasive means of assessing the course of the disease and response to treatment. Typical features of PAH occur primarily as a result of increased pulmonary vascular resistance and the resultant increased right ventricular (RV) afterload. Several MRI-derived diagnostic markers have emerged, such as ventricular mass index, interventricular septal configuration, and average pulmonary artery velocity, with diagnostic accuracy similar to that of Doppler echocardiography. Furthermore, prognostic markers have been identified with independent predictive value for identification of treatment failure. Such markers include large RV end-diastolic volume index, low left ventricular end-diastolic volume index, low RV ejection fraction, and relative area change of the pulmonary trunk. MRI is ideally suited for longitudinal follow-up of patients with PAH because of its noninvasive nature and high reproducibility and is advantageous over other biomarkers in the study of PAH because of its sensitivity to change in morphologic, functional, and flow-related parameters. Further study on the role of MRI image based biomarkers in the clinical environment is warranted.
Journal of thoracic imaging 03/2014; 29(2):68-79. · 1.42 Impact Factor
[show abstract][hide abstract] ABSTRACT: Established as a method to study anatomic changes, such as renal tumors or atherosclerotic vascular disease, magnetic resonance imaging (MRI) to interrogate renal function has only recently begun to come of age. In this review, we briefly introduce some of the most important MRI techniques for renal functional imaging, and then review current findings on their use for diagnosis and monitoring of major kidney diseases. Specific applications include renovascular disease, diabetic nephropathy, renal transplants, renal masses, acute kidney injury, and pediatric anomalies. With this review, we hope to encourage more collaboration between nephrologists and radiologists to accelerate the development and application of modern MRI tools in nephrology clinics.Kidney International advance online publication, 25 September 2013; doi:10.1038/ki.2013.361.
Kidney International 09/2013; · 7.92 Impact Factor
[show abstract][hide abstract] ABSTRACT: Rationale: Air trapping and ventilation defects on imaging are characteristics of asthma. Airway wall thickening occurs in asthma and is associated with increased bronchial vascularity and vascular permeability. Vascular endothelial cell products have not been explored as a surrogate to mark structural airway changes in asthma. Objectives: Determine whether reporters of vascular endothelial cell perturbation correlate with airway imaging metrics in patients with asthma of varying severity. Methods: Plasma from Severe Asthma Research Program subjects was analyzed by ELISAs for soluble von Willebrand factor mature protein (VWF:Ag) and propeptide (VWFpp), P-selectin, and platelet factor 4. Additional subjects were analyzed over 48 hours after whole-lung antigen challenge. We calculated ventilation defect volume by hyperpolarized helium-3 magnetic resonance imaging and areas of low signal density by multidetector computed tomography (less than -856 Hounsfield units [HU] at functional residual capacity and -950 HU at total lung capacity [TLC]). Measurements and Main Results: VWFpp and VWFpp/Ag ratio correlated with and predicted greater percentage defect volume on hyperpolarized helium-3 magnetic resonance imaging. P-selectin correlated with and predicted greater area of low density on chest multidetector computed tomography less than -950 HU at TLC. Platelet factor 4 did not correlate. Following whole-lung antigen challenge, variation in VWFpp, VWFpp/Ag, and P-selectin among time-points was less than that among subjects, indicating stability and repeatability of the measurements. Conclusions: Plasma VWFpp and P-selectin may be useful as surrogates of functional and structural defects that are evident on imaging. The results raise important questions about why VWFpp and P-selectin are associated specifically with different imaging abnormalities.
American Journal of Respiratory and Critical Care Medicine 07/2013; 188(2):167-78. · 11.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Magnetic resonance imaging (MRI) with (3)He does not require ionizing radiation and has been shown to detect regional abnormalities in lung ventilation and structure in adults with asthma, but the method has not been extended to children with asthma. Measurements of regional lung ventilation and microstructure in subjects with childhood asthma could advance our understanding of disease mechanisms. OBJECTIVE: We sought to determine whether (3)He MRI in children can identify abnormalities related to the diagnosis of asthma or prior history of respiratory illness. METHODS: Forty-four children aged 9 to 10 years were recruited from a birth cohort at increased risk of asthma and allergic diseases. For each subject, a time-resolved 3-dimensional image series and a 3-dimensional diffusion-weighted image were acquired in separate breathing maneuvers. The numbers and sizes of ventilation defects were scored, and regional maps and statistics of average (3)He diffusion lengths were calculated. RESULTS: Children with mild-to-moderate asthma had lower average root-mean-square diffusion length (X(rms)¯) values (P = .004), increased regional SD of diffusion length values (P = .03), and higher defect scores (P = .03) than those without asthma. Children with histories of wheezing illness with rhinovirus infection before the third birthday had lower X(rms)¯ values (P = .01) and higher defect scores (P = .05). CONCLUSION: MRI with (3)He detected more and larger regions of ventilation defect and a greater degree of restricted gas diffusion in children with asthma compared with those seen in children without asthma. These measures are consistent with regional obstruction and smaller and more regionally variable dimensions of the peripheral airways and alveolar spaces.
The Journal of allergy and clinical immunology 12/2012; · 9.17 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background: Heat shock protein 27 (HSP27) is a small HSP up-regulated in response to stress in the kidney. The relationship between HSP27 and intrarenal oxygenation in patients with native and transplant kidney disease is unknown. Methods: We compared HSP27 levels, intrarenal oxygenation measured by blood oxygen-level dependent (BOLD) imaging using R2* values, and perfusion determined by arterial spin labeling (ASL) magnetic resonance imaging (MRI), between patients with native and transplant kidney disease (n=28). Results: There were no statistical differences in mean age (53.9 vs. 47.1 years), kidney function (63.6 vs. 50.7 ml/min per 1.73 m2), mean arterial blood pressure (91.6 vs. 91.1 mm Hg), hematocrit (40.6% vs. 39.3%), diuretic or angiotensin-converting enzyme inhibitor use, serum or urine levels of hydrogen peroxide, nitric oxide, F2 isoprostanes and HSP27 between native and transplant kidneys. BOLD-MRI studies demonstrated comparable patterns in intrarenal oxygen bioavailability (medullary R2* 18.1 vs. 18.3/s and cortical R2* 12 vs. 11.7/s, respectively). However, medullary perfusion was significantly lower in transplant kidneys (36.4 vs. 78.7 ml/100 g per minute, p=0.0002). There was a linear relationship between serum HSP27 concentrations and medullary perfusion in kidney allografts (HSP27 concentration [ng/mL] = 0.78 + 0.09 medullary perfusion, R2=0.43, p=0.01). Conclusions: Our study demonstrates that medullary perfusion is significantly lower in kidney allografts compared with native kidneys with comparable renal function. We further noted a direct association between serum HSP27 levels and medullary perfusion after transplantation. Additional studies are needed to examine the role of HSP27 as a biomarker of kidney disease progression.
Journal of nephrology 02/2012; · 2.02 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background/Aims: Hypercholesterolemia in midlife increases risk for Alzheimer's disease (AD) and contributes to cerebrovascular dysregulation - an early finding in preclinical AD pathology. Statins improve vascular reactivity, but it is unknown if they increase regional cerebral blood flow (CBF) in individuals at risk for AD. Methods: In a randomized, controlled, double-blind pilot study, 16 asymptomatic middle-aged adults with parental history of AD were randomized to atorvastatin or placebo daily for 4 months. At baseline and month 4, regional CBF was measured using arterial spin-labeling magnetic resonance imaging and endothelial function was measured using brachial artery ultrasound. Results: At baseline, participants with low HDL-cholesterol, higher global vascular risk, and greater endothelial dysfunction had reduced regional CBF in areas of the brain related to memory and learning (all p < 0.03). Using voxel-based analysis, 4 months of atorvastatin increased CBF in bilateral hippocampi, fusiform gyrus, putamen and insular cortices compared to placebo. Conclusion: In this pilot study, atorvastatin increased regional CBF in persons at risk for AD. Further research is warranted to confirm whether statins increase CBF in areas of the brain related to memory and learning and whether such perfusion changes are associated with a delay in the onset of AD. Clinical Trial Registration: http://clinicaltrials.gov Identifier: NCT00751907.
Current Alzheimer research 11/2011; 9(8):990-7. · 4.97 Impact Factor
[show abstract][hide abstract] ABSTRACT: The National Heart, Lung, and Blood Institute Severe Asthma Research Program (SARP) has characterized over the past 10 years 1,644 patients with asthma, including 583 individuals with severe asthma. SARP collaboration has led to a rapid recruitment of subjects and efficient sharing of samples among participating sites to conduct independent mechanistic investigations of severe asthma. Enrolled SARP subjects underwent detailed clinical, physiologic, genomic, and radiological evaluations. In addition, SARP investigators developed safe procedures for bronchoscopy in participants with asthma, including those with severe disease. SARP studies revealed that severe asthma is a heterogeneous disease with varying molecular, biochemical, and cellular inflammatory features and unique structure-function abnormalities. Priorities for future studies include recruitment of a larger number of subjects with severe asthma, including children, to allow further characterization of anatomic, physiologic, biochemical, and genetic factors related to severe disease in a longitudinal assessment to identify factors that modulate the natural history of severe asthma and provide mechanistic rationale for management strategies.
American Journal of Respiratory and Critical Care Medicine 11/2011; 185(4):356-62. · 11.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: Hyperpolarized (HP) (13)C-labeled pyruvate studies with magnetic resonance (MR) have been used to observe the kinetics of metabolism in vivo. Kinetic modeling to measure metabolic rates in vivo is currently limited because of nonspecific hyperpolarized signals mixing between vascular, extravascular, and intracellular compartments. In this study, simultaneous acquisition of both (1)H and (13)C signals after contrast agent injection is used to resolve specific compartments to improve the accuracy of the modeling. We demonstrate a novel technique to provide contrast to the intracellular compartments by sequential injection of HP [1-(13)C] pyruvate followed by gadolinium-chelate to provide T(1)-shortening to extra-cellular compartments. A kinetic model that distinguishes the intracellular space and includes the T(1)-shortening effect of the gadolinium chelate can then be used to directly measure the intracellular (13)C kinetics.
[show abstract][hide abstract] ABSTRACT: To examine both inter-visit and intra-visit reproducibility of a MR arterial spin labeling (ASL) perfusion technique in native and transplanted kidneys over a broad range of renal function.
Renal perfusion exams were performed at 1.5 T in a total of 24 subjects: 10 with native and 14 with transplanted kidneys. Using a flow-sensitive alternating inversion recovery (FAIR) ASL scheme, 32 control/tag pairs were acquired and processed using a single-compartment model. Two FAIR-ASL MR exams were performed at least 24 h apart on all the subjects to assess inter-visit reproducibility. ASL perfusion measurements were also repeated back-to-back within one scanning session in 8 native subjects and in 12 transplant subjects to assess intra-visit reproducibility. Intra-class correlations (ICCs) and coefficients of variation (CVs) were calculated as metrics of reproducibility.
Intra-visit ICCs ranged from 0.96 to 0.98 while CVs ranged from 4.8 to 6.0%. Inter-visit measurements demonstrated slightly more variation with ICCs from 0.89 to 0.94 and CVs from 7.6 to 13.1%. Medullary perfusion demonstrated greater variability compared with cortical blood flow: intra-visit ICCs from 0.72 to 0.78 and CVs from 16.7 to 26.7%, inter-visit ICCs from 0.13 to 0.63 and CVs from 19.8 to 37%.
This study indicates that a FAIR-ASL perfusion technique is reproducible in the cortex of native and transplanted kidneys over a broad range in renal function. In contrast, perfusion measurements in the medulla demonstrated moderate to poor reproducibility for intra-visit and inter-visit measures respectively.
Journal of Magnetic Resonance Imaging 06/2011; 33(6):1414-21. · 2.57 Impact Factor
[show abstract][hide abstract] ABSTRACT: A radiofrequency coil based on a solenoid design was developed and integrated with a novel device for MR-guided breast interventions using a circumferential approach. The transmit/receive tapered solenoid design conforms to the shape of the pendent breast, and provides open circumferential needle access to breast tissue under rotational symmetry. Phantom and in vivo studies using a healthy volunteer demonstrated a superior uniformity using the tapered solenoid coil compared with a commercial 8-channel diagnostic imaging coil. The solenoid coil design has important advantages due to localized transmit/receive such as B(1) -homogeneity and reduced specific absorption ratio (SAR) especially at high-field strengths. Because it provides open access and a rotationally symmetric local field, the tapered solenoid design can easily be adapted for bilateral imaging and 3D MR-guided breast interventions.
Magnetic Resonance in Medicine 06/2011; 65(6):1799-804. · 3.27 Impact Factor