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Biomedical subjects

Hongyu An

Publications and source records attributed to Hongyu An.

9 recordsLinked to original sources

Proteomic profiling identifies systemic drivers of blood-brain barrier injury in sickle cell disease.

Sickle cell disease (SCD) causes brain injury and cognitive disability. Systemic inflammation and endothelial injury are central to SCD pathophysiology, yet the relationship between systemic drivers of blood-brain barrier (BBB) disruption and brain injury remains understudied. This cross-sectional study assessed whole-brain and regional BBB permeability (Ktrans) using dynamic contrast-enhanced magnetic resonance imaging for 37 adults with SCD in steady state and 37 adults without SCD. Cerebral oxygen extraction fraction (OEF) and white matter mean diffusivity (MD) measured tissue hypoxia and microstructural injury, respectively. The SCD cohort showed elevated Ktrans compared with controls (3.6 &#xd7; 10-4&#xb7;min-1 vs 2.58 &#xd7; 10-4&#xb7;min-1; 95% confidence interval [CI] median difference, 0.36 &#xd7; 10-4&#xb7;min-1 to 1.30 &#xd7; 10-4&#xb7;min-1; P< .001), indicating BBB disruption. In SCD, white matter Ktrans was associated with MD (&#x3b2;, 6.25 [95% CI, 1.72-10.77]; P = .008), independent of OEF (&#x3b2;, 0.22 [95% CI, 0.09-0.35]), and silent cerebral infarcts (&#x3b2;, 0.01 [95% CI, 0.00-0.02]). The interaction (P = .037) between Ktrans and OEF on MD suggested a combined, deleterious effect of BBB disruption and hypoxia on microstructural injury. High-throughput plasma proteomics followed by differential expression analysis, and weighted gene correlation network analysis in a subset of 61 participants revealed that 79 proteins associated with BBB permeability belonged to iron homeostasis, response to hypoxia, immune dysregulation, extracellular matrix degradation, lipoprotein homeostasis, and arginine-proline metabolism pathways. All pathways were independently associated with microstructural injury. BBB permeability was a mediator of brain injury for all pathways except extracellular matrix degradation. Targeting specific systemic pathways to protect the BBB may represent a therapeutic approach to preserve brain health in SCD.

Humans↗

Nanoscale metal-organic frameworks as potential multimodal contrast enhancing agents.

Nanoscale metal-organic frameworks (NMOFs) based on Gd3+ centers and benzenedicarboxylate and benzenetricarboxylate bridging ligands were synthesized using reverse microemulsions and characterized using SEM, PXRD, and TGA. These NMOFs exhibit extraordinarily large R1 and R2 relaxivities because of the presence of up to tens of millions of Gd3+ centers in each nanoparticle and are thus efficient T1 and T2 contrast agents for MRI. The NMOFs can also be made highly luminescent by doping with Eu3+ or Tb3+ centers. The results from this work suggest that NMOFs can be used as potential contrast agents for multimodal imaging.

Contrast Media↗

An independent component analysis approach for minimizing effects of recirculation in dynamic susceptibility contrast magnetic resonance imaging.

In dynamic susceptibility contrast (DSC) perfusion-weighted imaging, effects of recirculation are normally minimized by a gamma-variate fitting procedure of the concentration curves before estimating hemodynamic parameters. The success of this method, however, hinges largely on the extent to which magnetic resonance signal is altered in the presence of a contrast agent and a temporal separation between the first and subsequent passages of the contrast agent. Moreover, important physiologic information might be compromised by imposing an analytic equation to all measured concentration curves. This investigation proposes to exploit independent component analysis to minimize effects of recirculation in DSC. Results obtained from simulation, normal healthy volunteers, and acute stroke patients show that such a technique can greatly minimize the effects of recirculation despite a substantial overlap between the first passage and recirculation. This in turn should improve estimation of cerebral hemodynamics particularly when an overlap between the first passage and recirculation is suspected as in an ischemic lesion.

Adult↗

Neuroimaging in human immunodeficiency virus infection.

Human immunodeficiency virus (HIV) is associated with central nervous system (CNS) changes that may affect cerebral blood flow (CBF), metabolism, structure, and diffusion. Each of the available neuroimaging techniques offers unique insight into the neural mechanisms underlying HIV, as well as a potential means of monitoring disease progression and treatment response. The purpose of the article is to provide a review of experimental studies evaluating changes related to HIV with imaging techniques, including single-photon emission computed tomography (SPECT), positron emission tomography (PET), volumetric magnetic resonance imaging (MRI), functional MRI (fMRI), magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI), and perfusion MRI (pMRI).

AIDS Dementia Complex↗

Magnetic resonance cerebral metabolic rate of oxygen utilization in hyperacute stroke patients.

The purpose of this study was to explore the feasibility of obtaining magnetic resonance-measured cerebral metabolic rate of oxygen utilization (MR-CMRO(2)) in acute ischemic stroke patients. Seven stroke patients were serially imaged: 4.5 +/- 0.9 hours (tp1), 3 to 5 days (tp2), and 1 to 3 months (tp3) after symptom onset. Diffusion-weighted, perfusion-weighted, and multiecho gradient-echo/spin-echo images were acquired; cerebral blood flow and oxygen extraction fraction maps were obtained from which CMRO(2) was calculated as the product of cerebral blood flow and oxygen extraction fraction. The final infarct lesions obtained from tp3 T2-weighted images and the "penumbra" obtained from the tp1 perfusion-weighted image-defined lesion were coregistered onto tp1 CMRO(2) maps. CMRO(2) values in the region of brain that eventually infarcted were reduced to 0.40 +/- 0.24 of the respective region on the contralateral hemisphere. The "salvaged penumbra" defined by the area of mismatch between the final infarct and the tp1 perfusion-weighted lesion demonstrated an average CMRO(2) value of 0.55 +/- 0.11 of the contralateral hemisphere. Although our results are preliminary and require further evaluation, the ability to obtain in vivo measurements of MR-CMRO(2) noninvasively potentially can provide information for determining brain tissue viability in acute ischemic stroke patients.

Acute Disease↗

Impact of intravascular signal on quantitative measures of cerebral oxygen extraction and blood volume under normo- and hypercapnic conditions using an asymmetric spin echo approach.

An asymmetric spin echo (ASE) single shot echo planar imaging (EPI) sequence is proposed for obtaining quantitative estimates of R2', cerebral venous blood volume fraction (vCBV), and oxygen extraction fraction (OEF) noninvasively in normal volunteers. The impact of the presence of intravascular signal on the estimates of vCBV and OEF were examined in five subjects with different levels of flow attenuation. A significant reduction in the estimates of vCBV and a small increase in the measurements of OEF were observed in the presence of flow suppression gradients. In addition, mild hypercapnia was induced in normal subjects (n = 4). R2', vCBV, and OEF were measured under both normocapnia and experimentally induced hypercapnia. In agreement with the well-documented cerebral vascular responses to hypercapnia, estimates of R2' and OEF decrease, while measures of vCBV increase during hypercapnia.

Brain↗

Practical consideration for 3T imaging.

In the past 10 to 15 years, 1.5T has been one of the most commonly used field strengths for day-to-day clinical operations. However, recent advances in high field technology and the increased availability of high field (> 1.5T) human scanners have opened the doors for a variety of exciting improvements in clinical and research applications of MR imaging. In particular, 3T has continued to gain wide acceptance as one of the main field strengths for clinical and research studies. Therefore, in this article the authors focus on the pros and cons of 3T imaging and comparisons between results obtained at 3T and 1.5T.

Brain↗

Cerebral oxygen extraction fraction and cerebral venous blood volume measurements using MRI: effects of magnetic field variation.

The presence of magnetic background field inhomogeneity (DeltaB) may confound quantitative measures of cerebral venous blood volume (vCBV) and cerebral oxygen extraction fraction (MR_OEF) with T2*-based methods. The goal of this study was to correct its effect and obtain more accurate estimates of vCBV and MR_OEF. A 3D high-resolution gradient echo sequence was employed to obtain DeltaB maps by two algorithms. The DeltaB maps were then used to recover the signal loss in images acquired by a 2D multiecho gradient echo / spin echo sequence. Finally, both quantitative estimates of MR_OEF and vCBV were obtained from the DeltaB- corrected 2D multiecho gradient echo / spin echo images. A total of 12 normal subjects were studied. An overestimated vCBV was observed in the brain (4.29 +/- 0.78%) prior to DeltaB correction, while the measured vCBV was substantially reduced after DeltaB correction. Whole brain vCBV of 2.97 +/- 0.44% and 2.68 +/- 0.47% were obtained by the two different DeltaB correction methods, in excellent agreement with the reported results in the literature. Furthermore, when MR_OEF was compared with and without DeltaB correction, no significant differences (P = 0.467) were observed. The ability to simultaneously obtain vCBV and MR_OEF noninvasively may have profound clinical implications for the studies of cerebrovascular disease.

Algorithms↗

Cerebral venous and arterial blood volumes can be estimated separately in humans using magnetic resonance imaging.

Approaches to obtain quantitative, noninvasive estimates of total cerebral blood volume (tCBV) and cerebral venous blood volume (vCBV) separately in humans are proposed. Two sequences were utilized, including a 3D high-resolution gradient-echo (GE) sequence and a 2D multi-echo GE/spin-echo (MEGESE) sequence. Images acquired by the former sequence provided an estimate of background magnetic field variations (DeltaB), while images obtained by the latter sequence were utilized to obtain separate measures of tCBV and vCBV with and without contrast agent. Prior to the calculation of vCBV and tCBV, the acquired images were corrected for signal loss induced by the presence of DeltaB. vCBV and tCBV were estimated to be 2.46% +/- 0.28% and 3.20% +/- 0.41%, respectively, after the DeltaB correction, which in turn provided a vCBV/tCBV ratio of 0.77 +/- 0.04, in excellent agreement with results reported in the literature. Our results demonstrate that quantitative estimates of vCBV and tCBV can be obtained in vivo.

Blood Volume↗