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Biomedical subjects

Weili Lin

Publications and source records attributed to Weili Lin.

At least 19 recordsLinked to original sources
PubMed2025

The Consortium for Clarity in ADRD Research Through Imaging (CLARiTI): Overview of consortium sites and anticipated enrollment.

INTRODUCTION: The Consortium for Clarity in Alzheimer's disease related dementias (ADRD) Research Through Imaging (CLARiTI) is a study that aims to collect standardized imaging and plasma biomarkers on 2000 Clinical Core participants enrolled across all Alzheimer's Disease Research Centers (ADRC) sites. We sought to summarize the known heterogeneity across centers regarding scientific focus and initial enrollment plans for CLARiTI. METHODS: We developed and distributed a survey capturing information on the 36 CLARiTI site's theme/expertise, recruitment plans, and the intersection of CLARiTI with other ADRC imaging efforts. RESULTS: Anticipated CLARiTI enrollees spanned 11 different categories of suspected etiologies underlying impairment. A wide range of risk factors were endorsed across sites regarding the enrollment of unimpaired individuals. Variability also existed regarding site-level strategies in enrollment into CLARiTI versus other imaging efforts. DISCUSSION: We anticipate that the 2000 individuals that will enroll into CLARiTI will reflect the clinical heterogeneity already in place across the ADRC network. HIGHLIGHTS: The ADRC Consortium for Clarity in ADRD Research Through Imaging (CLARiTI) will leverage and contribute to the existing Alzheimer's Disease Research Centers (ADRC) program by supporting standardized imaging and plasma collection across all centers. We summarize the variation in scientific focus and enrollment plans across ADRC sites participating in CLARiTI. The anticipated CLARiTI cohort will reflect the clinical heterogeneity that already exists across the ADRC network. CLARiTI will contribute to scientific goals related to the detection of multi-etiological signatures relevant for Alzheimer's disease and related disorders (ADRDs).

Humans↗
PubMed2006

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↗
PubMed2006

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↗
PubMed2005

Influence of ptsP gene on pyocyanin production in Pseudomonas aeruginosa.

A pyocyanin overproducer with insertional inactivation of ptsP gene was isolated from a mini-Mu insertion library in Pseudomonas aeruginosa PA68. The mutation was complemented by a functional ptsP gene in trans. The pyocyanin-overproducing phenotype was also found in a ptsP mutant constructed by gene replacement in the P. aeruginosa PAO1 strain. Reporter plasmids with P(qscR)-lacZ, P(lasI)-lacZ and P(rhlI)-lacZ were constructed and the beta-galactosidase activity in the ptsP mutant/wild-type background was measured. The results showed that lack of Enzyme I(Ntr) (EI(Ntr), encoded by ptsP) decreased transcription from the P(qscR) promoter and increased the activity of the P(lasI) and P(rhlI) promoters. Normally, QscR represses the quorum-sensing LasR-LasI and RhlR-RhlI systems involved in pyocyanin regulation. Our results showed that the ptsP gene has an important role in the regulation of pyocyanin production and that two quorum-sensing systems and their repressor QscR are involved in this regulation.

Base Sequence↗
PubMed2005

Magnetic resonance angiography visualization of abnormal tumor vasculature in genetically engineered mice.

Previous research on the vasculature of tumor-bearing animals has focused upon the microvasculature. Magnetic resonance angiography (MRA) offers a noninvasive, complementary approach that provides information about larger vessels. Quantitative analysis of MRA images of spontaneous preclinical tumor models has not been previously reported. Eleven TgT121;p53+/- mice, which invariably develop choroid plexus carcinoma (CPC), and nine age-matched healthy controls were imaged using T1, T2, and a high-resolution three-dimensional time-of-flight MRA sequences at 3 T. Tumors and vessels were segmented to determine tumor volume and vascular attributes, including number of terminal branches, vessel count, and the average vessel radii of MRA-visible vessels within the tumor. Differences in the vasculature between tumor-bearing animals and healthy controls were analyzed statistically. Although the spatial resolution of MRA prohibits visualization of capillaries, a high density of intratumor blood vessels was visualized in CPC mice. A significant increase in terminal branch count and vessel count, but not average vessel radius, was observed in CPCs when compared with normal controls. Both terminal branch count and vessel count were highly correlated with tumor volume. This study represents the first MRA analysis of a spontaneous preclinical brain tumor model. Although the spatial resolution of MRA is less than histologic analysis, MRA-obtained vascular attributes provide useful information with full brain coverage. We show that consistent tumor vasculature properties can be determined by MRA. Such methods are critical for developing preclinical therapeutic testing and will help guide the development of human brain tumor analyses.

Animals↗
PubMed2005

Vessel tortuosity and brain tumor malignancy: a blinded study.

RATIONALE AND OBJECTIVES: Malignancy provokes regional changes to vessel shape. Characteristic vessel tortuosity abnormalities appear early during tumor development, affect initially healthy vessels, spread beyond the confines of tumor margins, and do not simply mirror tissue perfusion. The ability to detect and quantify tortuosity abnormalities on high-resolution magnetic resonance angiography (MRA) images offers a new approach to the noninvasive diagnosis of malignancy. This report evaluates a computerized, statistical method of analyzing the shapes of vessels extracted from MRA in diagnosing cancer. MATERIALS AND METHODS: The regional vasculature of 34 healthy subjects was compared with the tumor-associated vasculature of 30 brain tumors before surgical resection. The operator performing the analysis was blinded to the diagnosis. Vessels were segmented from an MRA of each subject, a region of interest was defined in each tumor patient and was mapped to all healthy controls, and a statistical analysis of vessel shape measures was then performed over the region of interest. Many difficult cases were included, such as pinpoint, hemorrhagic, and irradiated tumors, as were hypervascular benign tumors. Tumors were identified as benign or malignant on the basis of histological evaluation. RESULTS: A discriminant analysis performed at the study's conclusion successfully classified all but one of the 30 tumors as benign or malignant on the basis of vessel tortuosity. CONCLUSIONS: Quantitative, statistical measures of vessel shape offer a new approach to the diagnosis and staging of disease. Although the methods developed under the current report must be tested against a new series of cases, initial results are promising.

Adult↗
PubMed2005

Analyzing attributes of vessel populations.

Almost all diseases affect blood vessel attributes (vessel number, radius, tortuosity, and branching pattern). Quantitative measurement of vessel attributes over relevant vessel populations could thus provide an important means of diagnosing and staging disease. Unfortunately, little is known about the statistical properties of vessel attributes. In particular, it is unclear whether vessel attributes fit a Gaussian distribution, how dependent these values are upon anatomical location, and how best to represent the attribute values of the multiple vessels comprising a population of interest in a single patient. The purpose of this report is to explore the distributions of several vessel attributes over vessel populations located in different parts of the head. In 13 healthy subjects, we extract vessels from MRA data, define vessel trees comprising the anterior cerebral, right and left middle cerebral, and posterior cerebral circulations, and, for each of these four populations, analyze the vessel number, average radius, branching frequency, and tortuosity. For the parameters analyzed, we conclude that statistical methods employing summary measures for each attribute within each region of interest for each patient are preferable to methods that deal with individual vessels, that the distributions of the summary measures are indeed Gaussian, and that attribute values may differ by anatomical location. These results should be useful in designing studies that compare patients with suspected disease to a database of healthy subjects and are relevant to groups interested in atlas formation and in the statistics of tubular objects.

Cerebral Arteries↗
PubMed2005

Automatic segmentation of MR images of the developing newborn brain.

This paper describes an automatic tissue segmentation method for newborn brains from magnetic resonance images (MRI). The analysis and study of newborn brain MRI is of great interest due to its potential for studying early growth patterns and morphological changes in neurodevelopmental disorders. Automatic segmentation of newborn MRI is a challenging task mainly due to the low intensity contrast and the growth process of the white matter tissue. Newborn white matter tissue undergoes a rapid myelination process, where the nerves are covered in myelin sheathes. It is necessary to identify the white matter tissue as myelinated or non-myelinated regions. The degree of myelination is a fractional voxel property that represents regional changes of white matter as a function of age. Our method makes use of a registered probabilistic brain atlas. The method first uses robust graph clustering and parameter estimation to find the initial intensity distributions. The distribution estimates are then used together with the spatial priors to perform bias correction. Finally, the method refines the segmentation using training sample pruning and non-parametric kernel density estimation. Our results demonstrate that the method is able to segment the brain tissue and identify myelinated and non-myelinated white matter regions.

Aging↗
PubMed2005

Hemodynamic and permeability changes in posterior reversible encephalopathy syndrome measured by dynamic susceptibility perfusion-weighted MR imaging.

BACKGROUND AND PURPOSE: The physiological mechanism that gives rise to posterior reversible encephalopathy syndrome (PRES) is currently unknown. We sought to better understand the mechanism of the edema formation in PRES and specifically hypothesized that this edema is caused by increased vascular permeability. METHODS: Eight consecutive patients with PRES who had been studied by using perfusion MR imaging were retrospectively identified. Perfusion images were obtained using a gradient-echo echo planar sequence with contrast enhancement. Measures of apparent diffusion coefficient (ADC), cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT) and vascular permeability (K2) were calculated in the affected posterior brain areas and normalized to values obtained in unaffected anterior brain. These values were compared with those found in healthy subjects. RESULTS: Regions of interest within the posterior affected brain indicated a significant increase in ADC values in all but one patient, a significant decrease in CBV and CBF values in all patients with PRES (average 30% of control), variable changes in MTT, and no measurable change in K2. CONCLUSION: The decrease in both CBV and CBF in PRES supports the theory of autoregulatory vasoconstriction; changes in K2 were not detected.

Adolescent↗
PubMed2004

3 Tesla magnetic resonance imaging of the brain in newborns.

While it has been hypothesized that brain development is abnormal in schizophrenia and other neurodevelopmental disorders, there have been few attempts to study very early brain development in children. Twenty unsedated healthy newborns underwent 3 Tesla magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI). The left ventricle was significantly larger than the right; females had significantly larger ventricles than males. Fractional anisotropy (FA) increased significantly with gestational age in the genu and splenium of the corpus callosum. It is feasible to study brain development in unsedated newborns using 3 T MRI.

Brain↗
PubMed2004

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↗
PubMed2004

Abnormal vessel tortuosity as a marker of treatment response of malignant gliomas: preliminary report.

Despite multiple advances in medical imaging, noninvasive monitoring of therapeutic efficacy for malignant gliomas remains problematic. An underutilized observation is that malignancy induces characteristic abnormalities of vessel shape. These characteristic shape abnormalities affect both capillaries and much larger vessels in the tumor vicinity, involve larger vessels prior to sprout formation, and are generally not present in hypervascular benign tumors. Vessel shape abnormalities associated with malignancy thus may appear independently of increase in vessel density. We hypothesize that an automated, computerized analysis of vessel shape as defined from high-resolution MRA can provide valuable information about tumor activity during the treatment of malignant gliomas. This report describes vessel shape properties in 10 malignant gliomas prior to treatment, in 2 patients in remission during treatment, and in 2 patients with recurrent disease. One subject was scanned multiple times. The method involves an automated, statistical analysis of vessel shape within a region of interest for each tumor, normalized by the values obtained from the vessels within the same region of interest of 34 healthy subjects. Results indicate that untreated tumors display statistically significant vessel tortuosity abnormalities. These abnormalities involve vessels not only within the tumor margins as defined from MR but also vessels in the surrounding tissue. The abnormalities resolve during effective treatment and recur with tumor recurrence. We conclude that vessel shape analysis could provide an important means of assessing tumor activity.

Cerebrovascular Circulation↗
PubMed2003

Rapid perfusion abnormality estimation in acute stroke with temporal correlation analysis.

BACKGROUND AND PURPOSE: Determination of the presence or absence of ischemic penumbra through diffusion-perfusion mismatch requires rapid delineation of both abnormalities. Although singular value decomposition-based perfusion parameter estimation has offered valuable insights into the underlying cerebral hemodynamics, the associated postprocessing procedures have limited its widespread use. We explored the utility of a simple technique to define perfusion abnormality in acute stroke patients. METHODS: Twenty acute stroke patients were studied. The MR dynamic contrast approach was used to obtain cerebral blood flow, cerebral blood volume, and mean transit time (MTT). Temporal correlation was used to correlate 4 reference functions-an arterial input function (AIF), a normal tissue function, a lesion function, and a venous output function-with dynamic contrast MR images, and correlation coefficients (CCs) were calculated pixel by pixel. In addition, chronic-state T2-weighted images were coregistered onto the images acquired acutely for assessing the sensitivity and specificity of CC-defined lesion. RESULTS: Statistically significant differences in cerebral blood flow and MTT were found between CC-defined normal and abnormal tissues with all 4 reference functions used. When the final infarct volume was used as the gold standard, a similar sensitivity between MTT (78%) and AIF (76%) CC-defined lesion was obtained, whereas the specificity was higher for AIF (61%) than that obtained with MTT-defined lesion (52%). CONCLUSIONS: We explored CC maps as a simpler alternative of estimating perfusion abnormality, and results demonstrated the potential clinical utility of a correlation-based technique for estimating brain perfusion status.

Acute Disease↗
PubMed2003

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↗
PubMed2003

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↗
PubMed2003

Evidence-based neuroimaging in acute ischemic stroke.

The imaging work-up of patients with acute neurologic deficits should begin with noncontrast CT to exclude intracerebral hemorrhage. Based on positive results from the NINDS t-PA trial, the overriding objectives of imaging in the selection of patients for t-PA treatment are the detection of hemorrhage and rapid evaluation (speed of imaging). Despite its limited sensitivity for the identification of an ischemic stroke lesion, CT has multiple advantages over MR imaging in the initial diagnostic work-up. Advanced MR techniques promise to provide anatomic, physiologic, and vascular information in a single examination, and the ability to increase treatment specificity and improve outcome. Clinical outcome data are lacking; therefore, the routine use of screening MR imaging before t-PA therapy is not supported. Rigorous validation and correlation to clinical outcomes will be required.

Acute Disease↗
PubMed2003

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↗