Semiautomatic carotid intraplaque hemorrhage volume measurement using 3D carotid MRI.

Background: Presence of intraplaque hemorrhage (IPH) is a known risk factor for stroke and plaque progression. Accurate and reproducible measurement of IPH volume are required for further risk stratification.

Purpose: To develop a semiautomatic method to measure carotid IPH volume.

Negative Carotid Artery Remodeling in Early Type 2 Diabetes Mellitus and Increased Carotid Plaque Vulnerability in Obesity as Assessed by Magnetic Resonance Imaging.

Background Ischemic stroke from carotid plaque embolism remains a major cause of morbidity in patients with type 2 diabetes mellitus (T2 DM ). However, the effect of early T2 DM and obesity on carotid remodeling and plaque burden remains elusive. We assessed carotid remodeling and plaque composition by carotid magnetic resonance imaging in patients with short-duration T2 DM compared with a sex- and age-matched control group.

Voruciclib, a clinical stage oral CDK9 inhibitor, represses MCL-1 and sensitizes high-risk Diffuse Large B-cell Lymphoma to BCL2 inhibition.

Aberrant regulation of BCL-2 family members enables evasion of apoptosis and tumor resistance to chemotherapy. BCL-2 and functionally redundant counterpart, MCL-1, are frequently over-expressed in high-risk diffuse large B-cell lymphoma (DLBCL). While clinical inhibition of BCL-2 has been achieved with the BH3 mimetic venetoclax, anti-tumor efficacy is limited by compensatory induction of MCL-1.

Imaging of the high-risk carotid plaque: magnetic resonance imaging.

The emergence of the concept of high-risk atherosclerotic plaque has led to considerable interest in noninvasive imaging techniques to identify high-risk features before clinical sequelae. For plaques in the carotid arteries, magnetic resonance imaging has undergone considerable histologic validation to link imaging features to indicators of plaque instability, including plaque burden, intraplaque hemorrhage, fibrous cap disruption, lipid rich necrotic core, and calcification. Recently introduced imaging technologies, especially those focused on three-dimensional imaging sequences, are now poised for integration into the clinical workup of patients with suspected carotid atherosclerosis.

Multidrug Analyses in Patients Distinguish Efficacious Cancer Agents Based on Both Tumor Cell Killing and Immunomodulation.

The vision of a precision medicine-guided approach to novel cancer drug development is challenged by high intratumor heterogeneity and interpatient diversity. This complexity is rarely modeled accurately during preclinical drug development, hampering predictions of clinical drug efficacy. To address this issue, we developed Comparative In Vivo Oncology (CIVO) arrayed microinjection technology to test tumor responsiveness to simultaneous microdoses of multiple drugs directly in a patient's tumor.

Semi-automatic carotid intraplaque hemorrhage detection and quantification on Magnetization-Prepared Rapid Acquisition Gradient-Echo (MP-RAGE) with optimized threshold selection.

Background: Intraplaque hemorrhage (IPH) is associated with atherosclerosis progression and subsequent cardiovascular events. We sought to develop a semi-automatic method with an optimized threshold for carotid IPH detection and quantification on MP-RAGE images using matched histology as the gold standard.

Methods: Fourteen patients scheduled for carotid endarterectomy underwent 3D MP-RAGE cardiovascular magnetic resonance (CMR) preoperatively.

A Platform for Rapid, Quantitative Assessment of Multiple Drug Combinations Simultaneously in Solid Tumors In Vivo.

While advances in high-throughput screening have resulted in increased ability to identify synergistic anti-cancer drug combinations, validation of drug synergy in the in vivo setting and prioritization of combinations for clinical development remain low-throughput and resource intensive. Furthermore, there is currently no viable method for prospectively assessing drug synergy directly in human patients in order to potentially tailor therapies. To address these issues we have employed the previously described CIVO platform and developed a quantitative approach for investigating multiple combination hypotheses simultaneously in single living tumors.

Summary of clinical and laboratory data of study subjects with and without DCE-MRI plaque measurements in the AIM-HIGH clinical trial.

This brief data article summarizes the clinical risk factors and laboratory data of a group of subjects recruited for the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes) and an associated magnetic resonance imaging (MRI) substudy. The sample is restricted to those on statin therapy at the time of enrollment and data are presented stratified by whether dynamic contrast enhanced MRI (DCE-MRI) markers of carotid plaque vascularity and inflammation were available or not. The data provided herein are directly related to the article "Longer Duration of Statin Therapy is Associated with Decreased Carotid Plaque Vascularity by Magnetic Resonance Imaging" [2].

In Vivo Validation of Simultaneous Non-Contrast Angiography and intraPlaque Hemorrhage (SNAP) Magnetic Resonance Angiography: An Intracranial Artery Study.

Objectives: Simultaneous Non-contrast Angiography and intraPlaque hemorrhage (SNAP) technique was recently proposed for joint MRA and intraplaque hemorrhage (IPH) imaging. The purpose of this study is to validate SNAP's MRA performance in patients with suspected intracranial artery disease.

Methods: SNAP and time-of-flight (TOF) techniques with matched field of view and resolution were applied on 15 patients with suspected intracranial artery disease.

Longer duration of statin therapy is associated with decreased carotid plaque vascularity by magnetic resonance imaging.

Objective: Plaque neovasculature is a major route for lipoprotein and leukocyte ingress into plaques, and has been identified as a risk factor for carotid plaque disruption. Vp, a variable derived from pharmacokinetic modeling of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), correlates with plaque neovasculature density. Because lipid-lowering therapy has been associated with regression of neovasculature in animal models, we sought to determine clinical correlates of carotid plaque neovasculature (as assessed by Vp) in participants on statin therapy for established cardiovascular disease.

Modeling hemodynamic forces in carotid artery based on local geometric features.

Hemodynamic wall shear stress (WSS) plays an important role in the initiation and progression of carotid atherosclerosis. This study aims at developing a technique to model WSS distribution based on point-wise geometric features that can be efficiently computed. Computational fluid dynamic analysis was performed for ten subjects.

Minimally invasive in tumor multidrug comparative analysis with contrast-enhanced MRI in mice.

Purpose: To facilitate decision making in the oncology clinic, technologies have recently been developed to independently inject and assess multiple anticancer agents directly in a patient's tumor. To increase the flexibility of this approach beyond histological readouts of response, contrast-enhanced MRI was evaluated for the detection of cell death in living tumors after injection.

Methods: A six-needle arrayed microinjection device designed to provide head-to-head comparisons of chemotherapy responses in living tumors was used.

High resolution FDG-microPET of carotid atherosclerosis: plaque components underlying enhanced FDG uptake.

This study sought to discover which atherosclerotic plaque components co-localize with enhanced [(18)F]-fluorodeoxyglucose (FDG) uptake in carotid positron emission tomography (PET) images. Although in vivo PET currently lacks the resolution, high-resolution ex vivo FDG-microPET with histology validation of excised carotid plaque might accomplish this goal. Thirteen patients were injected with FDG before carotid endarterectomy.

Albumin-bound nanoparticle (nab) paclitaxel exhibits enhanced paclitaxel tissue distribution and tumor penetration.

Purpose: nab-paclitaxel demonstrates improved clinical efficacy compared with conventional Cremophor EL (CrEL)-paclitaxel in multiple tumor types. This study explored the distinctions in drug distribution between nab-paclitaxel and CrEL-paclitaxel and the underlying mechanisms.

Methods: Uptake and transcytosis of paclitaxel were analyzed by vascular permeability assay across human endothelial cell monolayers.

In vivo semi-automatic segmentation of multicontrast cardiovascular magnetic resonance for prospective cohort studies on plaque tissue composition: initial experience.

Automatic in vivo segmentation of multicontrast (multisequence) carotid magnetic resonance for plaque composition has been proposed as a substitute for manual review to save time and reduce inter-reader variability in large-scale or multicenter studies. Using serial images from a prospective longitudinal study, we sought to compare a semi-automatic approach versus expert human reading in analyzing carotid atherosclerosis progression. Baseline and 6-month follow-up multicontrast carotid images from 59 asymptomatic subjects with 16-79 % carotid stenosis were reviewed by both trained radiologists with 2-4 years of specialized experience in carotid plaque characterization with MRI and a previously reported automatic atherosclerotic plaque segmentation algorithm, referred to as morphology-enhanced probabilistic plaque segmentation (MEPPS).

A technology platform to assess multiple cancer agents simultaneously within a patient's tumor.

A fundamental problem in cancer drug development is that antitumor efficacy in preclinical cancer models does not translate faithfully to patient outcomes. Much of early cancer drug discovery is performed under in vitro conditions in cell-based models that poorly represent actual malignancies. To address this inconsistency, we have developed a technology platform called CIVO, which enables simultaneous assessment of up to eight drugs or drug combinations within a single solid tumor in vivo.

Scan-rescan reproducibility of quantitative assessment of inflammatory carotid atherosclerotic plaque using dynamic contrast-enhanced 3T CMR in a multi-center study.

Background: The aim of this study is to investigate the inter-scan reproducibility of kinetic parameters in atherosclerotic plaque using dynamic contrast-enhanced (DCE) cardiovascular magnetic resonance (CMR) in a multi-center setting at 3T.

Methods: Carotid arteries of 51 subjects from 15 sites were scanned twice within two weeks on 3T scanners using a previously described DCE-CMR protocol. Imaging data with protocol compliance and sufficient image quality were analyzed to generate kinetic parameters of vessel wall, expressed as transfer constant (K trans ) and plasma volume (v p ).

Atherosclerotic plaque inflammation quantification using dynamic contrast-enhanced (DCE) MRI.

Inflammation plays an important role in atherosclerosis. Given the increasing interest in using in-vivo imaging methods to study the physiology and treatment effects in atherosclerosis, noninvasive intraplaque inflammation quantitative method is needed. Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) has been proposed and validated to quantitatively characterize atherosclerotic plaque inflammation.

Relationships between local geometrical features and hemodynamic flow properties.

Stroke is among the leading causes of death and disability worldwide. Most strokes are ischemic, mostly caused by the blockage of a cerebral artery by a thrombotic embolus. Carotid atherosclerosis and the subsequent plaque rupture can be a major source of these emboli.

A framework for the co-registration of hemodynamic forces and atherosclerotic plaque components.

Local hemodynamic forces, such as wall shear stress (WSS), are thought to trigger cellular and molecular mechanisms that determine atherosclerotic plaque vulnerability to rupture. Magnetic resonance imaging has emerged as a powerful tool to characterize human carotid atherosclerotic plaque composition and morphology, and to identify plaque features shown to be key determinants of plaque vulnerability. Image-based computational fluid dynamics has allowed researchers to obtain time-resolved WSS information of atherosclerotic carotid arteries.

Adventitial perfusion and intraplaque hemorrhage: a dynamic contrast-enhanced MRI study in the carotid artery.

Background And Purpose: Autopsy studies have suggested a relationship between intraplaque hemorrhage (IPH) and vasa vasorum, which arise primarily from the adventitia. Adventitial vasa vasorum can be characterized in the carotid arteries by estimating perfusion parameters via dynamic contrast-enhanced MRI. The purpose of this investigation was to use dynamic contrast-enhanced MRI to test in vivo in a clinical population whether adventitial perfusion, indicative of vasa vasorum microstructure, is associated with IPH.

MRI of carotid atherosclerosis.

Objective: Although MRI is widely used to observe atherosclerosis impacts on the vessel lumen, MRI also depicts the size of the plaque itself, its composition, and plaque inflammation, providing information beyond simple stenosis. This article summarizes the state of evidence for a clinical role for MRI of carotid atherosclerosis.

Conclusion: MRI of carotid atherosclerosis has a proven role in pharmaceutical trials and may improve patient management once large-scale clinical trials have been completed.

Carotid artery disease and stroke: assessing risk with vessel wall MRI.

Although MRI is widely used to diagnose stenotic carotid arteries, it also detects characteristics of the atherosclerotic plaque itself, including its size, composition, and activity. These features are emerging as additional risk factors for stroke that can be feasibly acquired clinically. This paper summarizes the state of evidence for a clinical role for MRI of carotid atherosclerosis.

Utilizing imaging tools in lipidology: examining the potential of MRI for monitoring cholesterol therapy.

Lipid abnormalities play important roles in the development of atherosclerosis. Lipid therapies result in alterations in atherosclerotic plaques including halting of progression of the plaque, lipid transport out of the plaque and reducing inflammatory activity, which lead to plaque morphologies that are less prone to disruption, the main cause of clinical events. In order to investigate and monitor plaque morphological changes during lipid therapy in vivo we need an imaging method that can provide accurate assessment of plaque tissue components and activity.

Mapping contrast agent uptake and retention in MRI studies of myocardial perfusion: case control study of dogs with Duchenne muscular dystrophy.

Myocardial perfusion studies using dynamic contrast-enhanced cardiac magnetic resonance imaging (CMRI) could provide valuable, quantitative information regarding heart physiology in diseases such as Duchenne muscular dystrophy (DMD), that lead to diffuse myocardial damage. The goal of this effort was to develop an intuitive but physiologically meaningful method for quantifying myocardial perfusion by CMRI and to test its ability to detect global myocardial differences in a dog model of DMD. A discrete-time model was developed that parameterizes contrast agent kinetics in terms of an uptake coefficient that describes the forward flux of contrast agent into the tissue, and a retention coefficient that describes the rate of decay in tissue concentration due to contrast agent efflux.