Biomedical subjects

David E Sosnovik

Publications and source records attributed to David E Sosnovik.

8 recordsLinked to original sources

PubMed2006

Emerging concepts in molecular MRI.

Molecular magnetic resonance imaging (MRI) offers the potential to image some events at the cellular and subcellular level and many significant advances have recently been witnessed in this field. The introduction of targeted MR contrast agents has enabled the imaging of sparsely expressed biological targets in vivo. Furthermore, high-throughput screens of nanoparticle libraries have identified nanoparticles that act as novel contrast agents and which can be targeted with enhanced diagnostic specificity and range. Another class of magnetic nanoparticles have also been designed to image dynamic events; these act as 'switches' and could be used in vitro, and potentially in vivo, as biosensors. Other specialized MR probes have been developed to image enzyme activity in vivo. Lastly, the use of chemical exchange and off-resonance techniques have been developed, adding another dimension to the broad capabilities of molecular MRI and offering the potential of multispectral imaging. These and other advances in molecular MRI offer great promise for the future and have significant potential for clinical translation.

Animals↗

PubMed2006

Molecular imaging of myocardial infarction.

Molecular tools are rapidly elucidating the molecular and cellular processes underlying myocardial infarction. To further understand these biological processes in vivo, investigators are embracing the burgeoning field of molecular imaging. Here we review important aspects of molecular imaging technology and then devote the majority of the text to studies that shed light on the in vivo pathogenesis of myocardial infarction. In particular, we focus on post-infarction healing and remodeling and discuss molecular imaging of proteolytic activity, angiogenesis, transglutaminase activity, and apoptosis. In the future, novel reporter agents and high-resolution cardiac imaging systems should enable imaging of emerging targets such as activated macrophages and myeloperoxidase activity, as well as stem cell-based and gene therapy-based myocardial regenerative strategies, in both experimental and clinical subjects.

Animals↗

PubMed2006

Noninvasive vascular cell adhesion molecule-1 imaging identifies inflammatory activation of cells in atherosclerosis.

BACKGROUND: Noninvasive imaging of adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) may identify early stages of inflammation in atherosclerosis. We hypothesized that a novel, second-generation VCAM-1-targeted agent with enhanced affinity had sufficient sensitivity to enable real-time detection of VCAM-1 expression in experimental atherosclerosis in vivo, to quantify pharmacotherapy-induced reductions in VCAM-1 expression, and to identify activated cells in human plaques. METHODS AND RESULTS: In vivo phage display in apolipoprotein E-deficient mice identified a linear peptide affinity ligand, VHPKQHR, homologous to very late antigen-4, a known ligand for VCAM-1. This peptide was developed into a multivalent agent detectable by MRI and optical imaging (denoted VINP-28 for VCAM-1 internalizing nanoparticle 28, with 20 times higher affinity than previously reported for VNP). In vitro, VINP-28 targeted all cell types expressing VCAM-1. In vivo, MRI and optical imaging in apolipoprotein E-deficient mice (n=28) after injection with VINP-28 or saline revealed signal enhancement in the aortic root of mice receiving VINP-28 (P<0.05). VINP-28 colocalized with endothelial cells and other VCAM-1-expressing cells, eg, macrophages, and was spatially distinct compared with untargeted control nanoparticles. Atheromata of atorvastatin-treated mice showed reduced VINP-28 deposition and VCAM-1 expression. VINP-28 enhanced early lesions in juvenile mice and resected human carotid artery plaques. CONCLUSIONS: VINP-28 allows noninvasive imaging of VCAM-1-expressing endothelial cells and macrophages in atherosclerosis and spatial monitoring of anti-VCAM-1 pharmacotherapy in vivo and identifies inflammatory cells in human atheromata. This clinically translatable agent could noninvasively detect inflammation in early, subclinical atherosclerosis.

Amino Acid Sequence↗

PubMed2005

Magnetic resonance imaging of cardiomyocyte apoptosis with a novel magneto-optical nanoparticle.

The ability to image cardiomyocyte apoptosis in vivo with high-resolution MRI could facilitate the development of novel cardioprotective therapies. The sensitivity of the novel nanoparticle AnxCLIO-Cy5.5 for cardiomyocyte apoptosis was thus compared in vitro to that of annexin V-FITC and showed a high degree of colocalization. MRI was then performed, following transient coronary artery (LAD) occlusion, in five mice given AnxCLIO-Cy5.5 and in four mice given an identical dose (2 mg Fe/kg) of CLIO-Cy5.5. MR signal intensity and myocardial T2* were evaluated, in vivo, in hypokinetic regions of myocardium in the LAD distribution. Ex vivo fluorescence imaging was performed to confirm the in vivo findings. Myocardial T2* was significantly lower in the mice given AnxCLIO-Cy5.5 (8.1 versus 13.2 ms, P<0.01), and fluorescence target to background ratio was significantly higher (2.1 versus 1.1, P<0.01). This study thus demonstrates the feasibility of obtaining high-resolution MR images of cardiomyocyte apoptosis in vivo with the novel nanoparticle, AnxCLIO-Cy5.5.

Analysis of Variance↗

PubMed2005

Effects of region-of-interest length on estimates of myocardial ultrasonic attenuation and backscatter.

Measurements of tissue properties using an image-based technique that makes use of an external reference may have the potential for practical clinical implementation in echocardiography. The objective of this study was to quantify the ability of this technique to distinguish myocardial attenuation and backscatter properties for specific lengths of the region-of-interest (ROI). We chose to exploit the anisotropic properties of the myocardium as a model for distinguishing tissue with different acoustic properties. Excised lateral wall segments from seven healthy adult sheep hearts were imaged using a commercially available (Philips/ATL) clinical scanner operating in the fundamental imaging mode with a linear array (L 7-4). Statistical and receiver operating characteristic (ROC) analyses were used to evaluate the ability of the video signal analysis method to differentiate midmyocardial from subendocardial regions based on measurements of the acoustic properties for specific lengths of the ROI. Results demonstrate that the ability to distinguish tissue properties increases with ROI length for both slope of attenuation and backscatter coefficient measurements. Statistically significant differences were observed for measurements utilizing the ROI lengths as short as 0.4 cm with corresponding progressively increasing areas under the ROC curves for increasing ROI lengths. [NIH R37 HL40302]

Animals↗

PubMed2004

Value of fat suppression in the MRI evaluation of suspected arrhythmogenic right ventricular dysplasia.

OBJECTIVE: Arrhythmogenic right ventricular dysplasia (ARVD) is characterized by intramyocardial fibrofatty change. Fat suppression performed during conventional spin-echo imaging has been used to confirm fatty infiltration. The utility of fat suppression for enhancing the interpretation of studies of suspected ARVD has not previously been formally tested. We investigated the value of fat suppression for enhancing the interpretation of intramyocardial fatty infiltration. MATERIALS AND METHODS: Twenty-six consecutive patients clinically referred for evaluation of possible ARVD underwent cardiac MRI. Two independent observers reviewed the images retrospectively. Intramyocardial areas (n = 101) that had increased signal intensity relative to normal surrounding myocardium on T1-weighted conventional spin-echo images ("index areas") were identified. The index areas were interpreted for presence of fatty infiltration using two sets of images: The first set was obtained without fat suppression, and the second set was obtained with fat suppression. Agreement between reviewers and confidence of interpretation were determined and compared. RESULTS: Interobserver agreement was measured using a 5-point scale: 1, definitely not fat; 2, probably not fat; 3, equivocal; 4, probably fat; and 5, definitely fat. The resulting kappa values were 0.35 for non-fat-suppressed images and 0.55 for fat-suppressed images. Interobserver kappa increased from 0.67 without fat suppression to 0.90 with fat suppression using a 3-point scale: 1, not fat; 2, equivocal; and 3, fat. Confidence in the diagnosis increased from 7.2 without fat suppression to 8.8 with fat suppression (p < 0.0001) on a 10-point scale ranging from 1, not confident, to 10, very confident. CONCLUSION: The use of fat-suppressed in addition to non-fat-suppressed conventional T1-weighted spin-echo imaging increased interobserver agreement and confidence in diagnosis and evaluation of intramyocardial fatty infiltration in patients who were suspected to have ARVD.

Adolescent↗

PubMed2003

Measurement of radial artery contrast intensity to assess cardiac microbubble behavior.

OBJECTIVES: We sought to determine whether analysis of the contrast signal from the radial artery is better able to reflect changes in left ventricular (LV) microbubble dynamics than the signal from the LV itself. BACKGROUND: Assessment of microbubble behavior from images of the LV may be affected by attenuation from overlying microbubbles and nonuniform background signal intensities. The signal intensity from contrast in a peripheral artery is not affected by these artifacts and may, thus, be more accurate. METHODS: After injection of a contrast bolus into a peripheral vein, signal intensity was followed simultaneously in the LV and radial artery. The measurements were repeated using continuous, triggered, low and high mechanical index harmonic imaging of the LV. RESULTS: Peak and integrated signal intensities ranged from 25 dB and 1550 dB/s, respectively, with radial artery imaging to 5.6 dB and 471 dB/s with ventricular imaging. Although differences in microbubble behavior during the different imaging protocols could be determined from both the LV and radial artery curves, analysis of the radial artery curves yielded more consistent and robust differences. CONCLUSIONS: The signal from microbubbles in the radial artery is not affected by shadowing and is, thus, a more accurate reflection of microbubble behavior in the LV than the signal from the LV itself. This may have important implications for the measurement of myocardial perfusion by contrast echocardiography.

Albumins↗

PubMed2002

Non-invasive imaging of plaque vulnerability: an important tool for the assessment of agents to stabilise atherosclerotic plaques.

Disruption of a vulnerable atherosclerotic plaque is well-recognised as the primary cause of stroke, non-fatal myocardial infarction and sudden cardiac death. Novel therapeutic agents are being developed to stabilise such plaques. The initial evaluation of these drugs would be facilitated by the use of non-invasive imaging techniques to identify vulnerable plaque and document serial changes in plaque stability. The aim of this review is to explain the characteristics of the leading non-invasive imaging modalities and discuss their role in examining the vulnerable plaque. This knowledge will be extremely important for physicians and scientists involved in the clinical evaluation of novel agents to stabilise the vulnerable plaque.

Animals↗