Lyubomir Zagorchev

A comparative study of transformation functions for nonrigid image registration

Transformation functions play a major role in nonrigid image registration. In this paper, the characteristics of thin-plate spline (TPS), multiquadric (MQ), piecewise linear (PL), and weighted mean (WM) transformations are explored and their performances in nonrigid image registration are compared. TPS and MQ are found to be most suitable when the set of control-point correspondences is not large (fewer than a thousand) and variation in spacing between the control points is not large. When spacing between the control points varies greatly, PL is found to produce a more accurate registration than TPS and MQ. When a very large set of control points is given and the control points contain positional inaccuracies, WM is preferred over TPS, MQ, and PL because it uses an averaging process that smoothes the noise and does not require the solution of a very large system of equations. Use of transformation functions in the detection of incorrect correspondences is also discussed.

Micro computed tomography for vascular exploration.

Vascular exploration of small animals requires imaging hardware with a very high spatial resolution, capable of differentiating large as well as small vessels, in both in vivo and ex vivo studies. Micro Computed Tomography (micro-CT) has emerged in recent years as the preferred modality for this purpose, providing high resolution 3D volumetric data suitable for analysis, quantification, validation, and visualization of results. The usefulness of micro-CT, however, can be adversely affected by a range of factors including physical animal preparation, numerical quantification, visualization of results, and quantification software with limited possibilities. Exacerbating these inherent difficulties is the lack of a unified standard for micro-CT imaging. Most micro-CT today is aimed at particular applications and the software tools needed for quantification, developed mainly by imaging hardware manufacturers, lack the level of detail needed to address more specific aims. This review highlights the capabilities of micro-CT for vascular exploration, describes the current state of imaging protocols, and offers guidelines and suggestions aimed at making micro-CT more accurate, replicable, and robust.

The antiangiogenic activity of rPAI-1(23) inhibits vasa vasorum and growth of atherosclerotic plaque.

Plaque vascularity has been implicated in its growth and stability. However, there is a paucity of information regarding the origin of plaque vasculature and the role of vasa vasorum in plaque growth. To inhibit growth of vasa vasorum in atherogenic mice and assess its effect on plaque growth, we used a truncated plasminogen activator inhibitor (PAI)-1 protein, rPAI-123, that has significant antiangiogenic activity. Female LDLR−/−ApoB-48–deficient mice fed Paigen’s diet without cholate for 20 weeks received rPAI-123 treatment (n=21) for the last 6 weeks. Plaque size and vasa vasorum density were compared to 2 controls: mice fed Paigen’s diet and treated with saline for the last 6 weeks (n=16) and mice fed Paigen’s diet until the onset of treatment (n=14). The rPAI-123 treatment significantly reduced plaque area and plaque cholesterol in the descending aorta and plaque area in the innominate artery. Measurements of reconstructed confocal microscopy images of vasa vasorum demonstrate that rPAI-123 treatment decreased vasa vasorum area and length, which was supported by microCT images. Confocal images provide evidence for vascularized plaque in the saline-treated group but not in rPAI-123–treated mice. The increased vessel density in saline-treated mice is attributable, in part, to upregulated fibroblast growth factor-2 expression, which is inhibited by rPAI-123. In conclusion, rPAI-123 inhibits growth of vasa vasorum, as well as vessels within the adjacent plaque and vessel wall, through inhibition of fibroblast growth factor-2, leading to reduced plaque growth in atherogenic female LDLR−/−ApoB-48–deficient mice.

A paintbrush laser range scanner

A new hand-held laser range scanner is introduced that can capture multi-view range images of an object and integrate the images without registering them. The scanner uses a reference double-frame that acts as the coordinate system of the object. Range images captured from different views of the object are in the coordinate system of the double-frame and, thus, automatically come together. A single-view image is obtained by sweeping a laser line over the object while keeping the camera fixed and analyzing the acquired laser stripes. The laser line generator and the camera can move independently, making it possible to conveniently scan an object just like painting over it with a paintbrush while viewing it from different views. The hardware and software organization of the scanner are described, the characteristics of the scanner are investigated, and example images captured by the scanner are presented.

Differences in Regional Brain Volumes Two Months and One Year after Mild Traumatic Brain Injury

Conventional structural imaging is often normal after mild traumatic brain injury (mTBI). There is a need for structural neuroimaging biomarkers that facilitate detection of milder injuries, allow recovery trajectory monitoring, and identify those at risk for poor functional outcome and disability. We present a novel approach to quantifying volumes of candidate brain regions at risk for injury. Compared to controls, patients with mTBI had significantly smaller volumes in several regions including the caudate, putamen, and thalamus when assessed 2 months after injury. These differences persisted but were reduced in magnitude 1 year after injury, suggesting the possibility of normalization over time in the affected regions. More pronounced differences, however, were found in the amygdala and hippocampus, suggesting the possibility of regionally specific responses to injury.

Molecular imaging of vessels in mouse models of disease

Vascular imaging of angiogenesis in mouse models of disease requires multi modal imaging hardware capable of targeting both structure and function at different physical scales. The three dimensional (3D) structure and function vascular information allows for accurate differentiation between biological processes. For example, image analysis of vessel development in angiogenesis vs. arteriogenesis enables more accurate detection of biological variation between subjects and more robust and reliable diagnosis of disease. In the recent years a number of micro imaging modalities have emerged in the field as preferred means for this purpose. They provide 3D volumetric data suitable for analysis, quantification, validation, and visualization of results in animal models. This review highlights the capabilities of microCT, ultrasound and microPET for multimodal imaging of angiogenesis and molecular vascular targets in a mouse model of tumor angiogenesis. The basic principles of the imaging modalities are described and experimental results are presented.

A Curvature-Adaptive Implicit Surface Reconstruction for Irregularly Spaced Points

A curvature-adaptive implicit surface reconstruction for noisy and irregularly spaced points in 3D is introduced. The reconstructed surface traces the zero crossings of a signed field obtained from the sum of first-derivative anisotropic Gaussians centered at the points. The standard deviations of the anisotropic Gaussians are adapted to surface curvatures estimated from local data. A key characteristic of the formulation is its ability to smooth more along edges than across them, thereby preserving shape details while smoothing noise. The behavior of the proposed method under various density and organization of points is investigated and surface reconstruction results are compared with those obtained by well-known methods in the literature.

Fibroblast Growth Factor-2 Is Required for Vasa Vasorum Plexus Stability in Hypercholesterolemic Mice

Objective—Vasa vasorum are angiogenic in advanced stages of human atherosclerosis and hypercholesterolemic mouse models. Fibroblast growth factor-2 (FGF-2) is the predominant angiogenic growth factor in the adventitia and plaque of hypercholesterolemic low-density lipoprotein receptor–deficient/apolipoprotein B100/100 mice (DKO). FGF-2 seems to play a role in the formation of a distinct vasa vasorum network. This study examined the vasa vasorum structure and its relationship to FGF-2. Methods and Results—DKO mice treated with saline, antiangiogenic recombinant plasminogen activator inhibitor-123 (rPAI-123), or soluble FGF receptor 1 were perfused with fluorescein-labeled Lycopersicon esculentum lectin. Confocal images of FGF-2–probed descending aorta adventitia show that angiogenic vasa vasorum form a plexus-like network in saline-treated DKO similar to the FGF-2 pattern of distribution. Mice treated with rPAI-123 and soluble FGF receptor 1 lack a plexus; FGF-2 and vasa vasorum density and area are significantly reduced. A perlecan/FGF-2 complex is critical for plexus stability. Excess plasmin produced in rPAI-123-treated DKO mice degrades perlecan and destabilizes the plexus. Plasmin activity and plaque size measured in DKO and DKO/plasminogen activator inhibitor-1−/− mice demonstrate that elevated plasmin activity contributes to reduced plaque size. Conclusion—An FGF-2/perlecan complex is required for vasa vasorum plexus stability. Elevated plasmin activity plays a significant inhibitory role in vasa vasorum plexus and plaque development.

Advances in imaging angiogenesis and inflammation in atherosclerosis

Advances in imaging technology have provided powerful tools for dissecting the angiogenic and inflammatory aspects of atherosclerosis. Improved technology along with multi-modal approaches has expanded the utilisation of imaging. Recent advances provide the ability to better define structure and development of angiogenic vessels, identify relationships between inflammatory mediators and the vessel wall, validate biological effects of anti-inflammatory and anti-angiogenic drugs, delivery and/or targeting specific molecules to inflammatory regions of atherosclerotic plaques.

Manual annotation, 3-D shape reconstruction, and traumatic brain injury analysis

Bitmask drawing is still the established standard for manual annotation of brain structures by experts. To alleviate problems such as bitmask inconsistencies between slices that lead to jagged contours in corresponding orthogonal cross-sections, we propose a 2-D spline-based contour editing tool in combination with a new algorithm for surface reconstruction from 3-D point clouds. This approach uses a new implicit surface formulation that adapts to the local density of points. We show that manual segmentation of the brainstem, cerebellum, corpus callosum, caudate, putamen, hippocampus and thalamus can be performed with high reproducibility in Magnetic Resonance (MR) data and sufficient accuracy to analyze volume changes for mild Traumatic Brain Injury (TBI) patients. In addition, we show that the new surface reconstruction method allows to reconstruct the shape of brain structures such as the brainstem better than other established surface reconstruction approaches. Our tool can, therefore, not only be used for volume measurements, but may also be used to assess local shape changes of brain structures going along with the progression of neurodegenerative diseases such as TBI.