Rule-Based Ventral Cavity Multi-organ Automatic Segmentation in CT Scans

We describe a newmethod for the automatic segmentation of multiple organs of the ventral cavity in CT scans. The methodisbasedonasetofrulesthatdeterminetheorderin which theorgansare isolatedand segmented, from the sim- plestonetothemostdifficultone. First,thebodyisisolated from the background. Second, the trachea and the left and right lungsare segmentedbasedon theirair content.Third, thespleenandthekidneys–theorganswithhighbloodcon- tent–aresegmented. Finally,thekidneyissegmentedbased onthesurroundingorganssegmentation. Eachorganisindi- vidually segmentedwitha four-stepprocedure that consists of: 1) definition of an inclusive region of interest; 2) identi- fication of the largest axial cross-section slice; 3) Semoval of background structuresbymorphologicaloperations,and; 4) 3D region growing segmentation. Ourmethod is unique in that ituses the same generic segmentation approach for all organsand in that it relieson the segmentationdifficultyof organs toguide the segmentationprocess. Experimental re- sultson15CTscansoftheVISCERALAnatomy2Challenge trainingdatasetsyieldaDicevolumeoverlapsimilarityscore of 79.1 for the trachea, 97.4 and 97.6 for the left and right lungs, 89.2 for the spleen, and 92.8 for the left kidney. For the5CT scans testdatasets, theDice scoresare97.9,97.0, 85.6, 93.4 and 90.2, respectively. Our method achieved an overallDICE score of 92.8 andwas ranked first among the fivemethodsthatparticipated inthechallenge. Copyright c © by the paper’s authors. Copying permitted only for private and academic purposes

Quantification of bound microbubbles in ultrasound molecular imaging

Molecular markers associated with diseases can be visualized and quantified noninvasively with targeted ultrasound contrast agent (t-UCA) consisting of microbubbles (MBs) that can bind to specific molecular targets. Techniques used for quantifying t-UCA assume that all unbound MBs are taken out of the blood pool few minutes after injection and only MBs bound to the molecular markers remain. However, differences in physiology, diseases, and experimental conditions can increase the longevity of unbound MBs. In such conditions, unbound MBs will falsely be quantified as bound MBs. We have developed a novel technique to distinguish and classify bound from unbound MBs. In the post-processing steps, first, tissue motion was compensated using block-matching (BM) techniques. To preserve only stationary contrast signals, a minimum intensity projection (MinIP) or 20th-percentile intensity projection (PerIP) was applied. The after-flash MinIP or PerIP was subtracted from the before-flash MinIP or PerIP. In this way, tissue artifacts in contrast images were suppressed. In the next step, bound MB candidates were detected. Finally, detected objects were tracked to classify the candidates as unbound or bound MBs based on their displacement. This technique was validated in vitro, followed by two in vivo experiments in mice. Tumors (n = 2) and salivary glands of hypercholesterolemic mice (n = 8) were imaged using a commercially available scanner. Boluses of 100 μL of a commercially available t-UCA targeted to angiogenesis markers and untargeted control UCA were injected separately. Our results show considerable reduction in misclassification of unbound MBs as bound ones. Using our method, the ratio of bound MBs in salivary gland for images with targeted UCA versus control UCA was improved by up to two times compared with unprocessed images

Protective role of chaperone-mediated autophagy against atherosclerosis

Significance Cardiovascular diseases remain the leading cause of death worldwide, with atherosclerosis being the most common source of clinical events. Metabolic changes with aging associate with concurrent increased risk of both type 2 diabetes and cardiovascular disease, with the former further raising the risk of the latter. The activity of a selective type of autophagy, chaperone-mediated autophagy (CMA), decreases with age or upon dietary excesses. Here we study whether reduced CMA activity increases risk of atherosclerosis in mouse models. We have identified that CMA is up-regulated early in response to proatherogenic challenges and demonstrate that reduced systemic CMA aggravates vascular pathology in these conditions. We also provide proof-of-concept support that CMA up-regulation is an effective intervention to reduce atherosclerosis severity and progression

Discriminant analysis of intermediate brain atrophy rates in longitudinal diagnosis of alzheimer's disease

Diagnosing Alzheimer's disease through MRI neuroimaging biomarkers has been used as a complementary marker for traditional clinical markers to improve diagnostic accuracy and also help in developing new pharmacotherapeutic trials. It has been revealed that longitudinal analysis of the whole brain atrophy has the power of discriminating Alzheimer's disease and elderly normal controls. In this work, effect of involving intermediate atrophy rates and impact of using uncorrelated principal components of these features instead of original ones on discriminating normal controls and Alzheimer's disease subjects, is inspected. In fact, linear discriminative analysis of atrophy rates is used to classify subjects into Alzheimer's disease and controls. Leave-one-out cross-validation has been adopted to evaluate the generalization rate of the classifier along with its memorization. Results show that incorporating uncorrelated version of intermediate features leads to the same memorization performance as the original ones but higher generalization rate. As a conclusion, it is revealed that in a longitudinal study, using intermediate MRI scans and transferring them to an uncorrelated feature space can improve diagnostic accuracy

Morphometry Based on Effective and Accurate Correspondences of Localized Patterns (MEACOLP)

Local features in volumetric images have been used to identify correspondences of localized anatomical structures for brain morphometry. However, the correspondences are often sparse thus ineffective in reflecting the underlying structures, making it unreliable to evaluate specific morphological differences. This paper presents a morphometry method (MEACOLP) based on correspondences with improved effectiveness and accuracy. A novel two-level scale-invariant feature transform is used to enhance the detection repeatability of local features and to recall the correspondences that might be missed in previous studies. Template patterns whose correspondences could be commonly identified in each group are constructed to serve as the basis for morphometric analysis. A matching algorithm is developed to reduce the identification errors by comparing neighboring local features and rejecting unreliable matches. The two-sample t-test is finally adopted to analyze specific properties of the template patterns. Experiments are performed on the public OASIS database to clinically analyze brain images of Alzheimer's disease (AD) and normal controls (NC). MEACOLP automatically identifies known morphological differences between AD and NC brains, and characterizes the differences well as the scaling and translation of underlying structures. Most of the significant differences are identified in only a single hemisphere, indicating that AD-related structures are characterized by strong anatomical asymmetry. In addition, classification trials to differentiate AD subjects from NC confirm that the morphological differences are reliably related to the groups of interest

MRI Contrast-enhancement with superparamagnetic iron oxide nanoparticles amplify macrophage foam cell apoptosis in human and murine atherosclerosis

(Ultra) Small superparamagnetic iron oxide nanoparticles, (U)SPIO, are widely used as magnetic resonance imaging contrast media and assumed to be safe for clinical applications in cardiovascular disease. As safety tests largely relied on normolipidemic models, not fully representative of the clinical setting, we investigated the impact of (U)SPIOs on disease-relevant endpoints in hyperlipidemic models of atherosclerosis.RAW264.7 foam cells, exposed in vitro to Ferumoxide (dextran-coated SPIO), Ferumoxtran (dextran-coated USPIO), or Ferumoxytol (carboxymethyl dextran-coated USPIO) (all 1 mg Fe/ml) showed increased apoptosis and ROS accumulation for Ferumoxide and Ferumoxtran, whereas Ferumoxytol was tolerated well. Pro-apoptotic (TUNEL+) and pro-oxidant activity of Ferumoxide (0.3 mg Fe/kg) and Ferumoxtran (1 mg Fe/kg) were confirmed in plaque, spleen, and liver of hyperlipidemic ApoE-/- (n = 9/group) and LDLR-/- (n = 9-16/group) mice that had received single IV injections compared to saline-treated controls. Again, Ferumoxytol treatment (1 mg Fe/kg) failed to induce apoptosis or oxidative stress in these tissues. Concomitant antioxidant treatment (EUK-8/EUK-134) largely prevented these effects in vitro (-68%, P Ferumoxide and Ferumoxtran, but not Ferumoxytol, induced apoptosis of lipid-laden macrophages in human and murine atherosclerosis, potentially impacting disease progression in patients with advanced atherosclerosis.Biopharmaceutic

Carotid Plaque Imaging with SPECT/CT and PET/CT

A major contributor to the occurrence of ischemic stroke is the existence of carotid atherosclerosis. A vulnerable carotid atherosclerotic plaque may rupture or erode, thus causing a thrombotic event. Currently, clinical decision-making with regard to carotid endarterectomy or stenting is still primarily based on the extent of luminal stenosis, estimated with CT angiography and/or (duplex) ultrasonography. However, there is growing evidence that the anatomic impact of stenosis alone has limited value in predicting the exact consequences of plaque vulnerability. Various molecular processes have, independently of degree of stenosis, shown to be importantly associated with the plaque's capability to cause thrombotic events. These molecular processes can be visualized with nuclear medicine techniques allowing the identification of vulnerable patients by non-invasive in vivo SPECT(/CT) and PET(/CT) imaging. This chapter provides an overview of SPECT(/CT) and PET(/CT) imaging with specific radiotracers that have been evaluated for the detection of plaques together with a future perspective in this field of imaging.</p

Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial

Background: An increased rate of brain atrophy is often observed in older subjects, in particular those who suffer from cognitive decline. Homocysteine is a risk factor for brain atrophy, cognitive impairment and dementia. Plasma concentrations of homocysteine can be lowered by dietary administration of B vitamins.Objective: To determine whether supplementation with B vitamins that lower levels of plasma total homocysteine can slow the rate of brain atrophy in subjects with mild cognitive impairment in a randomised controlled trial (VITACOG, ISRCTN 94410159).Methods and Findings: Single-center, randomized, double-blind controlled trial of high-dose folic acid, vitamins B₆ and B₁₂ in 271 individuals (of 646 screened) over 70 y old with mild cognitive impairment. A subset (187) volunteered to have cranial MRI scans at the start and finish of the study. Participants were randomly assigned to two groups of equal size, one treated with folic acid (0.8 mg/d), vitamin B₁₂ (0.5 mg/d) and vitamin B₆ (20 mg/d), the other with placebo; treatment was for 24 months. The main outcome measure was the change in the rate of atrophy of the whole brain assessed by serial volumetric MRI scans.Results: A total of 168 participants (85 in active treatment group; 83 receiving placebo) completed the MRI section of the trial. The mean rate of brain atrophy per year was 0.76% [95% CI, 0.63-0.90] in the active treatment group and 1.08% [0.94-1.22] in the placebo group (P=0.001). The treatment response was related to baseline homocysteine levels: the rate of atrophy in participants with homocysteine &gt; 13μmol/L was 53% lower in the active treatment group (P=0.001). A greater rate of atrophy was associated with a lower final cognitive test scores. There was no difference in serious adverse events according to treatment category.Conclusions and significance: The accelerated rate of brain atrophy in elderly with mild cognitive impairment can be slowed by treatment with homocysteine-lowering B vitamins. Sixteen percent of those over 70 y old have mild cognitive impairment and half of these develop Alzheimer's disease. Since accelerated brain atrophy is a characteristic of subjects with mild cognitive impairment who convert to Alzheimer's disease, trials are needed to see if the same treatment will delay the development of Alzheimer's disease.</p

Molecular imaging of inflammation and intraplaque vasa vasorum: A step forward to identification of vulnerable plaques?

Current developments in cardiovascular biology and imaging enable the noninvasive molecular evaluation of atherosclerotic vascular disease. Intraplaque neovascularization sprouting from the adventitial vasa vasorum has been identified as an independent predictor of intraplaque hemorrhage and plaque rupture. These intraplaque vasa vasorum result from angiogenesis, most likely under influence of hypoxic and inflammatory stimuli. Several molecular imaging techniques are currently available. Most experience has been obtained with molecular imaging using positron emission tomography and single photon emission computed tomography. Recently, the development of targeted contrast agents has allowed molecular imaging with magnetic resonance imaging, ultrasound and computed tomography. The present review discusses the use of these molecular imaging techniques to identify inflammation and intraplaque vasa vasorum to identify vulnerable atherosclerotic plaques at risk of rupture and thrombosis. The available literature on molecular imaging techniques and molecular targets associated with inflammation and angiogenesis is discussed, and the clinical applications of molecular cardiovascular imaging and the use of molecular techniques for local drug delivery are addressed