Semi-Automatic Graphical Tool for Measuring Coronary Artery Spatially Weighted Calcium Score from Gated Cardiac Computed Tomography Images.

The current standard for measuring coronary artery calcification to determine the extent of atherosclerosis is by calculating the Agatston score from computed tomography (CT). However, the Agatston score disregards pixel values less than 130 Hounsfield Units (HU) and calcium regions less than 1 mm2. Due to this thresholding, the score is not sensitive to small, weakly attenuating regions of calcium deposition and may not detect nascent micro-calcification. A recently proposed metric called the spatially weighted calcium score (SWCS) also utilizes CT but does not include a threshold for HU and does not require elevated signals in contiguous pixels. Thus, the SWCS is sensitive to weakly attenuating, smaller calcium deposits and may improve the measurement of coronary heart disease risk. Currently, the SWCS is underutilized owing to the added computational complexity. To promote translation of the SWCS into clinical research and reliable, repeatable computation of the score, the aim of this study was to develop a semi-automatic graphical tool that calculates both the SWCS and the Agatston score. The program requires gated cardiac CT scans with a calcium hydroxyapatite phantom in the field of view. The phantom allows for deriving a weighting function, from which each pixel's weight is adjusted, allowing for the mitigation of signal variations and variability between scans. With all three anatomical views visible simultaneously, the user traces the course of the four main coronary arteries by placing points or regions of interest. Features such as scroll-to-zoom, double-click to delete, and brightness/contrast adjustment, along with written guidance at every step, make the program user-friendly and easy to use. Once tracing the arteries is complete, the program generates reports, which include the scores and snapshots of any visible calcium. The SWCS may reveal the presence of subclinical disease, which may be used for early intervention and lifestyle changes.

Review of radiographic findings in COVID-19.

The purpose of this study is to review the published literature for the range of radiographic findings present in patients suffering from coronavirus disease 2019 infection. This novel corona virus is currently the cause of a worldwide pandemic. Pulmonary symptoms and signs dominate the clinical picture and radiologists are called upon to evaluate chest radiographs (CXR) and computed tomography (CT) images to assess for infiltrates and to define their extent, distribution and progression. Multiple studies attempt to characterize the disease course by looking at the timing of imaging relative to the onset of symptoms. In general, plain CXR show bilateral disease with a tendency toward the lung periphery and have an appearance most consistent with viral pneumonia. Chest CT images are most notable for showing bilateral and peripheral ground glass and consolidated opacities and are marked by an absence of concomitant pulmonary nodules, cavitation, adenopathy and pleural effusions. Published literature mentioning organ systems aside from pulmonary manifestations are relatively less common, yet present and are addressed in this review. Similarly, publications focusing on imaging modalities aside from CXR and chest CT are sparse in this evolving crisis and are likewise addressed in this review. The role of imaging is examined as it is currently being debated in the medical community, which is not at all surprising considering the highly infectious nature of Severe Acute Respiratory Syndrome coronavirus 2.

Prednisolone-containing liposomes accumulate in human atherosclerotic macrophages upon intravenous administration.

Drug delivery to atherosclerotic plaques via liposomal nanoparticles may improve therapeutic agents' risk-benefit ratios. Our paper details the first clinical studies of a liposomal nanoparticle encapsulating prednisolone (LN-PLP) in atherosclerosis. First, PLP's liposomal encapsulation improved its pharmacokinetic profile in humans (n=13) as attested by an increased plasma half-life of 63h (LN-PLP 1.5mg/kg). Second, intravenously infused LN-PLP appeared in 75% of the macrophages isolated from iliofemoral plaques of patients (n=14) referred for vascular surgery in a randomized, placebo-controlled trial. LN-PLP treatment did however not reduce arterial wall permeability or inflammation in patients with atherosclerotic disease (n=30), as assessed by multimodal imaging in a subsequent randomized, placebo-controlled study. In conclusion, we successfully delivered a long-circulating nanoparticle to atherosclerotic plaque macrophages in patients, whereas prednisolone accumulation in atherosclerotic lesions had no anti-inflammatory effect. Nonetheless, the present study provides guidance for development and imaging-assisted evaluation of future nanomedicine in atherosclerosis. FROM THE CLINICAL EDITOR: In this study, the authors undertook the first clinical trial using long-circulating liposomal nanoparticle encapsulating prednisolone in patients with atherosclerosis, based on previous animal studies. Despite little evidence of anti-inflammatory effect, the results have provided a starting point for future development of nanomedicine in cardiovascular diseases.

Relationship between particulate matter exposure and atherogenic profile in "Ground Zero" workers as shown by dynamic contrast enhanced MR imaging.

In this pilot study, we hypothesize that dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) has the potential to evaluate differences in atherosclerosis profiles in patients subjected to high (initial dust cloud) and low (after 13 September 2001) particulate matter (PM) exposure. Exposure to PM may be associated with adverse health effects leading to increased morbidity. Law enforcement workers were exposed to high levels of particulate pollution after working at "Ground Zero" and may exhibit accelerated atherosclerosis. 31 subjects (28 male) with high (n = 19) or low (n = 12) exposure to PM underwent DCE-MRI. Demographics (age, gender, family history, hypertension, diabetes, BMI, and smoking status), biomarkers (lipid profiles, hs-CRP, BP) and ankle-brachial index (ABI) measures (left and right) were obtained from all subjects. Differences between the high and low exposures were compared using independent samples t test. Using linear forward stepwise regression with information criteria model, independent predictors of increased area under curve (AUC) from DCE-MRI were determined using all variables as input. Confidence interval of 95 % was used and variables with p > 0.1 were eliminated. p < 0.05 was considered significant. Subjects with high exposure (HE) had significantly higher DCE-MRI AUC uptake (increased neovascularization) compared to subjects with lower exposure (LE). (AUC: 2.65 ± 0.63 HE vs. 1.88 ± 0.69 LE, p = 0.016). Except for right leg ABI, none of the other parameters were significantly different between the two groups. Regression model indicated that only HE to PM, CRP > 3.0 and total cholesterol were independently associated with increased neovascularization (in decreasing order of importance, all p < 0.026). HE to PM may increase plaque neovascularization, and thereby potentially indicate worsening atherogenic profile of "Ground Zero" workers.

Tumor angiogenesis phenotyping by nanoparticle-facilitated magnetic resonance and near-infrared fluorescence molecular imaging.

One of the challenges of tailored antiangiogenic therapy is the ability to adequately monitor the angiogenic activity of a malignancy in response to treatment. The α(v)ß(3) integrin, highly overexpressed on newly formed tumor vessels, has been successfully used as a target for Arg-Gly-Asp (RGD)-functionalized nanoparticle contrast agents. In the present study, an RGD-functionalized nanocarrier was used to image ongoing angiogenesis in two different xenograft tumor models with varying intensities of angiogenesis (LS174T > EW7). To that end, iron oxide nanocrystals were included in the core of the nanoparticles to provide contrast for T(2)*-weighted magnetic resonance imaging (MRI), whereas the fluorophore Cy7 was attached to the surface to enable near-infrared fluorescence (NIRF) imaging. The mouse tumor models were used to test the potential of the nanoparticle probe in combination with dual modality imaging for in vivo detection of tumor angiogenesis. Pre-contrast and post-contrast images (4 hours) were acquired at a 9.4-T MRI system and revealed significant differences in the nanoparticle accumulation patterns between the two tumor models. In the case of the highly vascularized LS174T tumors, the accumulation was more confined to the periphery of the tumors, where angiogenesis is predominantly occurring. NIRF imaging revealed significant differences in accumulation kinetics between the models. In conclusion, this technology can serve as an in vivo biomarker for antiangiogenesis treatment and angiogenesis phenotyping.

Regression of inflammation in atherosclerosis by the LXR agonist R211945: a noninvasive assessment and comparison with atorvastatin.

OBJECTIVES: The aim of this study was to noninvasively detect the anti-inflammatory properties of the novel liver X receptor agonist R211945. BACKGROUND: R211945 induces reversal cholesterol transport and modulates inflammation in atherosclerotic plaques. We aimed to characterize with (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) and dynamic contrast-enhanced cardiac magnetic resonance (DCE-CMR) inflammation and neovascularization, respectively, in atherosclerotic plaques with R211945 treatment compared with atorvastatin treatment and a control. METHODS: Twenty-one atherosclerotic New Zealand white rabbits were divided into 3 groups (control, R211945 [3 mg/kg orally], and atorvastatin [3 mg/kg orally] groups). All groups underwent (18)F-FDG-PET/CT and DCE-CMR at baseline and at 1 and 3 months after treatment initiation. Concomitantly, serum metabolic parameters and histology were assessed. For statistical analysis, continuous DCE-CMR and PET/CT outcomes were modeled as linear functions of time by using a linear mixed model, whereas the histological data, animal characteristics data, and nonlinear regression imaging data were analyzed with a 2-tailed Student t test. RESULTS: (18)F-FDG-PET/CT detected a decrease in mean and maximum standard uptake values (SUV) over time in the R211945 group (both p = 0.001), indicating inflammation regression. The atorvastatin group displayed no significant change (p = 0.371 and p = 0.600, respectively), indicating no progression or regression. The control group demonstrated an increase in SUV (p = 0.01 and p = 0.04, respectively), indicating progression. There was a significant interaction between time and group for mean and maximum SUV (p = 0.0003 and p = 0.0016, respectively) . DCE-CMR detected a trend toward difference (p = 0.06) in the area under the curve in the atorvastatin group, suggesting a decrease in neovascularization. There was no significant interaction between time and group (p = 0.6350 and p = 0.8011, respectively). Macrophage and apolipoprotein B immunoreactivity decreased in the R211945 and atorvastatin groups (p < 0.0001 and p = 0.0004, respectively), and R211945 decreased oxidized phospholipid immunoreactivity (p = 0.02). CONCLUSIONS: Noninvasive imaging with (18)F-FDG-PET/CT and DCE-CMR and histological analysis demonstrated significant anti-inflammatory effects of the LXR agonist R211945 compared with atorvastatin. The results suggest a possible role for LXR agonists in the treatment of atherosclerosis.

Comparison of template-matching and singular-spectrum-analysis methods for imaging implanted brachytherapy seeds.

Brachytherapy using small implanted radioactive seeds is becoming an increasingly popular method for treating prostate cancer, in which a radiation oncologist implants seeds in the prostate transperineally under ultrasound guidance. Dosimetry software determines the optimal placement of seeds for achieving the prescribed dose based on ultrasonic determination of the gland boundaries. However, because of prostate movement and distortion during the implantation procedure, some seeds may not be placed in the desired locations; this causes the delivered dose to differ from the prescribed dose. Current ultrasonic imaging methods generally cannot depict the implanted seeds accurately. We are investigating new ultrasonic imaging methods that show promise for enhancing the visibility of seeds and thereby enabling real-time detection and correction of seed-placement errors during the implantation procedure. Real-time correction of seed-placement errors will improve the therapeutic radiation dose delivered to target tissues. In this work, we compare the potential performance of a template-matching method and a previously published method based on singular spectrum analysis for imaging seeds. In particular, we evaluated how changes in seed angle and position relative to the ultrasound beam affect seed detection. The conclusion of the present study is that singular spectrum analysis has better sensitivity but template matching is more resistant to false positives; both perform well enough to make seed detection clinically feasible over a relevant range of angles and positions. Combining the information provided by the two methods may further reduce ambiguities in determining where seeds are located.

Multifunctional nanoemulsion platform for imaging guided therapy evaluated in experimental cancer.

Nanoparticle applications in medicine have seen a tremendous growth in the past decade. In addition to their drug targeting application and their ability to improve bioavailability of drugs, nanoparticles can be designed to allow their detection with a variety of imaging methodologies. In the current study, we developed a multimodal nanoparticle platform to enable imaging guided therapy, which was evaluated in a colon cancer mouse model. This "theranostic" platform is based on oil-in-water nanoemulsions and carries iron oxide nanocrystals for MRI, the fluorescent dye Cy7 for NIRF imaging, and the hydrophobic glucocorticoid prednisolone acetate valerate (PAV) for therapeutic purposes. Angiogenesis-targeted nanoemulsions functionalized with αvß(3)-specific RGD peptides were evaluated, as well. When subcutaneous tumors were palpable, the nanoemulsions were administered at a dose of 30 mg of FeO/kg and 10 mg of PAV/kg. MRI and NIRF imaging showed significant nanoparticle accumulation in the tumors, while tumor growth profiles revealed a potent inhibitory effect in all of the PAV nanoemulsion-treated animals as compared to the ones treated with control nanoemulsions, the free drug, or saline. This study demonstrated that our nanoemulsions, when loaded with PAV, iron oxide nanocrystals, and Cy7, represent a flexible and unique theranostic nanoparticle platform that can be applied for imaging guided therapy of cancer.

Dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI) of atherosclerotic plaque angiogenesis.

Atherosclerosis is a progressive systemic disease of the large arteries characterized by the formation of plaques in the vessel wall. Despite our knowledge of its pathogenesis, many vulnerable plaques still remain undiagnosed while in their asymptomatic phase and manifest for the first time with dramatic clinical events, such as stroke or myocardial infarction. In recent years, it is becoming clearer that sudden clinical events do not necessarily correlate with the degree of luminal obstruction caused by lesions, but rather with plaque composition. In particular, the degree of plaque inflammation is important in the pathogenesis of atherosclerosis and is considered a good marker of high-risk/vulnerable plaques. The presence of inflammatory infiltrate and plaque neovascularization are both histological hallmarks of atherosclerotic plaque inflammation. Therefore, plaque angiogenesis represents an attractive target to try and identify asymptomatic high-risk lesions. Dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI) is a technique that has been used extensively in the past to study the vascularity of tumors and its changes following therapeutic intervention. Recently, delayed and dynamic contrast enhanced (CE) MRI have been proposed as non-invasive tools to study the extent of plaque neovascularization in animals and patients with atherosclerosis. In this review, we will provide a brief introduction on DCE-MRI acquisition and analysis techniques. We will follow this with a description of contrast enhanced MR methods for the detection and quantification of neovasculature in atherosclerosis, with an emphasis on DCE-MRI. Finally, we will examine the current limitations and challenges faced by DCE-MRI and briefly discuss its future applications in the context of atherosclerosis.

Angle-dependent ultrasonic detection and imaging of brachytherapy seeds using singular spectrum analysis.

Transrectal-ultrasound-guided brachytherapy uses small titanium-shelled radioactive seeds to locally treat prostate cancer. During the implantation procedure, needles inserted transperitoneally cause gland movement resulting in seed misplacement and suboptimal dosimetry. In a previous study, an algorithm based on singular spectrum analysis (SSA) applied to envelope-detected ultrasound signals was proposed to determine seed locations [J. Mamou and E. J. Feleppa, J. Acoust. Soc. Am. 121, 1790-1801 (2007)]. Successful implementation of the SSA algorithm could allow correcting dosimetry errors during the implantation procedure. The algorithm demonstrated promise when the seed orientation was parallel to the needle and normal to the ultrasound beam. In this present study, the algorithm was tested when the seed orientation deviated up to 22 degrees from normality. Experimental data from a seed in an ideal environment and in beef were collected with a single-element, spherically focused, 5 MHz transducer. Simulations were designed and evaluated with the algorithm. Finally, objective quantitative scoring metrics were developed to evaluate the algorithm performance and for comparison with B-mode images. The results quantitatively established that the SSA algorithm always outperformed B-mode images and that seeds could be detected accurately up to a deviation of approximately 10 degrees .

Angle-dependent ultrasonic detection and imaging of two types of brachytherapy seeds using singular spectrum analysis.

Brachytherapy to treat prostate cancer uses transrectal ultrasound to guide implantation of titanium-shelled radioactive seeds. Transperitoneal implantation allows errors in placement that cause suboptimal dosimetry. Conventional ultrasound cannot reliably image implanted seeds; therefore, seed misplacements cannot be corrected in the operating room. Previously, an algorithm based on singular spectrum analysis was shown to image palladium seeds better than B-mode ultrasound could. The algorithm is now applied to imaging an iodine seed in gel and in beef tissue as a function of seed angle relative to the incident ultrasound. Results indicate that both seed types are imaged reliably by the algorithm.