Lower attenuation and higher kurtosis of coronary artery calcification associated with vulnerable plaque - an agatston score propensity-matched CT radiomics study.

BACKGROUND: Coronary artery calcification (CAC) burden assessed by Agatston score (AS) is currently recommended to stratify patients at risk for future acute coronary syndrome (ACS). Besides the CAC burden, the biostructure of CAC may also play a vital role in the vulnerability of CAC, which CT radiomics could reveal. Propensity-score matching of the traditional risk factors and CAC burden between the ACS and asymptomatic groups could radically remove biases and allow the exploration of characteristic features of CAC in ACS. METHODS: We retrospectively identified 77 patients with ACS who had a CAC scan before percutaneous coronary intervention between 2016 and 2019. These 77 patients were one-to-two propensity-score matched for traditional risk factors of ACS and AS ranks to select 154 subjects from 2890 asymptomatic subjects. A validation cohort of 30 subjects was also enrolled. Radiomics features of each plaque were extracted and averaged in each person. Conditional logistic regression and area-under-curve analysis were used for statistical analysis. RESULTS: A higher number of coronary segments involved, lower mean, median, first quartile, and standard deviation of attenuation, and increased kurtosis of attenuation of CAC were associated with the ACS group compared to the control group (p < 0.05 for all). Multivariable analysis showed that the lower median attenuation (OR = 0.969, p < 0.001) and higher Kurtosis (OR = 18.7, p < 0.001) were associated with the ACS group. The median attenuation and kurtosis significantly increase across AS ranks 1 to 4 (p = 0.001). The AUC of kurtosis (0.727) and median attenuation (0.66) were both significantly higher than that of the standard AS (AUC = 0.502) and the number of TRF (AUC = 0.537). The best cut-off of kurtosis at 2.74 yielded an accuracy of 74%, and the cut-off of median attenuation at 196 yielded an accuracy of 68%. The accuracy of kurtosis was 64%, and the accuracy of median attenuation was 55% in the validation cohort. CONCLUSION: After propensity-matching traditional risk factors and CAC burden, CT radiomics highlighted that lower median attenuation and higher kurtosis were the CAC characteristics of vulnerable plaques. These features improve the understanding of the biomechanics of CAC evolution and enhance the value of CAC scan in ACS risk assessment.

ACR Appropriateness Criteria® Suspected Acute Aortic Syndrome.

Acute aortic syndrome (AAS) includes the entities of acute aortic dissection, intramural hematoma, and penetrating atherosclerotic ulcer. AAS typically presents with sudden onset of severe, tearing, anterior, or interscapular back pain. Symptoms may be dominated by malperfusion syndrome, due to obstruction of the lumen of the aorta and/or a side branch when the intimal and medial layers are separated. Timely diagnosis of AAS is crucial to permit prompt management; for example, early mortality rates are reported to be 1% to 2% per hour after the onset of symptoms for untreated ascending aortic dissection. The appropriateness assigned to each imaging procedure was based on the ability to obtain key information that is used to plan open surgical, endovascular, or medical therapy. This includes, but is not limited to, confirming the presence of AAS; classification; characterization of entry and reentry sites; false lumen patency; and branch vessel compromise. Using this approach, CT, CTA, and MRA are all considered usually appropriate in the initial evaluation of AAS if those procedures include intravenous contrast administration. Ultrasound is also considered usually appropriate if the acquisition is via a transesophageal approach. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Asymptomatic Patient at Risk for Coronary Artery Disease: 2021 Update.

Coronary atherosclerotic disease is a leading cause of mortality and morbidity due to major cardiovascular events in the United States and abroad. Risk stratification and early preventive measures can reduce major cardiovascular events given the long latent asymptomatic period. Imaging tests can detect subclinical coronary atherosclerosis and aid initiation of targeted preventative efforts based on patient risk. A summary of available imaging tests for low-, intermediate-, and high-risk asymptomatic patients is outlined in this document. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Blunt Chest Trauma-Suspected Cardiac Injury.

Blunt cardiac injuries range from myocardial concussion (commotio cordis) leading to fatal ventricular arrhythmias to myocardial contusion, cardiac chamber rupture, septal rupture, pericardial rupture, and valvular injuries. Blunt injuries account for one-fourth of the traumatic deaths in the United States. Chest radiography, transthoracic echocardiography, CT chest with and without contrast, and CT angiography are usually appropriate as the initial examination in patients with suspected blunt cardiac injury who are both hemodynamically stable and unstable. Transesophageal echocardiography and CT heart may be appropriate as examination in patients with suspected blunt cardiac injuries. This publication of blunt chest trauma-suspected cardiac injuries summarizes the literature and makes recommendations for imaging based on the available data and expert opinion. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

The novel coronavirus disease (COVID-19) complicated by pulmonary embolism and acute respiratory distress syndrome.

Acute respiratory distress syndrome and coagulopathy played an important role in morbidity and mortality of severe COVID-19 patients. A higher frequency of pulmonary embolism (PE) than expected in COVID-19 patients was recently reported. The presenting symptoms for PE were untypical including dyspnea, which is one of the major symptoms in severe COVID-19, especially in those patients with acute respiratory distress syndrome (ARDS). We reported two COVID-19 cases with coexisting complications of PE and ARDS, aiming to consolidate the emerging knowledge of this global health emergency and raise the awareness that the hypoxemia or severe dyspnea in COVID-19 may be related to PE and not necessarily always due to the parenchymal disease.

Endothelial Activation, Innate Immune Activation, and Inflammation Are Associated With Postbronchodilator Airflow Limitation and Obstruction Among Adolescents Living With HIV.

BACKGROUND: Chronic inflammation, innate immune activation, T-cell imbalance and endothelial activation have been linked with lung diseases. We sought to determine whether markers of these pathophysiologic pathways were associated with spirometry and chest computed tomography (CT) abnormalities among adolescents living with HIV (ALWH). SETTING: Coptic Hope Center for Infectious Diseases in Nairobi, Kenya. METHODS: We performed a cross-sectional study of ALWH (10-19 years old). Participants underwent chest CT, spirometry, and venipuncture for serum biomarkers. We also collected demographic, anthropometric, T-cell subset, antiretroviral therapy, and exposure data. We compared characteristics and biomarkers by airflow obstruction [postbronchodilator FEV1/FVC z-score (zFEV1/FVC) < -1.64]. We used multivariable linear regression to determine associations of log10-transformed biomarkers and chest CT abnormalities with lower postbronchodilator zFEV1/FVC (airflow limitation). We performed exploratory principal components analysis on biomarkers, and determined associations of factors with postbronchodilator zFEV1/FVC and chest CT abnormalities. RESULTS: Of 47 participants with acceptable quality spirometry, 21 (45%) were female, median age was 13 years and 96% had perinatally-acquired HIV. Median CD4 was 672 cells/µL. Overall, 28% had airflow obstruction and 78% had a chest CT abnormality; airflow obstruction was associated with mosaic attenuation (P = 0.001). Higher endothelial activation (sVCAM-1, sICAM-1), inflammation and innate immune activation (serum amyloid-A, sTREM-1, sCD163), and T-cell imbalance (lower CD4/CD8) markers were associated with airflow limitation. Factors comprising endothelial and innate immune activation were associated with airflow limitation. CONCLUSIONS: Endothelial activation, innate immune activation, T-cell imbalance, and chronic inflammation are associated with airflow limitation and obstruction, providing insights into chronic lung disease pathophysiology among ALWH.

Radiologic computed tomography features of Mycobacterium abscessus in cystic fibrosis.

INTRODUCTION: Mycobacterium abscessus infection in cystic fibrosis (CF) patients can lead to poor outcomes. Early diagnosis is important, but there are no studies outlining specific imaging features of M. abscessus in CF. OBJECTIVES: To describe the computed tomography (CT) findings of early M. abscessus infection in our CF population. METHODS: Thirteen CF patients with sputum cultures positive for M. abscessus from 2006 to 2013 were identified at our institution. Clinical characteristics including culture dates and lung function were reviewed. Positive cultures were classified as "disease" versus "colonization" based on published criteria. Chest CT scans were reviewed at times closest to initial infection, and features including bronchiectasis, mucous plugging, consolidation, ground glass opacities, nodules, and cavitation were evaluated. Brody scores were calculated to evaluate extent of CF lung disease. RESULTS: All patients had bronchiectasis and mucous plugging, with 10 of 13 (76.9%) in an upper lobe distribution. Consolidation was seen in 12 of 13 (92.3%) patients, 8 (61.5%) patients had nodules, and 5 (38.5%) with cavitation. The average Brody score was 59.5, which was no different than previously described CF cohorts without M. abscessus. There were no significant differences between subjects with disease versus colonization. CONCLUSION: The most common CT features of early M. abscessus in our CF population include bronchiectasis, mucus plugging, and consolidation, but the findings did not reveal a unique radiologic signature. CT at this initial time point may not distinguish early M. abscessus infection from background lung disease or mycobacterial colonization in CF patients.

Tracheal diverticula in advanced cystic fibrosis: Prevalence, features, and outcomes after lung transplantation.

BACKGROUND: Tracheal diverticula (TD) are rare anomalies that may harbor infected secretions, posing potential risk to patients with lung disease. In an end-stage cystic fibrosis (CF) cohort, we describe the characteristics and associated post-lung transplant (LTx) outcomes of TD. METHODS: Pre-transplant computed tomography (CT)'s were reviewed in CF patients undergoing LTx. TD were characterized radiographically and on autopsy when available. Pre-transplant clinical variables and post-transplant outcomes were compared by TD status. RESULTS: Of 93 patients, 35 (37.6%) had TD. 58% of TD had fat-stranding, and post-mortem TD examinations revealed histology carrying intense submucosal inflammation, and purulent contents that cultured identical species to sputum. There was no difference in post-LTx survival [HR 1.77 (0.82-3.82), p=0.147], bacterial re-colonization, or rejection in patients with TD compared to those without. Patients with TD were more likely to die from infection, but the result was not statistically significant [HR 2.02 (0.62-6.63), p=0.245]. CONCLUSIONS: We found a high prevalence of TD in end-stage CF, where diverticula may represent a large-airway bacterial reservoir. TD were not associated with differences in post-LTx outcomes, but given the infectious concerns further investigation is necessary.

ACR Appropriateness Criteria® Chronic Chest Pain-High Probability of Coronary Artery Disease.

In patients with chronic chest pain in the setting of high probability of coronary artery disease (CAD), imaging has major and diverse roles. First, imaging is valuable in determining and documenting the presence, extent, and severity of myocardial ischemia, hibernation, scarring, and/or the presence, site, and severity of obstructive coronary lesions. Second, imaging findings are important in determining the course of management of patients with suspected chronic myocardial ischemia and better defining those patients best suited for medical therapy, angioplasty/stenting, or surgery. Third, imaging is also necessary to determine the long-term prognosis and likely benefit from various therapeutic options by evaluating ventricular function, diastolic relaxation, and end-systolic volume. Imaging studies are also required to demonstrate other abnormalities, such as congenital/acquired coronary anomalies and severe left ventricular hypertrophy, that can produce angina in the absence of symptomatic coronary obstructive disease due to atherosclerosis. Clinical risk assessment is necessary to determine the pretest probability of CAD. Multiple methods are available to categorize patients as low, medium, or high risk for developing CAD. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Imaging of Heart Disease in Women.

Ischemic heart disease is the number one cause of death of women in the United States, accounting for over a quarter of a million annual female deaths. Evidence within the last several decades supports sex-specific differences in the prevalence, symptoms, and prognosis of ischemic heart disease between men and women. Despite women having a lower burden of obstructive coronary artery disease compared with men, the prevalence of angina and mortality from ischemic heart disease is higher for women than men. In addition to ischemic heart disease, certain nonischemic conditions may also have sex-specific differences in clinical presentation and occurrence. With the rising utilization of noninvasive modalities for the diagnosis and management of ischemic heart disease, it is important for radiologists to be familiar with the unique considerations for imaging women with heart disease. The purpose of this review is to discuss challenges for detection of heart disease in women, examine performance of noninvasive modalities in the detection of ischemic heart disease, and discuss nonischemic cardiomyopathies unique to or prevalent in women. Considerations for cardiac imaging in pregnancy are also discussed. © RSNA, 2017.

The direct incorporation of perfusion defect information to define ischemia and infarction in a finite element model of the left ventricle.

This paper describes the process in which complex lesion geometries (specified by computer generated perfusion defects) are incorporated in the description of nonlinear finite element (FE) mechanical models used for specifying the motion of the left ventricle (LV) in the 4D extended cardiac torso (XCAT) phantom to simulate gated cardiac image data. An image interrogation process was developed to define the elements in the LV mesh as ischemic or infarcted based upon the values of sampled intensity levels of the perfusion maps. The intensity values were determined for each of the interior integration points of every element of the FE mesh. The average element intensity levels were then determined. The elements with average intensity values below a user-controlled threshold were defined as ischemic or infarcted depending upon the model being defined. For the infarction model cases, the thresholding and interrogation process were repeated in order to define a border zone (BZ) surrounding the infarction. This methodology was evaluated using perfusion maps created by the perfusion cardiac-torso (PCAT) phantom an extension of the 4D XCAT phantom. The PCAT was used to create 3D perfusion maps representing 90% occlusions at four locations (left anterior descending (LAD) segments 6 and 9, left circumflex (LCX) segment 11, right coronary artery (RCA) segment 1) in the coronary tree. The volumes and shapes of the defects defined in the FE mechanical models were compared with perfusion maps produced by the PCAT. The models were incorporated into the XCAT phantom. The ischemia models had reduced stroke volume (SV) by 18-59 ml. and ejection fraction (EF) values by 14-50% points compared to the normal models. The infarction models, had less reductions in SV and EF, 17-54 ml. and 14-45% points, respectively. The volumes of the ischemic/infarcted regions of the models were nearly identical to those volumes obtained from the perfusion images and were highly correlated (R² = 0.99).

Magnetic resonance imaging safety in cardiothoracic imaging.

Patient safety is a priority for patients undergoing magnetic resonance imaging (MRI). This article reviews MRI safety issues related to devices, pharmacologic stress agents, contrast agents, anesthesia, and external equipment, focusing on cardiothoracic MRI.

Plasmodium falciparum purine nucleoside phosphorylase: crystal structures, immucillin inhibitors, and dual catalytic function.

Purine nucleoside phosphorylase from Plasmodium falciparum (PfPNP) is an anti-malarial target based on the activity of Immucillins. The crystal structure of PfPNP.Immucillin-H (ImmH).SO(4) reveals a homohexamer with ImmH and SO(4) bound at each catalytic site. A solvent-filled cavity close to the 5'-hydroxyl group of ImmH suggested that PfPNP can accept additional functional groups at the 5'-carbon. Assays established 5'-methylthioinosine (MTI) as a substrate for PfPNP. MTI is not found in human metabolism. These properties of PfPNP suggest unusual purine pathways in P. falciparum and provide structural and mechanistic foundations for the design of malaria-specific transition state analogue inhibitors. 5'-Methylthio-Immucillin-H (MT-ImmH) was designed to resemble the transition state of PfPNP and binds to PfPNP and human-PNP with K(d) values of 2.7 and 303 nm, respectively, to give a discrimination factor of 112. MT-ImmH is the first inhibitor that favors PfPNP inhibition. The structure of PfPNP.MT-ImmH.SO(4) shows that the hydrophobic methylthio group inserts into a hydrophobic region adjacent to the more hydrophilic 5'-hydroxyl binding site of ImmH. The catalytic features of PfPNP indicate a dual cellular function in purine salvage and polyamine metabolism. Combined metabolic functions in a single enzyme strengthen the rationale for targeting PfPNP in anti-malarial action.

Effect of dietary p-aminobenzoic acid on murine Plasmodium yoelii infection.

Plasmodia species, unlike humans, can utilize p-aminobenzoic acid (PABA) for the de novo generation of folate. Plasmodial enzymes for the synthesis of PABA via the shikimate pathway are being investigated as novel targets for malaria chemotherapy. We show that, despite the presence of biosynthetic machinery to synthesize PABA, Plasmodium yoelii, a rodent malaria species, requires exogenous dietary PABA for survival. Mice fed low-PABA diets do not die from lethal doses of P. yoelii. The initiation of a PABA-deficient diet after P. yoelii infection is established leads to the clearance of parasites and subsequent resistance to infection by P. yoelii. An intact immune system is not necessary for protection, given that mice with severe combined immunodeficiency were also protected by PABA-deficient diet. Our studies suggest that the PABA content in the diet will affect the host clearance of malaria parasites and may affect the efficacy of treatments that target the shikimate pathway.

8-Aza-immucillins as transition-state analogue inhibitors of purine nucleoside phosphorylase and nucleoside hydrolases.

The 8-aza-immucillins (8-aza-9-deazapurines linked from C9 to C1 of 1,4-dideoxy-1,4-iminoribitol) have been designed as transition-state analogues of the reactions catalyzed by purine nucleoside phosphorylase and nucleoside hydrolases. Syntheses of the 8-aza-immucillin analogues of inosine and adenosine are described. They are powerful inhibitors of the target enzymes with equilibrium dissociation constants as low as 42 pM.

Purine-less death in Plasmodium falciparum induced by immucillin-H, a transition state analogue of purine nucleoside phosphorylase.

Plasmodium falciparum is responsible for the majority of life-threatening cases of malaria. Plasmodia species cannot synthesize purines de novo, whereas mammalian cells obtain purines from de novo synthesis or by purine salvage. Hypoxanthine is proposed to be the major source of purines for P. falciparum growth. It is produced from inosine phosphorolysis by purine nucleoside phosphorylase (PNP). Immucillins are powerful transition state analogue inhibitors of mammalian PNP and also inhibit P. falciparum PNP as illustrated in the accompanying article (Kicska, G. A., Tyler, P. C., Evans, G. B., Furneaux, R. H., Kim, K., and Schramm, V. L. (2002) J. Biol. Chem. 277, 3219-3225). This work tests the hypothesis that erythrocyte and P. falciparum PNP are essential elements for growth and survival of the parasite in culture. Immucillin-H reduces the incorporation of inosine but not hypoxanthine into nucleic acids of P. falciparum and kills P. falciparum cultured in human erythrocytes with an IC(50) of 35 nm. Growth inhibition by Imm-H is reversed by the addition of hypoxanthine but not inosine, demonstrating the metabolic block at PNP. The concentration of Imm-H required for inhibition of parasite growth varies as a function of culture hematocrit, reflecting stoichiometric titration of human erythrocyte PNP by the inhibitor. Human and P. falciparum PNPs demonstrate different specificity for inhibition by immucillins, with the 2'-deoxy analogues showing marked preference for the human enzyme. The IC(50) values for immucillin analogue toxicity to P. falciparum cultures indicate that inhibition of PNP in both the erythrocytes and the parasite is necessary to induce a purine-less death.

Transition state analogue inhibitors of purine nucleoside phosphorylase from Plasmodium falciparum.

Immucillins are logically designed transition-state analogue inhibitors of mammalian purine nucleoside phosphorylase (PNP) that induce purine-less death of Plasmodium falciparum in cultured erythrocytes (Kicska, G. A., Tyler, P. C., Evans, G. B., Furneaux, R. H., Schramm, V. L., and Kim, K. (2002) J. Biol. Chem. 277, 3226-3231). PNP is present at high levels in human erythrocytes and in P. falciparum, but the Plasmodium enzyme has not been characterized. A search of the P. falciparum genome data base yielded an open reading frame similar to the PNP from Escherichia coli. PNP from P. falciparum (P. falciparum PNP) was cloned, overexpressed in E. coli, purified, and characterized. The primary amino acid sequence has 26% identity with E. coli PNP, has 20% identity with human PNP, and is phylogenetically unique among known PNPs with equal genetic distance between PNPs and uridine phosphorylases. Recombinant P. falciparum PNP is catalytically active for inosine and guanosine but is less active for uridine. The immucillins are powerful inhibitors of P. falciparum PNP. Immucillin-H is a slow onset tight binding inhibitor with a K(i)* value of 0.6 nm. Eight related immucillins are also powerful inhibitors with dissociation constants from 0.9 to 20 nm. The K(m)/K(i)* value for immucillin-H is 9000, making this inhibitor the most powerful yet reported for P. falciparum PNP. The PNP from P. falciparum differs from the human enzyme by a lower K(m) for inosine, decreased preference for deoxyguanosine, and reduced affinity for the immucillins, with the exception of 5'-deoxy-immucillin-H. These properties of P. falciparum PNP are consistent with a metabolic role in purine salvage and provide an explanation for the antibiotic effect of the immucillins on P. falciparum cultured in human erythrocytes.