Daniel Vargas

Aortitis: imaging spectrum of the infectious and inflammatory conditions of the aorta.

Aortitis is a general term that refers to a broad category of infectious or noninfectious conditions in which there is abnormal inflammation of the aortic wall. These inflammatory conditions have different clinical and morphologic features and variable prognoses. The clinical manifestations are usually vague and nonspecific and may include pain, fever, vascular insufficiency, and elevated levels of acute phase reactants, as well as other systemic manifestations. As a result, aortitis is often overlooked during the initial work-up of patients with constitutional symptoms and systemic disorders. A multimodality imaging approach is often required for assessment of both the aortic wall and aortic lumen, as well as for surveillance of disease activity and treatment planning. Noninvasive cross-sectional imaging modalities such as magnetic resonance (MR) imaging, MR angiography, and computed tomographic angiography play a critical role in initial evaluation and further assessment of aortitis. Radiologists should be familiar with the clinical features and imaging findings of the different types of aortitis.

Imaging Appearances of the Sternum and Sternoclavicular Joints

The sternum and sternoclavicular joints--critical structures of the anterior chest wall--may be affected by various anatomic anomalies and pathologic processes, some of which require treatment. Pectus excavatum and pectus carinatum are common congenital anomalies that are usually benign but may warrant surgical treatment if they cause compression of vital internal structures. By contrast, developmental variants such as the sternal foramen are asymptomatic and do not require further evaluation or treatment. Arthritides of the sternoclavicular joint (osteoarthritis, septic arthritis, and seronegative arthropathies) are common and must be differentiated before an appropriate management method can be selected. The recognition of complications of sternotomy (eg, sternal dehiscence, secondary osteomyelitis) is critical to avoid life-threatening sequelae such as acute mediastinitis. Likewise, the detection of sternal fractures and sternoclavicular dislocations is important, especially where they impinge on vital structures. In addition, sternal malignancies (most commonly, metastases and chondrosarcoma) must be distinguished from benign neoplasms. To achieve accurate and timely diagnoses that facilitate appropriate treatment, radiologists must be familiar with the appearances of these normal anatomic variants and diseases of the sternum.

Neuroimaging in drug and substance abuse part II: Opioids and solvents

The central nervous system is one of the primary targets for the detrimental effects of drugs of abuse. Diagnostic imaging, especially MRI, plays an important role in the detection of complications associated with drug abuse. We present the imaging findings associated with the abuse of opioids and other morphine derivatives, as well, as solvents. Of the morphine derivatives, heroin is the most commonly abused. Several CNS pathologic effects have been described in association with its abuse. These include neurovascular complications such as microvascular ischemic changes or ischemic stroke. A rare form of leukoencephalopathy has been described in those abusers who inhale heroin vapors. Other neurologic complications include atrophy and various infectious processes. Solvent inhalation is a common practice among adolescents and young adults secondary to its ease of access and low cost. The most important component of industrial solvents is toluene. Complications of toluene abuse may be either acute, showing no neuroradiological changes, or chronic, characterized by cerebral and cerebellar demyelination as well as atrophy.

Rhenium-186 liposomes as convection-enhanced nanoparticle brachytherapy for treatment of glioblastoma

Although external beam radiation is an essential component to the current standard treatment of primary brain tumors, its application is limited by toxicity at doses more than 80 Gy. Recent studies have suggested that brachytherapy with liposomally encapsulated radionuclides may be of benefit, and we have reported methods to markedly increase the specific activity of rhenium-186 ((186)Re)-liposomes. To better characterize the potential delivery, toxicity, and efficacy of the highly specific activity of (186)Re-liposomes, we evaluated their intracranial application by convection-enhanced delivery in an orthotopic U87 glioma rat model. After establishing an optimal volume of 25 µL, we observed focal activity confined to the site of injection over a 96-hour period. Doses of up to 1850 Gy were administered without overt clinical or microscopic evidence of toxicity. Animals treated with (186)Re-liposomes had a median survival of 126 days (95% confidence interval [CI], 78.4-173 days), compared with 49 days (95% CI, 44-53 days) for controls. Log-rank analysis between these 2 groups was highly significant (P = .0013) and was even higher when 100 Gy was used as a cutoff (P < .0001). Noninvasive luciferase imaging as a surrogate for tumor volume showed a statistically significant separation in bioluminescence by 11 days after 100 Gy or less treatment between the experimental group and the control animals (χ(2)[1, N= 19] = 4.8; P = .029). MRI also supported this difference in tumor size. Duplication of tumor volume differences and survival benefit was possible in a more invasive U251 orthotopic model, with clear separation in bioluminescence at 6 days after treatment (χ(2)[1, N= 9] = 4.7; P = .029); median survival in treated animals was not reached at 120 days because lack of mortality, and log-rank analysis of survival was highly significant (P = .0057). Analysis of tumors by histology revealed minimal areas of necrosis and gliosis. These results support the potential efficacy of the highly specific activity of brachytherapy by (186)Re-liposomes convection-enhanced delivery in glioma.

Influence of aging and caloric restriction on activation of Ras/MAPK, calcineurin, and CaMK-IV activities in rat T cells.

The signaling cascade mediated by Ras (p21ras) and MAPK (mitogen-activated protein kinase) and calcium/calmodulin regulating enzymes, calcineurin (CaN) and CaMK-IV, are considered to be essential for T-cell growth and function. In the present study, the effect of aging and caloric restriction (CR) on the induction of Ras and MAPK activation by concanavalin A (ConA) was studied. Splenic T cells were isolated from young (4-6 months) and old (22-24 months) rats that had free access to food (control group), and from caloric restricted old (22-24 months) rats that beginning at 6 weeks of age were fed 60%(40% caloric restriction) of the diet consumed by the control rats. We found that the induction of Ras activity in T cells isolated from control old rats was lower (P<0.001) than that in control young rats. However, the levels of Ras activity in T cells isolated from CR old rats were similar to the levels in the age-matched control rats. The induction of MAPK activity in T cells isolated from control old rats and CR old rats was significantly less than in T cells isolated from control young rats, and caloric restriction significantly (P<0.05) reduced the age-related decline in MAPK activation. We also measured the induction of CaN and CaMK-IV activities by ConA in T cells from control young and old and CR old rats. The induction of both CaN and CaMK-IV activity decreased with age. Caloric restriction significantly (P<0.05) reduced the age-related decline in CaN activity, but had no significant effect on CaMK-IV activity. The changes in Ras/MAPK activation and in CaN and CaMK-IV activity with age or with CR were not associated with alterations in their corresponding protein levels. Thus, caloric restriction has a differential effect on the activation of the upstream signaling molecules that are altered with age.

Primary Pericardial Tumors

Primary pericardial tumors are rare and may be classified as benign or malignant. The most common benign lesions are pericardial cysts and lipomas. Mesothelioma is the most common primary malignant pericardial neoplasm. Other malignant tumors include a wide variety of sarcomas, lymphoma, and primitive neuroectodermal tumor. When present, signs and symptoms are generally nonspecific. Patients often present with dyspnea, chest pain, palpitations, fever, or weight loss. Although the imaging approach usually begins with plain radiography of the chest or transthoracic echocardiography, the value of these imaging modalities is limited. Cross-sectional imaging, on the other hand, plays a key role in the evaluation of these lesions. Computed tomography and magnetic resonance imaging allow further characterization and may, in some cases, provide diagnostic findings. Furthermore, the importance of cross-sectional imaging lies in assessing the exact location of the tumor in relation to neighboring structures. Both benign and malignant tumors may result in compression of vital mediastinal structures. Malignant lesions may also directly invade structures, such as the myocardium and great vessels, and result in metastatic disease. Imaging plays an important role in the detection, characterization, and staging of pericardial tumors; in their treatment planning; and in the posttreatment follow-up of affected patients. The prognosis of patients with benign tumors is good, even in the few cases in which surgical intervention is required. On the other hand, the length of survival for patients with malignant pericardial tumors is, in the majority of cases, dismal.

Age-related decline in activation of calcium/calmodulin-dependent phosphatase calcineurin and kinase CaMK-IV in rat T cells

We have previously shown that the DNA binding activity of the transcription factor NFAT which plays a predominant role in IL-2 transcription decreases with age. Because the transactivation (dephosphorylation and nuclear translocation) of the NFAT-c (cytoplasmic component of the NFAT complex) is mediated by the calcium/calmodulin-dependent phosphatase, calcineurin (CaN), and because Ca2+/calmodulin-dependent kinases (CaMK-II and IV/Gr) have been shown to play a critical role in calcium signaling in T cells, it was of interest to determine what effect aging has on the activation and the levels of these calcium regulating enzymes. The induction of calcineurin phosphatase activity, and CaMK-II and IV/Gr activities, were studied in splenic T cells isolated from Fischer 344 rats at 6, 15, and 24 months of age. In addition, the changes in the protein levels of these enzymes were measured by Western blot. The calcineurin phosphatase activity and CaMK-II and IV kinase activities were at a maximum after the cells were incubated with anti-CD3 antibody for 5-10 minutes. The induction of calcineurin activity by anti-CD3 and by calcium ionophore (A23187) declined 65 and 55%, respectively, between 6 and 24 months of age. The induction of CaMK-IV activity, but not CaMK-II activity by anti-CD3, was significantly less (by 54%) in T cells from old rats compared to T cells from young rats. The decline in the activation of these enzymes with age was not associated with changes in their corresponding protein levels. These results demonstrate that alterations in calcineurin phosphatase activity and CaMK-IV activity may contribute to the well-documented age-related decline in T cell function.

Cardiovascular complications of cocaine: Imaging findings

Cocaine is the second most commonly abused illicit drug in the US and the most common one involved in emergency department visits, the majority of which are related to the cardiovascular system. Cardiovascular complications related with cocaine abuse include myocardial ischemia and infarction, myocarditis, hypertrophic cardiomyopathy, dilated cardiomyopathy, aortic dissection, thrombosis, stroke and cerebral hemorrhage, and different forms of visceral ischemia, among others. In an era where cocaine use has reached epidemic proportions, it is necessary for the radiologist to understand the pathophysiology, clinical presentation, and imaging characteristics of its cardiovascular complications.

Neuroimaging in drug and substance abuse part I: Cocaine, cannabis, and ecstasy

Multiple neurological complications of cocaine abuse have been described including both ischemic and hemorrhagic cerebrovascular events, atrophy in the case of chronic abuse, and an increase in incidence of congenital malformations in the setting of maternal use. The abuse of cannabis may cause a number of neurovascular changes that, in turn, may result in ischemic events, however, a direct connection between these has not been fully established. The use of MDMA (ecstasy), a popular recreational drug, has been related to ischemic and hemorrhagic cerebrovascular events, as well as atrophy. Neuroimaging studies are vital in the assessment of the extent of neurologic damage in these patients.

Hypertrophic Cardiomyopathy from A to Z: Genetics, Pathophysiology, Imaging, and Management

Hypertrophic cardiomyopathy (HCM) is a heterogeneous group of diseases related to sarcomere gene mutations exhibiting heterogeneous phenotypes with an autosomal dominant mendelian pattern of inheritance. The disorder is characterized by diverse phenotypic expressions and variable natural progression, which may range from dyspnea and/or syncope to sudden cardiac death. It is found across all racial groups and is associated with left ventricular hypertrophy in the absence of another systemic or cardiac disease. The management of HCM is based on a thorough understanding of the underlying morphology, pathophysiology, and clinical course. Imaging findings of HCM mirror the variable expressivity and penetrance heterogeneity, with the added advantage of diagnosis even in cases where a specific mutation may not yet be found. The diagnostic information obtained from imaging varies depending on the specific stage of HCM-phenotype manifestation, including the prehypertrophic, hypertrophic, and later stages of adverse remodeling into the burned-out phase of overt heart failure. However, subtle or obvious, these imaging findings become critical components in diagnosis, management, and follow-up of HCM patients. Although diagnosis of HCM traditionally relies on clinical assessment and transthoracic echocardiography, recent studies have demonstrated increased utility of multidetector computed tomography (CT) and particularly cardiac magnetic resonance (MR) imaging in diagnosis, phenotype differentiation, therapeutic planning, and prognostication. In this article, we provide an overview of the genetics, pathophysiology, and clinical manifestations of HCM, with the spectrum of imaging findings at MR imaging and CT and their contribution in diagnosis, risk stratification, and therapy.