Tina D. Tailor

Chemical and Biological Applications of Digital-Microfluidic Devices

Digital-microfluidic lab-on-a chip (LoC) technology offers a platform for developing diagnostic applications with the advantages of portability, sample and reagent volume reduction, faster analysis, increased automation, low power consumption, compatibility with mass manufacturing, and high throughput. In addition to diagnostics, digital microfluidics is finding use in airborne chemical detection, DNA sequencing by synthesis, and tissue engineering. In this article, we review efforts to develop various LoC applications using electrowetting-based digital microfluidics. We describe these applications, their implementation, and associated design issues.

Effect of Pazopanib on Tumor Microenvironment and Liposome Delivery

Pathologic angiogenesis creates an abnormal microenvironment in solid tumors, characterized by elevated interstitial fluid pressure (IFP) and hypoxia. Emerging theories suggest that judicious downregulation of proangiogenic signaling pathways may transiently “normalize” the vascular bed, making it more suitable for drug delivery and radiotherapy. In this work, we investigate the role of pazopanib, a small-molecule inhibitor of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptors, on tumor IFP, angiogenesis, hypoxia, and liposomal drug delivery. Nude mice bearing A549 human non–small cell lung cancer xenografts were treated with 100 mg/kg pazopanib (n = 20) or vehicle (n = 20) through oral gavage for 8 days, followed by a one-time intravenous dose of 10 mg/kg Doxil (liposomal doxorubicin). Pazopanib treatment resulted in significant reduction of tumor IFP and decreased vessel density, assessed by CD31 staining. Despite these trends toward normalization, high-performance liquid chromatography revealed no differences in doxorubicin concentration between pazopanib-treated and control tumors, with Doxil penetration from microvessels being significantly reduced in the pazopanib group. Additionally, tumor hypoxia, evaluated by CA-IX immunostaining and confirmed in a second study by EF5 expression (n = 4, 100 mg/kg pazopanib; n = 4, vehicle), was increased in pazopanib-treated tumors. Our results suggest that the classic definition of tumor “normalization” may undermine the crucial role of vessel permeability and oncotic pressure gradients in liposomal drug delivery, and that functional measures of normalization, such as reduced IFP and hypoxia, may not occur in parallel temporal windows. Mol Cancer Ther; 9(6); 1798–808. ©2010 AACR.

Dynamic Contrast-Enhanced MR Imaging in Head and Neck Cancer: Techniques and Clinical Applications

SUMMARY: In the past decade, dynamic contrast-enhanced MR imaging has had an increasing role in assessing the microvascular characteristics of various tumors, including head and neck cancer. Dynamic contrast-enhanced MR imaging allows noninvasive assessment of permeability and blood flow, both important features of tumor hypoxia, which is a marker for treatment resistance for head and neck cancer. Dynamic contrast-enhanced MR imaging has the potential to identify early locoregional recurrence, differentiate metastatic lymph nodes from normal nodes, and predict tumor response to treatment and treatment monitoring in patients with head and neck cancer. Quantitative analysis is in its early stage and standardization and refinement of technique are essential. In this article, we review the techniques of dynamic contrast-enhanced MR imaging data acquisition, analytic methods, current limitations, and clinical applications in head and neck cancer.

Case 215: Voriconazole-induced Periostitis

History A 74-year-old woman presented with multifocal bone pain, including pain in multiple ribs, bilateral shoulders, and bilateral hips. The pain began several months before presentation and was quite severe, ultimately necessitating control with narcotics. At examination, strength in both lower extremities was slightly reduced, sensation and reflexes were intact, and range of motion was full, though painful. There were no notable constitutional symptoms of fever or weight loss. Laboratory work-up was remarkable for elevated alkaline phosphatase level (277 U/L [4.6 mkat/L]). The patient had undergone left lung transplantation 8 years prior for pulmonary fibrosis. A thorough pulmonary work-up for the cause of fibrosis, which included gathering an exposure, occupational, allergy, and previous infectious history, and a rheumatoid work-up were negative. The patients posttransplantation course was complicated by bronchiolitis obliterans from chronic rejection and by recent pulmonary embolism, for which she was undergoing anticoagulation therapy at the time of presentation. Additionally, the patient experienced repeated pulmonary infections with Aspergillus, leading to multiple hospitalizations and long-term antifungal prophylaxis with voriconazole. A bone scan from an outside hospital was reviewed, and further imaging was performed.

The Pseudocavitation Sign of Lung Adenocarcinoma: A Distinguishing Feature and Imaging Biomarker of Lepidic Growth.

Purpose: Our purpose was to evaluate whether pseudocavitation, characterized by round or oval areas of low attenuation in a lesion on computed tomography (CT), can help distinguish adenocarcinoma from other types of non–small cell lung cancer (NSCLC). We also sought to determine whether pseudocavitation is associated with lepidic growth on histopathology. Materials and Methods: This retrospective HIPAA-compliant study was approved by our institutional review board. The need for informed consent was waived. CT scans and pathology records from 158 NSCLCs in 149 patients were retrospectively reviewed. The frequency of pseudocavitation was compared among types of NSCLC, specifically adenocarcinoma versus other types of NSCLC. Subgroup analysis of adenocarcinomas was performed to identify any difference in the frequency of pseudocavitation between adenocarcinomas with reported lepidic growth and those without lepidic growth. Results: There was a significantly greater frequency of pseudocavitation in adenocarcinomas versus other types of NSCLC [19/86 (22.1%) vs. 4/72 (5.6%), P=0.007]. The sensitivity and specificity of the pseudocavitation sign for adenocarcinoma were 0.22 and 0.94, respectively. Among adenocarcinomas, the pseudocavitation sign was more frequent in tumors with lepidic growth versus those without lepidic growth [10/24 (41.7%) vs. 9/62 (14.5%), P=0.015]. Conclusions: Pseudocavitation at CT is more common in primary lung adenocarcinoma than in other types of NSCLC. It is also more common in adenocarcinomas with lepidic growth, suggesting a correlation between the imaging finding of pseudocavitation and the pathologic finding of lepidic growth. As the subtype of NSCLC guides treatment, predicting tumor pathology by imaging may improve diagnostic workup for patients with NSCLC.

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.

Needle embolism in intravenous drug abuse.

Although intravenous drug users report the breaking of a needle as a relatively common occurrence, central embolism of needle fragments occurs infrequently in the literature. Central needle embolism also poses a conundrum for the radiologist, as the needle may be easily overlooked when the clinical history is nonspecific. We present two cases of needle embolism to the lung, one complicated by inflammatory mass and progressive pleuritic chest pain requiring wedge resection. We hope that our experiences may increase radiologists’ and emergency physicians’ familiarity with this unusual cause of chest pain. The radiological findings are subtle and may be easily overlooked, particularly without thorough clinical history.

Geographic Access to CT for Lung Cancer Screening: A Census Tract-Level Analysis of Cigarette Smoking in the United States and Driving Distance to a CT Facility

PURPOSE Spatial access to health care resources is a requisite for utilization. Our purpose was to determine, at a census tract level, the geographic distribution of US smokers and their driving distance to an ACR-accredited CT facility. METHODS The number of smokers per US census tract was determined from US Census Bureau data (American Community Survey, 2011-2015) and census tract smoking prevalence estimates. Driving distance, from the centroid of each census tract to the nearest CT facility, was determined using a geographic information system. Distance variations were assessed, and relationships with tract population density were examined with regression models. RESULTS Most US smokers (81.8%) were within 15 miles of a CT facility; however, there was considerable inter- and intrastate variability. For census tracts containing ≥500 smokers, median distance to a CT was 4.3 miles. At the state level, median distance ranged from 1.4 (Washington DC) to 29.1 miles (Wyoming). Within each state, this variation was higher, with Washington, DC, exhibiting the lowest range (range, 4.3; 0.2-4.5 miles) and Maine exhibiting the highest range (range, 244.8; 0.2-245.0 miles). Distance to a CT facility was inversely associated with census tract population density. CONCLUSIONS Geographic variability in CT facility access has implications for lung cancer screening (LCS) implementation. Individuals in densely populated areas have relatively greater spatial access to CT facilities than those in sparsely populated tracts. Further work is needed to identify access disparities to LCS to optimize LCS for all eligible populations.

Non-dysbaric arterial gas embolism associated with chronic necrotizing pneumonia, bullae and coughing: a case report

Arterial gas embolism (AGE) can be clinically devastating, and is most often associated with exposure to changes in ambient pressure, medical procedure or congenital malformation. Here we report a case of AGE in a 78-year-old male without these traditional risk factors. Rather, the patients history included chronic obstructive pulmonary disease, necrotizing pneumonia, bullous disease and coughing. He was safely treated with hyperbaric oxygen (HBO₂) therapy for AGE, with initial clinical improvement, but ultimately died from his underlying condition. Pathophysiology is discussed. This case illustrates the possibility that AGE can occur due to rupture of lung tissue in the absence of traditional risk factors. HBO₂ therapy should be considered in the management of such patients.

Penetrating Injury From Plastic Airsoft Pellet Shows Beam-hardening Artifact On Computer Tomography

Purpose: To describe a case of left eye corneal perforation, cataract, hyphema, and intraocular foreign body after airsoft pellet injury. Methods: The authors reviewed the medical history and diagnostic imaging of a 12-year-old boy injured by a pellet from an airsoft gun. Typically, plastic airsoft pellets cause blunt trauma to the globe, which can lead to visual disability from corneal abrasion or hyphema. Initial computed tomography of the left orbit showed a 6.1 mm × 7.6-mm radiodense foreign body with beam-hardening artifact, a radiographic feature associated with metallic objects. Results: The patient was taken to the operating room for globe repair, lensectomy, vitrectomy, and removal of intraocular foreign body. The removed foreign body was a plastic airsoft pellet. Conclusion: This is the first report of a plastic intraocular foreign body showing beam-hardening artifact. This finding may have implications in the diagnosis and management of retained intraocular or intraorbital plastic foreign bodies.